1

I HC HU
TRNG I HC Y DC
B MN VI SINH VT

Tham gia bin son GIO TRNH

VI SINH VT Y HC

GVC.ThS. Trn Vn Hng GVC.ThS. L Vn An GVC.TS. Trn nh Bnh GVC.ThS. Trn Th Nh Hoa (SCH DNGGV.ThS. Ng Vit 6 NM) CHO BC S Y HC D PHNG H Qunh Trm

MC LC
Trang Phn I: i cng vi sinh y hc i tng nghin cu v lch s pht trin ca vi sinh vt hc Hnh th, cu to v sinh l ca vi khun Di truyn vi khun Tit trng, kh trng v khng sinh i cng virus Bacteriophage Phng nga v iu tr bnh virus Nhim trng v c lc ca vi sinh vt Khng nguyn vi sinh vt S khng ca c th chng li cc vi sinh vt gy bnh K thut min dch s dng trong chn on vi sinh vt Vacxin v huyt thanh Vi sinh vt trong t nhin v k sinh ngi.Cc ng truyn bnh Nhim trng bnh vin Phn II: Cc vi khun gy bnh thng gp Cc cu khun gy bnh H vi khun ng rut (Enterobacteriaceae) Vi khun dch hch v Legionella pneumophila Haemophilus v Bordetella Trc khun m xanh v Burkholderia pseudomallei Vibrio Campylobacter v Helicobacter Cc xon khun gy bnh Vi khun bch hu Trc khun than v Listeria monocytogenes Cc Clostridia gy bnh H Mycobacteriaceae Rickettsia, Chlamydia v Mycoplasma Phn III: Cc virus gy bnh thng gp 88 88 97 108 113 117 121 125 128 135 139 142 148 153 160 62 68 78 83 1 1 5 12 23 30 39 42 49 54 57

Anh hng ca cc nhn t ngoi cnh n s pht trin ca vi sinh vt 17

Cc virus h Herpesviridae Adenovirus Enterovirus Rotavirus Virus cm Paramyxoviridae Flaviviridae Virus di Cc virus sinh khi u Cc virus vim gan Virus HIV/AIDS Cc virus gy bnh khc 212 174

160 167 170 177 181 185 190 193 197 206

PHN I

I CNG VI SINH Y HC I TNG NGHIN CU V LCH S PHT TRIN CA VI SINH VT HC

Mc tiu hc tp 1. Trnh by c i tng nghin cu ca vi sinh vt hc. 2. Trnh by c lch s pht trin ca vi sinh vt hc v hng gii quyt bnh nhim trng hin nay.

I. I TNG NGHIN CU CA VI SINH VT HC

Vi sinh vt hc (Microbiology) l khoa hc kho st hot ng ca cc vi sinh vt (t Hylp micros l nh b, bios l s sng v logos l khoa hc). Vi sinh vt l cc sinh vt nh b mt trn khng thy v ch c pht hin bng knh hin vi. Mun o kch thc ca vi sinh vt, ngi ta s dng cc n v sau: Micromet (m, micrometre) Nanomet (nm, nanometre) Angstrom = 10-6m = 10-9m = 10-10m

Vi sinh vt bao gm vi khun, nm men, nm mc, to, nguyn sinh ng vt v virus. Trc khi khm ph vi sinh vt ngi ta chia sinh vt lm hai gii: gii ng vt v gii thc vt. Sau khi khm ph vi sinh vt ngi ta nhn thy vi sinh vt kt hp nhng c tnh ca thc vt v ng vt vi tt c nhng t hp c th c, cho nn vic phn loi sinh vt thnh hai gii lm pht sinh mt s iu khng hp l. V d nh nm men c phn loi l thc vt v phn ln khng di ng mc d chng t c nhng tnh cht ca thc vt v cho thy nhng lin h sinh tin ha m nt vi nguyn sinh ng vt. Nm 1866 nh khoa hc c E. Haeckel ngh xp vi sinh vt vo mt gii ring, gii Nguyn sinh (Protista). Gii ny phn bit vi thc vt v ng vt s t chc n gin ca chng: d n bo hoc a bo, t bo ca chng khng bit ha thnh m. Nm 1969 nh sinh thi hc M R.H. Whittaker xut h thng phn loi nm gii: l gii Khi sinh (Prokaryota hay Monera) bao gm vi khun v vi khun lam, gii Nguyn sinh (Protista), gii Nm (Fungi), gii Thc vt (Plantae) v gii ng vt (Animalia). Theo kin ngh ca nh sinh vt hc Trung Quc Trn Th Tng nm 1979 th nhm gii sinh vt nhn tht bao gm gii Thc vt, gii Nm v gii ng vt,

nhm gii sinh vt nhn nguyn thu bao gm gii Vi khun v gii Vi khun lam, cn gii Virus thuc v nhm gii sinh vt cha c t bo. Theo quan im hin i (P.H. Raven, G.B. Johnson, 2002) th mi sinh vt trn th gii thuc v 6 gii khc nhau: gii C khun (Archaebacteria), gii Vi khun (Eubacteria), gii Nguyn sinh (Protista), gii Nm (Fungi), gii Thc vt (Plantae) v gii ng vt (Animalia). Phn ln vi sinh vt nm trong 4 gii: C khun, Vi khun, Nguyn sinh v Nm ca h thng 6 gii ni trn. T bo nhn tht c nhn cha mt s i nhim sc th, mng nhn ni lin vi li ni cht nguyn sinh. Nguyn tng ca t bo nhn tht c li ni cht nguyn sinh, khng bo v nhng plastit t sao chp. Nhng plastit cha ADN ring v nhn ln bng phn lit. Nhng plastit bao gm ti lp th cha h thng chuyn ch in t ca s phosphoryl ha v lc lp nhng sinh vt quang hp cha lc dip t v nhng thnh phn quang hp khc. Nguyn tng bn cht lipoprotein nm bn trong mng t bo. Nhiu vi sinh vt t bo nhn tht c vch t bo to nn bi celluloza, chitin hoc oxyt silic.T bo nhn tht c th di ng nh nhng lng. Nhng lng ny gm mt b 9 si nh bao quanh 2 si nh trung tm. T bo nhn nguyn thu (T bo nhn s) c cu trc t bo n gin. Nhn ch gm c mt nhim sc th khng mng nhn, nhng vch t bo li phc tp hn. T bo nhn nguyn thu khng c plastit t sao chp nh ti lp th v lc lp. Enzyme cytochrom c tm thy mng t bo; nhng c th quang hp, nhng sc t quang hp c tm thy nhng phin mng nm di mng t bo. Vi khun thng tch t vt liu d tr di hnh thc nhng ht nh khng ha tan, dng polyme, trung tnh, tr thm thu. Vt liu cacbon c bin i bi mt s vi khun thnh polyme polyaxit-- hydrobutyric v bi nhng vi khun khc thnh polyme glucoza tng t nh glycogen gi l granuloza. Nhng ht nh d tr c s dng nh ngun C lc s tng hp protein v axit nucleic c thc hin tr li. Mt cch tng t mt vi vi khun oxy ha sulfua bin i lng tha H 2S mi trng bn ngoi thnh nhng ht sulfua ni bo. Nhiu vi khun tch tr pht pht hu c thnh nhng ht nh polymemetaphosphate gi l volutin. Virus khc vi tt c cc c th c t bo k c vi khun v Rickettsia. Virion hay l ht virus gm mt phn t ADN hoc ARN nm bn trong mt v protein gi l capsid. Vo bn trong t bo vt ch, axit nucleic ca virus s dng b my tng hp ca t bo hnh thnh axit nucleic v nhng thnh phn khc ca virus. Axit nucleic v nhng thnh phn protein c hiu kt hp thnh ht virus xm nhim hon chnh gi l virion. Virion c phng thch vo mi trng bn ngoi v bt u qu trnh xm nhim t bo vt ch.

II. S LC LCH S PHT TRIN CA VI SINH VT HC

1. S pht hin vi sinh vt S pht hin vi sinh vt gn lin vi s pht minh knh hin vi. Anton van Leeuwenhoek (1632 - 1723) ngi H Lan, l ngi u tin th k XVII nhn thy vi sinh vt nh nhng knh hin vi phng i 270 - 300 ln m ng ch to (1676). Do s hn ch v phng i v phn gii ca knh hin vi cho nn nhng nghin cu hin vi ca c th sng rt b hn ch v mi n u th k XIX chic knh hin vi hon chnh u tin mi ra i v t cho n nay con ngi ln lt sng to ra hng lot cc loi knh hin vi quang hc khc nhau th nhiu s kin quan trng mi c pht hin.

2. S trng thnh ca vi sinh vt hc Trong th k XVII v sut th k XVIII vi sinh vt hc ch ch trng v phn m t, tuy nhin cng c mt s cng trnh xut sc nh Spallanzani s dng mi trng nui cy kh khun bng nhit, Edward Jenner pht minh vaccine u ma, Zinke pht hin tc nhn ca bnh di trong nc bt ca ch b di. Th k XIX mi cho thy nhng bc pht trin ln v vi sinh vt hc nh cng lao ca Louis Pasteur v Robert Koch. L.Pasteur (1822 - 1895) hon chnh vic nghin cu vi sinh vt. Vi sinh vt khng nhng c m t chnh xc m cn c kho st y v nhng tnh cht sinh l. L.Pasteur l nh vi sinh vt hc v i c cng: - Chm dt tranh lun v thuyt t sinh bng cc th nghim xut sc vi bnh c ngng. - Pht hin tc nhn ca s ln men nh ln men ru, ln men thi l vi sinh vt: cc vi sinh vt pht trin to thnh cc enzyme chu trch nhim v hin tng ln men. - Xc nh vai tr tc nhn gy bnh ca cc vi sinh vt trong bnh nhim trng - Khi qut ha vn vaccine v tm ra phng php iu ch mt s vaccine phng bnh nh vaccine bnh than, vaccine bnh t g... v pht minh vaccine di. R.Koch (1843 - 1910) cng ng gp ln lao cho vi sinh vt hc nh nhng cng trnh: - Pht trin nhng k thut c nh v nhum vi khun. - S dng mi trng c phn lp vi khun rng. - Nu tiu chun xc nh bnh nhim trng. - Khm ph vi khun lao, vi khun t. Nh cng lao ca L.Pasteur, R.Koch v nhiu nh bc hc khc, phn ln cc vi khun gy bnh ngi v ng vt u c khm ph u th k XX. Lc by gi vi sinh hc tr thnh mt khoa hc ng dng quan trng trong lnh vc y hc, nng nghip v cng nghip. Trong lm sng, khoa ly thnh lp tip nhn bnh nhn nhim trng, khoa ngoi s dng phng php phu thut st trng, tin ca phng php phu thut v trng ngy nay. 3. Nhng thnh tu hin i Trong nhng thp k gn y t mt khoa hc ng dng, vi sinh vt hc tr thnh mt khoa hc c bn lm pht sinh mt ngnh khoa hc mi: sinh hc phn t v di phn t v cng vi cc ngnh khoa hc khc to nn mt cuc cch mng khoa hc k thut hin i. Nh nhng hiu bit v di truyn hc hin i m m hnh nghin cu l E.coli, Watson v Crick pht hin mu cu trc ca ADN v c ch sao chp bn bo tn lm c s cho s hnh thnh sinh hc phn t v di phn t. Nhng pht

hin k diu v c cu ca m di truyn v cc cu trc khc ca t bo sng c s dng lm c s cho s pht trin cng nghip sinh hc, ngnh cng nghip cho php con ngi can thip vo qu trnh hnh thnh v pht trin ca sinh vt phc v li ch ca con ngi . Gn y nhng k thut tng hp gen, tho ghp gen lm cho cng ngh sinh hc tr thnh mt lc lng sn xut mi nhn ca nn kinh t th gii. Trong lnh vc y hc nhng k thut trn c nhiu trin vng gii quyt cc bnh di truyn, phng chng cc bnh nhim trng, bnh ung th . III. NHNG VN HIN NAY CA VI SINH VT Y HC Trong y hc, vi sinh vt l cn nguyn ca cc bnh nhim trng. V vy khi xt v tm quan trng hin nay ca vi sinh vt y hc phi cp ti tnh hnh cc bnh nhim trng. T ngn xa bnh nhim trng l mt tai ha cho nhn loi. Bnh u ma, bnh dch hch, bnh dch t ... git cht hng triu ngi, tn ph nhiu lng mc, thnh ph. T khi vi sinh vt hc trng thnh cho n nay con ngi c kh nng dn dn ch ng c bnh nhim trng. Nhng con ng ch ng tin ti xa b bnh nhim trng l con ng kh khn v lu di. Thnh tu vang di u tin xy ra vo nm 1891 lc Von Behring cu sng mt em b nh huyt thanh khng bch hu, m u thi k huyt thanh liu php. Thc t cho thy huyt thanh liu php c nhng mt hn ch v ch hu hiu i vi nhng bnh nhim c t vi khun nh bch hu, un vn, hoi th sinh hi .v.v... Thnh tu vang di th hai l cng lao ca G.Domagk pht minh sulfonamit nm 1935. Nhng dn dn v kh sulfonamit t ra yu km khng kh nng iu tr phn ln cc bnh nhim trng thng gp. Nm 1940 Fleming, Florey v Chain pht minh penicillin v a vo iu tr m u thi i khng sinh. Trong sut hai thp k, nhiu khng sinh hu hiu c pht minh v ngi ta c th ch ng mt cch hu hiu cc bnh nhim trng. Nhng thi gian cho thy bnh nhim trng vn cn lu mi gii quyt xong v cc vi khun khng thuc c quan st trong cc loi vi khun. May mn l cc khng sinh hu hiu mi khm ph gi khng cho cc vi khun khng thuc pht trin quy m qu ln khng ch ng c. u thp k 80, thc t cho thy cc vi khun khng thuc xut hin ngy cng nhiu nhng cc khng sinh hu hiu mi khm ph tr nn him dn. Tr nhng khng sinh thuc nhm quinolon, nhng khng sinh c gi l mi ch l s xp xp li hay l s thay i cu trc phn t ca nhng khng sinh khm ph t trc bng k thut bn tng hp hoc tng hp. Hin nay, phn ln cc bnh nhim trng c ch ng mt cch hu hiu, cc v dch c dp tt nhanh chng nhng vn cn nghin cu nhiu ch ng cc vi khun khng thuc v tm cc thuc hu hiu iu tr cc bnh virus. Hng gii quyt bnh nhim trng hin nay c th l s dng ng thi ba bin php sau: - Thc hin mt chin lc khng sinh hn ch cc vi khun khng thuc.

- Tip tc tm kim cc khng sinh hu hiu mi iu tr bnh vi khun v pht minh cc thuc khng virus hu hiu. - iu ch cc vaccine hu hiu bng cc k thut hin i nh cng ngh gen phng nga cc bnh nhim trng, dn dn tin n xa b chng nh trng hp bnh u ma trn phm vi ton th gii.

HNH TH , CU TO V SINH L CA VI KHUN

Mc tiu hc tp 1. M t c cc loi hnh th ca vi khun 2. M t c cu trc ca t bo vi khun 3. Trnh by c cc nt c bn ca sinh l vi khun

I. HNH TH CA VI KHUN
Vi khun thng thng c hnh th nht nh do vch t bo xc nh. Mt s khng vch ( hnh thc L) nh Mycoplasma khng c hnh th nht nh. ng knh trung bnh ca vi khun khang 1m . Nhng i din nh nht nh Mycoplasma c ng knh khang 0,1m v nhng i din ln hn c kch thc hng chc m nh Spirilium volutans 20m. Cc vi khun gy bnh c kch thc t 0,2m n 10m V hnh th ngi ta c th chia vi khun thnh cu khun, trc khun v vi khun hnh xon. 1. Cu khun : L nhng vi khun hnh cu, hnh trng hay hnh ht c ph 1.1. Micrococci (n cu) y l nhng cu khun xp hng u hoc khng u, l nhng tp khun tm thy trong khng kh v nc. 1.2. Diplococci (Song cu) L nhng cu khun xp tng i phn chia trong mt mt phng. Mt s gy bnh cho ngi nh ph cu, lu cu, cu khun mng no. 1.3. Stretococci (Lin cu): L nhng cu khun xp thnh chui ngn hoc di. Mt s lai gy bnh cho ngi nh Streptococcus pyogenes thuc nhm A ca Lancefield. 1.4. Tetracocci (T cu) Cc cu khun hp thnh 4, phn chia theo hai mt phng, rt t khi gy bnh. 1.5. Sarcina (Bt cu) Cc cu khun xp thnh 8-16 con, phn chia theo ba mt phng, thng tm thy trong khng kh. 1.6. Staphylococci (T cu) Cc cu khun hp thnh m nh chm nho, phn chia theo mt phng, mt s loi gy bnh cho ngi v thng pht trin nhanh chng tnh khng vi nhiu khng sinh. 2. Trc khun L nhng vi khun c hnh que thng. 2.1.Bacteria L nhng trc khun hiu kh, khng to nha bo nh vi khun ng mt, vi khun bch cu, vi khun lao... 2.2. Bacilli L nhng trc khun hiu kh tuyt i to nha bo v d trc khun bnh than. 2.3.Clostridia L nhng trc khun k kh Gram dng to nha bo, v d trc khun un vn, trc khun ng c tht.

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3. Vi khun hnh xon 3.1. Phy khun Ch c mt phn ca hnh xon nn c hnh du phy, v d phy khun t.

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3.2.Xon khun C nhiu vng xon, v d xon khun giang mai, Leptospira, Borrelia.

II. CU TO CA T BO VI KHUN
Khc vi cc thnh vin ca protista lp trn c nhn tht nh t bo ng vt v thc vt, vi khun c t bo nhn s, nhn ch c mt nhim sc th, khng c mng nhn, khng c ti lp th, khng c b my phn bo nhng cc t bo li phc tp hn. 1. Vch t bo S hin din ca vch t bo vi khun c pht hin bng hin tung ly tng, bng cch nhum v bng phn lp trc tip. Tc dng c hc nh siu m phi hp vi ly tm cho php thu hoch vch t bo rng, tch ri khi nguyn tng. 1.1.Vch t bo vi khun gram dng Knh hin vi in t cho thy vch t bo dy t 15 n 50 nm. Thnh phn ch yu l mucopeptit gi l murein, mt cht trng hp m nhng n v ho hc l nhng ng amin. N-acetyl glucosamin v axt N-acetyl muramic v nhng chui peptit ngn cha alanin, axt glutamic v axt diaminopimelic hoc lysin. Ngoi ra vch t bo ca mt s vi khun gram dng cn cha axt teichoic. mt vi lai vi khun, axt teichoic chim ti 30% trng lng kh ca vch t bo. 1.2. Vch t bo vi khun Gram m gm ba lp Lp mucopeptit mng hn khang 10nm v hai lp lipoprotein v lipopolysaccharide bn ngoi, lp lipoprotein cha tt c nhng axt amin thng thng. Khng c axt teichoic, vch t bo vi khun gram m cha mt lng lipit ng k, khong 20 % trng lng kh ca vch t bo. 1.3.Chc nng ca vch t bo Vch t bo vi khun c nhiu chc nng: - Duy tr hnh th ca vi khun: Vch cng to nn b khung, lm cho vi khun c hnh th nht nh . - Quyt nh tnh bt mu gram ca vi khun: S bt mu gram khc nhau vi khun gram dng v gram m l do tnh thm thu khc nhau i vi cn ca hai nhm vi khun . Nu dng lysozym bin i vi khun gram dng thnh protoplast khng c vch th protoplast li bt mu gram m. - To nn khng nguyn thn O ca vi khun ng rut: iu ch khng nguyn 0 ca vi khun ng rut x l vi khun khng di ng bng nhit v cn. - To nn ni c t ca vi khun ng rut. Ni c t ch c gii ta lc vi khun b li gii. vi khun ng rut, ni c t l nhng phc hp lipopolysaccarit dn xut t vch t bo. 2. Mng nguyn tng L mng bn thm dy khong 10nm nm st vch t bo. Ngi ta c th chng minh s hin din ca n bng hin tng ly tng hoc nhum vi xanh Victoria 4R. N cha 60-70% lipit, 20-30% protein v mt lng nh hydrat cacbon. Mng nguyn tng c chc nng ro cn thm thu ca t bo, ngn cn khng cho nhiu phm vt vo bn trong t bo nhng li xc tc vic chuyn ch hat ng ca nhiu phm vt khc vo bn trong t bo. Hn na mng t bo cha nhiu h thng enzyme v v vy c chc nng ging nh ti lp th ca ng vt v thc vt. Mng nguyn tng cho thy nhng ch lm vo gi l mc th. vi khun Gram dng mc th kh pht trin cho thy hnh nh nhiu l ng tm. vi khun Gram m mc th ch l vt nhn n gin. 3. Nguyn tng

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L cu trc c bao bc bn ngoi bi mng nguyn tng, trng th gel, cu trc ny gm 80% nc, cc protein c tnh cht enzyme, cacbohydrat, lipid v cc ion v c nng cao, v cc hp cht c trng lng phn t thp. Nguyn tng cha dy c nhng ht hnh cu ng knh 18nm gi l ribsm. Ngoi ra cn c th tm thy nhng ht d tr glycogen, granulosa hoc polymetaphotphat. 4. Nhn t bo C th thy vi knh hin vi nh sng sau khi nhum hoc soi trc tip knh hin vi pha tng phn. Nhn c th hnh cu, hnh que, hnh qu t hoc hnh ch V. Kho st knh hin vi in t nhn khng c mng nhn v b my phn bo. N l mt si DNA trng lng phn t 3x109 dallon v cha mt nhim sc th duy nht di khong 1mm nu khng xon. Nhn ni lin mt u vi th mc. S ni lin ny gi mt vai tr ch yu trong s tch ri 2 nhim sc th con sau khi si nhim sc th m tch i. Trong s phn chia nhn hai mc th qua ch ni lin vi mng nguyn tng di chuyn theo nhng hng i nghch theo hai nhm con ni lin vi chng. Nh th mng nguyn tng t ng nh mt b my th s ca s gin phn vi mc th m nhn vai tr thai v sc. 5. Lng ca vi khun Lng chu trch nhim v tnh di ng ca vi khun. Ngi ta quan st s di ng ca vi khun knh hin vi nhn git treo hoc t mt git vi khun lam knh v ph mt l knh mng. Lng di 3-12 m hnh si gn sng, mnh 10- 20nm ) nn phi nhum vi axt tannic to thnh mt lp kt ta lm dy lng d pht hin. Lng pht xut t th y ngay bn di mng nguyn tng v c chuyn ng xoay trn. Bn cht protein n to nn do s tp hp nhng n v ph gi l flagellin to thnh mt cu trc hnh tr rng. Cch thc mc lng l mt c tnh di truyn. mt s loi nhiu lng mc quanh thn, mt s lai mt lng mc cc v mt s loi khc mt chm lng mt cc. Nu lng b lm mt i bng c hc th lng mi c to thnh nhanh chng. Lng ng vai tr khng nguyn nh khng nguyn H vi khun ng rut. 6. Pili L nhng ph b hnh si, mm mi hn lng, mnh hn nhiu v c xu hng thng ng knh 2-3 nm v di t 0,3-1nm, tm thy t mt n hng trm mt ngoi vi khun, bn cht protein. Pili pht xut trong mng nguyn tng v xuyn qua vch t bo. Pili c tm thy vi khun gram m nhng cng c th tm thy mt s vi khun gram dng. Pili F c nhim v trong s tip hp. Nhng pili khc gip cho vi khun bm vo nim mc hoc b mt khc ca t bo. 7. V ca vi khun V l mt cu trc nhy bc quanh vch t bo ca mt s vi khun, thng l polysaccharide, ch c v ca B.anthracis l mt polypeptide acid D-glutamic. V c th pht hin d dng huyn dch mc tu, n hin ra nh mt vng sng gia mi trng m c v t bo vi khun trng r hn. Cng c th pht hin bng phn ng phnh v hoc bng k thut nhum c bit. S t bin to thnh v rt d nhn bit v t bo c v to nn khun lc bng lng hoc nhy M trong khi t bo khng v to nn khun lc x x R. Nhim v duy nht c bit ca v l bo v vi khun chng thc bo v chng virut mun gn vo vch t bo . 8. Nha bo

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Nhng thnh vin ca Bacillus, Clostridium v Sporosarcina to thnh ni nha bo di nh hng ca mi trng bn ngoi khng thun li, mi t bo lm pht sinh mt nha bo. Nha bo c th nm gia, u nt hoc gn u nt ty theo loi, vch nha bo cha nhng thnh phn mucopeptide v axt dipicolinic. S d khng ca nha bo vi ha cht c l do tnh khng thm thu ca vch nha bo, s khng vi nhit lin h n trng thi mt nc cao. V chu ng vi iu kin khng thn li bn ngoi nha bo gp phn quan trng trong kh nng ly bnh ca trc khun hiu kh to nha bo nh trc khun than hoc trc khun k kh to nha bo nh Clostridia, nht l trc khun un vn, hoi th, sinh hi, ng c tht.

III. SINH L VI KHUN

Nh cc sinh vt khc vi khun cng dinh dng, chuyn hoa v pht trin. 1. S dinh dng pht trin vi khun i hi mi trng nui cy cha y nhng yu t dinh dng bao gm nhng hp cht cn thit cung cp nng lng v nhng hp cht c dng lm nguyn liu tng hp nhng vt liu mi ca t bo. V nguyn liu tng hp, vi khun i hi nhng nhu cu v mui khong nh PO 43-, K+, Mg2+ vi lng ng k, mt s ion ( nguyn t vi lng ) ch cn mt nng rt thp nh Fe2+, Zn2+, Mo2+, Ca2+, cc ion ny thng tm thy trong nc v trong cc mui khong khng tinh khit. Ngun C do thc n nng lng cung cp. Ngun N thng thng l protein hoc mt mui amoni. Phn ln vi khun nu c cung cp y nhng yu t trn th c kh nng tng hp cc cht cu to ca t bo. Nhng mt s vi khun mt kh nng tng hp mt vi hp cht v i hi c cung cp trong mi trng nui cy. l nhng yu t pht trin; chng c chia thnh hai loi, mt loi cn c cung cp tng lng nh v m nhn chc v xc tc nh mt thnh phn ca mt enzyme v d vitamin B, mt loi cn c cung cp tng lng ln v c dng lm nguyn liu cu to t bo nh axit amin, purin, pyrimidin. Ngoi ra nhng iu kin vt l nh nhit pH, p sut oxy cng nh hng n s pht trin cn c iu chnh thch hp. 2. S chuyn ha Bao gm tt c nhng phn ng ha hc xy ra nhng t bo sng. Nh nhng phn ng nng lng c chit t mi trng v c s dng cho sinh tng hp v pht trin. Trong chuyn ha quan trng nht l s oxy ha sinh hc. 2.1. S oxy ha sinh hc S oxy ha c nh ngha nh l s loi b in t t mt c cht km theo s loi b ion hydr tc l s loi b nguyn t hydr. V vy s oxy ha c xem nh l s vn chuyn nguyn t hydr. C cht b oxy ha c gi l cht cho hydr v phm vt b kh c gi l cht nhn hydro. Phn ln hp cht hu c mt ion hydr do loi b in t. in t khng th trng thi t do trong dung dch v khng th loi b khi mt c cht nu khng c mt cht thch hp nhn n. S vn chuyn in t l ct li ca s oxy ha v s kh. Ty theo bn cht ca cht nhn hydro cui cng ngi ta chia s oxy ha sinh hc thnh ba hnh thc : H hp hiu kh, h hp k kh v ln men. Cht nhn hydr cui cng l oxy phn t (O2) trong s h hp hiu kh, l mt hp cht v c (nitrat, sulfat, cacbonat ) trong s h hp k kh, l mt hp cht hu c trong s ln men. V nhu cu oxy ngi ta chia thnh : - Vi khun hiu kh bt buc nh vi khun lao v mt vi trc khun to nha bo, nhng vi khun ny i hi oxy v thiu kh nng ln men.

14

- Vi khun k kh bt buc nh Clostridia, Propionibactrium, chng ch pht trin khi khng c oxy. - Vi khun ty nh nm men, vi khun ng rut. Nhng vi khun ny c th sng khng c oxy nhng i thnh chuyn ha h hp lc c oxy. 2.2. S h hp hiu kh Cht nhn hydr cui cng l oxy phn t. C cht thng thng l ng nhng cng c th l axt bo, axt amin. in t c chuyn t cht cho hydr n cht nhn hydr qua nhiu bc. in t ly t cht cho hydro c th u tin chuyn n mt coenzyme th nht A, A do b kh thnh AH2. Mt enzyme khc li xc tc s chuyn in t t AH2 n mt coenzyme th hai B. AH2 do c oxy ha tr li thnh A v B tr nn tr thnh BH. Qu trnh ny c th tip din qua nhiu bc to nn dy chuyn h hp in t t cht cho hydr n oxy

Hnh 1: minh ho v dy chuyn in t Kt qu cui cng l s hnh thnh mt sn phm oxy ha, mt sn phm kh v nng lng. Nng lng pht sinh hoc c d tr trong cc dy ni sn nng lng hoc ta thnh nhit. 2.3. S h hp k kh C cht c th l hp cht hu c nhng cng c th l cht v c. Cht nhn in t y khng phi oxy khng kh m l nitrat, sulfat, cacbonat.... 2.4. S ln men C cht l hp cht hu c nhng cht nhn in t cng l hp cht hu c. y, trong dy chuyn in t thng thng ch c NAD l cht mang in t trung gian.

Hnh 2: S chuyn in t trong s ln men So vi s h hp, s ln men km hiu qu hn nhiu, n cung cp ATP 19 ln t hn i vi 1 mol glucoza chuyn ha. Mt vi khun pht trin vi mt lng gii hn glucoza cho thy hiu sut pht trin (trng lng kh vi khun / trng lng c cht chuyn ha) ln hn trong iu kin hiu kh so vi iu kin k kh. 3. S pht trin ca vi khun T bo nhn ln trong s pht trin. vi khun n bo, s pht trin lm gia tng s lng vi khun mt sn phm cy. Vi khun nhn ln bng phn lit. Mt th h c nh ngha nh l s tng i t bo. Thi gian th h l khan thi

15

gian cn thit d tng i s t bo. Thi gian th h thay i ty lai vi khun, 20 pht E.coli, 20 - 24 gi vi khun lao. 3.1. S pht trin ly tha : V hai t bo con c th pht trin cng mt tc nh t bo m nn s t bo trong rut sn phm cy tng ln vi thi gian nh mt cp s nhn 2 0, 21, 22, 23.....Ngha l s pht trin ly tha. Tc pht trin ca mt sn phm cy mt thi gian xc nh t l vi s t bo hin din thi gian . S lin h ny c th biu th di dng phng trnh sau dN = kN (1) dT Phn tch phng trnh trn ta c : N = N0 e kt (2) Trong N0 l s t bo thi gian 0 v N l s t bo bt k thi gian t sau . Trong phng trnh (2), k l hng s pht trin : Gii phng trnh theo k ta c : Ln N - Ln N0 k = (3) t Chuyn sang logarit thp phn log N - log N0 k = 2,302 t2 - t1 Nh vy k biu th tc logarit t nhin ca s t bo tng ln vi thi gian v c th xc nh bng th.

Hnh 3. Tc logarit t nhin ca s t bo tng ln vi thi gian. 3.2. ng biu din pht trin : Cy vo mt mi trng lng nhng vi khun ly t mt sn phm cy trc pht trin n bo ha, ln lt xc nh s t bo trong mt 1ml v biu din logarit ca nng t bo theo thi gian th thu c ng biu din pht trin. ng biu din gm 4 pha:

16

Hnh 4. ng biu din pht trin A :Pha tim n B: pha ly tha C: pha dng D: pha cht. - Pha tim n: Biu th giai an t bo bt u thch nghi vi mi trng mi. Enzyme v cht chuyn ha trung gian c to thnh v tch ly cho n khi t n mt nng m s pht trin c th bt u tr li. - Pha ly tha: Trong pha ny tc pht trin khng i. Tt c cc vi khun iu nhn ln vi mt tt khng i v kch thc trung bnh ca t bo cng khng i. Hin tng ny c tip tc duy tr cho n khi mt trong hai s kin sau ny xy ra. Mt hay nhiu thc n trong mi trng b thiu ht hoc sn phm chuyn ha c tch t nhiu. i vi vi khun hiu kh thc n u tin tr nn gii hn l oxy. Lc nng t bo khong 107/ml trong trng hp vi khun hiu kh, tc vi khun gim xung nu oxy khng c cho vo mi trng bng cch khuy hoc bm khng kh. Lc nng t bo t n 4-5 x 10 9/ml tc khuch tn ca oxy khng th tho mn nhu cu ngay c mi trng thong kh v s pht trin dn dn gim tc . - Pha dng: giai on ny s thiu ht thc n v s tch ly vt phm c lm cho s lng t bo dng li hon ton. Cc vi khun sinh sn t dn v s pht trin v khi lng cng gim dn, c mt s t bo cht nhng c b li nh s to thnh mt s t bo mi. - Pha cht: Bt u sau mt thi gian pha ng, thi gian ny thay i theo tng loi vi khun v iu kin nui cy. Vi khun cht cng ngy cng nhiu. Thng thng sau khi t bo cht, mt s t bo tip tc sng nh thc n phng thch t nhng t bo b ly gii.

17

DI TRUYN VI KHUN
Mc tiu hc tp 1. Trnh by c cc c ch vn chuyn di truyn vi khun. 2. Trnh by c cc c ch di truyn tnh khng thuc vi khun. Di truyn l s duy tr cc c im qua nhiu th h. C s vt cht ca di truyn l nhim sc th. Nhim sc th ca vi khun v d nh ca E.coli gm 5x106 i nucleotide chia thnh nhiu on gi l gen, mi gen quyt nh s tng hp mt protein c hiu. Nhng protein c hiu nh enzyme v nhng cu to khc ca t bo xc nh tt c cc tnh trng ca mt c th. Nhim sc th chu s nhn i trc khi phn bo. Do mi t bo con nhn mt b gen tng ng vi t bo m. S nhn i ca nhim sc th l mt qu trnh chnh xc, tuy nhin mi gen c mt xc xut nh v sai st trong sao chp, do lm pht sinh t bin. t bin xy ra ngu nhin khng cn s can thip ca mi trng bn ngoi vi mt tn sut rt nh t 10-5 n 10-9.

I. S VN CHUYN DI TRUYN VI SINH VT

S tin ha ca vi sinh vt ph thuc vo s bin d v s chn lc. N din ra chm chp, lc s bin d xy ra do tch ly nhng bin d lin tip mt chng sinh vt. Qu trnh ny tr nn nhanh chng vi sinh vt nh cc vi sinh vt pht trin nhng c ch vn chuyn di truyn gia cc c th. Vi khun vn chuyn nhng yu t di truyn qua ba c ch: bin np, ti np v tip hp. Trong bin np, mt on ADN c vn chuyn vo t bo nhn. y l mt c ch th s ca s vn chuyn gen. Trong ti np v tip hp, nhng plasmid c vn chuyn qua trung gian ca phage hoc qua tip xc. Plasmid l nhng phn t ADN dng vng trn nm ngoi nhim sc th v c kh nng t sao chp. Plasmid c trng khi nh so vi nhim sc th. Hai plasmid gi l khng ph hp nu chng khng th tn ti bn vng trong cng mt t bo. Nhng plasmid F mang nhn t sinh sn F. Nhng plasmid cng tn ti trong mt vi khun vi nhn t F gi l Fi+ nu chng ngn cn s tip hp ca F, gi l Fitrong trng hp ngc li. 1. Bin np (Transformation) Bin np l s vn chuyn ADN ha tan ca nhim sc th t vi khun cho sang vi khun nhn. Khi t bo vi khun b v do lm tan (lysis), ADN dng vng trn ca chng thot ra mi trng thnh cc on thng vi chiu di khc nhau, c kh nng gy bin np cho cc t bo nhn khc. Griffith nm 1928 khm ph s bin np ph cu bng th nghim sau chut nht : - Tim vo chut ph cu sng S1 c v th chut cht v nhim khun huyt. - Tim vo chut ph cu R1 sng khng v th chut khng cht.

18

- Tim vo chut ph cu S1 cht th chut khng cht. - Tim vo chut hn hp ph cu S1 cht vi R1 sng th chut cht v nhim khun huyt. T mu chut phn lp c S1 sng c v. Griffith cng nh cc nh khoa hc thi by gi cha hiu ngha su xa ca s kin. Alloway nm 1933 thc hin th nghim ng nghim v phn lp c ph cu S1 hn hp ph cu S1 cht v ph cu R1 sng. Avery, Mac-Leod, Mac-Carthy nm 1944 phn lp c nhn t bin np v xc nh l ADN. Nhng lc by gi gii khoa hc cha chp nhn ADN l cht liu di truyn. n nm 1952 lc Hershey v Chase chng minh ADN ca Phage i vo bn trong vi khun trong khi v Protein b gi bn ngoi th ADN mi c cng nhn l nhn t bin np. S bin np c khm ph thm nhiu vi khun khc: Hemophilus, Neisseria, Streptococcus, Bacillus, Acinetobacter... Trong bin np, t bo nhn phi trng thi sinh l c bit c gi l kh np (competence) mi c kh nng tip nhn ADN ha tan ca t bo cho. Trng thi kh np xut hin trong mt giai on nht nh ca qu trnh pht trin ca t bo vo lc t bo ang tng hp vch. Sau khi xm nhp, phn t ADN si kp b mt endonuclease ct mng t bo thnh on ngn si n v i vo nguyn tng . on ADN si n kt i vi ADN ca t bo nhn on tng ng ri ti t hp; bng cch ADN bin np kt hp vo nhim sc th ca t bo nhn. Nhim sc th ti t hp l phn t ADN si kp ca t bo nhn trong mt on ngn ca mt si c thay th bng mt on ADN ca t bo cho. i vi vi khun ng rut, s tip nhn i hi s bin i b mt ca t bo bng cch x l vi CaCl2 . ngha ca s bin np: S bin np cho php kt hp vo nhim sc th vi khun ADN tng hp hoc ADN bin i invitro. Bin np cng c s dng xc nh nhng vng rt nh trn bn di truyn ca vi khun. Bin np c th xy ra trong thin nhin. Ngi ta chn lc vi khun ti t hp c lc tng lc tim 2 chng ph cu vo phc mc chut nht. Nh th s bin np c mt ngha dch t hc, tuy nhin s vn chuyn di truyn bng bin np khng hu hiu bng s vn chuyn di truyn bng plasmid. 2. Ti np (Transduction) Ti np l s vn chuyn ADN t vi khun cho n vi khun nhn nh phage. Trong ti np chung, phage c th mang bt k gen no ca vi khun cho sang vi khun nhn. Trong ti np c hiu, mt phage nht nh ch mang c mt s gen nht nh ca vi khun cho sang vi khun nhn. 2.1. S ti np chung Kiu ti np ny c Zinder v Lederberg khm ph nm 1951 lc kho st s tip hp Salmonella. Lc lai ging chng L22 v chng L2, mi chng mang mt

19

cp tnh trng t bin khc nhau th thu c vi mt t l nh mt s t bo ti t hp mang mt cp tnh trng t bin nh t bo hoang di gc, phage P22 c tm thy trong nc lc canh khun ca 2 chng vi khun trn. Phage P 22 c lc vi chng L2 nhng n ha vi chng L22. Lc cho P22 vo canh khun L2 th tt c t bo ca L2 b dung gii v phng thch phage P22 trong c mt t phage cha mt mnh ADN ca L2. Lc cho chng L22 vo dung dch phage P22 ni trn th mt s phage vn chuyn nhng gen ca L2 vo L22 v vi khun t dng nh type hoang di c pht sinh qua ti t hp. 2.2 S ti np c hiu Nm 1954 Mores nhn thy phage n ha c th thc hin mt kiu ti np khc gi l ti np c hiu. N ch vn chuyn mt nhm gii hn gen, nhm gen c chuyn nm st ch prophage gn vo nhim sc th. S ti np c hiu vn chuyn nhng gen c hiu nhim sc th v i hi s tch hp ca phage. Hn na khc vi ti np chung, phage ti np c hiu ch c phng thch lc chiu tia cc tm ch khng bao gi t tch ri khi nhim sc th. Lc chiu tia cc tm vo mt canh khun E.coli K12 Gal+ sinh tan vi phage th trong nhng phage c phng thch c khong 10 -6 d Gal. dGal l phage mang gen Gal nhng thiu mt dan ADN m n li trn nhim sc th ca vi khun. l phage khng hon chnh khng th nhn ln nu khng b sung on ADN b thiu nhng c th vn chuyn gen Gal. Lc cho dch dung gii ni trn vo canh khun E.coli K12 Gal- th thu c khang 10-6 vi khun ti np galactose dng tnh. l hin tng ti np tn s thp LFT (Low Frequency Transduction). Mt s t t bo trong canh khun E.coli K12 Gal- nhim dch LFT tr nn hai ln sinh tan vi phage bnh thng v phage dGal. Nhng t bo ny hnh thnh clon t bo hai ln sinh tan. Lc chiu tia cc tm vo nhng t bo ni trn th thu c mt dch phage trong nhng phage v phage dGal bng nhau. l s ti np tn s cao (High Frequency Transduction). ngha ca s ti np: S ti np c th cho php xc nh nhng gen rt gn nhau nhim sc th, do c s dng thit lp bn di truyn. Da vo tn s ti np hai gen cng mt lc ngi ta c th xc nh khong cch gia cc gen v nh th xc nh v tr ca chng. Trong thin nhin s ti np gi mt vai tr c ngha trong ly lan cc plasmid khng thuc vi khun gram dng nh plasmid penicillinase t cu. Ngoi ra prophage c th em li cho vi khun mt s tnh cht c bit quan trng v d prophage trc khun bch hu. 3. Tip hp (Conjugation) Tip hp l hin tng vn chuyn nhng yu t di truyn t vi khun cho (c) sang vi khun nhn (ci) khi hai vi khun tip xc vi nhau. Lederberg v Tatum ln u tin nm 1946 pht hin ra s tip hp vi khun. Hn hp hai bin chng E.coli K12 vi nhau. Chng 1 khuyt dng vi Biotin v Methionin nhng c kh nng tng hp Threonin v Leucin k hiu B-M-T+ L+. Chng 2 khuyt dng vi Threonin v Leucin nhng tng hp c Biotin v Methionin, k hiu B+M+T- L-.

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C hai bin chng ny khng mc c trong mi trng tng hp ti thiu khng cha bn cht trn nn khng to thnh khun lc. Nu trn hai bin chng trn vi nhau ri cy vo mi trng ti thiu th thy mc cc khun lc vi tn s 10-6 . iu ny cho thy hai chng lai vi khun qua trao i gen to thnh cc t bo ti t hp c kh nng tng hp bn cht: Biotin, Methionin, Threonin, Leucin, k hiu B+, M+, T+, L+. Hin tng tip hp lin quan n nhn t sinh sn F. Nhn t F l mt plasmid. T bo cha F l t bo c hay t bo F + ng vai tr t bo cho. T bo khng cha F hay l t bo ci F- dng vai tr t bo nhn. Trong th nghim tip hp trn, chng (1) ng vai tr chng cho v chng (2) ng vai tr chng nhn. T cc t bo F+, Cavalli phn lp c cc t bo Hfr (High frequency of recombination) c kh nng vn chuyn gen vi mt tn s cao. Khi lai Hfr x F - th thu c cc t bo ti t hp 1000 ln nhiu hn khi lai F+x F-. Trong cc t bo F+ nhn t F to nn mt lc c bit gi l lc tip hp. Chnh nh lc ny m xy ra s tip hp gia cc vi khun. Trong cc t bo Hfr nhn t F tch hp vo nhim sc th ca vi khun v ch c kh nng sao chp cng vi nhim sc th. t bo Hfr nhn t F cng to nn mt lc tip hp, nhng trong qu trnh tip hp v nm cui b gen, n y b gen vo t bo nhn qua cu nguyn tng ni lin hai t bo tip hp. t bo Hfr trong mt s trng hp F c th tch ri khi nhim sc th v mang theo mt on ADN ca nhim sc th v c gi l F. F c kh nng t sao chp v c th vn chuyn vo t bo nhn. F c th vn chuyn mt s tnh trng ca mt vi khun ny sang mt vi khun khc. F c s dng phn lp v vn chuyn mt s gen chn lc. Tip hp thng xy ra gia nhng vi khun cng loi nhng cng c th xy ra gia nhng vi khun khc loi nh E.coli vi Salmonella hoc Shigella nhng tn s ti t hp thp. ngha ca s tip hp: S tip hp l mt cng c kho st quan trng trong nhiu lnh vc sinh l v di truyn vi khun v n cho php to nn nhng vi khun phi hp nhiu t bin khc nhau. Nh k thut tip hp ngt qung ngi ta thit lp bn nhim sc th ca vi khun. Ngoi ra chng F c s dng nghin cu hot ng ca mt s gen. Trong thin nhin s tip hp gi mt vai tr ng k trong bin d ca vi khun c bit trong ly lan tnh khng thuc gia cc vi khun Gram m.

II. DI TRUYN V TNH KHNG THUC

Cc vi khun khng thuc c tm thy khp ni k c nhng ni cha bao gi s dng khng sinh. Ngay khi pht minh penicilin nm 1940, vi khun khng penicilin c bo co. Ngy nay vn khng thuc tr thnh mi bn tm hng u trong iu tr cc bnh nhim trng v khng sinh l mt th nghim hng ngy cc phng xt nghim vi trng. S hnh thnh tnh khng thuc vi sinh vt l do s bin i gen nhim sc th hoc do tip nhn plasmid khng thuc.

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Vi khun tr nn khng thuc qua 4 c ch: t bin, ti t hp hoc thu hoch plasmid khng thuc hoc thu hoch transposon . 1. t bin thnh khng thuc Nhiu th nghim chng minh tnh khng thuc pht sinh do t bin, nh th tnh khng thuc lin h n s bin i gen nhim sc th v c th di truyn cho cc th h sau. S t bin xy ra vi tn sut 10-5 - 10 -9 . Trong tnh khng thuc, khng sinh gi vai tr chn lc ch khng phi vai tr ch o. Vic s dng rng ri khng sinh lm pht trin nhanh chng cc vi khun khng thuc bng cch git cht cc vi khun nhy cm, to iu kin cho vi khun khng thuc pht sinh do t bin chim u th. 2. S ti t hp Lc mt t bin khng thuc xut hin mt qun th vi khun th vi khun khng thuc c th vn chuyn gen khng thuc n cc vi khun nhy cm theo mt trong 3 c ch vn chuyn di truyn: bin np, ti np v tip hp ty theo loi vi khun. S ti t hp gia 2 vi khun, mi vi khun khng mt khng sinh lm xut hin nhng vi khun khng vi c 2 loi khng sinh. Trong thin nhin, s vn chuyn gen khng thuc trong ti np v tip hp xy ra vi mt tn sut thp khong 10-5. Trong bin np tn sut cha c bit, nhng c th cn thp hn na. 3. Thu hoch plasmid khng thuc Hai c ch khng thuc trn lin quan n gen khng thuc nm trn nhim sc th. y tnh khng thuc lin h n plasmid nm ngoi nhim sc th. Plasmid khng thuc c vn chuyn theo nhng c ch khc nhau ty theo vi khun Gram dng hoc vi khun Gram m. 3.1. Plasmid khng thuc vi khun Gram m Nm 1946 ln u tin Nht Bn ngi ta phn lp nhiu chng Shigella khng vi nhiu khng sinh : streptomycin, chloramphenicol, tetracyclin, sulfonamit. Nhn t chu trch nhim v tnh khng nhiu thuc l mt plasmid khng thuc goi l nhn t R. Nhn t R in hnh l mt plasmid ln vi 2 phn, chc nng ring bit. Phn th nht RTF gi l nhn t vn chuyn khng (Resistance transfer factor), khong 80 kb cha nhng gen ca s t sao chp v ca s tip hp. Phn kia nh hn l quyt nh khng (R determinant), kch thc rt thay i v cha gen khng thuc (R genes) RTF v quyt nh khng thng thng to nn mt n v. Nhn t R thng ti t hp vi nhau lm pht sinh nhng t hp mi v khng thuc. Nhn t R khng nhng c th ly truyn rng ri trong nhiu loi vi khun ng rut m cn c th ly truyn cho nhiu vi khun khc nh vi khun t, vi khun dch hch... Nhn t R ly truyn trong vi khun qua tip xc nn tnh khng thuc lan trn trong mt qun th vi khun nhy cm nh mt bnh truyn nhim . 3.2. Plasmid khng thuc vi khun Gram dng S khng ca nhiu chng t cu vng vi penicillin, erythromycin v nhiu khng sinh cng do plasmid gy nn. Plasmid vi khun Gram dng khng th vn chuyn bng tip hp m bng ti np qua trung gian ca phage. Hin nay

22

phn ln nhng chng t cu khng penicillin bnh vin u mang plasmid penicillinase. 4.Thu hoch transposon Transposon cn gi l gen nhy l nhng on ADN, kch thc nh cha mt hay nhiu gen c 2 u tn cng l nhng chui nucleotic ging nhau nhng ngc chiu nhau (inverted repeat). c th nhy t plasmid vo nhim sc th hoc t nhim sc th vo plasmid hoc t plasmid n plasmid. Tt c mi gen trong c gen khng thuc c th nm trn transposon. Nhng transposon ch o s khng kim loi nng, s to thnh c t v kh nng s dng mt s cht chuyn ha (lactose, raffinose, histidin, hp cht lu hunh) c m t. c bit quan trng trong vi sinh hc l nhng transposon khng khng sinh nh Tn3 mang gen khng ampicillin, Tn5 mang gen khng kanamycin, Tn10 mang gen khng tetracyclin, Tn4 mang gen khng ba khng sinh ampicillin, streptomycin v sulfamit.

NH HNG CA CC NHN T NGOI CNH N S PHT TRIN CA VI SINH VT

Mc tiu hc tp 1. Trnh by c tc ng ca mt s nhn t vt l, ho hc v sinh hc ln s pht trin ca vi sinh vt. 2. Gii thch c c ch tc ng ca mt vi yu t vt l, ho hc v sinh hc ln s pht trin ca vi sinh vt. S tn ti v pht trin ca vi sinh vt chu nh hng trc tip ca cc nhn t ca mi trng xung quanh nh nhit , nh sng, ha cht, cc bc x, pH...Cc nhn t ny c th chia lm 3 nhm ln: cc nhn t vt l, cc nhn t ha hc v cc nhn t sinh hc. Hiu c nh hng ca cc nhn t ny i vi s pht trin ca vi sinh vt ng dng trong cng tc tit trng, kh trng cc dng c y t, dc phm, ty u mi trng, phng m, phng bnh nhn, nghin cu vi sinh vt... I. NHN T VT L 1. Vn ng c gii Vi sinh vt chu nh hng ca cc tn s rung ng ca mi trng, yu t ny c th c tc dng kch thch hay c ch s pht trin ca vi sinh vt v tiu dit vi sinh vt. - Khi lc canh khun vi tn s va (1-60 ln / pht ) th c tc ng tt n s pht trin ca vi khun do tng kh nng thng kh, thc y s phn bo... - Khi lc mnh th li c ch s pht trin ca vi khun, nu lc ko di th c th tiu dit cc vi sinh vt.

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Vn ng c gii thng c ng dng khi nui cy vi sinh vt lm tng sinh khi hoc thu nhn s lng ln sn phm do vi khun bi tit ra... 2. Lm mt nc Nc cn thit cho hot ng sng ca vi sinh vt, lm mt nc th vi sinh vt s cht. Tc cht ty thuc vo mi trng vi khun sng. - Huyn dch vi khun trong nc nu em lm kh th vi khun cht rt nhanh. - Huyn dch vi khun trong th keo khi lm kh vi khun cht chm hn. - Huyn dch vi khun nu lm ng bng nhanh trc ri mi tin hnh lm mt nc th vi khun cht rt t. Phng php ny c p dng lm ng kh vi khun nhm bo qun vi khun trong thi gian di. Trng thi nha bo l trng thi mt nc t nhin ca vi khun. Nha bo chu c kh hanh lu di. 3. Hp ph Than hat, gel albumin, mng lc s... c kh nng hp ph vi khun v s hp ph ny lm thay i kh nng sng ca vi khun. c p dng lm v khun cc sn phm ca huyt thanh, cc sn phm khng chu nhit...

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4. pH pH ca mi trng c nh hng n hat ng sng ca vi khun do lm thay i s cn bng v trao i cht gia mi trng v vi khun c th git cht vi khun. Mi loi vi khun ch thch hp vi mt gii hn pH nht nh (t 5,5 n 8,5), a s l pH trung tnh (pH=7), bi v pH ni bo ca t bo sng l trung tnh. mi trng kim, Pseudomonas v Vibrio pht trin tt, c tnh ny rt hu ch phn lp chng. Trong khi Lactobacillus pht trin tt hn pH=6 hoc thp hn. Trong qu trnh iu ch cc mi trng nui cy phi m bo pH thch hp th vi khun mi pht trin tt. Trong tit khun hoc kh khun ngi ta c th s dng cc ha cht c pH rt axit hoc rt kim loi tr vi khun. 5. p sut 5.1. p sut thy tnh (p sut c gii) Vi khun c kh nng chu c p sut cao ca khng kh, thng t 20005000 atm i vi virus, phage; t 5000-6000 atm i vi cc vi khun khng c nha bo; t 17000-20000 atm i vi cc vi khun c nha bo. C ch tc ng ca p sut c gii i vi vi khun cha c r. 5.2. p sut thm thu p sut thm thu ca mi trng xung quanh c tc ng mnh n t bo vi khun do tnh thm thu ca mng nguyn tng. a s cc vi khun pht trin thch hp khi mi trng c p sut thm thu bng 7 atm (dung dch NaCl 0,9%). - Trong dung dch nhc trng, do p sut thm thu bn trong t bo cao hn mi trng nn nc b ht vo t bo vi khun lm t bo phnh to ln v v. - Trong dung dch u trng, p sut thm thu mi trng cao nn nc b ht ra mi trng lm t bo b teo li. 6. Nhit Nhit l yu t nh hng rt ln n s pht trin ca vi khun. Mi loi vi sinh vt pht trin trong mt gii hn nhit nht nh, da vo khong nhit pht trin ti u, vi khun c th c chia lm 3 nhm: nhm a m c nhit ti u gia 20oC-45oC, nhm a lnh c nhit ti u di 20oC v nhm a nng c nhit ti u trn 45oC. nhit qu thp vi khun khng pht trin c nhng c th cn sng; cn nhit cao hoc rt cao th vi khun b tiu dit. - Nhit thp: nhit thp cc phn ng chuyn ha ca vi khun b gim i, c th b ngng li. Mt s vi sinh vt b cht nhng a s vn sng trong thi gian di. Lc lm ng bng vi sinh vt th mt s b cht, nhng nu lm ng bng rt nhanh th s vi sinh vt sng st nhiu hn. Ngi ta s dng c im ny bo qun cc chng vi khun nhit thp. - Nhit cao: Nhit cao c kh nng git cht vi khun. Sc khng ca vi khun vi nhit cao ty tng chng loi v ty theo trng thi sinh trng hay trng thi nha bo. a s cc vi khun trng thi sinh trng nhit 56-60oC trong 30 pht l cht v 1000C th cht ngay. Th nha bo chu c nhit cao hn v lu hn 1210C trong 15-30 pht ni hp mi cht hoc 1700C trong 30 pht - 1 gi nhit kh mi b tiu dit. - C ch tc dng ca nhit cao i vi vi khun: + Protein b ng c

25

+ Enzyme b ph hy + Tn thng mng nguyn tng lm thay i tnh thm thu. + Ph hy cn bng l - ha trong t bo do tng tc phn ng sinh vt ha hc. + Gii phng axit nucleic 7. Bc x - nh sng mt tri: nh sng mt tri do c tia cc tm c bc sng t 200300 nm, nht l 253,7nm, c tc dng st khun. - Tia Rnghen: c hiu ng dit khun v gy t bin i vi vi sinh vt - Nguyn t phng x: to ra cc bc x , v trong tia , c tc dng dit khun hay c ch vi khun pht trin. Cn tia t c tc dng. C ch tc dng ca bc x: Do nguyn tng ca vi khun c thnh phn cu to bng cc phn t rt phc tp, cc phn t ny c kh nng hp th mt cch chn lc nhng tia bc x c bc sng khc nhau. Th d nh axit nucleic ca vi khun c kh nng hp th tia bc x di 253,7nm, lc qu trnh sao chp ca DNA b bin i hoc b c ch hoc DNA b ph hy khng thun nghch lm vi khun cht. 8. Siu m Khi nhng tn s ca chn ng vt qu 20.000 ln/1 pht th gi l siu m (do tai ta khng nghe c na). Siu m c kh nng git cht vi khun do nhng chn ng c tn s cao pht sinh ra p sut co gin cao lm cho t bo vi khun b x tan; cng c th nc trong t bo vi khun di tc dng ca siu m pht sinh ra H2O2 c tc dng git cht vi khun; siu m cng c th ph hy h thng keo lm cho cht keo ng li. 9. Tia laser Tia laser do nng lng cao v tp trung nn trong mt thi gian cc k ngn c th lm cho vt cht nng chy v bay hi, c th tng nhit , p sut ti ch ln rt cao nn cng c tc dng git cht vi khun. II. CC NHN T HA HC Cc ha cht trong mi trng c nh hng hoc kch thch hoc c ch s pht trin ca vi khun. Cc ha cht c tc dng kch thch s pht trin vi khun c ng dng trong nui cy vi khun... Cc ha cht c tc dng c ch hoc tiu dit vi khun c s dng lm cht ty u, cht kh khun hoc st khun ty theo mc ch s dng v nng s dng. 1. Cht ty u, cht kh khun - Cht ty u l nhng ha cht c kh nng git cht cc vi khun gy bnh v vi sinh vt khc, cn i vi nha bo th tc dng git khun mt phn. Cht ty u s dng trn b mt cc dng, cc dng c y t, cc cht thi ca bnh vin... - Cht kh khun l nhng ha cht c tc dng ngn cn s pht trin ca vi khun, cht ny ch c tc dng git cht vi khun mt phn nhng c tc dng c ch vi khun rt mnh. Cht kh khun c th dng v khun vt m, ni tim chch...Thc ra cht ty u v kh khun ch khc nhau v nng khi s dng. V

26

d: phnol nng 2-5% th dng ty u, cn khi nng thp hn 100 -1000 ln th dng lm cht kh khun. - Ch s phenol l t l gia nng ti thiu ca cht ty u c tc dng dit khun v nng ti thiu ca phenol khi s dng i vi mt chng vi khun nht nh. Ch s ny c dng lm n v nh gi tc dng dit khun ca mt ha cht. 2. Cc nhn t ha hc nh hng n s pht trin ca vi khun 2.1. Axit v baz Axit v baz c kh nng phn li thnh ion H+ v OH- rt mnh, lm cho pH ca mi trng thay i v c tc dng dit khun hoc c ch s pht trin ca vi khun. 2.2. Cc mui kim loi Khi ha tan vo trong nc th mui ca nhiu kim loi nng c kh nng phn li thnh ion v c tac dng dit khun, kh nng dit khun ca cc mui kim loi nng c th do s kt hp ca cc ion kim loi vi nhng nhm -SH ca protein t bo. Hot tnh dit khun theo th t Hg, Ag, Cu, Zn. V d : - Mui thy ngn: c dng nhiu nht ty u nh sublim (HgCl2),... - Mui bc: c tc dng st khun nh nitrat bc (dung dch argyrol). - Mui ng: sunpht ng dng cha bnh nm ngoi da. - Mui vng: c dng iu tr cc bnh do vi khun khng cn- axit di dng mui thiosunpht. 2.3. Nhm Halogen Tc dng dit khun do phn ng oxy ho v halogen ho cc cht hu c. Phn ng oxy ho xy ra nhanh v khng thun nghch, cn halogen ho th chm hn v khng mnh bng. Nhng phn ng ny xy ra vi nhiu cht hu c khc nhau, do s lm gim hot tnh dit khun trong nhng dung dch c nhiu cht bn hu c hay cc cht oxy ho v halogen ho khc, nht l amoniac. + It: Cn it (7% I, 3% KI...) thng c s dng st trng da, c ch s phenol cao. + Clo: thng c dng dng kh nguyn cht v dng hp cht hu c hay v c. Clo dng kh khun nc sinh hot, nc b bi. Cl2 + H2O 2HClO HCl + HClO 2HCl + O2

(HClO c hot tnh gii phng oxy, nhng khng dit c cc vi khun lao v virus ng rut). Chlorua vi thng c s dng nht kh trng cht nn, cht thi v dng c th hoc rc h x. Chloramin tinh khit 1% trong nc c kh nng kh trng bn tay bng cch ngm 5 pht trong dung dch ny v c th kh khun dng c bng cch ngm 20 pht. 2.4. Phenol L mt cht ty u tt c s dng t rt sm. Tuy nhin phenol c vi da, nim mc v gy c thn kinh.

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- Nng : khong 1% c th git cht vi khun trng thi sinh trng - Nng 5% c th git cht vi khun trng thi nha bo. 2.5. Cn Ru ethylic c tc dng st trng da. Tc dng dit khun ty theo nng , cao nht l dung dch ethanol 70% v nng thp hn th tc dng dit khun gim. Cn tuyt i th tc dng dit khun km. Ngoi dung dch ethanol, dung dch isopropanol 70% cng thng c s dng. 2.6. Andehyt (cc tc nhn ankyl ha) Rt c i vi t bo vi khun. Formol l cht dit khun mnh nht ca nhm ny, n c s dng ph hu hiu lc ca c t hoc ca virus m khng ph hu kh nng sinh khng, c th s dng ty u cc phng bnh, qun o, chn mn... 2.7. Cc cht oxy ho khc v cc thuc nhum: H2O2, KMnO4, thuc nhum thng pha thnh dung dch lng dng lm cht st khun. Thuc nhum thng c dng c ch s pht trin ca tp khun trong cc mi trng chn lc. 2.8. Cc tc nhn c hot tnh b mt Nhng hp cht ny c gi l thuc ty tng hp. Dit khun mnh m nht l nhng thuc ty cation trong hiu qu hn c l nhng hp cht amonium bc 4 nh benzalkonium chlorua. Nhng hp cht ny c s dng rng ri kh khun. Chng tc ng bng cch lm tan mng t bo vi khun do ha tan mng lipit che ch vi khun v lm bin th protein. 3. C ch tc ng ca cc ha cht i vi t bo vi khun. - Ph hy mng t bo: do ion ha, thay i sc cng b mt, lm tan mng lipit che ch vi khun... - Bin i chc nng ca protein v cc axit nucleic... - Tc ng ha hc lm gii phng oxy phn t, clo... c tc dng git cht vi khun. 4. Cc yu t nh hng n tc dng ca cc cht ty u v st khun. - Nng ca ha cht: nng cng cao th tc dng cng mnh. - Thi gian tip xc: tip xc cng lu th tc dng cng mnh. - Nhit - Thnh phn ca mi trng xung quanh: do cc cht hu c c tc dng bo v vi khun hoc tc dng vi ha cht lm gim hiu lc. - Mt vi sinh vt ti ni kh trng - Kh nng khng ca vi sinh vt (virus c lp v lipit s nhy cm vi cht ho tan lipit nh cn, phenol hn l nhng virus khng c v). III. NHN T SINH VT Trong qu trnh tn ti ca vi sinh vt nu chng phi sng trong iu kin c vi sinh vt khc th chng c th b cnh tranh sinh tn, b tiu dit hoc song song tn ti.

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1. Cht i khng (Bacterioxin) Nhiu loi vi khun khi pht trin th tng hp cc cht i khng c tc dng c ch cc vi khun cng loi hoc cc loi ln cn. V d : Colixin ca E.coli, Staphylococxin ca T cu...Chng c bn cht protein hoc phc hp gluxit-lipitprotein, c tc ng c hiu vi cc vi khun nhy cm. 2. Phage L virus ca vi khun, phage xm nhp cc vi khun c hiu, nhn ln v ph v t bo vi khun. Phage cng c th cng tn ti v nhn ln vi vi khun trng thi n ha.

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3. Interferon L cht do t bo sn sinh ra khi b virus xm nhp, c bn cht glycoprotein, c tc dng c ch s nhn ln ca virus. 4. Cht kch thch Mt s vi khun khi pht trin sn sinh ra mt cht lm thun li cho vi khun khc pht trin. V d nh Hemophilus mc tt xung quanh khun lc T cu (do T cu sinh ra yu t V cn thit cho Hemophilus pht trin) ...

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TIT TRNG - KH TRNG V KHNG SINH

Mc tiu hc tp 1. Nu c cc phng php tit trng v kh trng trong phng th nghim. 2. Trnh by c nh ngha khng sinh, cc c ch tc dng ca khng sinh. 3. K c cc nhm thuc khng sinh v hiu qu ca chng vi cc nhm vi khun chnh. 4. M t c cc c ch khng ca vi khun vi khng sinh, ngun gc ca s khng, cch theo di s khng v mc ch ca phi hp khng sinh trong iu tr bnh nhim trng

I. TIT TRNG V KH TRNG

1. Tit trng Tit trng l s lai b tt c vi sinh vt sng (gm th dinh dng v nha bo ca chng) bng nhit , bng tia bc x, bng cc ha cht hoc bng cc bin php c hc. Tit trng l cng vic cn thit trong y hc nhm git cht cc vi sinh vt sinh bnh khi dng c y t, sinh vt phm, dc phm... Trong phng th nghim vi sinh vt, tit trng l bin php khng th thiu c cho vic phn lp, nui cy v lu gi cc vi khun thun khit. Ngi ta dng nhiu phng php tit trng khc nhau trong phng th nghim vi sinh hc. - Cc phng php tit trng bng dng nhit nh t nng trn ngn la ,dng l sy kh 160-1700C, dng nhit m trong ni p sut, hoc chng cch thy ngt qung kiu Tyndal . - Tit trng bng cc tia bc x: cc tia bc x cc tm , tia gamma, tia beta c tc dng git cht vi sinh vt, c dng tit trng dng c, ch phm sinh hc... - Tit trng bng c hc dng cc my lc, vi khun s b gi li pha trn my lc. Phng php ny dng tit trng cc mi trng nui cy vi khun. 2. Kh trng (hay kh khun) Thut ng ny dng cho cc tc nhn vt l, v thng l ha hc c kh nng git cht vi sinh vt sng trn cc dng, dng c th nghim, phng th nghim, phng bnh ... Tc nhn vt l nh tia cc tm c dng kh trng phng m, phng nui cy vi khun . Nhiu ha cht c bit c dng cho mc ch kh trng phng lm vic, phng th nghim, kh trng cc dng, dng c th nghim nh x phng, phenol , cc hp cht halogen, cc mui kim loi, cn... Thut ng st khun (antiseptic) c s dng cho cc ha cht dng git cht vi sinh vt trn b mt ca c th con ngi hoc ng vt m khng lm tn thng t chc ca c th. Cc ha cht ny t c vi c th v thng nng thp. Nh vy mt ha cht c th s dng lm dung dch kh khun hoc s dng st khun ph thuc vo mc ch s dng v nng cht s dng v d phenol khi nng 2-5% c dng nh cht kh trng, cn khi nng thp hn 100 n 1000 ln c dng lm cht st khun .

II. CC CHT KHNG SINH

1. nh ngha

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Thut ng khng sinh theo nh ngha ban u l nhng tc nhn khng khun c ngun gc t vi sinh vt, chng c tc dng chng vi khun hu hiu nng rt thp. Lc u cc khng sinh u chit t mi trng nui cy nm mc hoc vi khun, sau nhiu khng sinh c bn tng hp bng cch bin i cu trc phn t ca khng sinh thu c khng sinh mi. Hin nay khng sinh c xem nh l nhng hp cht ha hc c tc dng cn khun hoc dit khun vi c ch tc ng mc phn t, hu hiu liu lng thp v c th s dng iu tr bnh nhim trng. Cc khng sinh c tc dng c hiu i vi mt loi vi khun hoc mt nhm vi khun nht nh. Cc khng sinh c hot tnh khc nhau, c loi c ph khng khun rng, c loi c ph khng khun hp. 2. C ch tc dng ca khng sinh 2.1. c ch tng hp vch t bo Khc vi t bo ng vt, vi khun c vch t bo. Loi b vch hoc ngn cn s to thnh vch u lm tan t bo vi khun. Vch t bo vi khun cha mucopeptit cn gi l murein hay peptidoglycan. Cc penicilline v cephalosporin tc ng ln cc phn t protein chn lc c hiu nn c ch s lin kt ngang cui cng ca cu trc mucopeptit ca vch t bo, vi khun d dng b tan. Cc khng sinh khc nh bacitracin, vancomycin, novobiocin, D-cycloserin cng c ch s to vch ca vi khun bng c ch s hnh thnh mucopeptit ca vch . 2.2. c ch chc nng ca mng nguyn tng Mng nguyn tng hot ng nh mt mng bn thm. Mng ny thm thu cc cht chn lc v nh vy kim sot c cc thnh phn bn trong ca cc t bo. Nu s ton vn ca mng nguyn tng b ph v th cc thnh phn ni bo thot ra khi t bo v t bo cht. Mng t bo ca mt s vi khun v nm d b ph v bi mt s thuc khng sinh hn t bo ng vt do hot tnh tc dng chn lc ca cc khng sinh ny ln cc nhm cu trc ha hc c bit c mng ca vi khun hoc ca nm m khng c t bo ng vt. Polymycin c tc ng mng nguyn tng ca vi khun gram m, polyen c tc ng mng nguyn tng ca nm. 2.3. c ch tng hp protein Nhiu thuc khng sinh c ch tng hp protein ca vi khun: 2.3.1.Chloramphenicol: chloramphenicol v cc dn cht thuc nhm ny ngn cn s kt hp axit amin vo chui peptit mi sinh n v 50S ca ribosome vi khun qua vic cn tr tc ng ca enzyme peptidyl-transferaza. 2.3.2. Cc tetracyclin: tetracyclin v cc thuc khng sinh nhm ny c ch s tng hp protein ca vi khun bng cch ngn cn s gn lin ca amino acyl-RNA vn chuyn vo n v 30S ca ribosome . 2.3.3. Cc macrolid v lincomycin: Cc khng sinh nhm ny ngn cn s tng hp protein bng cnh tranh v tr kt hp ca axit amin ribosome v bng cch phong b phn ng dy chuyn aminoacyl. 2.3.4. Cc aminoglycoside: cc thuc khng sinh nhm aminoglycoside c ch tng hp protein bng cch gn vo protein tip nhn trn n v 30S ca ribosome lm c sai thng tin ca ARN thng tin lm hnh thnh cc protein khng c hat tnh, ngoi ra cn lm tch cc ribosome trng thi polymer thnh monomer 2. 4. Tc dng c ch s hnh thnh acid nucleic 2.4.1. Cc sulfonamid v trimethoprim: i vi nhiu vi sinh vt, axit paraaminobenzoic (vit tt l PABA) l mt cht chuyn ha cn thit trong qu trnh tng hp axit folic cn thit tng hp purin v ADN. Sulfonamid do c cu trc tng

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t nh PABA nn c th i vo phn ng thay cho PABA, hu qu l mt cht tng t nh axit folic nhng khng c hat tnh c to thnh v ngn cn s pht trin ca vi khun. Trimethoprim c ch enzyme dihydro folic reductase, enzyme ny bin i axit dihydro folic thnh axit tetrahydro folic, mt giai an trong chui phn ng tng hp purin v DNA. S phi hp mt trong cc sulfonamid vi trimethoprim, hai cht tc ng hai khu khc nhau ca mt qu trnh tng hp lm tng r hat tnh ca thuc, cotrimoxazol (sulfamethoxazol v trimethoprim) l ch phm phi hp s dng hiu qu trong iu tr cc bnh nhim trng 2.4.2. Rifampin: Rifampin v cc dn cht kt hp vi ARN polymerase ph thuc ADN v nh th c ch s tng hp ARN vi khun. 2.4.3.Cc quinolone: Cc quinolon v cacboxy fluoroquinolon kt hp vo ADN gyrase nn c ch tng hp ADN. 3. Cc nhm thuc khng sinh 3.1. Sulfonamid L nhng hp cht thay th nhm amit (SO2NH2) hoc nhm amin (NH2) ca axit sulfanilamic. Sulfonamid c tc dng cn khun i vi vi khun gram m v vi khun gram dng. Chng c ch nhiu vi khun gram dng v vi khun ng rut bao gm E.coli, Klebsiella v Proteus. Cc sulfonamid c s dng rng ri nh sulfaguanidin, sulfadiazim, sulfisoxazol, sulfamethoxazol, sulfadimethoxin.... Tr ngi chnh ca cc thuc nhm sulfamid l vi khun tr nn khng vi thuc nhanh chng, thm vo nhiu sulfamid c th gy phn ng ph nghim trng. Nn hin nay cc thuc nhm sulfamid ch c dng hn ch. Ch phm sulfamid ang c dng rng ri hin nay l cotrimoxazol l phi hp ca sulfamethoxazol v trimethoprim. Thuc ny c dng trong iu tr cc nhim trng ng tiu ha, h hp v tit niu. Dng phi hp khc l fansidar bao gm sulfadoxin v pyrimethamin c hiu qu trong iu tr st rt, t hiu qu i vi bnh nhim trng . 3. 2. Cc beta- lactamin Cc thuc ny trong cng thc ha hc c cha vng beta-lactam bao gm cc penicillin v cc cephalosporin. 3.2.1 Cc penicillin Cc penicillin c nhn chung l axit 6 amino-penicillanic hp bi mt vng thiazolidin v mt vng -lactam cc penicillin ny khc vi penicillin khc ch gc R gn vo nhn chung. Cc penicillin dng trong iu tr thuc 3 nhm chnh : - Cc penicillin c hot tnh cao i vi vi khun gram dng, b ph hy bi enzyme penicillinase: penicillin G, penicillin V (phenoxy methylpenicillin), benzathin penicillin. - Cc penicillin c hot tnh i vi vi khun gram dng, khng i vi enzyme penicillinase: methicillin, nafcillin, oxacillin, dicloxacillin . - Cc penicillin c hot tnh rng i vi c vi khun gram dung v vi khun gram m, b ph hy bi enzyme penicillinase. Cc penicillin nhm ny bao gm: + Cc aminopenicillin: ampicillin, amoxicillin, becampicillin, metampicillin. + Cc carboxy penicillin: carbenicillin, ticarcillin. + Cc ureidopenicillin: azlocillin, mezlocillin, piperacillin.

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Ngoi 3 nhm chnh trn hin nay ngi ta cn c cc penicillin phi hp trong ngi ta kt hp cc penicillin khc nhau vi nhng cht c ch enzyme lactamase dng iu tr cc nhim trng do vi khun khng sn xut enzyme lactamase. Hai cht c ch enzyme ny c dng phi hp vi cc penicillin l axit clavulanic v sulbactam: cc thuc ca s kt hp ny nh: timentin gm ticarcillin v axit lavulanic, augmentin (amoxicillin v a.clavulanic), unasyn (ampicillin & sulbactam).

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3.2.2 Cc cephalosporin Cc cephalosporin c mt nhn chung l axit faminocephalo-sporanic hnh thnh bi mt vng lactam kt hp vi mt vng dihydrotiazin thay th hydro cu nhm amin bng cc gc R khc nhau th thu c cc cephalosporin bn tng hp . Cc cephaloporin c hot tnh vi c vi khun gram dng v vi c vi khun gram m . Da vo tnh khng khun cc cephalosporin c chia cc th h: - Cc cephalosporin th h th nht: Bao gm cephalothin, cephazolin, cephalein, cefaclor. Cc thuc ny c hot tnh i vi t cu lin cu A, ph cu, E. coli, Klebsiella, Proteus.. - Cephalosporin th h th hai: Cc thuc nhm ny c hot tnh tt hn cc thuc cephalosporin th h th nht chng li E. coli, Klebsiella, Proteus, Citrobacter, Enterobacter, H.influenzae, N.gonorrhoe, N. meningitidis. Cc thuc nhm ny gm: cefamandol, cefuroxime, cefonicid, cefoxitin... - Cephalosporin th h th ba: C ph tc dng khng khun bao trm ton b vi khun ng tiu ha, tuy nhin c tc dng km vi vi khun gram dng, thuc nhm ny c th chia 02 nhm, nhm c tc dng chng Pseudononas aeruginosa gm ceftazidime v cefoperazone, v cc nhm khng c tc dng chng P. aeruginosa bao gm cefotaxim, ceftazidime, ceftizoxime, moxalactam. Nhiu thuc nhm ny thm vo mng no tt nn c dng iu tr vim mng no do vi khun gram m. 3.2.3. Monobactam v Carbapenem: Hai nhm thuc ny khc vi cc beta-lactam v cu to ha hc nhng c ch tc dng l c ch tng hp vch tng t nh cch tc dng ca cc beta lactam, aztreonam l thuc thuc nhm monobactam c sn hin nay, ph khng khun gii hn trn vi khun gram m tng t nh cc aminoglycoside. Imipenem l khng sinh carbapenem c sn hin nay, ph khng khun ca thuc ny c xem l rng nht trong cc thuc khng sinh hin nay bao trm ln cc vi khun gram dng gm c lin cu D, c tc dng chng li hu ht cc vi khun gram m k c P.aeruginosa, v c tc dng chng li vi khun k kh. 3.3. Cc khng sinh aminoglycoside Gm streptomycin, neomycin, gentamycin, tobramycin, amikacin, kanamycin Cc khng sinh nhm ny c tc dng dit khun bao gm c vi khun gram dng v nhiu vi khun gram m. gentamycin, tobramycin, neomycin c tc dng chng P.aeruginosa, tri li streptomycin c tc dng vi vi khun lao nn l thuc dnh ring iu tr lao. 3. 4. Cc thuc tetracyclin C cng thc ha hc tng t nhau. Cc thuc khc nhau ch cc gc R khc nhau. Cc thuc ny bao gm tetracyclin, chlotetracyclin, oxytetracyclin, doxycyclin, minocyclin, thuc nhm ny c tc dng cn khun vi vi khun gram dng v gram m, cc tetracyclin c hiu qu vi Rickettsia, Chlamydia, Mycoplasma pneumoniae v Leptospira. 3. 5. Chloramphenicol Lc u chit xut t Streptomyces venezuelae nhng hin nay c tng hp. Thuc ny c tc dng cn khun v ph khng khun rng. N c hiu qu trong bnh thng hn v cc nhim trng do Rickettsia. 3. 6. Macrolit v cc thuc tng t

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Cc thuc khng sinh macrolit gm erythromycin, oleandomycin, spiramycin. Cc khng sinh thuc nhm ny c tc dng cn khun, chng tc dng tt trn vi khun gram dng, mt s vi khun gram m nh phy khun t. Erythromycin l thuc an ton nn c dng lm thuc thay th penicillin trong cc nhim trng do vi khun gram dng bnh nhn d ng vi penicillin. Lincomycin v clindamycin c c ch tc dng v hat ph tng t nh erythromycin. 3.7. Polypeptid Khng sinh nhm polypeptit ch yu l polymycin, ph tc dng ch yu dit khun vi vi khun gram m k c Pseudomonas. Polymycin c vi thn kinh v thn, hin nay t c dng ng ton thn iu tr cc nhim trng gram m. Cac thuc c polymycin thng c dng iu tr nhim trng ti ch. 3.8. Rifamycin L khng sinh chit sut t Streptomyces mediterranei, cht dn xut bn tng hp l rifampin, hai thuc ny c hat ph i vi mt s vi khun gram m v gram dng, vi khun ng rut, vi khun khng acid cn. Rifamycin do vy l thuc s dng ch yu iu tr bnh lao hin nay. 3.9. Cc quinolon v cacboxy - fluoroquinolon Hp cht quinolon tng hp u tin l axit nalidixic ch yu dng iu tr nhim trng ng tit niu. Cc cacboxy-fluoroquinolon l cc dn cht t axit nalidixic, cc thuc ny c tc dng dit khun i nhiu vi khun gram dng v vi khun gram m k c t cu khng vi methicillin v P.aeruginosa, chng cn cn c tc dng chng Mycoplasma v Chlamydia. Cc fluoroquinolon c s dng trong nhiu nhim trng cc c quan. Mt s fluoroquinolon thng dng hin nay gm ciprofloxacin, enoxacin, norfloxacin, pefloxacin. 4. S khng ca vi khun vi thuc khng sinh 4.1. C ch khng thuc khng sinh ca vi khun Nhiu c ch khng thuc khng sinh ca vi khun c kho st. nhng chng vi khun khc nhau, s khng vi mt lai khng sinh c th do mt hc nhiu c ch khc nhau. 4.1.1.Tng s ph hy thuc do enzyme y l c ch khng thng thng qua trung gian ca plasmid. V d in hnh l enzyme beta lactamase gy nn s khng vi cc khng sinh beta lactamin. Cc vi khun sn xut enzyme penicillinase th khng vi cc penicillin, cc vi khun to c enzyme cephalosporinase th khng vi cc cephalosporin, cc aminoglycoside b bt hat bi cc enzyme phosphorylase, adenylase, acetylase. Chloramphenizol b bt hat bi acetylase. 4.1.2. S bin i receptor ca thuc y l c ch quan trng. S bin i protein c hiu vi thuc ribosome lm vi khun tr nn khng i vi thuc khng sinh nh s khng vi cc thuc nhm aminoglycoside, erythromycin, khng vi rifampin trn c s thay i mt amino axit trn tiu n v beta ca enzyme ARN polymerarase ph thuc ADN lm thay i s gn vo enzyme ny ca rifampin. S khng ca sulfonamid v trimethoprim cng tng t do s bin i ca phn t enzyme nn sulfamid khng c nhn vo phn ng tng hp acid folic. 4.1.3.Gim tnh thm mng nguyn tng Tnh cht ny do s mt hoc thay i h thng vn chuyn mng nguyn tng. S khng ny gp cc khng sinh nh cc beta lactamin, chloramphenicol, quinolon, tetracyclin v trimethoprim. Ngoi ra ro cn thm thu bnh thng ca mng nguyn tng cng chu trch nhim cho s khng t nhin ca nhiu thuc.

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4.1.4.Tng s to thnh mt enzyme C ch ny c th lin quan n s sn xut gia tng s lng enzyme c ch nh c thy mt s vi khun mang plasmid khng thuc hoc lin h n s to thnh mt enzyme mi c i lc mnh hn vi mt c cht khc so vi thuc nh trong trng hp khng vi sulfonamid.

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4.2. Ngun gc ca tnh khng thuc Khng thuc khng sinh vi khun ch yu do s hnh thnh nhng gen khng thuc nhim sc th hoc plasmid tuy nhin mt vi trng thi sinh l c bit vi khun tr thnh khng vi thuc khng sinh. Cc vi khun trng thi ng ngha l khng nhn ln c th khng chu tc ng ca thuc nh vi khun lao. hnh thc mt vch ca mt s t bo vi khun (dng L) s khng b nh hng bi cc thuc c ch to thnh vch nh penicillin sau thi gian dng thuc cc vi khun ny c th ly li cu trc nguyn vn. 4.2.1. Khng thuc do t bin nhim sc th Mt qun th vi khun c th cha nhng bin chng t nhy cm hn vi mt th thuc. S hin din ca thuc khng sinh nh th ch chn lc cho php cc chng t nhy cm hn sng st. Nh vy vai tr ca thuc ch nh mt yu t chn lc ch khng c vai tr gy nn s t bin khng thuc. Mt khi c s hin din ca bin chng vi khun khng thuc th bin chng ny c th truyn tnh khng thuc ny n nhng vi khun khc bng nhiu c ch khc nhau: Chuyn th, chuyn np, giao phi. 4.2.2.Khng thuc qua plasmid Plasmid l mt phn t ADN t sao chp nh hin din trong nguyn tng nhiu vi khun. Phn t ADN nh ny thng mang cc gen khng thuc (resistance) nn gi l R plasmid. Cc plasmid ca vi khun thng cn mang trn n cc gen cho php chng gn vo b mt nim mc, to ra c t, v xm nhp, cc plasmid khng thuc ny c th truyn cho nhau gia cc vi khun lm lan nhanh s khng. 4.2.3.Cc c ch lm lan truyn tnh khng thuc Nh nu trn mt khi xut hin bin chng mang gen khng thuc nhim sc th hoc plasmid, cc bin chng ny c th lan truyn nhanh tnh khng cho vi khun khc bng 3 c ch trao i vt liu di truyn sau : - Bin np. - Ti np do bacteriophage. - Tip hp. Cc phng tin lm ly lan nhanh tnh khng thuc: - Plasmid: thm vo cc gen khng thuc, trn cc plasmid cn mang cc gen thc y s trao i gen gia cc vi khun. - Do transposon: y l nhng gen c kh nng di chuyn. Cc transposon c mang nhng gen khng khng sinh c th nhy t plasmid ny n mt plasmid khc hoc t plasmid qua nhim sc th. Mt s transposon khng thuc tm thy vi khun Gram m cn mang gen thc y s ly truyn. - Do cc integron y l vector c th mang gen khng khng sinh, integron c th chn vo cc v tr nht nh trn nhim sc th 4.2.4.Xc nh nhy cm ca vi khun vi khng sinh Hin nay nhiu vi khun khng vi khng sinh gy nn nhiu v dch nhim trng nng, iu ny dn n nhu cu cn c nhng chng trnh theo di tnh khng thuc ca vi khun trn phm vi quc gia v quc t. Kho st v dch t hc tnh khng thuc ca vi khun gip cho cc thy thuc lm sng chn thuc khng sinh thch hp iu tr bnh nhim trng. Xc nh nhy cm ca vi khun vi thuc khng sinh bng nhng phng php phng th nghim tin cy v thng nht c cc d kin c th so snh c. Th nghim nhy cm ca vi khun trong phng th nghim, cn gi l khng sinh , c th c thc hin bng phng php ha long hoc bng phng php khuch tn trn mi trng c. Khi thc hin khng sinh vi khun cn phi c nui cy thun khit, a s vi

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khun gy bnh ngi khi phn lp cn 16-18 gi mi pht trin, nu bnh phm ch thun mt lai vi khun th cn thm 16-18 gi na lm khng sinh , nh vy kt qu khng sinh sm nht cng mt 36 - 48 gi, trong trng hp bnh phm nhiu vi khun, hoc nhiu vi khun pht trin chm cn thi gian lu hn. i vi mt s vi khun m tnh khng sinh n nh v r rng th khng cn thit phi lm khng sinh nh vi khun bch hu, lin cu A tan mu . Tnh cht khng khng sinh ca vi khun c tnh cht dch t, do vy kt qu khng sinh ca cc vi khun gy bnh c th khc nhau gia bnh vin ny v bnh vin khc v nhng vng khc nhau, ngay c trong cng mt bnh vin nhy cm ca vi khun cng thay i hng ngy. V vy cc phng th nghim vi khun bnh vin cn lm khng sinh chn khng sinh thch hp trong iu tr bnh nhim trng . 4.2.5. Phi hp khng sinh Phi hp khng sinh iu tr bnh nhim trng nhm mt s mc tiu sau : - Gim kh nng xut hin chng vi khun khng. i vi vi khun khng do t bin th phi phi hp khng sinh lm gim tn sut t bin kp, v d t bin ca vi khun lao khng streptomycin l 10-7, t bin khng rifamycin l 10-9 th xc xut t bin khng c vi c hai th thuc trn l 10 -7x10-9 = 10-16. y chnh l l do phi phi hp khng sinh iu tr lao. - iu tr cc nhim khun hn hp : Mt lai khng sinh c ph tc ng trn mt nhm vi khun nht nh. Trong cc nhim khun do nhiu lai vi khun th phm nh vim phi, vim phc mc... thng do c vi khun i kh v vi khun k kh. Phi hp khng sinh th s dit dc c hai lai vi khun ny. - tng kh nng dit khun: V d phi hp sulfamethoxazol v trimethoprim lm tng kh nng dit khun i vi nhiu vi khun so vi khi dng n c mt trong hai thuc trn. Mc ch ny c dng trong trng hp iu tr cc nhim trng do Pseudomonas aeruginosa thng ngi ta phi hp carbenicllin v gentamicin...

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I CNG VIRUS
Mc tiu hc tp 1. Trnh by c nhng c im , kch thc, hnh th v cu trc ca virus. 2. Trnh by c s nhn ln ca virus v hu qu ca s nhn ln ca virus trong t bo. 3. Trnh by c cc hnh thi nhim virus v cc phng php nui cy virus.

I. S LC LCH S PHT HIN VIRUS

Nm 1796 E.Jenner cho chng u phng bnh u ma. L.Pasteur d tm ra vaccine chng bnh di vo nm 1885, nhng cha chng minh c tc nhn gy bnh v chng khng trng thy c knh hin vi quang hc v khng mc mi trng nui cy nhn to. Nm 1892 D.I. Ivanovski chng minh c rng mm bnh gy bnh khm thuc l c th chui qua cc lc vi khun bng s. Ivanovski cho rng l mt cht c tng t nh c t do cy b bnh tit ra. Nm 1898 M.W.Beijerinck chng minh rng chnh tc nhn gy bnh khm thuc l ch khng phi cht c ca n i qua c lc vi khun v ng dng ting Latin l virus (mm c) gi mm bnh ny. Nm 1898 F.Loeffler v P.Frosch chng minh c tnh qua lc s ca tc nhn gy bnh l mm long mng b . Nm 1915 - 1917 F.W.Twort v F.H. dHrelle pht hin ra virus ca vi khun v t tn l Bacteriophage, sau ny thng gi tt l phage. Nm 1935, W.M. Stanley ln u tin tch bit v kt tinh c virus khm thuc l. T nm 1940 tr i knh hin vi in t c hon thin dn cho php quan st c hnh dng v cc thnh phn cu trc ca virus.

II. NHNG C IM CA VIRUS

Virus l tc nhn nhim trng nh nht (ng knh t 20 - 300 nm ) c th lt qua cc lc vi khun, c cu to rt n gin. Virus l mt i phn t nucleoprotein c c tnh c bn ca mt sinh vt, nhng khng c kh nng t sinh sn, khng c cu to t bo, khng c qu trnh trao i cht v c th coi chng l trung gian gia cc cht sng v cht v sinh. Virus khc bit vi cc vi sinh vt khc cc c im sau y: - Virus ch cha mt loi axit nucleic duy nht: hoc l ADN hoc l ARN, khng bao gi cha ng thi c 2 loi axit nhn. - Virus sinh sn bng cch sao chp t vt liu di truyn duy nht ca chng, khng phn chia bng cch phn i nh cc vi khun. - Virus k sinh bt buc trong t bo sng, chng da vo ngun nng lng v b my ca t bo (v d cc ribosome, ARN vn chuyn...) tng hp protein.

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- Virus tng hp cc thnh phn ca chng mt cch ring r v sau t lp rp vi nhau to thnh nhng ht virus mi. - Virus khng nhy cm vi cc khng sinh thng thng.

III. KCH THC, HNH TH V CU TRC CA VIRUS

1. Kch thc Virus c kch thc rt nh b, c th qua c cc lc vi khun. Chnh v th m ch c th quan st thy virus qua knh hin vi in t. n v o kch thc ca virus l nanomet (nm) 1 nm =1/1000 micromet Mi loi virus c mt kch thc nht nh (t 20-300 nm) v khng thay i trong sut qu trnh pht trin. 2. Hnh th Phn ln cc virus c mt hnh th nht nh, c trng cho tng loi virus. Mt s loi hnh th virus thng gp: -Hnh cu : virus cm, si, bi lit. -Hnh khi a din : Adenovirus, Papovavirus. -Hnh que : virus khm thuc l. -Hnh vin gch : virus u ma -Hnh di trng (inh ghim): phage T2 ca E.coli 3. Cu trc Virus c cu trc rt n gin, khng c cu to t bo. Tt c cc ht virus u c hai thnh phn c bn: axit nucleic l thnh phn mang mt m di truyn ca virus v capsid l v protein bao quanh axit nucleic. Li axit nucleic v capsid hp li to thnh nucleocapsid. i vi mt s virus, nucleocapsid cn c bao quanh bi mt v lipit hay lipoprotein gi l bao ngoi (envelope hoc peplos) 3.1. Axit nucleic ca virus Mi mt ht virus u c mt trong hai loi axit nucleic hoc l ADN hoc l ARN. Axit nucleic nm gia ht virus to thnh li hay h gen ca virus. Phn t ADN ca virus phn ln dng ADN 2 si v c mt s t dng ADN 1 si nh Parvoviridae. Phn t ARN ca virus a s dng ARN 1 si, tr mt s t dng ARN 2 si nh Reoviridae. Cc axit nucleic ch chim 1-2% trng lng phn t ca ht virus nhng c chc nng c bit quan trng : - Axit nucleic mang ton b m thng tin di truyn c trng cho tng virus. - Axit nucleic quyt nh kh nng gy nhim trng ca virus trong t bo cm th. - Axit nucleic quyt nh chu k nhn ln ca virus trong t bo cm th - Axit nucleic mang tnh khng nguyn c hiu ca virus. 3.2. Capsid

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Capsid l cu trc bao quanh li axit nucleic. Bn cht ha hc ca capsid l protein. Capsid c cu to bi cc n v hnh thi gi l capsomer bao gm cc phn t protein c sp xp c trng cho tng loi virus. Cc capsomer c sp xp theo mt trt t khng gian xc nh to nn cc kiu i xng ca capsid : hoc i xng xon hoc i xng khi hoc i xng phc hp. Capsid ca virus c cc chc nng sau y: - V protein c tc dng bo v axit nucleic ca virus. - Protein capsid mang tnh khng nguyn c hiu ca virus. - Capsid ng vai tr quan trng trong giai on bm v xm nhp t bo ca virus. - Capsid gi cho hnh th v kch thc ca virus lun lun c n nh. 3.3. V ngoi (envelope) Cc virus nh Herpesviridae, Flaviviridae, Orthomyxoviridae, Paramyxoviridae,... cn c thm mt lp v bao bc ngoi capsid gi l envelope hoc peplos. Bn cht ha hc ca v ngoi l mt phc hp lipid, protein v gluxit. V ngoi c ngun gc t mng bo tng hoc mng nhn ca t bo ch nhng b virus ci to v mang tnh khng nguyn c hiu cho virus. V ngoi c th b cc dung mi ha tan lipid (nh ether, mui mt , ...) ph hy. V ngoi ca virus c chc nng : - Tham gia vo s bm ca virus vo t bo cm th - Tham gia vo giai on lp rp v gii phng virus ra khi t bo sau chu k nhn ln. Nhng virus khng c v ngoi gi l virus trn. 3.4. Gai protein Trn v ngoi ca mt s virus c nhng mu gai protein li ln c th c nhng chc nng ring bit nh ngng kt hng cu t hoc enzyme neuraminidase hot ng . 3.5. Mt s enzyme Virus khng c mt h enzyme chuyn ha hon chnh nh vi khun, nhng trong thnh phn cu trc ca mt s virus c mt vi loi protein c hot tnh enzyme. Ph bin nht l cc polymerase nh ARN polymerase, ADN polymerase, ADN polymerase ph thuc ARN (enzyme sao chp ngc)... 4. Virion Ht virus hon chnh c kh nng gy nhim trng cho t bo cm th c gi l virion. Ty theo tng loi virus, virion c th c capsid trn hoc capsid c v ngoi. 5. Pseudovirion Ht virus nhn vt liu di truyn ca t bo ch trong qu trnh sao chp thay cho axit nucleic ca virus c gi l pseudovirion. Nhng ht pseudovirion ny khi quan st di knh hin vi in t chng ging ht cc virion bnh thng, nhng chng khng c hot tnh nhim trng v khng th nhn ln c. Cc ht ny c

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kh nng chuyn cc gen ca t bo t mt t bo ch ny n mt t bo ch khc. 6. Viroid Viroid l mt tc nhn nhim trng nh b gy bnh thc vt v c th mt vi nhim trng virus chm ca ng vt. Tc nhn ny ch c axit nucleic (phn t ARN dng vng kn, trng lng phn t 70.000-120.000) khng c lp protein cu trc.

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IV. PHN LOI VIRUS

C nhiu cch phn loi virus. Hin nay vic phn loi virus da theo nhng tiu chun c bn sau y: - Loi axit nucleic (ADN hoc ARN) v cu trc ca chng (s si). - i xng ca capsid. - C hoc khng c v ngoi (envelope). - Cu trc gen virus - ng knh v s lng capsomer ca virus - Cc enzyme - Nhy cm vi ether - Tnh khng nguyn - Triu chng hc Cn c vo cc tiu chun trn chia virus ra thnh cc h (...viridae), ging (...virus), loi v type virus. Theo s phn loi hin nay, cc virus ca ngi v ng vt c xng sng c chia thnh 22 h khc nhau: 8 h virus cha ADN v 14 h virus cha ARN. Cc h virus cha ADN gm c: - Parvoviridae - Polyomaviridae - Papillomaviridae - Adenoviridae Cc h virus cha ARN gm c: - Reoviridae - Picornaviridae - Astroviridae - Caliciviridae - Togaviridae - Flaviviridae - Orthomyxoviridae - Paramyxoviridae - Rhabdoviridae - Filoviridae - Arenaviridae - Coronaviridae - Bunyaviridae - Retroviridae - Iridoviridae - Poxviridae - Hepadnaviridae - Herpesviridae

V. S NHN LN CA VIRUS
Virus khng c qu trnh trao i cht, khng c kh nng t nhn ln ngoi t bo sng. V vy s nhn ln ca virus ch c th c thc hin trong t bo sng nh vo s trao i cht ca t bo ch. iu ny cho thy tnh k sinh ca virus trong t bo sng l bt buc. S nhn ln ca virus l mt qu trnh phc tp, trong axit nucleic ca virus gi vai tr ch o truyn t cc thng tin di truyn ca chng cho t bo ch. Virus hng cc qu trnh trao i cht ca t bo ch sang vic tng hp cc ht virus mi.

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Ni chung qu trnh nhn ln ca virus trong t bo c chia thnh 5 giai on : Hp ph Gii phng. Xm nhp Tng hp cc thnh phn cu trc Lp rp

1. S hp ph ca virus vo b mt t bo S hp ph xy ra khi cc cu trc c hiu trn b mt ht virus gn c vo cc th th (receptor ) c hiu vi virus nm trn b mt ca t bo. Do tnh c hiu trn m mi loi virus ch c th hp ph v gy nhim cho mt loi t bo nht nh gi l cc t bo cm th vi chng. V d virus cm ch gy nhim t bo biu m ca ng h hp trn, virus HIV ch xm nhp t bo bch huyt gi l t bo lympho CD4. 2. S xm nhp ca virus vo trong t bo Cc virus ng vt sau khi gn vo cc th th c hiu trn b mt t bo cm th s xm nhp vo t bo theo c ch m bo. Khi lt vo t bo, capsid ca virus s c enzyme ci v (decapsidase) ca t bo phn hy, gii phng ra axit nucleic ca virus. l giai on ci o. i vi phage, sau khi hp ph ln b mt t bo th bao ui co rt, li bn trong chc thng mng t bo v bm axit nucleic vo t bo cn casid nm li bn ngoi. 3. S tng hp cc thnh phn cu trc ca virus Ngay sau khi axit nucleic ca virus c gii phng, virus b mt kh nng ly nhim v i vo giai on tim n, trong giai on ny khng thy virus trong t bo na. y chnh l giai on cc virus truyn t nhng thng tin di truyn ca mnh cho t bo ch v bt t bo ch chuyn hng hot ng ca mnh sang vic tng hp cc thnh phn ca virus. Trc ht, cc axit nucleic ca virus c nhn ln, sau protein ca virus c tng hp. Cc axit nucleic ca virus xc nh tnh c hiu ca protein. Nh vy cu trc khng nguyn ca virus khng b ph thuc vo t bo ch m do cc axit nucleic ca virus quyt nh. C ch nhn ln ca cc ADN v ARN ca virus c khc nhau. Di y l v d v ba loi virus c ba loi axt nucleic khc nhau: - cc virus cha ADN hai si: u tin cc thng tin di truyn ca virus c sao chp t ADN sang ARN thng tin nh ARN polymerase ph thuc ADN. Cc ARN thng tin ca virus s ng vai tr truyn tin to ra cc ADN v cc protein ca virus. - cc virus cha ARN mt si dng: cc thng tin di truyn ca virus c m ha trong phn t ARN s sao chp sang mt ARN b sung nh c ARN polymerase ph thuc ARN v t chng c lm khun mu to ra cc ARN ca virus. ng thi cc ARN ca virus cng ng vai tr ca ARN thng tin tng hp nn cc protein ca virus. - cc virus cha ARN c enzyme sao chp ngc: cc thng tin di truyn c m ha trong ARN ca virus c sao chp ngc to ra mt ADN trung gian nh c enzyme sao chp ngc (reverse transcriptase; ADN polymerase ph thuc ARN).T ADN trung gian cc m thng tin di truyn ca virus s c sao chp sang ARN thng tin, t chng tip tc c sao chp tng hp ra cc ARN virus v cc protein virus.

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4. S lp rp cc thnh phn ca virus Sau khi cc thnh phn c bn ca virus c tng hp v c tch ly phong ph trong t bo ch th s bt u qu trnh lp rp. Hnh nh c ch lp rp cc thnh phn ca virion xy ra t pht do kt qu ca s tng tc phn t c bit ca cc cao phn t capsid vi axit nucleic virus to thnh cc virion. Vic lp rp ng s to ra cc virus hon chnh (cc virion) v nu lp rp sai s to ra cc virus khng hon chnh (ht DIP) hoc to ra cc virus gi (Pseudovirion). 5. S gii phng cc ht virus ra khi t bo Virus thot ra khi t bo ch theo nhiu kiu khc nhau ty theo loi virus. Nhiu virus c gii phng theo kiu ph v mng t bo lm hy hoi t bo v cc virus ng lot c phng thch. Hoc c gii phng nh s xut bo (exocytosis) hoc qua cc rnh c bit m khng lm hy hoi t bo ch. Cc virus c v ngoi c gii phng theo kiu ny chi qua cc ch c bit ca mng t bo ch v virus s nhn c mt phn ca mng t bo ch. Thi gian nhn ln ca virus thng ngn hn rt nhiu so vi vi khun.V d t virus ban u, mt t bo b nhim virus cm c th to ra hng nghn virus mi sau khong 5 - 6 gi.

VI. HU QU CA S NHN LN CA VIRUS TRONG T BO

Khi virus xm nhp v nhn ln trong cc t bo to ra cc th h virus mi th c th gy nhiu hu qu khc nhau ty thuc vo bn cht sinh hc ca t bo v ca virus. 1.T bo b hy hoi Sau khi virus xm nhp v nhn ln trong t bo th hu ht cc t bo b ph hy . Do cc hot ng bnh thng ca t bo b c ch , cc cht cn thit cho t bo khng c tng hp m ch tng hp ra cc ht virus mi v vy t bo b cht. y l trng hp hay gp nht . nui cy t bo in vitro c th thy cc t bo b nhim virus bin dng, dnh li vi nhau, ly gii . 2. T bo b tn thng nhim sc th Virus c th lm cho nhim sc th ca t bo ch b gy, b phn mnh, b o ln v trt t sp xp v gy ra cc hu qu nh: 2.1. D tt bm sinh, thai cht lu ph n c thai, c bit trong ba thng u ca thi k mang thai, m b nhim virus th s lm sai lch nhim sc th c th dn ti mt s thiu ht bm sinh trong qu trnh hnh thnh bo thai v gy ra trng thi nhim virus cho bo thai . 2.2. T bo tng sinh v hn to khi u Cc t bo b nhim mt s loi virus (ch yu l cc virus gy ra khi u) c hin tng mt c ch tip xc khi t bo sinh sn nn to ra nhng m t bo chng cht ln nhau . 3. To ra cc tiu th c trng cho cc virus khc nhau

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Trong cc t bo nhim virus c th xut hin cc th vi trongnhn (Adenovirus ), hoc trong bo tng (tiu th Negri ca virus di ), hoc c hai ni (virus si ). Bn cht cc tiu th c th do tch t nhng virion hoc nhng thnh phn ca virion hoc c th l cc ht phn ng ca t bo khi nhim virus . Cc tiu th ny c th nhum soi thy di knh hin vi quang hc v da vo c th chn on gin tip s nhim virus trong t bo . 4. To ht virus khng hon chnh (DIP: Defective interfering particles) Ht virus khng hon chnh l virus ch c capsid, khng c hoc c khng hon chnh axit nucleic. Do vy cc ht DIP khng c kh nng nhn ln c lp khi vo trong cc t bo, c ngha l ht DIP khng c kh nng gy nhim trng cho t bo. Nhng ht DIP c th giao thoa c hiu vi nhng virus ng chng . 5. Cc hu qu ca s tch hp genom virus vo ADN t bo ch Axt nucleic ca virus tch hp vo ADN ca t bo ch c th dn ti cc hu qu khc nhau: - Chuyn th t bo (transformation) v gy nn cc khi u hoc ung th. - Lm thay i khng nguyn b mt ca t bo. - Lm thay i mt s tnh cht ca t bo. - T bo tr thnh t bo sinh tan. 6 . Kch thch t bo tng hp Interferon Interferon l nhng glycoprotein c trng lng phn t khong 17.000 25.000 Daltons do cc t bo tng hp ra sau khi b kch thch bi cc cht cm ng sinh interferon nh cc virus hoc cc cht cm ng khc. C 3 loi Interferon: Interferon-alpha, interferon-beta v interferon-gama. Cc loi ny c phn bit bi cc khng th c hiu. Interferon-alpha thng do cc t bo bch cu sinh ra. Interferon-beta c sn xut bi cc nguyn bo si. Interferon-gama l mt lymphokin do cc t bo lympho T sinh ra. Mt s tnh cht ca interferon: - Tnh khng nguyn yu. - Xut hin sm (vi gi ) sau kch thch ca cht cm ng. -Tnh cht chng virus ca interferon mang tnh c hiu loi nhngkhng c hiu vi virus: Interferon do cc t bo loi no sinh ra th ch c tc dng c ch s nhn ln ca virus t bo ca loi (v d ch c interferon sn xut t cc t bo c ngun gc t ngi mi c tc dng bo v cho ngi). Tri li, interferon c ph tc dng rng c ch s nhn ln ca nhiu loi virus khc nhau ch khng phi ch vi virus cm ng sinh interferon. - Interferon khng tc ng trc tip ln virus nh khng th m phn ng c ch s nhn ln ca virus xy ra bn trong t bo. C ch sinh interferon ca t bo: t bo ngi c 15 gen khc nhau m ha cho interferon-alpha, ch c 1 gen m ha cho interferon-beta v 1 gen m ha cho interferon-gama. Bnh thng cc gen ny trng thi c ch v khng hot ng. Cc cht cm ng sinh interferon c tc dng gii c ch cho cc gen ny lm cho chng tr li dng hot

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ng v do t bo s tng hp ra cc Interferon. Cht cm ng quan trng nht i vi cc gen alpha v beta l cc virus, nhng i vi gen gama l cc cht hot ha lympho bo T. Hai loi interferon-alpha v interferon-beta c tc dng chng virus mnh hn so vi interferon-gama. Cc interferon-gama c tc dng iu ha min dch v c ch cc t bo ung th mnh hn cc interferon-alpha v interferonbeta. C ch tc dng chng virus ca interferon: Interferon gn vo cc th th c hiu dnh cho interferon trn b mt mng t bo, gy ra gii c ch mt s gen m ha cc protein c ch virus. Di tc dng kch thch ca interferon c t nht 2 gen ca t bo c hot ha tng hp ra 2 enzyme l: elF2 kinase v 2, 5-oligoadenylate synthetase. elF2 l yu t khi ng cn thit cho vic gn ARN thng tin vo ribosome; elF2 kinase phosphoryl ha yu t elF2 v lm bt hot elF2 do ngn cn s tng hp protein ca virus. Oligoadenylate c tc dng hot ha ribonuclease ca t bo phn hy ARN thng tin ca virus, do c ch s tng hp protein virus. Nh vy, interferon ch th hin tc dng chng virus trong t bo sng v thc cht l kch thch t bo dng c ch enzyme phn hy ARN thng tin ca virus v c ch tng hp protein ca virus.

VII. KH NNG GY BNH

Virus c kh nng gy bnh cho ngi. Mt virus c th gy ra nhiu hi chng khc nhau v ngc li mt hi chng c th do nhiu virus khc nhau gy ra. Nhim virus c th chia lm hai loi chnh ty theo thi gian c tr ca virus trong c th: 1. Tc ng ca virus ln c th xy ra trong thi gian ngn Loi ny bao gm hai hnh thi nhim virus sau y: - Nhim virus cp tnh: c c im l thi gian bnh ngn( t mt vi ngy n mt vi tun l ) v tip theo sau cc triu chng c trng cho tc nhn gy bnh pht trin. Nhim virus cp c th kt thc khi hon ton, hoc mt phn, hoc t vong.Trong qu trinh hi phc virus b thi tr. - Nhim virus khng biu l: nhim virus khng c triu chng, virus trong c th mt thi gian ngn v thi tr nhanh. Xc minh c virus trong c th nh pht hin hiu gi khng th trong huyt thanh. 2. Tc ng ko di ca virus trong c th C bn hnh thi nhim trng ca loi ny u c c im l trng thi mang virus ko di: - Nhim virus tn ti dai dng: virus tn ti dai dng khng c triu chng nhng c km theo thi virus ra mi trng chung quanh. Hnh thi ny c th c hnh thnh sau khi bnh phc sc khe. N ng vai tr quan trng trong dch t v l nguy c trc tip gy nhim mi trng. V d bnh vim gan B. - Nhim virus tim tng: virus tn ti dai dng, khng c triu chng nhng khng thi virus ra mi trng xung quanh. Trong nhim virus tim tng virus c th di dng tin virus, axit nucleic ca virus c th tch hp vo b gen ca t bo ch. Trong mt vi trng hp do nh hng ca mt hay nhiu tc nhn nh chn

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thng, stress, gim min dch, v.v..., tin virus c th c hot ha v chuyn sang trng thi nhn ln, gy bnh cp tnh cho c th. V d bnh herpes. - Nhim virus mn tnh: virus tn ti dai dng c km theo mt hoc vi triu chng lc ban u, sau tn thng bnh l tip tc pht trin trong mt khang thi gian di. c im trong tin trin ca nhim virus mn tnh l c nhng thi k sc khe bnh nhn kh ln, bnh thuyn gim, xen k vi nhnhg giai on bnh bng pht, ko di mt vi thng c khi hng nm. - Nhim virus chm: y l mt hnh thi tc ng c bit gia virus vi c th v c nhng c im l thi gian nung bnh khng c triu chng ko di nhiu thng hoc nm, tip theo l s pht trin chm nhng khng ngng tng ln ca cc triu chng v kt thc bng nhng tn thng rt nng hoc t vong.

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VIII. NUI CY VIRUS

Virus ng vt c th nui cy c trn mt h thng t bo sng bao gm ng vt cm th, phi g v cc t bo nui trong ng nghim (in vitro) 1. ng vt th nghim cm th Trc khi k thut phi g v nui cy t bo c pht minh th tim nhim ng vt l phng php duy nht nui cy virus. Mi loi virus c mt vi ng vt cm th ring. V d i vi Arbovirus, ng vt th nghim cm th thng c s dng l chut nht trng mi . Ty theo loi virus c th s dng nhng ng vt cm th khc nhau nh chut nht cn b, chut nht, chut lang, th, kh... v nhng ng gy nhim khc nhau: tim, ung, nh mi, mt. Hin nay ng vt c s dng sn xut vaccine v phn lp mt s t virus m ng vt th nghim l vt ch nhy cm duy nht hoc vt ch c chn l. 2.Phi g Thng dng trng g p 9-12 ngy, lc phi to thnh, khoang i v khoang niu pht trin y . Ty theo mc ch : phn lp, th nghim, sn xut vaccine v ty theo loi virus, c th tim nhim vo mng niu m (virus u ma, u vaccine, Herpesvirus),vo khoang i (virus cm, quai b), vo khoang niu (virus cm, quai b , virus Newcastle). 3. Nui cy t bo X l m bng trypsin tch ri t bo ri nui t bo trong ng nghim c cha cc mi trng nui c bit. T bo pht trin thnh mt lp t bo u n bm vo mt trong cu ng nghim c gi l nui cy t bo mt lp. Cc loi t bo thng dng trong nui cy virus: - T bo nguyn pht: l nhng t bo c ngun gc t m ng vt, thc vt hay cn trng c nui cy thnh mt lp t bo trong ng nghim thng dng nui cy phn lp virus. Cc t bo nguyn pht c c im ch s dng mt ln, khng th cy truyn nhiu ln c. Nhng m thng dng sn xut t bo nguyn pht l thn kh, thn bo thai ngi, thn chut ng, m ca phi g v.v... - T bo thng trc: c ngun gc t m ng vt, thc vt hay cn trng c cy truyn nhiu ln m khng b thoi ho. Cc t bo thng trc hin nay thng dng nh t bo Hela, Hep-2, Vero, C6 / 36,... - T bo lng bi ca ngi: l dng t bo bo thai ngi. Dng t bo ny c hnh thi bnh thng, nhim sc th lng bi c hnh th bnh thng , c th cy truyn c nhiu ln (t 40-100 ln), chng khng cha cc virus tim tng nh cc loi t bo nguyn pht nui mt ln, do thng c s dng trong sn xut vaccine sng .

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BACTERIOPHAGE
Mc tiu hc tp 1. Trnh by c hnh thi v cu trc ca phage. 2. Nu c mi quan h gia phage v vi khun tc ch. Bacteriophage thng gi tt l phage c Twort pht hin T cu nm 1915 v sau dHerelle cng pht hin c vi khun l. Phage l virus c kh nng xm nhim vi khun. Mi vi khun c th l vt ch ca mt hoc nhiu phage. Phage c s dng kho st s lin h gia k sinh v vt ch, s nhn ln ca virus, vn chuyn cc yu t di truyn trong nghin cu sinh hc phn t.

I. HNH THI V CU TRC CA PHAGE

Nhng phage c kho st nhiu nht l nhng phage xm nhim E.coli. Hnh thi ca nhng phage ny di knh hin vi in t trng ging nh hnh thi ca tinh trng gm c u v ui. u c cu trc i xng hnh khi, capsid hp bi nhiu capsomer kt hp thnh mt cu trc hnh lng tr, thng thng c thit din thng hnh 6 cnh. Bn trong u cha axit nucleic. Phn ln phage cha ADN 2 si, cng c phage cha ADN 1 si. Nhng phage cha ARN 1 si cng c tm thy. ui c cu trc dng hnh xon. phage T2 mt nh ca u c ko di thnh ui di 95 nm. N hp bi 2 phn lng vo nhau: ng bn trong cng ng knh 8 nm thng vi u, v bn ngoi hnh xon ng knh 20 nm co rt c theo chiu dc nh ci l xo. Tn cng l mt tm 6 gc mi gc c mt si nh vo. Phn tn cng ca ui to nn mt h thng ca phage bm vo b mt vi khun.

II. MI QUAN H GIA PHAGE V VI KHUN TC CH

1. Phage c lc v phage n ha Lc gp vi khun cm th, phage hp ph ln b mt ca vi khun v axit nucleic c bm vo bn trong. Axit nucleic cung cp m di truyn t bo vi khun cho tng hp axit nucleic v cc n v protein capsid ca phage. Cc thnh phn ny t lp rp hnh thnh nhng phage con. Vi khun b ly gii v phage t do c phng thch. l phage c lc. Nhiu phage c gi l phage n ha lc xm nhim vi khun th axit nucleic ca phage tch hp vo nhim sc th ca vi khun. Trong qu trnh phn bo axit nucleic ca phage c sao chp ng thi vi nhim sc th ca vi khun. dng tch hp axit nucleic ca phage c gi l prophage. Vi khun cha prophage nhim sc th gi l vi khun sinh tan. Sau mt s ln phn bo prophage c th tch ri khi nhim sc th v tr thnh phage c lc. N cho tng hp nhng phage con, lm tan vi khun v phng thch nhng phage c lc. Cng c trng hp vi khun sinh tan mt prophage v tr thnh vi khun bnh thng.

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2. H thng sinh tan Nhng phage n ha khng ly gii vi khun m chng nhim v hnh nh sao chp ng thi vi vi khun trong nhiu th h. vi khun sinh tan axit nucleic ca phage tch hp vo nhim sc th ca vi khun v c gi l prophage. H thng sinh tan c nhng c im sau : 2.1. Min dch Lc mt vi khun mang mt prophage n tr nn min dch vi phage tng ng. Phage c th c hp ph nhng ri b loi ra khi t bo lc phn bo. Nhng phage n ha lm xut hin t bo cht trn p c ch s nhn ln ca phage v phong ta s tch ri ca phage. 2.2. S cm ng Nhng vi khun sinh tan c th cm ng bng nhiu cch khc nhau phng thch phage c lc, v d : di nh hng ca tia cc tm phn ln vi khun sinh tan phng thch phage. Cng c mt s trng hp prophage t ng tch ri nhim sc th v tr thnh phage sinh dng. 2.3. t bin thnh c lc Hu qu ca s nhim phage mt vi khun hnh nh c xc nh bi s cnh tranh gia s sao chp ca phage v s to thnh cht trn p. Nu qu trnh sao chp tin xa trc khi xut hin cht trn p th vi khun b ly gii. Nu cht trn p xut hin sm th vi khun sng st v tr nn sinh tan. Phage n ha cng c th t bin thnh phage c lc. Hai type bin chng c quan st. Trong type th nht s t bin lm cho phage khng vi cht trn p, trong type th 2 phage mt kh nng to thnh cht trn p. 3. Phng php kho st phage V cng nh tt c virus phage ch nhn ln t bo sng. V kch thc khng cho php quan st trc tip nu khng c knh hin vi in t nn cn thit theo di hot ng ca chng bng phng tin gin tip. Trong mc ch ny ngi ta s dng s kin mt ht phage cho vo mt lp vi khun ang phn chia trn thch dinh dng s to nn mt vng phn gii sng trn film m c ca vi khun ang pht trin. Vng phn gii ny gi l mt plaque; n c to thnh do t bo vi khun b nhim phage phn gii v phng thch nhiu ht phage mi, nhng phage ny lin xm nhim nhng t bo vi khun k cn. Qua trnh ny tun t lp li cho n khi s pht trin ca vi khun trn da thch ngng li do ht thc n v tch t phm vt c. Lc thao tc kho lo, mi ht phage to nn mt plaque. Mi vt liu cha phage c th nh lng nh th bng cch pha long thch hp v cho vo da thch dinh dng mc dy c vi khun nhy cm. m plaque cng tng t nh m khun lc trong nh lng vi khun. Phn lp v tinh ch: kho st nhng tnh cht vt l v ha hc ca phage cn phi iu ch mt lng y virus tinh ch khng cha vt liu t bo. Trong mc ch mi trng lng nui cy vi khun vt ch c tip chng phage v cho n khi mi trng nui cy hon ton ly gii. Lc ny dch thy phn ch cha ht phage v mnh vn vi khun, chng c ly ring bng li tm phn bit. Phn phage li tm c th lm dung dch treo v ra ri kho st nhng tnh cht vt l v ha hc hoc soi knh hin vi in t.

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III. NG DNG CA BACTERIOPHAGE

1. ng dng trong nghin cu sinh hc phn t Phage c dng lm phng tin vn chuyn gen trong nghin cu sinh hc phn t, rt nhiu phage c s dng nghin cu di truyn vi khun. S chuyn np l qu trnh vn chuyn gen vi khun qua trung gian ca phage. Mt vi chng phage v d phage P22 c th vn chuyn bt c gen no ca vi khun, l s chuyn np tng qut. Trong s chuyn np c hiu, mt s phage c hiu v d phage ch vn chuyn mt s gen ca vi khun cho sang vi khun nhn. 2. ng dng trong chn on vi khun v dch t hc Phage c s dng nh type phage vi khun. Mi loi vi khun c th gm nhiu type phage khc nhau do bn cht ca receptor vi khun i vi cc phage khc nhau. Ngi ta chn mt s b phage. Trong mi b phage, mi phage ch lm li gii mt type phage ca mt loi vi khun. Vic nh type phage c gi tr v chn on vi khun v nht l v dch t hc. Phage n ha c th tch hp vo nhim sc th vi khun bch hu; ch trng thi sinh tan vi khun bch hu mi to thnh c t. 3. ng dng khc Tuy c kh nng xm nhim vi khun, phage khng c s dng iu tr bnh nhim trng v nhng th nghim iu tr khng em li kt qu.

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PHNG NGA V IU TR BNH VIRUS

Mc tiu hc tp 1.Trnh by c cc bin php phng nga s tip xc vi tc nhn nhim trng. 2. Trnh by c phng php phng nga v iu tr bng liu php min dch c hiu. 3.Trnh by c phng php phng nga v iu tr bng liu php ho hc.

I. PHNG NGA S TIP XC VI TC NHN NHIM TRNG

Cc bin php phng nga nh: ci thin v sinh, ci thin ngun nc sinh hot, cch ly bnh nhn, kh trng tit trng dng c v mi trng, dit tc nhn trung gian truyn bnh... c p dng thch hp trong tng bnh, tng v dch. Nhng bin php k trn gp phn ng k gii quyt bnh virus, nhng vic thc hin i hi nhiu cng sc v tin ca. Bin php dit tc nhn trung gian truyn bnh l mt bin php phng dch hu hiu.

II. PHNG NGA V IU TR BNG LIU PHP MIN DCH C HIU

Liu php min dch nhm lm tng cng min dch bo v c hiu ca c th i vi cc thnh phn ca virus. Bao gm liu php min dch ch ng l chng nga cc vaccine chng virus v liu php min dch th ng l tim cc globulin min dch. 1. Liu php min dch ch ng Cc vaccine chng virus, cng nh tt c cc loi vaccine, d trn s kch thch ch ng h thng min dch bng cch a vo trong c th khng nguyn ca tc nhn nhim trng c lm mt kh nng gy bnh cho ngi, lm cho c th t to ra tnh trng min dch chng li tc nhn gy bnh. Tnh trng min dch m c th c c sau khi s dng vaccine l kt qu ca s p ng min dch i vi cc thnh phn khng nguyn c trong vaccine. Vic s dng vaccine phng bnh l mt phng thc ch yu lm gim t l mc v t l t vong ca cc nhim trng virus. Cc vaccine virus c s dng hin nay c th bao gm virus sng c lm gim c lc, virus b bt hat, hoc cc thnh phn cu trc ca virus. Cc thnh phn cu trc ca virus c th c ch to nh k thut ti t hp ADN hoc thu c t virion. 1.1. Vaccine bt hot (cn c gi l vaccine cht ) Loi vaccine ny c sn xut bng cch lm bt hot virus bng cc tc nhn l ha nh nhit, formol, beta propiolacton hoc tia cc tm. Nh vy, loi vaccine ny bao gm cc virion tinh khit v b git cht, do mt kh nng gy nhim trng, mt kh nng gy bnh. Vaccine bt hot gy nn s p ng min dch tt lc tim liu lng, ng thi gian. N c th chng nga cho nhng i tng b suy gim min dch cng nh ph n c thai.

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Vaccine bt hot thng khng gy c min dch lu bn so vi vaccine sng gim c lc v thng phi tim nhiu ln duy tr min dch. Loi vaccine ny hu nh ch kch thch c th tit ra cc IgG v IgM khng virus trong mu. V th n ngn cn km s xm nhp ca cc virus hoang di vo trong cc nim mc ng tiu ha v h hp, nhng n chng li s nhim trng giai on nhim virus mu nu c mt nhim trng lan ta. Cc vaccine virus bt hot c s dng cho ngi l vaccine cm, vaccine di, vaccine bi lit (vaccine Salk ), vaccine vim no Nht bn, v. v.... Mt dng khc ca vaccine bt hot (Subunit (Subvirion) vaccine) ch bao gm thnh phn khng nguyn quan trng nht v phng din sinh min dch ca virion c tinh khit v lm bt hot. V d loi vaccine vim gan B c iu ch t HBsAg c trong huyt tng nhng ngi nhim khng nguyn ny. 1.2. Vaccine sng gim c lc Loi vaccine ny cha virus t bin mt phn ln c lc ca chng i vi ngi. Virus vaccine gy ra min dch nhng khng gy bnh ngi mc d chng nhn ln c gii hn ngi c chng vaccine. sn xut loi vaccine ny cn phi s dng mt chng virus khng c kh nng gy bnh ( khc vi chng virus c lc hoang di )nhng ng nht khng nguyn hoc gn ging vi virus hoang di gy bnh v cu trc khng nguyn. c trng ch yu ca vaccine sng gim c lc l to ra trong c th mt qu trnh ging nh qu trnh nhim trng t nhin, kch thch c th p ng c min dch ton th v min dch ti ch, c min dch dch th v min dch t bo. c bit l s kch thch ngay ti ng vo ca virus vaccine trong c th to ra p ng min dch bo v ti ch m ch yu l tit ra IgA chng virus. V d cho tr em ung vaccine bi lit sng gim c lc (vaccine Sabin) to ra c min dch ti ch nim mc ng tiu ha c tc dng phng nga s xm nhp sau ny ca virus bi lit hoang di vo ng tiu ha. Nhng vaccine ny cn c u im l gy c min dch mc cao v tn ti trong mt thi gian di, thng ch tim chng mt ln v c th dng bng ng ung. Tuy nhin iu cn lu c bit l tnh an ton ca vaccine sng phi m bo khng cn kh nng gy bnh hoc ch gy bnh rt nh v chng virus vaccine phi c tnh di truyn n nh khng t bin tr li c lc ban u. Cc vaccine virus sng gim c lc c cho php s dng ngi gm c vaccine bi lit (vaccine Sabin), vaccine si, vaccine quai b, vaccine Rubella, vaccine thy u, vaccine st vng, v.v... 1.3. Vaccine ti t hp Mt loi vaccine ti t hp gm cc thnh phn ca virus c sn xut bng k thut ti t hp ADN. V d nh vaccine vim gan B ti t hp ADN c iu ch bng cng ngh sinh hc phn t v cng ngh di truyn. Mt loi vaccine ti t hp khc gm c chng virus vaccine b bin i. Ngha l dng k thut ti t hp ADN gn thm vo vt liu di truyn ca virus vaccine mt gen m ha cho thnh phn sinh min dch ca mt virus gy bnh no . Khi virus vaccine ny pht trin trong c th vt ch, sn phm gen ngoi lai cng c to thnh v min dch chng li c hai loi virus trn c to ra.

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Cc vaccine ti t hp thuc loi ny nh cc vaccine chng virus vim gan B v virus gy suy gim min dch ang c kim nh v nh gi v hi lc v s an ton.

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1.4. Mt s vaccine phng bnh virus ang c dng Vit Nam 1.4.1.Vaccine phng bnh bi lit Vaccine phng bnh bi lit ang c dng Vit Nam thuc loi vaccine sng gim c lc, dng nc ung, c tn vaccine Sabin gm 3 tp virus Sabin: tp 1, tp 2, v tp 3, do Trung tm khoa hc - sn xut vaccine Sabin ca nc ta sn xut. Vaccine Sabin to min dch c bn cho tr di 1 tui: ung 3 liu vo cc thng 2, 3, 4 sau khi sinh. Mi liu 2 git ( tng ng 0, 1 ml ). To min dch b sung cho tr em t 0 - 5 tui bng cch hng nm ung 2 liu cch nhau 1 thng trong cc chin dch ung vaccine phng bi lit. 1.4.2. Vaccine phng bnh si Vaccine si ang dng nc ta c nhp t nc ngoi ( Php, Canada, Nht, n ...).Vaccine si l vaccine sng gim c lc, dng ng kh. Khi dng, vaccine ng kh c pha vi nc ct tim di da vng cnh tay vi liu 0, 5 ml cho tr 9 thng n 11 thng tui. Hin nay nhiu nc nh M , B, Php, n ,... vaccine phng bnh si c sn xut di dng vaccine tam lin phng 3 bnh Si - Quai b - Rubella, c bit dc l M - M -R. y l vaccine sng gim c lc, ng kh, tim di da hoc bp tht vi liu 0,5ml cho tr em trong khong 12 thng n 15 thng tui. 1.4.3. Vaccine phng bnh vim gan B Vaccine phng bnh vim gan B ang dng Vit Nam c sn xut bi Vin V sinh Dch t (H Ni) hoc c nhp t nc ngoi nh B, M, Hn Quc,... Vaccine vim gan B hin c 2 loi : loi th nht (th h 1) sn xut t khng nguyn b mt (HBsAg) ca virt vim gan B c trong huyt tng ngi lnh. Loi th 2 (th h 2) sn xut t HBsAg c to ra nh cng ngh ADN ti t hp thc hin trn t bo nm men. Vaccine vim gan B dng nc tim phng bnh cho cc i tng bao gm tr s sinh, tr ln, ngi khe mnh, ngi c nguy c cao nhim virus vim gan B. Cch dng vaccine vim gan B theo ch dn ca nh sn xut vaccine mi nc. 1.4.4. Vaccine phng bnh vim no Nht Bn Vaccine phng bnh vim no Nht bn c sn xut bi Vin V sinh Dch t (H Ni) hoc c nhp t nc ngoi (Nht bn, Hn quc,...). y l loi vaccine virus bt hot, dng nc, tim di da vi liu 0,5ml i vi tr di 5 tui, vi liu 1ml i vi tr t 5 tui tr ln. - To mim dch c bn bng cch tim 3 liu: + Liu th nht: vo thi im chn tim . + Liu th hai: Sau liu th nht t 1 - 2 tun. + Liu th ba: Sau liu th nht 1 nm. Nn tim trc thng c dch. - Tim nhc li : + Mi nm tim 1 liu vng c dch vim no lu hnh . Nn tim vo thng gn trc thng pht dch . + Bn nm tim mt liu vng khng c dch vim no lu hnh .

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1.4.5.Vaccine phng bnh di cho ngi C 2 loi vaccine phng bnh di cho ngi ang dng nc ta: - Vaccine di Fuenzalida do Vit Nam sn xut, dng ng kh v dng nc, tim trong da 6 mi cch nht : Trn 15 tui: mi liu tim 0,2 ml Di 15 tui: mi liu tim 0,1ml Khng dng cc thuc c ch min dch nh ACTH, corticoid trong thi gian 6 thng k t khi tim vaccine phng di. - Vaccine di Verorab ca Php c sn xut trn t bo Vero, dng ng kh, tim di da hoc bp tht 5 liu,mi liu 0,5ml vo cc ngy: ngy 0 (thi im chn tim), ngy 3, ngy 7, ngy 14, ngy 30. Ty tim nhc li liu 0,5ml vo ngy 90. Vaccine di cn c tim sm cho nn nhn b ch (hoc mo) cn, sau khi x l ti ch vt cn . Cc vaccine thng c s dng phng bnh nhng c th tim vaccine trong thi k bnh iu tr bnh virus. i vi nhng bnh c thi k bnh di nh bnh di th vic tim vaccine t ra hu hiu nu thc hin ngay khi mi b nhim virus. 2. Liu php min dch th ng Thng s dng globulin min dch c bo ch t huyt thanh ngi v c chia ra lm 2 loi: - Globulin min dch bnh thng hay cn c gi l globulin min dch huyt thanh ngi c bo ch t huyt thanh ca tt c nhng ngi khe mnh, khng c s chn lc, do n cha cc khng th chng li nhng virus ph bin trong cng ng. Trn thc t loi huyt thanh ny c hiu qu trong vic phng nga bnh si v vim gan A. - Globulin min dch c hiu c iu ch t huyt thanh ca nhng ngi ang thi k hi phc sau khi mc bnh nhim trng no khi , hoc ca nhng ngi mi c tim chng vaccine. Nh c s chn lc thch hp ngi cho mu nn trong globulin min dch c hiu nng khng th chng li virus l cn nguyn ca bnh nhim trng m ngi cho mc hoc c tim chng thng cao gp hng chc ln so vi loi globulin min dch bnh thng. Ngoi globulin min dch bo ch t huyt thanh ngi, cn c globulin min dch bo ch t huyt thanh ng vt c tim vaccine kch thch sn xut khng th. Ngy nay vic s dng huyt thanh ng vt gim i nhiu v t l gy ra phn ng cao hn hn so vi khng th c sn xut t huyt thanh ngi. Cc khng th kt hp vi cc protein virus nm b mt bn ngoi ca virion c th ngn cn s hp ph ca virion vo cc th th (receptor) c hiu vi virus trn b mt t bo. C nhng bng chng c th cho thy khi tim globulin min dch sm trong thi k bnh c th ngn chn hoc lm gim s trm trng ca nhiu bnh virus nh: si, thy u, vim gan virus, di, u ma, u vaccine. Cn s dng lng globulin min dch y v tim sm trc giai on nhim virus mu. Khng th

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s pht huy hiu lc ngay sau khi c tim vo c th , nhng ch tn ti trong mt thi gian ngn khng qu 3 tun l.

III. PHNG NGA V IU TR BNG LIU PHP HA HC

Khc vi vi khun, cc virus k sinh bt buc bn trong t bo sng, chng khng c chuyn ha v s sao chp ca virus hon ton nm trong t bo ch nn chng khng nhy cm vi cc khng sinh thng dng. Do mt thuc iu tr c hiu cho virus phi t c nhng yu cu sau : -Thuc phi xm nhp c vo trong t bo, c bit l cc t bo b nhim virus. -Thuc ngn cn qu trnh tng hp ra cc virus nhng khng hoc t nh hng n hot ng ca t bo . 1.Thuc c ch s ci o ca virus Amantadine v rimantadine ngn cn s xm nhp v/hoc s ci o ca mt vi virus ARN c v ngoi; nhng trn lm sng n ch c hiu qu chng li virus cm type A ngi. Thuc ny c tc dng gim c s lng ngi mc bnh, gim nh biu hin lm sng v rt ngn thi gian b bnh. C 2 thuc ny u ngn cn s nhn ln ca virus thng qua s tng tc vi protein M2 ca virus cm type A, do ngn cn qu trnh ci o. Cc chng virus cm A t bin khng amantadine c tm thy bnh nhn b cm. S khng ph thuc vo s t bin gen m ha protein bao ngoi. Rimantadine l mt dn xut ca amantadine c tc dng chng virus cm A tng t amantadine, nhng c t tc dng ph hn. Nhng bin chng khng amantadine th cng khng vi rimantadine. Amantadine c ch s ci o ca b gen (genome) virus, do sau khi xm nhim axit nucleic ca virus khng c phng thch khi capsid tin hnh qu trnh sao chp. 2.Thuc c ch giai on tng hp cc thnh phn ca virus 2.1. Cc thuc c cu trc tng t nucleoside Ch tr cc virus nh cha ADN (Polyomavirus, Papillomavirus v Parvovirus), cn tt c cc virus u m ha enzyme polymerase ca ring chng tng hp nn cc axt nucleic ca virus. Cc enzyme polymerase ca virus l nhng ci ch l tng ca cc thuc khng virus loi tng t nucleoside. Ni chung, nhng thuc tng t nucleoside khng virus c phosphoryl ha thnh nucleoside triphosphate nh cc enzyme kinase ca virus hoc ca t bo ch. Sau triphosphate s tc ng nh mt cht c ch cnh tranh vi nucleoside triphosphate bnh thng c trong t ba v c t bo s dng nh mt tin cht cho s tng hp axit nucleic. i vi mt cht tng t nucleoside c c tc dng chng virus, n phi c 3 c tnh sau: c th phosphoryl ha thnh triphosphate, c i lc vi enzyme polymerase ca virus cao hn i lc vi enzyme polymerase ca t bo ch v c th kt hp vo chui axit nucleic ang ni di ra v tr ca cht tng ng cnh tranh ca n. Hai thuc chng virus c s dng rng ri nht trong thc hnh lm sng l aciclovir v zidovudine. 2.1.1. Aciclovir

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Aciclovir c cu to tng t deoxyguanosine, mt nucleoside cn thit cho qu trnh tng hp nn cc ADN. N c hiu qu trong iu tr cc nhim trng do virus herpes simplex v virus thy u gy ra. Aciclovir c phosphoryl ha tr thnh monophosphate nh enzyme kinase ca virus v sau thnh ra triphosphate nh cc enzyme ca t bo ch. Aciclovir triphosphate c i lc vi ADN polymerase ca virus mnh hn nhiu i lc vi ADN polymerase ca t bo. V th, nhng nng m n c ch chc nng ca ADN polymerase virus th hu nh khng c ch ADN polymerase ca t bo. Aciclovir triphosphate cng c s dng nh l mt tin cht cho s tng hp ADN. Khi kt hp vo chui ADN ang ni di ra v tr ca deoxyguanosine triphosphate th lm cho s ni di chui ADN b gin on. Nh vy, cch thc tc ng ca aciclovir l ngn cn qu trnh tng hp ADN ca virus. Aciclovir nng iu tr l thc s khng c bi v s phosphoryl ha cn phi c enzyme kinase ca virus; cho nn, khng c aciclovir triphosphate trong cc t ba khng b nhim virus herpes simplex hoc virus thy u. tm thy trong lm sng cc chng virus herpes simplex t bin khng aciclovir. C l s t bin c nh hng n gen kinase hoc gen ADN polymerase. 2.1.2. Zidovudine (azidothymidine, AZT) Zidovudine l mt cht tng t thymidine. N c tc dng c ch enzyme sao chp ngc ca virus (reverse transcriptase) do ngn cn s pht trin ca HIV. Zidovudine c phosphoryl ha thnh dn xut triphosphate nh cc enzyme kinase ca t bo ch. Triphosphate ch c ch mt mnh enzyme sao chp ngc ca HIV, cho nn qu trnh sao m ngc t si ARN b gen ca virus thnh si ADN b xung b c ch. N cng c kt hp vo chui ADN ang ni di thay th cho axit thymidylic, c th lm cho s ni di chui ADN b gin on. Nh vy, Zidovudine c ch s tng hp ADN virus t ARN b gen virus. Zidovudine c mt s hn ch l: ch c ch enzyme sao chp ngc ca HIV ti t boTCD4, khng tc ng c trn HIV nhn ln mnh m cc i thc bo hoc mt s t bo khc. C c tnh cao nh gy bun nn, nn, au u mt ng, c bit gy thiu mu, gim bch cu do c ch ty xng (gp 50% bnh nhn). khc phc tnh trng , phi lun phin dng mt s thuc cng nhm. Hin nay c hai dideoxynucleoside c a vo iu tr AIDS l: Zalcitidine (dideoxycytidine hoc ddC) v didanosine (dideoxyinosine hoc ddI).Ging nh Zidovudine, c ddC v ddI u tc ng nh nhng cht c ch enzyme sao chp ngc ca HIV. 2.1.3. Ribavirin Ribavirin l mt loi nucleoside tng hp tng t guanosine c tc dng c ch in vitro s pht trin ca nhiu virus cha ADN v virus cha ARN. N kh c i vi t bo ch, gy ra qui thai ng vt. Mc d gy c t bo, ribavirin c s dng c kt qu trn lm sng trong hai trng hp: bng ng tnh mch iu tr bnh st Lassa v bng ng kh dung iu tr cc nhim trng ng h hp do virus hp bo ng h hp (R.S virus) gy ra tr nh. 2.1.4 Vidarabine (Adenine arabinoside, ARA-A) y l mt nucleoside tng hp c cu to tng t adenosine. N bin thnh dng triphosphate nh cc enzyme ca t bo v khi tr thnh cht c ch

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ADN polymerase ca virus. N c dng iu tr nhim trng herpes tr s sinh, bnh thy u nhng bnh nhn b suy gim min dch. 2.1.5. Ganciclovir (Dihydroxy-propoxy-methyl-guanine, DHPG) Ganciclovir l mt nucleoside gn ging acyclovir, n c hot ha thnh dng triphosphate nh cc enzyme ca t bo v nh mt enzyme protein kinase ca virus. N l mt cht c ch mnh enzyme ADN polymerase ca Cytomegalovirus. Ganciclovir c dnh iu tr cc nhim trng nng do Cytomegalovirus gy ra nh vim phi, vim vng mc, vim i trng. 2.1.6. Idoxuridine v Trifluridine y l nhng cht tng t nucleoside c tc dng khng virus. Chng rt c. Do vy cm dng ng ton thn, ch dng ti ch bn ngoi trong iu tr vim gic mc do virus Herpes.

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2.2. Foscarnet (trisodium phosphonoformate) Foscarnet c cu trc tng t pyrophosphate. N c ch ADN polymerase ca virus herpes cng nh ca virus vim gan B v enzyme sao chp ngc ca HIV. Tri vi cc nucleoside khng virus, c hiu lc foscarnet khng cn c s phosphoryl ha trc . N c dng iu tr vim vng mc do Cytomegalovirus nhng bnh nhn AIDS. Foscarnet v ganciclovir c tc dng c ch hip ng ln s sao chp ca Cytomegalovirus in vitro. 2.3. Methisazone (Marboran, IBT) Methisazone l thiosemicarbazone c tc dng c ch s nhn ln ca Poxvirus bng cch phong ta cc ARN thng tin mun ca virus (c ch s dch m ca Poxvirus). Thuc ny c tc dng phng nga bnh u ma v c s dng iu tr cc bin chng ca bnh u vaccine nh chm, u lan ton thn. 2.4.Cc thuc c ch protease ca HIV C mt s loi thuc c ch enzyme protease ca HIV c s dng trong iu tr HIV nh saquinavir, ritonavir, indinavir, nelfinavir, amprnavir v lopinavir. Cc thuc c ch protease cnh tranh vi polyprotein gn vo v tr hot ng ca protease, ngn cn s ct polyprotein ca virus dn n s to thnh cc ht virus khng c kh nng gy nhim. 2.5. Interferon Interferon (IFN) c tc dng chng virus, iu ha min dch v chng li cc t bo ung th. Hai loi IFN - alpha v IFN - beta c tc dng khng virus, IFN gama c tc dng iu ha min dch v c ch t bo ung th. Nhng c tnh chng virus quan trng ca IFN l c hiu lc nng nanogram, c tc dng chng li tt c cc loi virus, v khng c bin chng khng IFN. Ni chung, tc dng chng virus ca IFN c tnh c hiu loi. V th, IFN dng iu tr cho cc nhim trng ngi phi l IFN sn xut t cc nui cy t bo ngi. Tc dng chng virus ch yu ca IFN l c ch s dch m ca ARN thng tin ca virus. 3.Thuc c ch s gii phng virus ra khi t bo Trong qu trnh nhn ln ca virus cm, cc virion c gii phng ra khi t bo theo kiu ny chi vi s tham gia ca neuraminidase. Nu enzyme ny b c ch th virion khng c gii phng. Cc thuc Zanamivir v Oseltamivir ngn cn s gii phng cc virion mi c hnh thnh bng cch c ch enzyme neuraminidase ca virus cm A v B. Cc thuc ny tc ng vo v tr hot ng ca enzyme neuraminidase, lm bt hot enzyme ny.

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NHIM TRNG V C LC CA VI SINH VT

Mc tiu hc tp 1. Trnh by c cc khi nim lin quan n s tng tc gia vi sinh vt nhim trng v c th vt ch 2. M t c vai tr gy bnh ca vi sinh vt gm cc yu t c lc ca vi sinh vt, s lng vi sinh vt v ng xm nhp 3. Trnh by c c s di truyn ca c lc vi khun v cc phng thc vi khun trnh c s loi b n ca c th vt ch

I . I CNG
i vi vi khun, c th con ngi l mi trng sng thch hp cho nhiu vi sinh vt, mi trng ny c nhit , m v thc n thch hp cho chng pht trin c. Nhiu vi khun c tr (colonization) trn b mt ca c th con ngi m khng gy hi cho c th vt ch, chng sng cng sinh (commensal) bnh thng vi c th vt ch v to nn thnh phn khun ch ( normal microflora) ca c th, tuy nhin nhng vi khun ch ny s tr thnh tc nhn gy bnh khi vt qua ro cn ca c th ( da, nim mc) xm nhp vo trong c th vt ch. Nhng vi khun c c lc nh vi khun bch hu, thng hn, t, vi khun l.. chng lun c c ch lm d dng cho chng pht trin c th vt ch v gy tn thng t chc hoc c quan ca c th v gy nn bnh nhim trng. Khi vi sinh vt gy bnh xm nhp vo c th vt ch, trong nhng iu kin t nhin v x hi nht nh v gy nn mt qu trnh phn ng tng tc phc tp gi l nhim trng. Trong qu trnh ny vi sinh vt l nguyn nhn, c th con ngi l i tng cm th. Hon cnh khch quan nh hng trc tip hc gin tip n s nhim trng. Khi vi sinh vt cha xm nhp vo c th th yu t han cnh c nh hng trc tip n con ngi v vi sinh vt gy bnh to iu kin thun li hoc khng thun li cho qu trnh nhim khun. Khi vi sinh vt xm nhp vo c th th han cnh ch tc ng vo con ngi v c nh hng n vi sinh vt.

II. CC HNH THI CA S NHIM TRNG

Qu trnh nhim trng a n tn thng t chc hoc c quan ca c th vt ch, lm ri lan c ch iu ha thn kinh, min dch v lm xut hin nhng triu chng r ca chng bnh. l nhng bnh nhim trng th lm sng. trm trng ca cc triu chng bnh ph thuc vo c quan b nh hng v mc tn thng ca c quan do s nhim trng ngi kho mnh bnh thng, a s trng hp nhim trng ch gy nn tn thng t chc khng ng k v v mt lm sng khng c nhng biu hin r rng cua chng bnh l nhim trng th n. Nhim trng khng triu chng lm cho c th vt ch c c tnh min dch vi tc nhn nhim trng, gip cho c th loi b hiu qu s nhim trng do vi sinh vt vo ln sau. V phng tin dch t hc, cc nhim trng th n rt nguy him v l ngun ly lan mm bnh m khng bit trong cc v dch nh dch t, dich bi lit, vin gan t l bnh nhim trng th n rt cao so vi th lm sng.

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Din bin ca mt bnh nhim trng thng qua bn giai an: bnh, khi pht, tan pht v hi phc. Phn ln bnh nhim trng sau khi hi phc c th c min dch trong mt thi gian di ty theo tng bnh. Bnh nhim trng c th biu hin ti ch hoc ton thn, cp tnh hay mn tnh. Lc vi sinh vt gy bnh trc tip truyn t ngi ny sang ngi khc, gy nn nhng qu trnh nhim trng mi th chng lm pht sinh bnh truyn nhim. Bnh truyn nhim c th tn pht hay pht trin thnh dch a phng hoc thnh i dch.

III. VI SINH VT GY BNH

Vi sinh vt gy bnh l nguyn nhn ca bnh nhim trng. Khng c vi sinh vt gy bnh th khng c nhim trng. Kh nng gy bnh ca vi sinh vt ph thuc vo c lc, s lng vi sinh vt xm nhp v ng xm nhp. 1. c lc vi sinh vt L kh nng gy bnh mnh hay yu ca mt loi vi sinh vt, vi khun Salnonella typhi v Salmonella paratyphi u gy nn bnh st thng hn, nhng bnh st thng hn do Salmonella typhi biu hin vi nhng triu chng bnh trm trng hn. nh gi c lc ca mt chng vi khun, ngi ta dng liu gy cht 50 (LD 50). LD 50 l liu lng vi sinh vt hoc c t ca chng lm cht 50% qun th sc vt th nghim trong mt khong thi gian nht nh. Hin nay ngi ta c xu hng dng n v ny hn l liu gy cht ti thiu (MLD). MLD l liu lng nh nht ca mt chng vi sinh vt hoc c t ca n git cht mt sc vt th nghim c trng lng nht nh, trong mt khong thi gian thc nghim nht nh. MLD t chnh xc v ph thuc vo trng thi, chc nng ca h min dch v thn kinh ca mi con vt th nghim. c lc ca mt chng vi sinh vt khng phi l c nh. Khi mi phn lp c c th bnh nhn vi sinh vt thng c c lc cao nhng qua qu trnh cy chuyn th c lc gim dn v c khi mt hn, do chn lc li nhng bin chng thch nghi trong iu kin mi. Trn c s ny nhiu loi vacxin vi sinh vt sng gim c c iu ch v d nh vacxin bi lit, vacxin BCG. vacxin BCG vi khun c ngun gc u tin l chng vi khun lao b (M. bovis) rt c nhng qua nui cy trn mi trng mt b nhiu nm v cy chuyn nhiu ln Calmette v Guerin to c mt chng vi khun hon ton khng c gi l vi khun BCG dng lm vacxin phng lao (Bacille de Calmette et Guerin). Mt khc mt chng vi sinh vt gim c khi tim truyn vo c th sc vt c th lm gia tng c lc ca chng. c lc ca vi sinh vt bao gm c t, kh nng bm dnh v kh nng xm nhim ca chng. 1.1 Kh nng bm dnh Bm dnh l bc u tin trong qu trnh nhim trng, nhiu vi khun c trn b mt ca chng nhng i phn t gi l cc yu t bm dnh (adhesin) n lm trung gian cho s bm dnh ca vi khun vo cc receptor c hiu tm thy trn mt s t bo ng vt nhng khng tm thy nhng t bo khc. Nhng thnh phn bm dnh vi khun c th do pili m nhim, E.coli bm dnh vo t bo rut hoc

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t bo biu m bng quang hn vo nim mc ming. Shigella gy bnh bm dnh vo biu m rut. Tng t nh vy Neisseria gonorrhoae bm dnh vo biu m niu o. Khng th ca thnh phn b mt vi khun khng nhng c tc dng opsonin ha vi khun m cn trung ha khng nguyn ngn cn vi khun bm dnh vo biu m. Hn na glycoprotein trong cht tit ca c th cnh tranh vi cc recepor bm ca vi khun v ngn cn s bm dnh ca vi khun, s bong t bo biu m b mt cng l mt c ch bo v khc v n loi b vi khun bm dnh vo t bo 1.2 Kh nng xm nhim L kh nng i vo bn trong t chc ca c th vt ch, nhn ln ri lan trn sang cc vng khc. 1.2.1. Kh nng to v: V ca nhiu vi khun gip cho vi khun khng li s thc bo, v d r rng nht l ph cu: so snh mt chng ph cu c v (khun lc dng S) v mt chng ph cu khng c v (khun lc dng R), th chng ph cu c v (S) gy bnh chut nht trong khi chng khng c v (R) th khng bnh. Streptococcus pyogenes yu t khng i thc bo nm mt ngoi ca vch t bo. 1.2.2. Cc enzyme: Nhiu vi khun gy bnh to c nhiu enzyme gp phn vo kh nng xm nhim ca chng. - Enzyme hyaluronidase do t cu, lin cu tit ra lm thy phn axit hyaluronic l thnh phn c bn ca m lin kt, lm cho vi khun phn tn vo m d dng. - Collagenase phn hy collagen thnh phn ca m c. - Streptokinase lm tan cc mu ng. - Leucocidin git cht bch cu. - Hemolysin lm tan hng cu. - Mucinase c mt s vi khun ng tiu ha tit ra, lm ph v lp nim dch bao ph nim mc rut, to iu kin vi khun tip xc trc tip vi t bo v xm nhp vo bn trong biu m. 1.3. Kh nng sinh c t c t c to thnh trong qu trnh chuyn ha ca vi khun. Ngi ta chia c t ca vi khun thnh ngoi c t v ni c t. 1.3.1. Ngoi c t: Do mt s vi khun gram dng v vi khun gram m to thnh v phn tit ra mi trng xung quanh, bn cht ha hc ca n l protein, c tnh cht sinh khng cao v d b ph hy bi nhit (600C). Nhiu ngoi c t ca vi khun nh ngoi c t ca bch hu, un vn, ng c tht c chit xut di dng tinh khit. Ngoi c t c c tnh mnh,v d ch cn 0,02mg ngoi c t bch hu c th git cht mt ngi.

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Ngoi c t khi c x l bng focmol hoc bng nhit sau mt thi gian th mt tnh c m vn gi hon ton tnh cht khng nguyn, ch phm ny c gi l gii c t dng lm vacxin phng bnh c hiu. 1.3.2. Ni c t: c t ny lin h cht ch vi vch t bo vi khun gram m, n khng khuych tn ra mi trng bn ngoi, ch khi no vi khun cht, t bo b ph hy th ni c t mi c phng thch ra bn ngoi. Cu to ha hc vch ca vi khun gram m l mt hn hp glucit, lipit v protein trong thnh phn c c tnh ca ni c t ch yu l thnh phn lipid A ca lp lipopolysacarit ca vch t bo. Ni c chu nhit cao, c tnh yu hn so vi ngoi c t. Hin nay ngi ta bit r rng ni c t ca vi khun gram m (-) c nhng tc ng sinh hc va c li cho c th vt ch kch thch p ng min dch mt khc n cng tc ng c gy chong v cht. Tnh cht sinh min dch ca ni c t yu, khng c kh nng bin thnh gii c t khi x l vi focmol. 2. c lc ca virus Khc vi vi khun, virus l tc nhn xm nhp ni bo bt buc. Virus c cu trc n gin, virus khng cha cc enzyme v cc b my phn bo cn thit chuyn ha v pht trin. Virus ch nhn ln c khi xm nhp vo trong t bo ca c th vt ch, chng s dng cc vt liu c sn ca t bo tng hp v nhn ln trn c s thng tin di truyn ca chng. Cc virus mi hnh thnh trong t bo vt ch s ph v t bo phng thch cc virus mi ra mi trng v tip tc chu k nhn ln cc t bo k cn. Nh vy tnh cht gy bnh ca virus lin h n. - Ph v qun th t bo b xm nhim - Thay i hnh thi, cu trc v lm cho t bo mt chc nng. 3. S lng vi sinh vt C th con ngi c nhng c ch bo v hu hiu. Vi sinh vt ch gy bnh lc s lng xm nhp t mt mc no . Nu s lng t qu th vi sinh vt dng b c th vt ch loi b. Th nghim nhng ngi tnh nguyn cho thy s lng Salmonella typhi nut vo rut c th gy bnh vo khong 106 hoc gy bnh t thc nghim, nhng ngi tnh nguyn phi ung cc dung dch natri bicarbonate lm kim ha dch d dy ng thi ung mt lng khong 10 9 vi khun t. 4. ng xm nhp ng xm nhp cng nh hng n kh nng gy bnh nhim trng. Nhiu vi sinh vt c c tnh hng c quan, chng chn lc b mt t chc m chng xm nhim. No m cu v ph cu thng tm thy vng mi hu nhng ph cu th xm nhim ng h hp di gy nn vim phi trong khi no m cu xm nhim ng h hp trn v xm nhp gy vim mng no. Vi sinh vt ch gy bnh lc chng xm nhp c th qua ng thch hp: Vi khun thng hn qua ng ming, lu cu qua ng sinh dc, trc khun un vn qua ng vt thng, vim gan virus A, virus bi lit qua ng ming, virus vim gan B qua ng tim chuyn...

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IV. C S DI TRUYN CA C LC VI SINH VT

Cc yu t c lc ca vi sinh vt c th c m ho trn DNA nhim sc th, trn DNA ca bacteriophage, trn cc plasmid hoc trn cc on gen nhy nm trn plasmid hoc nm trn nhim sc th. c t ca nhiu vi khun gy bnh c m bi mt on gen trn nhim sc th ca vi khun nh c t rut ca vi khun t, c t rut ca cc loi Shigella, hoc ngoi c t A ca Pseudomonas aeruginose. Cc yu t xm nhim ca E. coli, c t bong da ca S. aureus, c t ca vi khun than c m ho bi mt on gen trn plasmid ca vi khun. nhiu vi khun chng c kh nng to c t khi chng b nhim bi cc bacteriophage c hiu, cc bacteriophage tch hp on DNA ca chng vo DNA ca vi khun, trng thi ny vi khun sn xut c t nh c t ca bch hu, c t sinh ca Streptococcus pyogenes. Vi cc k thut phn t hin nay ngi ta d dng xc nh cc gen c lc ca cc vi khun gy nhim trng, iu ny rt c ngha tm ngun gc dch t hc ca chng vi khun gy bnh, v chn on nguyn nhn cc bnh nhim trng

V. S TRNH N VI P NG MIN DCH CA VI SINH VT

V l thuyt, vi khun tn ti trong c th vt ch cng lu th chng cng c nhiu thi gian gy tn thng cho c th, v vy nhng vi sinh vt trnh n c sc khng ca c th vt ch th c kh nng hn gy bnh 1. S ln trnh trong t chc hoc t bo Nhiu vi sinh vt nm bn trong t bo trnh c tc dng c hi cho chng ca khng th v thuc khng sinh. Mycobacterium tuberculosis v M. leprae thot khi c ch min dch t bo do ngn cn s ha nhp cc lysozim ca i thc bo vi cc phagosom ca li nguyn tng c cha vi khun. Virus herpes simplex v virus zoster sau khi xm nhp vo t bo biu m, cc virus ny n vng hch r thn kinh lng v chng tn ti trong mt thi gian di, Epstein-Barr virus tn ti c trong t bo lympho B... 2. Cc yu t ha tan ca vi sinh vt Nhiu vi khun c kh nng to ra cc yu t ha tan lm tr ngi p ng min dch ca c th vt ch chng li n. V d nhiu chng t cu sn sinh protein A kt hp vi vng Fc ca phn t khng th nh hng n chc nng ca khng th trong qu trnh opsonin ha, lu cu v nhiu no m cu to ra enzyme protease ph hy phn t IgA min dch 3. Thay i khng nguyn S thay i khng nguyn vi sinh vt thy r rng nht virus cm. Virus ny c hai quyt nh khng nguyn chnh: khng nguyn ngng kt hng cu (H) v khng nguyn neuramidase (N). Nhng thay i nh v c tnh khng nguyn lm xut hin typ virus mi. typ mi ny thot khi s bt hot ca khng th c trong mu ca ngi bnh b nhim trng trc y bi typ virus b m.

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KHNG NGUYN VI SINH VT

Mc tiu hc tp 1. Trnh by c cc khng nguyn ca vi khun. 2. Trnh by c cc khng nguyn ca virus. i vi c th ngi v ng vt th vi sinh vt v nhng cht c ca chng l nhng khng nguyn. Mi chng vi sinh vt c cu to bi nhiu cht phc tp v c tnh khng nguyn khc nhau, cho nn mi chng vi sinh vt u c nhiu khng nguyn.

I. KHNG NGUYN CA VI KHUN

Chia lm 2 loi : 1. Cc khng nguyn ha tan l nhng khng nguyn do vi khun bi tit ra mi trng xung quanh trong qu trnh pht trin. Chng bao gm cc khng nguyn ngoi t bo c bn cht l protein nh cc c t v cc enzyme. 1.1. Khng nguyn ngoi c t Cc vi khun bch hu, un vn, ng c tht.v.v... C ngoi c t l nhng khng nguyn mnh v c kh nng bin i thnh gii c t sau khi x l vi formol 400C trong mt thi gian. Gii c t khng cn c tnh nhng vn gi c kh nng sinh min dch, c dng lm vaccine phng bnh rt tt. Cc vaccine phng bnh bch hu, bnh un vn u l nhng gii c t. Vi khun t v mt s E.coli nh ETEC gy bnh bng c ch sinh ra c t rut (enterotoxin). c t rut c tnh khng nguyn cao, kch thch s hnh thnh khng th IgA tit ti rut, ch yu chng li phn B ca c t rut. 1.2. Khng nguyn enzyme Trong cc enzyme ngoi t bo c tnh khng nguyn mnh, ng k nht l cc dung huyt t. V d nh dung huyt t Streptolysin O ca lin cu l mt khng nguyn mnh, kch thch c th hnh thnh antistreptolysin O (ASO) , phn ng huyt thanh ASO thng c dng trong chn on bnh lin cu. Enzyme Streptokinase do nhiu chng lin cu tan mu to thnh cng l mt khng nguyn tt khch ng s hnh thnh antistreptokinase (ASK). 2. Cc khng nguyn t bo T bo vi khun c bao nhiu thnh phn cu to th c by nhiu loi khng nguyn. 2.1. Khng nguyn ca vch t bo vi khun - Vi khun Gram dng: Cu to chnh ca vch t bo vi khun Gram dng l peptidoglycan gi l murein. Nhim v chnh ca murein l lm sn c bn ca vch t bo cn vai tr sinh min dch rt th yu. Nhng thnh phn cu to khc ca vch t bo mc d t l thp nhng c tnh khng nguyn cao, l:

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+ Cc protein: thng l khng nguyn gy ngng kt c hiu, cn c vo c th chia vi khun thnh nhiu nhm, mi nhm thnh nhiu type, th d nh protein A ca t cu, protein M ca lin cu A. + Polysaccharide: thng l nhng hapten, ch khi no gn vi mt protein th mi tr thnh c tnh sinh min dch, v d nh polysaccharide C ca lin cu, ph cu. - Vi khun Gram m : vch t bo vi khun Gram m, thnh phn khng nguyn ch yu l phc hp protein - lipid - polysaccharide trong thnh phn protein lm cho phc hp c tnh cht khng nguyn, phn polysaccharide quy nh tnh c hiu ca khng nguyn, phn lipid c tnh c. Khng nguyn vch t bo vi khun Gram m thng c gi l khng nguyn O c bn cht l lipopolysaccharide (LPS) . Khng nguyn O (LPS) l ni c t ca vi khun Gram m. 2.2. Khng nguyn v ca vi khun Mt s vi khun c v bc ngoi vch t bo, che ch vi khun chng hin tng thc bo. Khng nguyn v bn cht thng l nhng polysaccharide c hiu type nh ph cu dng S, E.coli..., nhng cng c th l polypeptide nh v ca trc khun than, trc khun dch hch. 2.3. Khng nguyn lng ca vi khun Mt s vi khun Gram m c khng nguyn lng bn cht l protein mang tnh c hiu type. Khng nguyn lng khng ng vai tr quan trng trong vic gy bnh, nhng c tc dng trong vic chn on v xp loi vi khun. Khng nguyn lng thng c gi l khng nguyn H. 2.4. Khng nguyn b mt Vi Mt vi loi Salmonella c mt lp polysaccharide mng bao bc bn ngoi vch t bo vi khun, khng nhn thy c knh hin vi quang hc. V d nh khng nguyn Vi ca Salmonella typhi.

II. KHNG NGUYN CA VIRUS

Cc khng nguyn ca virus c chia ra lm 2 loi: cc khng nguyn ha tan v cc khng nguyn l thnh phn cu to ht virus. 1. Cc khng nguyn ha tan l nhng khng nguyn thu c t nui cy t bo nhim virus sau khi loi b virus v cc thnh phn ca t bo. Cc khng nguyn ny c th l cc enzyme ca virus, nhng thnh phn cu to m virus tng hp tha trong qu trnh nhn ln. Cc khng nguyn ny t c ngha thc t. 2. Cc khng nguyn ht virus Mi virus u c 2 thnh phn cu to c bn l axit nucleic v capsid. Mt s virus cn c v ngoi (envelope). 2.1. Khng nguyn nucleoprotein L phc hp khng nguyn to nn bi axit nucleic v protein. virus cm, ribonucleoprotein l khng nguyn c hiu type. 2.2. Khng nguyn ca capsid

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L khng nguyn quan trng v mnh nht ca virus v capsid cha phn ln protein ca virus . N c th l khng nguyn ring bit hoc gn vi nucleoprotein thnh mt khng nguyn phc hp. V protein gy nn trong c th nhng khng th trung ha m bo min dch c hiu chng li virus. Khng nguyn ny ng vai tr quan trng trong phn loi cc virus khng c v ngoi (envelope). 2.3. Khng nguyn ca v ngoi (envelope) Bn cht ho hc ca v ngoi thng l lipoprotein, mt s virus l glycoprotein. Trn v thng cha cc khng nguyn c hiu nh yu t gy ngng kt hng cu hoc neuraminidase, khng nguyn ngng kt hng cu gip ch nhiu cho vic pht hin v chn on virus.

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S KHNG CA C TH CHNG LI CC VI SINH VT GY BNH

Mc tiu hc tp Trnh by c cc c ch bo v khng c hiu v c hiu ca c th chng li cc vi sinh vt gy bnh. C th con ngi phi i ph rt nhiu loi vi sinh vt. Chng khc nhau v cu trc, thnh phn ha hc, cch xm nhim cng nh hot ng trong c th con ngi. C ch bo v khng c hiu c huy ng u tin ngn cn vi sinh vt xm nhp c th hoc gim s lng cng nh kh nng gy nhim ca chng. Trong qu trnh chng vi sinh vt c s phi hp cht ch ca c ch bo v khng c hiu vi c ch bo v c hiu cng nh c ch min dch th dch v c ch min dch t bo.

I. C CH BO V KHNG C HIU
C ch ny bao gm nhiu h thng sn c ca c th nn n hot ng u tin nhm mc ch ngn cn s xm nhp ca mi loi vi sinh vt gy bnh. 1. Da v nim mc Da v nim mc l ro cn u tin ngn chn s xm nhp ca cc vi sinh vt vo c th bng cc c ch sau: 1.1. C hc Cc t bo sng ha da, t bo biu m c lng ca nim mc ng h hp v tiu ha l cc vt cn v y li cc vi sinh vt l xm nhp. 1.2. Vt l v ha hc S bi tit cc cht b nhn (axit bo), bi tit m hi (axit lactic) trn b mt da v pH thp (mi trng axit) ca mt s v tr da v nim mc d dy hay ng tit niu sinh dc... c tc dng c ch v dit cc vi sinh vt. Lysozym c trong nc bt, nc mt, dch nhy mi hng... c tc dng dit vi sinh vt. 1.3. Cnh tranh sinh hc Xy ra gia cc vi sinh vt gy bnh xm nhp vo da v nim mc vi qun th vi sinh vt bnh thng c tr trn b mt da, nim mc ca c th. Chnh iu ny to ra s bo v t nhin cho c th. 2. Phn ng vim Khi vi sinh vt qua c da v nim mc, c th chng li bng phn ng vim ti ch ni vi sinh vt va lt vo. Vim l mt phn ng tch cc ca c th vi cc biu hin sng, nng, v au. Ti ch vim c s tp trung cc t bo nh bch cu a nhn trung tnh, cc i thc bo, cc lympho bo... v cc cht c hot tnh sinh hc nh histamin, serotonin, cc men gy phn hy t chc. Ti ch vim: tun hon chm, gin mch, cc cht dit khun c trong mu trn vo vim, c s thay i sinh ha nh tng axit lactic, pH gim lm cho vi sinh vt pht trin khng thun li. C hng ro fibrin bao bc ngn cch vim khng cho vi sinh vt lan rng.Qu trnh vim c th lan ta, c th khu tr trong cc vim, song u

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nhm mt mc ch l ngn cn s xm nhp v lan ta ca cc vi sinh vt gy bnh v cc sn phm c hi ca chng. 3. Bch cu trung tnh Xm nhp vo bn trong c th vi sinh vt b cc bch cu trung tnh v t bo mono tn cng. Trn b mt bch cu trung tnh c cc th th (receptor) dnh ring cho Fc ca IgG v th th cho C3 ca b th nn d bm v bt cc vi khun gn vi khng th v b th, l hin tng opsonin ha. Hin tng ny lm cho thc bo xy ra nhanh chng hn, nht l vi khun c v polysaccharide nh ph cu. Vi kh nng bt v tiu dit vi khun, bch cu trung tnh rt quan trng trong cc phn ng vim cp tnh. 4. i thc bo Nu vi sinh vt thot khi bch cu trung tnh th chng theo mu v bch huyt n cc t chc. y chng b cc i thc bo tn cng. Cc t bo n nhn thc bo bt ngun t mt lai t bo ty xng, pht trin thnh t bo chn tun hon trong mu ngoi vi ri n cc t chc khc nhau: T bo mono tm thy trong ty xng v mu, cc i thc bo trong cc t chc. Chc nng quan trng ca i thc bo l bt gi v x l cc vt l. Gi l thc bo lc vt l c kch thc ln nh t bo, vi khun, k sinh trng n bo... hoc m bo nu vt l l phn t di dng ha tan. Thc bo phi qua cc giai on : bm, nut v tiu ha. Phn ln cc vi sinh vt b cc lysosom tiu dit, chng b nhn chm trong cc bng ni bo lin kit vi cc lysosom hnh thnh cc phagolysosom. Cc i thc bo v t bo mono tiu dit vi sinh vt theo mt c ch ging nh bch cu trung tnh thng qua cc th th (receptor) dnh cho Fc v C3. Mt s vi khun c lc nh vi khun lao, Listeria, Brucella... khng nhng khng b tiu dit m cn c th nhn ln trong i thc bo v that khi tc dng ca cc cht trong huyt thanh c kh nng tiu dit chng. 5. Khng th t nhin C mt s protein trong huyt thanh bnh thng vi nhng c tnh cu trc ca globulin min dch. Chng phn ng c hiu vi mt vi khng nguyn mc d c nhn trong chng c tm thy cha h tip xc vi nhng khng nguyn . Chng c tm thy trong huyt thanh hiu gi thp v c th c mt vai tr c ngha trong s khng vi mt vi nhim trng. S thc bo i vi cc vi khun gy bnh c tng cng bi cc khng th t nhin do tc dng opsonin ha. Khng th t nhin c hnh thnh do c th tip xc vi mt vi sinh vt no c chung thnh phn khng nguyn vi vi sinh vt gy bnh hoc do tip xc khng bit vi khng nguyn hin din trong thin nhin v d nhim trng khng biu hin hoc trong thc n. 6. B th Tm thy trong huyt thanh ca ng vt, khng bn vi nhit (560/30 pht). B th (C ) gm chn thnh phn C1 - C9. Lc thnh phn th nht b khch ng bi mt phc hp min dch th n c kh nng khch ng nhiu phn t ca thnh phn th hai v nh th to nn mt hiu ng dy chuyn khuch i. Theo cch ny s khch ng mt phn t ca C 1 lm khch ng hng nghn phn t ca thnh phn tip theo. mi giai an, s khch ng lm xut hin hat tnh enzyme mi. Thnh phn cui lm thng mt l trn mng t bo v lm cho t bo cht. Nh th qua phn ng khuch i dy chuyn, s khch ng thnh phn C1 c th dn n s tiu bo nhn bit bng mt.

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Hot tnh sinh hc ca b th: 6.1.Lm tan t bo M hnh ph bin l phan ng min dch lm tan hng cu. Khi qut hn phn ng kt hp b th gy tan vi khun, t bo ung th. B th lm tan vi khun ln u tin c Pfeiffer pht hin lc tim vi khun t vo phc mc chut lang min dch vi phy khun t. 6.2.D phn vo hin tng opsonin ha B mt ca bch cu trung tnh c th th dnh cho Fc ca IgG v th th dnh cho C3b ca b th nn bch cu trung tnh d bm v bt cc vi khun gn vi khng th v b th. l hin tng opsonin ha. 6.3.Min dch kt dnh Phn ng min dch kt dnh xy ra gia cc phc hp c bao ph bi C3b vi mt s t bo nh bch cu trung tnh, i thc bo, t bo mono ngi. i vi t bo, hin tng min dch kt dnh c tc dng thc y hin tng thc bo. N cn c tc dng khi ng s gii phng cc enzyme t lysosom ca bch cu trung tnh lm nhim v thc bo . 6.4.Hat tnh ha hng ng Mt s sn phm phn ha c phng thch trong phn ng ca chui b th nh C5a, Phc hp C5, C6, C7 .... c hat tnh ha hng ng i vi bch cu mu ngoi vi ca ngi. 6.5. Hat tnh phn v C3a, v C5a l sn phm phn ha ca C3 v C5.Cc sn phm ny gy nn co bp c trn, gy nn hin tng gin huyt qun v tng tnh thm thu ca mao mch tng t nh histamin. 7. Properdin Thu c t huyt thanh bnh thng bng cch hp ph ln Zymosan, mt thnh phn ca vch t bo nm men. N c th git cht nhiu vi khun v virus vi s hin din ca Mg++ v b th qua s hat ha theo con ng tt. 8. Interferon (INF) Khi c th b nhim virus, mt cht c vai tr quan trng trong giai on u c ch v dit virus l IFN. IFN l nhng glycoprotein do nhiu loi t bo sn xut ra sau khi c tc dng kch thch ca virus. IFN xut hin sm (vi gi) sau nhim virus v tn ti ngn khong vi ngy n vi tun. IFN c tnh c hiu loi, IFN do cc t bo loi no sinh ra th ch bo v c cho cc t bo ca loi . N c tc ng ngn cn s nhn ln ca nhiu loi virus khc nhau ch khng phi ch vi virus kch thch sinh ra IFN. Nh vy IFN khng tc dng c hiu cho tng loi virus gy bnh. IFN khng tc ng trc tip ln virus nh khng th. Chng tc ng n t bo, kch thch t bo dng c ch enzyme ngn cn s nhn ln ca virus.

II. C CH BO V C HIU
Cc c ch min dch khng c hiu c th hat ng c lp nhng thng tc ng hp ng vi c ch min dch c hiu, do lm tng hiu qu ca c ch min dch c hiu ln rt nhiu, nht l i vi cc vi sinh vt c c lc cao.

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Cc c ch bo v c hiu ch c c khi c th tip xc vi cc khng nguyn ca mt vi sinh vt gy bnh no (do nhim trng hoc do dng vacxin). C ch bo v c hiu gm c min dch dch th bo v v min dch t bo bo v. 1. C ch min dch dch th bo v S hi phc ca c th vt ch trong nhiu trng hp nhim vi sinh vt ph thuc vo s xut hin ca khng th bo v. S tn ti ca khng th ny cng gip cho c th phng ti nhim. Khng th c nhng tc dng khc nhau i vi vi sinh vt . 1.1. Ngn cn vi sinh vt bm i vi nhiu loi vi sinh vt gy bnh, vic bm vo nim mc ng tiu ha, tit niu, h hp l bc quan trng chng c th gy bnh nh E.coli, lu cu, vi khun t, Mycoplasma, cc lai virus. Cc khng th thng l IgA tit ( IgAs ) c kh nng ngn cn cc vi sinh vt bm vo nim mc. 1.2. Trung ha c lc ca virus, Rickettsia, ngoi c t v enzyme Cc khng th IgG, IgA v IgM khi kt hp c hiu vi cc khng nguyn trn, lm cho cc virus, Rickettsia, ngoi c t v enzyme mt kh nng gy bnh. 1.3. Lm tan cc vi sinh vt trong trng hp c b th tham gia Cc khng th IgG, IgA v IgM khi kt hp c hiu vi cc khng nguyn l cc vi sinh vt hot ha b th n ti lm tan t bo vi sinh vt (vi khun Gram m, virut ). 1.4. Ngng kt vi sinh vt v kt ta cc sn phm ha tan ca vi sinh vt Cc khng th IgG, IgA v IgM khi kt hp c hiu vi cc vi sinh vt gy ngng kt cc vi sinh vt ny, khi kt hp vi cc sn phm ha tan ca cc vi sinh vt cng gy nn s kt ta ca cc sn phm ny. 1.5. Opsonin ha Lc opsonin ha tc l kt hp vi khng th v b th vi sinh vt d dng b bch cu trung tnh v i thc bo thu tm v trn b mt ca bch cu trung tnh v i thc bo c cc th th dnh cho Fc ca khng th v C3b ca b th v do b tiu dit nhanh chng hn. Qua opsonin ha s thc bo ngay c vi nhng vi sinh vt c c lc cng c thc hin mnh m. 1.6. Hin tng gy c t bo do t bo ph thuc khng th (Antibody dependent cellular cytotoxicity: ADCC) Gi tt l hiu qu ADCC. Cc t bo gy nn hin tng ny l cc lympho K cn gi l t bo Null. Ngoi ra i thc bo v t bo mono cng gy ra hiu qu trn y. Cho n nay cha hiu ht c ch lm tan t bo do hiu qu ADCC. Mt s nghin c cho rng hin tng tan t bo do hiu qu ADCC c im ging tan t bo do lympho T gy c, mt s khc li cho rng hin tng tan t bo ny dn n v mng t bo ging nh s tc ng ca khng th v b th. Hiu qu ADCC lin quan n t bo ung th, nhng cc vi sinh vt cng b tiu dit theo c ch ny. Tuy in virto ngi ta chng minh kh nng git vi khun v t bo nhim virus theo c ch ca hiu qu ADCC nhng cho n nay cha hiu ht tm quan trng ca hiu qu ny. Trong bnh vin gan B c th hiu qu ADCC c vai tr

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quan trng trong vic tiu dit cc t bo gan nhim virus. tr em b si hiu qu ADCC cng c tc dng dit t bo nhim virus nhng cha r ngha lm sng ca hiu qu ny. 2. C ch min dch qua trung gian t bo bo v Mt s vi khun nh vi khun lao, vi khun phong cng nh Listeria, Brucella v tt c cc virus c kh nng sng v tip tc pht trin bn trong t bo nn khng th khng th tip cn vi cc vi sinh vt ny. Chnh c ch min dch qua trung gian t bo gi tt l p ng min dch t bo c vai tr quan trng trong vic chng li cc vi sinh vt k sinh bn trong t bo . C hai hnh thc p ng min dch t bo : Mt hnh thc do lympho T gy qu mn mun (Delayed-typee hypersensitivity T lymphocyte: Lympho TDTH) v i thc bo ph trch, mt hnh thc do lympho T gy c (Cytotoxicity T lymphocyte: lympho Tc) ph trch. 2.1. Hnh thc p ng min dch t bo do lympho T gy qu mn mun (lympho TDTH : Delayed-type hypersensitivity) v i thc bo ph trch Gm hai giai an: Trong giai an u xy ra s tng tc ga i thc bo lm nhim v trnh din khng nguyn vi cc lympho TDTH cho cc lympho TDTH nhn din cc quyt nh khng nguyn. Ngoi s kch thch ca khng nguyn, lympho TDTH cn nhn s kch thch ca Interleukin 2 do Lympho T cm ng tit ra . Sau khi nhn hai kch thch , mt ca quyt nh khng nguyn, mt ca Interleukin 2, lympho TDTH tr thnh dng hat ha v phn chia tng sinh. Trong giai an 2, lympho TDTH hat ha tit ra cc lymphokin, l nhng cht ha tan c tc dng trn cc hot ng ca cc t bo khc nh i thc bo, bch cu trung tnh...Sau khi c hat ha bi lymphokin, cc i thc bo tr nn c kh nng tiu dit cc vi sinh vt ni bo nh vi khun lao, Brucella, Listeria, Salmonella typehi. 2.2. Hnh thc p ng min dch t bo do lympho T gy c (lympho Tc: Cytotoxicity) ph trch Nhng nghin cu trn t bo ngi cho thy ngi cng c hnh thc p ng min dch t bo do lympho Tc m nhn. Lympho Tc ca ngi b si c th dit cc t bo ch nhim virus in vitro. Lc lympho T c v t bo ch ly t mt c th th kh nng tiu dit t bo ch t ti a. Lympho Tc c kh nng tiu dit cc t bo ch b nhim virus (si, cm, Epstein Barr....) khi cc lympho Tc nhn din c khng nguyn virus ln khng nguyn ph hp t chc trn b mt t bo ch. Ngoi s kch thch ca khng nguyn, lympho Tc cn nhn s kch thch ca interleukin 2. Sau khi nhn hai kch thch, mt ca khng nguyn, mt ca Interleukin 2, tin lympho T c c hat ha thnh lympho Tc hat ng c kh nng dit t bo ch nhim virus. C ch lympho Tc dit cc t bo ch nhim virus hin nay cha c sng t.

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K THUT MIN DCH S DNG TRONG CHN ON VI SINH VT

Mc tiu hc tp 1.Trnh by c nguyn l ca mt s k thut min dch. 2.Bit p dng mt s k thut huyt thanh hc trong chn on bnh nhim trng.

I. BN CHT CA S KT HP GIA KHNG NGUYN V KHNG TH

S kt hp gia khng nguyn v khng th ph thuc vo cu trc b mt ca khng nguyn v khng th. S kt hp ny xy ra gia mt phn rt gii hn gia phn t khng nguyn (nhm quyt nh) v mt phn rt gii hn ca phn t khng th (trung tm hot ng). Theo Pauling, phn t khng th thng ha tr hai ngha l cng mt lc c th kt hp vi hai phn t khng nguyn. Cn khng nguyn a ha tr nn cng mt lc c th kt hp vi nhiu phn t khng th. Cho nn khng nguyn v khng th kt hp vi nhau to thnh mt phc hp hnh mng li trong khng gian ba chiu. V kch thc qu ln nn phc hp kt ta hoc ngng kt. Khng nguyn v khng th c th kt hp vi nhau theo bt c t l no nhng phn ng yu i nu tha hoc thiu khng nguyn hoc khng th. Phn ng r rt nht lc s phn t khng nguyn tng ng vi s phn t khng th. S kt hp gia phn t khng nguyn v khng th xy ra nh cc lc nh: lc lin kt ion (lc tnh in Coulomb) gia cc nguyn t hoc cc nhm ho hc mang in tri du, v d gia NH3+ v COO-, lc lin kt ca cc cu ni hydro gia cc nguyn t hydro mang in tch dng vi cc nguyn t mang in tch m, lc Van der Walls (lc hp dn lin phn t) gia hai phn t ph thuc vo tng tc gia cc lp my in t mt ngoi v lc thu nu din tip xc c pha khng nguyn v khng th u c cc axt amin thu th khi khng nguyn khng th kt hp, nc s b y ra to nn mt lc gn gia cc axt amin thu , s kt hp ny khng phi l mt phn ng ha hc. Phn ng kt hp gia khng nguyn v khng th rt c hiu. Mt khng nguyn ch kt hp vi khng th do n kch thch c th to thnh. Do phn ng kt hp khng nguyn - khng th c s dng xc nh khng nguyn hoc khng th nu mt trong hai phn t bit. Hiu gi ca khng th trong huyt thanh ngi hoc ng vt c th xc nh nh khng nguyn bit v do cho bit s tip xc trc vi khng nguyn. Ngc li nh khng th bit nhng khng nguyn khc nhau ca mt vi sinh vt c th nhn mt. Mt khc s hiu bit cu to khng nguyn cho php chn la thch ng vi sinh vt dng lm vaccine phng nga bnh nhim trng.

II. PHN NG KT TA
1. Nguyn l

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Phn ng kt ta l s kt hp gia khng nguyn ha tan lc gp khng th tng ng, to thnh ta c th quan st trc tip bng mt thng hoc nh soi knh lp. Khng nguyn a ha tr kt hp vi khng th ha tr hai to thnh kt ta hnh mng li 3 chiu. Phn ng c th thc hin mi trng lng hoc mi trng gel. 2. Phn ng kt ta mi trng lng 2.1. Phn ng nh tnh c thc hin vi khng huyt thanh pha long hoc khng pha long. Khng huyt thanh v khng nguyn c trn vi nhau v quan st kt ta to thnh. Cng c th cho khng huyt thanh vo mt ng nghim nh ri sau cho khng nguyn dn dn vo theo thnh ng. Mt vng kt ta c quan st mt phng phn cch. 2.2. Phn ng nh lng Cho php xc nh lng khng th kt ta vi mt lng khng nguyn bit. Cho mt lng khng nguyn tng dn vo mt lng khng huyt thanh khng i,ly kt ta bng ly tm v nh lng protein bng nhng phng php thng thng xc nh lng khng th phn ng. 3. Phn ng kt ta mi trng gel 2.1. Phn ng khuch tn i Ouchterlony Khng nguyn v khng th c t vo nhng l c trong thch. Chng khuch tn v to nn nhng ng kt ta trn mt thch. Mt phm vt cha nhiu khng nguyn to thnh nhiu ng kt ta. Nhng lin h min dch gia hai khng nguyn c th kho st bng phn ng khuch tn i. Nhng di kt ta to thnh c th cho bit s tng ng min dch, s ng nht tng phn hoc s khng lin h. 2.2. Phn ng khuch tn n C th lm cho s khuch tn mi trng gel nhy hn bng cch trn khng th vo thch. Khng nguyn c cho khuch tn t mt l c trn mi trng thch cha khng th. Lc bt u khuch tn, khng nguyn cn nng cao nn to thnh nhng phc hp ha tan. Lc khuch tn xa hn, nng h dn cho n khi t mt tr s thch nghi vng kt ta c to thnh. Phng php ny khng nhng c th ng dng nhn mt khng nguyn m cn c th cho php nh lng IgG trong huyt thanh.

III. PHN NG NGNG KT

1. Nguyn l Phn ng ngng kt l s kt hp gia khng nguyn hu hnh vi khng th tng ng, to thnh cc ht ngng kt c th quan st c bng mt thng. Khng nguyn c th l vi khun, hng cu, bch cu, tinh trng.v.v... Phn ng ngng kt chi xy ra nu c cht in gii, r nht, nhanh nht pH t 7 n 7,2 v nhit 370C. 2. Phn ng ngng kt trc tip

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Vi sinh vt sng v cht u c kh nng ngng kt vi khng th. Vi vi sinh vt sng, thc hin phn ng trn mt phin knh. Phn ng ny thng c s dng nhn mt vi khun. Ngoi vi khun, cc tbo nh hng cu, tinh trng... u c kh nng ngng kt vi khng th i ng. Trng hp khng nguyn l vi sinh vt cht, thc hin phn ng trong ng nghim xc nh hiu gi khng th trong huyt thanh trong chn on bnh nh phn ng Widal trong chn on bnh thng hn. 3. Phn ng ngng kt gin tip y khng nguyn v khng th ch ngng kt khi c s hin din ca mt nhn t th 3. Phn ng Coombs l mt v d. Ngi m Rh- sinh a con Rh+ (khng nguyn D). Lc sinh con, hng cu Rh+ lt vo mu ngi m v khch ng s to thnh khng th D. Khng th D c th lt qua nhau trong nhng ln mang thai sau. Phn ng gia khng th D v khng nguyn D c th ph hy hng cu v gy nn chng tan mu tr s sinh. phng nga cho b m Rh- khi b nhy cm ha bi khng nguyn D ca a con Rh+, tim vo ngi m ngay trc khi sinh a con th nht mt lng nh khng th D. 4. Phn ng ngng kt th ng Khng nguyn ha tan c hp ph ln b mt nhng nn mn nh ht bentonit, ht latex nhng thng dng nht l hng cu cu. Nhng ht ny ngng kt vi khng th nh s hin din ca khng nguyn dnh vo b mt chng. Nhng ht ny kh ln nn phn ng dng tnh c th khm ph bng mt thng. Trong trng hp hng cu c s dng lm gi mang khng nguyn th phn ng c gi l phn ng ngng kt hng cu th ng. pht hin khng nguyn, ngi ta gn khng th ln nn mn. Khi khng th gp khng nguyn c hiu, hin tng ngng kt s xut hin. Loi ny c gi l phn ng ngng kt th ng ngc. Phn ng ngng kt th ng nhy hn phn ng ngng kt trc tip nh hnh th tng i ln ca nhng ht mang khng nguyn v c hiu cao hn phn ng ngng kt trc tip v c th tinh ch c cc khng nguyn hoc khng th trc khi gn ln nn mn. Loi phn ng ny c dng trong chn on nhiu bnh nhim trng nh dch hch, Whitmore, vim mng no m... 5. Phn ng ngn ngng kt hng cu C mt s virus c kh nng ngng kt hng cu ca mt s ng vt v phn ng b c ch bi khng huyt thanh ca virus. l phn ng ngn ngng kt hng cu. Phn ng ngn ngng kt hng cu c s dng chn on nhiu chng bnh virus nh cm, quai b, st xut huyt, u ma.v.v...

IV. PHN NG KT HP B TH
1. Nguyn l Khng th c hiu vi s tham gia ca b th s gy ly gii t bo vi khun hoc mt s t bo ng vt khc. 2. Cc giai on tin hnh phn ng kt hp b th Trong phng th nghim ngi ta thc hin phn ng kt hp b th bng cch ghp 2 h thng phn ng:

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- Trong h thng 1, khng nguyn c cho tc dng vi khng th (mt yu t bit, mt yu t cha bit). Nu khng nguyn v khng th phn ng c hiu th tt c lng b th kt hp vo phc hp khng nguyn - khng th (KN-KT) - H thng th hai c s dng nhn mt b th t do (khng kt hp). Thm vo h thng th nht nhng hng cu cu v huyt thanh khng hng cu cu (h thng tan mu). Lc b th kt hp vo phc hp KN-KT ca h thng 1 th khng cn b th ly gii hng cu cu nhy cm ha. Nu h thng 1, khng nguyn v khng th khng phn ng c hiu vi nhau th b th t do kt hp vi phc hp hng cu cu - khng hng cu cu v do lm tan hng cu cu. Cho nn c kt qu phn ng dng tnh lc khng c tan mu v m tnh lc c tan mu. Phn ng kt hp b th c s dng chn on bnh giang mai, bnh virus cng nh nhn mt khng nguyn v khng th.

V. CC PHN NG TRUNG HA
1.Nguyn l Khng th c hiu c kh nng trung ho c t, c lc ca vi sinh vt, lm mt i mt tnh cht no ca vi sinh vt hoc sn phm ca n. 2. Phn ng trung ha c t c t ni y l ngoi c t. N mt liu ch mng hay ln hn c t c hn hp vi mt lng thch nghi khng c t i ng ri tim hn hp vo mt ng vt nhy cm th con vt khng b nguy him. Tnh c ca c t b khng c t trung ha. Cng nh nhng phn ng min dch khc, phn ng ny rt c hiu: mt c t ch trung ha vi khng c t tng ng. Lng khng c t cn thit trung ha mt lng c t ph thuc vi cch thc hn hp 2 cu trc vi nhau v ty theo iu kin th nghim c t c kh nng kt hp vi khng c t nhng t l khc nhau. Nu thay v cho mt lng c t bit vo mt lng khng c t trung ha, ngi ta cho lng c t lm hai ln vo lng khng c t th hn hp khng trung ha i vi ng vt th nghim. l hin tng Danysz. Ngi ta cho rng lc cho na lng c t vo khng c t th c t kt hp vi nhiu khng c t hn v do s lng phn t khng c t t do cn li t khng trung ha lng c t cn li. 3. Phn ng trung ha virus Nhiu loi virus pht trin nui cy t bo th ph hy cc t bo (hin tng t bo bnh l) nhng nu cho khng th tng ng ca virus vo ng thi vi virus th virus b trung ha khng nhn ln c v hin tng t bo bnh l khng xy ra. Phn ng ny c s dng xc nh hm lng khng th trong huyt thanh cng nh nh type virus. Mt khc cng c th nh lng khng th ca virus trong huyt thanh bng cch hn hp khng huyt thanh vi virus ri tim hn hp vo mt nhm ng vt nhy cm. Nu ng vt th nghim khng cho thy triu chng bnh th s hin din ca khng th trung ha c chng minh. 4. Phn ng trung ha enzyme Nhiu enzyme ca vi khun c tnh cht sinh khng tt v kch thch s to thnh khng th nh streptolysin O, streptokinase ca lin cu khch ng s to

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thnh khng streptolysin O (antistreptolysin O - ASO), khng streptokinase (anti streptokinase - ASK). Da trn nguyn tc phn ng trung ha c th nh lng khng streptolysin O (ASO), khng streptokinase (ASK) c trong huyt thanh ca bnh nhn chn on nhim lin cu. c bit phn ng ASO pht hin khng th khng streptolysin O c s dng trong chn on bnh thp tim v vim cu thn cp sau nhim lin cu nhm A.

VI. PHN NG MIN DCH HUNH QUANG

1.Nguyn l Nhng thuc nhum hunh quang nh Fluorescein, Rhodamin c th kt hp vi khng th m khng ph hy tnh cht c hiu ca khng th. Khng th lin hp y c kh nng kt hp vi khng nguyn v phc hp KN-KT c th quan st knh hin vi hunh quang. 2. Phng php trc tip Khng th c lin hp vi thuc nhum hunh quang ri cho tc dng vi khng nguyn. V d trong chn on vi khun t sau 6 - 8 gi nui cy nc pepton kim, lm mt phin pht ri nhum vi khng huyt thanh lin hp vi Fluorescein. Quan st knh hin vi hunh quang, ta pht hin thy khun t pht hunh quang xanh lc nu mu phn dng tnh. 3. Phng php gin tip Khng th c cho tc dng trc tip vi khng nguyn ri cho kt hp vi khng globulin ngi lin hp vi Fluorescein. Trc ht cho khng nguyn c nh ln tiu bn ri cho tc dng vi huyt thanh bnh nhn, ra loi b khng th tha sau nh mt git globulin ngi gn Fluorescein ri quan st knh hin vi hunh quang. Phng php ny c s dng chn on bnh giang mai (phn ng FTA - Abs), bnh t min... Phng php gin tip c nhiu u im nh: S pht hunh quang mnh hn, tit kim c thi gian nu nhiu huyt thanh c th nghim cng mt lc.

VII. PHN NG MIN DCH ENZYME (Enzyme-linked immunosorbent assay: ELISA)

Nguyn l: K thut ny s dng khng th hoc khng nguyn c nh vo mt tm polystyren. Sau n c dng bt khng nguyn hoc khng th i ng dung dch th nghim v phc hp c pht hin nh enzyme gn vi khng th hoc khng nguyn tc ng ln c cht c hiu. C cht ca enzyme thy phn o quang ph k, t l vi nng ca khng th hoc khng nguyn khng bit trong dung dch th nghim. Khng nguyn hoc khng th lin hp vi enzyme vn gi hot tnh min dch. Enzyme c s dng c th l photphatase kim hoc peroxydase. Th nghim cho kt qu khch quan v rt nhy. Th nghim min dch lin kt enzyme c p dng chn on nhng vi khun nh giang mai, Brucella, Salmonella, vi khun t..v cc virus nh virus vim gan, virus si, virus rota...

VIII. PHN NG MIN DCH PHNG X (Radioimmunoassay: RIA)

Nguyn l: Dng ng v phng x nh Thymidin H 3 Cacbon 14, I125... nh du khng nguyn hoc khng th theo di phn ng kt hp khng nguyn khng th.

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C th xc nh v tr ca khng nguyn (hoc khng th) nh du ng v phng x bng cch cho nh tng nh ln trn tiu bn t chc hc, sau pht hin bng cc phng php chp nh thng thng. pht hin v o lng ng v phng x trong mi trng lng, v d cc ng v pht x beta (nh thymidin H3, Cacbon C14 ), cn dng mt dung dch nhp nhy v o trong my m t ng. Phng php ng v phng x khng nhng c th khu tr v tr kt hp mt cch chnh xc m cn lm tng nhy cm phn ng ln hng nghn ln.

IX. K THUT SC K MIN DCH

Nguyn l: Phc hp khng khng th (KKT) gn cht mu c phn b u trn bn giy sc k. Khng nguyn (KN) c th ca vi sinh vt c gn c nh ti vch phn ng. Khi nh huyt thanh cn xc nh khng th (KT) ln bn sc k, KT c hiu (nu c) trong huyt thanh s kt hp vi KKT gn mu, phc hp min dch KT-KKT gn mu ny di chuyn trn giy sc k s b gi li ti vch phn ng do KT kt hp vi KN vi sinh vt, kt qu vch phn ng hin mu. Nu trong huyt thanh khng c KT c hiu, vch phn ng KN khng th gi c KKT gn mu, v vy khng hin mu.

X. NHN NH KT QU CC PHN NG KT HP KHNG NGUYN KHNG TH

Trong nhn nh kt qu ca cc phn ng gia khng nguyn v khng th trc ht phi lu n nhy 1. Kt qu nh tnh Kt qu nh tnh cho bit trong mu xt nghim c hay khng c khng th hoc khng nguyn. Thng thng kt qu cc phn ng c k hiu bng cc mc dng tnh (+, + +, + + +) , khng r dng tnh hay m tnh (+/-), m tnh (-). Cc k hiu ny tuy c tiu chun quy nh nhng ph thuc vo ch quan ca ngi c kt qu. 2. Kt qu nh lng Chn on gin tip cc bnh nhim trng qua vic xc nh khng th trong huyt thanh c gi l chn on huyt thanh hc. Kt qu nh lng trong chn on huyt thanh cho bit hiu gi khng th. Nng khng th trong huyt thanh cao hay thp c nh gi qua hiu gi khng th. Thng thng khng th ngi bnh c pha long dn theo cp s 2 hoc 4. m huyt thanh thp nht cho kt qu dng tnh th m l hiu gi. Cc phn ng nh lng cn thit theo di ng lc khng th ca cc huyt thanh kp thng ly cch nhau 7 ngy. ng lc khng th l i lng c trng cho mc thay i hiu gi khng th theo thi gian. Trong nhn nh, quan trng l s thng ch khng phi hiu s gia hai ln kt qu. i vi bnh virus hiu gi khng th tng ln 4 ln mi c gi tr chc chn. 3. Ranh gii hiu gi L ranh gii gia hiu gi khng th bnh thng v hiu gi bnh l. Lin cu thng c tr hu ht mi ngi nn trong huyt thanh ca hu ht mi ngi u c khng th khng streptolysin O (ASO). V th ngi ta xem 1/200 (200 n v /ml), l hiu gi ranh gii. Ch khi no trong huyt thanh c 400 n v/ml tr ln mi l bnh l.

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4. Kt qu dng tnh gi Hay gp lc lm phn ng huyt thanh hc v k thut v trong mt vi trng thi sinh l bnh l ca ngi bnh. Trong huyt thanh hc c in chn on giang mai vi cc khng nguyn lipoit c th thy nhiu kt qu dng tnh gi (st rt, mt s bnh k sinh trng khc...). Trong thc t ngi ta thc hin nhiu phn ng huyt thanh hc khc nhau cng mt lc kim tra dng tnh gi. V d Kolmer, Kaln, VDRL v nht l dng cc khng nguyn c hiu trnh dng tnh gi, v d TPI, FTA-Abs... 5. Kt qu m tnh gi C nhiu nguyn nhn dn n hin tng m tnh gi nh: cc thnh phn tham gia phn ng khng c chun , lng khng th qu nhiu so vi khng nguyn v ngc li, khng th mu hoc khng nguyn mu b hng... khc phc hin tng dng tnh gi, m tnh gi phi chun cc thnh phn tham gia phn ng, m bo ng cc iu kin ca phn ng (dung dch m, nhit , thi gian ...) v phi lun lun c chng dng, chng m.

VACCINE V HUYT THANH

Mc tiu hc tp 1. Trnh by c nguyn l s dng v phn loi vaccine v huyt thanh. 2. Trnh by c nguyn tc s dng vaccine v huyt thanh. Vaccine v huyt thanh l nhng ch phm phng nga bnh nhim trng bng phng tin min dch. Nhng phng tin ny bin i tnh th cm ca vt ch thnh s khng tm thi hoc vnh vin. Chng to nn tnh min dch hot ng (vaccine) hoc th ng (huyt thanh) thng thng rt c hiu.

I. VACCINE
1. Nguyn l s dng vaccine S dng vaccine l a vo c th khng nguyn c ngun gc t vi sinh vt gy bnh hoc vi sinh vt c cu trc khng nguyn ging vi sinh vt gy bnh, c bo ch m bo an ton cn thit, lm cho c th t to ra tnh trng min dch chng li tc nhn gy bnh. S bo v hnh thnh nh s p ng min dch va dch th (globulin min dch c hiu nht l IgG, c th IgA v IgM), va trung gian t bo (i thc bo v t bo lympho). Cng v hiu qu ca s p ng min dch bin thin theo : - Vaccine: Tnh cht v nng ca khng nguyn, nhng cht ph gia min dch, thng s dng l nhng mui kim loi: Al hoc Ca c th tng cng s p ng ca mt vi vaccine bt hot.

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- Vt ch: Tui l mt nhn t quan trng. Tr s sinh cn t thng t s trng thnh min dch (dch th), ngoi ra khng th t sa m c th ng vai tr ngn nga bnh nhim trng. Ngc li s p ng min dch gim dn vi tui nhng khng bin mt ngi ln tui. Nhng nhn t di truyn, cn cha bit r cng nh hng n cng ca s p ng min dch. Cui cng l mt vi nhn t lm suy gim s p ng min dch, chng c th do di truyn nh khng c globulin huyt, gim st t bo min dch hoc do mc phi nh trong bnh u c tnh, iu tr gim min dch, suy dinh dng... 2. Cc loi vaccine 2.1. Vaccine sng gim c lc L nhng tc nhn nhim trng t nhin, c lm gim c mt cch nhn to phng th nghim. Vaccine u ma, vaccine u tin trong lch s, l mt virus ng vt (u b) c kh nng em li s bo v cho chng li virus u ma m n rt gn gi. Phn ln nhng vaccine sng hin c l nhng vaccine virus: vaccine st vng, vaccine bi lit, si, rubon, quai b. Mt vaccine vi khun sng thng s dng l BCG. i vi vaccine sng, s chng nga thng mt ln, gy nn s nhim trng nh hoc khng biu hin, s nhn ln ca virus trong c th gy nn min dch thng lu bn, tng ng vi s min dch do s nhim trng t nhin. Nhng thun li ca vaccine sng l tin li (tim 1 ln), gi thnh thng r. iu bt tin l c th em li nguy c nhim trng (phn ng v bin chng). 2.2. Vaccine cht L nhng ch phm khng nguyn mt kh nng nhim trng nhng cn bo tn tnh cht gy min dch. Ngi ta phn bit : 2.2.1. Nhng vaccine cht ton th Loi vaccine ny cha tt c cc thnh phn ca tc nhn nhim trng, git cht bng nhit, formol hoc propiolacton, bao gm vaccine vi khun nh ho g, thng hn TAB, dch t hoc vaccine virus nh cm, bi lit, di. 2.2.2. Nhng vaccine cht ch cha khng nguyn tinh ch Loi vaccine ny ch bao gm thnh phn khng nguyn quan trng nht v phng din sinh min dch ca vi khun hoc virus c tinh khit v lm bt hot. V d nh vaccine cha gii c t vi khun bn cht protein (vaccine un vn, vaccine bch hu), vaccine cha thnh phn polysaccharide ca vi khun (vaccine no m cu, vaccine ph cu), vaccine cha thnh phn khng nguyn virus (vaccine virus vim gan B c iu ch t HBsAg c trong huyt tng nhng ngi nhim khng nguyn ny). Nhng vaccine cht c u im khng c nguy c nhim trng. Nhng bt li bao gm: gi thnh thng cao, nguy c mn cm, mt lch chng nga nhiu ln v lp li. 2.3. Vaccine ti t hp L nhng vaccine c sn xut da vo k thut di truyn v cng ngh gen, nh vaccine vim gan B ti t hp. 3. Nguyn tc s dng vaccine Vic s dng vaccine phi m bo cc nguyn tc sau:

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- Tim chng trn phm vi rng, t t l cao. - Tim chng ng i tng. - Bt u tim chng ng lc, bo m ng khong cch gia cc ln tim chng, tim chng nhc li ng thi gian. - Tim chng ng ng v ng liu lng. - Nm vng phng php phng v x tr cc phn ng khng mong mun do tim chng. - Bo qun vaccine ng quy nh. 3.1. Phm vi v t l tim chng 3.1.1. Phm vi tim chng Phm vi tim chng c quy nh tu theo tnh hnh dch t ca tng bnh. Phm vi tim chng ng nhin khng ging nhau gia cc nc. Ngay c cc khu vc trong mt nc cng c th c s khc nhau. Nhng quy nh ny li c th thay i theo thi gian do s thay i v dch t hc ca bnh nhim trng. V l thuyt, ngi ta thng ni tim chng cng rng cng tt. Thc t th khng th thc hin c iu v nhng l do sau y: th nht, s rt tn km (chi ph cho vic mua hoc sn xut vaccine v cho vic t chc tim chng): th hai, tuy cc phn ng khng mong mun do vaccine gy ra rt it nhng khng phi khng c.

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3.1.2. T l tim chng Nhng khu vc c lu hnh bnh truyn nhim, tim chng phi t trn 80% i tng cha c min dch mi c kh nng ngn nga c dch. Nu t l tim chng ch t trong khong 50 n 80%, nguy c xy ra dch ch gim bt. Nu t l tim chng di 50% dch vn d dng xy ra. 3.2. i tng tim chng i tng cn c tim chng mt loi vaccine no l tt c nhng ngi c nguy c nhim vi sinh vt gy bnh m cha c min dch. Tr em l i tng cn c c bit quan tm. Sau khi ht min dch th ng do m truyn (trong thi gian khong 6 thng), nguy c mc bnh nhim trng ca tr rt ln. Mt khc min dch th ng nh khng th truyn qua rau thai hoc qua sa ch c i vi nhng bnh m c ch bo v ch yu l do min dch dch th. i vi nhng bnh nhim trng m c ch bo v l min dch qua trung gian t bo th tr c th b bnh ngay t nhng thng u tin sau khi sinh. Nhng hiu bit ny l c s cho vic quy nh thi im bt u tim chng cho tr em. Tr nhng i tng chng ch nh, tt c tr em u phi c tim chng. i vi ngi ln, i tng tim chng thu hp hn. Thng ch tin hnh tim chng cho nhng nhm ngi c nguy c cao. Nhng ngi i du lch n cc vng dch t cn phi c tim chng. Trong nhng nm gn y, phng bnh un vn s sinh, ph n la tui sinh c tim phng un vn. Din chng ch nh tim chng c hng dn ring cho mi vaccine. Ni chung khng c tim chng cho cc i tng sau y: - Nhng ngi ang b st cao. Nhng trng hp ang b nhim trng nh khng st hoc ch st nh th khng cn phi hon tim chng. - Nhng ngi ang trong tnh trng d ng. Nhng ngi c c a d ng hoc c lch s gia nh b d ng vn tim chng c, nhng cn phi theo di cn thn hn. - Vaccine sng gim c lc khng c tim chng cho nhng ngi b thiu ht min dch, nhng ngi ang dng thuc c ch min dch hoc nhng ngi mc bnh c tnh. - Tt c cc loi vaccine virus sng gim c lc khng c tim cho ph n ang mang thai. 3.3. Thi gian tim chng Vic tim chng c tin hnh thng xuyn hoc tp trung tim chng hng lot tu thuc vo yu cu ca mi loi vaccine v cc iu kin c th khc. 3.3.1. Thi im t chc tim chng Khi xc nh c quy lut xut hin dch, cn phi tin hnh tim chng n trc ma dch, c th c thi gian hnh thnh min dch. i vi vaccine c tim chng ln u, thi gian tim tng ko di t 24 gi (trung bnh khong 1 tun), tu thuc vo bn cht vaccine v tnh phn ng ca c th. Hiu gi khng th t c nh cao nht sau khong 4 ngy n 4 tun (trung bnh 2 tun). l kt qu ca p ng tin pht. Khi tim chng nhc li, thi gian tim tng s rt

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ngn, hiu gi khng th t c nh cao nht ch sau mt s ngy nh nhng t bo lympho c tr nh min dch. l kt qu ca p ng min dch th pht. 3.3.2. Khong cch gia cc ln tim chng i vi nhng vaccine phi tim chng nhiu ln (khi to min dch c bn), khong cch hp l gia cc ln tim chng l 1 thng. Nu khong cch ny ngn hn, mc d tim chng ln sau nhng kt qu p ng ca c th vn ch nh tin pht, p ng min dch th pht s khng c hoc b hn ch. Ngc li v mt l do no phi tim chng ln tip theo sau hn 1 thng, hiu qu min dch vn c m bo, v vy ln tim chng trc vn c tnh. Tuy nhin khng nn ko di vic tim chng nu khng c nhng l do bt buc, v tr c th b mc bnh trc khi c tim chng y . 3.3.3. Thi gian tim chng nhc li Thi gian tim chng nhc li tu thuc vo thi gian duy tr c tnh trng min dch c hiu lc bo v ca mi loi vaccine. Thi gian ny khc nhau i vi cc loi vaccine khc nhau. Khi tim chng nhc li thng ch cn 1 ln. Vi ln tng cng ny, c th s p ng min dch nhanh v mnh hn, cho d khng th ca ln tim chng trc ch cn li rt t. 3.4. Liu lng v ng a vaccine vo c th 3.4.1. Liu lng Liu lng vaccine tu thuc vo loi vaccine v ng vo c th. Liu lng qu thp s khng kh nng kch thch c th p ng min dch. Ngc li, liu lng qu ln s dn n tnh trng dung np c hiu i vi ln tim chng tip theo. 3.4.2. ng tim chng Mi loi vaccine i hi mt cch thc chng nga thch hp. Ngi ta s dng nhiu phng php chng nga : - Chng (rch da): y l ng c in nht, c thc hin ngay t lc Jenner sng ch ra vaccine phng bnh u ma. i vi vaccine ny, ng chng vn c dng cho n khi bnh u ma b tiu dit hon ton trn hnh tinh ca chng ta (1979), khng cn phi chng u na. Ngy nay ng chng vn cn c s dng cho mt s t vaccine (BCG, dch hch). - ng tim: c th tim trong da, tim di da hoc tim bp, khng bao gi tim vaccine vo ng tnh mch. a s cc vaccine c th tim di da, ch mt s vaccine khng cho php s dng cch chng nga ny, BCG phi tim trong da, tim di da thng hay gy lot. Phng php tim trong da c nhiu u im : ch cn mt lng vaccin tng i nh (0,1ml), t gy phn ng, hiu ng min dch khng km g phng php tim di da. Tim trong da c th c thc hin bng bm kim tim hoc bng bm nn p lc khng kim, phng php ny gip vic tim chng nhanh chng d thc hin vi quy m rng ri, nhng cn lu ng k thut. - ng ung: ng ung l ng a vaccine vo c th d thc hin nht. Tuy nhin ch thc hin c i vi nhng vaccine khng b dch ng tiu ho ph hu. S hiu bit tt hn v vai tr ca min dch ti ch do IgA tit, nhng vaccine phng nhim trng ng tiu ho hoc nhim trng ni khc nhng vi sinh vt xm nhp vo c th theo ng tiu ho c s dng (nh vaccin bi

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lit) hoc ang c nghin cu a vo c th bng cch ung. ng ung c li im l kch thch min dch ti ch mnh hn nhiu so vi ng tim, nhng ng ung khng bo m s c nh ca virut trong vaccine, cho nn ung ba ln lin tip vaccin bi lit c xem nh cn thit to thnh min dch. - Ngm di li: hin nay c mt s vaccine ng rut iu ch di dng vin ngm di li. Cn phi c mt liu lng khng nguyn cao mi bo m tc dng gy min dch. - Nh mi: c s dng rng ri cho vaccine cm. - Ngoi ra vaccine cn c a vo c th theo mt s ng khc nh kh dung, tht i trng, nhng ng ny t c s dng. 3.5. Cc phn ng ph do tim chng V nguyn tc, vaccine phi m bo an ton. Song trn thc t khng th t c mc an ton tuyt i. Tt c cc vaccine u c th gy ra phn ng ph mt s ngi. - Phn ng ti ch: Nhng phn ng nh thng gp sau tim chng l ni tim c th hi au, mn , hi sng hoc ni cc nh. Nhng phn ng ny s mt i nhanh chng sau mt vi ngy, khng cn phi can thip g. Nu tim chng khng m bo v trng, th ni tim chng c th b vim nhim, lm m. - Phn ng ton thn: Trong cc phn ng ton thn, st hay gp hn c (10 - 20%). St thng ht nhanh sau mt vi ngy. Co git c th gp nhng vi t l rt thp (1/10.000), hu ht khi khng li di chng g. Mt s vaccine c th gy ra phn ng nguy him hn, trong c sc phn v, tuy nhin t l rt thp. Khi bn n nhng phn ng do vaccine, rt cn thit phi nhn mnh rng mc nguy him do vaccine nh hn rt nhiu so vi mc nguy him do bnh nhim trng tng ng gy ra. Th d, t l bin chng nguy him do bnh ho g gp hng trm n hng nghn ln phn ng nguy him do vaccine bch hu - ho g - un vn (vaccine DPT) gy ra. 3.6. Bo qun vaccine Vaccine rt d b hng nu khng c bo qun ng. Cht lng vaccine nh hng trc tip n hiu lc to min dch, v vy cc vaccine cn phi c bo qun tt ngay t lc n c sn xut cho ti khi c tim chng vo c th. Thng quy bo qun cc vaccine khng ging nhau, nhng ni chung cc vaccine u cn c bo qun trong iu kin kh, ti v lnh. Nhit v nh sng ph hu tt c cc loi vaccine, nht l nhng vaccine sng nh vaccine si, bi lit v vaccine BCG sng. Ngc li, ng lnh ph hu nhanh cc vaccine gii c t (nh vaccine phng un vn v bch hu). Trong qu trnh s dng cng ng, cc vaccine cn c bo qun nhit trong khong t 20C n 80C. Mt trong nhng cng vic quan trng nht trong vic t chc tim chng l to lp c dy chuyn lnh. Dy chuyn lnh khng n thun l c cc nh lnh, t lnh, cc phch hoc cc hp cch nhit m cn phi lu c nhng khu trung gian trong qu trnh vn chuyn vaccine v tin hnh tim chng. Vaccine nu b ph hu d c c bo qun li iu kin thch hp cng khng th c hiu lc tr li, cng khng c tc dng na, phi loi b. 4. Tiu chun ca vaccine

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Hai tiu chun c bn nht ca vaccine l an ton v hiu lc. 4.1. An ton Mt vaccine l tng khi s dng s khng gy bnh, khng gy c v khng gy phn ng. Sau khi sn xut vaccine phi c c quan kim nh nh nc kim tra cht ch v mt v trng, thun khit v khng c. - V trng: vaccine khng c nhim cc vi sinh vt khc, nht l cc vi sinh vt gy bnh. - Thun khit: ngoi khng nguyn a vo kch thch c th p ng min dch chng vi sinh vt gy bnh, khng c ln cc thnh phn khng nguyn khc c th gy ra cc phn ng ph bt li. - Khng c: liu s dng phi thp hn rt nhiu so vi liu gy c. Tuy nhin, khng c vaccine no t c an ton tuyt i. Khi cn nhc quyt nh xem mt vaccine no c c a vo s dng hay khng, cn phi so snh gia mc phn ng do vaccine v tnh nguy him ca bnh nhim trng tng ng. 4.2. Hiu lc Vaccine c hiu lc ln l vaccine gy c min dch mc cao v tn ti trong mt thi gian di. Hiu lc ca nhng vaccine rt khc nhau. Ngi ta nh gi bng cch o s p ng min dch. S p ng dch th c th khm ph r rng v nh lng bng nhng th nghim huyt thanh khc nhau, phn nh s bo v nhiu hoc t ty theo lng khng th trong mu. Min dch trung gian t bo kh nh gi hn tr trng hp s dng nhng k thut tm s mn cm nh th nghim tuberculin. Nhng nh nh gi nhng kt qu dch t hc ngi ta o hiu lc thc s ca s chng nga. Vic ny i khi gp kh khn v c th lm pht sinh nhng mu thun. Ngoi 2 tiu chun trn, chn mt vaccine tim chng, ngi ta cn quan tm n gi thnh v tnh thun li cho vic tin hnh tim chng. 5. Phi hp vaccine Mc ch chnh ca vic phi hp vaccine l gim bt s mi tim chng hoc lm gim bt s ln t chc tim chng. C hai loi phi hp vaccine: - Tim chng vaccine phi hp (trn cc vaccine vi nhau, tim chng cng mt ln, cng mt ng). - Tim chng nhiu vaccine ring bit trong cng mt thi gian, c th cc v tr khc nhau hoc theo nhng ng khc nhau. Phi hp vaccine phi m bo gi c hiu lc to min dch v khng gy ra tc hi g. Hiu lc to min dch i vi mi thnh phn vaccine t nht phi bng khi chng c tim chng ring r. Mt s trng hp khi phi hp vaccine to ra c p ng min dch mnh hn. Ngc li c nhng trng hp phi hp khng hp l lm gim hiu lc to min dch. S phi hp vaccine hp l s khng lm tng t l phn ng ph, ngha l an ton vn c m bo nh khi chng c tim chng ring r nhng thi gian khc nhau. 6. Lch tim chng

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C s xy dng lch tim chng l nhng hiu bit v dch t hc ca bnh truyn nhim v s p ng min dch ca i tng c tim chng. Trc khi lp ra lch tim chng cn phi xc nh nhng vn c bn sau y: tui tt nht cho vic tin hnh tim chng i vi mi vaccine, thi gian no tr c nguy c mc bnh ln nht, tnh nguy him ca bnh cc la tui khc nhau v kh nng p ng ca tr khi c tim chng. Tuy nhin, dch t hc ca bnh truyn nhim mt thi gian no c th b thay i do chnh vic s dng vaccine, khi lch tim chng cn c iu chnh cho ph hp vi tnh hnh mi. Cn c vo dch t hc ca cc bnh truyn nhim ti cc nc ang pht trin v kh nng cung cp vaccine, T chc Y t th gii a ra chng trnh tim chng m rng vi mc tiu l lm gim t l tr em mc v t vong do cc bnh bch hu, ho g, un vn, lao, si v bi lit bng tim chng vaccine. Lch tim chng cc vaccine trong chng trnh tim chng m rng c T chc Y t th gii khuyn co nh sau:
Vaccine BCG (phng lao) Sabin (phng bi lit) DPT (phng bch hu, ho g, un vn) Si Liu lng 0,1 ml 2 git 0,5 ml 0,5 ml ng tim chng Trong da (thng cnh tay tri) Ung Tim bp (thng i) Di da (thng cnh tay tri) Tui tim chng S sinh hoc bt k lc no sau S sinh v lc 2,3,4 thng tui Lc 2,3,4 thng tui Lc 9 thng tui hoc sm nht sau

Lch tim chng thng dng l mt hng dn m ngi ta c th p dng vi mt mc tng i uyn chuyn ty theo hon cnh c nhn. Lc c s chm tr trong p dng lch, khng cn bt u li c chng trnh, ch cn ly li giai on b gin on. Tr nh min dch c bit hiu qu ngay trong thi gian di. Ngoi tim chng m rng tr di 1 tui, tim chng c ch nh trong nhng trng hp sau: - Hon cnh c nhn b thng tch: vt thng, tim gii c t un vn; ng vt di cn, tim vaccine di. Nhng tim chng thc hin sau khi b thng tch hoc b cn ch hiu qu nu thi gian bo v ca vaccine ln hn thi gian bnh. Bnh un vn nh th c th trnh khi bng mt mi tim nhc li. Trong bnh di, thi gian bnh thng thng kh lu nn c th tim chng s khi. - Nguy c ngh nghip: tim vaccine vim gan B cho nhng cn b c nguy c bnh vin. - Nguy c bnh dch: tim chng nhanh cho tp th c nguy c dn n bnh bi lit, si, u ma, no m cu, t.

II. HUYT THANH

1. Nguyn l s dng huyt thanh Dng huyt thanh min dch l a vo c th khng th c ngun gc t ngi hay ng vt, gip cho c th c ngay khng th c hiu chng li tc nhn gy bnh iu tr huyt thanh em li tnh min dch th ng tc thi nhng thong qua, iu ny tri ngc vi tnh min dch hot ng v bn vng trong tim chng.

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2. Phn loi huyt thanh Ngi ta s dng 2 loi huyt thanh: - Huyt thanh khc loi c in, ngun gc ng vt ch yu l nga. Nhng huyt thanh ny c hiu i vi mt bnh nhim trng nht nh c bit m ng vt cho c min dch ha trc . Loi huyt thanh ny c li im r nhng c nhng bt li l dung np km, c th gy qu mn tc thi nh shock phn v hoc qu mn chm nh bnh huyt thanh, hiu lc li ngn hn ch ko di n 2 hay 3 tun l sau ln tim th nht, vi ngy sau nhng ln tim tip theo. S dng huyt thanh khc loi phi nn hn ch v phi trnh tim li cng mt ngi. - Huyt thanh ng loi ngun gc ngi, mi c s dng gn y. l ch phm globulin min dch ch yu l globulin ngi tinh ch, loi tt c nguy c nhim trng nh virus vim gan, HIV... i vi huyt thanh ng loi ngi ta phn bit globulin min dch a gi (bnh thng) c ly t mu ngi kho mnh hoc t mu rau thai v globulin min dch c hiu c bo ch t mu nhng ngi c min dch nh ngi lnh bnh nhim trng hoc mi c tim chng. Trong globulin min dch c hiu, nng khng th chng li vi sinh vt, l cn nguyn ca bnh nhim trng, thng cao gp hng chc ln trong globulin min dch a gi. Globulin min dch ngi rt t tin, nht l loi c hiu v c sn xut gii hn v ph thuc vo ngi cho, nhng c u im thng c dung np tt, c th tim li cng mt ngi v c kh nng bo v lu di, nhiu tun l cho n 1 thng. 3. Nguyn tc s dng huyt thanh Cc nguyn tc c bn phi thc hin khi s dng huyt thanh l: - ng i tng - ng liu lng - ng ng - phng phn ng - Phi hp s dng vaccine 3.1. i tng Huyt thanh c s dng nhiu nht cha v d phng cc bnh nhim trng. Ngoi ra n cn c s dng cho mt s mc ch khc nh iu tr thiu ht min dch, d ng v d phng bnh tan mu s sinh. - Nhng huyt thanh chng nhim trng ch c hiu lc vi nhng bnh m c ch bo v ch yu nh min dch dch th. Kinh in nht l huyt thanh khng un vn (SAT) v huyt thanh khng bch hu (SAD). Huyt thanh khng ho g, khng si c tim cho tr cha c tim chng c tip xuc vi bnh nhn. Huyt thanh khng di c tim cho nhng ngi b ch di cn hoc nghi di cn vi vt thng nng hoc gn u. Ngoi ra cn c cc huyt thanh khng virus vim gan, vius quai b, rubon. Globulin min dch cn c tim cho nhng bnh nhn vim ng h hp ti pht nhiu ln. - Globulin min dch ngi a gi thng c s dng trong nhng trng hp sau:

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+ iu tr suy gim min dch th bm sinh hoc thu hoch. + Mt vi hon cnh bnh l c nguy c nhim trng trm trng nh bng. + Phng nga mt vi bnh nhim trng ph bin nh si, vim gan A. - Globulin min dch khng D c dng cho ngi m c nhm mu Rh (-) mi sinh con c Rh (+) c tc dng ngn cn s hnh thnh khng th khng Rh v do trnh c nguy c tan mu s sinh cho a tr sau. C ch ca hin tng ny l globulin min dch khng D s ph hu cc hng cu Rh (+) ca a tr xm nhp vo dng tun hon ca ngi m khi sinh. Do c ch ny, vic tim globulin khng D ch c hiu qu trong thi gian 72 gi sau khi sinh. Globulin min dch ngi c th trung ha hiu lc ca mt vi vaccine sng, v vy nn trnh tim vaccine si trong 3 thng sau khi tim globulin min dch ngi. 3.2. Liu lng Liu lng huyt thanh s dng tu thuc vo tui v cn nng ca bnh nhn, trung bnh t 0,1 n 1 ml/kg cn nng tu theo loi huyt thanh v mc ch s dng. Huyt thanh khng un vn c tnh theo n v, trung bnh l 250 n v cho mt trng hp. Nu vt thng qu bn hoc tim chm sau 24 gi th liu lng phi tng gp i. 3.3. ng a huyt thanh vo c th Huyt thanh thng c a vo c th bng ng tim bp. i vi nhng loi huyt thanh c tinh ch t tiu chun cao, c th tim tnh mch nhng cng rt nn hn ch. Tuyt i khng tim tnh mch nhng huyt thanh c ngun gc t ng vt (d c tinh ch) hoc huyt thanh ngi cha t tinh ch cao. 3.4. phng phn ng bnh nhn tim huyt thanh nga mt ln th ln tim th 2 c th gy nn hin tng qu mn, nn khi tim huyt thanh cn thc hin tt cc vic sau y ngn nga phn ng do huyt thanh gy ra: - Trc ht phi hi xem bnh nhn tim huyt thanh nga ln no cha? Trng hp bnh nhn tim huyt thanh ri th cn phi cn nhc cn thn. Nu thy tht cn thit mi tim li ln th 2 v t l phn ng cao hn nhiu so vi ln th nht. - Lm phn ng gii mn cm (phn ng Besredka) trc khi tim: pha long huyt thanh 10 ln vi nc mui sinh l 0,85 %, tim 0,1 ml trong da. Nu khng c mn sau 30 pht th tim c lng huyt thanh cn thit. Nu c mn m khng c huyt thanh ng loi tim v tnh trng bnh nhn bt buc phi s dng huyt thanh th phi tim dn dn t liu nh n liu ln cch nhau 20-40 pht v c nh th cho n khi tim ht liu cn thit trong 2 gi. - Trong qu trnh tim huyt thanh cn theo di bnh nhn lin tc kp thi can thip nu c phn ng xy ra, c bit l phi chun b y cc iu kin x tr sc phn v. 3.5. Tim vaccine phi hp Khng th do tim huyt thanh s pht huy hiu lc ngay sau khi tim, nhng ch tn ti mt thi gian ngn. Hiu gi khng th ny gim nhanh trong my ngy

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u, sao gim chm hn nhng cng s b loi tr ht sau khong 10 - 15 ngy, do phn ng vi cc khng nguyn vi sinh vt v do b c th chuyn ho ging nh s phn cc protein l khc. Vic tim vaccine phi hp nhm kch thch c th to ra min dch ch ng thay th lc min dch th ng do tim huyt thanh ht hiu lc. 4. Cc phn ng do tim huyt thanh Ni chung loi globulin min dch c ngun gc t ngi c tinh ch cao v a vo c th bng ng tim bp t gy ra cc phn ng nguy him. Tuy nhin cn phi lu rng, t l phn ng do tim huyt thanh cao hn nhiu so vi phn ng do tim chng vaccine. Nhng phn ng khi tim huyt thanh do hai c ch chnh: - Do c th phn ng vi cc thnh phn khng nguyn l, nht l i vi cc huyt thanh cha c tinh ch cao. - Do c th sn xut khng th chng li chnh globulin min dch. Cc phn ng do tim huyt thanh c th l ti ch hoc ton thn. 4.1. Phn ng ti ch Ni tim c th b au, mn . Nhng phn ng ny thng nh, khng gy nguy him v s ht sau mt t ngy. 4.2. Phn ng ton thn Bnh nhn c th b st, rt run, kh th, au cc khp, mt s trng hp c th b nhc u v nn. Sc phn v l phn ng nguy him nht. Nu tim huyt thanh ln u, phn ng thng xut hin sau 10 - 14 ngy. Nu tim huyt thanh ln th hai, phn ng c th xy ra ngay sau khi tim n sau mt vi ngy, tu thuc vo lng khng th ln tim trc cn nhiu hay t. Cc triu chng ca sc phn v nh kh th do ph n ng h hp trn v co tht thanh qun; nga ton thn; ni m ay v ban sn khp ngi, sng mt. Bnh nhn c th au bng v b i do cc c trn b co tht. Ngoi ra cn gp cc triu chng do phc hp khng nguyn khng th ng li trong cc tiu ng mch nh vim cu thn, vim c tim, van tim, vim khp...

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VI SINH VT TRONG T NHIN V K SINH NGI CC NG TRUYN BNH

Mc tiu hc tp 1.Trnh by c s phn b ca vi khun trong t, trong nc v trong khng kh v cc yu t nh hng n s phn b 2. Trnh by c cc vi khun k sinh trn c th ngi v vai tr ca chng 3. Trnh by c cc ng ly truyn bnh Vi sinh vt phn b khp ni trong t nhin. Ngi ta thy chng trong t, trong nc, trong khng kh, trn cy c, trong thc n, trn nhiu dng c khc nhau v trn c th ngi v ng vt. Mi quan h gia vi sinh vt v mi trng ngoi cnh l rt cht ch gi l sinh thi hc. l mi quan h thch ng, c ngha l vi sinh vt c kh nng thch ng tn ti trong iu kin ngoi cnh nht nh. Nhim v quan trng ca vi sinh vt y hc l nghin cu vi sinh vt gy bnh c ngoi cnh tm cc phng php phng nga chng, ng thi nghin cu s phn b ca vi sinh vt trn c th ngi c bin php phng bnh thch hp.

I. VI SINH VT TRONG T NHIN

1. Vi sinh vt trong t t cha rt nhiu vi sinh vt v l mi trng thch hp cho s pht trin ca vi sinh vt, v trong t c nc, c khng kh, c cc cht v c v cc cht hu c to thnh mt mi trng thin nhin thch hp cho vi sinh vt. Ty theo tnh cht v thnh phn ca t mi ni c khc nhau v kh hu c khc nhau m s lng v chng loi vi sinh vt cng phn b khc nhau. V d: b mt ca t do tc dng ca nh sng mt tri v s kh ro, s lng vi sinh vt t. su 10 - 20 cm th s lng vi sinh vt nhiu, chng loi a dng. Nhng n su mt mt tr i th s lng v chng loi vi sinh vt gim dn v ch c mt s t vi sinh vt tn ti m thi v su ny, thiu xy v cc cht hu c nn vi sinh vt hiu kh khng pht trin. t cn b nhim phn v cc cht bi tit ca ngi v ng vt vi mc khc nhau nn s lng v thnh phn vi sinh vt cng khc nhau. Tuy rng trong t c nhiu vi sinh vt khc nhau nhng ngi ta phn chia thnh 3 loi: - Loi th nht: vi sinh vt t dng: t tng hp cc cht cn thit sng. - Loi th hai: vi sinh vt d dng l vi sinh vt lm thi ra xc ng vt, thc vt trong t. - Loi th ba: vi sinh vt gy bnh theo thi th hoc theo cht bi tit ca ng vt v ca con ngi ri vo trong t. Loi vi sinh vt ny i hi phi c nhiu cht dinh dng v mt s iu kin thch hp, cho nn loi ny rt d cht, ch c cc vi khun sinh nha bo th c kh nng tn ti lu trong t. T t, vi sinh vt gy bnh c th ly sang c th ngi v ng vt. ng ly ch yu l gin tip do s

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nhim ca t bn vi d rau qu xanh b nhim vi sinh vt. Nghin cu vi sinh vt trong t l mt vn lun c t ra, nht l nhng vng c lin quan n cht thi cng nghip, cht thi sinh hot, cht thi t cc l m, bnh vin... ra nhng bin php dit tr v phng cc mm bnh c th ly lan t t sang ngi, nht l khu bo v mi trng. 2. Vi sinh vt trong nc Nc l mt mi trng t nhin trong vi sinh vt c th pht trin c, bi v vi sinh vt ch sinh sn trong iu kin m t. Vi sinh vt vo nc t t, bi, khng kh v t cht thi b ca ngi v ng vt. S lng v chng loi vi sinh vt thay i tu theo bn ca nc. Nc sng, h gn ch dn c ng c c nhiu vi sinh vt, nc bin v cc h ln th t vi sinh vt hn. Nc c kh nng t lm sch do tc dng thanh khun ca nh sng mt tri v do s cnh tranh sinh tn ca cc vi sinh vt trong nc. Ngoi nhng vi sinh vt sng trong nc, cn c nhng vi sinh vt gy bnh do ngi v ng vt lm nhim. Do vy nc cng l ngun truyn bnh nguy him nht l cc bnh ng rut, nh vi khun Salmonella, Shigella, Vibrio cholerae... Cc vi sinh vt gy bnh ny ch tn ti trong nc mt thi gian nht nh v gy bnh cho ngi trong mt thi k nht nh. Nu mt ngun nc b nhim phn th thng thy xut hin E.coli - vi khun ny thng c dng trong vic nh gi s nhim phn ca nc. Ngoi ra trong mt ngun nc c mt vi khun Clostridium perfringens chng t ngun nc b nhim phn t trc. 3. Vi sinh vt trong khng kh Khng kh khng phi l mi trng thun li cho vi sinh vt pht trin v khng c cht dinh dng, thm vo li c nh sng mt tri. Tuy nhin trong khng kh vn c vi khun do cun theo bi t v do con ngi bi tit ra khi ho, khi ht hi... Vi sinh vt trong khng kh c nhiu chng loi, nhng loi no c bo t, c sc t v nm chu c kh hanh v nh sng mt tri mi tn ti c. S lng vi sinh vt trong khng kh ty thuc tng vng. nhng vng dn c ng c th trong khng kh c nhiu vi sinh vt, ni cao v trn cc i dng th khng kh c rt t vi sinh vt. thnh th khng kh cha nhiu vi sinh vt hn nng thn. Trong khng kh, ngoi cc tp khun, nm, nm mc, ngi ta thng gp cc vi sinh vt gy bnh l: trc khun lao, trc khun bch hu, lin cu tan mu, t cu gy bnh, trc khun ho g, virus cm, si... t bnh nhn hoc t ngi lnh mang trng bi tit ra khng kh v lm ly lan t ngi ny sang ngi khc ch yu l hnh thc gin tip thng qua nhng ht nc bt nh mang vi sinh vt. Trong khng kh lu thng, nhng ht ny tn ti khng lu nn kh nng nhim bnh gim xung, do v mt phng bnh cn lu vn lu thng khng kh ni bung bnh v ni cng cng.

II. VI SINH VT TRN C TH NGI

Da, nim mc v cc t nhin nui dng nhiu chng loi vi sinh vt, nhng vi sinh vt c xp vo 2 nhm : - Khun ch bnh thng: gm nhng chng lai vi khun tng i c nh, tm thy u n mt vng nht nh, mt la tui nht nh, nu b ph hy th t thit lp li mt cch nhanh chng.

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- Khun ch tm thi: gm nhng vi sinh vt c hoc khng c kh nng gy bnh, c ng da, nim mc trong khong thi gian gii hn, pht sinh t mi trng xung quanh, khng pht sinh chng bnh, khng t nh c thng xuyn b mt c th. Thnh phn ca khun ch tm thi thng khng c ngha khi khun ch binh thng cn nguyn vn. Tuy nhin nu khun ch bnh thng b ph hy th khun ch tm thi c th pht trin v pht sinh chng bnh. 1. Vai tr ca khun ch bnh thng Khun ch bnh thng mi vng nht nh ca c th gi mt vai tr nht nh trong vic duy tr sc khe v cc chc nng bnh thng. - Khun ch bnh thng da v nim mc: l hng ro ngn cn u tin cn tr qu trnh xm nhim ca cc vi sinh vt theo c ch cnh tranh sinh tn hoc giao hon vi khun. - Thnh phn khun ch bnh thng rut gip c th tng hp mt s vitamin nh K, B1, B6 ... v gp phn thun li cho vic nui dng c th. Tuy nhin thnh phn khun ch bnh thng c th gy nn bnh trong mt s hon cnh v nhng vi sinh vt ny thch nghi vi kiu sng khng xm nhim, nu b bt buc ri khi ch c ng bnh thng v a vo mu hoc m th chng tr nn gy bnh. V d : + Streptococus viridans thng k sinh ng h hp trn, nu vo mu do nh rng hoc ct amygdales th c th gy nn bnh vim mng trong tim bn cp (bnh Osler) + Xon khun v trc khun hnh thoi : bnh thng khoang ming, nu m b hy hoi do chn thng, c th suy dinh dng hoc nhim trng nng... th chng pht trin mnh m biu m hoi t v gy vim hng (goi l vim hng Vincent). 2. Nhng vi sinh vt k sinh c th ngi 2.1. Cc vi sinh vt trn da Chng loi vi sinh vt sng trn da v nim mc rt thay i, chng ph thuc vo hon cnh, tnh hnh v sinh c nhn v ngh nghip. V da tip xc thng xuyn vi mi trng xung quanh, da cha ng nhiu vi sinh vt tm thi, tuy nhin nhng khun ch bnh thng khng i c tm thy nhng vng gii phu khc nhau. Cc vi sinh sinh vt bnh thng thng thy da l : - Staphylococcus coagulase m tnh, streptococcus viridans, coliformes, cc loi trc khun Gram dng (bacilli gram positive). - Nm men : thng thy cc ln da - Cc Mycobacteria khng gy bnh: thng thy trn da nhng vng sn cht xut tit, c quan sinh dc, ng tai ngoi... - Trn da cng c th c cc vi sinh vt gy bnh nh Staphylococcus aureus, Pseudomonas aeruginosa... Chng loi vi sinh vt sng trn da thay i theo vng: vng c nhiu vi khun nh da u, mt, k ngn tay... Vng c t vi khun nh mt ngoi ca cc chi, bn tay, da bng... Nhng yu t c th ph hy cc vi sinh vt thng thy da l: pH

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thp, axit bo ca cht xut tit nhy v lysozym. S lng vi sinh vt b mt c th gim bt bng cch ch st mnh trong trng hp v sinh da trc khi m, nhng khun ch nhanh chng lp li t tuyn nhn v m hi sau . 2.2. Vi sinh vt ung h hp - mi c nhiu trc khun gi bch hu (diphteroides) v ch yu l t cu, ng ch l c nhiu t cu vng mi trc t 20 - 50 % ngi lnh mang t cu vng trong mi. - hng mi: s lng v chng loi vi sinh vt kh phong ph. Hng thng v khun lc mi sinh, nhng cng c th ly nhim trong khi sinh. Sau sinh trong vng 4 - 12 gi u tin th Streptococcus viridans xut hin nh l thnh phn ch yu v tn ti sut i. Sau cc loi thuc Diphteroides, Lactobacilus, Staphylococci, Neisseria sm c thm vo. - tuyn hnh nhn (amygdales): c th c lin cu nhm A tan mu . y l vi khun ch yu gy vim hng (80 -90%) v gy bnh thp tim tin trin. - kh qun, ph qun: do cu to sinh l c nim dch, i thc bo nn ng h hp di thng khng c vi sinh vt. 2.3. Vi sinh vt ng tiu ha Lc mi sinh ng tiu ha v khun, nhng vi sinh vt c nhanh chng a vo theo thc n. 2.3.1. ngi trng thnh: vi sinh vt ng tiu ha rt a dng v thay i. - ming v thc qun: ming c s cn bng sinh thi gia cc vi khun vi nhau. Phn ln cc vi khun sng chung, tuy vy cng c mt s c kh nng gy bnh quyt nh tnh trng nhim khun, v d nhim khun ti ch tai mi hng, rng, hoc i khi gy bnh cho ton thn do c t hoc vi khun xm nhp vo mu. Thng thy ming l cc cu khun Gram (+), cu khun Gram (-), trc khun Gram (+), cc vi khun k kh nh Clostridium, cc xon khun. Ngoi ra cn thy cc vi khun ng rut, trc khun m xanh trong cc trng hp c bit nh c a yu hoc s dng khng sinh ph rng, ko di. - d dy: bnh thng pH rt thp (pH=2) nn c rt t vi sinh vt, a s l vi sinh vt t ming nut vo. V d dy c pH l axit nn ch c vi khun lao tn ti c. Nhiu cng trnh nghin cu chng minh c mt loi xon khun l Helicobacter c kh nng pht trin trong mi trng axit ca d dy c bit l hang v. Trong ging ny c Helicobacter pylori l cn nguyn ca vim lot d dy, t trng. Trong mt s trng hp nh ung th, let d dy, t trng... th pH thay i nn c th c t cu v nm. - rut: + rut non: pH kim v c enzyme li gii vi sinh vt nn ch cn nhng vi sinh vt sng st khi i qua d dy. Ch c mt s t lin cu, t cu, cc loi thuc Lactobacilus ti rut non. ngi b let d dy - t trng, vim rut, x gan th c th thy E.coli rut non . + rut gi: c rt nhiu vi sinh vt, c 1011 vi sinh vt trong 1 gam cht cha to nn 10 - 20 % khi lng phn kh. Cc vi sinh vt rut gi ch yu l vi khun k kh (99%) bao gm cc loi thuc Bacteroides, Clostridium spp., Lactobacilus..., cc vi khun hiu kh ch c 1% gm E.coli, lin cu D, t cu, Proteus...

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2.3.2. tr em: Sau sinh mt vi gi c vi sinh vt pht trin. tr em nui bng sa m, vi sinh vt ch c mt loi hnh th - ch yu 99% l Bifidobacterium bifidum, sau l E.coli, cn tr em nui bng sa b th c nhng loi vi sinh vt nh ngi ln. mt ngi th vi sinh vt rut tng i n nh, tuy vy cng c th thay i do: ch n ung, tui: ngi gi th tng E.coli v cc loi Clostridium. Trong mt s iu kin nht nh th c s thay i ln i ng vi sinh vt rut nh a chy, to bn... S dng khng sinh cng lm o ln i ng vi sinh vt, n lm gim s lng khun ch bnh thng bng cc vi sinh vt khng thuc t ngoi vo. 2.4. Vi sinh vt ng sinh dc- tit niu Trong iu kin bnh thng, ch bn ngoi b my sinh dc mi c vi sinh vt. nam gii th c Mycobacterium smegmatis, l niu o c t cu, trc khun Gram m. n gii l ngoi niu o c t cu, trc khun gi bch hu, vi khun ng rut... Sau sinh th Lactobacilus (trc khun Doderlin) xut hin c quan sinh dc v tn ti sut i chng no pH vn cn axit. Lc pH tr nn trung tnh th c cc vi khun khc nh cc cu khun v trc khun. tui dy th, Lactobacilus gim v lc b ph hy v iu tr khng sinh... th Candida albicans v nhng vi khun khc c th pht trin gy nn bnh.

III. NGUN GC V CC NG TRUYN BNH NHIM TRNG

1. Ngun truyn bnh Bao gm bn ngoi v bn trong c th. 1.1. Ngun gc bn ngoi - Mi trng truyn cho ngi: mt s vi sinh vt gy bnh trong t c nha bo tn ti lu, c th gy bnh cho ngi. - Ngi truyn cho ngi: chim a s, bao gm ngi bnh v ngi lnh mang trng. Ngi bnh t trc lc thy r triu chng cho n sau khi khi bnh mt thi gian vn cn mang vi khun. - ng vt truyn sang cho ngi: nhiu bnh truyn nhim do ng vt truyn sang cho ngi: bnh dch hch (chut), bnh di (ch)... 1.2. Ngun gc bn trong C mt s vi sinh vt bnh thng sng da, nim mc hay cc t nhin (khun ch bnh thng). Lc c yu t thun li: c th suy yu, s dng khng sinh... chng pht trin mnh m v gy nn bnh, v d : E.coli t i trng n ng tit niu th gy bnh. 2. Phng thc truyn bnh 2.1. Truyn bnh do tip xc Ngi khe tip xc vi ngi m hay ng vt m qua cc hnh thc c xt, giao hp, b, lim, cn, qua nhau thai, qua s dng c, dng c nhim vi sinh vt hay dng c y t, thuc, mu, huyt thanh ca ngi bnh hay ngi lnh mang trng nhim vi sinh vt. 2.2. Truyn bnh qua n ung

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a s bnh ung rut ly truyn do n ung phi thc n, nc ung b nhim khun do ngi bnh hoc ngi lnh mang trng bi tit ra nh t, l, thng hn, bi lit... qua mi gii nc, rui nhng, gin, tay chn bn... 2.3. Truyn bnh do cn trng tit tc a s cc bnh nhim trng theo ng mu do cn trng tit tc truyn bnh nh mui, rn, b cht... 3. i tng truyn bnh i tng truyn bnh l c th cm nhim. Khi c ngun bnh v ng ly truyn thch hp nhng nu khng c c th cm nhim th khng th pht sinh bnh. Do c th cm nhim l khu quan trng trong qu trnh ly truyn ca bnh nhim trng. C th cm nhim l nhng i tng v l do dinh dng, bnh tt... m kh nng khng (bao gm min dch th ng, min dch khng c hiu v c min dch ch ng c hiu) u b suy gim v nh vy khi gp vi sinh vt xm nhim th d dng mc bnh nhim trng. C th cm nhim thng gp l tr em, ngi gi, ngi mc cc bnh mn tnh, ph n c thai...

NHIM TRNG BNH VIN

Mc tiu hc tp 1. Nu c nh ngha th no l nhim trng bnh vin (NTBV). 2. M t c tm quan trng ca NTBV, cc vi sinh vt gy nhim trng, cha, phng thc ly truyn, v cc yu t nh hng n NTBV. 3. Trnh by c cc NTBV thng gp.

I. NH NGHA
Nhim trng bnh vin (NTBV) l nhim trng xy ra lc ngi bnh nm iu tr bnh vin, nhim trng ny khng biu hin cng khng thi k bnh lc ngi bnh vo vin. Nhng nhim trng mc phi bnh vin nhng ch biu hin sau khi ngi bnh ri bnh vin cng c k vo. Mc d nhiu NTBV c th phng nga nhng c mt s khng th phng nga nn NTBV khng tng ng vi nhim trng do thy thuc tc l nhim trng do can thip chn on hoc iu tr nh t ng thng niu o hoc thng tnh mch. Nhim trng c hi xy ra nhng bnh nhn m c ch bo v b suy gim v thng gy nn do nhng tc nhn nhim trng bnh thng khng gy bnh ngi khe mnh. Nhim trng c hi gy nn do vi khun khun ch ca ngi bnh v thng khng trnh khi v lin quan n tn thng ro cn nim mc hoc nhng c ch bo v khc ca ngi bnh.

II. CN NGUYN V DCH T HC

1.T l bnh NTBV xy ra t 2 n 10 % (trung bnh 5%) ngui bnh iu tr bnh vin. T l NTBV thay i ty theo bnh vin, thng cao nhng bnh vin trung ng; iu ny phn nh tnh trng nng hn ca chng bnh ngi bnh v vic s dng nhiu hn nhng phng tin chn on v iu tr d gy chn thng.

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NTBV c th nghim trng v dn n t vong. Trung bnh NTBV c t l t vong 1%, ph tn iu tr NTBV kh ln. Hn na NTBV lm gim nng sut lao ng v ngi bnh phi c iu tr thm mt thi gian. 2. Vi sinh vt gy NTBV Thng gp nht l vi khun hiu kh Gram m, t cu, lin cu rut. - Trc khun Gram m quan trng nht trong cc vi sinh vt gy NTBV v chng l tc nhn chnh ca nhim trng ng tiu v cn gy bnh nhng v tr khc. Nhng trc khun ng rut nh E. coli, Klebsiella thng tm thy trong NTBV nhng bnh nhn m c ch bo v b suy gim. Nhiu trc khun Gram m nh Pseudomonas v Klebsiella c nhu cu dinh dng ti thiu nn c th to nn nhng bnh mi trng bnh vin cng nh ngi bnh. Cc trc khun Gram m pht trin s khng thuc nhanh hn cc cu khun Gram dung, trc khun Gram m tr nn khng thuc qua thu hoch plasmid R. Ngoi ra Enterobacter, Pseudomonas v Serratia cn c c ch t bin nhim sc th khng penicillin v cephalosporin. - Trong cc cu khun Gram dng S. aureus hin nay vn cn l tc nhn gy bnh quan trng. N thng gy nhim trng vt thng phu thut, bng v thng tnh mch. T cu vng tm thy khp ni, da, tc, t hu ca ngi bnh v nhn vin bnh vin, tay nhn vin bnh vin, dng c v hu ht vt tm thy bnh vin. Nhiu chng S. aureus khng thuc c tm thy nhiu bnh vin, chng c th gy nn nhng v dch nhim trng nhng n v chm sc tch cc. Chng khng vi erythromycin, clindamycin v aminoglycoside. Nhng chng t cu khng methicillin (MRSA: methicillin resistant S. aureus ) cng l tc nhn gy nhim trng bnh vin gp kh ph bin nhiu ni trn th gii: an Mch gp vi t l 0,1%, Thu in 0,3%, H Lan 1,5%, Thu S 1,8%, mt s nc khc tm thy cao hn 20% chng t cu khng methicillin nh o 21,6%, Begium 25,6%, Ty Ban Nha 30,3%, Php 33,6% Nhng chng S. epidermidis cng mang nhng gen a khng v c th truyn nhng gen cho S. aureus. - Lin cu rut c bit t lu l mt tc nhn NTBV quan trng v ng tiu, n l tc nhn c ngha vt thng ca nhng ngi bnh iu tr vi cc cephalosporin. c bit nhiu chng enterococci khng aminoglycoside nh gentamicin v vancomycin - Danh sch nhng vi sinh vt quan trng trong NTBV ang tng ln ng k. Nhng nhim trng c hi gy nn bi nhng vi khun c lc thp ( S. epidermidis) v nm (Aspergillus, Candida) cng thng gp. Vim rut kt do Clostridium difficile l hu qu ca s bin i khun ch ng rut do iu tr khng sinh. - Virus ng h hp nh virus hp bo ng h hp v virus cm, gn y virus corona gy bnh SARS (severe acute respiratory syndrome) l cc tc nhn NTBV. Nhng virus khc nh virus vim gan, HIV lin h n nhim trng do truyn mu hoc cc sn phm mu, do tai bin. Cytomegalovirus, virus varicella-zoster v rotavirus cng gi mt vai tr ng k trong NTBV, nhng tc nhn ny gy nhim trng bnh vin nhng ngi suy min dch, nhng bnh nhn ghp c quam . 3. cha Nhn vin y t, bnh nhn v nhng ngi n thm l cha u tin. Hu ht nhim trng bnh vin xut pht t vi khun sng trn c th ngi bnh

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Cc vi khun gy bnh thng c tr cc v tr gm: hc mi nh t cu vng, t cu khng methicillin; trn da S. epidermidis; ng tiu ho nh enterococci, cc vi khun h ng rut, cc loi Candida. ng sinh dc tit niu enterococci, vi khun h ng rut. Nhng bnh nhn b nhim trng hay tnh trng mang cc vi khun khng nh enterococci khng thuc, t cu khng methicillin, Clostridium difficile s lm nhim bn mi trng. V mi trng b nhim bn li tr thnh cha th pht. Mt s mi trng l cha u tin mt s vi khun gy bnh nh: nc cha vi khun Legionella, cc loi Pseudomonas; thc n cha cc vi khun ng tiu ho 4. S ly truyn vi sinh vt trong NTBV 4.1. Ly trc tip Trong bnh vin, tay nhn vin y t thng b nhim bn tm thi v thng l mi gii truyn vi khun t ngi ny n ngi khc. Nhng nhn vin y t kho mnh thng mang cc vi khun gy bnh nh t cu vng, Streptococcus pyogenes, Salmonella enteritidis v truyn cc vi khun ny cho ngi bnh. 4.2. Ly qua dng c Cc dng c nh nhit k in t, thuc men, cc loai dch chuyn tnh mch, thc n, sa, cc loai dung dch ung c th truyn cc vi khun gy nhim trng bnh vin cho ngi bnh. 4.3. Ly qua khng kh Khng kh trong bnh vin, h thng thng kh c th truyn cc tc nhn nh M. tuberculosis, virus varicella-zoster, virus corona gy SARS, cc loi nm Aspergillus. Bi nc b nhim bn c th truyn cc vi khun Legionella 5. Nhng yu t nh hng n NTBV Cng nh phn ln nhng nhim trng, NTBV l hu qu ca s tng tc gia 2 nhn t 5.1. Yu t vi sinh vt: c lc v kh nng lan trn ca vi sinh vt gy bnh, 5.2. S khng ca ngi bnh: Tui, chng bnh, s ton vn ca nim mc v da v tnh trng min dch l nhng nhn t chnh quyt nh t l bnh v hu qu ca NTBV. Nhng c ch bo v c th: vt l (suy gim trong trng hp bng hoc chn thng), ha hc (thiu HCl dch v, ct d dy lm gii hn axit dch v) hoc min dch (bnh Hodgkin, ha liu php chng ung th.v.v...) nh hng mnh m n NTBV. Ngoi ngi bnh v vi sinh vt, nhng nhn t khc lin quan n NTBV bao gm cc bin php chn on thm d chc nng, nhng phng thc iu tr, nhng bnh nhn nhiu nguy c NTBV l nhng bnh nhn suy gim min dch, bnh nhn iu tr vi thuc lm gim sc bo v (corticosteroid .v.v...) v bnh nhn trong qu trnh iu tr l i tng vi nhiu ln can thip. S dng ngy cng nhiu nhng phng php chn on gy chn thng lm tng xc sut NTBV. Nhn vin bnh vin cng c nguy c NTBV, nhn vin phng xt nghim c mu nghim mu c th mc bnh vim gan virus, HIV v nhng khoa ly (lao, ho g...).

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III. NHNG NHIM TRNG BNH VIN THNG GP

1. Nhim trng ng tiu Nhim trng ng tiu chim khong 40% NTBV v thng do a dng c vo niu o, bng quang v thn. yu t thun li cho nhim trng ngc dng l t ng thng niu o lm bt hot ro cn bnh thng. Kho st cho thy 10-15% bnh nhn ngi ln c thng niu o, trong nhiu trng hp khng cn thit t. ng tit niu l tiu im nhim trng thung gp nht a n nhim khun huyt do vi khun Gram m. 2. Nhim trng vt thng Phn ln nhim trng vt thng gy nn do vi khun trc tip a vo m trong thi gian phu thut. Thng thng vi khun c ngun gc l khun ch ca ngi bnh, tuy nhin nhn vin phu thut c th l ngun gc ca nhim trng, c bit vi lin cu A v S. aureus. Nhng yu t nh hng n t l nhim trng vt thng bao gm loi phu thut, thi gian phu thut, k nng ca thy thuc v sc khe c bn ca ngi bnh. Phu thut nhng v tr b nhim bn nh rut, c quan sinh dc n thng d b nhim trng hn l nhng v tr v trng trc khi m. Phu thut thi gian di hoc phu thut trong nhng m cht, vt th l hoc bu mu c ly i thng tng t l nhim trng vt thng. Nhng nhn t thun li khc bao gm ngi ln tui, tnh trng dinh dng km, s hin din ca mt tiu im nhim trng u , bnh i ng, suy thn v iu tr corticosteroid. Nhng vt thng khng m gm bng, lot do nm, lot da do tc ngn tnh mch hoc ng mch cng l v tr ca NTBV. Nhng vi khun gy nhim trng cng tng t nh vt thng m tr nhim trng bng thng do P. aeruginosa v nhim trng let vng chu cng nh nhng chi di thng do khun ch rut. 3. Vim phi Nhim trng ng h hp di thng l nguyn nhn a n t vong NTBV mc d v t l n ng th ba sau nhim trng ng tiu v nhim trng vt thng. Nhng vi khun gy bnh ch yu l trc khun Gram m v S. aureus, nhng vi khun ny thng n ng h hp di do t hng hn l qua ng mu. Vim phi bnh vin thng xy ra cc i tng sau: - Ngi bnh tr m phn x nn v ho khng hiu qu - Ngi bnh c chng bnh phi hoc suy tim xung huyt - Ngi bnh cn dng dng c hoc h tr thng kh. S ly truyn virus ng h hp bnh vin cng hay gp c bit khoa nhi, nhng tr trng hp cm, hp bo ng h hp, gn y virus corona gy vim phi cp v suy h hp cp tnh nng c t l t vong cao trn 10% bnh nhn b nhim trng. Nhn vin bnh vin thng nhim virus h hp ca ngi bnh v s ly lan do hit phi hoc tip xc trc tip qua nim mc cc git cht tit c virus t bnh nhn khi sn sc , khi tip xc vi ngi bnh. Cc phng thc ly khc nh dng cc dng cu h tr h hp, qua tay...Bin php phng nga s ly nhim cc virus h hp nh SARS gm pht hin v cch ly bnh sm, s dng bin php bo v nh dng khu trang c lc, mang gng v cc trang phc bo v mt, u khi sn sc ngi bnh.

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4. Nhim khun huyt Mc d nhim khun huyt c th xy ra bt c NTBV no, nhng canuyn huyt qun b nhim bn l nguyn nhn thng thng v d phng nga nht ca nhim khun huyt tin pht bnh vin. Nhim trng do iu tr tnh mch chim khong 5% tng s NTBV v 10% ca tng s cy mu dng tnh. Nhng vi khun gy bnh thng gp l S. epidermidis, S. aureus, trc khun Gram m v lin cu rut. Lc dinh dng bng dch qua ng thng th Candida cng l tc nhn quan trng. Vi khun c th vo bt c v tr no khi c ng chuyn dch, thng v tr vo da lc t Canuyn hoc nhng th thut sau v vi sinh vt theo canuyn vo mu. dch truyn c th b nhim khun gy nn nhim khun huyt do mt trong nhng vi khun km c lc nh Enterobacter, Serratia, Citrobacter freundii, nhng vi khun ny c th pht trin dch truyn cha 5% glucose. Nhim khun huyt tm thi sau nhng thao tc chn on hoc iu tr ming, ng h hp, ng tiu ha, ng sinh dc thng c ngi bnh dung np tt. Tuy nhin nhng ngi c bnh tim hoc van tim bm sinh c th c nguy c vim mng trong tim lc chu nhng thao tc ni trn v cn c phng nga bng khng sinh. 5. Nhim trng cc virus vim gan B, C v HIV Nhim trng do virus vim gan B v virus HIV lin quan khng nhng ngi bnh v c nhn vin y t trong sn sc bnh nhn hoc thao tc mu mu ca ngi bnh. Ngi bnh nhiu nguy c l ngi bnh nhn chuyn mu hoc ch phm mu hoc nhng bnh nhn qua thm phn lc mu. Vic xt nghim sng lc loi tr nhng ngi cho mu b nhim trng cc virus ny cng vi vic x l mu trc khi chuyn loi tr HIV lm gim t l vim gan do virus B v C v HIV sau truyn mu. S ly nhim HIV xy ra cho nhn vin y t do cc tai bin kim tim hoc cc dng c sc nhn m vo tay trong qu trnh ly mu, m x..Nhim trng HIV trong nh rng t bc s n ngi bnh cng c cp Nhng bin php phng nga nhim trng cc virus vim gan v HIV bao gm: 5.1. Cn ph bin thc phng bnh gii hn s ly truyn do kim tim hoc tip xc trc tip. 5.2. Dn nhn hiu v thao tc cn thn tt c mu mu v m ca ngi bnh. 5.3. Khuyn co nhn vin c nguy c nhim trng nn tim phng vacxin 5.4. Cn lu nhng trng hp nhim trng HIV trong giai on sm cc xt nghim sng lc tm khng th s cho kt qu m tnh. Nhng mu mu nghi ng cn c kim tra k bng tm khnh nguyn hoc axit nucleic ca virus. 5.5. Tim ngay globulin min dch vim gan B v vacxin vim gan B cho nhn vien v ngi bnh c nguy c c bit vim gan B nh b kim tim ngi bnh vim gan B m vo da.

IV. KIM TRA NHIM TRNG BNH VIN

1. Mc tiu Kim tra NTBV bao gm nhng mc tiu : 1.1. Lm gim nguy c NTBV ngi bnh. 1.2. Chm sc y nhng ngi bnh b nhim trng ly truyn mnh.

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1.3. Gim n mc ti thiu nguy c nhim trng nhn vin bnh vin. Phn ln nhng bnh vin thnh lp mt ban kim tra NTBV. Ban ny c nhim v : - Tm bin php thch hp x l bnh nhim trng. - Xc nh v theo di nhng ngi bnh b bnh truyn nhim. - Phng nga s ly truyn bnh nhim trng ngi bnh v nhn vin. - Theo di vic s dng khng sinh v mc nhy cm vi khng sinh ca cc vi sinh vt thng gy NTBV. 2. Bin php Nhng bin php ch yu bao gm ra tay gia nhng ln tip xc vi ngi bnh, cch li thch ng nhng bnh nhim trng d ly truyn, p dng nhng bin php dch t hc xc nh v loi b kp thi nhng nhim trng. Nhng bin php phng nga khng nhng p dng vi ngi bnh m c vi nhn vin bnh vin. Lc nhp vin phi chn la ring ngi bnh ly, iu ny c bit quan trng vi khoa nhi, khoa ung th v khoa ghp c quan v nhng bnh nhim trng t quan trng nh thy u, si c th nguy him vi ngi bnh nhng khoa .

PHN II

CC VI KHUN GY BNH THNG GP CC CU KHUN GY BNH

Mc tiu hc tp 1. Trnh by c mt s tnh cht vi khun hc ca mt s cu khun gy bnh. 2. Nu c kh nng gy bnh ca cc cu khun ny. 3. Trnh by c mt s phng php chn on vi khun hc i vi cc cu khun gy bnh. Cu khun gy bnh bao gm T cu, Lin cu, Ph cu v Neisseria. l nhng vi khun hnh cu v c gi chung l cu khun sinh m. Tr Neisseria, cc cu khun sinh m u Gram dng.

I. T CU (STAPHYLOCOCCI)
T cu tm thy khp ni v c th phn lp t khng kh, bi, thc phm, c th ngi v ng vt. T cu l thnh vin ca khun ch da hoc nim mc t hu ngi. C 3 loi t cu c kh nng gy bnh nhim trng ngi: Staphylococcus aureus (S.aureus: t cu vng) c xem l t cu gy bnh, Staphylococcus epidermidis (S. epidermidis) v Staphylococcus saprophyticus (S. saprophyticus) thng xem nh l t cu khng gy bnh; tuy nhin 2 loi sau cng c th gy nhim khun ng tit niu hoc nhim khun trong phu thut tim, trong thng tnh mch. Ni dung bi ny tp trung vo S. aureus. 1.c im sinh vt hc 1.1. Hnh thi

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Vi khun hnh cu hoc hnh thun, ng knh 0,8-1m, canh thang thng hp thnh tng cm nh chm nho, hnh thc tp hp ny do vi khun phn bo theo nhiu chiu trong khng gian. Trong bnh phm vi khun hp tng i hoc m nh. Vi khun bt mu Gram (Gram dng). Vi khun khng di ng, khng sinh nha bo, thng khng c v. 1.2. Tnh cht nui cy Vi khun pht trin d dng mi trng thng thng, hiu kh hoc k kh ty , mc tt 37 0C nhng to sc t tt 20 0C. canh thang sau 5 - 6 gi lm c mi trng, sau 24 gi lm c r. mi trng c, khun lc trn li, bng lng, ng nh c th c mu vng m, mu vng cam hoc mu trng, tng i ln sau 24 gi. Nhng chng khc nhau lm tan mu nhng mc khc nhau, thch mu typ tan mu thng c quan st xung quanh khun lc. 1.3. Tnh cht sinh ha v khng T cu c h thng enzyme phong ph, nhng enzyme c dng trong chn on l: catalase (phn bit vi lin cu), S. aureus c coagulase (tiu chun quan trng phn bit t cu vng vi cc t cu khc). T cu ln men chm nhiu loi ng, to axt nhng khng sinh hi, S. aureus ln men ng mannt. T cu tng i chu nhit v thuc st khun hn nhng vi khun khc, chu kh v c th sng mi trng nng NaCl cao (9%), nhy cm thay i vi khng sinh, nhiu chng khng vi penicillin v cc khng sinh khc. 1.4. Cu trc khng nguyn Vch t bo vi khun cha khng nguyn polysaccharide, khng nguyn protein A b mt. Ngi ta c th cn c vo cc khng nguyn trn chia t cu thnh nhm, tuy nhin phn ng huyt thanh khng c gi tr trong chn on vi khun. Cn c vo s nhy cm vi phage, ngi ta chia t cu thnh type phage. Nhng b phage cho php xp loi phn ln cc chng t cu thnh 4 nhm phage chnh. nh type phage t cu c gi tr v dch t hc v chn on. 1.5. Cc c t v enzyme Kh nng gy bnh ca t cu l do vi khun pht trin v lan trn rng ri trong m cng nh to thnh nhiu c t v enzyme. 1.5.1. Hemolysin: c 4 loi hemolysin c xc nh l , , v . Mt chng t cu c th to thnh nhiu hn mt loi hemolysin. l nhng phm vt bn cht protein gy tan mu nhng tc ng khc nhau trn nhng hng cu khc nhau. Chng c tnh sinh khng. Mt vi loi hemolysin gy hoi t da ti ch v git cht sc vt th nghim. 1.5.2. Leucocidin: l nhn t git cht bch cu ca nhiu loi ng vt, bn cht protein, khng chu nhit. T cu gy bnh c th b thc bo nh t cu khng gy bnh nhng li c kh nng pht trin bn trong bch cu. 1.5.3. Coagulase: lm ng huyt tng ngi hoc th chng ng vi citrat natri hoc oxalat natri. Coagulase lm dnh t huyt vo b mt vi khun v do hnh nh cn tr s thc bo. Tt c cc chng S. aureus u c coagulase dng tnh. 1.5.4. Hyaluronidase: thy phn axit hyaluronic ca m lin kt, gip vi khun lan trn vo m. 1.5.5. -lactamase: s khng penicillin ca t cu vng l do a s t cu vng sn xut c enzyme -lactamase.

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Ngoi ra, t cu cn c nhng enzyme khc nh staphylokinase l mt fibrinolysin lm tan t huyt, nuclease, lipase. 1.5.6. c t rut: do mt s chng t cu to thnh, c bit lc pht trin nng CO 2 cao (30%) v mi trng c va. N khng s un si trong 30 pht cng nh tc ng ca enzyme rut. C 5 typ huyt thanh A, B, C, D, E; typ A, B thng gy ng c thc n. 1.5.7. c t gy hi chng shock nhim trng (Toxic schock syndrome toxin: TSST): thng gp nhng ph n c kinh nguyt dng bng bng dy, bn hoc nhng ngi b nhim trng vt thng. C ch gy shock ca n tng t vi ni c t. 1.5.8. Exfoliatin toxin hay epidermolitic toxin: l mt ngoi c t, gy nn hi chng phng rp v chc l da (Scaded skin syndrome) tr em. 85% cc chng t cu vng thuc loi phage nhm II to c t ny. N gm 2 loi A v B, u l polypeptid, loi A bn vng vi nhit 100 0C/20pht, cn loi B th khng. C th xc nh chng bng k thut min dch (nh ELISA hoc RIA hay min dch khuch tn). Khng th c hiu c tc dng trung ho c t ny. 1.5.9. Alpha toxin: bn cht protein, gy tan cc bch cu a nhn v tiu cu, t gy ra p xe, hoi t da v tan mu. c t c tnh khng nguyn nhng khng th ca n khng c tc dng chng nhim khun. 2. Kh nng gy bnh ng xm nhp l da (gc chn lng, ch b thng) v nim mc. T cu khng gy nn mt chng bnh nht nh nhng thng lm pht sinh nhiu hnh thc nhim khun khc nhau. T cu thng gy nn nhng im nung m da, nim mc nhng c th xm nhp vo nhng c quan khc nhau. S nhim trng xy ra nhng c th khng st km nh gi yu, tr cn b, bnh i tho ng. 2.1. Cc nhim trng da v nung m su L mt hnh thc c bit, nng l inh ru, tip n l chc l, vim ty xng, vim phi mng phi, vim mng ngoi tim, vim mng no. 2.2. Nhim trng huyt T nhng im nung m, vi khun c th i vo mu v gy nn nhim trng huyt. Nhim trng huyt do t cu l mt bnh thng gp bnh vin, thng xy ra ngi c sc khng gim st. 2.3. Vim rut cp tnh Thng gp cc bnh nhn ung khng sinh c khng khun ph rng, khng sinh hy dit nhng vi khun bnh thng rut, lm pht trin chng t cu sinh c t rut v gy nn chng bnh. 2.4. Ng c thc n Do t cu sinh c t rut c bit type huyt thanh A v B gy nn. Chng bnh c nhng c im: thi gian bnh ngn (1-8 gi), bun nn d di, nn, au bng, a chy, khng st, bnh phc trong vng 24 gi. 2.5. Hi chng da phng rp (Scalded skin syndrom) Mt s chng t cu vng tit c t exfoliatin, gy vim da hoi t v phng rp. Bnh ny thng gp tr mi v tin lng xu. 2.6. Hi chng shock nhim c (Toxic shock syndrome) Thng gp nhng ph n c kinh nguyt dng bng v sinh dy, bn, b nhim vi khun t cu vng. Bnh khu tr m o v cn nguyn l t cu vng, lin quan n c t gy hi chng shock nhim trng, cy mu khng tm thy t cu vng. 3. Chn on vi khun

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Bnh phm l m, mu, m gii, phn, nc no ty ty theo chng bnh. Phn lp thch mu, canh thang hoc thch Chapman. Xc nh nh hnh thi knh hin vi v tnh cht sinh ha. T cu c xem nh S. aureus nh 4 tiu chun : sc t vng, tan mu, ln men ng mannit, to thnh coagulase. Trong 2 tiu chun coagulase v ln men ng mannit l quan trng nht, ch c th thiu mt trong 2 tiu chun ch khng th thiu c 2. Phn ng huyt thanh khng c gi tr chn on vi khun. Ngi ta nh typ t cu bng phage. Nh nhng phage chnh c hiu ngi ta xp t cu vo mt trong 4 nhm phage chnh (I, II, III v IV). T cu thuc nhm no th b ly gii bi mt hoc nhiu phage trong nhm . nh typ phage c gi tr v dch t hc. 4. Phng nga v iu tr 4.1. Phng nga Ngun t cu trong thin nhin l ngi. S ly nhim t ngi ny sang ngi khc l do tip xc trc tip hoc qua khng kh. Nhng ngi lnh mang trng c khuyn co khng nn lm vic phng sinh, phng tr s sinh, phng m hoc cc x nghip thc phm. 4.2. iu tr Nhiu chng T cu khng vi nhiu khng sinh nht l penicillin nn cn lm khng sinh . C trng hp s dng vaccine bn thn v vaccine tr liu c kt qu.

II. LIN CU (STREPTOCOCCI)

Lin cu l nhng cu khun xp thnh hnh chui, phn b rng ri trong thin nhin. Mt vi loi l thnh vin ca khun ch bnh thng ngi. Mt vi loi gy nn nhng chng bnh quan trng. 1. c im sinh vt hc 1.1. Hnh th Vi khun hnh cu, ng knh1 m, Gram dng, thng xp thnh chui di ngn khc nhau, c th ng i hoc ring l. Vi khun khng c lng, khng to nha bo. Nhiu chng thuc nhm A v C to v axit hyaluronic. 1.2. Tnh cht nui cy Lin cu l nhng vi khun hiu k kh ty , ch pht trin tt mi trng c mu hoc c cc dch ca c th khc. Nhng chng gy bnh thng i hi nhiu yu t pht trin. Phn ln lin cu tan mu gy bnh pht trin tt 37 0C. Cc lin cu rut pht trin tt khong nhit t 10 n 450C. mi trng lng vi khun d to thnh cc chui, sau 24 gi canh thang vn trong v c nhng ht, nhng cm dnh vo thnh ng sau lng xung y ng. thch mu, khun lc nh trn li mu hi xm, bng hoc m c. Nhng chng ca lin cu A c v to nn nhng khun lc ly nhy. Lin cu gy nn 3 typ tan mu: tan mu ca lin cu tan mu A, tan mu ca lin cu viridans v tan mu ca lin cu khng tan mu. 1.3. Tnh cht sinh vt ha hc Lin cu khng c catalase (khc vi t cu). Lin cu A c bit nhy cm vi bacitracin. phn bit lin cu v ph cu, ngi ta da vo kh nng ca lin cu khng vi mt hoc mui mt hoc vi optochin trong khi ph cu th ngc li. 1.4. Cu trc khng nguyn Lin cu c cu trc khng nguyn phc tp. 1.4.1. Khng nguyn v axit hyaluronic

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Tm thy v mt s lin cu A, khng c tnh cht sinh khng. 1.4.2. Khng nguyn carbohydrat C c hiu nhm y l khng nguyn nm vch t bo vi khun. Da vo khng nguyn carbohydrat C, Lancefield chia lin cu tan mu thnh nhiu nhm huyt thanh t A n O. Phn ln nhng lin cu gy bnh ngi thuc nhm A, tuy nhin nhng chng nhm B, C v G cng tm thy trong nhim trng h hp, nhim trng huyt v vim mng trong tim. 1.4.3. Khng nguyn M c hiu typ Khng nguyn M cng nm vch t bo vi khun, l protein M lin h n Lin cu A v tm thy nhng vi khun to thnh khun lc m c hoc ly nhy. N cn tr s thc bo. Cn c vo khng nguyn ny ngi ta chia lin cu A thnh nhiu typ, hin c trn 55 typ trong typ 12 gy bnh rt nghim trng. 1.4.4. Phm vt T Bn cht protein, khng lin quan n c lc, thu c bng cch thy phn ph hy protein M. Phm vt T cho php phn bit mt s typ lin cu. 1.5. Cc enzyme v c t Lin cu to thnh nhiu enzyme v c t. 1.5.1. Streptokinase Tm thy nhiu chng lin cu tan mu . N bin i plasminogen thnh plasmin c kh nng thy phn t huyt v nhng protein khc. Streptokinase kch ng s to thnh khng th khng streptokinase (ASK) v enzyme ny c s dng iu tr nhng tr ngi do ng mu gy nn. 1.5.2. Streptodornase Enzyme ny c kh nng thy phn DNA do lm lng m. Mt ch phm cha streptokinase v streptodornase c dng lm lng dch ngoi tit c, gip cho khng sinh n ch nhim trng v c s dung trong lam sng iu tr vim m mng phi. 1.5.3. Hyaluronidase : Thy phn axit hyaluronic, cht cn bn ca m lin kt v gip cho vi khun bnh trng su rng vo cc m. 1.5.4. Dung huyt t : Lin cu tan mu to thnh 2 loi dung huyt t : - Streptolysin O: c hot tnh tan mu trng thi kh oxy, nhng nhanh chng b bt hot trng thi oxy ha. C tnh cht sinh khng mnh, n kch ng to thnh khng th khng streptolysin O (ASO). Trong chn on bnh thp khp cp v vim cu thn cp, vic nh hiu gi ASO rt c gi tr khng nh nhim lin cu. - Streptolysin S: chu trch nhim v s hnh thnh vng tan mu xung quanh khun lc thch mu, khng b bt hot bi oxy v khng c tnh sinh khng. 1.5.5. c t sinh : Gy pht ban trong bnh tinh hng nhit, thng tm thy lin cu A. 2. Phn loi lin cu Da vo kh nng lm tan mu, s khng vi tc nhn l ha v th nghim sinh ha ngi ta chia lin cu thnh 4 nhm : 2.1. Lin cu tan mu To dung huyt t ha tan chu trch nhim v typ tan mu thch mu. Chng to thnh cacbohydrat C c hiu nhm. Da vo cacbohydrat C ngi ta chia lin cu tan mu thnh nhiu nhm t A n O.

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2.2. Lin cu viridans Khng gy tan mu thch mu. Nhiu loi gy tan mu , nhng cng c nhng loi khng tc dng vi mu. Lin cu viridans khng to thnh cacbohydrat C. Chng l thnh phn ch yu ca khun ch ng h hp v ch gy bnh lc xm nhim van tim khng bnh thng hoc mng no hoc ng tiu. 2.3. Lin cu rut To thnh cacbohydrat C c hiu nhm D, pht trin tt nhit t o 10-45 C, nng 6,5% NaCl v thch 40% mui mt. Kh nng tan mu thay i. Chng c tm thy khun ch bnh thng rut v c th gy bnh lc xm nhim m, mu, ng tiu hoc mng no. 2.4. Lin cu lactic Tan mu thay i, pht trin thch cha 40% mt nhng khng pht trin 45oC, khng gy bnh, thng tm thy trong sa. 3. Kh nng gy bnh Trong cc lin cu th lin cu nhm A l nhm lin cu gy bnh nhiu nht ngi. Chng gy nn nhng bnh cnh sau : 3.1. Cc nhim khun ti ch Nh vim hng, vim t hu, chc l, vim qung ngi ln, nhim khun cc vt thng. 3.2. Cc nhim khun th pht Nh vim mng trong tim cp, st hu sn hoc nhim khun huyt m im xut pht l t da, t cung hoc t vng t hu. 3.3. Bnh tinh hng nhit Thng gp tr em trn 2 tui cc nc n i. 3.4. Cc di chng ca nhim lin cu A c im ca nhim khun Lin cu A l s xut hin cc di chng 2-3 tun l sau bnh lin cu, c bit l sau vim hng. Di chng c th l vim cu thn cp hoc thp khp cp. 3.4.1. Vim cu thn cp Xy ra mt s ngi 1-3 tun l sau khi nhim lin cu A, c bit l nhim cc typ 12, 4, 49 hoc 57 hng hoc da, do s tc ng ca phc hp khng nguyn-khng th ln mng c bn ca tiu cu thn. Triu chng l tiu mu, ph thng, cao huyt p. Cc gi thuyt cho rng l do s tc ng ca khng th chng li khng nguyn vch ca lin cu nhm A phn ng cho vi mng y ca cu thn. 3.4.2. Thp khp cp L mt di chng nghim trng nht v n a n ph hy c tim v van tim. Mt vi chng lin cu A c khng nguyn mng t bo phn ng cho vi si c tim. Huyt thanh ca bnh nhn thp khp cp cha khng th phn ng vi nhng khng nguyn . Thp khp cp c xu hng tr nn nghim trng trong nhim trng ti pht. Ngoi ra, phc hp min dch globulin min dch-b th-khng nguyn ca lin cu c chng minh bng min dch hunh quang thng tn ca tiu cu thn v c tim. 4. Tnh min dch S khng vi lin cu c tnh cht c hiu typ. Ch c khng th khng M c hiu typ c kh nng chng li s nhim trng. Lin cu A c trn 55 typ huyt thanh. Nhn chung khng ngi no tr nn min dch vi tt c nhm lin

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cu A. Cc khng th khng Streptolysin O v khng Streptokinase khng c kh nng bo v c th. 5. Chn on vi sinh vt 5.1. Chn on trc tip Bnh phm thch hp, c th l mu, m, m gii, nc tiu, nc no ty v..v..ri nui cy ln trn cc mi trng thch hp; phn lp v nh danh vi khun da vo c im hnh th, tnh cht nui cy, tnh cht khun lc, tnh cht tan mu. Nhng chng lin cu A rt nhy cm vi bacitracin. Xc nh nhm ca lin cu tan mu nht l nhm A, B, C, G bng th nghim ng ngng kt. 5.2. Chn on gin tip Trong cc trng hp nh thp khp cp c th s dng phn ng ASO nh hiu gi ASO trong mu bnh nhn. y l mt phn ng trung ha enzyme, bnh thng hiu gi ASO < 200 n v. Trong trng hp bnh l ASO tng cao. ASK t c s dng. 6. Phng bnh v iu tr 6.1. Phng bnh Ngun nhim lin cu A l ngi, ch yu l phng bnh chung nh pht hin sm nhng nhim trng da, hng do lin cu A gy nn iu tr vi khng sinh thch hp. Cn pht hin v iu tr nhng ngi lnh mang trng phc v cc nh h sinh, nh tr, phng m. 6.2. iu tr i vi lin cu A phi iu tr sm liu lng y vi khng sinh git khun nh penicillin, erythromycin. i vi lin cu viridans, lin cu rut, cn phi hp khng sinh gia nhm lactamin v aminoglycosit nh penicillin v streptomycin hoc iu tr theo khng sinh .

III. PH CU (STREPTOCOCCUS PNEUMONIAE)

Ph cu thng gp vng t hu ca ngi bnh thng vi t l kh cao (20-40%). 1. c im sinh vt hc 1.1. Hnh th Ph cu l cu khun Gram dng, hnh ngn nn, xp thnh i, 2 u ging nhau nhn vo nhau to thnh hnh mt knh hay s 8. Trong mi trng nui cy, ph cu thng xp thnh chui ngn d nhm vi lin cu. Trong bnh phm hay trong mi trng nui cy giu albumin th vi khun to v. Nui cy lu ngy mi trng nhn to th khng c v. Vi khun khng c lng, khng to nha bo. Nhng enzyme t ly gii lm cho vi khun mt mu Gram ri ly gii. 1.2. Tnh cht nui cy Ph cu l vi khun hiu k kh ty , mc tt mi trng giu cht dinh dng v kh trng 5 - 10% CO2. Nhit thch hp 370C, pH 7,2 - 7,6. thch mu khun lc sau 24 gi nh, trn, b u, trong, lc u li, sau lm gia vi b cao xung quanh, to vng tan mu xung quanh khun lc.

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1.3. Tnh cht sinh ha Ph cu ln men nhiu loi ng, khng sinh hi, catalase m tnh, phn ng Neufeld dng tnh (tan trong dung dch mt hay mui mt), khng mc mi trng c optochin. 1.4. Sc khng Ph cu d b git cht bi nhng cht st khun thng thng (Phenol, Cl2Hg) v nhit (60 0C trong 30 pht). Trong qu trnh gi chng, vi khun d b gim c lc hoc bin i t dng khun lc S sang dng R (khng c v). Ph cu khng chu c nhit qu lnh v qua nng. Nhit gi chng thch hp l 18oC - 30oC. 1.5. Cu trc khng nguyn 1.5.1. Khng nguyn v: bn cht polysaccharide. Da vo khng nguyn v, ph cu c chia thnh 85 typ huyt thanh. V gi vai tr quan trng trong c lc ca vi khun. 1.5.2. Khng nguyn thn: bao gm carbohydrat C c hiu nhm v protein M c hiu typ tng t nh lin cu A. 2. Kh nng gy bnh Ph cu thng gp t hu vi t l kh cao. Lc ng h hp b thng tn, ph cu xm nhp vo c th gy bnh ng h hp, in hnh l vim thy phi, thng do typ 1, 2, 3 gy nn. Bnh xy ra l t, c th tr thnh dch c bit v ma ng. N cng thng gy vim ph qun, p xe phi, vim mng phi c m. Ph cu cn l mt tc nhn thng gy vim mng no m tr em. Ngoi ra ph cu cn gy cc nhim khun khc nh vim xoang, vim tai, vim hng, vim kt mc mt, vim mng ngoi tim, vim khp, nhim khun huyt. 3. Chn on vi sinh vt Nhum Gram, nu thy nhiu cu khun Gram dng hnh ngn nn xp tng i ng thi vi bch cu a nhn v i thc bo s b chn on vim do ph cu v c th bt u iu tr. ng thi nui cy chn on xc nh. nh danh vi khun da vo c im hnh th, khun lc v mt s th nghim phn bit vi lin cu tan mu nh neufeld dng tnh, optochin dng tnh. nh typ ph cu bng phn ng phnh v. 4. Phng bnh v iu tr 4.1. Phng bnh Hin nay vaccine polysaccharide v cha ph bin. Ch yu l phng bnh chung: lc sc khng ca c th gim nh b cm cn bi dng sc khe, tr em ngi gi yu d b ph vim cn mc m v ma ng, lc c s thay i t ngt nhit . 4.2. iu tr Cn iu tr sm. Ph cu nhy cm vi erythromycin, penicillin, ampicillin, chloramphenicol, bactrim.

IV. NO M CU (NEISSERIA MENINGITIDIS)

1. c im sinh vt hc 1.1. Hnh th Cu khun Gram m hnh ht c ph 0,8 x 0,6 m, thng ng thnh i ring l hoc thnh m nh. Xem trc tip t bnh phm c th tm thy vi khun trong bch cu a nhn. Vi khun khng lng, nhiu chng c v. 1.2. Tnh cht nui cy

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No m cu hiu kh tuyt i, ch mc cc mi trng giu cht dinh dng nh thch mu, thch chocolat, Thayer - Martin 37 0C kh trng 5 -10% CO2. Khun lc to thnh sau 24 gi, nh, trn, li, bng, m u, mu xm. 1.3. Tnh cht sinh ha Oxydase dng tnh, catalase dng tnh, glucose dng tnh khng sinh hi, maltose dng tnh, sacharose m tnh. 1.4. Cu trc khng nguyn No m cu c cc thnh phn khng nguyn sau 1.4.1. Khng nguyn v: bn cht polysaccharide, c tnh cht c hiu nhm. Da vo khng nguyn ny, no m cu c chia thnh nhiu nhm huyt thanh: A, B, C, 29-E, H, I, K, L,W-135, X, Y, Z. Khng nguyn polysaccharide ca no m cu c phng thch ra trong dch no ty trong thi k u ca bnh nn c th chn on sm bnh bng cch xc nh khng nguyn ny trong dch no ty. 1.4.2. Khng nguyn vch: bn cht protein, nm mng ngoi cng ca ca vch t bo vi khun, c tnh c hiu typ. No m cu nhm B c 12 typ. 1.5. Sc khng No m cu c sc khng km. Rt d cht, trong bnh phm nc no ty n ch sng khong 3-4 gi sau khi ra khi c th. D b cht bi nhit (600C trong 10 pht). 2. Kh nng gy bnh No m cu thng sng vng t hu m khng gy nn triu chng, trng thi ngi lnh mang trng c th ko di trong t ngy n nhiu thng. Trong nhng iu kin khng thun li cho c th nh mc khng m, cm lnh vi khun i vo mu s gy nn vim mng no m. Him hn, n c th gy nn nhim khun huyt ti cp rt nng, vi st cao, pht ban, t vong cao do xut huyt thng thn. Rt him khi nhim khun huyt do no m cu tr thnh mn tnh v ko di nh st khng r cn nguyn. 3. Chn on vi sinh vt - Nhum soi: bnh phm l mu, dch no ty. Nhum Gram v nhum xanh mtylen kho st bch cu v tm song cu Gram m, hnh ht c ph. - Phn lp nui cy vi khun: ng thi cy bnh phm ln thch mu hoc thanh chocolat, 37 0C bnh c 5-10% CO 2. Phn lp v nh danh da vo tnh cht hnh th, tnh cht khun lc v s ln men cc loi ng: glucose dng tnh khng sinh hi, maltose dng tnh, sacharose m tnh. - Tm khng nguyn polysaccharide trong nc no ty bng k thut in di min dch i lu vi khng huyt thanh mu th c th chn on trong giai on sm. 4. Phng bnh v iu tr 4.1. Phng bnh 4.1.1. Phng bnh khng c hiu: cho tr em mc m v ma lnh, pht hin ngi lnh mang trng, pht hin sm v cch ly bnh nhn. Nhng ngi tip xc vi bnh phi cho ung khng sinh phng, thng dng rifampicin. 4.1.2. Phng bnh c hiu: Hin nay vaccine hn hp bao gm khng nguyn polysaccaride t 4 nhm no m cu A, C, Y v W-135 t ra rt hiu qu trong phng bnh. 4.2. iu tr iu tr bng khng sinh thch hp sm v liu lng cao. Cc khng sinh thng dng l peniciline, chloramphenicol, cc cephalosporin... Cc sunfamit thm qua mng no tt nhng t l no m cu khng thuc ny cao nn khng c dng mt mnh iu tr no m cu.

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V. LU CU (NEISSERIA GONORRHOEAE)
1. c im sinh vt hc 1.1. Hnh th Ging nh no m cu, lu cu l cu khun Gram m hnh ht c ph, kch thc 0,8 x 0,6 m, thng xp thnh i. Trong lu cp tnh, lu cu thng rt nhiu v nm trong bch cu a nhn. Trong lu mn tnh lu cu t hn thng nm ngoi t bo. 1.2. Tnh cht nui cy Nui cy kh khn v khi ra ngoi c th vi khun rt d cht, cn phi cy ngay vo mi trng. Lu cu ch mc mi trng giu cht dinh dng nh thch chocolat, thch Thayer-Martin. Vi khun pht trin tt trong iu kin hiu kh pH 7,2-7,6, nhit 35-360C v kh trng c 5-10% CO2. Khun lc sau 48 gi nh, trn, dt, mu xm nht. 1.3. Tnh cht sinh ha Oxydase dng tnh, catalase dng tnh, glucose dng tnh khng sinh hi, maltose m tnh, sacharose m tnh. 1.4. Sc khng Lu cu c sc khng km, cht nhanh khi ra khi c th. Trong bnh phm, vi khun cht nhit phng trong 1-2 gi, nhit 58 0C trong1 gi. Dung dch nitrat bc 1% git cht lu cu trong vng 2 pht. 1.5. Cu trc khng nguyn Lu cu c nhiu khng nguyn c hiu nhm v typ. Trong thc t, cc khng nguyn khng gip ch g cho vic xc nh vi khun. 2. Kh nng gy bnh Lu cu ch tm thy ngi, khng tm trong thin nhin. Ngi mc bnh do ly truyn trc tip qua ng sinh dc, qua da, nim mc, gic mc. N gy vim niu o (bnh lu) c nam v n. N cn gy nhim khun nhng b phn khc nhau ca ng sinh dc: nam gy vim tin lit tuyn, vim mo tinh v n gy vim c t cung, vim t cung, vim vi trng. Ngoi ra, lu cu c th gy nhim khun cc c quan khc nh nhim khun huyt a n nhim khun khp, vim mng trong tim, vim kt mc. tr s sinh, c th xy ra vim kt mc do lu cu khi i qua ng sinh dc ca m b bnh, nu khng iu tr kp thi c th gy m la. 3. Chn on vi sinh vt 3.1. Chn on trc tip - nam, ly m niu o lc sng sm trc khi i tiu ln u tin trong ngy. - n, ly m l niu o, c t cung, cc l ca tuyn m o. 3.1.1. Nhum Gram - Chn on bnh lu cp tnh: soi knh hin vi tiu bn nhum Gram, nu c nhiu bch cu a nhn trung tnh v nhiu song cu Gram m ni bo th c th xc nh bnh nhn mc bnh lu. - Chn on bnh lu mn tnh: trn tiu bn nhum gram bnh phm, thng t thy lu cu v lu cu nm ngoi bch cu a nhn, c th c nhiu tp khun khc, cn nui cy xc nh vi khun. 3.1.2. Chn on bng k thut PCR 3.2. Nui cy: Trong c hai trng hp cp v mn, cn cy bnh phm vo mi trng thch hp, phn lp v nh danh vi khun nh vo tnh cht nui cy v sinh ho. 3.2. Chn on huyt thanh

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- Tm khng th khng lu bng khng th n dng gn hunh quang. - Tm IgM bng ELISA chn on lu ngoi ng sinh dc. 4. Phng bnh v iu tr 4.1. Phng bnh Lu cu khng to nn min dch bo v sau khi khi bnh. Ch yu pht hin bnh v iu tr trit , ci thin hon cnh x hi. i vi tr s sinh phng nga vim kt mc do lu cu, sau khi tr lt lng nh mt git nitrat bc 1%. 4.2. iu tr Hin nay, xut hin nhng chng lu cu khng vi penicillin G, do cn phi lm khng sinh la chn khng sinh thch hp cho vic iu tr bnh. Tuy nhin trong thc t, penicillin G vn l khng sinh thng dng v nhiu trng hp cho kt qu tt. Ngoi ra khng sinh nh ampicillin, oxacillin, spectinomycin, cefoxitin, rifamycin cng dng iu tr tt bnh lu. Cn iu tr trit trnh chuyn sang lu mn tnh. i vi lu mn tnh, chn on kh v iu tr phc tp, tn km.

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H VI KHUN NG RUT (Enterobacteriaceae)

Mc tiu hc tp 1. Trnh by c i cng v h vi khun ng rut. 2. Trnh by c cc c im sinh vt hc v kh nng gy bnh ca cc vi khun E.coli, Salmonella, Shigella, Klebsiella v Proteus. 3. Nu c phng php chn on vi sinh vt, nguyn tc phng v iu tr bnh i vi E.coli, Salmonella, Shigella, Klebsiella v Proteus.

I. I CNG V H VI KHUN NG RUT

1. Ni c tr Cc vi khun ng rut thng sng ng tiu ha ca ngi v ng vt, c th gy bnh hoc khng gy bnh. Ngoi ra chng c th sng ngoi cnh (t, nc) v trong thc n. 2. Hnh th Cc vi khun thuc h Enterobacteriaceae l nhng trc khun gram m khng sinh nha bo. Mt s ging vi khun thng khng di ng (Klebsiella, Shigella), mt s vi khun khc di ng nh c lng xung quanh thn t bo. Mt s ging c v nhn thy c nh knh hin vi thng nh Klebsiella. 3. Nui cy Cc vi khun ng rut hiu kh k kh ty tin, pht trin c trn cc mi trng nui cy thng thng. Trn cc mi trng c, cc khun lc ca cc vi khun ng rut thng nhn, bng (dng S). Tnh cht ny c th bin i sau nhiu ln nui cy lin tip thnh cc khun lc c b mt kh v x x (dng R). Cc khun lc ca cc vi khun c v nh Klebsiella l khun lc nhy, ln hn khun lc dng S v c xu hng ha ln vo nhau. Nghin cu cc tnh cht sinh vt ha hc gip cho vic nh loi vi khun. 4. Tnh cht sinh vt ha hc Cc vi khun thuc h Enterobacteriaceae ln men glucose, c sinh hi hoc khng sinh hi, oxidase m tnh, catalase dng tnh, kh nitrate thnh nitrite. Ln men hoc khng ln men mt s ng (v d lactose). C hay khng c mt s enzyme nh urease, tryptophanase. Kh nng sinh ra H2S khi d ha protein, axt amin hoc cc dn cht c lu hunh... 5. Cu trc khng nguyn cc vi khun ng rut ngi ta c th phn bit: Cc khng nguyn thn hoc khng nguyn O Cc khng nguyn lng hoc khng nguyn H

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Cc khng nguyn b mt (v hoc mng bc) c gi l khng nguyn K. Vic nghin cu cc khng nguyn khc nhau ny cho php phn chia cc vi khun thuc cng mt loi hoc mt ging ra cc type huyt thanh.

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5.1 Khng nguyn O L khng nguyn nm trong vch t bo vi khun, bn cht l lipopolysaccharide (LPS) bao gm: Thnh phn protein lm cho phc hp c tnh cht khng nguyn. Thnh phn polysaccharide quyt nh tnh c hiu ca khng nguyn. Thnh phn lipid A chu trch nhim v tnh c. Khng nguyn O (LPS) l ni c t, khi tim cho ng vt, n gy ra cc phn ng gim bch cu, st v nhim c. Cc phn ng ny u thy bnh nhn mc bnh thng hn v sc ni c t. C th ngi hoc ng vt p ng li vi khng nguyn O bng khng th O. Khng nguyn O khi gp khng th tng ng s xy ra phn ng ngng kt gi l hin tng ngng kt O: thn vi khun ngng kt vi nhau di dng nhng ht nh, lc kh tan. 5.2. Khng nguyn H L khng nguyn ca lng ch c nhng vi khun di ng v c bn cht l protein ging nh myosin ca c. Khng nguyn H kch thch c th hnh thnh khng th H v khi gp nhau s xy ra hin tng ngng kt H, trong cc vi khun ngng kt li vi nhau do cc lng kt dnh li to nn cc ht ngng kt rt d tan khi lc. Cc vi khun di ng khi cho tip xc vi cc khng th H tng ng th chng b bt ng. 5.3. Khng nguyn b mt L khng nguyn bao quanh thn ca vi khun hoc di dng mt ci v nhn thy c r rng knh hin vi thng (v d khng nguyn K ca Klebsiella) hoc l di dng mt mng bc khng nhn thy c knh hin vi thng (v d khng nguyn Vi ca Salmonella typhi) 6. Phn loi C nhiu cch phn loi h Enterobacteriaceae. Theo cch phn loi ca Bergeys Manual (1984) chia Enterobacteriaceae lm 13 ging chnh nh sau: Cc ging : I. III. V. VII. IX. XI. XIII. Escherichia Edwardsiella Salmonella Enterobacter Proteus Morganella Erwinia II. IV. VI. VIII. X. XII. Shigella Citrobacter Klebsiella Serratia Providencia Yersinia

Trong cc ging k trn th cc ging vi khun c ngha y hc nht l : Escherichia; Shigella; Salmonella; Klebsiella; Enterobacter; Proteus; Yersinia; cn cc ging khc t ngha

II. ESCHERICHIA COLI

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Escherichia coli (E.coli) l nhng vi khun k sinh, bnh thng c rut, nhng ng thi cng l tc nhn gy bnh khi chng xm nhp vo cc c quan khc nh ng niu, ng mu..., v c mt s chng E. coli c kh nng gy bnh a chy nh ETEC, EPEC, EIEC...

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1. c im sinh vt hc 1.1. Hnh th E.coli l trc khun gram m, di ng do c lng quanh thn, mt s chng E.coli c v polysaccharide, khng sinh nha bo. 1.2. Tnh cht nui cy E.coli l vi khun hiu kh hoc k kh khng bt buc, pht trin d dng trn cc mi trng nui cy thng thng, mt s c th pht trin c mi trng tng hp n gin. Nhit thch hp 370C, pH thch hp l 7 - 7,2. 1.3. Tnh cht sinh vt ha hc E.coli ln men nhiu loi ng sinh axit v sinh hi nh: Glucose, lactose, ramnose; indol dng tnh, methyl dng tnh, VP m tnh, citrat m tnh, urease m tnh, H2S m tnh. 1.4. Khng nguyn ca E.coli E.coli c rt nhiu type huyt thanh m cng thc da vo s xc nh khng nguyn thn O, khng nguyn v K v khng nguyn lng H. Khng nguyn O : C khong 150 yu t khc nhau v mt huyt thanh. Khng nguyn K : c chia ra thnh loi L, A hoc B ty theo sc khng i vi nhit. C chng 100 khng nguyn K khc nhau. Khng nguyn H : xc nh c khong 50 yu t H. 2. Kh nng gy bnh cho ngi E.coli l thnh phn vi khun hiu kh ch yu rut ca ngi bnh thng. S c mt ca E.coli ngoi cnh v trong thc n chng t c s nhim bn do phn. Tuy th vai tr gy bnh ca n c ni ti t lu. E.coli c th gy nhim khun nhiu c quan trong c th ngi. 2.1. Bnh tiu chy do E.coli Cc E.coli gy bnh tiu chy ngi gm c: 2.1.1. Enterotoxigenic E.coli (ETEC) L loi E.coli sinh c t rut. ETEC l mt nguyn nhn quan trng gy tiu chy nng ging triu chng do Vibrio cholerae 01 gy ra ngi. Bnh tiu chy do ETEC xy ra ch yu cc x nhit i v c th gp cc la tui khc nhau, nhng c bit tr nh thng thy bnh cnh lm sng nng d dn ti tnh trng kit nc v ri lon in gii. ETEC cn l mt nguyn nhn thng gy tiu chy cho khch du lch t cc nc pht trin sang cc nc ang pht trin. C ch gy bnh: ETEC vo rut s gn vo nim mc rut nh cc yu t bm dnh, ng thi sn sinh ra c t rut tc ng ln t bo nim mc rut gy xut tit ra mt s lng ln mt cht dch ng trng vi huyt tng. Bnh nhn nn, tiu chy lin tc, phn ln c au nhc bp c, au bng v st nh. C hai loi c t rut c nghin cu k v tnh cht sinh l, sinh ha v tnh truyn bng plasmid l : c t rut LT (Heat-labile toxin) c t rut ST (Heat-stable toxin)

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Nhng chng ETEC c th sinh ra mt hoc hai loi c t rut ty thuc vo plasmid m chng mang. LT loi c t rut b hy bi nhit, l mt protein gm 2 tiu phn A (Active) v B (Binding) c chc nng ring bit. Tiu phn A c hai tiu n v A 1 v A2, tiu phn B c 5 tiu n v B1, B2, B3, B4 v B5. Cc tiu n v B c chc nng gn vi th th ganglioside GM1 b mt t bo biu m rut v chun b m ng cho tiu phn A m ch yu l A1 xm nhp vo bn trong t bo. Tiu n v A tc ng ti v tr ch mt trong mng bo tng ni iu ha enzyme adenylate cyclase. Adenylate cyclase b hot ha v lm tng hm lng adenosine monophosphate vng (AMP vng). Hin tng ny dn ti s tng thm ca cc in gii v nc qua mng rut, gy tiu chy cp v kit nc, ri lon in gii. ST, loi c t rut khng nhit, l mt phn t c trng lng thp nht v khng c tnh khng nguyn. Th th dnh cho ST khc vi th th LT. Sau khi gn vi th th, ST s hot ha guanylate cyclase trong t bo nim mc rut. Hin tng ny dn ti s tng guanosine monophosphate vng (GMP vng) v do xy ra tnh trng tng tit dch rut. 2.1.2. Enteropathogenic E.coli (EPEC) EPEC hin nay c bit gm mt s type huyt thanh thng gy bnh tiu chy cp (bnh vim d dy - rut) tr em la tui nh (tr di mt tui), c th gy thnh dch. Cc v dch do EPEC thng hay gp trong bnh vin, c ch gy bnh ca EPEC cha c bit r. Cc EPEC phn lp t cc v dch thng l thuc cc type huyt thanh: O26 : B6 O55 : B5 O86 : B7 O111 : B4 O119 : B4 O125 : B15 O126 : B16 O127 : B18 O128 : B12

2.1.3. Enteroinvasive E.coli (EIEC) L loi E.coli gy bnh bng c ch xm nhp t bo biu m nim mc rut, gy tiu chy ngi ln v tr em vi nhng triu chng bnh l ging Shigella: ngha l au bng qun, mt rn, i tiu nhiu ln, phn c nhiu mi nhy v mu. Ngi ta chng minh c rng kh nng xm nhp t chc rut ca EIEC c chi phi bi plasmid. EIEC c th khng ln men lactose, khng di ng v ging Shigella v nhiu mt k c cu trc khng nguyn. Do vy nhng v dch tiu chy do EIEC gy nn d b ln ln vi tiu chy do Shigella. 2.1.4. Enteroadherent E.coli (EAEC) L loi E.coli bm dnh ng rut gy bnh do bm vo nim mc v lm tn thng chc nng rut. 2.1.5. Enterohemorrhagic E.coli (EHEC) EHEC l mt trong nhng tc nhn gy tiu chy c th dn ti vim i trng xut huyt v hi chng tan mu - ure huyt. EHEC l nhng chng E.coli c kh nng sn xut mt c t gy c t bo Vero (Verocytotoxin), gi l VT. 2.2. Cc nhim khun khc do E.coli E.coli c th gy nn nhim khun ng tit niu: s ng nc tiu do si, thai nghn... to iu kin thun li cho bnh nhim khun ng tit niu d

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xy ra . Mt khc, khi thng niu o, ngi ta c th gy ra nhim khun ngc dng. E.coli c th gy ra nhim khun ng sinh dc, nhim khun gan mt, vim mng no tr cn b, nhim khun huyt ... 3. Chn on vi sinh vt Ch yu l chn on trc tip phn lp vi khun t bnh phm. Trong bnh tiu chy do E.coli th cy phn phn lp vi khun. Gia cc nhm E.coli khng th phn bit c bng cc th nghim sinh vt ha hc. i vi EPEC th xc nh type huyt thanh bng cc khng huyt thanh mu. i vi ETEC thng c xc nh bng cc th nghim tm kh nng sinh c t rut thng thng nht l tm c t rut bng th nghim ELISA. i vi EIEC cn xc nh tnh xm nhp, c th dng th nghim Sereny xc nh. i vi EHEC tm kh nng sinh verocytotoxin. Trong nhim khun ng tit niu th ly nc tiu gia dng ca bnh nhn nui cy. Ch nui cy khi nhum soi knh hin vi cn nc tiu thy nhiu bch cu a nhn cng vi vi khun. Cn phi nh lng vi khun trong 1 ml nc tiu c th khng nh vai tr gy bnh ca vi khun phn lp c nc tiu. 4. Phng bnh v cha bnh Hin nay cha c vaccine c hiu. Ch yu l phng bnh chung m ch yu l tn trng cc ni quy v v sinh. Qua nhiu cng trnh nghin cu cho thy mt s ln cc chng E.coli gy bnh khng cc khng sinh v hin tng mt chng vi khun E.coli khng vi nhiu loi khng sinh cng kh ph bin. Do vy nn da vo kt qu ca khng sinh la chn khng sinh thch hp trong cha bnh.

III. SHIGELLA
Shigella l tc nhn gy ra bnh l trc khun ngi. 1. c im sinh vt hc Shigella l trc khun Gram m tnh, khng c lng, v vy khng c kh nng di ng, khng c v khng sinh nh bo. Shigella ln men glucose khng sinh hi, ln men manitol (tr Shigella dysenteriae khng ln men manitol), hu ht Shigella khng ln men lactose, ch c Shigella sonnei ln men lactose nhng chm. Khng sinh H2S, urease m tnh, phn ng indol thay i, phn ng metyl dng tnh, phn ng VP m tnh, phn ng citrat m tnh Shigella c khng nguyn thn O, khng c khng nguyn H. Cn c vo khng nguyn O v tnh cht sinh ha, ngi ta chia Shigella ra lm 4 nhm: 1.1. Nhm A (Shigella dysenteriae) Khng ln men manitol, c 10 type huyt thanh c k hiu bng cc ch s Rp t 1 - 10. Cc type huyt thanh trong nhm khng c quan h v khng nguyn vi nhau v cng khng c quan h khng nguyn vi cc nhm khc. Type 1 (Sh. dysenteriae type 1) hay cn gi l trc khun Shiga l type c ngoi c t. 1.2. Nhm B (Shigella flexneri)

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Ln men manitol, c 6 type huyt thanh. Cc type ny c 1 khng nguyn nhm chung v mi mt type huyt thanh li c 1 khng nguyn c hiu type. 1.3. Nhm C (Shigella boydii) Ln men manitol, c 15 type huyt thanh, mi type c khng nguyn c hiu type. 1.4. Nhm D (Shigella sonnei) Ln men manitol, ln men lactose chm, ch c 1 type huyt thanh. 2. Kh nng gy bnh cho ngi Shigella gy bnh l trc khun ngi, y l mt bnh truyn nhim c th gy thnh cc v dch a phng. Thng tn c hiu khu tr rut gi, trn lm sng biu hin bng hi chng l vi cc triu chng: au bng qun, i ngoi nhiu ln, phn c nhiu mi nhy v thng c mu. Shigella gy bnh bng c ch xm nhp vo t bo biu m ca nim mc rut v nhn ln vi s lng ln trong t chc rut. Cc Shigella u c ni c t. Ring trc khun Shiga cn c thm ngoi c t bn cht l protein . Ni c t Shigella cu to nh khng nguyn thn, c c tnh mnh nhng tnh khng nguyn yu. Tc dng chnh ca ni c t l gy phn ng ti rut. Ngoi c t ca trc khun Shiga khng ging nh c t rut ca Vibrio cholerae 01 v ETEC, hot tnh sinh hc ch yu ca ngoi c t trc khun Shiga l tc dng c i vi t bo. Vit Nam, Shigella gy bnh l trc khun thng gp nht l nhm B (Shigella flexneri) v nhm A (Shigella dysenteriae). Dch t hc: Bnh ly theo ng tiu ha, do n ung phi cc thc n, nc ung b nhim khun. Rui l vt ch trung gian truyn bnh. Ngi lnh mang vi khun v ngi bnh ng vai tr quan trng gy dch. Dch thng xy ra vo ma h. Min dch: Ngi ta cho rng khng th dch th khng c hiu lc v thng tn ca bnh trn b mt ca ng tiu ha. Ngc li cc min dch ti ch rut c th c mt vai tr quan trng trc ht l cc IgA tit c trong ng rut v cc i thc bo c hot ha. 3. Chn on vi sinh vt Cy phn l phng php chn on tt nht. Bnh phm cn c ly sm trc khi s dng khng sinh, ly ch phn c biu hin bnh l (c mu c nhy) v phi chuyn n phng xt nghim vi trng nhanh chng. Nui cy phn lp vi khun trn cc mi trng thch hp: mi trng khng c cht c ch (thch lactose) v mi trng c cht c ch (DCA, SS hoc Istrati). Xc nh vi khun da vo cc tnh cht sinh vt ha hc v lm phn ng ngng kt vi khng huyt thanh mu ca Shigella. Trong bnh l trc khun, cy mu khng tm c vi khun. 4. Phng bnh v cha bnh 4.1.Phng bnh

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Ch yu l cch ly bnh nhn, kh trng phn v nc thi, pht hin v iu tr ngi lnh mang vi khun, p dng cc bin php v sinh v kim tra dch t i vi ngun nc, thc n... Hin nay vn cha c vaccine phng bnh c hiu lc nh mong mun... ang th nghim dng vaccine sng gim c lc ng ung nhm to nn min dch ti ch rut. Vaccine sng ny ch c kh nng bo v c hiu i vi type. 4.2.Cha bnh Dng khng sinh tiu dit vi khun, vic chn khng sinh thch hp da vo kt qu khng sinh . Vic s dng khng sinh ba bi, thiu thn trng s c nguy c lm tng nhanh cc chng c sc khng i vi khng sinh v tng nguy c b lon khun vi tt c cc hu qu nghim trng ca n.

IV. SALMONELLA
Hin nay c ti 2000 type huyt thanh Salmonella khc nhau. Chng gy bnh cho ngi hoc ng vt hoc c hai. Cc bnh do Salmonella gy ra ngi c th chia thnh 2 nhm: thng hn v khng phi thng hn. 1. c im sinh vt hc 1.1. Hnh th Salmonella l trc khun gram m. Hu ht cc Salmonella u c lng xung quanh thn (Tr Salmonella gallinarum v Salmonella pullorum), v vy c kh nng di ng, khng sinh nha bo.

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1.2. Tnh cht sinh vt ha hc Salmonella ln men glucose c sinh hi (tr Salmonella typhi ln men glucose khng sinh hi) khng ln men lactose, indol m tnh, methyl dng tnh, VP m tnh, citrat thay i, urease m tnh, H2S dng tnh (tr Salmonella paratyphi A: H2S m tnh)... 1.3. Cu trc khng nguyn 1.3.1. Khng nguyn O Mi Salmonella c th c mt hoc nhiu yu t khng nguyn. Hin nay ngi ta bit c 67 yu t khng nguyn O. Vic xc nh cc yu t khng nguyn O l ht sc quan trng nh nhm v nh type. 1.3.2. Khng nguyn H Ch c nhng Salmonella c lng. Khng nguyn H ca Salmonella c th tn ti di 2 pha: pha 1 c ghi bng ch vit thng a, b, c, d... v pha 2 c ghi bng cc ch s rp 1, 2,,, 1.3.3. Khng nguyn Vi L khng nguyn b mt bao bn ngoi vch t bo vi khun, di dng mt mng mng khng nhn thy c knh hin vi thng. Khng nguyn Vi ch c 2 type huyt thanh Salmonella typhi v S. paratyphi C. Ngi ta da vo s khc nhau v cu trc khng nguyn xp loi Salmonella. Mt s type huyt thanh Salmonella ch yu gy bnh cho ngi bao gm : Salmonella typhi: Ch gy bnh cho ngi. nc ta bnh thng hn ch yu do S. typhi gy ra. Salmonella paratyphi A: Ch gy bnh thng hn cho ngi v cng hay gp nc ta sau S.typhi. Salmonella paratyphi B: Gy bnh thng hn ch yu cho ngi, i khi c sc vt. Bnh thng gp cc nc chu u. Salmonella paratyphi C: Gy bnh thng hn, vim d dy rut v nhim khun huyt. Bnh thng gp cc nc ng Nam . Salmonella typhimurium v Salmonella enteritidis: Gy bnh cho ngi v gia sc, gp trn ton th gii. Chng l nguyn nhn gy nhim trng, nhim c thc n do n phi thc n nhim Salmonella. Salmonella cholerae suis: Loi ny hay gy nhim khun huyt. 2. Kh nng gy bnh cho ngi 2.1. Bnh thng hn nc ta, bnh thng hn ch yu do S. typhi, sau n S. paratyphi A, cn S. paratyphi B v S. paratyphi C th t gp. Bnh ly t ngi ny sang ngi khc, qua thc n, nc ung b nhim khun. Sau khi khi bnh v mt lm sng, khong 5% bnh nhn tr thnh ngi lnh mang vi khun ko di hng thng hoc hng nm. h, cha Salmonella l ng mt v vi khun vn c tip tc o thi theo phn ra ngoi cnh. Ngi lnh mang vi khun l ngun lan truyn bnh quan trng.

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Sinh bnh hc: Trc khun thng hn vo c th qua ng tiu ha n rut non th chui qua nim mc rut ri vo cc hch mc treo rut. chng nhn ln v mt phn vi khun b dung gii, gii phng ra ni c t. Ni c t kch thch thn kinh giao cm bng, gy thng tn mng Peyer, xut huyt tiu ha, c th gy thng rut. Ngoi ra, ni c t theo mu ln kch thch trung tm thn kinh thc vt no tht ba, gy ra trng thi st ko di, li b, v gy ra bin chng try tim mch... T cc hch mc treo rut vi khun lan trn vo mu gy nn nhim khun huyt v lan i khp c th, ri vi khun vo mt v t quay tr li rut. Vi khun theo phn ra ngoi cnh. 2.2. Cc bnh khc Cc bnh khng phi thng hn do Salmonella gy ra thng l mt nhim trng gii hn ng tiu ha trong cc trng hp nhim trng nhim c thc n m Salmonella typhimurium... l tc nhn hay gp nht, sau l Salmonella enteritidis... Nhim trng nhim c do Salmonella c thi gian nung bnh t 10 n 48 gi. Bnh biu hin c st, nn, tiu chy. Bnh khi sau 2 - 5 ngy, khng c bin chng. Ngoi ra, Salmonella c th gy nn cc tn thng ngoi ng tiu ha nh vim mng no, th nhim trng huyt n thun, nhim trng phi... 3. Chn on vi sinh vt 3.1. Chn on trc tip Phn lp vi khun t cc bnh phm nh mu (cy mu), phn (cy phn) v cc bnh phm khc . 3.1.1.Cy mu Ly 5ml n 10ml mu tnh mch bnh nhn lc st cao cy vo bnh canh thang c mt b, m 370C, sau 24 n 48 gi nu vi khun mc, cn phi kim tra hnh th, tnh cht bt mu khi nhum Gram, kim tra tnh cht sinh vt ha hc, xc nh cng thc khng nguyn vi cc khng huyt thanh Salmonella mu. i vi bnh thng hn, nu bnh nhn cha s dng khng sinh th gi tr ca phng php cy mu cao. Nu cy mu vo : Tun l u ca bnh th t l dng tnh t 90% Tun l th hai ca bnh, dng tnh t 70% - 80% Tun l th ba, t l dng tnh t 40% - 60% Nu bnh ti pht, cy mu s tm thy vi khun thng xuyn trong nhiu ngy. 3.1.2. Cy phn Thng dng tnh t tun th 2 tr i. Nui cy phn lp vi khun mi trng tng sinh v mi trng c cht c ch (mi trng SS, DCA, Istrati, Endo...). Xc nh vi khun da vo tnh cht sinh vt ha hc v lm phn ng ngng kt vi khng huyt thanh mu. Khi nghi ng mt trng hp mc bnh thng hn phi ng thi xt nghim cy mu, cy phn v lm huyt thanh chn on.

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Cy phn l bin php duy nht chn on vi sinh vt trong trng hp ng c thc n nghi do Salmonella v trong vic xc nh ngi lnh mang mm bnh. 3.1.3. Cy cc bnh phm khc Vi khun thng hn cn c th phn lp bng cch cy ty xng, nc tiu, dch o ban, dch mt ca bnh nhn. 3.2. Chn on huyt thanh Sau khi nhim Salmonella t 7 n 10 ngy, trong mu bnh nhn xut hin khng th O ca Salmonella, sau ngy th 12 n ngy th 14 xut hin khng th H. Khng th O, tn ti trong mu trung bnh 3 thng, khng th H tn ti 1 n 2 nm. Ly huyt thanh cc bnh nhn tm khng th ngng kt ca Salmonella bng phn ng ngng kt Widal. Trong bnh thng hn, chn on huyt thanh (Widal) t tun l th hai tr i, lm 2 ln cch nhau mt tun l tm ng lc khng th.

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4. Phng bnh v cha bnh 4.1. Phng bnh Thc hin cc bin php v sinh v phn, nc, rc, tch cc dit rui. Phi n chn, ung si, ra tay trc khi n... Qun l cht ch bnh nhn. Pht hin ngi lnh mang mm bnh iu tr trit . Tim vaccine T.A.B l loi vaccine cht. Mt s nc dng vaccine thng hn sng gim c lc v vaccine chit t khng nguyn Vi ca Salmonella. 4.2. Cha bnh Dit vi khun Salmonella bng khng sinh. Nhng thuc khng sinh thng dng l chloramphenicol, ampicillin vi liu lng thch hp trnh bin chng tru tim mch v thuc dit vi khun lm gii phng ra qu nhiu ni c t. Tuy nhin ngy nay cng xut hin nhng chng Salmonella khng vi cc khng sinh trn, v vy cn lm khng sinh chn khng sinh thch hp.

V. KLEBSIELLA PNEUMONIAE
Loi Klebsiella c nhiu type c kh nng gy bnh cho ngi nh: - Klebsiella pneumoniae: Thng gy ra cc bi nhim ng h hp. - Klebsiella rhinoscleromatis : Gy bnh x cng mi. - Klebsiella ozenae: Gy bnh tr mi Klebsiella pneumoniae hay cn gi l ph trc khun Friedlander l loi vi khun rt ph bin trong thin nhin (nc, t), n k sinh ng h hp trn ca ngi, l tc nhn gy bnh c hi. 1. c im sinh vt hc 1.1. Hnh th Trong bnh phm K. pneumoniae c hnh trc khun ngn, gram m, bt mu m hai cc, vi khun ny c nhiu hnh th, c khi nh cu khun, c khi li hnh di, c v, khng di ng, khng sinh nha bo. 1.2. Tnh cht nui cy Vi khun d mc trn mi trng nui cy thng thng. Trn thch dinh dng hay thch mu, khun lc ly nhy, mu xm. Trong canh thang, vi khun mc nhanh v c u, ay ng c lng cn. 1.3. Tnh cht sinh vt ha hc Ln men nhiu loi ng sinh acid v hi nh : Glucose, lactose, manit. Phn ng indol m tnh, phn ng metyl m tnh, phn ng VP dng tnh, phn ng citrat dng tnh, urease dng tnh, H2S m tnh. 1.4. Cu trc khng nguyn Khng nguyn thn O : C 5 type Khng nguyn v K : Bn cht l polysaccharide, mang tnh cht c hiu type, c 72 type, trong type 1 v type 2 hay gp nht trong nhim khun ng h hp. 2. Kh nng gy bnh cho ngi

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Klebsiella pneumoniae l loi vi khun gy bnh c iu kin gi l gy bnh c hi. Nhng nhim trng c hi xy ra ch yu mi trng bnh vin v trn nhng bnh nhn b suy kit, suy gim min dch. Nhng iu kin cc nhim trng c hi xut hin l : - Ngy cng c nhiu loi khng sinh ph rng, vic s dng khng sinh rng ri v thiu thn trng lm mt th qun bnh ca vi khun ch bnh thng, ng thi lm cho vi khun c chn lc bi khng sinh v to nn sc khng i vi khng sinh. - Cc th thut nh ni soi, thng tim... c pht trin v p dng ngy cng nhiu trong cc bnh vin. Khi p dng cc th thut ny c th a vi khun vo c th qua ng thng... - Nhng bnh nhn m sc khng gim st nghim trng do mc cc bnh lm suy gim min dch (v d: K mu, suy ty...) Klebsiella pneumoniae c th gy ra : Nhim trng ng h hp di nh vim phi, vim ph qun phi th pht sau cm, sau si, sau ho g hoc cc bnh nhn ang hi sc h hp (ang dng my h hp nhn to). Nhim trng mu : Thng gp nhng bnh nhn b suy kit nh x gan, ung th mu, suy ty... Ngoi ra cn c th gy nhim trng ng tit niu, ng mt hoc ng sinh dc, vim mng no, vim tai, vim xoang v vim ni tm mc. 3. Chn on vi sinh vt Ch yu da vo chn on trc tip, phn lp vi khun t cc bnh phm m, mu v.v... ty theo th bnh. Nui cy ln cc mi trng thch hp phn lp v xc nh vi khun da vo hnh th, tnh cht nui cy c bit (khun lc nhy, dnh), tnh cht sinh vt ha hc, kh nng gy bnh thc nghim. Xc nh type bng phn ng ngng kt hoc phn ng phnh v vi khng huyt thanh c hiu type. 4. Phng bnh v cha bnh 4.1. Phng bnh Cha c vaccine phng bnh c hiu. Ch yu l trnh nhng iu kin thun li cho nhim trng c hi xut hin bng cch nng cao sc khng ca ngi bnh v d phng tt cc nhim trng bnh vin. 4.2. Cha bnh Da vo kt qu ca khng sinh chn khng sinh cng hiu. Klebsiella pneumoniae thng c sc khng cao vi khng sinh.

VI. PROTEUS
Ging Proteus k sinh rut v cc hc t nhin ca ngi (v d : ng tai ngoi). Chng l loi vi khun gy bnh c hi. 1. c im sinh vt hc 1.1. Hnh th

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Trc khun gram m, rt di ng. Vi khun c nhiu hnh th thay i trn cc mi trng khc nhau, t dng trc khun n dng hnh si di. 1.2. Tnh cht nui cy Vi khun mc d dng trn cc mi trng nui cy thng thng. Trn mi trng thch dinh dng, khun lc c mt trung tm lan dn ra, tng t, tng t , mi t l mt gn sng v c mi thi c bit. Trn mi trng c natri deoxycholate: Proteus mc thnh khun lc trn, ring bit khng gn sng, c mt im en trung tm, xung quanh mu trng nht.

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1.3. Tnh cht sinh vt ha hc Khng ln men lactose. a s Proteus : H2S dng tnh v urease dng tnh. Da vo tnh cht sinh vt ha hc ngi ta phn loi ging Proteus thnh cc loi: Proteus mirabilis, Proteus vulgaris, Proteus myxofaciens, Proteus penneri. 1.4. Cu trc khng nguyn Cu trc khng nguyn ca Proteus rt phc tp v khng c vn dng vo cng tc thc t hng ngy. Ngi ta thy c mt mi tng quan c bit gia khng nguyn O ca mt s chng Proteus (c gi l OX2 ; OX19; OXK) v Rickettsia. V vy, ngi ta dng cc chng ny lm khng nguyn trong chn on huyt thanh bnh do Rickettsia (phn ng Weil - Felix). 2. Kh nng gy bnh Proteus l mt loi vi khun "gy bnh c hi". Chng c th gy ra : - Vim tai gia c m - Vim mng no th pht sau vim ti gia tr cn b. - Nhim khun ng tit niu - Nhim khun huyt ... 3. Chn on vi sinh vt Phn lp vi khun t cc bnh phm nh : m tai, nc tiu, mu ... ty theo th bnh lm sng. c im ca cc tn thng v m do Proteus gy ra c mi thi nh trong hoi th do vi khun k kh gy nn. Nui cy trn cc mi trng thng thng. Xc nh vi khun da vo hnh thi khun lc gn sng, mi thi c bit trn da mi trng v trc khun Gram m urease dng tnh v mt s tnh cht sinh vt ha hc khc. Mun phn lp thnh khun lc ring r th nui cy trn mi trng c Natri desoxycholat, Proteus s mc thnh khun lc ring bit c chm en gia sau 48 gi. 4. Phng bnh v cha bnh 4.1. Phng bnh Nng cao th trng ngi bnh, khi p dng cc th thut thm khm phi tuyt i v trng d phng tt cc nhim trng bnh vin. 4.2. Cha bnh S dng khng sinh da vo kt qu ca khng sinh . Vi khun ny thng c sc khng cao vi khng sinh.

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VI KHUN DCH HCH V LEGIONELLA PNEUMOPHILA

Mc tiu hc tp 1. Trnh by c c tnh sinh vt hc ca vi khun dch hch v Legionella pneumophila 2. Trnh by c kh nng gy bnh ca hai vi khun ny 3. Trnh by c phng php chn on sinh vt hc, phng php phng nga v iu tr

I. VI KHUN DCH HCH (Yersinia pestis)

Yersinia pestis thuc ging Yersinia, thuc h vi khun ng rut (Enterobacteriaceae) Trc khun dch hch c A. Yersin phn lp nm 1894 trong mt v dch hch Hng Kng. Nm 1896, Lehmann v Neumann t tn cho vi khun ny l Bacterium pestis. Nm 1944, Van Loghen chuyn chng sang ging Yersinia ghi cng ca A. Yersin. Vi khun dch hch gy nn bnh dch hch l bnh ca mt s loi ng vt (ch yu l cc loi chut), ly sang ngi qua b cht, c bnh thin nhin, d pht thnh dch ln. Dch hch l bnh ti nguy him, c xp vo nhm 4 bnh thuc din phi khai bo bt buc: dch hch, dch t, u ma v st vng. nc ta, bnh dch hch c pht hin ln u tin nm 1898 Nha trang, sau bnh pht trin mnh min Nam. Hin nay vn cn mt s dch hch ch yu vng Ty nguyn. 1. c im sinh vt hc 1.1. Hnh thi v tnh cht bt mu Vi khun dch hch l trc khun ngn, hnh bu dc nh, kch thc 0,5 -0,8 x 1-2 m, Gram m, bt mu m hai u, nht l khi nhum Wayson hay xanh methylen. Trong bnh phm vi khun ng ring l hoc xp i v c v. Trong mi trng nui cy 37oC th c v, nu nui cy 28 oC th khng c v. Khng sinh nha bo, khng di ng. 1.2. Tnh cht nui cy Trc khun dch hch d mc trn cc mi trng nui cy thng thng, nhng chm. Hiu k kh tu tin, nhit thch hp l 28oC. - Trn canh thang Yersinia pestis lc u lm c u nh, dn dn sau 24 - 48 gi vi khun pht trin to mt vng mng trn b mt v lng cn di y, canh thang tr nn tng i trong. - Trn thch thng: vi khun mc chm to khun lc rt nh (0,1mm) sau 24 gi. Sau 48 - 72 gi 280C, ng knh mi t c 1- 1,5 mm, b tri mng ra, khng u, trung tm li, hi trong, mu xm nht. 1.3. Tnh cht sinh vt ha hc

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Vi khun dch hch khng di ng. Oxydase m tnh, catalase dng tnh. Ln men ng glucose khng sinh hi, manitol dng tnh, ONPG dng tnh, c enzyme Dnase, kh nitrat thnh nitrit. Citrat simmon thay i tu theo chng, lactose m tnh, rhamnose m tnh, saccharose m tnh. Indol m tnh, Voges Proskauer m tnh, khng to enzyme urease, khng sinh H2S, ornithin decarboxylase (ODC) m tnh, lysin decarboxylase (LDC) m tnh, arginin dihydrolase (ADH) m tnh. Vi khun dch hch b ly gii bi phage c hiu. 1.4. Sc khng Vi khun b tiu dit 550C/30 pht hoc 1000C/1 pht. Trong iu kin kh hanh hoc phi nng vi gi vi khun c th cht. Trong cc t chc, trong xc chut, t m, trong nc vi khun c th tn ti t vi chc ngy n vi thng. 1.5. Khng nguyn v cc yu t gy bnh - Khng nguyn v: Cn gi l khng nguyn F1 (Fraction 1), c trong iu kin nui cy vi khun 37oC hoc trong bnh phm ca c th ang b bnh. Bn cht l protein. Khng nguyn v gip cho vi khun chng li hin tng thc bo. - Khng nguyn V v W: L mt phc hp gm protein V v lipoprotein W. Cc khng nguyn ny lin quan n kh nng chng li hin tng thc bo. - Khng nguyn thn: l khng nguyn chung vi cc vi khun h ng rut. - c t: vi khun dch hch c 2 loi c t : + Ni c t: bn cht l Lipopolysaccharide gn lin vi vch t bo vi khun, gy ra cc triu chng st trong bnh dch hch. + c t chut (murine toxin) bn cht l protein nh mt ngoi c t, c tc ng lm tan hng cu, c hot tnh trn h thng mch mu gy ra mu v gy sc. 2. Kh nng gy bnh 2.1. Dch t hc Bnh dch hch l bnh ca loi gm nhm hoang di, trong loi chut Rattus vi 2 chng: chut ng v chut nh c vai tr quan trng nht. Ngi ch l vt ch ngu nhin mc phi do b b cht nhim khun t. - cha: Cc loi gm nhm hoang di - Cn trng mi gii: Ch yu l cc loi b cht Xenopsylla cheopis, ngoi ra c th gp Xenopsylla astia v cc cn trng ht mu nh Pulex irritans ... - i tng cm th: ng vt gm nhm hoang di v c th ly sang ngi. ng truyn bnh: u tin dch xy ra cc loi gm nhm hoang di ri truyn n chut ng, chut nh, sau truyn sang ngi l con ng hay gp nht hoc ngi ti bnh hoang di cng c th b b cht nhim khun t v mc bnh. Bnh dch hch c th truyn t ngi bnh sang ngi lnh do chy rn hoc c th truyn bnh trc tip t ngi sang ngi nu ngi mc bnh dch hch th phi. cha

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(gm nhm hoang di) Cn trng mi gii

- Xennopsylla cheopis - Xenopsylla astia - Pulex irritans - Rui ht mu

- Chut ng Chut - Chut nh

Cn trng mi gii Ngi

Th phi

Ngi

Chy, rn Hnh 1: S dy chuyn dch t 2.2. Gy bnh cho ngi Vi khun dch hch sau khi vo c th s vo h thng bch huyt v nhn ln trong hch, sau vo mu, ri c tr gan, lch, thn v cc hch su. Thi gian bnh t 3- 6 ngy, i khi ngn hn, ty thuc vo sc khng ca c th v c lc ca vi khun. Bnh dch hch c 3 th lm sng: - Th hch: Sau khi b b cht nhim khun t, ti ni t ni mn nc, i khi en gia. Vi khun xm nhp vo hch bch huyt gn vt t nht lm cho hch sng to, rn, dnh cht khng di ng v rt au. Bnh nhn st cao, mt v chng mt, triu chng nhim c nng. Nu khng c iu tr kp thi, bnh nhn s t vong vo ngy th 5 hoc th 6 ca bnh v nhim khun huyt. Th hch l th lm sng thng gp nht. - Th phi: C th nguyn pht do ly trc tip qua th phi ca ngi bnh hoc l th pht sau th hch. Bnh khi pht t ngt, st cao, ho, au lng ngc, m c mu. Bnh tin trin nhanh v rt nng, t vong sau 2 - 3 ngy nu khng c iu tr kp thi. Th phi rt d ly lan. - Th nhim khun huyt: C th l tin pht, nhng thng do bin chng ca th hch v th phi nguyn pht, gy thng tn c m da, mn xut huyt v huyt niu, st cao, cy mu dng tnh. T vong sau 2 - 3 ngy. 3. Chn on vi sinh vt 3.1. Chn on trc tip : Bnh phm l dch chc hch trong th hch, mu trong th nhim khun huyt, m trong th phi. T bnh phm lm tiu bn nhum gram (i vi th hch) hoc xanh methylen hoc Wayson. Phng php nhum trc tip c gi tr kt hp vi triu chng lm sng c hng iu tr kp thi.

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Mt khc cn nui cy bnh phm vo cc mi trng thch hp nh canh thang, nc pepton, thch mu, thch thng ..., 28oC . Sau xc nh cc tnh cht sinh vt ha hc, nh typ phage v tim truyn sc vt. 3.2. Chn on gin tip : Bnh dch hch l bnh nhim khun cp tnh nn ngi ta khng lm phn ng huyt thanh chn on bnh. Ngi ta thng lm chn on huyt thanh iu tra dch t hc, thng dng phn ng ngng kt hng cu th ng pht hin khng th khng F1. 4. Phng bnh v iu tr 4.1. Phng bnh 4.1.1. Phng bnh c hiu: Hin nay c hai loi vaccine: vaccine sng gim c v vaccine cht. Vaccine cht tim hai ln, gy min dch c 6 thng. Vaccine sng gim c tim mt ln, gy min dch nhanh v thi gian min dch ko di n mt nm. Ch tim vaccine cho nhng ngi ang sng vng dch hoc phi lm nhim v nhng vng . 4.1.2. Phng bnh chung: Ct t dy truyn dch t bng cch: dit chut, dit cn trng mi gii, bnh nhn phi khai bo v cch ly, phong ta khu vc c dch. Khi c dch xy ra cn phi ung khng sinh d phng cho ngi nh bnh nhn, nhn vin y t tip xc vi th phi. 4.2. iu tr Vi khun dch hch nhy cm vi cc khng sinh nh streptomyxin, chloramphenicol, tetracyclin, nhng phi iu tr sm. Khng sinh penicilin khng c tc dng.

II. LEGIONELLA PNEUMOPHILA

Nm 1977 Mac Dade phn lp c t t chc phi ca mt bnh nhn cht v vim phi mt trc khun Gram m mi m trc khoa hc cha bit. Nm 1978, trc khun ny c t tn l Legionella pneumophila. Loi Legionella pneumophila thuc ging Legionella, h Legionellaceae. Chng c kh nng gy bnh ng h hp ngi. 1. c im sinh vt hc 1.1.Hnh th Vi khun a hnh thi, thng gp dng trc khun Gram m (bt mu yu), i khi gp hnh cu trc khun hoc hnh si. Kch thc thay i 0,3-0,9 m x 220 m. Hnh th thay i theo nhng iu kin nui cy v mi trng nui cy khc nhau. Vi khun di ng, c mt lng mt u, khng sinh nha bo, khng c v. 1.2.Tnh cht nui cy Vi khun kh nui cy, hiu kh tuyt i, i hi mi trng giu cht dinh dng vi mt khong pH hp (chung quanh 6,5), t trong kh trng c 2,5 % CO 2 v nhit t 35-37OC. Mi trng tt nht hin nay phn lp vi khun Legionella pneumophila l mi trng BCYE (Buffered Charcoal Yeast Extract agar), y l mi trng thch c than hat v cao men (cha L- cystein l yu t c bn cho s phn lp Legionella). mi trng ny c cc khun lc rt nh, mu xanh xm d dng quan st knh lp, xut hin vo ngy th 3 sau khi cy.

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C th nui cy Legionella pneumophila cc nui cy t bo phi g, phi phi ngi, bch cu n nhn to ca ngi, cc t bo HeLa, Hep-2... Nui cy phi g l phng php tt nht thch hp vi tt c cc Legionella thuc cc loi khc nhau. 1.3. Tnh cht sinh vt ha hc Oxydase dng tnh yu, catalase dng tnh, lm lng gelatin, urease m tnh v khng ln men cc loi ng, c kh nng ly gii hippurat natri, th nghim ny dng chn on phn bit vi cc Legionella khc, sinh ra enzyme -lactamase. 1.4. Khng nguyn Khng nguyn O c hiu c chia thnh nhiu nhm huyt thanh khc nhau. Khng nguyn H chung vi cc Legionella khc. 1.5. Sc khng Vi khun d b dit bi tc nhn l ha, nhng li sng lu c trong nc. Vi khun c trong nc t nhin (ao, h), nc cha b v thp nc nhn to. Vi khun c mt trong h thng dn nc nng lnh, h thng my iu ha nhit , cc ng nc, vi nc... 2. Kh nng gy bnh Legionella pneumophila l nguyn nhn ca bnh l vim phi cp v st Pontiac. Vi khun t mi trng xung quanh vo ngi theo ng h hp do ht phi bi hoc hi nc c nhim khun. Bnh vim phi cp do Legionella l mt nhim trng cp tnh ng h hp c vim phi nng vi st cao t ngt, ho, au ngc, a chy, li b hoc m sng... Nu khng c iu tr th t l t vong t 10 % - 20 %. St Pontiac c c trng bi st, rt run, au c v khng c bnh l h hp. Tin trin lnh tnh. bnh vin c nhng v dch bnh xy ra do Legionella pneumophila nhng bnh nhn b bnh nng hoc c iu tr bng cc thuc c ch min dch. Trong nhiu trng hp c nhng nhim trng bn lm sng, ch pht hin c do s tng hiu gi khng th c hiu. Trng hp mc bnh l t, ch yu nhng ngi nghin ht thuc lu nm , b vim ph qun mn v nguy c mc bnh nhng ngi b bnh ung th. Bnh xy ra l t khp mi ni trn th gii. 3. Chn on vi sinh vt 3.1. Chn on trc tip: Pht hin vi khun trong mu nghim (m, cht dch ph qun, mnh sinh thit phi...) bng phng php min dch hunh quang trc tip, y l phng php c hiu, cho kt qu nhanh sau mt vi gi. 3.2. Phn lp vi khun: Bnh phm l mu, mnh phi (sinh thit hoc m t thi), dch mng phi, cht ht t ph qun, kh qun... Vt phm ngoi cnh: ly mu nc. Bnh phm c cy vo mi trng thch BCYE, 36OC trong kh trng c 2,5% CO2. Vi khun mc sau 48 gi. Quan st khun lc v nh danh vi khun.

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Mi trng cy mu c theo di trong 3 tun, nu vi khun mc cy chuyn vo mi trng BCYE. 3.3. Chn on huyt thanh: Dng cc k thut min dch hunh quang gin tip, ELISA pht hin khng th trong huyt thanh bnh nhn. Cn xc nh khng th trong huyt thanh kp, hiu gi ln hn 4 ln mi c gi tr chn on. 4. Phng bnh v cha bnh. 4.1. Phng bnh: Cn x l nc cc b nc, vi nc, iu ha nhit . Cn c nhng bin php ngn nga khng xy ra dch trong bnh vin. 4.2. Cha bnh: Vi khun nhy cm vi nhiu khng sinh nh erythromycin, rifampicin, fluoroquinolon. Cc -lactamin khng c tc dng trn vi khun ny v chng sn xut enzyme -lactamase.

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HAEMOPHILUS V BORDETELLA
Mc tiu hc tp 1.Trnh by c mt s tnh cht vi khun hc ca vi khun Haemophilus v Bordetella. 2.Nu ra c kh nng gy bnh ca hai loi vi khun ny. 3.Trnh by c mt s phng php chn on vi khun hc i vi Haemophilus v Bordetella.

I. HAEMOPHILUS
Ging Haemophilus thuc h Pasteurellaceae, gm nhng trc khun nh, Gram m, khng di ng, khng sinh nha bo, c v lin quan mt thit vi tnh cht gy bnh. Mi trng nui cy bt buc phi c mt hoc c hai yu t pht trin X v V (X: hematin, V: nicotinamidadenin dinucleotid = NAD). Thch chocolat c c hai yu t ny v thch hp cho s pht trin ca nhng Haemophilus i hi c hai yu t X v V. Cc Haemophilus i hi c hai yu t X v V ch c th pht trin trn mi trng thch mu nu cho thm yu t V bn ngoi vo. Cc Haemophilus k sinh bt buc trn nim mc ng h hp hoc i khi ng sinh dc ca ngi hay ng vt. Thuc nhm ny c nhiu thnh vin, y ch gii thiu Haemophilus influenzae, tc nhn ch yu gy nhim khun h hp cp tr nh v Haemophilus ducreyi, tc nhn gy bnh h cam. 1. Hemophilus influenzae Haemophilus influenzae do Richard Pfeiffer phn lp ln u tin t mt bnh nhn b cht trong v dch cm ln nm 1892 (nn cn gi l trc khun Pfeiffer). T tr i, trong mt khong thi gian di, ngi ta tin rng n chnh l cn nguyn gy ra bnh cm v t tn l Bacterium influenzae. Nm 1933, khi pht hin ra vius cm th cn nguyn ca bnh cm cng nh vai tr ca B. influenzae mi c lm sng t: virus cm gy ra bnh cm, cn B. influenzae l vi khun n theo (second invader) sau khi cc t bo nim mc ng h hp b tn thng nng n bi virus cm. V danh php, thut ng Bacterium influenzae do Lehmann v Neumann xut nm 1896. Nm 1917, Winslow v cng s, trn c s nhng hiu bit mi v B.influenzae, chuyn chng sang ging Haemophilus, v t n nay, chng mang tn Haemophilus influenzae. 1.1. c im sinh vt hc L vi khun a hnh thi, Gram m, khng di ng, khng sinh nha bo. Trong bnh phm vi khun thng c v polysaccharide mang khng nguyn c hiu typ. Trong khi cy truyn trn mi trng nhn to th vi khun mt v. Vi khun hiu kh, i hi CO2 (5 - 10%), nhit thch hp l 370C, pH thch hp 7,6 - 7,8. Vi khun ch mc c trn mi trng thch c c yu t X v V (mc tt trn mi trng thch chocolat), khun lc nh, trong, mt nhn (dng S), ng knh 0,5-0,8 mm, sau khi cy truyn cc khun lc tr thnh dng R; khng gy tan mu trn thch mu. Trong mi trng nui cy H.influenzae, yu t V c th thay th bng NAD hoc NADP, yu t X c th thay th bng Hemin hoc Hematin. Cng c th thay th yu t V bng cch cy t cu vng trn mi trng thch mu, cc khun lc trong, nh ca H.influenzae mc quanh ng cy t cu khun (do t cu vng tit ra yu t V), l th nghim "v tinh" (Satellitism), c s dng khi khng c yu t V trong mi trng nui cy H. influenzae.

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H.influenzae ln men ng glucose, khng ln men ng lactose v mannit. H.influenzae khng rt km vi cc yu t ngoi cnh. Trong bnh phm, chng cht nhanh chng nu b nh sng mt tri chiu trc tip, kh hay lnh. H.influenzae b cc cht st khun thng thng git cht mt cch d dng. 1.2. Kh nng gy bnh ngi H.influenzae l loi vi khun k sinh bnh thng ng h hp, thng phn lp c nim mc mi hng ngi lnh vi t l khong 25%. N c th gy nn cc nhim khun khc nhau: - Nhim khun ng h hp: H.influenzae typ b l mt trong cc tc nhn ch yu gy cc nhim khun khc nhau ca ng h hp, thng gp tr nh tui. Bnh do H.influenzae thng l th pht (sau si, cm) gm: vim ng h hp trn (thanh qun, tai gia, xoang), vim ng h hp di (vim ph qun cp v mn tnh, vim phi). Vim thanh qun do H.influenzae typ b l chng bnh t gp nhng rt nghim trng. - Vim mng no m tr em: vim mng no do H.influenzae l mt bnh nng v c tnh cht cp tnh, cn c chn on v iu tr ngay. - Ngoi ra H.influenzae cn gy nhim khun huyt, vim ni tm mc (him), vim niu o v cc nhim trng sinh dc (m o, c t cung, tuyn Bartholin, vi trng). 1.3. Chn on vi sinh vt Bnh phm: tu theo bnh cnh lm sng m ly bnh phm khc nhau. Bnh phm c th l m, cht nhy mi hng, cht dch kh qun, ph qun hoc dch no ty, m... 1.3.1. Chn on trc tip - Soi ti, nhum gram i vi dch no tu thy c nhiu bch cu a nhn v vi khun khun gram m a hnh thi. - Tm khng nguyn v typ b trong bnh phm: chn on nhanh cc nhim trng do H.influenzae typ b gy ra. Dng k thut min dch pht hin khng nguyn typ b trong dch no tu, mu v nc tiu. Cc phng php min dch c p dng l min dch i lu, ngng kt th ng, ng ngng kt v ELISA vi khng th n dng. - Tm ADN: dng mt on ADN mu nh du phng x hoc dng k thut khuch i gen (PCR: polymerase chain reaction) tm on ADN c trng ca H.influenzae trong bnh phm. 1.3.2. Nui cy Nui cy bnh phm trn mi trng thch chocolat, bnh kn cha 10% CO2. Xc nh H. influenzae bng th nghim "v tinh" vi t cu v th nghim vi cc yu t X v V. 1.4. Phng bnh v iu tr 1.4.1. Phng bnh - Phng bnh khng c hiu: vim mng no do H.influenzae typ b l mt bnh ly, bnh nhn cn phi c cch ly. Ngi lnh tip xc vi bnh nhn phi ung khng sinh d phng (Rifampicin). - Phng bnh c hiu: dng vaccine cha polysaccharide v ca H.influenzae typ b (Hib). 1.4.2. iu tr iu tr cc nhim trng do H.influenzae cn phi da vo khng sinh . Trong khi cha c kt qu khng sinh hoc khi khng phn lp c vi khun,

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chloramphenicol c u tin la chn. Vim mng no cn dng cephalosporin th h 3. 2. Haemophilus ducreyi (Trc khun h cam) c Ducreyi pht hin nm 1889 trong m mn lot c quan sinh dc ca bnh nhn mc bnh h cam, v th c gi l trc khun h cam. Vi khun c t ch tn thng, phi phn lp trn mi trng c 20 - 30 % mu ti, vi khun ch cn yu t X. Bnh nhn mc bnh h cam c phn ng vi hn dch vi khun b git cht tim ni b. Phn ng thng xut hin vo ngy th 8 v tn ti rt lu, c gi tr h tr chn on. Bnh ly qua ng sinh dc nn d phng ch yu l quan h tnh dc hp v sinh v khng quan h vi nhiu ngi. Cha bnh bng khng sinh nh ampicillin, chloramphenicol, bactrim...

II. BORDETELLA PERTUSSIS (Trc khun ho g )

Trc khun ho g thuc ging Bordetella, h Alcaligenaceae. 1. c im sinh vt hc B. pertussis hnh trc khun rt nho, kch thc 0,5-0,8 m x 0,2-0,3 m, Gram m, khng di ng, khng sinh nha bo, c th c v, vi khun hiu kh. Mun phn lp t bnh phm phi c mi trng c bit, l mi trng Bordet Gengou (mi trng cha khoai ty, glycerol v 15-20% mu), vi khun mc chm sau 2 - 4 ngy, khun lc nh, trn, li, xm nht nh x c hoc c nh kim loi (ging nh git thy ngn), xung quanh c vng tan mu hp. Catalase m tnh, Oxydase dng tnh, Urease m tnh. Trong qu trnh nui cy trn mi trng nhn to, trc khun ho g bin d t dng S sang dng R. Hin tng ny c chia lm 4 pha : - Pha I: Tng ng vi khun lc dng S, vi khun hnh bu dc, c v, ng ring r hoc tng i, t khi thnh chui, c c lc, c khng nguyn c hiu ca pha I l nhng khng nguyn mnh to c min dch i vi bnh ho g. - Pha IV : Tng ng vi khun lc dng R, vi khun hnh si t o hn v hay xp thnh chui ngn, khng c v, khng c c lc, mt khng nguyn pha I. - Pha II v pha III: l nhng giai on trung gian S bin i pha c ngha quan trng trong sn xut vaccine. Mun iu ch vaccine tt cn phi dng vi khun pha I. Trc khun ho g sn xut cc yu t lm thnh c lc v c vai tr quan trng trong c ch bnh sinh: - c t ho g: bn cht protein, do vi khun pha I tit ra, lm tng lng AMP vng dn n s tng tit dch v cht nhy ng h hp (triu chng c trng ca cn ho trong bnh ho g). Khng th khng c t ho g c vai tr bo v chng nhim trng. - c t Adenylate cyclase: c th xm nhp vo t bo ng h hp lm tng tit AMP vng, c ch hin tng ho hng ng bch cu a nhn trung tnh v c ch hin tng thc bo. c t ny c vai tr bo v vi khun trong giai on sm ca bnh. - c t t bo kh qun (tracheal cytotoxin): gy tn thng c hiu cc t bo lng chuyn ca biu m ng h hp. - c t khng chu nhit v ni c t (lipopolysaccharide): vai tr sinh bnh khng r. - Khng nguyn thn: chu nhit, cn gi l ngng kt nguyn, khng nguyn ny chung cho c ging Bordetella. 2. Kh nng gy bnh ngi

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B. pertussis gy bnh ho g, thng gp tr em, rt d ly v gy thnh dch. Bnh ho g ly trc tip qua ng h hp, ly nht thi k u ca bnh. Vi khun pht trin lin bo ng h hp, khng vo mu. Vi khun gii phng cc c t gy thng tn ng h hp v gy nn cc du hiu ton thn ca bnh ho g. Bnh ho g l mt bnh nhim khun cp tnh ng h hp, lm vim long ng h hp v xut hin nhng cn ho c bit, gy nhng bin chng phi v no, nh hng ti s pht trin tr tu ca tr, nht l tr s sinh. Bnh ho g xy ra quanh nm, thng gp tr mi n 5 tui. T vong nhiu nht l tr em di 1 tui. Bnh c th gp ngi ln v ch gy ho dai dng khng thnh cn r rt. Ngy nay, nh c vaccine tt t l mc bnh ho g gim rt nhiu. 3. Chn on vi sinh vt 3.1. Chn on trc tip - Ch yu l phn lp vi khun. C nhiu cch ly bnh phm, tt nht l ly bnh phm thi k u ca bnh. Ly bnh phm hng mi bng tm bng mm v n hi qua ng mi, cy vo mi trng Bordet-Gengou ngay ti ging bnh nhn. C th dng mt da mi trng m ra v cch ming bnh nhn 10cm hng nc bt bn ra trong cn ho khng kch thch khong 15 giy. t m 370C/ 2-3 ngy. Xc nh khun lc in hnh, nhum gram xc nh hnh th vi khun v lm phn ng ngng kt vi khng huyt thanh c hiu. Ngoi ra, c th dng khng th n dng tm c t ho g trong bnh phm, dng k thut khuch i gen (PCR: Polymerase Chain Reaction) tm on ADN c hiu ca vi khun. 3.2. Chn on gin tip Tm khng th khng c t ho g trong huyt thanh bnh nhn. 4. Phng bnh v iu tr 4.1. Phng bnh 4.1.1. Phng bnh khng c hiu: Pht hin bnh sm v cha tr kp thi, cch ly bnh nhn v hn ch tip xc nht l nhng bnh nhn ang thi k u ca bnh. 4.1.2. Phng bnh c hiu Vaccine ho g hin nay l vaccine cht, c lm t vi khun ho g pha I. Dng vaccine ho g tim ng lot cho tr em di 1 tui gy min dch c bn. Tim nhc li sau 1 nm cng c min dch v sau 5 nm tim nhc li mt ln na. Vaccine phng bnh ho g l mt trong 6 loi vaccine bt buc trong chng trnh tim chng m rng, thng dng di dng 1 vaccine hn hp Bch hu-Un vn-Ho g (DTC: Diphterie-Tetanie-Cough). Ngoi ra c th dng huyt thanh min dch hoc globulin min dch ngi phng bnh v cha bnh ho g tr cn b. 4.2. iu tr Phi pht hin sm cch ly v iu tr ngay bng khng sinh. Liu php khng sinh khng rt ngn c giai on kch pht nhng loi tr c vi khun gy bnh, gim ly lan, d phng bi nhim. Khng sinh chn lc l erythromycin.

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TRC KHUN M XANH V BURKHOLDERIA PSEUDOMALLEI

Mc tiu hc tp 1.Trnh by c c im sinh vt hc ca trc khun m xanh v Burkholderia pseudomallei 2.Trnh by c kh nng gy bnh ca hai vi khun ny 3.Trnh by c phng php chn on sinh vt hc, phng php phng nga v iu tr Trc khun m xanh v Burkholderia pseudomallei thuc h Pseudomonadaceae , h ny bao gm nhng trc khun Gram m, hiu kh, di ng bng mt hoc nhiu lng mt u (tr Burkholderia mallei khng di ng), chng chuyn ha nng lng bng hnh thc oxy ha carbohydrate, khng ln men cc loi ng. C enzyme oxydase v enzyme catalase. Chng phn b rng ri trong thin nhin, ch mt s loi c kh nng gy bnh ngi, ng vt hoc thc vt.

I. TRC KHUN M XANH (Pseudomonas aeruginosa)

Pseudomonas aeruginosa thng tm thy trong t, trong nc hoc trn c th ngi v ng vt. Trc khun m xanh l tc nhn chnh ca nhim trng bnh vin v cc nhim trng c hi. 1. c im sinh vt hc 1.1. Hnh th Trc khun Gram m, kch thc thay i thng thng nh v mnh, 1,5 - 3 m, thng hp thnh i v chui ngn, rt di ng, c lng mt u, him khi to v v khng to nha bo. 1.2. Nui cy Vi khun hiu kh, mc d dng trn cc mi trng nui cy thng thng nh thch dinh dng, thch mu, canh thang. Nhit thch hp 30 - 37 0C, nhng c th pht trin c 410C. pH thch hp l 7,2-7,5. Khun lc thng ln, trong, b u hoc khng u, c th c nh kim loi, mu xm nht trn nn mi trng mu hi xanh, mi thm. Cng c th gp loi khun lc x x hoc nhy. Tnh cht c trng ca trc khun m xanh l sinh sc t v cht thm. Trn mi trng nui cy c pepton, vi khun c th tit ra cc loi sc t sau : -Pyocyanin: l loi sc t phenazin c mu xanh l, tan trong nc v chlorofoc, khuch tn ra mi trng nui cy lm cho mi trng v khun lc c mu xanh. Sc t ny sinh ra thun li trong mi trng tip xc nhiu vi khng kh. Ch c trc khun m xanh sinh sc t pyocyanin. -Pyoverdin: l loi sc t hunh quang, pht mu xanh khi chiu tia cc tm c bc sng 400 nm, tan trong nc nhng khng tan trong chlorofoc. Ngoi trc khun m xanh cn c mt s loi Pseudomonas khc to thnh sc t ny. -Pyorubrin: sc t mu hng nht, ch 1% s chng trc khun m xanh sinh ra sc t ny.

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-Pyomelanin: sc t mu nu en, ch 1-2% s chng trc khun m xanh sinh sc t ny. C khong 5-10% s chng trc khun m xanh khng sinh sc t. 1.3. Tnh cht sinh ho Trc khun m xanh c oxydase dng tnh, lm lng gelatin, kh NO3 thnh N2. S dng carbohydrat bng hnh thc oxy ho c sinh axit nh glucose, mannitol, glycerol, arabinose...Lactose m tnh, Citrat simmon dng tnh, ADH dng tnh; Urease m tnh, indol m tnh, H2S m tnh. 1.4. Khng nguyn Vi khun c khng nguyn lng H khng bn vi nhit v khng nguyn O chu nhit. Da vo khng nguyn O, ti nay ngi ta chia trc khun m xanh lm 16 type huyt thanh. Cng c th nh type phage nhng thng nh typ bacterioxin (pyocin) trong cc v dch. Cng nh cc trc khun ng rut, khng nguyn O ca trc khun m xanh mang ni c t bn cht gluxit-lipit- protein. Nhng trong c ch sinh bnh quan trng hn l ngoi c t. Trong 3 loi ngoi c t do vi khun to thnh ngoi c t A c xem nh l nhn t ch yu v c lc, n khng bn vi nhit, git cht chut nht, chut ln v cn tr s tng hp protein tng t nh c t bch hu. 2. Kh nng gy bnh Trc khun m xanh l loi vi khun gy bnh c iu kin. V vy him gp nhim trng Pseudomonas aeruginosa ngi bnh thng tr nhim trng th pht nh vim tai ngoi mn. Nhim trng thng xy ra nhng ngi m c ch bo v b tn thng nh s dng corticoid hoc khng sinh di ngy, bng nng hoc tim tnh mch ma ty... V tr nhim trng thng thng l ng tiu v vt thng h (nht l vt bng). Ti ch xm nhp chng gy vim c m (m c mu xanh), c th suy gim sc khng chng c th xm nhp vo su hn trong c th v gy vim cc ph tng nh cc nhim trng nung m v nhng p xe nhng phn khc nhau c th ngi. Nhng trng hp vim mng trong tim, vim phi, vim mng no tuy him nhng cng xy ra hoc gy bnh ton thn (nh nhim khun huyt, nhim khun tr mi hoc non thng bnh rt trm trng). Nhim khun mu thng gy cht xy ra ngi suy nhc. Nhng nm gn y nhim trng trc khun m xanh tr nn quan trng do :iu tr v phng nga nhng nhim trng khc bng nhng khng sinh m n khng, s dng cc thuc corticoit, thuc chng chuyn ho v thuc gim min dch lm cho gim st sc khng ca c th, s dng cc dng c thm khm nh ng thng v cc dng c khc thm d cha c kh khun tt, s dng ngy cng rng ri mu v cc sn phm ca mu m ta khng th kh khun c trong khi cc cht ny c th b nhim Pseudomonas. Trc khun m xanh l mt tc nhn nhim trng bnh vin ng lu : nhim trng sau m v bng nng. Nhim trng trc khun m xanh trong nhng trng hp c th gy cht. T l t vong do nhim trng mu c th vt qu 80%. 3. Sinh l bnh hc Mt s tc gi chng minh rng trc khun m xanh gy bnh c l do:

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- Mt c t to thnh t mt hn hp cht c gm: dung huyt t, protease, lexitinase. - Khng nguyn nhy xung quanh vi khun gm mt ADN gn vi gluxit- lipit - protein ca khng nguyn O (ni c t) ca vi khun. Khng nguyn ng vai tr quan trng trong c lc ca vi khun (c th so snh vi vai tr ca ni c t). 4. Chn on Bnh phm l m ca cc vt thng b bi nhim, cht dch ph qun, nc tiu, dich mng phi... Trong chn on dch t hc: dch chuyn, dch ra vt thng, dng c ngoi khoa... l mu nghim. Mu nghim c cy ln mi trng thng thng nh thch dinh dng hoc mi trng c cht c ch nh mi trng Cetrimide. 37 0C trong kh trng thng. Chn khun lc dt, ln, b khng u, b mt c nh kim loi, to sc t ha tan nhum xanh khun lc v nhum xanh mi trng xung quanh khun lc. Xc nh vi khun da vo trc khun Gram m, khng sinh nha bo, oxidase dng tnh, chuyn ho ng theo kiu oxy ho, c bit khun lc c mi thm v sinh sc t nhum mu mi trng xung quanh khun lc. i vi cc chng khng sinh sc t cn cy vo cc mi trng tng sinh sc t nh: King A (tng sinh pyocyanin) v King B (tng sinh pyoverdins). Ngi ta c th s dng nhng k thut khc nhau xc nh c ngun gc ca cc chng trc khun m xanh trong cc nhim trng bnh vin. 5. Phng nga v iu tr Nhim trng do Pseudomonas aeruginosa kh iu tr v khng vi nhiu khng sinh. Nhng chng thng gp cho thy vi khun thng khng vi 3 khng sinh hoc hn. Trong iu tr phi lm khng sinh . Hin nay thng s dng tobramycin, amikacin, carbenicillin, cefaperazon, ceftazidim. Gn y min dch liu php hot ng v th ng c s dng bnh nhn bng vi kt qu kh tt. Nhim trng ti ch c th ra vi 1% axt axetic hoc bi thuc m Colistin hoc Polymycin B.

II. BURKHOLDERIA PSEUDOMALLEI (Trc khun Whitmore)

B. pseudomallei l tc nhn gy ra bnh Melioidosis, mt bnh thng gp vng ng - Nam chu . Bnh Melioidosis thng nng, t l t vong cao do chn on lm sng kh khn, bnh hay ti pht v do B. pseudomallei khng li nhiu khng sinh. 1. c im sinh vt hc 1.1. Hnh th Trc khun Gram m ngn, bt mu thuc nhum mnh hai u, ng ring l hoc chui ngn, i khi c hnh dng cu trc khun. Kch thc 0,8 x1,5 m. Vi khun di ng c mt chm lng mt u, khng sinh nha bo. 1.2. Tnh cht nui cy Vi khun mc c cc mi trng nui cy thng thng, kh phn lp nui cy ln u. Hiu kh, nhit thch hp 370C, nhng c th pht trin c t 5-420C v mi trng c 3% NaCl.

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Trn mi trng lng, vi khun mc bng cch to vng, theo thi gian vng cng dy. Trn mi trng c, to khun lc kh, b my nhn nheo, b rng ca, mu trng c hoc mu kem. C th quan st thy nhiu dng khun lc c kch thc v hnh thi khc nhau trn cng mt mi trng. B. pseudomallei khng sinh sc t ho tan. Nui cy to ra mi thm (ging mi nho). 1.3. Tnh cht sinh ho Oxydase dng tnh(+), catalase dng tnh(+). S dng carbohydrat theo li oxy ho sinh axit nh: arabinose, dulcitol, glucose, lactose v mannitol, lm lng gelatin, ADH (arginin ihydrolase) dng tnh(+), citrat simmon dng tnh(+), indol m tnh(-), kh nitrat thnh N2 , di ng mnh. 1.4. Sc khng B. pseudomallei c mt trong t nhin, c bit c tm thy trong cc cnh ng la nc vng ng Nam . Chng sng hng tun n hng thng ni m nu gp iu kin thch hp nh khng c nh sng mt tri v lnh. 1.5. Min dch Do vi khun phn b rng ri trn ng rung, 30-50% nng dn kho mnh sng trong vng B. pseudomallei lu hnh c khng th chng vi khun ny. Khi b bnh, khng th tng cao v cn tn ti vi thng sau khi khi bnh. Tuy nhin, khng th ny khng c vai tr bo v, bnh nhn c th b ti nhim hoc ti pht mt cch d dng. 2. Kh nng gy bnh 2.1. ngi Vi khun gy bnh Mlioidosis thng gp Min in, Thi Lan, Vit Nam, Lo, Campuchia, Indonesia v chu c. Vi khun xm nhp vo c th ch yu qua vt thng, nhng ch sy st trn da. Ti ni xm nhp chng hnh thnh nhng mn m nh, c khi to thnh mt p xe rt ln. nhng ngi suy gim min dch, mc cc bnh mn tnh ko di vi khun thng vo mu v gy ra bnh cnh lm sng nng ca mt nhim khun huyt. T mu vi khun n cc ph tng gy nn p xe nh nhiu c quan nh phi, thn, gan, lch. Sau cc p xe nh to thnh cc p xe ln gy ra cc triu chng lm sng nhiu c quan khc nhau. Vi khun c th sng trong cc i thc bo, iu ny c th gii thch nhng trng hp bnh ti pht. Bnh c th din bin cp tnh, bn cp v mn tnh - Th cp tnh nhim khun huyt vi a chy v st c tnh, thng cht trong vi ngy. - Th ban cp dng thng hn vi p xe phi, thn, gan, c, cht sau vi tun l. - Th mn tnh c th khu tr (p xe xng hoc da) hoc nhim khun huyt kiu ln sng. 2.2. Kh nng gy bnh thc nghim Ngi ta c th gy bnh c cho phn ln cc ng vt nh th, chut lang, chut nht, nga bng nhiu ng khc nhau: qua da, tim tnh mch, tim phc mc hoc ng h hp. Bnh melioidose sc vt c th ly sang ngi.

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3. Chn on vi sinh vt 3.1. Phn lp vi khun Bnh phm l m p xe, mn m, mu trong nhim khun huyt, m trong vim ph qun, dch mng phi, dch mng tim...Cy bnh phm vo mi trng nui cy thng thng nh thch thng, thch mu, canh thang hoc mi trng chn lc c cha gentamicin. Xc nh vi khun da vo hnh th, tnh cht bt mu, hnh thi khun lc v tnh cht sinh ha. 3.2. Chn on huyt thanh - Trong iu tra dch t hc: dng phn ng ngng kt hng cu th ng tm khng th ngng kt - Trong chn on bnh: dng phn ng ngng kt hng cu th ng v ELISA vi khng nguyn protein 4. Phng nga v iu tr 4.1. Phng bnh Hin nay cha c vaccine. Tng cng sc khng chung, gi gn v sinh, trnh cc tn thng da trong khi lm vic ni c vi khun. 4.2. iu tr Dng khng sinh nh tetracyclin, chloramphenicol, bactrim, ceftazidim. V vi khun ln trnh trong t bo nn cn lu chn la khng sinh khuch tn tt vo trong t bo v dng trong thi gian di phng nga ti pht. Vi khun khng gentamycin, ampicillin, polymycin. Dng bin php chc ht m p xe, tng cng sc khng, iu tr triu chng.

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VIBRIO
Mc tiu hc tp 1.Trnh by c cc c im sinh vt hc. 2.Trnh by c kh nng gy bnh ca vi khun t v V.parahaemolyticus. 3.Trnh by c phng php chn on vi sinh vt. Ging Vibrio thuc vo h Vibrionaceae. Chng l nhng vi khun hnh que hi cong nh du phy, Gram m, khng sinh nha bo, di ng nh mt lng mt u, oxydaza dng tnh ... Ging Vibrio c chia thnh : - Vibrio cholerae O1: thuc nhm huyt thanh O1 c kh nng sinh c t rut v gy ra bnh dch t. Vibrio cholerae O1 bao gm type sinh hc c in v type sinh hc El Tor. Cc sinh type ny ngng kt vi khng huyt thanh nhm 01. Trong nhm ny c 3 type huyt thanh l Ogawa, Inaba v Hikojima. - Vibrio cholerae khng phi O1/ khng phi O139: bao gm cc nhm huyt thanh t O2 - O138 khng c kh nng gy dch t. C tnh cht sinh ha tng t nh V.cholerae O1 nhng khng ngng kt vi khng huyt thanh O1. Cc nhim trng do nhm ny thng lin quan n mi sinh, chng gy ra vim rut cp nhng c ch gy bnh vn cha c gii thch. - Vibrio cholerae O139: l tc nhn gy ra bnh dch t c pht hin ln u tin vo nm 1992 ti n v Bangladesh. c lc ca n l c t rut v khng nguyn pili ng iu ha c t (Toxin coregulated pili - TCP). - Cc Vibrio khc : V. mimicus; V. parahaemolyticus; V.hollisae. V. fluvialis; V.furnissii; V.vulnificus; V.alginolyticus; V.damsela; V.cincinnatiensis; V.metschnikovii.

I. VI KHUN T (Vibrio cholerae)

1. c im sinh vt hc 1.1. Hnh th Vi khun t hnh que ngn, hi cong hnh cung hoc hnh du phy, Gram m, rt di ng nh mt lng u, khng c v, khng sinh nha bo. 1.2. Tnh cht nui cy Vi khun t rt hiu kh, mc c trn cc mi trng dinh dng thng, pH kim. Thng dng nc pepton pH 8,5 , mi trng thch TCBS (thiosulfate Citrate - Bile salt) pH 8,6 , TTGA (Taurocholate - Tellurite - Gelatin Agar) pH 8,5 nui cy phn lp vi khun t. 1.3. Tnh cht sinh vt ha hc Vi khun t c oxidase, ln men khng sinh hi glucose, saccharose, Dmannitol, maltose, khng ln men arabinose. Phn ng indol dng tnh, phn ng Voges-Proskauer m tnh i vi sinh type c in v dng tnh i vi sinh type El Tor.

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1.4. Cu trc khng nguyn - Khng nguyn thn O: bn cht l lipopolysaccharide. N quyt nh tnh sinh min dch ca vaccine t c in (vaccine t cht). Ngi ta phn bit thnh nhiu nhm huyt thanh O. V.cholerae sinh type c in v sinh type El Tor thuc nhm huyt thanh O1. Trong nhm O1 c 3 type huyt thanh : Ogawa, Inaba v Hikojima. - Khng nguyn lng H: Khng c gi tr trong thc tin. - Khng nguyn c t rut bn cht l protein, c t rut ca V.cholerae 01 kch thch c th sinh khng c t. 1.5. Sc khng Vi khun t cht nhit 100oC hoc 80oC/5 pht v b tiu dit bi cc ha cht nh cloramin, cresyl, vi cc ... Kh hanh v nh nng mt tri cng lm vi khun d cht. Trong nc , nc bin, nc ao h vi khun sng c vi ngy. 2. Kh nng gy bnh 2.1. Sinh bnh hc Cc vi khun t xm nhp c th bng ng tiu ha, chng phi vt qua hng ro dch v ca d dy c pH axt xung rut non l ni c pH thch hp cho s pht trin ca vi khun. axt bnh thng ca dch v l mt cn tr rt ln i vi qu trnh sinh bnh ca vi khun t. Vo n rut non, V.cholerae bm dnh vo t bo nim mc rut nh c cc yu t bm dnh nh khng nguyn TCP, khng nguyn ngng kt hng cu nhy cm vi mannose..., vi khun nhn ln v tit ra c t rut. Cc vi khun khng xm nhp vo trong cc t bo nim mc rut. c t rut ca vi khun t l mt protein gm 2 tiu phn A (Active) v B (Binding) c chc nng ring bit. Tiu phn A c hai tiu n v A1 v A2, tiu phn B c 5 tiu n v B1, B2, B3, B4 v B5. Tiu phn B c chc nng gn c t rut vo th th ganglioside GM1 trn mng ca t bo nim mc rut, cn tiu phn A m ch yu l A1 xm nhp vo bn trong t bo hot ha enzyme adenylate cyclase, lm tng nng AMP vng ni bo lm cho t bo nim mc rut gim hp thu Na+, tng tit nc v Cl-, gy ra a chy cp tnh. Nu khng c iu tr tch cc bnh nhn s cht v kit nc v mt cc cht in gii. c t t cn gy nn c ch min dch t bo bng cch tc ng trc tip ln macrophage v t bo lympho T. Trong qu trnh sinh bnh t, c t t v vi khun t khng gy nn thng tn nim mc rut. V vy c ch hp th li mui, nc v glucose vn nguyn vn. y l c s sinh l cho vic b dch bng ng ung dung dch c in gii v glucose (ORESOL) c tc dng tt (glucose y nhm to iu kin hp th li Na cao hn, ch khng phi l cung cp nng lng). 2.2. Kh nng gy bnh Trong iu kin t nhin bnh thng, V.cholerae ch gy bnh t cho ngi. Bnh t l mt bnh nhim trng nhim c cp tnh, ly rt mnh gy thnh dch ln. Thi gian bnh t 2 n 5 ngy. Du hiu c trng ca thi k ton pht ca bnh l tiu chy v nn, phn lng v trng nh nc vo go. Bnh nhn mt nc, mt mui rt nhanh, c th mt 1 lt nc trong 1 gi do ch vi gi l xut hin hi chng mt nc cp tnh lm cho ton thn st i rt nhanh v rt nng. Nu khng c iu tr, t l cht rt cao (50 n 60%).

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Lm sng bnh t c nhiu biu hin rt khc nhau t th nh d b qua cho n th nng vi hi chng t in hnh. 2.3. Min dch p ng min dch dch th trong bnh t lm xut hin IgG trong mu v IgA tit nim mc rut. Cc khng th ny chng li vch t bo vi khun, ngn cn vi khun bm dnh vo nim mc v chng li c t t, ngn cn c t t (tiu phn B) gn vo mng t bo nim mc rut. 2.4. Dch t hc Bnh t ly truyn qua ng tiu ha qua thc n, nc b nhim khun. Ngun truyn nhim l ngi bnh v ngi lnh mang vi khun t. K t nm 1817 cho n nay trn th gii xy ra 7 i dch t. Su i dch t u do V.cholerae sinh type c in gy nn. i dch t ln th 7 do V.cholerae sinh type El Tor gy nn, bt u t nm 1961 ko di cho n ngy nay. V.cholerae El Tor khng vi tc nhn ha hc, tn ti lu hn ngi v sng trong thin nhin lu hn V.cholerae sinh type c in. Ngoi ra i vi vng bnh t El Tor lu hnh th nhng trng hp nng thng t hn v nhng trng hp nh khng triu chng li nhiu hn. Bt u t nm 1992 dch t xy ra Madras v nhiu ni khc thuc n v Bangladesh do Vibrio cholerae O139 gy nn vi c ch bnh sinh hon ton ging nh Vibrio cholerae O1. Sau dch t do chng O139 ly lan ra cc nc khc. 3. Chn on vi sinh vt 3.1. Chn on trc tip Bnh t l mt bnh cp tnh nn cy phn phn lp vi khun t l phng php chn on tt nht. 3.1.1. Bnh phm Ly phn sm ngay trong thi k u ca bnh trc khi iu tr khng sinh. Bnh phm phn cn a ngay v phng xt nghim trong vng 2 gi. Nu gi bnh phm i xa phi cho vo mi trng bo qun v vn chuyn Cary Blair, v a v phng xt nghim cng sm cng tt. 3.1.2. Xt nghim knh hin vi Soi ti c th thy vi khun t di ng rt nhanh. Nhum Gram thy nhiu phy khun Gram m. Xt nghim bnh phm knh hin vi c tc dng chn on s b. 3.1.3. Nui cy Bnh phm c cy vo cc mi trng chn lc v mi trng phong ph phn lp vi khun. Xc nh tnh cht sinh vt ha hc. Lm phn ng ngng kt trn phin knh vi khng huyt thanh a gi O1 v vi khng huyt thanh n gi c hiu type Inaba hoc Ogawa xc nh chn on. 3.1.4. Phng php chn on nhanh xc nh nhanh vi khun t c th dng cc k thut nh bt ng vi khun, khng th hunh quang trc tip. 3.2. Chn on gin tip

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Phng php chn on huyt thanh khng gip ch cho chn on bnh. N c th c dng trong iu tra dch t hc. 4. Phng bnh v cha bnh 4.1. Phng bnh 4.1.1. Phng bnh chung - Gim st dch t hc, ch ng pht hin ngun bnh sm, kp thi cch ly, bao vy v x l. - Lm sch mi trng sng bng cc bin php nh x l rc v nc thi theo ng yu cu v sinh; kim tra v sinh thc phm; thc hin n chn ung si v sch ... 4.1.2. Phng bnh c hiu - Vaccine cht, dng ng tim trong da, c hiu lc thp v thi gian bo v ngn. Hin nay nhiu nc khng s dng loi vaccine c in ny. - Vaccine sng gim c lc: to ra cc chng t bin khng c lm vaccine ung. Hin nay ang th nghim. - Vaccine cht, ung: Loi vaccine ny c th dng ton t bo bt hot n thun hoc dng kt hp vi tiu n v B ca c t t c tinh ch. Vit Nam dng loi vaccine t ng ung n lin cha cc t bo Vibrio cholerae O1 c in v El Tor c bt hot bng nhit v formalin. Hin nay ang th nghim loi vaccine t bt hot (Vaccine biv-WC) gm c Vibrio cholerae O1 v Vibrio cholerae O139. 4.2. Cha bnh Phi b nc v in gii sm, nhanh v cho bnh nhn. Dng khng sinh Tetracycline, Doxycycline ...

II. VIBRIO PARAHAEMOLYTICUS

V.parahaemolyticus c phn lp ln u Nht Bn nm 1950 t phn bnh nhn tiu chy do n c bin. 1. c im sinh vt hc V.parahaemolyticus c hnh hi cong v ngn. Gram m v di ng. L vi khun a mn (halophile) tn ti trong nc bin v cc ng vt bin nh c, tm, s, c ... Vi khun mc tt mi trng kim v mn. Nhit thch hp cho s nhn ln l 37 o C. V.parahaemolyticus c oxidase dng tnh, ln men D-mannitol, maltose, L.arabinose, khng ln men saccharose. V.parahaemolyticus b cht 65 o C sau 10 pht, chng khng pht trin c nhit di 15 o C. Vi khun c 3 loi khng nguyn : + Khng nguyn thn 0 : chu nhit, c chia thnh 12 type. + Khng nguyn lng H.

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+ Khng nguyn v K : khng chu nhit, c chia thnh 59 type. 2. Kh nng gy bnh V.parahaemolyticus l mt trong nhng nguyn nhn gy nhim trng nhim c thc n. Ngi mc bnh ch yu l do n phi thc n hi sn cha c nu chn hoc b nhim khun trong qu trnh ch bin v bo qun. Thi gian bnh bnh ngn t 2 - 6 gi. Bnh biu hin cc triu chng nn v tiu chy kiu t nh hoc tiu chy kiu l trc khun. Bnh do vi khun ny gy ra gp nhiu nht Nht Bn, ngoi ra cn gp nhiu nc khc. Vit Nam gp nhiu ln ti vng b bin Bc B. 3. Chn on vi sinh vt - Phn lp vi khun t bnh phm l phn, cht nn ca bnh nhn. - Phn lp vi khun t cc hi sn trong trng hp iu tra thc phm nhim khun. 4. Phng bnh v cha bnh - Cha c vaccine phng bnh. - Phng bnh chung bng cch nu k thc n hi sn, khng n sng hi sn. - iu tr bng cc khng sinh nhy cm nh tetracycline, chloramphenicol ...

CAMPYLOBACTER V HELICOBACTER
Mc tiu hc tp 1. Trnh by c mt s tnh cht vi khun hc ca Campylobacter v Helicobacter. 2. Nu c kh nng gy bnh ca cc vi khun ny. 3. Trnh by c mt s phng php chn on vi khun hc i vi Campylobacter v Helicobacter.

I. CAMPYLOBACTER JEJUNI
Ging Campylobacter thuc h Spirillaceae, gm c cc loi khc nhau c th gy bnh cho ngi. 1. c im sinh vt hc Campylobacter jejuni l nhng vi khun b, mnh, Gram m, hnh du phy nhn hai u, rt di ng nh c 1 lng 1 u, khng sinh nha bo. Nui cy C.jejuni trn mi trng nhn to thng kh khn v vi khun i hi iu kin vi hiu kh (micro-aerophile). Mc c 37 o C nhng mc tt hn 42 o C, khng mc 25 o C. Thng dng cc mi trng chn lc nh thch mu Columbia, thch mu tryptose phn lp vi khun. C.jejuni mc chm sau 2 - 3 ngy. Vi khun c Oxydase v Catalase, phn hy nitrat, khng oxy ha hoc khng ln men cc loi ng.

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C.jejuni c khng nguyn O chu nhit c chia thnh 23 typ huyt thanh v c khng nguyn H khng chu nhit. 2. Kh nng gy bnh C.jejuni l mt tc nhn gy vim rut cp tnh thng gp ngi. Chng xm nhp vo ngi do n ung cc thc n v nc b nhim khun, do tip xc vi ng vt, ch yu l vi gia cm, gia sc. Thi gian bnh 2-10 ngy. Th lm sng thng gp l bnh cnh ca mt vim rut cp tnh vi du hiu au bng, tiu chy d di, phn nc c khi c mu v m. C trng hp xy ra nhim khun huyt. Tiu chy do C.jejuni ko di 5-10 ngy. a s trng hp khi khng cn iu tr bng khng sinh. C ch gy bnh cha r. C.jejuni c c t rut, nhng c kin cho rng vi khun ny c kh nng xm nhp ging nh Shigella. C.jejuni nhn ln ch yu hi trng v hng trng. Bnh vim rut do C.jejuni xy ra nhiu ni trn th gii, gy tiu chy cp ngi, c bit tr em v khch du lch t cc nc pht trin n cc nc nhit i. 3. Chn on vi sinh vt Chn on vim rut cp do C.jejuni phi da ch yu vo phn lp vi khun t phn ca bnh nhn. Cy phn vo cc mi trng chn lc, nhit 42oC t 2 - 3 ngy trong kh trng c 5% oxy, 10% cacbonic v 85% nit. 4. Phng bnh v iu tr Cha c vaccin. Cn ch v sinh mi trng, v sinh n ung. Khng sinh ch nn dng trong nhng trng hp nhim khun huyt hoc tiu chy ko di.

II. HELICOBACTER PYLORI

T nm 1900 n nm 1980, thnh thong ngi ta ghi nhn c s hin din ca mt vi khun hnh xon nim mc d dy. Nhng nhng pht hin khng c quan tm ng mc, bi v cho n cui th k 20 ny, hu nh ngi ta vn quan nim rng d dy l mi trng khng c vi khun do pH acid ca n. Mi n nm 1979, Warren a ra gi thuyt chnh vi khun l cn nguyn gy ra vim, lot d dy - t trng. Nm 1981, Marshall bt u tm ra phng php phn lp vi khun ny, n nm 1982 ng nui cy thnh cng v thy vi khun ny ging nh Campylobacter jejuni , nm 1983 ng chnh thc cng b vi khun ny trn tp ch Lancet (Paris) vi tn l Campylobacter pyloridis, v sau c gi l Campylobacter pylori. Nm 1989, Goodwin nghin cu v cu trc t bo vi khun ny v thy chng khc hn cc Campylobacter khc nn ngh xp cc Campylobacter ny thnh mt ging mi, ging Helicobacter v t Campylobacter pylori c gi l Helicobacter pylori. 1. c im sinh vt hc L nhng vi khun nh, lc mi phn lp t mu sinh thit nim mc d dy th c hnh cong, hoc hnh ch S, ng thnh m. Nu cy chuyn nhiu ln th c hnh que. Vi khun Gram m, rt di ng nh c 2-6 lng mt u. Vi khun khng sinh nha bo. Vi khun i hi iu kin vi hiu kh. Yu cu dinh dng cao, mi trng nui cy cn c mu ng vt hoc huyt thanh. Vi khun mc chm, trn mi trng thch mu Colombia hoc thch mu tryptose sau 3 ngy 37 oC, c th thy khun lc nh, khng mu, c nh nhn. Vi khun khng ln men cc loi ng, c oxydase v catalase, urease dng tnh mnh. Urease dng tnh mnh l tnh cht dng phn bit H. pylori vi cc vi khun c hnh cong khc nh Campylobacter...

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2. Min dch 2.1. p ng min dch ti ch Ti ni H. pylori xm nhp, xut hin hin tng tp trung mt s lng ln cc bch cu trung tnh v cc t bo lympho. Cc t bo lympho v bch cu gii phng ra cc interleukin v cc gc t do oxy ho, nhng phn ng vim ti ch ny khng c kh nng loi b H. pylori. 2.2. p ng min dch dch th Khi nghin cu tm khng th trong mu nhng bnh nhn lot d dy - t trng c mt H. pylori, ngi ta pht hin thy c s gia tng khng th IgG, IgA v c bit l IgM. Cc khng th ny gim mt cch c ngha sau khi tit tr ht H. pylori. Vn ny c ng dng trong chn on huyt thanh hc v gim st kt qu iu tr. 3. Kh nng gy bnh ngi 3.1. Kh nng gy bnh T khi Marshall phn lp thnh cng vi khun ny, nhiu cng trnh nghin cu v vai tr gy bnh ca H. pylori c thc hin. Ngi ta cng tin hnh nghin cu trn ngi tnh nguyn, y l nhng ngi khng c hi chng vim, lot d dy; h c ung H. pylori. Sau mt thi gian, h b vim d dy; sau ngi ta li dng cc bin php tiu dit H. pylori th nhng ngi ny li ht vim d dy. Gn y, nhiu tc gi nhn xt rng, hu nh cc trng hp vim lot d dy - t trng u lin quan n nhim trng H. pylori; c bit trong th vim teo, mt th rt d dn n ung th d dy m li thy lun lun c mt vi khun ny. 3.2. C ch gy bnh H. pylori rt di ng, xm nhp qua lp cht nhy v xm ln biu m d dy, c bit l khong gian bo. Vi khun sn sinh urease rt mnh, enzyme ny c hot tnh phn gii ur thnh amoniac. Ur l sn phm chuyn ho ca cc m t bo, chng vo mu mt phn v c o thi ra ngoi qua thn. Mt lng ur t mu qua lp nim mc d dy vo dch d dy. Amoniac c phn ng kim lm tng tm thi pH ti ch n khong 6,5 v gip cho vi khun sng st c trong mi trng rt axit ca d dy. Ngoi ra amoniac cn gy c trc tip i vi t bo nim mc d dy. H.pylori cn lm gim cht nhy bo v thnh d dy cho nn axit dch v tc ng trc tip ln thnh d dy. S phi hp nhiu yu t trn gy vim, let d dy. Trn nhng bnh nhn b vim let d dy - t trng c th phn lp c H.pylori t 80%-90% trng hp.

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3.3. Dch t hc Tnh trng kinh t ca x hi c nh hng ln n hin tng nhim H. pylori. Ngay M, t l nhim H. pylori ngi da en cng cao hn ngi da trng, bi v lin quan n i sng tinh thn, vt cht v v sinh mi trng. Ngun truyn nhim l ngi, c th gp kh nhng khng ng k. ng ly ch yu l ngi truyn sang ngi. Phng thc ly truyn l ng phn ming v ng ming - ming, trong ng phn - ming ng vai tr ch yu. 4. Chn on vi sinh vt 4.1. Chn on trc tip Phn lp vi khun t bnh phm, bnh phm thng thng nht l mu sinh thit nim mc d dy khi ni soi, hoc c th l dch d dy. Nui cy ln cc mi trng thch hp nh thch mu Colombia, 37oC iu kin vi hiu kh, sau 3 ngy thy khun lc nghi ng th trch bit ri nhum Gram (cn thay th Safranin bng Fuchsin mu c r hn do vi khun nh), th nghim cc tnh cht sinh vt ha hc xc nh vi khun. 4.2. Chn on nhanh bng test urease Cho mu sinh thit vo mi trng Ure-christensen, nu trong mu nghim c H.pylori th chng s phn hy ure thnh amonium v carbon dioxide lm cho pH mi trng tr nn kim v i mu ca ch th mu phenol t mu hng sang cnh sen. 4.3. Th nghim o hm lng carbon ng v phng x C13 trong hi th Theo nguyn l l CO2 c to thnh sau phn ng phn hy ure s theo mu ri ti phi v thi ra ngoi theo hi th. a vo c th bnh nhn ure gn C13, o hm lng C13 thi ra theo hi th xc nh c hay khng nhim H.pylori. 4.4. Tm khng th khng H.pylori Tm khng th khng H.pylori trong huyt thanh, trong nc bt hoc trong dch d dy bng th nghim ELISA. Thng dng trong iu tra dch t hc nhim H.pylori. 4.5. K thut khuch i gen (PCR) K thut PCR c th pht hin c on gen c hiu ca H.pylori c mnh sinh thit d dy, dch d dy, nc bt v phn ca bnh nhn. 5. Phng bnh v iu tr 5.1. Phng bnh - Phng bnh chung: bnh d dy-t trng ph thuc rt nhiu vo cc iu kin kinh t - x hi. Vic nng vao i sng cho nhn dn l rt cn thit, trong v sinh mi trng cng ng vai tr quan trng, v bnh ly ch yu qua ng phn ming. - Phng bnh c hiu: phng bnh c hiu qu v l tng nht l dng vaccine. Hin nay, mt loi vaccine phng bnh vim lot d dy-t trng ang c cc nh nghin cu trn th gii quan tm v thc nghim, hy vng trong tng lai gn s c vaccine phng bnh ny. 5.2. iu tr Hin nay, trong iu tr vim lot d dy - t trng, ngoi s dng thuc khng tit, ngi ta cn dng khng sinh tiu dit cn nguyn vi khun H. pylori, thng dng hai loi khng sinh phi hp nh Metronidazol hoc Tinidazol vi Amoxicilline hoc Clarithrromycin th hiu qu tc dng tt hn l dng mt loi.

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CC XON KHUN GY BNH

Mc tiu hc tp 1. M t v tr li c cc cu hi v tnh cht vi khun hc ca cc xon khun gy bnh gm vi khun gaing mai, cc leptospira v cc borrelia gy bnh 2. Trnh by v tr li c tnh cht gy bnh ca cc xon khun gy bnh 3. Nu v tr li c cc phng php chn on phng th nghim, cc nguyn tc phng v iu tr cc xon khun gy bnh Cc xon khun c dng hnh xon, c kh nng di ng, cc xon khun c nhiu ni trong t nhin, nhiu loi k sinh trn c th ngi v ng vt. Mt s xon khun gy bnh cho ngi, chng ta s ln lt kho st 3 loi xon khun - Cc Treponema - Cc Leptospira - Cc Borrelia

I. XON KHUN GIANG MAI ( TREPONEMA PALLIDUM )

H vi khun Treponema bao gm nhiu loi, c th chia lm 2 loi. - Loi khng gy bnh: Loi ny chim s ng, chng sng nhiu ni khc nhau trong c th nh ng sinh dc c T.genitale; hc ming c T.macrodentium. - Loi gy bnh: gm loi T. carateum gy bnh pinta, loi T.pallidum vi di loi T. pallidium subspecies pallidum gy bnh giang mai hoa liu thng gp ngi, v thng c gi tt l T. pallidum. 1. c tnh sinh vt hc 1.1. c tnh hnh thi: Vi khun giang mai c dng hnh xon mnh di 8-20 m, rng 0,1-0,2 m vi khun c t 8 n 14 vng xon u, mi vng xon cch nhau khong 1 m. Vi khun khng c v, khng to nha bo, chng c lng 2 u nhng khng di ng bng lng m bng s un khc cc vng ln v quay quanh trc ca n. Vi khun giang mai c th bt mu thuc nhum Giemsa, nhng vi khun bt mu tt nht l phng php nhum thm bc, nn y l phng php thng dng dng nhum xon khun, xon khun giang mai bt mu nu en trn mt nn mu nu nht. Treponema pallidum cho n hin nay vn cha nui cy c trn mi trng nhn tao, cch gi chng duy nht hin nay l tim truyn nhiu ln qua tinh hon th. 1.2. Tnh cht khng Xon khun giang mai khng rt km, ra khi c th ng vt vi khun cht nhanh chng. Cc cht st khun thng thng nh iod, thy ngn, x phng d dng git cht vi khun, nhit 42oC vi khun b git cht trong khong 30 pht, trong huyt thanh ct gi nhit 4oC vi khun sng c 1 ngy, m 70oC vi khun tn ti c nhiu nm. Vi khun nhy cm vi cc thuc khng sinh nh penicillin, tetracyclin. 1.3. Tnh cht khng nguyn Cu trc khng nguyn ca vi khun giang mai t c bit, thn vi khun cha phc hp protein, lipid v polysaccharide. nhng bnh nhn mc bnh giang mai trong huyt thanh c cha mt loi khng th c th cho phn ng vi hp cht lipit chit xut t tim b gi l cardiolipin, y l c s cho phn ng huyt thanh hc c in xc nh bnh giang mai. 2. Kh nng gy bnh

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2.1. Dch t hc Vi khun c ly truyn ch yu qua tip xc sinh dc gia ngi lnh v ngi bnh b giang mai, kh nng ly truyn cao nht lc bnh nhn b giang mai giai on I. Cc ng ly truyn khc gm nim mc mt, nim mc ming hoc qua da b xy st. ph n c thai b bnh giang mai vi khun c th qua rau thai v gy giang mai bm sinh, mt khc a tr ca cc b m ny cng c th b nhim trng khi sinh, lc tr i qua ng sinh dc b m. Vi khun giang mai cng c th c truyn qua ng truyn mu. 2. 2. c im sinh bnh v bnh l 2.2.1.Giang mai mc phi Vi khun giang mai xm nhp nhanh qua nim mc ton vn hoc b xy st. Sau vi gi vi khun c h thng bch huyt v vo mu. Thi gian th h ca vi khun giang mai l 30-32 gi. Thi gian bnh t l vi s lng vi khun a vo. Ni chung nng vi khun phi t 10 7 vi khun/ 1 gam t chc trc khi xut hin tn thng lm sng. Thc nghim cho thy chch trong da s lng vi khun 106 c th gy nn tn thng bnh l sau 72 gi, khi chch liu thp thi gian di hn. Trong nhim trng t nhin ngi thi gian bnh trung bnh 21 ngy. Bnh din bin qua 3 thi k. - Giang mai giai on I: giai on ny ko di 2 n 6 tun l, biu hin bi tn thng tin pht thng b phn sinh dc l sng giang mai. Vi khun giang mai c nhiu tn thng nn kh nng ly nhim cao. - Giang mai giai an II: t 2 thng n 1 nm biu hin chnh trong giai on ny l ban trn da v cc tn thng c quan ni tng pht trin. - Giang mai giai on III: tn thng hnh thnh cc c quan ni tng nh tim, mch mu, xng, t chc thn kinh di dng gm giang mai. Tn thng h thng thn kinh trung ng gy lit v tn ph. 2.2.2. Giang mai bm sinh ph n c thai b bnh giang mai vi khun c th qua rau thai v gy bnh cho thai nhi, a b c th cht khi cn trong bng m hoc c th sng n khi sinh. nhng a tr ny trong c th c cc tn thng giang mai c quan lm cho a tr c th b tn ph. 3. Chn on phng th nghim C nhiu phng php chn on phng th nghim ty theo giai on ca bnh. Hai phng php chn on phng th nghim chnh thng dng. 3.1. Phng php chn on trc tip Phng php ny ch p dng vi giang mai giai on I khi c nhiu vi khun tn thng sng giang mai. Bnh phm l cht tit dch t tn thng v pht hin c s hin din ca vi khun bng cc k thut sau. - Kho st vi khun trn knh hin vi nn en. - Nhum nhum thm bc - Nhum khng th hunh quang trc tip. - Xc nh DNA ca xon khun giang mai bng k thut PCR 3.2. Phng php chn on gin tip Bng dng cc th nghim huyt thanh hc c hai loi phn ng huyt thanh hc c dng. Loi phn ng huyt thanh vi khng nguyn khng c hiu v loi phn ng huyt thanh vi khng nguyn giang mai c hiu. 3.2.1. Phn ng huyt thanh vi khng nguyn giang mai khng c hiu Trong loi phn ng ny khng nguyn dng l hp cht lipid t tim b (cardiolipin). C cc loi phn ng.

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- Phn ng ln bng nh phn ng VDRL, RPR. y l cc phn ng d thc hin, cho kt qu nhanh v thng dng hin nay cc phng th nghim - Phn ng ELISA (VISUWELL) khng nguyn dng l khng nguyn trong phn ng ln bng. y l k thut chn on mi cho kt qu tin cy. - Phn ng c nh b th c dng trc y, hin nay khng cn dng. Phn ng ln bng v phn ng c nh b th c khi cho nhng kt qu dng tnh gi trong mt s trng hp nh bnh st rt, bnh thn h nhim m, bnh lupus ban , ph n c thai. 3.2.2. Phn ng huyt thanh vi khng nguyn giang mai c hiu Cc phn ng c dng gm. - Phn ng hp th khng th hunh quang giang mai (Fluorescent treponema antibody-Absorption: FTA-Abs) phn ng ny dng tnh rt sm trong bnh giang mai v vn cn dng tnh ko di ngay sau khi bnh c iu tr hiu qu. - Phn ng khng th ngng kt hng cu giang mai (TPHA). - Phn ng ELISA xc nh IgM: khng th khng IgM (anti-IgM) c gn ln cc ging, khng th ny s bt IgM c trong huyt thanh ca bnh nhn, tip theo khng nguyn giang mai thun khit s xc nh IgM c hiu, phc hp ny s c xc inh khi cho khng th n dng gn enzyme. Phn ng rt hu ch chn on giang mai bm sinh tr em. - Phn ng bt ng xon khun giang mai (Treponema pallidum Immobilization:TPI). Huyt thanh bnh nhn cha khng th c th lm bt ng khng th giang mai. Phn ng ny cn dng vi khun giang mai sng nn khng dng trong chn on phng th nghim. Cc phn ng huyt thanh vi khng nguyn c hiu chnh xc, nhng i hi trang thit b t tin nn kh p dng rng ri. Cc phn ng c hiu dng tnh sm ngay trong thi gian cui giang mai giai on I nn y l loi phn ng c th dng chn an sm bnh giang mai. Tuy nhin do nhy cao cc phn ng ny t c dng theo di p ng vi iu tr. Sau khi iu tr c hiu qu chun khng th trong phn ng VDRL gim nhanh: gim 4 ln sau 3 thng v gim 8 ln sau su thng nn phn ng ny thng c dng theo di p ng vi iu tr. 4. Phng bnh v iu tr 4.1. Phng bnh Ch yu dng cc bin php chung nh bi tr mi dm, gio dc phng bnh STD, v sinh trong hot ng sinh l tnh dc.. 4.2. iu tr Khng sinh penicillin hin nay vn cn l thuc chn lc diu tr bnh giang mai, cc thuc khng sinh nh tetracyclin, erythromycin c th dng cho cc trng hp d ng vi penicillin hoc cho tr em.

II. XON KHUN GY ST VNG DA XUT HUYT ( LEPTOSPIRA)

Leptospira gm nhiu chng khc nhau c th chia lm 2 loi - Loi khng gy bnh chim a s, chng sng khp ni trong t nhin. - Loi gy bnh sng k sinh ng vt v gy bnh cho ng vt . Vit Nam bnh do Leptospira thng xy ra nhiu ri, nhiu a phng c dch lu hnh. 1. c im sinh vt hc 1.1. c im v hnh thi Leptospira l mt lai xon khun nh di 4-20 m, rng 0,1-0,2 m u un cong nh hnh chic mc cu, di knh hin vi nn en cc vng xon u v st

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nhau. Vi khun bt mu tt vi phng php nhum thm bc vi khun bt mu nu en.

Hnh 1. hnh th vi khun L. ictero hemorhagie 1.2. Tnh cht nui cy Leptospira c th pht trin trn mi trng nui cy nhn to. Vi khun pht trin nhit thch hp 28-30oC. pH hi kim 7,2 7,5. Mi trng nui cy xon khun Leptospira cn phi c huyt thanh th ti nh mi trng Terskich, mi trng Korthof. Trong cc mi trng ny xon khun Leptospira mc chm khong 1 tun, lm mi trng c nh. Ngoi ra vi khun c th pht trin trong phi g . 1.3. Tnh cht khng Leptospira khng km, vi khun c th sng lu trong nc c pH kim nh nhit trn 22oC. Leptospira b git cht khi un 50oC trong 10 pht nhng chu c lnh, trong bnh phm tng ph ca chut gi t lnh vi khun ny c th sng n 25 ngy. pH axit vi khun b git cht nhanh chng, cc ha cht c tc dng b mt nh x phng v ha cht phenol git cht vi khun d dng. Leptospira nhy cm vi nhiu khng sinh nh penicillin, tetracyclin, chloramphenicol. 1.4. Tnh cht khng nguyn: Cu trc khng nguyn ca Leptospira rt khc nhau ty theo mi chng. Vi khun ny c khng nguyn thn, bn cht ha hc l polysaccaride, gm 2 yu t c hiu cho loi c tnh cht c nh b th, v yu t c hiu nhm c tnh cht ngng kt. Hin nay Vit Nam chn 12 chng Leptospira dng trong chn on huyt thanh hc gm L. australis; L.autumnalis; L.bataviae; L. canicola; L.soi; L. grippotyphosa; L.hebdomadis; L.ictero-hemorrhagie; L.mitis; L. pomona; L.saxkoebing; L. sejroe. 2. Kh nng gy bnh 2.1. Dch t hc Vi khun Leptospira gy bnh thng k sinh c th ng vt, thng nht l chut, vi khun ny gy nn nhim trng th n chut v chng c o thi ra mi trng bn ngoi qua nc tiu ca chut gy nhim bn ngun nc, vng t m, cc h nc t ng, vng nc cc hm m. Trong iu kin thun li pH kim v nhit trn 22oC vi khun sng kh lu nhng ni ny.

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Vi khun xm nhp vo c th qua nhng ch da b xy xt, qua nim mc, hoc da lnh nhng ngm lu trong nc. Do vy bnh thng gp nhng ngi lm rung, th hm m, th rng hoc nhng ngi tm hoc li cc hm nc b nhim bn vi khun Leptospira. Bnh him khi c truyn qua vt cn ca chut. Bnh xy ra c 2 gii, gp mi la tui, khng c ma r rt.. 2.2. Bnh l ngi Thi gian bnh 2 - 26 ngy, bnh c trng bi hi chng nhim khun nng ng thi cc biu hin ca tn thng nhiu h thng c quan. - Hi chng mng no - Hi chng tn thng gan v thn - Hi chng xut huyt Bnh thng ko di 9 - 12 ngy. Cc trng hp nng t vong do tn thng nng nhiu c quan v suy thn. Tuy nhin s hi phc thng hon ton, khng li di chng cc c quan, thi gian hi phc ko di 1 - 2 thng. 2.3. Bnh ng vt ng vt nhy cm l chut, sau khi tim vo mng bng chut xon khun gy bnh, bnh khi pht vi st vng da v xut huyt nhiu tng ph. Chut cht m t thi chut tm c nhiu xon khun gan chut. 3. Chn on phng th nghim 3.1. Chn on trc tip Ly bnh phm l mu hoc nc tiu bnh nhn trong tun l u. Soi ti vi khun di knh hin vi nn en, hoc nhum xon khun bng nhum Fontana -Tribondeau. Bnh phm c nui cy vo mi trng Terskich hoc Korthoff. Kho st vi khun pht trin trong cc mi trng ny. Tim truyn vo chut lang l k thut phn lp tin cy, kho st bnh chut, tm xon khun Leptospira cc tng ph chut. Tm acid nucleic ca cc Leptospira c th thc hin bng th nghim lai DNA hoc PCR. 3.2. Chn on huyt thanh hc C nhiu phn ng huyt thanh hc khc nhau, thng dng v c hiu cao l phn ng ngng kt Martin- Pettit, cn gi l phn ng ngng kt tan. Trn huyt thanh bnh nhn vi hn dch c vi khun Leptospira, nu huyt thanh bnh nhn c khng th tng ng, cc vi khun s ngng kt sau vi khun b ly gii. 4. Phng bnh v iu tr 4.1. Phng bnh 4.1.1. Bin php chung Trang b phng tin bo h lao ng cho ngi tip xc vi ngun ly, dit chut. 4.1.2. Bin php c hiu: dng vaccine phng bnh c dng mt s nc. 4.2. iu tr -Nhiu khng sinh c hiu qu tt vi Leptospira nh penicillin, tetracyclin, chloramphenicol - Bin php iu tr h tr

III. CC BORRELIA GY BNH

Borrelia l mt nhm xon khun gy bnh cho ngi, trong phng thc truyn bnh xon khun ny c truyn do mi gii trung gian ve hay rn. Cc Borrelia gy nn bnh st hi quy v gn y Borrelia gy bnh Lyme. 1. c tnh chung ca cc Borrelia

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1.1. Hnh thi v bt mu y l nhng xon khun di, cc vng xon khng u nhau chiu di ca xon khun Borrelia thay i t 5 - 30m, rng khong 0,3 - 1,4 m. Thn vi khun nh nh si tc un cong kch thc thay i ty theo tng thi k, cc xon khun pht trin di ra trong 12-24 gi ri phn chia thnh 2 t bo, vi khun di ng mnh trn knh hin vi nn en. Nhum Wright xon khun bt mu , nhum Giemsa xon khun bt mu tm sm. 1.2. Nui cy Borrelia l loi vi khun k kh kh mc trn mi trng nhn to, vi khun pht trin c nhit 33oC trn mi trng lng Borbozur - Stoenner Kelly hoc c th cy trn phi g. Nhng thng thng l cy phn lp qua cy truyn trn chut. 1.3. Tnh cht khng: Vi khun ny d cht bi cc tc nhn vt l v ha cht cng nh nhy cm vi nhiu khng sinh penicillin, tetracyclin, chloramphenicol. 2. Kh nng gy bnh 2.1. Bnh st hi qui Ch yu do xon khun Borrelia obermejeri hay thng gi B.recurentis thng gy tthnh dch ln, vector trung gian truyn bnh chnh l rn. Ngoi ra cn B.dultoni, mi gii trung gian truyn bnh l ve, vi khun ny gy bnh c tnh cht a phng. Vi khun st hi qui sau khi xm nhp vo c th sau thi gian bnh 7-10 ngy bnh c trng bi st, bun nn, nn ma, st kh di 5-7 ngy trong t u ri tr v bnh thng trong 5-7 ngy ri st tr li. Nhng t st ti pht v sau ngn hn, t rm r hn v thi gian ngng st gia cc t ko di hn. Nu bnh khng c iu tr ti mt lc no xon khun cng b tiu dit v lc y bnh s khi hon ton. Nhng trng hp nng do vim c tim v c th gy cht

Hnh 2. Hnh nh loi ve l vector trung gian truyn bnh Lyme 2.2. Bnh Lyme c m t nm 1977 do xon khun Borrelia burgdorferi gy nn. Vector trung gian truyn bnh do cc loi ve. Bnh tm thy u tin M, hin nay nhiu nc trn th gii thng bo pht hin bnh ny. Sau khi xm nhp vo c th qua vt cn, vi khun gy phn ng vim ti ch ri lan trn vo bch huyt v vo mu. Bnh tin trin vi triu chng a dng v lin h n phn ng vim nhiu c quan t chc ca c th gm da, h thng c khp, thn kinh, tim, gan, thn, tiu ha, mt ... bnh din tin mn, ko di nhiu nm v c th phc hi hon ton. 3. Chn on phng th nghim 3.1. Kho st trc tip Soi ti trn knh hin vi nn en, hoc nhum trc tip bnh phm mu vi phng php Wright vi khun bt mu , nhum Giemsa vi khun c mu tm.

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3.2. Tim truyn cho chut Tim 1-2 ml mu ly t bnh nhn tim vo mng bng chut theo di xon khun mu chut bng nhum trc tip, tm xon khun tng chut. 3.3. Chn on huyt thanh Trong chn on on bnh Lyme, phn ng ELISA c dng u tin xc nh khng th lp IgM i vi B. burgdorferi. Phn ng western blot xc nh khng th IgG c hiu vi cc khng nguyn protein ca B. burgdorferi l phn ng chn on chc chn. Khi thc hin phn ng ELISA dng tnh cn lm thm phn ng western blot khng nh chn on. 3.4. Cc phng php khc Gn y k thut PCR c s dng chn on bnh Lyme. Tuy nhin k thut ny ch dng nhng phng th nghim c trang b 4. Phng bnh v iu tr 4.1. Phng bnh Dit cn trng tit tc trung gian bng phun thuc dit cn trng nhng vng dch t. 4.2. iu tr Borrelia nhy cm vi nhiu loi khng sinh thng thng nh penicillin, tetracyclin, chloramphenicol, cephalosporin ... hin nay cc thuc ny dng iu tr cc nhim trng do Borrelia.

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VI KHUN BCH HU (Corynebacterium diphtheriae)

Mc tiu hc tp 1.Trnh by c c im sinh vt hc ca vi khun bch hu 2.Trnh by kh nng gy bnh v c ch gy bnh ca vi khun ny 3.Trnh by c phng php chn on sinh vt hc, phng php phng nga v iu tr Nm 1826, Klebs quan st v m t trc khun bch hu, mt nm sau 1884 Loeffler phn lp c vi khun ny, sau Roux v Yersin tm ra ngoi c t (1888). Roux ch huyt thanh khng c t cha bnh (1894) v Ramon ch gii c t bch hu phng bnh (1924). Vi khun bch hu thuc h Corynebacteriaceae. H ny gm cc ging Conrynebacterium, Listeria, Erysipelothrix, phn ln khng gy bnh, k sinh t, sc vt v ngi, mt s t gy bnh cho ngi.

I. C IM SINH VT HC
1. Hnh th Vi khun bch hu c kch thc 0,5 -1x 2 - 8m, dng hnh que thng hoc hi cong, hai u trn v thng phnh ra to hn thn lm cho vi khun c dng hnh chy. Vi khun c th xp thnh hng ro hay thnh ch ci H, V, X, Y ... Vi khun khng di ng, khng c v, khng sinh nha bo. Trc khun bch hu bt mu Gram dng nhng khi ty mu ko di d mt mu tm. Khi nhum vi khun bng cc phng php nh Albert hoc Neisser th s thy c cc ht di nhim sc (ht volutin) nhng ht ny bt mu en khc vi mu ca thn vi khun. 2. Tnh cht nui cy Vi khun bch hu l vi khun hiu kh. Mc c mi trng nui cy thng thng, nhng mc tt v nhanh mi trng c mu v huyt thanh. Nhit thch hp l 37oC, pH thch hp 7,6 - 8. - mi trng huyt thanh ng Loeffler, mi trng trng, vi khun mc nhanh, 10-18 gi sau to thnh nhng khun lc nh, trn li, b u, mu xm nht. - mi trng c Tellurit kali 0,3% nh mi trng Mac-Leod, mi trng Schroer, vi khun bch hu mc thnh nhng khun lc en hoc xm en ty theo typ. - mi trng thch mu: vi khun mc to thnh khun lc b u, tm cao, mu trng c v c vng tan mu xung quanh khun lc tu theo typ. Da vo kh nng tan mu , ngi ta phn bit 3 typ: gravis, mitis v intermedius - canh thang vi khun lm c nh, to nn nhng ht dnh vo thnh ng v xut hin mng trn mt mi trng. 3. Tnh cht sinh ha

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Ln men v khng sinh hi cc loi ng: glucose, galactose, khng ln men ng saccharose v lactose. phn bit cc typ vi khun bch hu tht v cc trc khun gi bch hu (Corynebacterium hoffmani, Corynebacterium xerosis), ngi ta da vo bng cc tnh cht sinh vt ho hc di y:

Bng cc tnh cht sinh vt ho hc c bn Vi khun Corynebacterium diphteriae gravis Corynebacterium diphteriae mitis Corynebacterium intermedius Corynebacterium hoffmani Corynebacterium xerosis diphteriae Glucose + + + Saccarose Ln men tinh bt + Tan mu + -

4. Sc khng Vi khun nhy cm vi nhit, nhit 56oC cht trong vng 5 pht. trong gi mc v khi dnh vo chi, o qun, vi khun tn ti kh lu nhit bnh thng. Trong iu kin kh v lnh vi khun bch hu c sc khng cao hn cc vi khun khng nha bo khc. Cc cht st khun thng thng git cht nhanh vi khun sau 1 pht. 5. Kh nng sinh c t Trc khun bch hu to ngoi c t lc trng thi sinh dung gii vi phage . S hin din ca prophage mang li cho vi khun gen c kh nng tng hp nn c t. S to thnh c t ca chng cn ph thuc vo mt s yu t khc nh nng Fe++ trong mi trng, p sut thm thu, nng axit amin, ngun N2 v C thch hp. Bn cht ngoi c t bch hu l protein khng bn vi nhit, l 1 c t mnh, 1mg c t c th git cht 1.000 con chut lang nng 250g sau 96 gi. Nu cho tc dng vi formol 0,3-0,4 % nhit 40oC sau 1 thng th c t bch hu bin thnh gii c t c s dng lm vaccine phng bnh bch hu. 6. Cu trc khng nguyn - Khng nguyn c t: c t phn lp t tt c cc chng vi khun bch hu cho thy s tng ng v min dch ngha l to thnh 1 type c t sinh khng duy nht, iu ny m bo s thnh cng ca vaccine trong phng bnh. - Khng nguyn ca vi khun: Nhng kho st cho thy khng nguyn polysaccharide b mt vi khun c 3 type gravis, mitis, intermedius khng khc nhau trong khi cc trc khun gi bch hu khng c khng nguyn ny.

II. KH NNG GY BNH CHO NGI

Trc khun bch hu l nguyn nhn gy bnh bch hu ngi, thng gp nht l tr em, la tui t 2 - 7 tui. Bnh c khp ni trn th gii, xy ra

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quanh nm nhng gp nhiu v ma lnh, bnh ch yu ly trc tip qua ng h hp khi bnh nhi ni, ho hoc ht hi. Ngoi ra c th ly gin tip qua chi, o qun ca bnh nhi. Bnh bch hu l bnh nhim trng, nhim c cp tnh, c th gy thnh dch v t l t vong cn tng i cao. Bnh c 2 biu hin chnh l: gy mng gi hng cng vi ni hch c v nhim c ton thn.

III. C CH GY BNH
Vi khun bch hu vo ng h hp, c tr nim mc hu, hng, pht trin ng h hp trn v tit ra ngoi c t. Mt mt vi khun v c t kch thch gy lot ti ch to thnh mng gi mu trng xm, dnh cht vo nim mc, bc ra lm chy mu v cho vo nc khng tan. Mng gi thng xut hin trc tin hng ri lan trn ln ng mi hoc xung kh qun. Bch hu thanh qun c bit nghim trng v gy kh th. Mt khc ngoi c t theo ng mu n tc ng vo h thng thn kinh gy nn cc hin tng nh lit vm ming, c mt, t chi v thng tn ti tuyn thng thn, c t bch hu cn tc ng ln tim gy ri lon nhp, suy tim... Ngoi ra cng c bch hu da hoc cc vt thng, y mng gi cng c to thnh, tuy nhin s phn tn c t thng nh, khng gy nhng triu chng ng k.

IV. MIN DCH

c lc ca vi khun bch hu ph thuc vo 1 type c t duy nht nn min dch thu hoch sau chng bnh c bn l khng c t. Tr s sinh thu hoch min dch tm thi nh khng c t ca m i qua nhau thai, tnh min dch th ng ny ch ko di trong t thng. Phn ln tr em, c bit t 1 n 7 tui rt nhy cm vi vi khun bch hu. Trong qu trnh ln ln c th s t gy c min dch ch ng, do tr b bnh hoc b nhim trng nh, do sng gn ngi lnh mang vi khun. Hin nay nc ta, tr cng ln th kh nng mc bnh gim dn v ngi ln hu nh khng mc bnh bch hu. nh gi tnh trng min dch vi c t ca vi khun bch hu ngi ta dng phn ng Shick: tim ni b mt trc cnh tay 0,1ml c t bch hu. Phn ng dng tnh th sau 24 - 48 gi ch tim ni ln 1 qung , cm cng vi ng knh 1 - 2cm, p ng vim ti ch t cc i trong vng 5 ngy sau nht dn. iu ny chng t c t khng b khng c t trung ha, c th c kh nng th cm vi vi khun bch hu. Phn ng m tnh th ch tim khng c phn ng ngha l c t b trung ha bi khng c t. Tuy nhin cn phi tim ng thi vo tay i chng 1 lng c t tng t nhng chng 60oC trong15 pht ph hy tc dng ca c t, bn i chng s khng c phn ng hoc nu c th mt rt nhanh trong khi phn ng Shick dng tnh thc s th p ng vim ko di trong nhiu ngy.

V. CHN ON
Phng php duy nht l phn lp vi khun. Bnh phm l mng gi hoc cht ngoy hng ch c tn thng. 1. Kho st trc tip bnh phm: Lm tiu bn nhum Gram, nhum Albert pht hin vi khun. Nu thy hnh th vi khun in hnh th cho kt qu s b lm sng c hng iu tr kp thi.

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2. Nui cy, phn lp, nh danh: Cy bnh phm vo cc mi trng thch hp nh mi trng trng, mi trng c Tellurit nhit 37 oC trong 18 - 24 gi, ri chn khun lc in hnh kho st tnh cht v hnh th, sinh ha v xc nh c t ca vi khun bch hu bng 1 trong cc phng php sau: 2.1. Phn ng trung ha trong da th Co lng sn th dng bt ch chia cc vung nh. Tim ni b 0,2ml canh khun bch hu th nghim 48 gi vo 1 (ng thi tim ni b 0,2ml canh khun bch hu c lm chng vo bn cnh), 5 - 7 gi sau tim vo tnh mch 1.000 n v khng c t bch hu. Ngay sau tim ni b vo 1 khc 0,2ml canh khun th nghim. c kt qu sau 48 - 72 gi. Nu vi khun th nghim sinh ra c t th tim ln u xut hin nt hoi t 5 - 10 mm, bao quanh l mt vng ban 10 - 15mm ging nh lm chng, cn tim ln 2 th ch c mt nt hng 10 - 15mm. 2.2. Phn ng Eleck t 1 gii giy thm c cha khng c t bch hu vo gia y ca a thch c cha 20% huyt thanh nga hoc b. Vi khun th nghim c cy thng gc vi ming giy. Khng c t khuch tn ra mi trng gp c t ca vi khun s to thnh ng kt ta trng trong thch cng ging nh chng bch hu c lc lm chng. 2.3. Phn ng ng ngng kt Nui cy vi khun bch hu th nghim trn mi trng trng 37oC qua m ri cho vo mi trng 1ml dung dch m phosphat (PBS) (pH: 7,2) v trng trong 1 gi, sau ly PBS ra ly tm, tch nc ni xc nh ngoi c t bch hu bng cch dng 1 lam knh chia ra lm 3 : - 1: Trn nc ni bch hu th nghim vi t cu gn SAD (Serum Anti Diphterie). - 2: Gm t cu gn huyt thanh th vi nc ni bch hu. - 3: Gm t cu gn SAD vi dung dch m PBS. 2, 3 l 2 chng m. Lc nh lam knh 1 pht v c kt qu sau 15 - 30 pht. Phn ng dng tnh khi th nghim ( 1) c cc ht ngng kt c th quan st c bng mt thng hoc bng knh lp, cn 2 chng khng c ht ngng kt.

VI. PHNG BNH V IU TR.

1. Phng bnh Bnh bch hu ly ch yu qua ng h hp do vy cn cch ly trit v iu tr cho ngi bnh v ngi lnh mang mm bnh. Bin php phng bnh tt nht hin nay l tim vaccine gii c t bch hu c h thng cho tr em di 1 tui gy min dch c bn. Tim nhc li sau 1 nm v 5 nm cng c min dch. Hin nay nc ta ang dng vaccine hn hp DTC (Diphterie-Tetanie-Cough). 2. iu tr Trn nguyn tc chung l:

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- Trung ha c t bch hu bng cch tim khng c t bch hu (SAD) kp thi. - Dit vi khun bch hu bng cc khng sinh nh penicillin, erythromycin ... - Gii quyt tnh trng ngt th bnh nhn bng cch cho th oxy hoc m kh qun.

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TRC KHUN THAN, LISTERIA MONOCYTOGENES

Mc tiu hc tp 1.Trnh by c c im sinh vt hc ca trc khun than v Listeria monocytogenes 2.Trnh by c kh nng gy bnh ca hai vi khun ny 3.Trnh by c phng php chn on sinh vt hc, phng php phng nga v iu tr

I. TRC KHUN THAN (Bacillus anthracis)

1. c im sinh vt hc 1.1. Hnh th L nhng trc khun ln, gram dng, u vung, khng di ng v thng xp thnh chui. Trong bnh phm vi khun c v, khng c nha bo. Trong mi trng nui cy vi khun khng c v, hnh thnh nha bo hnh bu dc nm gia thn v khng lm bin dng vi khun. 1.2. Tnh cht nui cy D mc trn cc mi trng nui cy thng thng trong phm vi pH v nhit thay i mt khong rng. mi trng lng y ng c cn bng v nc trn trong. thch thng khun lc ln, vng nht v x x dng R, nu kh trng CO2 hnh thnh v. Trong mi trng ngho dinh dng to nha bo. 1.3. Tnh cht sinh ha Vi khun hiu k kh khng bt buc, ln men v khng sinh hi mt s loi ng, lm ly gii protein, lm lng gelatin v khng lm tan mu cu. Vi khun trng thi sinh trng d b tiu dit 380C/1gi, 550C/40 pht, 800C/1 pht. Vi khun trng thi nha bo c sc khng cao v tn ti rt lu ( trong t tn ti 20-30 nm). 1.4. Cu to khng nguyn B. anthracis c mt khng nguyn v l polypeptit, mt khng nguyn thn l polyosit v mt khng nguyn c t. Khng nguyn v cn tr s thc bo. Nhng chng khng v th khng gy bnh, nhng khng th khng v khng c tnh cht bo v. c t gm 3 protein khc nhau: yu t I gy ph, yu t II: l khng nguyn bo v v yu t III: gy cht. 2. Kh nng gy bnh 2.1. Kh nng gy bnh cho ng vt Bnh than l mt bnh truyn nhim ca sc vt, c bit l ca loi n c (cu, b, tru, nga...). Cc sc vt mc bnh thng b nhim khun huyt v cht. Khi sc vt cht chn su, cc nha bo c th vn lan trn mt t do giun t, mi... lm nhim khun cy c, t cc sc vt ny n phi cy c s b bnh v cht.

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2.2. C ch gy bnh Vi khun sau khi xm nhp vo c th bng ng da, ng tiu ho hoc h hp, nhng nha bo bt u pht trin v hnh thnh nhng trc khun dng hot ng, gy nn hin tng ph keo cc t chc v xung huyt cc m. Trc khun than i n cc hch lymph, lch ri n mu. mu, chng nhn ln nhanh chng, gy nn nhim khun huyt v xm nhp vo cc c quan, nhiu nht l lch, t chc phi. 2.3. Gy bnh cho ngi Bnh c th ngu nhin truyn sang ngi mt cch trc tip hoc gin tip do ngi tip xc vi sc vt b bnh hoc cc sn phm ca chng, mt s t trng hp do ht phi nha bo hoc n phi tht nhim khun. Bnh than khng truyn trc tip t ngi ny sang ngi khc. Bnh than l bnh ngh nghip v hu ht cc i tng tip xc vi ngun gy bnh trong khi lm vic. ngi c th gp 3 th lm sng sau: - Th da: Hay gp cng nhn thuc da, cng nhn l st sinh. Vi khun xm nhp vo da, ti ch xm nhp, xut hin nt phng , gia c mu en do hoi t, gi l nt m c tnh. Bnh tin trin 24-36 gi sau khi vi khun xm nhp vo da, hu qu l tn thng da hoi t. Thng gp l u, tay chn. Ngoi ra c th gp th ph c tnh xut hin sau mn m, hoc khng c mn m. - Th phi: Do ht phi bi cha nha bo, gy ra xung huyt hoc vim ph qun phi c th km theo vim thn, nhim c, dn n nhim khun huyt v t vong. - Th d dy - rut: Do n phi tht b nhim khun, bnh nhn nn, a chy, au bng d di, st cao. Th ny him gp. 3. Chn on vi sinh vt 3.1. Bnh phm: ty theo th lm sng m ly bnh phm thch hp: - Th da: dch ca nt m hoc ch ph n - Th phi: m, mu - Th d dy - rut: phn 3.2. Chn on trc tip Bnh phm c soi ti thy vi khun khng di ng, nhum gram thy c trc khun gram dng, c v, khng c nha bo. Nui cy trn mi trng thch mu hoc thch dinh dng, 350C/18-24gi, vi khun mc to nhng khun lc rt di, to, phng, trng ng, b khng u, bm chc trn mt thch. Bnh phm cn c tim truyn chut lang gy bnh thc nghim. 4. Phng bnh v cha bnh 4.1. Phng bnh - Sc vt cht v bnh than phi chn su, ph kn vi vi bt ngn ngavi khun v nha bo ca chng lan rng. i vi cng nhn lm vic cc l st sinh cn c bo h lao ng tt v phi m bo v sinh mi trng. - Tim vaccine cho sc vt. Vaccine phng bnh gm vaccine sng gim c lc cha nha bo khng c kh nng sinh v, a vo c th bng ng tim.

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Hiu lc bo v khong 1 nm. Loi vaccine chit xut t mi trng nui cy cc chng vi khun khng c v, s dng bng ng tim, hiu lc bo v 1 nm. Thng tim cho nhng ngi do ngh nghip phi tip xc thng xuyn vi sc vt v cc sn phm ca chng cha vi khun. 4.2. Cha bnh iu tr bng khng sinh rt c hiu qu nu c chn on sm. Thng dng l Penicilline, Tetracycline, streptomycin. Tc dng tt nht l penicillin. Trong trng hp vi khun khng penicillin th nn chn khng sinh khc v nn kt hp cc loi khng sinh a li kt qu tt hn.

II. LISTERIA MONOCYTOGENES

Listeria monocytogenes gy bnh sc vt, c th truyn sang ngi. 1. c im sinh vt hc L nhng trc khun Gram dng, khng c v, khng sinh nha bo. Trong bnh phm, chng nm trong t bo, c hnh th to v ngn. Trong mi trng nui cy chng thng xp nh hng ro v c hnh th di hn. Hiu k kh ty , d mc trn cc mi trng nui cy thng thng, nhit thch hp 370C nhng cng pht trin c 40C. Trn thch thng vi khun mc to thnh nhng khun lc nh, trn, xm l, bng. Trn thch mu sau 48 gi nui cy c vng tan mu nh kiu . Catalase dng tnh, thy phn Esculine, Urease m tnh, H2S m tnh. Vi khun c khng nguyn thn O v khng nguyn lng H. Cn c vo 2 loi khng nguyn ny, Listeria monocytogenes c chia thnh 4 typ huyt thanh I, II, III, v IV, thng gp l cc typ I v IV. Vi khun khng tit ra ngoi c t nhng c mt ni c t gy hoi t. 2. Kh nng gy bnh 2.1. Dch t hc cha vi khun bao gm cc ng vt b m, sc vt lnh mang mm bnh, sa ca ng vt b nhim khun mn tnh, thc n b nhim khun, bi...Vi khun tn ti trong ngoi cnh lu v c sc khng cao. ng ly truyn l ng tiu ho, t gp qua ng h hp. Bnh thng xy ra i vi phi thai, tr s sinh v ngi gi... tr s sinh bnh truyn qua rau thai hoc ly lc tr lt qua ng sinh dc ca ngi m. 2.2. Kh nng gy bnh ngi Listeria monocytogenes gy bnh cho rt nhiu loi ng vt, c th ly sang ngi, ch yu gy bnh tr s sinh nhng cng gp ngi ln. Chng gy ra vim mng no, vim mng no - no, nhim khun huyt, vim mng no nc trong, vim kt mc, nhim trng tit niu... Listeria monocytogenes gy bnh th n l ph bin nht. Nu ph n c mang th thng biu hin l st, hi chng gi cm, hoc nhim khun tit niu. Bnh c th hon ton yn lng nhng a li nhim khun cho thai nhi qua ng rau thai v dn ti sy thai hay non, tr ra i mc bnh. 3. Chn on vi sinh vt 3.1. Bnh phm

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Bnh phm ty theo i tng v th bnh m ly cho thch hp. - Tr s sinh: nc no ty, ct su, mu, dch vim kt mc... - thai nhi t vong: cc ht hoi t ca cc ph tng. - ngi m: sn dch, rau thai, mu. - Ngi ln: nc tiu, mu, nc no ty 3.2. Chn on trc tip Bnh phm c nhum soi trc tip, c th tm thy trc khun Gram dng ni t bo v ngoi t bo. Cy vo thch mu mi trng 4 0C lm phong ph vi khun hoc cy vo mi trng chn lc (c axit nalidixic), xc nh vi khun da vo hnh th, tnh cht di ng 200C, catalase dng tnh, ngng kt vi khng huyt thanh Listeria O. 4. Phng bnh v cha bnh - Ch yu l phng bnh chung, ch s dng cc sn phm ca ng vt phi c tit khun tt. Chn on sm ngi m mc bnh iu tr kp thi. - Cha bnh: Dng khng sinh trong thi gian di (v vi khun ni t bo), thng dng penicillin phi hp streptomycin, hoc dng bactrim, ampicillin... ko di 2-3 tun, i vi bnh nhn b suy gim min dch c th dng 4-6 tun.

CC CLOSTRIDIA GY BNH
Mc tiu hc tp 1.Trnh by c tnh cht vi khun hc ca cc vi khun Clostridia gy bnh gm Clostridium tetani, cc Clostridia gy hoi th, Clostridium botulinum v C. difficile. 2. M t c tnh cht gy bnh, phng php chn on vi khun hc v nguyn tc phng v iu tr cc nhim trng do cc vi khun Clostridia gy bnh Vi khun ging Clostridium l cc trc khun gram dng, k kh, sinh nha bo. Vi khun ny c trong t, trong ng tiu ha ca ngi v ng vt, phn ln trong chng l cc vi khun sng hoi sinh, phn hy cc cht hu c trong t mt s Clostridia gy bnh gm Clostridium tetani gy bnh un vn Cc Clostridia gy bnh hoi th Clostridium botulinum gy bnh ng c tht Clostridium difficile gy vim rut gi mc. Chng ta s kho st ln lt cc vi khun ny. I. VI KHUN GY BNH UN VN (CLOSTRIDIUM TETANI ) Vi khun ny gy bnh un vn nn cn c tn l trc khun un vn. 1. Cc tnh cht vi khun hc 1.1. Tnh cht hnh thi v bt mu Trc khun un vn mnh, hi cong, di 4-8m, rng 0,3- 0,8 m, khi mi nui cy trn mi trng c th vi khun di nh si ch bt mu gram, nu nui cy

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lu vi khun d dng mt mu gram. Vi khun c lng v di ng mnh trong mi trng k kh. Khi gp iu kin sng khng thun li vi khun ny sinh nha bo trong thn v nm mt u lm cho vi khun c dng hnh inh ghim thy d trn tiu bn nhum gram, nhit thch hp to nha bo 370C, nhit 240C hnh thnh nha bo 4-10 ngy, trn 420C th khng to nha bo. 1.2. Tnh cht nui cy Trc khun un vn khng cn ngun dinh dng ln, iu kin nui cy cn thit k kh, cc mi trng k kh dng cy vi khun un vn nh mi trng Brewer c cha cc ha cht kh oxy ha tan nh natrithioglycolate, gluthation, hoc mi trng canh thang tht bm hay gan cc. Trong cc mi trng ny vi khun pht trin lm c u mi trng v c cn lng. Mi trng c nh thch Veillon v thch VF, vi khun un vn pht trin to khun lc vn nh bng mu trng c, vi khun sinh nhiu hi lm nt thch. 1.3. Tnh cht khng Vi khun trng thi dinh dng d b git cht bi un 56 0C trong 30 pht, nhng trng thi nha bo vi khun tr nn rt khng, git cht nha bo phi hp trong ni p sut 1200C trong 30 pht hoc ngm trong dung dch phenol 5% trong 8-10 gi c im ny cn lu khi tit trng dng c y t. 1.4. Cu trc khng nguyn Da vo khng nguyn lng vi khun un vn c khong 10typ, tt c 10 typ ny u to ra ngoi c t mnh. Khi x l c t un vn bng formadehyde hoc nhit th lm mt c tnh nhng cn duy tr tnh cht khng nguyn, ch phm ny gi l gii c t dng lm vaccine. Ngoi ra vi khun un vn cn c khng nguyn thn ca vi khun. 1.5. c t ca vi khun un vn Vi khun un vn sn xut ngoi c t, tnh cht gy bnh ch yu ca vi khun un vn lin h n c t ca chng, c 2 thnh phn ca c t un vn. - Tetanospasmin bn cht ca n l protein, c t ny c i lc i vi t chc thn kinh, phn t c t gn vo receptor u tn cng ca t bo thn kinh, tc ng ca n do s ngn cn phng thch cc cht dn truyn thn kinh ( gamma-aminobutyric axit, glycine) cho cc xynap c ch, khng c tc dng c ch, gy nn s kich thch qu mc ca cc c vn. - Tetanolysin lm tan mu ngi mu th, Thc nghim th v kh cho thy rng c t ny gy nhng thay i trn in tim v gy gin nhp tim,vai tr ca c t ny t r trn lm sng. 2. Kh nng gy bnh 2.1. Dch t hc Vi khun un vn tm thy nhiu trong lp t b mt, vi khun sng hoi sinh ng tiu ha ngi v ng vt do vy vng ng dn c, nhit nng m t c nhiu phn sc vt v giu cht hu c cng c nhiu vi khun un vn. Vi khun hoc bo t xm nhp vo c th qua cc vt thng do ha kh, do tai nn lao ng c dy nhiu cht bn v d vt to iu kin d dng cho vi khun un vn pht trin v gy bnh.

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Un vn xy ra trong mi trng bnh vin lin quan n phu thut bi cc dng c hoc thao tc khng m bo v trng, un vn c th gp khi tim bp tht khng m bo v trng cc loi thuc nh quinin, hoc heroin. Un vn rn tr s sinh do ct rn bng dng c khng v trng. Bnh xy ra mi la tui v c hai gii 2. 2. Bnh sinh v c im lm sng Vi khun hoc bo t khi vo c th gp iu kin thun li nh t chc b hoi t, d vt, vt thng su mi trng ti ch k kh vi khun pht trin v to c t. Vi khun khng xm nhp qu v tr vt thng nhng c t ca chng hp th vo mu qua ng bch huyt hoc theo dy thn kinh v khuch tn qua t chc c gn k. Phn t c t gn vo receptor u cng ca t bo thn kinh ngn cn cc xynap c ch ca t bo thn kinh. Tc dng ny a n s co git v co cng c c th ca bnh un vn. Thi gian bnh trung bnh 15 ngy, cc triu chng nh cng hm, kh nut, ri dn dn cng c c, c lng, c bng ri co cng c ton thn a n t th n cong ngi. Bnh nng xut hin nhng cn co git c, co cng c v co git tng cng khi c kch thch nh cu vo, nh sng, m thanh... Un vn rn tr s sinh xy ra khong 10 ngy sau khi sinh, bnh thng nng v t vong nhanh. Triu chng bnh un vn tng dn n ngy th 9-10 sau gim dn, hi phc hon ton mat 3-4 tun. 3. Chn on phng th nghim t c gi tr, chn on bnh ch yu da vo lm sng. 4. Phng bnh v iu tr 4.1. Phng bnh 4.1.1. Bin php chung - Vt thng phi x l thch hp - Vt thng nghi ng nhim vi khun un vn nn h, tim huyt thanh phng un vn. - Tit trng k cc dng c y t nh kim tim, bm tim, dng c phu thut, ct rn phi m bo v trng trnh un vn rn. 4.1.2. Phng bnh c hiu Dng vaccine gii c t un vn. Bnh un vn hin l mt trong cc bnh nhim trng nm trong chng trnh tim chng, tr em cn tim vaccine c h thng t hiu qu phng bnh. 4. 2. iu tr Theo cc nguyn tc sau y. 4.2.1. Trung ha c t bng khng c t un vn 4.2.2. Dng khng sinh tiu dit vi khun 4.2.3. X l vt thng 4.2.4. iu tr triu chng v h tr

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II. CC VI KHUN GY BNH HOI TH y l nhm vi khun gram dng, k kh, ging nhau v mt hnh th, v tnh cht gy ra nhim trng nhim c vt thng v gy hoi th, cc vi khun ny cng c vai tr trong vim rut tha, vim mng bng, sy thai nhim khun... Cc vi khun nh Clostridium perfringens, Clostridium novyi, Clostridium septicum c xem l cc vi khun chnh gy bnh thng gp. 1. Cc vi khun gy bnh 1.1. Clostridium perfringens 1.1.1. c im vi khun Vi khun c hnh dng trc khun, khng di ng c v khi pht trin trong c th ng vt v ngi, vi khun sinh nha bo khi pht trin trong mi trng t nhin, chng bt mu gram nhng trong mi trng nui cy gi vi khun c th mt mu gram. Clostridium perfringens pht trin trn cc mi trng nui cy k kh nhit 370C lm c u mi trng, trn mi trng thch k kh vi khun sinh hi lm nt thch. Da vo kh nng sinh c t, ngi ta chia loi ny lm 6 type A, B, C, D, E, F, trong type A gy nhim trng hoi th vt thng, type C gy vim rut hoi t, cc type khc tm thy gy bnh cho ng vt. 1.1.2. c t v enzyme ca vi khun Clostridium perfringens sn xut nhiu c t, phn ln y l cc enzyme khc nhau, cc type khc nhau sn xut nhiu c t khc nhau, v d nh type A sn xut cc c t ng ch sau: - c t alpha ( toxin) l mt phospholipase C chng thy phn t chc c lecithine, ph hy hng cu, gy hoi t t chc phn mm, thc nghim cho thy c t ny c tc dng trn chc nng c tim lm h huyt p, chm nhp tim, lm tng tnh thm mch mu v gy chong, thng l tc dng gy cht trong bnh hoi th. - c t theta ( toxin) c tc dng tiu hng cu khi iu kin k kh v tiu t bo. - c t Mu ( toxin) c t ny l enzyme hyaluronidase phn hy axit hyaluronic ca t chc lin kt. - c t kappa ( toxin) c hot tnh ca enzyme collagenase phn hu collagen ca t chc lin kt. - Enterotoxin bn cht l protein c tc dng gy tiu chy trong nhim c thc n. 1.2. Clostridium novyi Vi khun ny c 4 type c t A, B, C, D. trong type A gy bnh cho ngi, cn cc type khc gy bnh cho ng vt. Clostridium novyi sn xut nhiu c t, nh type A sn xut cc c t alpha (), gamma (), delta (), epsilon () tc dng ca cc c t ny ging vi c t ca Clostridium perfringens. 1.3. Clostridium septicum

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Vi khun ny c mt type c t, vi khun ny sn xut 4 c t mnh: toxin, toxin, toxin, toxin, cc c t ny gy hoi t t chc v tan mu. 2. Bnh hoi th sinh hi Vi khun xm nhp vo t chc tn thng b gip nt c nhiu d vt, su v ngc ngch. Thng gp l cc vt thng do chin tranh, do ha kh gp iu kin thch hp vi khun pht trin v gy hoi t t chc. Thi gian bnh thng ngn 1-3 ngy triu chng au xut hin sm v gia tng nhanh, vng vt thng t chc b tn thng b ph n v sng ty, c th c cht dch r mu, da vng b tn thng cng tr thnh mu ti xm hoc xanh nh mu da cht, s c cm gic lo xo hi di t chc, dch r mu mi chua thi, tnh trng ton thn bnh nhn biu hiu nhim c nng khng iu tr bnh nhn cht do try tim mch, suy thn. 3. Chn on phng th nghim Chn on phng th nghim thng cho kt qu chm, t hu ch, chn on bnh ch yu da vo lm sng. Trong phng th nghim nhum gram trc tip dch r ly t vt thng, ng thi cy tm vi khun trn mi trng k kh. 4. Phng bnh v iu tr - Dng khng c t phng bnh cho nhng bnh nhn c vt thng gip nt. - X l vt thng sm thch hp bng ct lc sch t chc gip nt, ly cht bn, d vt. - iu tr bng truyn huyt thanh khng c t chng bnh hoi th v dng khng sinh dit khun.

III. VI KHUN GY BNH NG C THT (CLOSTRIDIUM BOTULINUM)

Vi khun ny c trong t, nhng khng tm thy trong phn ngi. Bnh ng c tht xy ra khi dng thc n d tr, ch yu cc loi thc phm ng hp b nhim vi khun Clostridium botulinum hoc bo t ca chng. 1. Tnh cht sinh vt hc ca vi khun 1.1. Hnh th Vi khun hnh trc di 4- 6m, rng 0,9-1,2m, c lng, sinh nha bo, nhum gram bt mu gram. 1.2. Nui cy Vi khun k kh tuyt i, pht trin thch hp 26-280C. Trong mi trng lng k kh vi khun mc mnh, u tin lm c mi trng, lu lng cn v mi trng tr nn trong sut. Trong mi trng c khun lc nh, vi khun sinh hi lm nt thch. 1.3. c t

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Vi khun sn xut ngoi c t khi pht trin trong mi trng nui cy k kh hoc trong thc phm c iu kin k kh. Kh nng sinh c t tng i c nh typ A, B, cc typ khc kh nng sinh c t thay i. c t ca Clostridium botulinum bn cht l protein, c i lc vi t chc thn kinh, chng tc ng ln cc tip gip thn kinh c lm ngn cn s gii phng acetyl choline t cc u tn cng ca cc dy thn kinh vn ng h Cholinergic. 1.4. Khng nguyn Vi khun Clostridium botulinum, c phn chia thnh 6 typ A, B, C, D, E v F ty theo tnh c hiu min dch v c t m chng to ra. Vi khun ny c khng nguyn thn v khng nguyn lng. 2. Kh nng gy bnh Bnh xy ra do n cc thc phm d tr ng hp b nhim vi khun Clostridium botulinum hoc bo t ca chng. Vi khun gp iu kin thun li v sn xut c t. Khi n thc phm ny vo d dy rut, c t khng b ph hy c hp th nhanh vo mu v n t chc ca c th. Cc triu chng thn kinh do tc ng ca c t ln t chc ny, chng tc ng ln cc tip ni thn kinh c lm ngn cn s gii phng acetyl choline cc u tn cng h thn kinh vn ng cholinergic. Bnh xut hin nhanh 6- 48 gi sau khi n thc phm nhim c. au bng, nn ma, nhc u chong vng, nhn i, ni khn n mt ting, lit c, ri lon nhp th, trng hp nng c th t vong. 3. Chn on phng th nghim Chn on bnh ch yu da vo lm sng, chn on phng th nghim t c gi tr. phng th nghim c th tin hnh phn ng trung ha trn chut. 4. Phng bnh v iu tr 4.1. Phng bnh Ch yu l loi b cc thc phm nghi ng b nhim c, nu k thc n. 4.2. iu tr Dng khng c t hn hp t nhiu typ.

IV. CLOSTRIDIUM DIFFICILE

Clostridium difficile c pht hin t nm 1935 v c xem l mt thnh phn khun chi ca tr em bnh thng, cho n gn y vi khun ny c xem l nguyn nhn ca bnh vim rut gi mc nhng bnh nhn dng khng sinh. Vi khun ny di ng, to nha bo, bt mu gram, vi khun c th phn lp t bnh phm phn trn cc mi trng nh thch manitol cycloserin, hoc thch mch mu manitol glycerin. Vi khun gy bnh do sn xut c t mnh, c t ny va c tnh cht ca c t rut (enterotoxin) va c hot tnh gy c t bo (cytotoxin). Khi tch ring cc hot tnh khc nhau ca c t chng c hai thnh phn ring bit gi l c t A v c t B. c t A ca vi khun ny l thnh phn chu trch nhm cho hot tnh ca c t rut. Trong lc thnh phn c t B c hot tnh c t bo mnh hn c t A. Tc dng c t A trn ng tiu ha gy phn ng vim, tm nhun t

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bo a nhn, phng thch cc cht trung gian ca phn ng vim, gy nn tit dch, thay i tnh thm mng t bo v gy hoi t xut huyt. Tc dng phn B gy c t bo lm cho t bo ha trn. Ngoi hai c t trn mt s chng Clostridium difficile cn c c t CDT (ADP-Ribosyl transferase) c tc dng c t bo. Bnh xut hin bnh nhn ang dng khng sinh nh clindamycin, ampicillin, cc cephalosporin v cc aminoglycoside. Bnh nhn st, au bng, tiu chy phn lng nc, bch cu mu tng cao, phn c nhiu bch cu. Bnh din bin thay i, c khi khi khi ngng thuc, nhiu bnh tiu chy ko di a n mt nc v suy kit. Chn on phng th nghim gm cy phn tm vi khun Clostridium difficile; th nghim tm c t ca vi khun ny trong phn bnh nhn. iu tr vim rut gi mc do Clostridium difficile gm - Ngng thuc khng sinh ang s dng. - Dng vancomycin hoc metronidazol.

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H MYCOBACTERIACEAE
Mc tiu hc tp 1.Trnh by c cc c im sinh vt hc ca vi khun lao v vi khun phong. 2.Trnh by c kh nng gy bnh ca vi khun lao v vi khun phong 3.Trnh by c phng php chn on vi sinh vt. H Mycobacteriaceae bao gm cc trc khun c tnh cht bt mu thuc nhum mt cch c bit: Vi khun kh bt mu thuc nhum ba d nhng khi bt mu thuc nhum ri th khng b dung dch cn axit ty mu. Ngi ta gi chng l vi khun khng axit. Phng php nhum Ziehl Neelsen ng dng c tnh trn ca vi khun khng axit. H Mycobacteriaceae gm nhiu loi; mt s sng hoi sinh t, nc, thc vt; mt s gy bnh ngi v ng vt. Nhm gy bnh lao: + Mycobacterium tuberculosis: vi khun lao ngi (90% lao ngi). + Mycobacterium bovis: vi khun lao b c th gy bnh ngi. + Mycobacterium avium: vi khun lao chim, t gy bnh ngi, thng gp trong lao hch ngi. Mycobacterium khng xp hng: L nhm vi khun khng axt c th gy bnh cho ngi nhng khng gy bnh cho chut lang hoc th (phn bit vi nhm gy bnh lao). Dch t hc cho thy Mycobacterium khng xp hng c th gy nn s nhim trng rng ln nhiu vng nhng chng bnh tng i nh. Mycobacteirum leprae: gy bnh phong.

I.TRC KHUN LAO (Mycobacterium tuberculosis)

1. c im sinh vt hc 1.1. Hnh th Trc khun lao thng gi l BK (Bacille de Koch) l trc khun mnh, hi cong 2 - 4m 0,2 - 0,5m. mi trng nui cy n c th bin i thnh hnh si. nhng chng khc nhau c th pht trin thnh nhng t bo nm ring r hoc tp hp thnh nhng dy ngon ngoo. Nhum Ziehl Neelsen vi khun bt mu c khi cho thy nhng ht mu bn trong t bo vi khun. 1.2. Cu to ha hc im ni bt l t l lipit cao chim 20 - 40% trng lng kh ca t bo. V sn lipit vch t bo (60%) vi khun c tnh cht k thy nn c xu hng dnh lin vi nhau lc pht trin mi trng lng. Tnh cht k thy cng ct ngha tnh cht khng axct v kh nng chm pht trin ca vi

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khun (thi gian th h 24 gi). Trong thnh phn lipit ng lu l sp v mt glycolipit gi l mycosit. 1.3. Tnh cht nui cy v kh nng khng Vi khun lao hiu kh bt buc, nhit thch nghi 37 o C, pH thch nghi 6,7 - 7.Vi khun c nui cy mi trng giu cht dinh dng nh mi trng c Lowenstein, Ogawa Mark, mi trng lng Sauton. mi trng Lowenstein khun lc xut hin khong sau mt thng, kh nhn nheo ging nh hoa su l. mi trng lng Sauton vi khun mc nhiu b mt cht lng thnh nhng mng nhn nheo, kh v dnh vo thnh ng. Vi khun lao pht trin chm, thi gian gia tng i l 12-24 gi trong khi ca E.coli l 20 pht. Nhng chng c lc to thnh nhng khun lc R. Nhng chng c lc km to thnh nhng khun lc t nhn nheo hn v pht trin t c trt t hn. So vi cc vi khun khng sinh nha bo khc vi khun lao khng khng hn vi nhit, tia cc tm v phenol. Kh trng theo phng php Pasteur (un 62 o C trong 30 pht) git cht vi khun lao. Tri li vi khun lao khng nhiu hn vi kh v mt s cht st trng; kh git cht vi khun lao vi nhng cht ty u thng thng nh dung dch cresyl 5%, nc Javel; cn it ch git cht vi khun lao trong khong t 2 n 5 gi. 2. Kh nng gy bnh Kh nng gy bnh ca vi khun lao ph thuc vo c lc ca vi khun v sc khng ca c th. S nhim trng ln u mt c nhn thng to thnh mt thng tn t gii hn nhng i khi chng bnh c th tin trin, hnh nh do sc khng km hoc do lng vi khun xm nhim qu nhiu. Do s thng bng ca sc khng v c lc ca vi khun thng tn lnh v tin trin c th tn ti mt c th v chng bnh cho thy mt qu trnh mn tnh lc khng c iu tr bng khng sinh. Bnh lao thng tri qua 2 giai on: - Lao s nhim: Ln u tin xm nhp c th vi khun lao thng gy nn thng tn vng ngoi vi rt thng kh ca phi. Lc c th tr nn qu mn trong 2 - 4 tun l sau th thng tn dng ht xut hin v ht lao in hnh c hnh thnh. Lc ny vi khun lao c th n nhng hch bch huyt k cn v sau qua ng bch huyt v ng mu c th i khp c th. - Lao ti pht: Phn ln bnh lao ngi l do s hot ng tr li ca bnh trm lng ca lao s nhim. Nhng bnh thng kh tr phn di hoc phn nh hoc gn nh ca phi, s nhim trng dai dng nh nng O 2 cao. Lc chng bnh c khm ph th thng tn b u thng ha lng v hang lao hnh thnh to iu kin thun li cho vi khun lao phn tn nhanh chng. Vi khun lao c th ly truyn sang ngi khc qua m gii v theo ph qun n nhng phn khc nhau ca phi. Ngoi phi phn ln nhng c quan khc ca c th cng c th l v tr ca bnh lao, thng thng l ng tiu, xng, khp, hch, mng phi, mng bng.

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3. Min dch v mn cm trong bnh lao 3.1. Hin tng Koch Vi khun lao c tim di da vo i phi ca chut lang. 10 n 14 ngy sau mt sn to thnh ch tim. Sn pht trin thnh lot dai dng. Ngoi ra vi khun cn xm chim nhng hch bch huyt k cn. Cui cng trong vng 6 - 8 tun l chut cht v lao ton thn. Nu trong tun l th 2 hoc th 3 tim vi khun lao ln 2 vo i tri chut lang th s p ng ln ny nhanh hn, mnh m hn nhng cng gii hn hn. Thng tn xut hin trong vng 2 - 3 ngy, lp tc l lot nhng li lnh nhanh chng. Nhng hch bch huyt k cn khng b xm nhim. Nh th c th chut lang hnh thnh mt s p ng bin th vi s nhim trng ln hai.nhng vi khun a vo ln sau kh tr hn ln u v pht trin chm hn. Con vt c th loi b nhng vi khun xm nhp ln sau, nh th n c min dch mt phn no. 3.2. Vaccine BCG c iu ch t mt chng lao b gim c bng cch cy truyn nhiu ln (230 ln trong 13 nm) mi trng cha mt b v glycerin. Vaccine ny tng sc khng ca c th i vi bnh lao nhng tnh min dch khng hon ton, ngi n gim s ngi mc bnh lao v t l t vong. Tim trong da 0,1 ml vaccine, mi ml cha 0,5 n 1 mg BCG. 3.3. Mn cm i vi bnh lao L mn cm kiu chm pht sinh sau khi nhim vi khun lao. Khm ph tnh mn cm bng phn ng tuberculin. Phn ng tuberculin l mt loi test ni b nh gi min dch lao. Bn cht ca n l mt phn ng qu mn mun. Tuberculin l mt sn phm chuyn ha ca vi khun lao. Tuberculin dng trong y t hin nay l dn cht protein tinh khit (tuberculin purified protein derivative: tuberculin PPD) c iu ch t sn phm chu nhit ca mi trng lng nui vi khun lao. Tim 0,1ml tuberculin PPD cha 5 n v tuberculin (5 TU) vo trong da mt trc cng tay. c kt qu sau 72 gi. Nu ti ni tim xut hin nt cng vi ng knh t 10mm tr ln l phn ng dng tnh, tc l c th c min dch vi vi khun lao. Phn ng tuberculin dng tnh trong cc trng hp: B bnh lao, nhim vi khun Mycobacteirum tuberculosis nhng khng mc bnh lao, nhim Mycobacteirum khc v sau tim vaccine BCG. Phn ng dng tnh mnh c th gy hoi t hoc lot. Phn ng tuberculin xut hin khong mt thng sau khi nhim trng v tn ti trong c th nhiu nm v c khi sut i. Phn ng m tnh lc cha nhim lao, lc nhim lao cha qu mt thng, lc b lao nng tnh trng suy nhc khng cn phn ng, lc mc bnh cp tnh nh si, bnh Hodgkin. 4. Chn on vi sinh vt Bnh phm thng thng l m. - Nhum theo phng php Ziehl-Neelsen trc tip hoc sau khi thun nht.

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- Phn lp vi khun: d kt qu nhum th no cng cn nui cy vi khun v nui cy nhy hn nhum. Hn na c tnh khun lc cn cho php phn bit vi khun lao vi nhng vi khun khng axit khng gy bnh v Mycobacteirum khng xp hng. Ngoi ra vi khun phn lp c s dng lm khng sinh . - Tim truyn sc vt: mt phn bnh phm c th tim di da vo chut lang. Th nghim tuberculin sau 3 - 4 tun v m xc sau 6 tun tm thng tn in hnh v vi khun lao. Vi khun khng INH khng gy bnh chut lang nhng pht trin tt mi trng nui cy. 5. Phng bnh v iu tr 5.1. Phng bnh Bnh lao l mt bnh x hi. Bin php phng bnh khng c hiu: nng cao i sng vt cht v tinh thn. Bin php phng bnh c hiu: dng vaccine BCG. 5.2. iu tr Nn iu tr ton din: ngh ngi, bi dng v thuc. i vi nhng trng hp dng thuc khng hiu qu th phi ct b mt phn ca phi hoc thy phi. S dng phi hp cc loi khng sinh gim tnh c ca thuc v s khng ca vi khun nh streptomycin, PAS v INH hoc ethambutol, INH v rifamycin.

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II. TRC KHUN PHONG (Mycobacterium leprae)

1. c im sinh vt hc Tuy c Hansen khm ph n nay trn 100 nm nhng vi khun phong cha nui cy c mi trng nhn to. l vi khun khng axit khng lng khng v, khng sinh nha bo, c th nm ring r nhng thng hp thnh b song song hoc cm. Vi khun thng tm thy u n nc mi hoc thng tn ngoi da ca ngi phong c tnh. Nhum Ziehl Neelsen vi khun hin ra di dng nhng que 1 - 8 m 0,3 - 0,5 m. Vi khun thng tm thy trong nhng t bo ni mch ca mch mu hoc t bo n nhn. Vi khun ly ngi phong cy vo chn chut c th gy nn nhng thng tn mn trn ti ch, vi khun pht trin gii hn. 2. Kh nng gy bnh Vi khun phong gy nn nhng thng tn nhng m lnh: da, dy thn kinh ngoi vi, mi, yt hu, thanh qun, mt v dch hon. Thng tn da c th xut hin nh vt sn nht mu ng knh 1 - 5 cm, hoc tm nhun ta lan da. Thng tn thn kinh biu hin di dng tm nhun thn kinh gy nn vim dy thn kinh, d gic, mn xng, ct ngn chn ngn tay. Nt mt c th b bin dng do tm nhun da v thng tn dy thn kinh. 3. Chn on vi sinh vt -Lm tiu bn vi nc mi hoc ly dao co da thng tn hoc tri tai lm tiu bn, nhum Ziehl Neelsen tm vi khun. - Sinh thit da hoc dy thn kinh b thng tn: Nhum Ziehl Neelsen th tm thy vi khun phong v hnh nh t chc in hnh. Trong phong c tnh tm thy t bo Virchow c nhiu l hng vi khun phong hp thnh cm trong phong c tm thy nhiu t bo khng l trong ri rt c vi khun phong. - Cha c chn on huyt thanh hc. iu ng lu l ngi phong thng c dng tnh gi vi th nghim huyt thanh v bnh giang mai. - Th nghim Lepromin: nu t chc cha vi khun phong, em lc th thu c mt phm vt gi l lepromin. Hin nay lepromin c tiu chun ha, n cha 160 x 106 vi khun khng axit / ml. Tim trong da 0,1 ml lepromin, c th xy ra: Phn ng sm, xy ra sau 48 gi gi l phn ng Fernandez, xut hin di hnh thc sn . Phn ng ny khng c hiu. Phn ng chm, xy ra sau 2-3 tun l gi l phn ng Mitsuda, xut hin di hnh thc sn ng knh 3 - 5 mm : (+), 5 - 10 mm : (++), >10 mm : (+++). Phn ng Mitsuda trong thc t ch tin lng bnh. 4. Dch t hc Bnh phong khng ly nhim mnh v khng cn cch ly bnh nhn. Hnh nh tr em nhy cm vi s nhim trng hn ngi ln. Thi gian bnh ko di nhiu nm (thng t 1 n 10 nm). Thng thng bnh c pht hin ngi trng thnh. Hnh nh phn ln bnh nhn nhim bnh lc cn nh tui vi ngi trong gia nh.

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5. Phng nga v iu tr 5.1. Phng nga - Khm ph v iu tr nhng trng hp bnh hot ng. - Phng nga bng Sulfon cho nhng ngi thng xuyn tip xc vi bnh nhn. - Tim BCG. C nhng kho st cho thy tim BCG tng s khng vi vi khun phong v s tin trin ca chng bnh. 5.2. iu tr Sulfon, clofazimine v rifamycin loai b s pht trin ca vi khun v s tin trin ca chng bnh. Ung trong nhiu thng.

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RICKETTSIA, CHLAMYDIA V MYCOPLASMA

Mc tiu hc tp 1.Trnh by c c im sinh vt hc ca Rickettsia, Chlamydia v Mycoplasma 2.Trnh by c kh nng gy bnh ca cc vi khun ny v mt s bnh do mt s loi Rickettsia, Chlamydia v Mycoplasma quan trng gy ra. 3.Trnh by c phng php chn on sinh vt hc, phng php phng nga v iu tr

I. RICKETTSIA
Rickettsia c Ricketts v Wilder pht hin nm 1910. Rickettsia c mt thi xem nh lin h mt thit vi virus v kch thc nh b v pht trin ni bo. Ngy nay Rickettsia c khng nh l vi khun v: - Rickettsia c tt c c tnh cu to ca vi khun, c bit l c vch t bo in hnh. - C tt c cc enzyme cn thit cho s chuyn ha. - Cha c 2 loi axt nucleic: ADN v ARN. - Phn bo ging vi khun. -S dng oxy v nhy cm vi mt s khng sinh (chloramphenicol, tetracyclin). Bnh do Rickettsia c nhng c im chung: + Ngun ly truyn l cn trng tit tc, Rickettsia thng khng gy bnh cn trng tit tc nhng gy bnh ngi. + Tr trng hp st Q, mu bnh nhn mc bnh do Rickettsia cha khng th ngng kt vi chng OX19 hoc OXK ca Proteus vulgaris. + Thng tn bnh l ch yu l vim mch tr trong st Q ph vim quan trng hn. + Tt c nhng bnh do Rickettsia u l nhng bnh cp tnh vi nhng triu chng lm sng: st, au u, ni ban tr trng hp st Q khng ni ban. - Da vo c im lm sng, dch t hc v min dch hc ngi ta chia Rickettsia lm 4 nhm: + Nhm I: St pht ban dch t, mm bnh l: R. prowazeki, R. mooseri. +Nhm II: St c nt, mm bnh l R. conori, R.rickettsi, R.canada, R.akari, R.australis. + Nhm III: Nhm st pht ban rng r (st sng Nht bn): R.tsutsugamushi (R.orientalis)hin nay l Oriental tsutsugamushi + Nhm IV: Nhm st Q (Query). Mm bnh l: R. burnetti. 1. c im sinh vt hc 1.1. Hnh th

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Rickettsia hnh dng thay i qua cc giai on pht trin: cu khun ng ring r hoc xp tng i, trc khun v hnh si. Thng gp nht l hnh trc khun. Kch thc 0,5x1m. Nhum Gram bt mu Gram m. Lc nhum Giemsa hoc Machiavello, Rickettsia c th quan st knh hin vi quang hc. Nhum Giemsa vi khun bt mu xanh, nhum Machiavello vi khun bt mu kh tng phn vi mu xanh ca t bo vt ch. 1. 2. Cu to ha hc Rickettsia cha ARN v ADN theo t l 3,5 : 1, vch t bo ging nh vch t bo vi khun Gram m cha phc hp glycopeptit. 1.3. Cu trc khng nguyn C 2 loi khng nguyn c phn bit. - Khng nguyn ha tan: c tnh c hiu nhm. - Khng nguyn khng ha tan: lin quan n b mt ca vi khun, phn bit loi. 1.4. c t Mt s Rickettsia sinh ra mt loi c t ho tan trong nui cy, c tnh cht gy tan mu v hoi t. Khi tim c t ny cho ng vt th chng b cht sau vi gi v tn thng bnh l ging nh do vi khun gy ra. Ngoi ra hot tnh gy bnh cn ph thuc vo enzyme gy tan huyt, c t gn cht vi thn vi khun. c t b ph hy lc un 60o trong 30 pht, nhng vn gi c tnh khng nguyn. c t b trung ha bi khng huyt thanh c hiu. 2. Kh nng gy bnh Rickettsia pht trin t bo ni mch vch huyt qun, chng nhn ln v bi tit ra yu t tin ng mu, qua trung gian ca c t lm cho nhng t bo phng ln ri hoi t nn mch mu b nghn ri b v nn nhng thng tn ca mch mu trng r da. no ngi ta tm thy thng tn mch mu ca cht xm. Tim cho thy nhng thng tn mch mu nh. 3. Chn on vi sinh vt 3.1. Tim truyn vo ng vt th nghim Ly mu lc bnh mi pht tim, vo chut lang, chut nht hoc trng g ln. i vi st sng Nht Bn, bnh phm c tim vo phc mc chut nht, ly cht ngoi tit ca phc mc chut pht ln lam nhum Giemsa, nhum min dch hunh quang. 3.2. Phn ng huyt thanh: - Phn ng khng c hiu: Phn ng Weil-Felix: Rickettsia v Proteus vulgaris hnh nh c chung mt s khng nguyn, lc nhim Rickettsia bnh nhn sn sinh mt s khng th ngng kt vi mt vi chng Proteus vulgaris (chng OX19, OX2, OXK) nh R.prowazeki (OX19), Oriental tsutsugamushi (OXK) v R.mooseri (OX19).

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- Phn ng c hiu: Khng nguyn thu hoch sn phm nui cy trng g ln c th lm cc phn ng ngng kt, phn ng kt hp b th hoc min dch hunh quang. 4. Phng nga v iu tr 4.1. Phng nga Bnh Rickettsia ly nhim do cn trng tit tc: ve, ch, rn, m... nn phi dit cn trng truyn bnh. Phng bnh bng vaccine cho nhng ngi i n dch. Vaccine iu ch bng khng nguyn thu hoch ti lng trng. Cng c th phng nga bng khng sinh. 4.2. iu tr Rickettsia nhy cm vi khng sinh. Tt nht l iu tr bng tetracyclin v chloramphenicol. Khng sinh c ch s pht trin ca Rickettsia. Khng nn dng sulfamid v thuc nay tng cng s pht trin ca vi khun. 5. Nhng bnh rickettsia quan trng Thng gp nhiu ni l st pht ban dch t st pht ban chut, st sng Nht Bn v st Q. 5.1. St pht ban dch t Do R.prowazeki l bnh cp tnh do ch rn ly truyn. c im: st cao, au u dai dng, ni ban, li b, n. Nhit c th ln n 39 - 40 oC trong ngy u hoc 2 - 3 ngy sau, khi nhit ln 40oC th gi nguyn, t thay i cho n khi lnh hoc iu tr. au u dai dng, nng kh ci thin vi mi c gng lm gim au. Ni ban t ngy th 4 n ngy th 7, lc u phn trn ca thn ri lan khp c th tr mt, lng bn tay, bn chn. Vim kt mc v mt ng cng c quan st. Nu iu tr tt nhit tr v bnh thng trong vng 2 - 5 ngy. Thi gian bnh phc ko di 2 - 3 thng. Trong nhng v dch t vong c th t 6 - 30%. Bnh gn lin vi chin tranh v ngho i. 5.2. St pht ban chut Do R. mooseri, trong thin nhin l bnh truyn nhim ca chut do b cht Xenopsylla cheopis truyn bnh t chut sang ngi. Bnh gp nhiu ni trn th gii nht l cc hi cng. Bnh st cp tnh c nhng nt chung vi bnh st pht ban dch t nhng nh hn, t khi cht tr trng hp bnh nhn gi yu. Bnh pht trin dn dn, st t khi 39oC, thng ln xung v chm dt sau 9 - 13 ngy, au u t nghim trng, ni ban t mnh m, thi gian ni ban ngn hn. 5.3. St sng Nht Bn Do Oriental tsutsugamushi. Bnh st cp tnh c th nh hay nng, do m truyn t loi gm nhm sang ngi. Bnh thng xy ra t ngt, vi st, n lnh, nhc u, vt b t b lot ri ng vy en, hch k cn sng to, vim kt mc cng thng c quan st. St c th ln n 40,5 oC v gi mc trong 14 ngy hay hn. nhng bnh nhn khng c iu tr, au u nghim trng v dai dng. Bn hin ra thn t ngy th 5 n ngy th 8. Ngoi ra nhng bnh nhn nng khng c iu tr cn c du chng vim phi, du chng thn kinh trung ng: m sng. Tnh cht nghim trng ca bnh thay i theo vng. 5.4. Bnh st Q (Query)

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Tc nhn l R.burneti. Ngun bnh l ve truyn sang gia sc. Bnh truyn t gia sc sang ngi phn ln do ht phi bi nhim khun, khng ni ban, khng c khng th ngng kt vi Proteus vulgaris. Bnh lu hnh nhiu ni trn th gii. Bnh thng xy ra t ngt: st, au u, mt mi, bnh ging nh cm, vim phi khng in hnh. au u nghim trng l nt kh c hiu, nhit ln xung v thng ko di 6 - 12 ngy. Du hiu ng h hp: phim X quang cho thy hnh nh thm nhim tng m tng t nh vim phi khng in hnh. Bnh thng khi khng li di chng.

II. CHLAMYDIA
Chlamydia gy nn nhiu bnh khc nhau, c bit l bnh mt ht, bnh Nicolas -Favre, bnh st vt - st chim (Ornithose- psittacose). Ngy nay ngi ta cn thy Chlamydia l tc nhn ca mt s bnh v ng sinh dc - tit niu, bnh vim nhim tiu khung, bnh vim niu o... 1. c im sinh vt hc Chlamydia sng k sinh ni bo, kch thc rt nh b nhng khng phi l virus m l vi khun v: - Cha 2 loi axt nucleic: ADN v ARN. - C vch t bo bn cht mucopeptit cha axt muramic. - Cha ribosom v nhiu enzyme chuyn ha. - Chng nhn ln theo kiu phn i - Nhy cm vi nhiu khng sinh. 1.1. Hnh thi v chu trnh pht trin Chu trnh pht trin ni tip gia 2 th: th c bn ng knh 300nm c v cng sng st lc phng thch khi t bo v th li ng knh trn 1000nm thch hp nhn ln bn trong t bo. Hai th nay v nhng th trung gian khc bt mu khi nhum Giemsa hay Machiavello.

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Phagolysoso me th li

th c bn

nhn t bo

5 4 3

ht vi Hnh1. S chu k nhn ln ca Chlamydia

Chlamydia c i lc vi t bo biu m ca nim mc. Th c bn xm nhim t bo biu m theo c ch m bo. Trong khong 8 gi th c bn t chc li thnh th li, th ny nhn ln bng phn lit. Sau 24 gi nhng th li t chc thnh nhng th c bn nm bn trong mt th vi trong nguyn tng ca t bo vt ch. Sau t bo b v v gii phng ra cc tiu th. Trn nui cy t bo, t bo vt ch b cht v t ly gii 40 - 60 gi sau khi nhim trng. 1.2. c tnh ha hc v chuyn ha Chlamydia thch nghi mnh m vi s sng ngoi bo v s pht trin ni bo. Chng ph thuc nhiu vo t bo vt ch. Chng cn tr s tng hp protein v ADN ca t bo vt ch. Chng to nn nhng i phn t ring ca chng nhng s dng nng lng chuyn ha ca t bo vt ch. 1.3. Khng nguyn C 2 loi khng nguyn: - Khng nguyn c hiu nhm: c th pht hin trong dch thy phn vi khun. - Khng nguyn c hiu typ: lin quan n lp ngoi cng ca v Chlamydia nguyn vn. 1.4. Min dch Bnh Chlamydia c xu hng mn tnh v c qu trnh ti pht nu khng c iu tr. Tnh cht mn tnh ca s nhim trng cho thy s p ng min dch khng hiu qu, nhng thng thng ngi bnh c th hn ch hoc khu tr chng bnh m khng pht sinh di chng nghim trng. Khng th trung ha kt hp vi khng nguyn v ca Chlamydia ngn cn s lan trn nhim trng Chlamydia n nhng t bo nhy cm nhng khng lm bt hot Chlamydia nm bn trong t bo. Ngi b nhim trng tim tng tng i min dch vi s ti

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nhim nhng c th tip tc phng thch vi khun v to nn ngi lnh mang trng. 1.5. Phn loi - Tc nhn gy bnh mt ht (Trachome): Chlamydia trachomatis. - Tc nhn gy bnh vim hch bch huyt hoa liu (Lymphogranulomatose venerienne) do Chlamydia lymphogranulomatosis. bn

- Tc nhn gy bnh st vt st chim (Ornithose- psittacose) do Chlamydia psittasi. - Tc nhn bnh tng t bo lympho li lnh tnh cn gi l bnh mo co (Lymphoreticulose benigne). - Tc nhn gy vim niu o, c t cung v kt mc th vi do Chlamydia oculogientalis 2. Mt s bnh do chlamydia gy nn 2.1. Bnh do Chlamydia trachomatis gy ra Chlamydia trachomatis gm 18 typ huyt thanh c k hiu t A n K v L1,2,3 2.1.1. Bnh mt ht Vim kt mc do mt ht do Chlamydia trachomatis typ A-C. Bnh lu hnh cc x nng, trn th gii c khong 460 triu ngi mc bnh, trong c 6 triu ngi b bin chng m hon ton. Bnh tin trin qua 4 giai on: - Giai on 1: Vim kt mc th nang thng km theo bi nhim vi khun. - Giai on 2: Vim kt mc th ht. - Giai on 3: C nhng bin chng c hc nh so, lot v bi nhim. - Giai on 4: Hi phc km theo so kt mc, lot gic mc v c th b m la nu khng c iu tr tch cc. iu tr bng thuc m tetracylin. 2.1.2. Bnh vim ng tit niu - sinh dc ly nhim qua ng tnh dc Do Chlamydia trachomatis typ D - K. Hin nay bnh tng v s lng v gy nhiu bin chng nng. nam gii biu hin u tin l vim niu o, sau c th dn n vim mo tinh hon. n gii biu hin vim trong c t cung, sau dn n vim niu o, nu khng c iu tr tt s dn n vim ng sinh dc thp, ri vim vi trng c th a n bin chng c thai ngoi t cung.... tr s sinh c th b ly nhim t ngi m qua rau thai hoc sau khi i qua c t cung, m o ca ngi m b bnh gy nn vim kt mc mt tr s sinh. 2.1.3. Bnh lymphogranulomatose y l tc nhn gy bnh vim hch bch huyt hoa liu bn hay bnh Nicolas Favre do Chl.trachomatis typ huyt thanh L1, 2, 3 . Bnh ly truyn qua ng sinh dc, sau 3 - 26 ngy tip xc bt u xut hin cc triu chng sau: tn thng khu tr ng sinh dc biu hin mt vt lot nh quy u, hu mn, m h... Vt lot thong qua sau lnh m khng c so, sau t 1 - 2 thng c nhiu hch

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bn, tp trung thnh khi ln ri b d ra nh mt p xe, ming ch d nh t ong hoc ming bnh ti. Vim hch bn lnh khng so. Tuy nhin thng tn c th gy bin chng: hp hu mn - trc trng, chn voi, vim no - mng no, au khp... km theo du hiu ton thn l st v lch to. 2.2. Bnh st vt - st chim (Psittacosis - Ornithosis) Bnh do Chlamydia psittaci. bnh 1 - 2 tun, bnh pht t ngt hoc m . n lnh, st au u v vim phi khng in hnh. Mm bnh c cc loi chim nui nh b cu, g, vt, vt v mt vi loi chim hoang di. Bnh ly qua ng h hp hoc do vt thng. Vi khun vo mu ri n phi, t ly sang ngi khc qua ng h hp. iu tr bng tetracyclin. Sulfamid v streptomycin khng c tc dng.

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2.3. Bnh do Chlamydia pneumoniae gy ra Vi vim phi k, vim ph qun, vim xoang, vim hng thng gp tui v thnh nin v thanh nin, ngi gi thng biu hin lnh tnh v khng triu chng. 3. Chn on vi sinh vt 3.1. Chn on trc tip Do vi khun k sinh ni bo nn mu nghim cn phi nhiu cc t bo biu m nh: - Dch no niu o, dch tin lit tuyn, tinh dch, dch trong c t cung, mu sinh thit vi trng, dch ti cng m o - Dch no kt mc mt trong bnh mt ht - Dch tit mi hu, dch tit ph qun phi, dch ra ph qun Mu nghim cn phi c bo qun 40C Nhum soi mu nghim trn tiu bn nhum bng phng php Gim sa hoc Machiavello, thy nhng tiu th ht a kim trong hoc ngoi t bo. C th phn lp Chlamydia trn cc nui cy t bo hoc cy vo trng g p quan st tnh cht xm nhim. Xc nh bng k thut min dch hunh quang trc tip hoc gin tip pht hin Chlamydia, c th dng k thut min dch enzyme (ELISA) pht hin khng nguyn ca Chlamydia. Hin nay c th dng phng php khuch i gen (k thut PCR) chn on nhim trng do Chlamydia trachomatis 3.2. Chn on gin tip - Phn ng vi lng min dch hunh quang (micro-immunofluorescence) xc nh khng th v cho php chn on loi nhim trng, c bit loi Chlamydia trachomatis. - Ngoi ra ngi ta cn s dng phn ng kt hp b th v phn ng ELISA pht hin khng th khng lipopolysaccharide. Tuy nhin phi ly huyt thanh lm 2 ln cch nhau 2 tun tm hiu gi khng th. 4. Phng nga v iu tr 4.1. Phng nga - i vi bnh mt ht: cn phi tng cng cc bin php v sinh nh khng dng khn chung, m bo ngun nc sch trong sinh hot... - i vi bnh sinh dc tit niu d ly lan do quan h tnh dc do cn pht hin sm v iu tr kp thi v c bin php phng bnh cho v hoc chng, bi tr mi dm, gio dc gii tnh Vic phng bnh bng vaccine hin nay vn ang c nghin cu 4.2. iu tr iu tr bng tetracyclin, sulfamid, erythromycin tu theo tng loi Chlamydia.

III. MYCOPLASMA
1. c im sinh vt hc 1.1. Hnh th

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Mycoplasma l vi khun khng vch t bo, kch thc nh, kh nhum vi thuc nhum kim, hnh th khc nhau ty thuc vo thi gian nui cy v thay i theo tng bc nhum, ngi ta c th quan st bng knh hin vi nn en, nhum Giemsa. 1.2. Tnh cht nui cy Mycoplasma c th pht trin trn mi trng c hoc khng c t bo sng, hiu kh hoc k kh tuyt i, nhit thch hp 35 - 37oC, pH 7 - 7,8. Trn mi trng lng kh quan st vi khun mc v canh khun trong sut. Trn mi trng c mc thnh khun lc c trung tm ti v dy, mc ln xung thch, ra khun lc mng v bt. 1.3. Cu trc ha hc - Cha ADN v ARN, t l ARN/ADN nh hn 1 - Khng c vch t bo nhng c mt v mng nh mng nguyn tng ca vi khun - Qu trnh nhn ln kh phc tp v ph thuc vo mi trng, ngi ta quan st thy c hin tng song phn v hin tng ny chi. Trn nui cy t bo, vi khun hu ht pht trin trn b mt t bo. 1.4. Cu trc khng nguyn Ngi ta tch vi khun nhng thnh phn ha hc mang tnh cht khc nhau. Mi thnh phn ha hc c kh nng tham gia vo mt loi phn ng huyt thanh nht nh. 1.5. Sc khng Mycoplasma tng i bn vng lc b ng bng ri tan bng. Trong huyt thanh vi khun c th tn ti 56oC trong 2 gi, chng d b ph hu bi siu m. Nhy cm vi pH axit hoc pH kim. 2. Kh nng gy bnh ngi Mycoplasma c mt i tnh vi nim mc h hp v nim mc ng sinh dc. a s loi sng hoi sinh. Ch c 4 loi gy bnh chc chn ngi l: Mycoplasma pneumoniae gy bnh h hp, Mycoplasma hominis, Mycoplasma genitalium v Mycoplasma (Ureaplasma) urealyticum l tc nhn ca bnh ng sinh dc. Cn cc loi khc kh nng gy bnh cha bit r. - M.pneumoniae l tc nhn gy bnh vim phi tin pht khng in hnh ngi. Cc triu chng chnh l st, rt run, tot m hi, ho khan d di, kh th v au ngc. Bnh c th gp bt k la tui no, nhng thng gp tr em. M.pneumoniae thng gy nn cc v dch nh vo ma xun v thu. - M. urealyticum, M. genitalium gy vim niu o p xe tuyn Bartholin, vim vi trng. M. hominis gy vim khung chu ph n c thai, c th gy sy thai. Tr s sinh c th b vim phi, nhim trng mu, vim mng no... do m b nhim trng sinh dc bi vi khun ny. - Kh nng gy bnh ca cc Mycoplasma khc nh M.fermentens, M.penetrans cha c xc nh mt cch r rng. 3. Chn on vi sinh vt

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- Bnh phm: Ly bnh phm thch hp nh dch ra ph qun, cht bi tit ca phi cng c th cht dch t c quan sinh dc. - Bnh phm nui cy trn cc mi trng chn lc c bit. Sau nh loi bng cch pht hin nhng canh khun in hnh bng thuc nhum Dienes, tm kh nng tan mu v hp th hng cu, tnh cht ln men glucose... - C th chn on huyt thanh bng cc phn ng kt hp b th, phn ng c ch ngng kt hng cu, ELISA...Phi tm ng lc khng th 4. Phng bnh v iu tr - Cha c vaccine phng bnh: ang nghin cu vaccine a gi phi hp. - iu tr bng khng sinh macrolide, tetracyclin, chloramphenicol, furadantin, spiramycin, fluoroquinolon...

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PHN III

CC VIRUS GY BNH THNG GP CC VIRUS H HERPESVIRIDAE

Mc tiu hc tp 1. M t c tnh cht virus hc ca cc virus ho herpes HSV1 &HSV2, Varicella zoster virus, cytomegalovirus v Epstein Barr Virus. 2. Trnh by c tnh cht gy bnh, chn on phng th nghim, cc nguyn tc phng bnh v iu tr i cc nhim trng do virus h Herpes.

I. I CNG
Herpes bao gm nhiu virus gy bnh cho ngi, chng gy nn cc nhim trng cp sau nhiu virus c th tn ti trong t chc ca c th v gy nn nhiu t ti pht. Cc nhim trng do virus herpes thng xy ra nhng bnh nhn b gim min dch. Nhiu thuc chng virus hin nay rt c hiu qu iu tr nhng nhim trng do mt s virus trong h ny. Virus h Herpesviridae c mt s tnh cht sau : - Li nucleocapsid c cu trc hnh khi a din. - Bn trong nucleocapsid c cha ADN chui i. - V ngoi cng l lipid nn ht virus trng thnh c kch thc khong 150 - 200 nm. Cc thnh vin ca virus herpes gm Tn khoa hc Tn thng gi tn vit tt - Di h alphaherpesvirinae(subfamily) Human Herpesvirus 1 Herpes simplex virus typ 1 HSV-1 Human Herpesvirus 2 Herpes simplex virus typ 2 HSV-2 Human Herpesvirus 3 Varicella zoster virus VZV Cc virus ny c mt s tnh cht sinh hc chung nh chu k pht trin ngn, chng gy ly gii t bo nhim trng v gy nhim trng tim n cc t bo thn kinh - Di h Betaherpesvirinae Human Herpesvirus 5 Cytomegalovirus CMV Virus ny c chu k pht trin di, chng gy t bo khng l t chc nhim trng, v gy nhim trng tim n t bo tuyn nc bt,t bo thn. - Di h gammaherpesvirinae Human herpesvirus 4 Epstein Barr virus EBV Chu k pht trin ca virus ny thay i, chng gy tng sinh t bo t chc nhim trng, v gy nhim trng tim n t chc lympho Gn y cc virus mi thuc h ny c m t l Human Herpesvirus 6 gy bnh st, hch c ln v pht ban tr em, Human herpesvirus 7 vai tr gy bnh ca virus ny ang c kho st.

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II. CC VIRUS HERPES SIMPLEX

1. Tnh cht ca virus 1.1. Cu to Ht virus c kch thc 130 - 200 nm, nucleocapsid l mt khi a din ng knh 78 nm c cu to bi 162 capsome. Cc capsome sp xp theo trc i xng 5:3:2, mi capsome l mt khi lng tr kch thc 9 x12 nm c l thng gia ng knh 4 nm to thnh ng tr rng. Trong l genome cha chui i ADN c trng lng phn t 100 x 10 6 dalton, cha cc gen m ha cho 70 hoc nhiu hn cc sn phm ca virus. V bn ngoi l 2 lp lipid c cha 5- 6 glycoprotein. Cc glycoprotein ny lm trung gian cho virus gn v xm nhp vo bn trong t bo vt ch. 1.2. S nhn ln ca virus Virus herpes simplex c th xm nhim hu ht dng t bo nui cy c ngun gc t cc ng vt xng sng nh t bo thn ngi, t bo thn th, t bo i, t bo lng bi. Virus gn vo cc receptor trn b mt t bo vt ch, v virus kt hp vi mng t bo gii phng nuclecapsid vo trong bo tng ca t bo, nucleocapsid c tho ri gii phng ADN ca virus. Khi ADN ca virus c sao chp, cc protein cu trc c tng hp, nucleocapsid s c lp rp li trong nhn t bo vt ch. Virus nhn v ngoi ca n khi nucleocapsid to chi qua mng trong nhn ra khong quanh nhn. mt s t bo b xm nhim s sao chp ca virus trong nhn to nn 2 loi ht vi: - Ht vi typ A a kim, nhum Feulgen (+) cha ADN ca virus - Ht vi a axit khng c axit nhn ca virus hoc protein ca n, ht vi ny l du hiu ca s nhim trng virus

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Hnh 2. Chu k pht trin HSV bn trong t bo Ht virus gii phng ra ngoi t bo qua li ni tng v b my golgi, cc glycoprotein c tm thy trn b mt ht virus cng nh trn b mt ca t bo b xm nhim 1. 3. Kh nng khng Virus b ph hy bi ether, cn, chng b bt hot 52 0C trong 30 pht. Virus mt kh nng xm nhim khi chiu tia cc tm nhit phng. Virus c bo qun trong dch treo t chc nhim virus trng thi lnh. 1. 4. Min dch p ng min dch dch th v p ng min dch t bo ng vai tr quan trng trong nhim trng do virus herpes. Cc glycoprotein b mt virus l nhng khng nguyn c nhn bit bi cc khng th qua phn ng trung ha v qua s tiu t bo min dch. Nhiu qun th t bo gm t bo git t nhin NK cell, i thc bo, qun th lympho T v cc lymphokin do cc t bo ny sn xut ra c vai tr bo v chng li s nhim trng ca virus herpes. 2. Kh nng gy bnh Virus herpes simplex gy nhiu bnh cnh lm sng khc nhau. Nhim trng c th nguyn pht hoc ti hot, nhim trng nguyn pht xy ra nhng ngi khng c khng th chng li virus herpes simplex. Tri li trong nhim trng ti hot tn thng xy ra nhng bnh nhn c khng th chng li virus ny. C 2 typ virus (virus herpes typ 1 v virus herpes typ 2) gy nhim trng cc t bo biu m v to cc nhim trng tim tng t bo thn kinh. Virus typ 1 thng gy cc nhim trng ming v mi hu nh vim ming, vim li, eczema do virus herpes, vim kt mc mt sng ha, vim no. Virus typ 2 gy cc tn thng ng sinh dc nam cng nh n, gy nhim trng herpes tr s sinh khi a b sinh qua ng sinh dc b m ang b nhim trng herpes ng sinh dc. C hai typ gy nhim trng c quan nh vim thc qun, vim phi, vim gan xy ra trn c a bnh nhn suy min dch. 3. Chn on phng th nghim Chn on phng th nghim nhim trng do virus herpes tr nn cn thit khi m nhiu thuc iu tr ang c sn. Trong nhiu nm gn y c nhiu phng php gip chn on nhanh nhim trng do virus herpes

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3.1. Chn on trc tip - Nhum trc tip t chc tn thng bng nhum Gimsa, Wright tm t bo khng l in hnh, tm tiu th ni bo trong nhn, tm virus bng knh hin vi in t. - Xc nh khng nguyn virus trong t chc bng th nghim min dch hunh quang; th nghim min dch phng x (RIA) hoc min dch lin kt enzyme (ELISA) vi khng th n dng. - Phn lp virus t cc tn thng mn nc, cht ngoy, t chc b bnh... cy ln cc t chc nui cy t bo. Sau 48 - 96 gi virus herpes simplex gy hiu ng t bo bnh l in hnh. - Hin nay nhiu k thut mi xc nh virus herpes t cc loi bnh phm nh xc nh chui nucleotid c hiu ca virus bng k thut lai ADN hoc bng phn ng khuch i chui gen PCR (polymerase chain reaction). Cc k thut ny vn cn t dng cc phng th nghim chn on thng quy nhim trng herpes. 3. 2. Chn on huyt thanh hc - Hin nay phn ng western blot v nhiu loi phn ng ELISA xc nh khng th IgM v IgG trong huyt thanh c sn chn on nhim trng HSV-1v HSV-2. 4. Phng bnh v iu tr 4.1. Phng nga Nhiu vaccine c th nghim trong phng th nghim, hin nay cha c loi vaccine no c a vo s dng. Nn trnh tip xc vi bnh nhn b nhim trng virus herpes ng sinh dc. 4.2. iu tr Hin nay c nhiu thuc chng virus herpes hu hiu v c sn iu tr nhim trng virus herpes ti ch hoc ton thn. Nhng thuc ny gm vidarabin, acyclovir v cc dn cht ca thuc ny nh famciclovir, valacyclovir l cc thuc thng dng. Cc thuc khc nh Trifluothymidin, Iodouridine c dng iu tr cc tn thng herpes ti ch.

III. VIRUS THY U - ZONA ( VARICELLA - ZOSTER VIRUS)

1. Tnh cht ca virus Virus thy u-zona ( vit tt l VZV ) l mt thnh vin ca h herpes virus nn c c tnh cu trc nh virus herpes simplex - Virus c v ngoi bng lipid, kch thc ca ht virus 150 - 200 nm - Li nucleocapsid c i xng hnh khi a din, trong cha phn t ADN chui i, trng lng phn t khong 80 x 106 dalton. Virus pht trin trong cc nui cy t bo nh t bo i, t bo x non, t bo lng bi. S nhn ln ca virus to ra cc m tn thng ring r lan rng, t bo b bnh c nhn to chit quang, nguyn tng co trn li, c tiu th ni bo a axit trong nhn. Virus rt d cht, mun bo qun phi gi t chc nui cy trong iu kin lnh. 2. Gy bnh cho ngi Virus thy u- zona gy 2 bnh cnh lm sng ngi l bnh thy u v bnh zona. 2.1. Bnh thy u

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Ngi l cha virus duy nht, bnh thu u l hu qu ca nhim trng nguyn pht virus VZV, bnh rt thng gp tr em, t khi gp ngi ln. Virus xm nhp vo ng h hp trn pht trin ti ch gy nhim virus mu phn tn n cc c quan, da, thn kinh... Tn thng da, t bo biu b sng phng to phng nc, km du hiu ton thn vi st, mt mi ton thn, bnh khi sau 10 ngy n 2 tun, tn thng da khng li so. Cc bin chng gm nhim trng da, bi nhim phi do vi khun, vim no. 2.2. Bnh zona y l mt hnh thc ti hot ca mt nhim trng tim tng virus VZV m ngi bnh b mc phi trc y. Bnh xy ra l t ngi ln. Bnh biu hin da bi tn thng phng nc dnh thnh chm v phn b theo vng cc dy thn kinh b nh hng, tn thng vim c tm thy cc r hch thn kinh b nhim trng, thng gp l r thn kinh c, lng, dy thn kinh s no. Biu hin tn thng vim no, vim mng no ty c t l thp. 3. Chn on phng th nghim Nhiu k thut phng th nghim dng chn on nhim trng do virus thy u- zona 3.1. Chn on trc tip - Kho st hiu ng t bo bnh l t chc tn thng, dng knh hin vi in t pht hin virus t chc nhng khng th phn bit c virus thy u-zona v virus herpes simplex. - Tm khng nguyn virus trn cc mu nghim bnh phm (dch phng nc, cht ngoy...) bng cc k thut min dch hunh quang, min dch lin kt enzyme vi khng th n dng ( monoclonal antibodies). - Phn lp virus trn nui cy t bo - Xc nh ADN ca virus bng k thut PCR 3.2. Chn on huyt thanh hc Chn on huyt thanh l phng php chn on chnh chn on nhim trng do virus ny h thng thn kinh. K thut thng dng gm phn ng c nh b th, th nghim min dch lin kt enzyme (ELISA), th nghim min dch khng th hunh quang vi khng nguyn mng (Fluorescent antibody to membrane antigenes: FAMA). 4. Phng bnh v iu tr 4.1. Phng bnh - Dng vaccine sng gim c chng bnh thy u-zona cho ngi bnh thng v nhng ngui c nguy c cao. Vaccine ny c th nghim cho thy c hiu qu phng bnh. - C th dng globulin min dch chng thy u-zona (VZIG varicella-zoster immunoglobulin) cho tr em < 15 tui b suy min dch cha mc thy u, c tip xc cng phng, cng nh vi bnh nhn b bnh. 4.2. iu tr - Hn ch bi nhim vi khun tn thng da, nim mc bng v sinh, khng sinh. - iu tr varicella - zona vi cc thuc chng virus: acyclovir, Vidarabin. - Dng Interferon c ngun gc t bch cu ngi.

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IV. CYTOMEGALOVIRUS
1. c tnh chung Cytomegalovirus l mt thnh vin ca h herpes virus. Virus c cu trc i xng hnh khi, v bn ngoi l lipoprotein. Nucleocapsid cha ADN chui i. Virus pht trin thch hp trong t chc nui cy t bo x non ngi, chu k pht trin ca virus ny chm hn cc virus herpes khc. Trong t bo nhim virus chng nhn ln bn trong nhn, qu trnh sao chp ca virus to nn cc ht vi ln trong nhn v nhiu ht vi nh hn trong nguyn tng. Trn c th ngi Cytomegalovirus nhn ln trong t bo ca nhiu c quan nh t bo tuyn nc bt, t bo gan, thn, phi. Gn y virus ny c xc nh trong t bo lymphocyte mu ca bnh nhn khe mnh c phn ng huyt thanh dng tnh. S tn ti ca Cytomegalovirus trong t bo lymphocyte c th chu trch nhim cho nhim trng virus sau truyn mu. 2. c im gy bnh ngui - Cytomegalovirus c th gy nhim trng thai nhi bm sinh do ngi m b nhim cytomegalovirus tin pht trong thi k mang thai. Cc nhim trng Cytomegalovirus thai nhi bm sinh c th tim tng n nng v lan ta vi gan lch to, xut huyt, vng da, no nh, chm pht trin - Cc nhim trng nng thng cht trong bng m. Nhng tr em nhim trng khng c triu chng c th xut hin cc bt thng v nghe, v th gic, v pht trin tm thn vn ng trong nhiu nm v sau. - Nhim trng Cytomegalovirus mc phi tr nh khi sinh qua ng sinh dc b m b bnh do virus ny. - Virus ny gy nhim trng c quan cc bnh nhn b tn thng min dch nh ghp c quan, bnh nhn gi, bnh nhn dng cc thuc c ch min dch. - nhng bnh nhn b AIDS, Cytomegalovirus gy cc nhim trng lan ta v gy t vong cho nhng bnh nhn ny. 3. Chn on phng th nghim 3.1. Chn on trc tip Cytomegalovirus c o thi qua nc bt, nc tiu, cht dch ph qun nhiu thng sau khi b bnh. Phn lp virus bng cy bnh phm vo t chc t bo x non ngi, xc nh hiu ng t bo bnh l in hnh. Nhiu phng php xc nh trc tip nhanh chng virus ny trong bnh phm gm : - Xc nh khng nguyn hunh quang sm: bnh phm cy ln nui cy t bo sau mt m cho phn ng vi khng th n dng chng li Cytomegalovirus ri gn vi hunh quang. - Xc nh khng nguyn bch cu: cc t bo n nhn t mu ngai vi c tch ly tm ri nhum vi khng th n dng gn enzyme hoc hunh quang. - Xc nh ADN ca virus trong bnh phm bng phn ng khuch i chui gen PCR 3.2. Chn an huyt thanh hc Nhiu k thut huyt thanh hc dng xc nh khng th khng cytomegalovirus trong huyt thanh bnh nhn. Khng th lp IgM c xc nh bng min dch lin kt enzyme hoc min dch hunh quang; khng th IgG xc ch bng ELISA hoc th nghim ngng kt hng cu th ng. 4. Phng bnh v iu tr 4.1. Phng bnh Cha c vaccine phng bnh c hiu, ch yu kim tra ngi cho c quan trc khi ghp.

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4.2. iu tr Hai thuc khng virus ganciclovir v foscarnet hin nay c sn iu tr nhim trng Cytomegalovirus nhng cn liu cao v t thuc ch nn dng khi nhim trng do cytomegalovirus c xc nh. Dn cht nucleoside l 9-(13dihydroxyl-2 propoxymethyl) guanin (DHPG) th nghim trong phng th nghim cho thy c hiu qu chng li cytomegalovirus.

V. EPSTEIN BARR VIRUS

1. Cc tnh cht ca virus Ht virus Epstein Barr lm thun khit t cc t bo lympho B nui cy c cu trc tng t nh cu trc ca virus herpes khc. Ht virus c nucleocapsid i xng hnh khi c bao bc bn ngai bi v phc tp, bn trong nucleocapsid cha chui i ADN c trng lng phn t khang 101 x 10 6 dalton cha gen m ha cho t nht 30 polypeptid. Virus Epstein Barr nhn ln trong t bo lympho B ngi nui cy v Lympho B ca vi loi linh trng khc, gn y nhiu nghin cu cho thy virus ny c trong cc t bo biu m mi hu (nasopharyn). Virus ny kh thu hoch dng v bo nui cy hng lot. Trong phng th nghim cc t bo lympho B c nh gi bng s chuyn dng ca t bo lympho B. Nhiu loi khng nguyn khc nhau ca virus Epstein Barr c xc nh trong nhng t bo nhim virus bng k thut min dch hunh quang. - Khng nguyn VCA: y l khng nguyn capsid ca virus Epstein Barr gm t nht ba (3) protein. Nhng bnh nhn b nhim trng do virus Epstein Barr trong huyt thanh c cha anti-VCA lp IgM v IgG - Khng nguyn mng MA: y l thnh phn khng nguyn mng cm ng bi virus Epstein Barr, khng nguyn ny cng c v ca virus. Khng nguyn ny kch thch to khng th trung ha. - Phc hp khng nguyn sm EA: Gm hai thnh phn . * EA- D: L thnh phn khng nguyn khuch tn c xc nh trong nguyn tng v trong nhn t bo b xm nhim. * EA- R: L thnh phn khng nguyn hn ch ch thy trong nguyn tng ca t bo. - Khng nguyn nhn ca virus Epstein Barr (EBNA): Khng nguyn ny tm thy trong nhn t bo b xm nhim. Khng th vi EBNA xut hin 6- 8 tun khi b bnh v ko di sut i. 2. Kh nng gy bnh 2.1. Dch t hc Virus c thi ra t ng mi n 18 thng sau khi b nhim trng tin pht. Bnh nhn v ngi lnh mang virus c kh nng gy ly nhim. S truyn bnh ch yu qua nc bt khi hn, khng truyn qua khng kh th, bnh c th truyn qua truyn mu. 2.2. Bnh ngi Virus Epstein Barr gy bnh tng bch cu n nhn nhim khun thng gp thiu nin v ngi ln tr. Biu hin mt mi, chn n, st vim hng v hch Lympho ln. Bnh thng khi sau 3 n 4 tun v mt nhiu thng mi ly li sc khe. Bin chng him khi xy ra, mt khi c th thng nng v lin h n nhiu c quan gm mu, h thn kinh, gan, tim, phi. Virus Epstein Barr cn gy cc bnh c tnh gm u lympho Burkitt, ung th hu hng v nhiu u lympho bo B.

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3. Chn on phng th nghim 3.1. Bnh tng bch cu n nhn nhim khun - Th nghim tm khng th vi hng cu cu, khng th ny c th ly i bng hp ph vi hng cu b, hng cu cu, v nga nhng khng b hp ph vi thn chut. N c tn l khng th heterophil. Khng th ny thy 50% tr em v 90 n 95% thiu nin v ngi ln b bnh tng bch cu n nhn nhim khun. Khng th ny gim chun , nhng cn dng tnh n 9 thng sau khi b bnh cp. - Xc nh khng th IgM v IgG vi VCA bng th nghim min dch hunh quang v min dch lin kt enzyme dng khng th n cln. C th tm khng th vi khng nguyn EBNA. Mt s phng th nghim c trang b, c th tm cc khng th tng ng vi cc khng nguyn sm (EA) v vi EBNA. 3. 2. Trong cc bnh c tnh Xc nh khng th vi khng nguyn EBNA, khng th IgA ca khng nguyn VCA bng min dch hunh quang v min dch enzyme. Trong c hai trng hp tm ADN ca virus bng k thut lai DNA hoc PCR c dng cc phng th nghim c trang b. 4. Phng bnh v iu tr 4.1. Phng bnh Cha c vaccine phng bnh hu hiu. 4.2. iu tr Acyclovir, interferon v propiolacton l nhng cht c ch s sao chp virus Epstein Barr trong phng th nghim. Vai tr ca cc thuc ny trong iu tr nhim trng virus Epstein Barr cha c nh gi.

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ADENOVIRUS
Mc tiu hc tp 1.Trnh by c c im virus hc ca Adenovirus 2.Trnh by c kh nng gy bnh ca Adenovirus. 3.Trnh by c phng php chn on virus hc, phng php phng nga v iu tr Nm 1953, Rowe v cng s phn lp c cc chng Adenovirus u tin t m si vm hng v hch hnh nhn ca ngi. V chng gy thoi ha t bo nn c gi l virus A.D ( Adenoid degenerative). Sau nhng virus tng t c phn lp t ngi lnh v ngi bnh vi cc tn gi khc nhau nh : virusAPC (Adeno Pharyngeal Conjunctival), virusARD (Acute Respiratory Diseases)...Nm 1956, tn Adenovirus c t cho nhm ny v tn ny c dng cho n ngy nay. Adenovirus thuc h Adenoviridae. C hai ging c cng nhn l Aviadenovirus (chim) v Mastadenovirus (ngi v ng vt c v). Cc Adenovirus ngi gm c 41 typ huyt thanh khc nhau, trong c nhiu typ huyt thanh c th gy bnh cho ngi.

I. CC TNH CHT CA VIRUS

1.Cu trc ht virus Adenovirus l nhng virus cha DNA hai si, kch thc virus t 70 n 80 nm ng knh, khng c v bc, capsid c i xng hnh khi v virus c hnh a gic u to nn bi 252 capsome. C hai loi capsome chnh l: 240 capsome gi l Hexon nm trn 20 mt hnh a gic u v 12 capsome gi l penton nm 12 nh ca hnh a gic u. Mi penton mang mt si nh ra bn ngoi v tn cng bi mt khi hnh cu nh. Li ADN 2 si c trng lng phn t 20x106 n 25x106 Dalton.
Hnh 1. Cu trc Adenovirus

2.Cu trc khng nguyn

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Adenovirus c cu trc khng nguyn phc tp. C 3 loi khng nguyn cu trc capsid l : - Hexon mang tnh c hiu nhm, th nhm v typ. - Penton mang tnh c hiu nhm v th nhm. - Si mang tnh c hiu th nhm v typ Hot tnh ngng ht hng cu lin quan n khng nguyn penton v si. Adenovirus c kh nng ngng kt hng cu kh v chut cng. 3. Sc khng ca virus Adenovirus khng vi ete, bn vng trong phm vi pH rng t 2 - 10. Adenovirus c th tn ti v khng gim hot tnh xm nhim khi 40 C trong nhiu tun hoc -250C trong nhiu thng. 4. S nhn ln ca virus Adenovirus nhn ln tt trong t bo ca ngi ( t bo i, tuyn gip, thn) v cc dng t bo thng trc HeLa, KB, Hep - 2. Virus nhn ln v chn trong nhn t bo tc ch. Cc t bo nhim virus trn li, trong nhn xut hin nhng ht vi. Thi gian cho mt chu k nhn ln trung bnh l 30 gi.

II. KH NNG GY BNH CHO NGI

Adenovirus ngi lu hnh rng ri khp ni trn th gii. Chng c kh nng gy ra nhiu bnh ng h hp, mt v ng tiu ha tr em v ngi ln. Bnh ly truyn ch yu theo ng h hp, virus c hng trong nhng ngy u ca bnh, ri theo phn ra ngoi trong nhiu tun l v tn ti nhiu nm hch hnh nhn. Adenovirus ngi c th gy cc hi chng lm sng sau : 1. Nhim virus cp tnh ng h hp trn Adenovirus c hng tnh c bit vi ng h hp trn, gy cc v dch ng h hp cp tnh trong mt tp th. Thi gian bnh 6-8 ngy triu chng ni bt u tin l st km theo nhc u, st ko di 2 n 4 ngy, cc triu chng ng h hp tn ti khong 1 n 2 tun l, bnh nhn khi hon ton. Hi chng ny thng do cc typ 3, 4, 7 gy ra. Ngi ta cn gp thm cc Adenovirus typ 1, 2, 5 v 6 gy dch a phng tr em.. 2. Vim phi Thi k nung bnh t 6 - 8 ngy. Bnh t ngt vi st cao 39 0C, ho, chy nc mi v cc du hiu tn thng thc th phi, cc tn thng ny lan rng v ko di. Bnh vim phi cp do Adenovirus typ 3,4,7 v 14 gy ra v thng xuyn xy ra trong cc tp th thanh thiu nin, c bit typ7 thng xy ra vim phi nng, ch yu tr em, t l t vong cao, khi khi li di chng phi. 3. St, vim thanh qun v kt mc Thi k nung bnh t 4 - 5 ngy. Bnh c ba triu chng c bit l st 38 0C, vim thanh qun cp tnh c ban kh nut v vim kt mc mt hoc hai bn. Hi chng ny thng do Adenovirus typ 3 gy ra. 4. Vim gic mc - kt mc thnh dch

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Vim kt mc do Adenovirus gy ra c th l mt biu hin lm sng ring bit hay l kt hp vi hi chng ng h hp. Thi k nung bnh t 5 - 7 ngy, bnh khi u t ngt, kt mc v cc t chc t bo quanh mt b ph thng. Bt u ch c mt mt b vim, khong 3 - 7 ngy sau lan sang mt th hai. xung quanh tai c hch v gic mc c nhng khang m trn, nh v nng. Cc thng tn ny xut hin trong vng 2 - 4 tun l, hu ht bnh nhn khi hon ton. Gy ra bi Adenovirus typ 8, 19, 37. 5. Vim d dy, rut Cc Adenovirus l mt tc nhn virus thng gp trong bnh vim d dy - rut cp tnh khng do vi khun. Adenovirus chim v tr th 2 sau Rotavirus trong bnh tiu chy do virus tr nh. Thi k bnh t 3 - 10 ngy. Bnh nhn tiu chy te nc ko di khong 7 ngy, c km theo st, nn, hi chng ng h hp v vim kt mc. Bnh thng do Adenovirus typ 40, 41 v 31 gy ra. 6. Nhim virus th n Mt s ln cc nhim trng Adenovirus l th n. Mt ngi c th nhim Adenovirus nhiu ln nhng u b b qua v khng c du hiu lm sng, ch pht hin c khi nui cy phn lp virus. Adenovirus c th sng m trong hch hnh nhn v trong rut ngi lnh trong nhiu tun.

III. CHN ON PHNG TH NGHIM

1. Chn on nhanh Dng k thut min dch hunh quang trc tip chn on trong cc th phi nng bng cch pht hin khng nguyn virus trong cc t bo biu m ng h hp trn (bnh phm) bng khng huyt thanh mu c gn cht mu hunh quang. Trong trng hp a chy do Adenovirus, c th xt nghim phn bng knh hin vi in t v n gin hn l da vo k thut ngng kt ht latex c gn khng th pht hin Adenovirus trong phn. 2. Phn lp virus Ly bnh phm ty theo hi chng lm sng, c th l cht tit ca mi hu hay mt, hay nc ra c hng, hay phn... Nui cy bnh phm vo cc nui cy t bo thch hp nh nui cy t bo HeLa, Hep-2..., pht hin hiu ng t bo bnh l, s hy hoi t bo nui cy xy ra sau 2 - 4 ngy. 3. Chn on huyt thanh C th dng phn ng ngn ngng kt hng cu, phn ng kt hp b th, phn ng trung ha pht hin cc khng th c trong huyt thanh bnh nhn. Khi hiu gi khng th tng ln mu ly ln th 2, th c gi tr chn on.

IV. PHNG BNH V IU TR

1. Phng bnh Cc bin php phng bnh chung ging nh phng bnh cc virus ng h hp khc. ang nghin cu vaccine sng gim c. 2. iu tr Cha c thuc iu tr c hiu. Cn phng bi nhim vi khun c bit tr suy dinh dng. Tuy nhin, cc bin chng do nhim khun th pht rt him.

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ENTEROVIRUS
Mc tiu hc tp 1.Trnh by c c im virus hc ca Poliovirus, Coxsackievirus v Echovirus 2.Trnh by c kh nng gy bnh ca ba loi virus trn 3.Trnh by c phng php chn on virus hc, phng php phng nga v iu tr Enterovirus thuc h Picornaviridae, h ny gm 2 ging: Enterovirus v Rhinovirus. c im chung l nh, cha ARN 1 si, capsid i xng hnh khi, khng c v bc. - Ging Enterovirus gm 4 loi: + Poliovirus: gm c 3 typ, gy bnh bi lit, vim mng no. + Coxsackievirus: gm c 29 typ, gy vim mng no v khun, vim c tim, vim hng p t, pht ban ngai da... + Echovirus: gm c 32 typ, gy vim mng no v khun, vim ng h hp, vim no, vim rut, vim c tim,... + Enterovirus typ 68-71 gy vim kt mc chy mu, vim tiu ph qun; typ 72 ca Enterovirus gy vim gan cp tnh (Hepatitis A virus). - Ging Rhinovirus: gy nhim trng ng h hp trn.

I. VIRUS BI LIT (POLIOVIRUS)

Poliovirus xm nhim hng v rut nn c th phn lp c 2 ni. N gm 3 typ: 1, 2, 3. Poliovirus gy nn bnh bi lit, mt bnh cp tnh tc ng ln h thn kinh trung ng. Nhng n ron vn ng ca ty sng hoc ca v no c th b ph hy v do gy nn lit mm. Trong mt v dch 90 - 93 % cc trung hp l th n, 4 8% bnh nh vi nhng triu chng ng h hp v ng rut, ch c 1 - 2% c hi chng bi lit. 1. c tnh virus hc 1.1. Hnh thi Virus bi lit l mt trong nhng virus nh nht c bit, ng knh 28 nm. Virus cha ARN mt si, capsid i xng hnh khi gm c 32 capsome. Phn t ARN mt si chim 30 % trng lng ca ht virus. Phn t ARN c th tch khi ht virus v vn gi kh nng xm nhim cc nui cy t bo. Capsid bo v axit nucleic, gip cho virus c nh ln b mt t bo cm th v mang khng nguyn c hiu hnh thnh tnh min dch i vi virus. 1.2. Sc khng Virus khng vi ete v thuc ty, bn vng pH 4 - 10 nhng b mt hot tnh 56 0C trong 30 pht hoc x l bng formalin, Cl2, H2O2, KMnO4. nhit bnh thng virus c th tn ti trong phn ngi t 1 ngy n nhiu tun l ty theo s lng virus, pH v m ca phn. Virus gi kh nng xm nhim trong mt thi gian tng i di trong nc, sa v cc thc n khc. 1.3. Tnh cht nui cy Ngi ta c th nhim virus cho cc loi kh Rhesus, kh Cynomolgus lc tim vo ty sng, vo no hoc nh vo mi. Poliovirus c th ly truyn bng ng tiu ha lc nhim virus cho kh qua ng ming. Hin nay ng vt khng cn c s dng chn on virus nhng c s dng th nghim vaccine. Phn ln nhng chng Poliovirus c th pht trin t bo ngui hoc t bo thn kh, hoc t bo thng trc nh t bo HeLa. Poliovirus gy nn nui cy t

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bo hiu ng t bo bnh l c trng: t bo tr nn trn, chit quang, nhn co rt trc khi thoi ha.

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1.4. Cu trc khng nguyn Poliovirus gm 3 typ: 1, 2, 3 xc nh nh phn ng trung ha, phn ng kt hp b th v phn ng kt ta mi trng gel. Khng nguyn trung ha v khng nguyn kt hp b th c th chit xut t nui cy t bo hoc t thn kinh trung ng b nhim virus. 2. Kh nng gy bnh 2.1. ng ly truyn bnh Bnh bi lit l mt bnh truyn nhim mnh, c th ly truyn bng ng tiu ha v ng h hp nhng ch yu l ng tiu ha. Ngi nhim virus do n thc n nhim virus hay tip xc vi cc vt dng nhim virus hoc h hp cc ht cht tit nh c cha virus. 2.2. S pht trin ca virus trong c th Sau khi xm nhp vo c th, virus xm nhim vng ming hng v rut, nhn ln v nhng hch bch huyt c v mng treo rut. Sau 2, 3 ngy virus c phng thch vo mu v s nhim trng th pht xy ra nhng m nhy cm khc m thn kinh v h thn kinh trung ng. S nhn ln ca nhng virus nhng v tr ban u v s nhim virus mu tip theo, trong nhiu trung hp khng c biu hin lm sng hoc cho thy mt chng bnh khng c hiu, chng bnh quan trng gi l bnh bi lit xy ra sau nhim virus mu v l hu qu ca s nhn ln ca virus v s ph hy t bo nhng v tr th pht. Thi gian nung bnh t 7 - 14 ngy, c khi ngn hn 3 ngy hoc di hn 35 ngy. 3. c im lm sng 3.1. S nhim trng khng biu hin Khong 90 - 95% nhim Poliovirus khng cho thy triu chng. Trong nhng trng hp ny s nhim trng ch gii hn ng tiu ha v ch c th xc nh bng cch phn lp virus phn hoc bng phn ng huyt thanh. 3.2. Chng bnh nh Bnh nhn st va trong 24 - 48 gi, chng bnh nh xy ra trc khi chng bnh nng. Triu chng: au u, bing n, nn ma, xung huyt mi v hu, au hng v i khi ri lon tiu ha. Chng bnh nh khng phi l mt nt thng thng ca bnh bi lit v ch xy ra 1/3 tr em v t hn ngi ln trong s ngi c chn on b bnh bi lit. Chng bnh nh c xem l biu hin lm sng ca nhim virus mu sau bnh nhn hi phc. Hi chng c gi l bnh bi lit non v chim khong 4 8% ca tt c nhng nhim Poliovirus. 3.3. Chng bnh nng Xut hin 1 - 3 ngy sau chng bnh nh hoc xy ra m khng c chng bnh nh. - Giai on trc bi lit: chng bnh phn nh s xm nhim ca Poliovirus vo h thn kinh trung ng, biu th nhng triu chng lm sng u tin ca s nhim trng trong phn ln nhng trng hp. c im: st, au u, bun nn, ma v du hiu kch thch va mng no gy nn au v cng c v lng, cng c th au t chi. mt vi bnh nhn chng bnh dng y m khng pht trin thnh lit v c gi l bnh bi lit khng lit. - Giai on lit: 1 - 5 ngy sau khi xut hin chng bnh nng hoc i lc lu hn, ngi bnh b lit mm nhng nhm c ring bit. Lit c pht trin trong 3 ngy k tip, quy m ph thuc vo v tr v tnh trng ca nhng thng tn h thn kinh trung ng. S phc hi bt u sau khi bnh ngng pht trin. S hot ng ca nhng c b lit c th c ci thin trong 4 - 6 tun l tip theo, mi ci

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thin thng hon tt trong vng 6 thng. Vt l tr liu c th h tr cho s hi phc. Him hn mt giai on lit th 2 xy ra 3 - 4 ngy sau giai on lit th nht. Khong 1 - 2% ngi b nhim Poliovirus pht trin thnh chng bnh nng.

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4. Cc hnh thc bi lit Nhng thng tn gy lit c thng thng xy ra nhng t bo ca sng trc ty sng (chng bi lit ty sng). Nhng thng tn tng t c th xa ra nhng vng ty sng v no (chng bi lit hnh no) v v no (chng bi lit no). Bi lit hnh no c bit nghim trng v thng tn ca nhng dy thn kinh s gy lit cho nhng c ca kh qun, thanh qun, vm ming, lm mt kh nng nut v nhanh chng cn tr s h hp nu khng c iu tr thch hp. Thng tn ca nhng trung tm h hp v vn mch c th dn n suy h hp v try tim mch nn chng bi lit hnh no c t l t vong cao. 5. Tnh min dch Tnh min dch thng xuyn i vi typ Poliovirus gy nn s nhim trng. Tuy nhin c th c mt mc thp v s khng khc typ c bit gia typ 1 v typ 2. Khng th khng bi lit ca m truyn cho con tun t bin mt trong 6 thng u ca i sng a b. Khng th tim vo c th ch tn ti trong 3 - 5 tun l. Khng th trung ha to thnh khong 7 ngy sau khi c th tip xc vi Poliovirus v tn ti sut i. V virus trong no v ty sng khng b nh hng bi khng th trong mu nn to min dch ch c gi tr lc thc hin trc khi xut hin nhng triu chng lin quan n h thn kinh. T lu ngi ta bit s khng bnh bi lit lin h cht ch vi amidan. Nhng kho st gn y cho thy sau khi ct amidan th mc khng th ming v hng gim xung r rt, c bit tr em nam. tr em b ct amidan th s p ng vi vaccine bi lit pht trin chm v hiu gi khng th thp hn tr em c amidan nguyn vn. 6. Chn on phng th nghim 6.1. Nc no ty Bch cu gia tng 10 - 200 /mm3, t khi ln 500 /mm3. Trong giai on sm ca bnh t l bch cu a nhn /lymph cao nhng trong vng t ngy t l o ngc li. S lng t bo ton phn chm tr li bnh thng. Protein trong nc no ty tng va, trung bnh 40 -50 mg/100ml v tn ti nh vy trong nhiu tun l trc khi s lng t bo gim xung. Lng glucose bnh thng. 6.2. Phn lp v xc nh virus - Bnh phm : L que bng ngoy hng trong thi gian bnh mi bc pht nhng c th ly ngoy hu mn hoc ly phn trong mt thi gian di hn. Kh nng tm thy virus tu thuc qu trnh chng bnh: 80% trong 2 tun l u nhng ch 25% trong tun l th 3. Trong trng hp bnh nhn cht th ly no v cht cha i trng. Bnh phm phi c lm lnh cng sm cng tt v nu gi n phng th nghim qu 1 ngy th phi gi trng thi ng lnh. - Phn lp v xc nh Nui cy t bo thn kh hoc t bo mng i hoc t bo thng trc (Hela, KB, WI-38). Virus bi lit gy nn hiu ng t bo bnh l c trng. Xc nh typ bng phn ng trung ha. - Phn ng huyt thanh : Ly huyt thanh kp: ln th nht sau khi bnh bc pht, ln th hai, 2 - 3 tun l sau tm ng lc khng th. C th s dng phn ng kt hp b th, phn ng trung ha. Khng th kt hp b th thay i trong qu trnh ca chng bnh. Khng th trung ha xut hin sm v thng c th khm ph trong thi gian bnh nhn nm vin. Khng th kt ta c hiu typ pht trin trong thi gian hi phc v t c s dng trong chn on.

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Phn ng huyt thanh ngoi gi tr chn on bnh, cn c gi tr xc nh c tnh trng nhim virus (th n) trong cng ng v xc nh hiu lc ca vaccine. 7. Phng nga v iu tr 7.1. iu tr Khng c thuc c hiu 7.2. Phng nga: Bng bin php chung kh thc hin, ch yu bng vaccine rt hu hiu. C 2 loi vaccine: vaccine Salk v vaccine Sabin. - Vaccine Salk: L vaccine cht cha 3 typ virus c lc nui cy t bo thn kh v git cht bng formol v propiolacton. Tim trong da vaccine to nn min dch dch th ngn nga khng cho virus xm nhim thn kinh trung ng. Vaccine an ton v hiu qu nu s dng ng nguyn tc. Tuy nhin vaccine ny c mt s nhc im: khng to nn min dch ti ch do virus vn c th nhn ln rut nn khng lm gim nguy c ly lan virus, ngoi ra phi tim nn kh thc hin quy m ln, hn na li t tin. - Vaccine Sabin: L vaccine sng gim c. y l mt vaccine sng hon chnh cha 3 typ virus bi lit 1, 2, 3 gim c. Virus nhn ln trong t bo rut to thnh khng th ti ch. Min dch thu hoch khng nhng ngn cn virus c lc hoang di xm nhim thn kinh m cn c ch s xm nhim v nhn ln ca cc virus ngay ti rut. Hn na vaccine Sabin r khong 100 ln so vi vaccine Salk v d thc hin v c th cho ung hoc nh t git vo mt thi ng ri cho ngm.

II. COXSACKIEVIRUS
Loi Coxsackievirus thuc h Picornaviridae gm 29 typ. Chng khc bit vi cc Enterovirus khc kh nng gy bnh chut , cc enterovirus khc th him hoc khng. Chng chia thnh 2 nhm: nhm A v nhm B c kh nng gy bnh chut khc nhau. Cng nh Poliovirus chng xm nhim rut ngi v c phn lp ln u tin phn ca 2 tr em Coxsackie, New York. Chng gy nhiu chng bnh khc nhau: Coxsackie A gy vim hng p t, pht ban ngai da, gy vim kt mc chy mu, vim mng no v khun..., Coxsackie B gy vim c tim tr s sinh, vim ng h hp trn, vim mng ngoi tim, vim mng trong tim...

III. ECHOVIRUS
Loi Echovirus (enteric cytopathogenic human orphan virus) thuc h Picornaviridae gm 33 typ. Chng cng tm thy ng tiu ha, gy nn hiu ng t bo bnh l nui cy t bo nhng khng gy nn nhng thng tn bnh l chut . Chng lin quan n mt hoc nhiu hi chng bnh t chng bnh h hp nh n thng tn no. Chng gy nn vim mng no v khun, nhim trng ng h hp trn cp tnh, vim no, vim rut, vim c tim, st pht ban...

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ROTAVIRUS
Mc tiu hc tp 1. Trnh by c c im virus hc ca Rotavirus 2.Trnh by c kh nng gy bnh ca Rotavirus 3.Trnh by phng php chn on virus hc, phng php phng nga v iu tr Rotavirus thuc ging Reovirus h Reoviridae gy nhim trng ng h hp v ng tiu ha. Rotavirus gy bnh tiu chy nng v e da tnh mng tr em di 2 tui trn ton th gii. Virus Norwalk tng t nhng nh hn Rotavirus cng gy bnh tiu chy nhng tr em ln tui v ngi trng thnh.

I. C IM VIRUS HC

Hnh 1 Rotavirus di knh hin vi in t

1. c im v cu trc Rotavirus c gi tn nh th v c dng trn nh bnh xe kch thc ht virus l 65 -70 nm. Axit nucleic l ARN hai si, c chia thnh 11 on nm trung tm ca ht virus, ng knh 38nm c bao bc bi hai lp capsid. Capsid i xng hnh khi gm capsid trong v capside ngoi. Cc capsome ca lp trong xp theo hnh nan hoa v ko ni cc capsome ca lp ngoi to nn hnh vng do vy cc virus ny mi c tn l rota (Rota = bnh xe).

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1.1.

c im v khng nguyn

Hnh 2. Cu trc ca ht Rotavirus

Hai lp capsid ca virus mang c im khng nguyn ring bit. Lp capsid ngoi mang tnh khng nguyn c hiu typ. Lp capsid trong mang khng nguyn c hiu nhm. Rotavirus gy bnh cho ngi v cc Rotavirus gy bnh cho ng vt c khng nguyn tng t nhau nhng khng c mi lin quan v mt khng nguyn vi cc virus thuc h Reoviridae. Rotavirus gy bnh cho ngi gm c 6 typ huyt thanh. Lc nhim typ huyt thanh no th p ng khng th cao vi typ v ch c p ng tng phn vi cc typ khc. 1.2. c im nhn ln v kh nng gy bnh Rotavirus vo c th ngi v nhn ln ch yu nim mc t trng. Chng cn gy tiu chy ln con, b s sinh hoc kh s sinh. Ngi ta c th nui cy Rotavirus nui cy t bo rut bo thai ngi, thn bo thai ln. S nhn ln ca virus c th pht hin bng min dch hunh quang v min dch hin vi in t, nhng hiu ng t bo bnh l khng c hoc ti thiu. 1.3. Sc khng Virus b bt hot nhanh chng khi b x l bng EDTA (ethylendiamintetracetic acid). Chng d b bt hot pH nh hn 3 v ln hn 10, nhng c sc khng tt vi vi clo v ete. Chng bn vng sau nhiu ngy trong phn nhit thng.

II. C CH SINH BNH

Rotavirus nhn ln trong lin bo nhung mao rut non ph hy cu trc lin bo v lm cn nhung mao rut non. T bo hp thu trng thnh ca nhung mao tm thi b thay th bi nhng t bo cha trng thnh khng th hp thu hu hiu ng v thc n, gy bi tit nc v cht in gii rut non, dn ti a chy thm thu do km hp thu. S hp thu thc n tr nn bnh thng lc cc nhung mao rut ti sinh v cc t bo nhung mao trng thnh.

III. KH NNG GY BNH

a chy nghim trng v st, i khi c nn l mt hi chng thng thng do Rotavirus gy nn tr nh di 2 tui, c bit l tr em b sa m. Sinh thit cho thy nim mc rut non l ch nhn ln chnh ca virus. Virus thi ra trong phn ti

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a trong 4 ngy u ca chng bnh nhng ngi ta c th pht hin virus 7 ngy sau khi b a chy. Trong nhim trng th nghim kh v ln con, s nhn ln ca virus v nhng thung tn bnh l xy ra nhng t bo cu ton b rut non, nhng rut gi v nhng c quan khc khng b nhim virus. Bnh c th xy ra t hnh thc nhim trng khng biu hin n a chy va, a chy nghim trng, c th cht. Bnh thng khi pht t ngt. Nn ma trc khi a chy xy ra trn 80% tr em b bnh, khong 1 phn 3 tr em nm vin c nhit trn 390C. Bnh thng ko di t 2 - 6 ngy. Dch nhy thng thy trong phn nhng bch cu v hng cu tm thy t hn 15% trng hp. Nhim Rotavirus cng thng cho thy nhng triu chng ng h hp, st, nn, ri a chy. Nhim trng Rotavirus c bit nghim trng v c th a n t vong tr em suy min dch.

IV. DCH T HC
Nhim Rotavirus xy ra khp ni trn th gii. Trong khong 3 tui u, mi tr em b nhim Rotavirus t nht mt ln. cc nc n i nhim trng xy ra nhng thng lnh v ma ng. nc ta cng nh cc nc nhit i bnh xy quanh nm, tn s tng ln cc thng mt tri v ma lnh: 10, 11, 12. Rotavirus l cn nguyn quan trng nht gy a chy mt nc nghim trng tr nh v tr di 3 tui cc nc pht trin cng nh cc nc ang pht trin v chim t 30 - 50 % cc trng hp a chy cn nm vin hoc cn b dch tch cc.

V. CHN ON PHNG TH NGHIM

5.1. Xc nh virus - Bnh phm: Ly phn bnh nhn trong tun l u ca bnh hoc ht dch t trng. - K thut xt nghim: Quan st ht virus trc tip di knh hin vi in t cho thy c hnh dng trn nh bnh xe (xem hnh 1 phn u ca bi). Cng c th pht hin virus trc tip t bnh phm bng th nghim ngng kt ht latex, ngng kt hng cu th ng. K thut min dch lin kt men (ELISA) cng c s dng pht hin Rotavirus mu nghim phn. K thut phn t in di ARN ca virus t mu nghim phn trn gel polyacrylamid cho php phn bit cc chng Rotavirus gy bnh ngi. 5.2. Chn on huyt thanh - Bnh phm l mu bnh nhn - S dng cc phn ng min dch lin kt enzyme (ELISA), min dch phng x, phn ng min dch hunh quang pht hin khng th IgG trong mu bnh nhn. Tuy nhin, chn on huyt thanh t c gi tr cho chn on lm sng.

VI. PHNG NGA V IU TR

Bnh xy ra ngay cc nc pht trin c phng tin y t hin i v cung cp y nc sch nn khng th phng nga bng bin php v sinh n thun. Nhng tin b trong mt s vaccine sng gim c cho php hy vng c th phng nga bng vaccine trong thi gian ti. iu tri bng cch cho ung oresol (ORS) b nc v cht in gii. Ch mt s trng hp n bnh vin qu nng mi phi truyn dch.

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VIRUS CM (Influenzavirus)
Mc tiu hc tp 1. Trnh by c cc tnh cht ca virus. 2. Trnh by c kh nng gy bnh ca virus. 3. Trnh by c cc phng php chn on phng th nghim v phng bnh. Virus cm l thnh vin ca h Orthomyxoviridae. Cc virus ny l nhng tc nhn gy bnh cm ngi v ng vt. Cc virus gy bnh cho ngi c phn bit thnh 3 type A, B v C. C nhiu tc nhn virus khc nhau nh virus cm, virus cm, virus hp bo h hp, virus adeno ... u c th gy ra hi chng ging cm. Nhng ch c virus cm mi l th phm gy ra bnh cm tht s.

I. CC TNH CHT CA VIRUS

1. Hnh th, cu trc ca virus Virus cm hnh cu ng knh t 80 - 120 nm nhng i khi c dng hnh si. Nucleocapsid i xng kiu xon trn c, cha ARN mt si c trng lng phn t khong 4x106 daltons km theo enzyme ARN polymerase ph thuc ARN. Cu trc ARN ca virus cm A v B phn lm 8 on gen, cn virus cm C phn lm 7 on, trn mi on gen virus c th ghi du cho nhiu mt m di truyn. Nucleocapsid c bao bc bi mng protein nn M1 (M: Matrix), pha ngoi mng li c bao bc bi v ngoi l lp lipid kp c ngun gc t mng bo tng ca t bo ch. Protein M2 m xuyn v nh ra khi v ngoi, to thnh cc knh ion. Trn b mt v ngoi c nhng cu trc si c cu to bi glycoprotein, to nn cc khng nguyn hemagglutinin (k hiu l H) v neuraminidase (k hiu l N). Mi si H v N di 8-10 nm, cch nhau 8 nm. Hai cu trc H v N l nhng khng nguyn quyt nh kh nng ngng kt hng cu ng vt. 2. S nhn ln ca virus Cc virus cm nui cy d dng trong phi g. Ngoi ra, ngi ta cn dng cc nui cy t bo thn phi ngi, thn kh v chut lang nui cy virus cm in vitro. Khi xm nhp vo t bo thch hp th ARN ca virus c tng hp trong nhn ca t bo vt ch, cn cc thnh phn khc ca virus c tng hp trong bo tng ca t bo. Cc ht virus mi c hnh thnh mng t bo. Mng t bo vt ch b y li ra, sau gii phng ra nhng ht virus hon chnh. S nhn ln ca virus trong t bo vt ch c th b c ch bi actinomyxin D. Mt chu k hon chnh ca virus khong 12 gi. Mt t bo b nhim virus cm sau khong 12 gi phn ln l sinh ra cc ht virus hon chnh (virion), nhng i khi c th sn sinh ra mt loi virus trng thi khng hon chnh (ht DIP: Defective interfering particles). Nhng ht virus khng

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hon chnh cha rt t hoc khng c ARN, mt kh nng gy xm nhim, nhng vn gi c kh nng ngng kt hng cu. 3. Sc khng vi cc tc nhn l ha hc - Ht virus b ph hy bi ether v deoxycholate natri do n c 20 - 30% lipit. - pH thch hp nht l 6,5 - 7,9. - Virus chu nhit km : 560C - 600C tnh xm nhim b ph hy trong mt vi pht, nhng hot tnh ngng kt hng cu vn c duy tr. 4. Cu to khng nguyn ca virus - Khng nguyn nucleocapsid: L thnh phn i xng hnh xon c nm bn trong v bc. l khng nguyn kt hp b th ha tan c thnh phn ha hc l nucleoprotein. Da vo khng nguyn nucleocapsid v protein M ngi ta chia cc chng virus cm ra lm 3 type huyt thanh A, B, C. Khng nguyn ca mi type khc nhau v khng phn ng cho vi khng nguyn ca hai type kia. - Khng nguyn protein nn M1: L thnh phn cu trc chnh bao bc nucleocapsid. -Khng nguyn hemagglutinin v khng nguyn neuraminidase: Bn cht l glycoprotein nm trn v bc ca virus. Hai khng nguyn ny c vai tr trong s xm nhm vo t bo v s that ra khi t bo ca ht virus. Nh c khng nguyn b mt ny m virus cm c th ngng kt hng cu ca 20 loi ng vt khc nhau, hay dng nht l 1% dch treo hng cu g, hng cu ngi nhm O v chut lang. Khng nguyn H c trng cho tp, khng nguyn N c trng th tp (subtype). Cc cu trc H v N ca virus cm c th thay i trong tng th tp. Hin nay c 16 cu trc khng nguyn H (H1 n H16) v 9 cu trc khng nguyn N (N1 n N9) khc nhau c hiu cho tng th tp ca cc tp cm A, B v C. - S thay i khng nguyn ca virus cm: Cu trc khng nguyn ca virus cm (khng nguyn H v khng nguyn N) thay i r nht, c bit vi virus type A. Trong type A v B nhng bin chng c th phn bit nh s sai bit khng nguyn H v khng nguyn N. Trong mt t thp k qua c khong 10 - 12 nm xut hin mt bin chng, ch yu l mt th tp ca type A v trong mt thi gian nht nh ch mt th tp duy nht chim u th. Genom ca virus cm phn lm nhiu on l nguyn nhn dn n s thay i khng nguyn. C 2 kiu thay i khng nguyn: + Hon v khng nguyn (antigenic shift): Hin tng hon v khng nguyn xy ra khi c 2 hay nhiu chng virus, vi nhiu on ARN khc bit nhau v mt di truyn, cng lc xm nhim vo mt t bo. Cc on genom hon v vi nhau, kt qu l to ra chng virus mi. Bin chng virus c th ly nhim vo vt ch mi. Hin tng hon v khng nguyn ch thy xy ra virus cm A v l nguyn nhn gy ra cc v i dch cm trn ton cu. + Bin th khng nguyn (antigenic drift): l qu trnh t bin ngu nhin xy ra gen m ha cho hemagglutinin dn n s thay i mt s axt amin trong protein hemagglutinin. Hin tng bin th khng nguyn xy ra c 2 virus cm A v B, l nguyn nhn gy ra cc v dch cm a phng trong thi gian gia cc i dch. Cc bin chng mi, khc vi chng c l n c nhng thnh phn khng nguyn mi, thay th cho nhng thnh phn khng nguyn c, do nhng khng

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th min dch c khng cn tc dng vi khng nguyn mi. Cu trc khng nguyn virus type A t bin nhiu hn virus type B, cn virus type C hin nay cha tm thy khng nguyn t bin.

II. KH NNG GY BNH CA VIRUS

Virus cm type A, B, C l tc nhn gy ra bnh cm ngi vi nhng c im rt c bit nh: Tnh cm th cao, thi gian bnh rt ngn t 1- 2 ngy, bnh din bin nhanh chng, gy ra mt sc min dch cao nhng khng lu bn, ly truyn trc tip qua ng h hp. l nhng nguyn nhn lm cho bnh cm d lan trn thnh cc v dch ln 1. S lan truyn ca virus trong c th Virus vo c th bng ng h hp, n xm nhim cc t bo nim mc ng h hp trn gy thng tn nim mc lm xut hin cc phn x ho v ht hi. Qu trnh pht trin ca virus ng h hp trn dn ti s hy hoi ca cc t chc lin bo, m ng cho virus vo ph qun v vo phi hay cng c th m ng cho cc vi khun gy xm nhim th pht khi cc t chc t bo mt ht kh nng t v bnh thng ca n. l cc th vim phi do virus hay cc bin chng khc do nhim khun th pht. 2. Hnh nh lm sng Thng gp l th in hnh vi cc c im l sau 1 - 2 ngy bnh, xut hin rt run, st, au khp mnh my, suy nhc, tn thng b my h hp, bnh khi nhanh nhng mt mi ko di. Ngoi ra c th gp th nng vi cc triu chng ca bnh ph qun - ph vim do virus hoc do nhim cc vi khun t cu, lin cu, ph cu, Klebsiella pneumoniae.., thng gp ngi gi v tr nh vi t l t vong cao. 3. Dch t hc Bnh ly trc tip qua ng h hp, thng gy dch ln, nht l type A. Dch cm thng xy ra vo ma ng xun. Sau khi nhim bnh cm s c min dch c hiu type ko di t 6 thng n 3 nm. Cc th tp H v N khc nhau ca cc virus cm c th gy bnh cho ngi v nhiu ng vt khc nhau. Mt s th tp thng gy bnh ngi nh H3N2, H1N1... Ring th tp H5N1 ca virus cm A l loi gy bnh gia cm nhng hin nay vt qua ro cn gii hn th th c hiu loi gy nhim ng vt c v v c ngi. T nm 1997 n nay, dch cm A (H5N1) xy ra lin tip nhiu nc chu c bit l Trung Quc, Thi Lan, Vit Nam,....

III. CHN ON PHNG TH NGHIM

1. Chn on phn lp v xc nh virus Virus c phn lp t bnh phm ngoy mi, ngoy hng, nc ra mi hng ca bnh nhn hoc t m phi trong nhng trng hp t vong. Ch yu ngi ta phn lp virus cm trn phi g bng cch tim truyn bnh phm vo ti i ca phi g t 10 - 13 ngy. Sau 3 ngy nhit 35 0C, ht nc khoang i xc nh virus. Virus phn lp ra c nh loi bng phn ng c ch ngng kt hng cu vi cc khng huyt thanh type. Ngoi ra ngi ta c th phn lp virus bng cch nui cy bnh phm trong cc nui cy t bo thn kh hoc thn phi ngi.

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2. Mt s phng php khc - Phng php min dch hunh quang trc tip xc nh virus cm trong nc sc hng ca bnh nhn. - Pht hin cc on ARN ca virus cm trong cc dch ng h hp nh dch mi, dch hu hng, dch t hu, dch kh ph qun bng k thut khuch i gen (RT- PCR: Reverse transcriptase - Polymerase chain reaction). K thut ny c nhy v c hiu cao gip chn on nhanh v sm bnh cm. 3. Chn on huyt thanh Ly 5ml mu bnh nhn vo ng nghim v khun, khi mu ng, tch ly phn huyt thanh. Phi ly mu 2 ln (huyt thanh kp) cch nhau 10 - 14 ngy tm ng lc khng th. C 2 phn ng huyt thanh thng c s dng l phn ng kt hp b th dng khng nguyn nucleocapsid, phn ng c ch ngng kt hng cu dng khng nguyn ngng kt hng cu.

IV. PHNG BNH V IU TR

1. Phng bnh Do phng thc truyn bnh trc tip gia ngi vi ngi, bnh lan trn rt nhanh cho nn cng tc phng bnh chung rt kh thc hin. Trong v dch phi ch trng trnh cc nhim khun th pht bng cch nng cao sc khng ca c th. - Phng bnh c hiu bng vaccine : C 2 loi vaccine + Vaccine cht : dng virus cm nui cy trong phi ga, git cht bng formol v nhit hoc bta-propiolacton, tim di da hoc phun vo mi. + Vaccine sng gim c lc: phun vo mi. Cc vaccine phng bnh cm thng l vaccine phi hp nhiu chng virus cm in hnh thng gp nht. Tuy vy cc vaccine ny c nhc im l khi virus lu hnh bin d th cc vaccine iu ch t cc chng virus c hu nh khng c tc dng. V vy hin nay ngi ta ang nghin cu cc bin php b sung cho vaccine, mt trong cc bin php l dng interferon v interferonogen phng chng cm. 2. iu tr Khi gp th nng nh vim phi nguyn pht tr em do virus cm... ngi ta tim gama-globulin. Dng khng sinh trong iu tr hoc d phng cc nhim khun th pht trn nhng c th suy kit hoc c bnh mn tnh nng nh bnh lao, bnh tim...

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PARAMYXOVIRIDAE
Mc tiu hc tp 1. Nu c cc tnh cht ca virus. 2. Trnh by c kh nng gy bnh ca virus. 3. Nu c cc phng php chn on phng th nghim v phng bnh. H virus ny l mt nhm gm nhiu tc nhn khc nhau v kh nng gy bnh, v s phn b trong gii ng vt v v tnh cht sinh vt hc ca chng. Cc virus ny c hnh th v cu trc rt gn gi vi h Orthomyxoviridae, nhng chng c nhng tnh cht khc bit nh: kch thc t 150 - 700nm, ARN c trng lng phn t t 5 - 7.106 daltons, nucleocapsid cun nh c ng knh t 12 n 18nm, s hin din thng xuyn ca mt protein lin kt t bo (gy ra cc hp bo), tnh vng bn ca cc khng nguyn... H Paramyxoviridae c phn chia thnh 3 ging: - Paramyxovirus: virus cm v virus quai b - Morbillivirus: virus si - Pneumovirus: virus hp bo ng h hp

I. VIRUS CM
1. Cc tnh cht chung ca virus Virus cm c nhiu hnh thi nh hnh cu, hnh bu dc, kch thc 100 250nm. Cha ARN 1 si. Virus nhn ln tt trong cc nui cy t bo thn kh, bo thai ngi... Virus cm type 1, 2, 3 v 4 ngng kt c hng cu chut lang, hng cu kh v ngi 40C - 370C. 2. Kh nng gy bnh cho ngi Virus cm gy nn tr s sinh v tr nh t nhng nhim trng nh ng h hp trn n vim tiu ph qun, vim phi, vim thanh qun - ph qun c bit nghim trng. Ch yu thng gp virus cm type 1, 2, 3 cn type 4 th t gp hn. 3. Chn on virus - Phn lp virus t nc ra c hng, nui cy trong cc nui cy t bo thn kh hoc bo thai ngi. - Chn on huyt thanh thng dng phn ng c ch ngng kt hng cu. 4. Phng bnh v iu tr - Phng bnh chung gp rt nhiu kh khn. Phng bnh c hiu bng vaccine bt hot virus cm type 1, 2, 3 rt t c kt qu. - iu tr: Khng c thuc c hiu, ch phng cc bin chng do nhim khun th pht.

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II. VIRUS QUAI B

1. Cc tnh cht ca virus Kch thc ca virus quai b thay i t 85 - 340nm, hnh th a dng nhng cng c th hnh si ch. Thnh phn ha hc ging nh cc Paramyxovirus n ngng kt c hng cu g, chut lang... v hp ph c hng cu trn cc t bo b xm nhim trong cc nui cy t bo hoc trong nc khoang i ca phi g b xm nhim. Virus quai b nhn ln tt trn phi g. Virus quai b c 3 loi khng nguyn: - Khng nguyn S l nucleoprotein. - Khng nguyn V to ra t v bc. l khng nguyn ngng kt hng cu v Neuraminidaza. - Khng nguyn d ng: Khng nguyn ny lm tng tnh cm th c hiu theo type khi ngi ta tim trong da c th b cm nhim bng cht dch ly t khoang i v khoang m phi g b xm nhim. 2. Kh nng gy bnh cho ngi Bnh quai b l mt bnh truyn nhim cp tnh, ly v gy dch do virus quai b gy nn. Th in hnh ca bnh c thi k nung bnh khong 2 - 3 tun. Khi u bnh nhn thy kh chu, hi s gi, nhc u v st ln dn. y l thi k ly nht, nhng on ngay ra bnh li rt kh. Hm sau thy nhai, nut ngng, au trc tai. Sau 1 bn tuyn mang tai bt u sng v au ri 2 - 3 hm sau lan sang bn kia. a s l sng c 2 bn, tuy nhin sng 1 bn cng hay gp. Cc tuyn nc bt khc cng c th b vim (tuyn di hm, tuyn di li). Bnh nhn st 390C - 400C trong 3 - 4 ngy. Phn nhiu bnh khi sau 8 - 10 ngy. Bnh quai b c th c mt s bin chng thng gp ngi ln nh: vim tinh hon, vim bung trng, vim ty... Cc trng hp vim no, vim mng no no rt him, nhng nu c th rt nng v c th t vong. Bnh quai b c quanh nm, tr em d mc bnh v ngi ln cha mc vn c th b ly bnh. bnh duy nht l ngi. Bnh ly trc tip qua ng h hp. Bnh quai b li mt trng thi min dch lu di, rt t khi gp ngi b mc bnh ln th hai. 3. Chn on phng th nghim 3.1. Phn lp virus Bnh phm l nc bt cy vo phi g hoc vo trong cc nui cy t bo thn kh, Hela, t bo i ca ngi. Xc nh virus bng phn ng c ch ngng kt hng cu v phn ng trung ha vi huyt thanh mu. 3.2. Phn ng huyt thanh Thng s dng phn ng kt hp b th v phn ng ngn ngng kt hng cu. 4. Phng bnh v iu tr 4.1. Phng bnh: Cch ly bnh nhn. Dng gamma globulin. Dng vaccine cht hoc vaccine sng gim c lc.

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4.2. iu tr: Khng c thuc c hiu: ch yu phi chm sc bnh nhn, trnh i li nhiu khi c bin chng vim tinh hon.

III. VIRUS SI
1. Cc tnh cht ca virus 1.1. Cu trc Hnh th ch yu ca virus l hnh cu, nhng c khi l hnh si ch, kch thc khong 140nm. Virus cha ARN 1 si, nucleocapsid i xng hnh xon c, c v bc. Trn b mt v bc ca virus c cc yu t ngng kt hng cu. 1.2. Sc khng Virus nhy cm i vi ete. Virus si c 1 sc khng cao. N c th sng st nhiu ngy 360C, 220C sng c trn 2 tun. 1.3. Tnh cht khng nguyn - Khng nguyn ribonucleoprotein hay cn gi l khng nguyn kt hp b th. - Khng nguyn ngng kt hng cu: nm trn b mt v bc. Virus si lm ngng kt hng cu kh. - Dung huyt t: Tnh cht dung huyt ca virus si c Peries m t nm 1961. Ht virus nguyn vn cng nh yu t ngng kt hng cu tch ri, u c hot tnh tan huyt. 1.4. Nui cy nui cy virus si, ngi ta hay dng nui cy t bo thn ngi v thn kh, t bo mng i ngi, t bo phi g... Virus si trong qu trnh pht trin nui cy t bo gy ra hiu ng t bo bnh l nh to ra nhng m t bo khng l c nhiu nhn v nhng ht vi a eosin trong bo tng v trong nhn. 2. Kh nng gy bnh ca virus Bnh si l 1 bnh pht ban truyn nhim v gy dch do virus si gy nn. 2.1. S lan truyn ca virus trong c th Virus si xm nhim vo ng h hp trn hoc c th vo mt v nhn ln cc t bo biu m v m bch huyt k cn. Qua t nhim virus mu tin pht ngn virus c c phn tn n m bch huyt xa hn. S nhn ln ca virus ng h hp v kt mc gy nn nhng triu chng nh: s mi, ho khan, au u, vim kt mc, st v du hiu Koplick nim mc ming. Nhim virus mu xy ra cui thi k bnh lm cho virus phn tn su rng hn na vo m bch huyt v lm pht ban ngoi da. Virus si cng nhn ln v ph hy i thc bo v lympho bo gy nn suy gim min dch nht l min dch qua trung gian t bo v qu mn mun. S suy gim min dch tr em mc bnh si c vai tr quan trng trong c ch nhim lao hoc cc vi khun khc sau si (lao s nhim, vim ph qun phi sau si,...) 2.2. Dch t hc Bnh si l mt trong nhng bnh d ly nht, lu hnh vng mt dn s cao, thnh thong li pht sinh thnh dch, ngi ln thng qua mt ln mc bnh.

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Bnh ly trc tip qua ng h hp v nim mc mt. Ly nht thi k khi pht v trong khi pht ban. Tr em trn 6 thng tui, min dch do ngi m truyn cho ht, lc tnh cm th tng rt cao. Bnh si trn ton th gii u do mt ging virus c nht v bn vng gy nn. Min dch thu c sau khi khi bnh bn vng sut i, nhng trng hp mc bnh ln th hai rt him. 3. Chn on phng th nghim 3.1. Phn lp v xc nh virus Phn lp virus t nc ra hng v mu 48 gi trc khi ban xut hin v 30 gi sau khi ni ban. Dng cc bnh phm nui cy vo trong cc nui cy t bo cm th. Xc nh virus bng cch tm cc t bo khng l, cc tiu th a axit trong bo tng v trong nhn. Hoc dng phn ng trung ha trong cc nui cy t bo. 3.2. Chn on huyt thanh C th dng cc phn ng huyt thanh nh phn ng trung ha, phn ng kt hp b th. 4. Phng bnh v iu tr 4.1. Phng bnh - Cch ly bnh nhn si cho n khi khi bnh. - i vi cc tr em c tip xc vi bnh nhn si th nn dng huyt thanh ca ngi mc bnh si c cha lng ln gamma globulin c hiu chng si c th ngn nga khng cho bnh xut hin hay t nht cng c th lm cho s tin trin ca bnh nh i rt nhiu. - Phng bnh c hiu bng vaccine: l bin php phng bnh c hiu qu nht. C 2 loi vaccine: + Vaccine si cht: hin nay khng dng v phi tim nhiu ln, gy min dch yu v hay gy hin tng qu mn khi tim nhc li. + Vaccine si sng gim c lc: Vaccine c tim 1 mi x 0,5ml di da pha ngoi cnh tay. Hiu lc ca vaccine n 95%. Phn ng ti ch v ton thn nh sau khi tim chng 6 - 8 ngy. Khng nn tim vaccine si cho tr t thng tui qu v di 6 thng tr vn cn khng th si ca m truyn cho. Tt nht l tim cho tr 9 - 11 thng tui. Hin nay nc ta ang dng loi vaccine si sng gim c lc trong chng trnh tim chng m rng. 4.2. iu tr: Trong cc trng hp khng c bin chng, cha bnh ch nhm gii quyt cc triu chng. Cho tr nm ngh, n cc thc n d tiu. Ch dng thuc khng sinh khi c bin chng nhim khun th pht. Dng gamma globulin c hiu chng si iu tr, c tc dng rt tt.

IV. VIRUS HP BO NG H HP (Respiratory syncytial virus: RS virus)

1. Cc tnh cht chung ca virus Virus hp bo ng h hp (virus RS) l mt virus cha ARN 1 si, c kch thc khong 65 - 300nm, nhy cm vi ete v c mt cu trc ging nh cu trc

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ca cc virus cm v si. Virus RS c tt c c tnh ch yu ca cc Paramyxoviridae, ch khc l ch khng gy ngng kt hng cu v khng gy hp ph hng cu, cng nh khng c kh nng nhn ln trong phi g. Virus RS b mt hot lc mau chng pH 3,0. Virus RS nhn ln trong mt s nui cy t bo nguyn pht nh t bo lng bi ca ngi, t bo thn kh, v nui cy t bo thng trc nh Hela, Hep-2,v.v... Trong cc nui cy t bo b nhim virus hnh thnh hp bo, cc t bo khng l, mt s t bo nui b thng tn trn li v thoi ha ring bit. 2. Kh nng gy bnh cho ngi Virus RS gy bnh ng h, ch yu tr em nh vim ng h hp trn, vim ph qun, vim tiu ph qun, vim ph qun-phi v vim thanh qun ph qun. Nhng th bnh nng thng xy ra tr cn b. Bnh ngi ln thng nh v gii hn ng hhp trn. Virus RS lu hnh rng ri nhiu vng trn th gii. Chng lan truyn rt nhanh v mnh t ngi sang ngi qua ng h hp. 3. Chn on phng th nghim - Phn lp virus bng cch cy bnh phm l cht tit mi v hng ca bnh nhn vo cc nui cy t bo Hep-2, Hela, t bo lng bi ca ngi,v.v... Nu bnh phm c cha virus RS th sau 3 - 14 ngy s xut hin cc hp bo in hnh trong cc nui cy t bo b nhim virus. Ngi ta nh loi virus phn lp c bng phn ng kt hp b th v bng phn ng trung ha trong nui cy t bo. - Chn on huyt thanh bng cc phn ng kt hp b th v trung ha. 4. Phng bnh v iu tr Hin nay, cha c bin php phng bnh c hiu no c hiu qu, cng nh cha c thuc iu tr c hiu.

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FLAVIVIRIDAE
Mc tiu hc tp 1. Trnh by c cc c im ca virus vim no Nht Bn v virus Dengue. 2. Trnh by c kh nng gy bnh ca virus vim no Nht Bn v virus Dengue. 3. Trnh by c cc phng php chn on virus hc v phng bnh. H Flaviviridae gm nhiu virus arbo (Arbovirus: Arthropod - borne viruses), l nhng virus do cc loi cn trng tit tc ht mu nh mui hoc ve mang v ly truyn gia cc ng vt c xng sng (k c loi ngi). Cc virus arbo mun truyn bnh t ng vt c xng sng ny sang ng vt c xng sng khc phi c mi gii trung gian l cn trng tit tc (tr nhng trng hp khng bnh thng). Khi cn trng tit tc ht mu ng vt ang giai on nhim virus huyt, virus s nhn ln trong c th cn trng tit tc vi ngy (thi k nung bnh bn ngoi), nu cn trng tit tc ny t ng vt cm th khc th s truyn bnh cho ng vt . Cc virus ny nhn ln trong t bo cc loi cn trng tit tc ( mui, ve...) nhng khng gy bnh cho chng. Trong cc virus thuc h Flaviviridae gy bnh Vit Nam thng gp nht l virus vim no Nht Bn v virus Dengue.

I. VIRUS VIM NO NHT BN

Virus vim no Nht Bn (VNNB) l tc nhn gy bnh vim mng no- no ngi. Virus VNNB lu hnh khu vc Ty Thi Bnh Dng v ng Nam , trong c Vit Nam. 1. c im virus hc - Virus VNNB thuc h Flaviviridae. Virus c hnh cu ng knh t 30 n 35nm. Virus cha ARN mt si, nucleocapsid i xng hnh khi. C mt v bc bn ngoi capsit. - Virus b mt hot lc 560C trong 30 pht. Virus b ph hy bi ether v desoxycholat Natri. - Virus c th nhn ln trong phi g v trong cc nui cy t bo thn kh, thn ln, thn cu, thn chut t vng (hamster). - C nhiu loi ng vt cm th tt i vi virus VNNB nh chut nht trng mi v trng thnh, mo, ch con, nga, ln, di v nhiu loi chim. - Virus VNNB c ngng kt hng cu t, c th gy ngng kt hng cu ngng v hng cu g con 01 ngy tui. 2. Kh nng gy bnh 2.1. Dch t hc - cha virus VNNB l cc loi chim hoang di v nhiu loi ng vt khc nh ln, ch, tru b, nga... Vit Nam phn lp c virus VNNB t chim liu iu (Garrulax perspicollatus) v ln.

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- Cn trng tit tc mi gii l mui Culex tritaeniorhynchus, Culex pipiens, Culex gelidus... Vit nam tm thy virus ny mui Culex tritaeniorhynchus. Cc cn trng mi gii ny c th gy nhim virus cho cc loi gia sc v gia cm, a s l th n, tuy vy c th gy ra cc v dch vim no gia sc nh nga, ln. Cc loi gia sc v gia cm d th bnh no, cng u c giai oi nhim virus huyt. Chnh v vy, cc loi mui ht mu giai on ny s l iu kin gy thnh dch ngi. Bnh vim no Nht Bn c mt t l cao th n, t l mc bnh th n trn th nhim virus c biu hin lm sng l 300/1 n 200/1. Bnh thng xy ra vo nhng thng h thu, mi la tui, nhng ch yu l tr em. 2.2. Kh nng gy bnh ngi Khi mui mang virus t ngi, ngi s mc bnh, phn ln l th n, mt s trng hp mc bnh nh ch biu hin: nhc u, st nh v kh chu trong vi ngy. Th in hnh l vim no, thi k bnh t 4 n 21 ngy. Bnh bt u t t hoc t ngt vi st cao 39- 40 0C, nn, nhc u d di. V sau xut hin cc triu chng thn kinh, tm thn v thc vt. St cao km theo cng gy, co git, ri lon trng lc c, lit vn ng, ri lon h hp, ri lon thc, hn m... Virus gy thng tn rt trm trng v no, cc hch y no, v tiu no v sng ty. T l t vong cao. Sau khi khi bnh, nu c di chng thng l di chng tm thn nh thiu nng tm thn, tm thn sa st, gim tr tu.... v di chng thn kinh nh lit, ng kinh...vv... 3. Chn on virus hc chn on xc nh bnh vim no Nht Bn phi cn c vo phn lp virus v chn on huyt thanh v hnh nh lm sng rt c th nhm ln vi nhiu tc nhn virus gy vim no khc. 3.1. Phn lp virus Bnh phm l mu ca bnh nhn trong giai on st hoc l no ca t thi c tim vo no ca chut nht trng mi 1 - 2 ngy tui (chut ) l nhng sc vt rt nhy cm vi cc Arbovirus. Theo di 8-10 ngy, thy chut lit v cht. Sau nh loi virus bng phn ng trung ha vi cc khng huyt thanh mu trn chut . C th phn lp virus trn nui cy t bo mui C6/36 hay AP-61. 3.2. Chn on huyt thanh C th dng phn ng ngn ngng kt hng cu, phn ng kt hp b th. Cn ly huyt thanh bnh nhn 2 ln cch nhau 10 - 14 ngy tm ng lc khng th. Nu hiu gi khng th trong huyt thanh ly ln th hai tng ln r rt mi kt lun l nhim virus vim no Nht bn. Hin nay, thng dng phn ng MAC ELISA pht hin khng th IgM. Phn ng ny c nhy cao, c hiu cao v ch ly mu mt ln. 4. Phng bnh v cha bnh 4.1. Phng bnh chung - Tiu dit cha.

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- Tiu dit cn trng trung gian truyn bnh: Dit mui v b gy bng ha cht, bng tc nhn sinh hc,... - i vi ngi bnh v ngi lnh phi nm mn, trnh mui t. 4.2. Phng bnh c hiu Dng vaccine phng bnh vim no Nht bn. Hin nay nc ta ang dng loi vaccine bt hot, dng nc, tim phng cho tr em vng c dch lu hnh. 4.3. Cha bnh Cha c thuc iu tr c hiu. Cha cc triu chng l ch yu, chm sc bnh nhn, nng cao th trng, hn ch cc di chng.

II. VIRUS DENGUE

Virus Dengue l tc nhn gy ra bnh st Dengue c in v bnh st xut huyt Dengue (SXHD). Bnh do virus Dengue gy ra c nhiu ni trn th gii. 1. c im virus hc - Virus Dengue thuc h Flaviviridae, gm c 4 type huyt thanh virus Dengue gy bnh cho ngi: Virus Dengue type 1, virus Dengue type 2, virus Dengue type 3 v virus Dengue type 4. - Virus Dengue cha ARN mt si, nucleocapsid i xng hnh khi, c mt v bao bc nucleocapsid. Ht virus hon chnh c ng knh khong 50nm. B gen ca virus di khong 11kb (kilobases), gm c 3 gen m ha cc protein cu trc l nucleocapsid hoc protein li (C), protein mng (M) v protein v bc (E), v 7 gen m ha cc protein khng cu trc (NS). Th t m ha cc protein nh sau : 5- C prM (M) - E - NS1 - NS2A - NS2B - NS3 - NS4A - NS4B - NS5 - 3. - Virus nhy cm vi ether v natri desoxycholat. N d b ph hy bi nhit , ngay c nhit 40C. Virus trong huyt thanh bnh nhn gi -700C hay di dng ng kh 50C c th tn ti c 8 - 10 nm. Virus b ph hy bi tia cc tm trong vng vi pht. Virus bt hot bi focmol v mt ht tnh cht sinh min dch. - Cc t chc ca mui Aedes aegypti hoc mui Toxorhynchites trng thnh c cm nhim cao nht vi virus Dengue do mui l tc ch t nhin ca virus Dengue. Hin nay ngi ta tm c nhiu loi nui cy t bo thng trc mui c cm nhim cao vi virus Dengue nh C6/36, AP-61, TRA-284SF. - Virus Dengue c khng nguyn kt hp b th v khng nguyn ngng kt hng cu. Nhng virus ny gy ngng kt hng cu ngng v hng cu g con 01 ngy tui. 2. Kh nng gy bnh 2.1. Dch t hc - cha virus Dengue ch yu l ngi, ng vt linh trng (kh, vn, hc tinh tinh) v mui Aedes. - Cn trng tit tc mi gii l cc loi mui Aedes, ch yu l Aedes aegypti, mui ny thng trng ch nc trong v sch. Mui Aedes c th b nhim virus khi t bnh nhn giai on nhim virus huyt, virus vo nhn ln ng tiu ha trong c th mui v c tr tuyn nc bt lan truyn cho ngi v ng vt. Ty theo iu kin nhit bn ngoi m thi gian nung bnh bn ngoi ny di ngn khc nhau (thi gian nung bnh bn ngoi l thi gian virus nhn ln trong c

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th mui). Sau khi ht mu bnh nhn, nu nhit bn ngoi l 22 0C th sau 9 ngy l c th truyn bnh. Nh vy ngi v vi loi kh mt vi vng v mui hp li thnh vng nhim virus, nh m virus Dengue tn ti trong t nhin. - Bnh SXHD chim mt v tr quan trng trong cc bnh nhim trng gy dch vng ng Nam . Vit Nam, dch SXHD xy ra nhiu ni, nht l cc vng ng dn c thnh ph, ng bng v ven bin. Bnh xy ra quanh nm, nhng pht trin mnh vo nhng thng ma nhiu v nng. Bnh xy ra mi la tui nhng i tng cm th ch yu l tr em. 2.2. Kh nng gy bnh ngi Khi mui mang virus ( thi gian nung bnh bn ngoi) t ngi bnh thng, virus xm nhp c th qua ch t. Virus xm nhim v nhn ln trong cc t bo ca h thng mono - i thc bo, virus lu hnh trong c th cc t bo mono, cc i thc bo... Virus xm nhim gy thoi ha t bo trong cc t chc ca c th nh gan, lch, thn, c, no, t chc lin kt, nim mc rut,... Virus Dengue c th gy ra ngi cc bnh sau:

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2.2.1. St Dengue c in Sau 1 thi gian bnh t 3 - 14 ngy bnh bt u t ngt bng st c rt run, nhc u, au h mt khi nhn cu di chuyn, au lng, au c v khp. St tng nhanh ln 400C. Cc hch bch huyt c, mm trn rng rc v bn thng sng to. Sau 48 - 96 gi h st nhanh chng v ra m hi nhiu, trong cng thi gian ny xut hin ngoi ban c bit dng si, mi u khu tr cc u chi, sau lan ra ton thn. Nhng trng hp khng c bin chng thng khi. Thi k hi phc sc khe ko di nhiu tun l. 2.2.2. St xut huyt Dengue Bnh khi pht t ngt vi cc triu chng ging th Dengue c in. Theo T chc Y t Th gii, tiu chun chn on SXHD / Dengue vi hi chng sc (Dengue shock syndrome: DSS) l: st cao, cc biu hin ca xut huyt, gan to v suy tun hon km theo gim tiu cu v c c mu. - C ch sinh bnh hc: Tui, tnh trng min dch, chng virus v tnh trng di truyn ca bnh nhn c coi l nhng yu t nguy c quan trng nht c lin quan ti SXHD nng v t vong. Tc gi S.B. Halstead a ra mt gi thuyt v c ch sinh bnh hc gii thch SXHD / DSS. Theo S.B. Halstead th mt yu t nguy c ca sc l trong bnh nhn c cc khng th Dengue mc khng trung ha virus dn ti mt nhim trng th pht do min dch tng cng. Nh vy, th ch c mt s ngi b nhim ln hai vi mt tp Dengue khc mi b SXHD / DSS. Gi thuyt ny cho rng bch cu n nhn l ni pht trin u tin ca virus Dengue. Mc khng th d ng di mc trung ha kt hp vi virus lm tng kh nng thc bo, khi virus vo trong t bo th phc hp ny b v ra v lm cho virus nhn ln mnh. nng nh ca bnh c lin quan ti s lng bch cu n nhn b nhim v tit vo mu cc cht trung gian, cc cht ny tc ng ln thnh mch, lm thot huyt tng qua mao mch v dn n hi chng sc trong SXHD / DSS. 3. Chn on virus hc 3.1 Phn lp virus Bnh phm l mu, huyt thanh, huyt tng bnh nhn (ly lc st cao) hoc ly t chc gan, lch, no t thi. Phn lp virus Dengue bng k thut tim vo cc t chc ca mui trng thnh (tim vo lng ngc hoc tim vo no mui Toxorhynchites), hoc cy vo cc loi nui cy t bo c ngun gc t mui nh C6/36, AP-61, TRA-284SF hoc cc loi nui cy t bo c ngun gc t ng vt nh LLC-MK2, Vero. Sau pht hin s hin din ca virus Dengue trong c th mui v trong cc t bo nui bng k thut khng th hunh quang trc tip. Nu phn ng dng tnh, tip tc nh type virus bng k thut min dch hunh quang gin tip vi cc khng th n dng Dengue 1, Dengue 2, Dengue 3, Dengue 4. 3.2. Pht hin cc khng nguyn ca virus Dengue C th pht hin cc khng nguyn ca virus Dengue trong cc m ca t thi, trong mu v trong dch no ty bng k thut min dch m ha hc, min dch hunh quang hoc min dch enzyme (ELISA). 3.3 Pht hin cc on ARN ca virus Dengue C th pht hin cc on ARN ca virus Dengue trong mu v trong dch no ty bng k thut khuch i gen (RT- PCR: Reverse transcriptase - Polymerase

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chain reaction). K thut ny c nhy cao gip chn on nhanh v sm bnh st xut huyt Dengue.

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3.4. Chn on huyt thanh Pht hin khng th khng Dengue trong huyt thanh bnh nhn bng phn ng c ch ngng kt hng cu, phn ng kt hp b th. Cn phi ly huyt thanh kp, mu 1 ly lc bnh mi khi pht, mu 2 ly sau mu 1 t 5 ngy n 2 tun tm ng lc khng th. Hin nay, thng dng phn ng MAC ELISA pht hin khng th IgM ca virus Dengue xut hin vo ngy th 5 ca bnh. Phn ng MAC ELISA c u im l ch cn ly mu mt ln trong tun u ca bnh (ngy th 5 - 7). 4. Phng bnh v cha bnh 4.1 Phng bnh Bin php c hiu qu nht phng bnh l tiu dit mui Aedes aegypti bng mi phng php c th thc hin c. Do cha c vaccine phng bnh nn vic gim st v dit mui l ng li chnh trong phng chng SXHD hin nay. Vaccine Dengue ang c nghin cu v th nghim. 4.2. Cha bnh Cha c thuc cha c hiu, ch cha triu chng v nng cao sc khng. i vi th nng c sc, cp cu phi khn trng, ch yu l b nhanh khi lng tun hon bng dch truyn, tt nht l plasma v khi c chy mu ni tng th truyn mu.

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VIRUS DI (RABIES VIRUS)

Mc tiu hc tp 1. Trnh by c mt s tnh cht virus hc ca virus di. 2. Nu c kh nng gy bnh ca virus ny. 3. Trnh by c nguyn tc iu tr d phng v cch phng bnh di. Bnh di l mt loi vim no -mng no, thng gy t vong. Tc nhn gy bnh l virus di thuc ging Lyssavirus, nm trong h Rhabdoviridae.

I. CC TNH CHT CA VIRUS

Virus di c hnh gy ging nh hnh vin n, di 130-240nm v ng knh 70-80nm. Nucleocapsid i xng hnh xon c, cha ARN 1 si, c mt v ngoi mang cc gai ngng kt hng cu, bn cht l glycoprotein. Virus di nhn ln c trong nhiu h thng t bo ngi v ng vt (t bo tin pht, cc t bo lng bi...) Virus nhn ln trong bo tng, cc nucleocapsid tp trung li thnh tng m li ni bo to thnh cc ht vi, cn gi l tiu th Negri. Virus di km bn vng, n nhy cm vi ete, 56 0C / 3 pht b kh hot tnh. Virus di ch c mt typ huyt thanh. Nm 1882, Louis Pasteur tim truyn vo no th chng virus di phn lp c t no ng vt b di v nhn thy tnh cht gy bnh ca n yu i khi gy ly cho ch bng ng di da, chng virus ny c gi l chng virus c nh, khc vi cc chng virus di ng ph mi phn lp c t ch b di. Chng virus di c nh Chng virus di ng ph Thi k bnh Ngn, c nh (7 ngy) Thay i, ngn hoc di ty theo v tr vt cn v c lc ca virus Kh nng gy bnh Yu Mnh To tiu th Negri Khng C (80-90%) Dng sn xut vaccine c Khng

II. KH NNG GY BNH

1. Sinh bnh hc Vius thng xuyn c mt trong h thng thn kinh trung ng v h thng thn kinh ngoi bin ca ng vt b di. Cc t bo thn kinh hch giao cm b bong ra lm cho tuyn nc bt b nhim virus. Virus di xm nhp vo c th thng l qua cc tn thng da(vt cn, vt co xc, vt lim...). Virus di khng truyn qua c da lnh, nhng nim mc nguyn vn vn c th cho virus xm nhp c. Virus nhn ln ti ch vng xm nhim (c, t chc lin kt v nht l cc t bo Schwann ca cc dy thn kinh cm gic) v tin dc theo dy thn kinh hng tm ti ty sng ri ln h thng thn kinh trung ng, nhn ln v ph hy cc t bo thn kinh ca v no, v tiu no, ty sng. Cui cng virus theo ng dy thn kinh ly tm i ti tuyn nc bt. S thi virus ra ngoi theo tuyn nc bt bt u t 1 n 2 ngy trc cc triu chng u tin v ko di mt vi ngy sau ng vt. Cc m khc c th b nhim virus nh thn, lch, phi. Thi k bnh lin h mt thit vi v tr vt cn, vt cn cng gn thn kinh trung ng th thi k bnh cng ngn, do ngi ta cn c t thi gian bo

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v ngi b cn trc khi virus xm nhp ti h thn kinh. B nhiu vt cn, vt cn su, vt cn vo vng c nhiu thn kinh th bnh rt nng.

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2. Dch t hc - cha: l cc ng vt mu nng gm cc ng vt hoang di nh co, ch rng, ch si, chn... lu hnh bnh di bnh t nhin, hoc cc ng vt nui trong nh nh ch, mo...Ngoi ra cn thy virus di tuyn nc bt ca mt vi loi di nh loi di ht mu (di qu) v di n cn trng. Di thng mang bnh di th n v c th o thi virus mt thi gian di. ng vt b di, virus c mt trong h thng thn kinh, nc bt, nc tiu, hch bch huyt, sa, v tn ti rt ngn trong mi trng bn ngoi. Cho nn ng vt b bnh di l cha duy nht ca virus v vic nhim virus gin tip rt him. - ng ly: Bnh di truyn t ng vt ny sang ng vt khc v sang ngi qua vt cn, co, xc trn da ...c dnh nc bt b nhim virus di. - i tng cm nhim: ngi v ng vt mu nng d mc bnh. nc ta, bnh di lu hnh hu ht cc a phng do nui ch nhiu nn s ngi b ch di cn nhiu, s ngi cht v bnh di cng chim mt t l ng k. 3. Biu hin lm sng 3.1. Bnh di ngi Bnh di l mt bnh vim no - mng no, thi k bnh thay i ty theo v tr vt cn v c lc ca virus, c th t 1-3 thng. Thi k khi pht thng c mt hi chng nhim trng nh, cm gic bt thng ch cn, tm thn khng n nh. Thi k ton pht c 3 th lm sng: - Th co git: hay gp nht, du hiu c trng nht l s nc, s gi. Bnh nhn thng cht t ngt do co tht cc c h hp. - Th lit: khi u l lit nh mt bn hoc 2 bn hoc lit ton thn (hi chng Landry), lit cc c h hp lm bnh nhn cht. - Th mt tr: tin trin thng nguy him. Khi bnh di ln cn th cht, iu tr ch c tc dng phng nga. 3.2. Bnh di sc vt Triu chng l con vt khng bnh thng, b n hoc n nhng th khng n c nh o rch, chi...Ting ch sa bin thnh ting r v cc dy thanh m b lit, nc di ri, con vt chy rong khp ni, cn x nhiu, ung nc nhiu. V sau xut hin ri lon h hp, ch gy v lit ri cht vo khong ngy th 5-7.

III. CHN ON PHNG TH NGHIM

V chn on vi sinh vt bnh di i vi ngi, ngi ta t lm bi v vic ly bnh phm rt kh khan, mc khc n cuing khng c ngha trng iu tr. Chn on thng c tin hnh ch yu cc ng vt ngi b di cn ngi cn ngi. 1. Xt nghim m bnh hc Bnh phm l no ca ng vt nghi b di. Tm cc ht vi trong bo tng ca t bo thn kinh, gi l tiu th Negri, nhng c 10-15% khng tm thy tiu th Negri. 2. Tm khng nguyn virus Phng php min dch hunh quang trc tip cho php tm ra cc khng nguyn virus di trong vi gi (cc ht vi bt mu hunh quang trong bo tng) trong cc t bo thn kinh, nht l sng Ammon hoc tiu no. y l phng php tt nht. 3. Phn lp virus Phn lp virus bng cch tim truyn cht nghin no hoc nc bt vo no chut nht con, sau pht hin cc khng nguyn virus di trong cc t bo no chut nht con b cht bng phng php min dch hunh quang. Ngi ta cn thng phn lp virus trong cc nui cy t bo. Chn on huyt thanh khng c gi tr trong chn on.

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IV. IU TR D PHNG
1. X tr vt cn i vi cc vt cn, c nhiu phng php x l khc nhau vi mc ch l lm sch virus hay lm mt hot lc ca virus. X tr vt cn cng nhanh cng tt, c th x tr vt cn nh sau: - Ra bng dung dch x phng 20% hoc bng dung dch Benzalkonium clorua 20% - h vt thng - Gy t ti ch bng Procain c tc dng lm chm qu trnh tin trin ca virus - Khi vt cn ch nguy him, tim huyt thanh chng d di da pha trn vt cn. 2. iu tr d phng bng vaccine Vic x dng vaccine chng di vi mc ch iu tr d phng l c th c v c hiu qu nu iu tr ng sau khi nhim bnh. Cc vaccine th h th nht nh vaccine Fermi simple c sn xut bng cch nui cy virus trong cc m thn kinh ca ng vt ln (ty hoc no) gy ra cc vim no d ng trm trng, c th dn ti t vong. Ngy nay, ngi ta x dng cc vaccine lm t no chut nht mi nh vaccine Fuenzalida khng cha thnh phn d ng nn loi vaccine ny khng gy ra cc bin chng nguy him nh cc vaccine th h u tin. Ngi ta cng sn xut vaccine di trn cc nui cy t bo lng bi ca ngi nhng s lng vaccine t ch dng cho nhng i tng cn thit vi mc ch d phng. Hin nay hai loi vaccine phng di c s dng ti Vit Nam l Fuenzalida (do Vit Nam sn xut) v Verorab (do Php sn xut). Khi ng trc mt ngi b ch cn th nn p dng mt s bin php sau: - Nu ch cn xong ln cn di hoc cht, hoc mt tch th tim khng huyt thanh di sau iu tr bng vaccine ngay. - Nu ch cn xong, ch vn sng bnh thng, nhng vt cn gn thn kinh trung ng hoc su v nhiu ch th phi tim huyt thanh ri th tim vaccine ngay, v theo di ch, nu sau 10 ngy ch vn bnh thng th ngng tim. - Nu ch cn xong vn bnh thng, vt cn xa thn kinh trung ng th tim huyt thanh khng di v theo di ch, nu c du hiu di ch th phi tim vaccine ngay. - Trng hp ch con cn phi tim ngay v tim liu v cc du hiu di ch con khng r rng nh ch ln.

V. PHNG BNH
1. ngi i vi nhng ngi v ngh nghip m h b bt buc gn cc ng vt c th bt ng ln cn di (nh th y, th lt da th, gc rng, nhn vin phng th nghim, chn an v nghin cu) ngi ta s dng mt loi vaccine chng di vi mc ch d phng. 2. ng vt Gm nhiu bin php, cn phi c thc hin ng b v nghim tc nh tim vaccine bt buc cho ch, mo vng c bnh di lu hnh, tiu dit cc con ch b di, bt gi ch chy rong...

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CC VIRUS SINH KHI U

Mc tiu hc tp 1. Trnh by c c im chung ca cc virus sinh khi u. 2. Nu c mt s virus sinh khi u ngi v kh nng gy bnh ca chng.

I. KHI NIM V VIRUS SINH KHI U

1. i cng v khi u ng vt c im ca m ng vt l s pht trin iu ha v gii hn ca t bo. Trong mt hin tng him, mt t bo c th that khi nhng b buc iu ha bnh thng v phn chia mt cch khng kim sot, to nn mt khi lng m khng bnh thng. Nhng khi lng nh th gi l khi u. Khi u c phn loi theo cch thc pht trin thnh 2 nhm: u lnh tnh v u c tnh. Nhm khng xm ln m xung quanh c gi l lnh tnh, chng pht trin bng cch di ch t bo k cn v him khi git cht c th tr trng hp chng xy ra no. U c tnh gi l ung th xm ln v git cht t bo xung quanh lc chng pht trin, chng cng phng thch vo mu v bch huyt nhng t bo c kh nng to nn nhng tiu im khi u mi gi l di cn. U lnh tinh v c tnh u c gi bng mt t tn cng l oma. Ung th to bi t nhng lp t bo gi l carcinoma, ung th pht sinh t m lin kt hoc mch mu gi l sarcoma. Nhiu ung th c gi tn theo t bo c hiu m chng to thnh. V d hepatoma hnh thnh t hepatocyte gan, melanoma t melanocyte da v lymphoma t lympho bo. Mt ngoi l trng hp leukemia pht sinh ty xng to thnh bch cu. 2. Virus sinh khi u Virus sinh khi u ln u tin c V. Ellerman v O.Bang khm ph nm 1908 lc chng minh bnh bch cu g (ALV) c th truyn cho g khc bi dch lc ca cc t bo mu. Nm 1911, P. Rous pht hin sarcoma g cng c th truyn mt cch tng t nh th v khng nh tc nhn truyn bnh l 1 virus, hin nay gi virus sarcoma ca Rous (RSV), l mt Retrovirus. Lc u s khm ph virus gy khi u g t c quan tm, nhng vo nm 1932 lc R. Syope cho thy papilloma th cng do mt virus gy nn th s lu gia tng. S quan tm tng ln nm 1936 lc J. Bitter chng minh virus u v chut (MTV) c th truyn qua sa t chut m sang chut con. Cng trnh ca Bitter cho ta hiu nhiu phng din quan trng ca virus ung th: mt ng vt b nhim virus ung th lc tre th c th khng pht trin khi u cho n lc trng thnh, mt virus sinh khi u khng phi lun lun hnh thnh khi u, nhiu nhn t nh mi trng xung quanh, sinh l ca vt ch cng quan trng. Chut ci nhim MTV lc nh pht trin khi u vi tn s cao lc mang thai. Nhng virus sinh khi u khm ph cho n nay phn ln l nhng virus ADN: poxvirus, adenovirus, herpesvirus, papovavirus, virus vim gan B v ch tm thy mt nhm virus ARN l Retrovirus. Nhng Retrovirus sau khi xm nhim t bo th ARN c sao m thnh ADN ri tch hp vo nhim sc th ca t bo. Nn ngi ta c th khng nh s sinh khi u l mt thuc tnh lin quan n ADN ca virus.

II. MT S VIRUS SINH KHI U

1. Virus ADN sinh khi u

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Hin nay cha mt virus no c khng nh chc chn l virus gy khi u ngi v khng th lm thc nghim virus gy khi u trn ngi. Tuy nhin mt s virus c nhng bng chng v dch t hc, huyt thanh hc hoc pht hin c genom hay khng nguyn ca chng t cc t bo khi u ngi. 1.1. Virus polyoma Virus c gi tn nh th v lc tim vo chut mi th lm pht sinh nhiu loi khi u. Chng c tm thy rng ri trong qun th chut hoang di cng nh chut phng th nghim v ly truyn qua cht phn tit v cht bi tit. Virus polyoma l thnh vin ca h Polyomaviridae, c cu trc i xng hnh khi, ng knh 42-45 nm, cha phn t ADN hai si. Virus ny tm thy nui cy t bo thn kh, chng to nn khi u chut t vng v bin i nhng t bo chut t vng in vitro. Mt s thnh vin khc ca Polyomavirus nh virus BK (BKV) v virus JC (JCV) gy nhim trng ph n mang thai, gy nhim trng bm sinh cng nh gy nhim trng ti hot nhng bnh nhn ghp thn, ghp ty xng, ngi cho c th l ngun nhim trng. JCV gy bnh no nhiu tin trin (Progressive multifocal leucoencephalopathy: PML) c th km cc lymphoma hoc cc u c tnh. Chn on virus c th nhum t chc b tn thng (thn, no), phn lp virus t nc tiu hoc t chc b bnh, chn on huyt thanh hc tm khng th c hiu. 1.2. Virus Papilloma ngi (human papilloma virus: HPV) Virus papilloma thuc h Papillomaviridae, cu trc virion ca virus papilloma tng t nh virion polyoma nhng hi ln hn v cng cha phn t DNA 2 si. Hin nay c t nht 60 type c bit. Nhng thnh vin ca HPV to nn u nh lnh tnh (mn cc) nhiu ng vt k c ngi, mn cc ngi thng bin mt t nhin, nhng cng c th pht trin thnh ung th biu b da, nht l nhng ngi c h thng min dch b tn thng. Virus papilloma typ 16 v18 c coi l gy ung th c quan sinh dc ph n, nh thnh m o, m o ngoi, c t cung. nam gii, HPV gy ung th dng vt. V chn on, k thut lai ADN hin nay thng c dng xc nh virus trn t chc tn thng. 1.3. Herpesvirus 1.3.1. Epstein-Barr virus (EBV) c Epstein v cng s pht hin nm 1964 trong nui cy t bo ca mt lymphoma Burkitt. EBV l Herpesvirus hng t bo lympho B ngi, ph bin khp ni trn th gii. EBV c xem l cn nguyn ca cc bnh ung th khc nhau: - Lymphoma Burkitt: l u t bo lympho B, xy ra c bit tr em. y l mt bnh tn pht Trung Phi v New Guinea v xy ra l t khp ni trn th gii. In vitro, t bo ca lymphoma pht trin thnh dng t bo dng nguyn bo lympho gi nhng c tnh ca t bo gc. ADN v khng nguyn nhn ca EBV c tm thy nhng t bo u lympho Burkitt. ADN v khng nguyn nhn ca EBV c tm thy nhng t bo u lympho Burkitt, ch mt on ngn ADN ca EBV tch hp, cn phn ln ADN ca virus ny dng vng kn v tn ti nguyn sinh cht t bo. iu kh khn chng minh rng EBV gy ung th ngi l vng dch t c t l nhim EBV rt cao, nhng t l ung th li rt thp. V bnh sinh, nhim trng EBV lm mt s iu ha min

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dch, tng sinh t bo lympho B lin quan n hot ha gen c-myc. C s chuyn dch gen c-myc t nhim sc th s 8 n nhim sc th s 14, 22 hoc 2, s chuyn dch ny a gen sinh khi u t bo ti cnh v tr khi ng (promoter) ca gen globulin min dch, lm mt s iu ha ca gen, lm hot ha c-myc a n s tng sinh v khng bit ha t bo lympho Burkitt. - Tng bch cu lympho nhim trng: thng gp tr trn 10 tui v nhng thanh nin b nhim virus tim tng lc nh cc nc phng Ty, khng gy thnh dch. Mt s trng hp bnh xy ra tr ln tui v ngi trung nin nhim EBV tin pht (cha b nhim EBV khi cn nh) do ly qua hn nhau (virus c trong tuyn nc bt) hoc bng ng truyn mu, ghp c quan khi ngi cho b nhim virus. - U t bo lympho nhng ngi suy gim min dch: nhim trng EBV tim tng nhng ngi c huyt thanh dng tnh c kim sot bi c ch min dch qua trung gian t bo. nhng ngi ghp c quan hoc b AIDS do mt s kim sot ny xy ra hin tng nhim trng ti hot khng triu chng, mt s trng hp gy nn bnh tng sinh bch cu lin quan EBV. - Bnh Hodgkin: trong nhng nm gn y, ngi ta tm ra nhng bng chng EBV ng vai tr mt phn trong gy bnh Hodgkin. 60% bnh nhn Hodgkin c ADN v protein ca virus trong cc Reed-Sternberg v t bo li ca khi u. Tuy nhin n cha chng minh EBV l bnh nguyn ca bnh Hodgkin, cn nghin cu thm v mi lin h ny. - U lympho bo T: ADN ca EBV c tm thy vi nhng t l thay i trong nhng loi u lympho bo T khc nhau. Cho n by gi, ngi ta thy r EBV c th gy nhim trng t bo lympho T, nhng vai tr ca virus trong c ch bnh sinh u lympho bo T vn ang cn c bn ci. - Carcinoma mi hu: y l mt loi ung th thng gp n ng ca mt vi nhm sc tc Trung Quc. Bnh nhn c mt chun khng EBV cao. Khi u gm c nhng t bo biu m thm nhim lympho. EBV hin din trong nhng t bo biu m. N cm ng lymphoma lc tim vo kh sc hoc kh c. - Ngoi ra, gn y c nhng bo co v mi lin quan gia EBV vi mt s ung th khc nh ung th biu m tuyn c, ung th tuyn nc bt, ung th d dy, c bit l ung th c trn. Tuy nhin mi lin quan ny cn c nghin cu thm. 1.3.2. Herpes simplex virus (HSV) HSV typ 2 (HSV-2) c coi l virus c th gy ung th cho ngi da trn hai loi bng chng chnh: - V dch t hc: nhng ph n nhim trng h tit niu HSV-2 c t l ung th c t cung cao hn l khng nhim HSV-2. Nhng ph n b bnh ny chun khng HSV thng tng hn l khng nhim HSV-2. - V sinh hc phn t: ngi ta tm thy ADN v protein ca HSV-2 trong cc t bo ung th c t cung. HSV-2 c th gy ra chuyn dng t bo in vitro. Phn ln cc pht hin ny c th c gii thch bng gi thuyt HSV-2 gy nhim trng n nhng bnh nhn c hot ng tnh dc sm lc tui nh. 1.4. Virus vim gan B (hepatitis B virus: HBV) Ung th biu m gan nguyn pht (hepatoma) thng gp nhiu nhng ngi nhim HBV hn nhng ngi khng nhim. Mi lin quan ny rt r chu Phi v chu , ni c t l nhim HBV v ung th gan nguyn pht cao. HBV m ng cho ung th t bo gan, mc d mt s bnh nhn ung th t bo gan khng

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c bng chng ca nhim HBV. C th tm thy ADN ca HBV v khng nguyn b mt ca HBV cc t bo ung th gan. S tch hp ADN ca HBV c l kch hot gen sinh ung th ca t bo. 2. Virus ARN sinh khi u: Retrovirus 2.1. Cu trc Retrovirus c c im cha enzyme reverse transcriptase (enzyme sao chp ngc) bin i ARN thnh ADN. Nhiu Retrovirus gy sarcoma, bnh bch cu, lymphoma v carcinoma g v cc ng vt c v. Ngoi ra, Retrovirus cn gm nhng thnh vin khng sinh khi u. V cu trc, Retrovirus mang nhng nt c th nh virus HIV. Virion c v bc v nhy cm vi ete, ng knh khong 100 nm, capsid i xng hnh khi cha ARN 1 si. Genom l mt phn t gm 8000 n 10.000 nucleotit. Nt c th ca Retrovirus l sau khi xm nhim t bo ARN si n c sao m thnh ADN b sung si kp (complementary DNA: cDNA). Sau khi hnh thnh, ADN b sung tch hp vo nhim sc th ca t bo v c gi l provirus cha nhng gen cn thit cho s sao chep ca virus. Virus c sao chp ng thi vi nhim sc th nn genom ca virus c truyn li cho t bo con, cho nn s nhim trng mt c th c th ko di sut i. Lc provirus c biu hin, RNA v nhng thnh phn protein ca virus xut hin trong t bo cht ri n tp trung mng t bo, virus c hnh thnh, m chi ri thot ra khi t bo. Tri vi nhiu virus khc, Retrovirus khng git cht t bo lc qu trnh sao chp hon tt, thay vo qua biu hin gen ngoi sinh n thay i phenotyp ca t bo vt ch. 2.2. Retrovirus gy khi u ngi Nhng virus ny ngoi nhng gen cn thit cho s sao chp cn cha thm mt hoc nhiu gen ph. Mt trong nhng gen ph ny gi l tat (transacting transcriptional activator) m ha mt protein lm kch ng s bin i nhng gen khc ca virus v c th mt vi gen ca t bo. Mt c im khc ca Retrovirus ngi l tnh hng lympho T4 h tr (CD4). Mc d nhng t bo khc c th b nhim, T4 h tr c u tin chn la v chng bnh gy nn lin quan n qun th t bo ny. n hin nay ngi ta phn lp c hai loi Retrovirus gy bnh bch cu v u lympho bo (human T cell leukemia virus, hay cn gi l: human T cell lymphotropic virus : HTLV) ngi l HTLV I v HTLV II. C hai bnh virus ny u lin quan n bnh bch cu (leuxemi) v u lympho bo (lymphoma). 2.2.1. HTLV I (hay HTLV1) Phn ln HTLV I cm ng bnh bch cu hoc lymphoma u lin quan n lympho T4: lympho T4 c dng khng l nhiu nhn hoc nhiu tiu thy, mt s trng hp khng c s thay i hnh thi r rt. In vitro, s nhim HTLV I lm cho nhng lympho T bnh thng bin i hoc mt chc nng min dch. Bnh bch cu hoc lymphoma do HTLV I gy nn thng mang mt hnh thc ung th c bit gi l bnh bch cu / lymphoma t bo T trng thnh (Adult T cell leukemia/lymphoma: ALT) c qu trnh xm nhim, thng tng bch cu mu, nhim trng c hi, phn na trng hp do thm nhim bch cu. HTLV I cng lin quan n bnh bch cu/ lymphoma t bo T c qu trnh mn tnh (15-20%). Nhng trng hp ALT in hnh hu nh lun lun c HTLV I dng tnh. 2.2.2. HTLV II (hay HTLV 2) HTLV II u tin c phn lp t mt dng t bo mt bnh nhn vi mt bin th ung th bch cu tua v c th phn bit vi HTLV I bng min dch phng

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x cnh tranh. Sau , virus c phn lp nhiu bnh nhn vi hnh thc mn tnh hn v ung th t bo. Nhn chung HTLV II c 55% tng ng v nucleotide vi HTLV I v ch c mt t khc bit v tnh cht sinh hc. Nhng test huyt thanh khng th phn bit khng th ca 2 virus. nhiu vng nc M, virus HTLV chim u th dn nghin l HTLV II.

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CC VIRUS VIM GAN

Mc tiu hc tp 1. M t c cc c im virus hc, tnh cht gy bnh ca cc virus gy vim gan 2. Trnh by c chn on phng th nghim , cch phng bnh v iu tr cc virus vim gan Bnh vim gan c cp trong y vn c Trung Quc v t thi Hy Lp c, nhng mi n nhng nm 60 ca th k trc cc virus gy vim gan mi dn dn c pht hin v nghin cu su hn trong sut 4 thp k qua. Hin nay cc virus vim gan c bit gm: Virus vim gan A ( HAV), vim gan virus B (HBV), virus vim gan C (HCV), virus vim gan D (virus Delta) v virus E (HEV)

I. VIRUS VIM GAN A ( HEPATITIS A VIRUS: HAV )

Virus vim gan A thuc h Picornaviridae, v thuc typ 72 ca Enterovirus. 1. c im sinh hc 1.1. Cu to Virus trng thnh c kch thc 27nm ht virus khng c v ngoi, c cu to gm 4 polypeptid c khi lng phn t khc nhau c k hiu t VP 1- VP4. Capsid ca virus c i xng hnh khi gm 32 capsome, genome ca virus cha ARN mt si c trng lng phn t 2,25x106 dalton. 1.2. khng So vi cc Enterovirus khc, HAV tng i n nh vi nhit , nhit 600C virus ch b bt hot mt phn, khi un si 5 pht lm bt hot tan b virus. HAV khng vi dung mi hu c nh ether, axit. N b bt hot khi tip xc vi formaldehyt 1/4000, chlorua Hg 1mg/lit/ 30 pht hoc chiu tia cc tm. 1.3.Nhn ln ca virus HAV nhn ln trong nguyn tng t bo gan, t bo b xm nhim gii phng ht virus vo mu gy nhim virus mu ri c thi qua mt vo trong phn. HAV c th nhn ln nhiu t chc nui cy t bo khc: - T chc nui cy t bo mt lp nguyn pht kh. - T bo thn thai kh. - T bo chuyn dng ca phi kh. Trong cc t chc nui cy t bo, s nhn ln ca virus ny khng gy nn hiu ng t bo bnh l. Tuy nhin s hin din ca HAV trong t chc nui cy t bo c th theo di bng nhiu k thut khc nhau: - Knh hin vi in t. - Min dch hunh quang. - Min dch phng x (RIA) v min dch lin kt enzyme. 1.4. Min dch

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Khng th khng HAV (anti-HAV) c xc nh trong huyt thanh bnh nhn trong giai on bnh cp tnh khi hot tnh enzyme aminotransferase mu tng cao v virus c thi ra trong phn. p ng min dch sm ch yu l khng th lp IgM, khng th ny c th tn ti trong nhiu thng. Trong giai on hi phc antiHAV ch yu thuc lp IgG, anti-HAV c tnh cht bo v bnh nhn chng li s ti nhim trng. 2. Kh nng gy bnh 2. 1. Dch t hc S truyn bnh xy ra gia ngi v ngi do n thc n v ung nc b nhim phn. S lan rng vim gan do HAV thng xy ra nhng ni ng dn, i sng thiu v sinh. Bnh xy ra khp ni trn th gii, dch vim gan do virus A c tnh cht a phng, tn pht hoc cc v dch nh, cc v dch thng xy ra vo cui thu v u ma ng. Bnh gp mi la tui, tr em bnh lnh tnh hoc khng c triu chng, tui cng ln nhim trng cng nng. 2. 2. Gy bnh cho ngi Sau khi n thc n b nhim HAV. Chng nhn ln ng tiu ha n nh v gan, gy virus mu v khi pht s nhim trng. Thi gian bnh 14-50 ngy pht bnh vi chn n mt mi, st, nhc u, vng da xut hin 1-2 tun sau khi b bnh, nc tiu m mu, gan to au, enzyme aminotransferase tng cao trong mu. Bnh thuyn gim vo tun th 4 hoc th 5 vi s bin mt cc triu chng, thi k hi phc cn 1- 2 thng sau. Sau khi khi bnh vim gan do HAV khng thy c tnh trng vim gan mn tnh. 3. Chn on phng th nghim 3. 1. Chn on trc tip - HAV c bi xut trong phn bt u t 1- 2 tun trc khi b bnh v ko di n 4 tun do vy c th tm virus trong phn bng th nghim min dch phng xa hoc min dch knh hin vi in t.. - Phn lp virus trn t chc nui cy t bo c thc hin trc y trong nghin cu, hin nay khng thc hin v nui cy virus ny rt kh khn. - Cc k thut sinh hc phn t nh dot blots, lai RNA, RT-PCR c th xc nh c RNA ca HAV trong gan, trong huyt thanh v phn ca ngi bnh 3. 2. Chn on huyt thanh hc Xc nh khng th anti-HAV trong huyt thanh bnh nhn bng cc k thut min dch phng x (RIA), min dch lin kt enzyme (ELISA), c bit tm khng th anti-HAV lp IgM. 4. Phng bnh v iu tr 4. 1. Phng bnh - V sinh ngun nc ung, v sinh thc phm. - Ci thin iu kin sng . - Pht hin v cch ly bnh nhn b bnh. Min dch th ng bng ch phm globulin min dch cha khng th antiHAV. Ch phm ny dng cho ngi tip xc thng xuyn vi bnh nhn b virus

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vim gan A. Globulin min dch cha anti-HAV lm gim nh chng bnh hoc bnh ch th bn lm sng. Min dch ch ng bng vaccine git cht ang c dng nhiu nc, c bit dng cho nhng ngi i n nhng vng c dch lu hnh, vaccine sng gim c c sn nhng cha c dng ngi. 4. 2. iu tr: Cha c thuc tr c hiu. Ch yu l ngh ngi, tit thc v c th dng cc loi sinh t.

II. VIRUS VIM GAN B (HEPATITIS B VIRUS: HBV)

Virus vim gan B thuc h Hepadnaviridae (Hepatotrophic DNA virus) v c xp l Hepadnavirus typ 1 . 1. c tnh virus hc 1. 1. Cu to Ht virus vim gan B nguyn vn c dng hnh cu c ng knh 42nm (tiu th Dane). V ngoi ca HBV c th tm thy trong huyt thanh bnh nhn dng hnh cu 22 nm v dng hnh si, c hai dng ny ging nhau v c tnh sinh ha v vt l. Chng c cu to bi 7- 9 polypeptide c trng lng thay i t 19.000-120.000 dalton v cc thnh phn carbohydrate. Cu trc v ca virus vim gan B mang khng nguyn b mt gi l HBsAg.

Hnh 1. Cu trc ca HBV Cu trc 42nm, hnh cu l ht virus HBV hon chnh Cc tiu th hnh cu 22nm (17-25nm) v dng hnh si bt ngun t v ngoi ca ht virus Li nucleocapsid c i xng hnh khi, kch thc 27nm, b mt ca li mang khng nguyn li HBcAg bn trong cha ADN polymerase, ADN ca virus v mt protein ha tan mang tnh khng nguyn l HBeAg. ADN ca HBV dng vng hai chui gm mt chui di v mt chui ngn, mang 4 on gen chnh - an tin gen S v S: Ch yu m ha cho cc protein ca v. - on gen C m ha cho cc cu trc HBcAg v HBeAg.

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- on gen P m ha ADN polymerase. - on gen X m ha cho mt protein c chc nng hot ha cho (transactivation). 1. 2. S nhn ln ca virus Virus vim gan B cha nui cy c trn t chc nui cy t bo, virus c th sao chp c trn t bo gan ngi. Nhng nghin cu gn y nhn thy virus vim gan B c qu trnh sao chp ngc nh Retrovirus. Sau khi xm nhp vo trong t bo gan, ADN ca virus lm thng tin to ra hai si ARN thng tin nh ARN polymerase ca t bo, t ARN thng tin ny c bc bi cc protein ca li, tip n ADN polymerase ca virus s sao m ngc hnh thnh ADN ca virus. Khi ADN ca virus c hnh thnh th hai si ARN thng tin t ph hy. Li cha ADN s nhn v ngoi khi c y ra qua h thng li ni bo hoc b golgi ra ngoi. Ton b ADN ca virus c th tch hp vo ADN ca t bo gan, hnh thi ny c tm thy trong ung th t bo gan (Hepatocellular carcinoma) tuy nhin khc vi cc retrovirus, s tch hp vo chromosome t bo khng phi l mt bc bt buc trong chu k sao chp ca cc virus thuc ho ny. T bo gan trng thi ny vn cn tit ra HBsAg nhng khng HBeAg, qu trnh sao chp ca virus trong giai on ny ngng hoc rt chm. 1. 3. Cc khng nguyn ca virus vim gan B Ba thnh phn khng nguyn ca virus vim gan B c m t : 1.3.1. Khng nguyn b mt ca virus (HBsAg) Khng nguyn ny hin din trong huyt thanh di dng hnh si hoc hnh cu ng knh 22nm. Cc cu trc ny l vt liu v virus HBV. Tt c HBsAg u mang khng nguyn nhm chung a v mt trong cc khng nguyn di typ (subtype) c hiu d v y hoc w v r (adw, ayw, adr, ayr....). Cc khng nguyn di typ ny khng lin h n c lc ca virus nhng chng c gi tr v mt dch t hc. Khng nguyn HBsAg xut hin sm trong huyt thanh bnh nhn b bnh v gim sau 2-3 thng, nhng trng hp HBsAg (+) tn ti ko di trong huyt thanh bnh nhn trn 4 thng sau khi b bnh cp l du hiu bnh c th chuyn qua mn tnh. Khng th tng ng ( k hiu anti-HBs) xut hin 1- 3 thng sau khi HBV xm nhp vo c th, thng sau khi HBsAg ht trong huyt thanh. Anti-HBs c vai tr chng li s ti nhim HBV. V vy khng nguyn HBsAg l thnh phn c s dng iu ch vaccine phng bnh vim gan B . 1.3.2. Khng nguyn li HBcAg L thnh phn khng nguyn do cc protein to nn b mt ca li nucleocapsid ca HBV, khng nguyn ny khng tm thy trong huyt thanh ngi bnh vi cc k thut thng thng. N c tm thy trong nhn t bo gan. HBcAg kch thch c th to khng th tng ng Anti-HBc, khng th ny c trong huyt thanh ngi bnh kh sm v tn ti kh lu. 1.3.3. Khng nguyn HBeAg L thnh phn protein ha tan c trong li ca virus vim gan B. HBeAg xut hin trong huyt thanh sm ngay trong thi k bnh trong vim gan cp do virus B. S tn ti ko di ca khng nguyn ny trong huyt thanh bnh nhn c ngha

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bnh din tin mn tnh. HBeAg kch thch to khng th anti-HBe c trong huyt thanh. 2 . Kh nng gy bnh 2. 1. Dch t hc Bnh vim gan do HBV xy ra khp ni trn th gii. Theo c tnh c trn 350 triu ngi mang HBsAg trn th gii to nn cha chnh ca virus HBV ngi. T l ngi mang HBsAg khc nhau cc quc gia, Hoa K v cc nc Ty u t l ny l 0,1- 0,5% t l ny cao hn nhiu nc phng ng v cc nc nhit i. Bnh nhn b bnh vim gan do HBV v ngi lnh mang HBsAg u c kh nng truyn bnh. Bnh ly ch yu qua truyn mu v cc sn phm ca mu, ng tim chch qua kim tim, bm tim, c bit nhng ngi nghin thuc chch bng ng tnh mch. Nhiu ng ly truyn khc cng chim v tr quan trng nh ng sinh dc, qua nhau thai. Ngi ta tm thy HBV hin din trong nhiu loi cht dch c th bnh nhn gm dch mng bng, nc bt, nc mt, dch khp, sa m, tinh dch. 2. 2. c im gy bnh Thi k bnh ca HBV di 40- 150 ngy. Bnh xy ra mi la tui, cc biu hin lm sng vim gan B cp tng t nh vim gan virus A. Bnh c th din tin nng a n hoi t gan cp v hn m gan. Sau vim gan cp do HBV c khong 6-10% ngi ln, v n 25-50% tr em din tin n vim gan mn v x gan. Theo T chc Y T Th Gii 80% ung th t bo gan nguyn pht do nhim trng HBV mn tnh.

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3. Chn an phng th nghim 3. 1. Chn on trc tip - Tm tiu th Dane trong huyt thanh bnh nhn bng knh hin vi in t. - Tm cc khng nguyn c trong huyt thanh bnh nhn nh HBsAg, HBeAg bng nhiu k thut khc nhau nh in di min dch i lu, k thut c nh b th, K thut ngng kt hng cu th ng ngc, k thut sc k min dch, k thut min dch phng x (RIA) hoc min dch lin kt enzyme (ELISA). Trong k thut ELISA l k thut thng dng hin nay. - K thut lai ADN dng xc nh ADN ca HBV trong cc mu sinh thit t bo gan hoc trong huyt thanh bnh nhn. K thut PCR cng c s dng rng ri chn on bnh, c bit n c ch khi dng k thut nh lng theo di s tng hoc gim lng virus mu trong iu tr khng virus bnh vim gan B mn. 3. 2. Chn on huyt thanh hc Tm s hin din cc khng th tng ng trong huyt thanh ngi bnh nh anti-HBs; anti-HBc gm lp IgM hoc IgG, anti-HBe. Cc k thut min dch phng x ( RIA) v min dch lin kt enzyme ( ELISA) l cc k thut thng dng hin nay cho chn on huyt thanh hc 4. Phng nga v iu tr 4. 1. Phng bnh 4.1.1. Bin php chung - Kim tra k ngi cho mu. - Tit trng k dng c y t, kim tim, bm tim ch dng 1ln. Thc hin an ton lao ng khi lm vic vi bnh phm mu v cc ch phm mu. - Trong cc n v thn nhn to cn pht hin bnh nhn b nhim HBV v dng dng c ring. 4.1.2. Phng bnh c hiu - Min dch th ng + Dng ch phm globulin min dch ngi bnh thng t hiu qu v cha lng anti-HBs thp. + Ch phm gamma globulin ngi c hiu vi vim gan B (HBIg) cha lng ln anti-HBs. Dng ch phm ny cho thy c hiu qu lm gim tn s mc bnh. i tng dng cc loi globulin min dch gm: + Nhng ngi b nhim mu hoc huyt thanh c cha virus vim gan B do tai bin. + Tr s sinh m m mang khng nguyn HBsAg. - Min dch hot ng Vaccine phng bnh vim gan B u tin l thnh phn HBsAg hnh cu ly t huyt tng ngi lnh mang HBsAg lm tinh khit v tiu dit HIV. Vaccine phng bnh vim gan B th h hai c sn xut bng cng ngh sinh hc. Ch

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phm Recombivax HB Hoa K c sn sut bng phng thc ny a vo s dng nhiu nc, hiu qu phng bnh cao v an ton. Tim vaccine nn thc hin cho tt c tr em cn b, thiu nin v cho nhng i tng c nguy c cao mc bnh vim gan B (nhn vin y t tip xc vi mu, bnh nhn chy thn nhn to, ngi nghin thuc chch tnh mch v tr s sinh c m mang HBsAg).

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4. 2. iu tr Cha c mt thuc khng virus no hiu qu hon ton cho nhim trng do HBV. Nhiu thuc khng virus gn y c dng iu tr vim gan virus B mn gm: - Interferon: Dng interferon bnh nhn vim gan B mn cho thy c th lm chm tin trin ca bnh. - Lamuvidine: c dng trong iu tr vim gan B mn cho thy lm mt HBeAg trong huyt thanh, v ci thin tn thng t bo gan. Tuy nhin khi dng ko di HBV tr nn khng do t bin. - Adefovir: c hiu qu nh lamuvidine trong iu tr vim gan mn - Ribavirin v adenin arabinoside t c hiu qu .

III. VIRUS VIM GAN C ( HEPATITIS C VIRUS: HCV)

Virus vim gan C c xp vo h Flaviviridae. 1. Tnh cht ca virus Virus vim gan C c dng hnh cu ng knh trung bnh khong 35- 50nm, v bn ngoi l glycoprotein. Genome ca virus cha ARN mt si mang cc gen m ha cho nucleocapsid ca li, cho protein mng, glycoprotein ca v v protein cn thit cho s sao chp ca virus. Hin nay c t nht 6 genotype ca virus ny c bit trn c s phn tch chui axit nucleic ca genome virus. Virus sao chp v nhn ln dng t bo gan ca ngi hoc vn, nhng mc sao chp ca virus thp. 2. Dch t hc Virus vim gan C truyn bnh qua ng truyn mu hoc cc sn phm ca mu, c bit gp nhng bnh nhn tip nhn cc yu t ng mu trn ln t nhiu ngi. Cc ng ly truyn khc nh ngi nghin chch thuc qua ng tnh mch, qua da, qua tip xc sinh dc, qua dng c thm phn mu... 3. Tnh cht gy bnh HCV gy vim gan cp v c khuynh hng tr thnh mn hu ht cc c nhn b nhim trng. Trn m hnh nhim trng thc nghim vn cho thy trong vim gan C cp c t hoi t cc b t bo gan trong giai on u, km thm nhim nh t bo lymphocyte trong t chc tn thng. ARN ca virus c tm thy t chc gan v tn ti nhiu tun. Vim gan cp do HCV khng a n suy gan cp, tr phi bnh xy ra nhng c nhn c nhim trng mn vi HBV trc. Khong 50- 70% vim gan C cp din tin n mn. C ch tn thng gan vim gan C mn tnh khng nhng do virus m cn lin h n bnh l t min dch ca c th. Bin chng ca vim gan C mn cui cng a n x gan 20 - 25% trng hp v ung th t bo gan. 4. Chn on Th nghim min dch lin kt enzyme (ELISA) c th xc nh khng th trong huyt thanh bnh nhn v y l k thut thng dng hin nay. Th nghim western blot (RIBA) xc nh khng th c dng khi ELISA cho kt qu nghi ng. Khng nguyn dng trong c hai loi k thut trn l cc protein ti t hp ca HCV. Tu theo cc thnh phn protein khng nguyn c dng trong cc th nghim m

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c cc th h ELISA1, ELISA2, v ELISA3, cng tng t nh th c RIBA1, RIBA2 v RIBA3. Cc th nghim th h sau c nhy tt hn.

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Hnh 2. Thnh phn khng nguyn trong cc th nghim chn on HCV Trong vim gan cp khng th (Anti-HCV) dng tnh chm sau hai thng, 60 - 80% dng tnh sau 6 thng, khng th HCV dng tnh 80% trng hp vim gan mn K thut khuch i chui gen (RT-PCR) xc nh ARN ca HCV trong huyt thanh ngi bnh, k thut RT-PCR nh lng xc nh lng virus mu c dng cho vic theo di kt qu iu tr 5. Phng v iu tr 5.1. Phng bnh Hin nay cha c vaccine phng bnh cho virus vim gan C. Phng s ly nhim bng kim tra mu k lng nhng ngi cho mu, m bo khng nhim virus HCV trong tim chch, tim truyn.... 5.2. iu tr Interferon c dng trong iu tr vim gan do HCV. Interferon cho thy lm gim nhanh amino tranferaza trong huyt thanh, ngoi ra ribavirin cng c th nghim v cho kt qu t r hn Interferon.

VI. VIRUS VIM GAN D ( HEPATITIS D VIRUS: HDV)

Virus vim gan D cn c tn l virus vim gan delta, hay virus vim gan khim khuyt v virus ny cn s h tr ca HBV hoc virus vim gan sc (Woodchuck hepatitis virus - WHV) pht trin. 1. Tnh cht ca virus vim gan D Ht virus trng thnh l mt tiu th hnh cu ng knh khong 35nm, genome ca virus cha ARN mt si, genome ca HDV cn cha protein cu trc gi l khng nguyn (HDAg) ca HDV. V ngoi cng ca ht virus l thnh phn v ngoi (HBsAg) ca HBV. HDV c th nhim trng t bo gan nguyn pht ca vn. Khi vo bn trong t bo HDV c th sao chp m khng cn c virus HBV. ARN v khng nguyn HDAg c tm thy trong nhn ca t bo. Virus t hp thnh ht virus khi cc thnh phn ARN, HDAg tng tc vi HBsAg ca HBV. 2. Tnh cht gy bnh 2.1. Dch t hc

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ng truyn bnh ca virus vim gan D tng t nh HBV, gm qua tip xc tnh dc, ng tim chch, truyn mu v cc sn phm ca mu. Nhim trng HDV thng tm thy nhng bnh nhn mang khng nguyn HBsAg mn .

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2.2. Lm sng Vim gan do HDV c th xy ra ng thi vi nhim trng do virus HBV, hoc c th b bi nhim trn bnh nhn b vin gan B mn. Triu chng tng t vi vim gan do cc virus khc, s nhim trng ng thi c hai virus HDV v HBV thng d a n vim gan trm trng hn so vi ch nhim trng do virus HBV. Mt s t trng hp s bi nhim ca virus HDV khng lm thay i din tin ca nhim trng mn do HBV, trong trng hp ny du hiu nhim trng do HDV ch cho thy s tng khng th anti-HD lp IgM. 3. Chn on Ngoi xc nh s c mt ca nhim trng do HBV, nhim trng do virus HDV c chn on bng tm khng nguyn HDV trong huyt thanh bng th nghim RIA hoc ELISA, trong nhim HDV mn khng nguyn HDAg thng m tnh. Khng th anti-HD xc nh bng th nghim RIA hoc ELISA. C th dng cc k thut sinh hc phn t tm ARN ca virus 4. Phng bnh v iu tr 4.1. Phng bnh Phng nhim trng bng vaccine v cc bin php phng khc i vi HBV s c hu hiu trong phng nga vim gan do virus D, v HDV khng th nhn ln c khi khng b nhim trng do HBV. nhng bnh nhn mang HBsAg cn phi hn ch chuyn mu, khi cn thit phi nhn truyn mu mi truyn v kim tra k ngun mu. 4.2. iu tr V iu tr cha c thuc iu tr cho HDV, interferon c dng trong iu tr HBV cng c dng cho c trng hp vim gan phi hp cho hai virus ny.

V. VIRUS VIM GAN E ( HEPATITIS E VIRUS: HEV)

Nhim trng do virus vim gan E trc y c cho l vim gan do virus khng A- khng B truyn qua ng tiu ha, virus ny trc y c xp vo h Caliciviridae, hin nay c tch ring v ang c xp loi trong thi gian ti. 1. c im virus hc Virus c dng hnh cu, ng knh khong 27-34nm, khng c v bn ngoi, genome ca HEV cha ARN chui n. Virus c th gy nhim trng t bo gan nguyn pht, t bo thn kh, s nhn ln ca HEV trong cc nui cy t bo ny c th xc nh bng nhum min dch hunh quang hoc bng lai ADN. Virus gy vim gan cc ng vt linh trng ngoi ngi. 2. c im gy bnh 2.1. Dch t hc Nhim trng do HEV xy ra nhiu quc gia nhit i v bn nhit i nh HAV, bnh truyn qua ng tiu ha v xy ra thnh dch lin h n thc n, nc ung b nhim bn. 2.2. Lm sng

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Thi gian bnh 15-40 ngy, trung bnh 35 ngy, triu chng lm sng tng t nh cc vim gan khc. Vim gan cp c th a n suy gan cp, c bit th nng thng gp ph n c thai, t vong do vim gan E nhm ny cao 20- 40%. Khng c bng chng tin trin mn tnh bnh nhn vim gan E. 3. Chn on Nhiu k thut chn on c dng xc nh vim gan HEV gm - Knh hin vi in t min dch xc nh ht virus trong phn. - Tm anti-HEV lp IgM hoc IgG vi nhiu k thut huyt thanh hc gm ELISA (IgG, IgM), western blot ( IgM/ IgG). - Xc nh ARN ca virus trong phn v trong huyt thanh bng k thut RTPCR. 4. Phng v iu tr Cha c vaccine phng bnh cho virus ny, ch yu l v sinh ngun nc ung. Cha c thuc khng virus c hiu.

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VIRUS HIV/ AIDS ( HUMAN IMMUNODEFICIENCY VIRUSES)

Mc tiu bi ging 1. M t c cc c dim virus hc, c ch suy min dch ca virus HIV. 2. Trnh by c dch t hc, chn on phng th nghim v cch phng nga v iu tr nhim trng HIV Virus HIV (gm HIV1 v HIV2) thuc vo h Retroviridae, ging Lentivirus. Nhng virus ny c dng hnh cu, c v, kch thc ht virus 80-100nm v ng knh, genom cha ARN chui n. Qu trnh sao chp axit nucleic ca chng (ARN) to ra chui i cDNA (ADN b sung) qua trung gian ca enzyme reverse transcriptase. S hnh thnh dng tin virus chromosom ca t bo vt ch l mt bc bt buc trong chu k pht trin ca chng. I. TNH CHT VIRUS HC 1. c im cu to Di knh hin vi in t virus c dng hnh cu, cu to gm v ngoi v li capsit trong. V ca virus to bi 72 nm gai l cc glycoprotein 120 ( gp120) ca v ngoi, thnh phn ny l receptor gn vo receptor CD4+ ca t bo v mt protein xuyn mng glycoprotein 41 (gp 41). Li ca virus hnh cu cha cc protein cu trc ca gen Gag, trong capsit cha 2 phn t ARN ging nhau, v cc enzyme ADN polymerase. Cu trc chi tit ca virus v genom ca HIV nh hnh sau

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Hnh 1. Hnh nh minh ho cu to virus HIV hon chnh Genom ca HIV c kch thc 9,8kb ( kilobase), gen m ho ca cc HIV c 3 on ln l on gen gag m ho cho s tng hp cho cc protein cu trc ca li ca virus, gen pol m ho cho s hnh thnh cc protein enzyme ca virus ( integrase, reverse transcriptase/RNase, protease) v on gen env m ho cho s hnh thnh cc glycoprotein ca v virus (gp 120, gp 41). Nhiu on gen nh m ho cho cc protein c vai tr trong qu trnh nhim trng v pht trin ca virus trong t bo. Bng 1. Cc protein ca HIV v chc nng ca n
Cc protein Gag Kch thc P25 P17 P9/ P6 Polymerase (Pol) Protease Integrase V Tat Rev Nef Vif Vpr 0 gp 41 p 14 p19 p27 1 P10 P 32 gp12 bo Protein b mt ca v Protein xuyn mng ca v Protein hot ha iu ha biu hin mRNA ca virus Cn cho s sao chp ca virus Lm tng tnh nhim trng ca virus P66/p5 m enzyme gn cDNA virus vo genom t Chc nng Protein cu trc capsid Protein nn Protein kt hp vi RNA/ Gip virus m chi ra ngoi t bo enzyme sao chp ngc enzyme x l cc protein sau dch

251 Vpu( ch c HIV1 ) Vpx( HIV2 ) Tev ch c p23 p18 p15 p26 Gip cho s sao chp ca virus Gip phng thch virus ra ngoi Gip cho virus trong nhim trng Hot ha gen Tat v Rev

2. Tnh cht khng HIV b bt hot nhit 56-60C trong khong 30pht, n cng b bt hot vi cc ho cht git khun thng thng nh dung dch natri hypochlorid 0,5%, cn etanol 70%, v povidone - iodine, pH < 6 hoc > 10 bt hot HIV1 trong khong 10 pht. Trong cc t chc nui cy virus nhit phng dng HIV t do c th xc nh n 15 ngy, nhit 37C c th n 11 ngy. 3. Chu k sinh hc ca HIV trong t bo xm nhp vo t bo, gp120 ca HIV gn vo cc receptor ca t bo: phn t CD4+ v receptor CCR5 i vo t bo. Trong nguyn tng ca t bo ARN si n ca virus c sao m ngc tr thnh ADN chui i qua trung gian ca enzyme reverse transcriptase, ADN chui i to thnh c chuyn vo nhn t bo v tch hp vo nhim sc th ca t bo, gi l tin virus (provirus), qua trung gian ca enzyme integrase. ADN tin virus l bn nn (template) cho vic to ra ARN ca virus mi v ARN thng tin cho s tng hp protein ca virus. S t hp v hnh thnh virus mi xy ra mng t bo. y ARN mi to thnh ca virus c gi trong cc protein ca li capsid. Capsid tip nhn c v ngoi khi ht virus i qua mng t bo bng phng thc y t t ht virus ra ngoi nh s ny mm cy (budding). Qu trnh nhn ln ca virus trong t bo tm tt trong s sau

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CD4 Gn vo CD4

Nguyn tng

Nhn

nst t bo

provirus CCR5 RNA T hp RNAtt Dch m Gii phng virus mi Protein Hnh 2. s minh ho chu k nhn ln ca HIV trong t bo S pht trin ca virus nui cy t bo to ra hiu ng t bo bnh l ty thuc vo cc chng phn lp, nhiu chng to ra cc hp bo in hnh (syncytium formation) v gy cht t bo, tuy nhin mt s chng khng to nn hnh nh ny. Tnh cht to t bo bnh l c dng phn loai cc phn type sinh hc ca HIV1. cDNA Sao m

II. C CH SUY MIN DCH V DCH T HC

1. C ch suy min dch do HIV Suy min dch do nhim trng HIV ch yu do s gim qun th t bo lymphocyte T c mang phn t CD4 b mt (T bo CD4+), s ph hy lm gim qun th t bo ny lin h n Cc tc dng t bo bnh l trc tip do virus v cc protein ca n trn t bo CD4+ gm: Ph hy t bo, Tc dng trn t bo gc, Tc dng trn sn xut cytokine, Tc dng trn in tch cc t bo, Tnh d v gia tng ca cc t bo. S nhim HIV t bo gy nn cht t bo c chng trnh ( apoptosis ). Ph hy t bo do s gn ca gp120 ln t bo CD4+ bnh thng: Hiu ng ADCC, Cc lymphocyte T c t bo ( CTL). Cc tc dng c ch min dch ca cc phc hp min dch v cc protein ca virus ( gp120, gp41,Tat.) Tc dng c t bo chng li CD4 ( gm cc t bo CD4+ v t bo CD8+) Cc yu t c ch ca t bo CD8+

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Cc t khng th chng li t bo CD4+ S ph hy t bo CD4+ do cytokine Hi chng suy gim min dch tm thy u tin nm 1981 nhng

2. Dch t hc ca nhim trng HIV

ngi nghin chch thuc. 1983 L. Montagnier Php phn lp c virus v gi n l LAV (lymphadenopathy-associated virus), R. Gallo Hoa k cng thi gian cng nui cy c virus t bnh nhn b suy gim min dch v phn tch v sinh hc phn t ca n v t tn virus ny l HTLV III (Human T cell leukemia virus type III), cc virus ny hu nh rt ging nhau. n 1986 U ban quc t v danh php virus thng nht tn gi cho cc virus ny l HIV ( Human immunodeficiency virus ). Hin nay c khong 30 triu ngi b nhim HIV trn ton th gii, c 2 tp virus gy bnh l HIV1 v HIV2. HIV1 gy bnh gp khp ni trn th gii, trong khi HIV2 ch gp mt s ni Ty phi. HIV1 c chia thnh cc di tp ( subtype) t A - J v di tp O v HIV2 thnh di tp t A - G. Nhim trng HIV mt nc hoc mt vng a l thng do mt vi di tp ni bt. ng truyn bnh ca HIV1 v HIV2 hon ton ging nhau 2.1.Truyn qua tip xc sinh dc ng sinh dc l mt trong cc ng chnh m virus HIV truyn t bnh nhn b nhim HIV qua ngi lnh, nhng t bo b nhim virus v virus t do trong dch m o v trong tinh dch u c kh nng truyn bnh. Kh nng truyn ph thuc vo nhiu yu t gm s ln tip xc sinh dc vi ngi b nhim, s c mt ca cc bnh nhim trng sinh dc nh giang mai, lu, nhim trng herpes, cc vim nhim v xy xt ng sinh dc.....cc yu t ny lm tng s ly nhim HIV 2.2. Truyn qua mu Virus truyn qua mu c th dng t do, trong t bo lymphocyte, hoc trong i thc bo. ng ly truyn ny thng gp do truyn mu, hoc cc sn phm ca mu c virus, do tim chch, nh rng, hoc cc tai bin ngh nghip do cc vt sc nhn nh dao, kim tim, ng nghim c dnh mu ngi bnh. Cc tn thng nng trn da c th l ng vo ca virus khi tip xc vi mu b nhim HIV. 2.3. Truyn t m cho co

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HIV c th truyn t m sang con trong thi k mang thai, trong khi sinh v sau khi sinh. HIV thng truyn qua con trong giai on sau ca thai k. Tuy nhin, truyn qua thai nhi sm khong 8 tun sau khi c thai cng c kho st.

III. CHN ON PHNG TH NGHIM

Cc th nghim dng chn on HIV v mt nguyn l khng khc vi chn on cc virus khc: Tm virus hoc khng nguyn ca chng, sau tm khng th vi virus, axit nucleic ca virus cng c th c xc nh cc phng th nghim cao cp. Chn on phng th nghim virus HIV khng phi l cc xt nghim khn cp. Khng th vi cc thnh phn ca HIV ch c th xc nh c khong 6-8 tun sau khi b nhim trng HIV, do vy chn on nhim trng HIV trong giai on sm ch bng cch tm khng nguyn hoc axit nucleic ca virus. S sau cho thy ng hc ca cc du n huyt thanh hc ca HIV.

Hnh 3. S biu th cc du n huyt thanh trong chn on HIV 1. Xc nh khng nguyn virus Tm protein 24 (p24) bng th nghim ELISA dng khng th n dng. 2. Phn lp virus Cy lymphocyte bnh nhn vo nui cy lymphocyte bnh thng, hiu ng t bo bnh l xut hin sau 7- 10 ngy nui cy vi s xut hin cc hp bo in hnh ( syncytial formation), tuy nhin mt s chng khng to hp bo khi nui cy. 3. Xc nh khng th Nhiu th nghim c dng pht hin khng th HIV trong huyt thanh bnh nhn. Cc th nghim sau c dng rng ri cc phng th nghim xc nh khng th vi virus HIV 3.1. Th nghim ELISA Vi nhiu k thut v khng nguyn khc nhau trong khng nguyn c gn trn ging, enzyme c th c gn vo khng khng th (k thut ELISA gin tip), hoc khng th gn enzyme ( k thut ELISA cnh tranh), hoc khng nguyn gn enzyme (K thut ELISA kiu sandwich). nhy ca th nghim ny t 97,5 n 100%, khi th nghim ELISA dng tnh cn phi dng th nghim Western blot chn on khng nh.

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Phn ng ELISA gin tip khng khng th gn enzyme khng th gn enzyme tranh chp Phn ng ELISA kiu sandwich Khng nguyn gn enzyme Hnh 4. S minh ho cc kiu k thut ELISA chn on HIV 3.2.Th nghim Western blot K thut ny c th xc nh c khng th vi cc protein c hiu ca virus, y l th nghim c ga tr khng nh nhim trng HIV, kt qu ng tnh khi c t nht 2 bng protein ca v ( gp 160, gp120, hoc gp 41) c th thm cc bng protein ca gen gag v pol hoc khng, phn ng m tnh khi khng cc tiu chun trn. 4. Xc nh axt nucleic ca virus Th nghim khuch i chui gen PCR dng xc nh ADN hoc ARN ca virus trong c th ngi bnh, k thut ny cng cho php nh lng virus trong mu bnh nhn Phn ng ELISA

IV. PHNG NGA V IU TR

1. Phng nga Kim tra ngi cho mu, x l mu trc khi chuyn loi tr HIV. Dng c y t m bo v trng, bm tim, kim tim ch nn dng mt ln. Cn khuyn co cho nhn vin trc tip lm vic vi bnh nhn hoc vi mu bnh nhn v cc ni quy an ton, trnh s ly nhim do bt cn. Ngn cm tim chch ma ty v t nn mi dm, gio dc v an ton tnh dc Hin nay cha c vaccine hiu qu phng bnh.

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2. iu tr Vic nghin cu cc thuc chng virus HIV nhm vo cc khu trong chu trnh pht trin ca virus: c ch s gn v vi ca virus vo mng t bo, c ch s ci o v vo bn trong t bo ca nucleocapsid, c ch qu trnh sao m ngc, c ch s gn cDNA ca virus vi chromosome ca t bo ( s hnh thnh provirus ), c ch qu trnh sao m mRNA, qu trnh dch m, c ch s t hp ca virus, v qu trnh y virus ra khi t bo. Nhiu ch phm sinh hc nh cc khng th v cc ha cht c th nghim trong phng th nghim. Hin nay hai nhm thuc c sn dng trong iu tr nhim trng HIV/AIDS l - Cc thuc c ch enzyme reverse transcriptase (RT) nh azidothymidine, dideoxycytidine, didanosine, lamuvidine... - Cc thuc c ch enzyme protease nh saquinavir, ritonavir, indinavir... S phi hp cc thuc trn lm gim lng virus mu nhanh, ko di i sng bnh nhn, hn ch c cc bin chng virus khng thuc.

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CC VIRUS GY BNH KHC

Mc tiu hc tp 1. Trnh by c tnh cht virus hc, dch t hc, tnh cht bnh, chn on phng th nghim v phng nga nhim trng corona gy SARS. 2. M t cc c trng v tnh cht virus, dch t, tnh cht gy bnh, chn on virus v phng bnh do virus rubella. 3. Trnh by cc tnh cht virus hc, tnh cht gy bnh, chn on phng th nghim v phng bnh nhim trng do hantavirus

I. CORONAVIRUS GY BNH CHO NGI

y l nhm virus tm thy chim v cc ng vt c v, chng ging nhau v hnh thi v cu trc ha hc. Cc Coronavirus ca ngi gm Coronavirus chng 229E v Coronavirus chng OC43, hai virus ny gy nhim trng h hp trn nh- bnh cm lnh. Nm 2003 mt chng virus mi ca h ny c tm thy gy bnh vim phi nng, ly truyn mnh v c t l t vong cao ngi c gi l Coronavirus gy SARS (SARSCoV: severe acute respiratory syndrome-associated coronavirus). Bi ny ch trng n corona gy SARS ngi. 1.Tnh cht ca virus: di knh hin vi in t virus c bao ngoi v hnh thi a dng, c ng knh t 60 -130nm trn b mt ca virus c cc gai glycoprotein nh hnh vng nim (corona), cc gai ny gip cho virus bm vo cc receptor ca t bo vt ch v xm nhp vo t bo. Nucleocapsid bn trong hnh xon cha ARN ln c chiu di 27-32 kb m ha cho cc thnh phn cu trc v chc nng ca virus. Hu ht cc virus corona ch gy nhim t bo ca loi tc ch t nhin ca chng, ring corona gy SARS (SARS-CoV) c th nhim trng nhiu loi t bo nh t bo thn kh vero, t bo khi u i trng ngi, chng gy hiu ng t bo bnh l sau 2-4 ngy

Hnh 1b. SARS-CoV knh HV Hnh 1a. cu trc SARS-CoV 2. Dch t hc in t Thng 2 nm 2003 bnh vim phi do virus nng (SARS) xut pht t Qung ng, Trung quc ri nhanh chng lan ra cc nc k cn gm Vit Nam, Hng cng, Singapour, Thi lan Canada.. n 24-25 thng 3/2003 cc nh khoa hc ca M v c cng b xc nh c virus gy bnh l mt virus thuc Coronavirus v gi tn l virus corona gy bnh SARS (SARS-CoV). V dch ln n nh vo thng 5 v chm dt vo u thng 7/2003. Tng s c 29 quc gia b nh hng vi s ngi b bnh l 8422 vi s ngi cht l 902

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Virus corona gy SARS v cc corona ngi ly truyn bnh ch yu qua ng h hp t cc git cht tit, ngoi ra cn c th truyn qua tip xc trc tip, cc dng c kh dung, ni soi ph qun. Ngi bnh virus thi ra trong phn ko di nhiu tun l, c th l ngun ly bnh qua ng phn ming. Ngi ta tm thy cc corona rt ging vi SARS-CoV ca ngi ng h hp mt s loi chn, do vy virus corona gy SARS c th l mt virus ng vt truyn cho ngi. 3. Lm sng Corona gy SARS gy nn bnh vim phi nng do virus ngi v ly lan thnh dch. bnh c thi gian bnh t 2 n 10 ngy, triu chng sm gm st, au c nhc u, triu chng h hp bt u xut hin t 3-7 ngy vi ho khan v kh th. Nhiu bnh nhn biu hin thm nhim phi trn X quang v suy h hp xy ra nhanh chng, phn ln bnh nhn cn phi h hp h tr. T l t c tnh t 14-15%, ngi ln tui t vong t n 50%. 4. Chn on phng th nghim Phn lp virus t bnh phm cht tit ng h hp, mu, phn trn nui cy t bo ( t bo thn kh). Tuy nhin ch c phng th nghim c mc an ton sinh hc cao (mc 3) mi c php nui cy virus ny. K thut chn on c dng hin nay l RT-PCR xc nh vt liu RNA ca virus, n cho kt qu nhanh. Chn on huyt thanh gm k thut min dch hunh quang hay ELISA xc nh IgM v IgG, nhng khng th thng xut hin mun sau 2-3 tun. 5. Phng bnh v iu tr Pht hin sm v cch ly bnh nhn b bnh l bin php hu hiu phng ly nhim cho ngi xung quanh, nhn vin y t v ngi tip xc vi bnh nhn cn phi eo khu trang, o qun bo v ng quy nh, x l tt cht thi ngi bnh. Quy nh ca quc t hin nay bnh SARS cn phi thng bo dch v kim dch quc t. Hin nay cha c vaccine phng bnh. Hin cha c thuc khng virus SARS-CoV c hiu, cc thuc khng virus c dng iu tr nhiu virus khc nhau c dng th nghim gm vibavirin, tamiflu, cc cht c ch enzyme protease l kaletra ( phi hp gm lopinavirritonavir) v interferon. Thm vo cc bin php iu tr h tr cn thit khc gm corticosteroid, th my..

II. VIRUS RUBELLA

Virus rubella thuc vo nhm rubivirus, h Togaviridae, tuy nhin virus ny c phng thc ly truyn khc vi cc alphavirus, n gy nhim trng qua ng h hp. 1. Tnh cht ca virus V cu trc virus ny c ng knh t 45-75nm, n c bao ngoi bng lipid v trn b mt c cc gai glycoprotein, capsid bn trong c dng hnh khi a din, genm cha RNA si n. Virus rubella khng gy tan t bo, nhng n gy hiu ng t bo bnh l mc nht nh trn mt s t bo nui cy nh t bo vero, t bo RK13. S nhn ln ca virus rubella cn tr s nhn ln ca cc virus thuc h Picornaviridae khi cho nhim loi sau thm vo. 2. Min dch Virus ny ch c mt typ huyt thanh, v ngi l tc ch duy nht ca rubellavirus, sau khi nhim virus mu, khng th bt u xut hin, khng th dch th c th ngn cn s lan rng virus, nhng min dch trung gian t bo ng vai tr quan trng trong loi b virus. Min dch thu c sau khi b nhim trng c vai tr bo v sut i. Khng th c trong huyt thanh m mang thai ngn cn c

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nhim trng cho bo thai. Mt khc khi khng th xut hin, phc hp min dch to ra c th c vai tr trong bnh sinh ca ni ban v au khp trong bnh rubella. 3. Dch t hc Virus rubella ly truyn qua cht tit ng h hp, virus rubella t ly hn so vi virus si v virus thy u, tuy nhin bnh ly d dng nhng ni ng ngi nh nh tr. Nhim trng xy ra thng tr em, c khong 20% ph n trong tui mang thai cha b nhim virus ny ln no, nhm ngi ny c th b bnh. 4. Lm sng Bnh rubella l mt bnh lnh tnh tr em, bnh c trng vi st, hch lympho ln v ni ban. ngi ln nhim trng rubella c th nng v thng tn thng xng, vim khp, gim tiu cu v him hn vim no sau nhim trng rubella. Cc tn thng bm sinh: y l hu qu ng s, nhim rubella m ang mang thai khng c khng th bo v (do nhim trng trc y hay tim vaccine) c th gy nn nhng bt thng cho tr. Virus c th nhn ln nhau thai v ly lan cho thai nhi qua ng mu. thai nhi virus c th nhn ln trong hu ht cc m ca thai, d virus khng lm tan t bo, nhng s pht trin ca m t bo, s phn bo, cu trc nhim sc th ca t bo thai nhi b ri lon do nhim trng virus. Hu qu dn n s pht trin khng bnh thng cho bo thai. Tnh cht bt thng thai lin quan n m b nhim trng v giai on pht trin ca thai nhi. Bt thng thng ln c th gy cht thai, cc bt thng sau khi sinh thng gp gm c thy tinh th, chm pht trin v tinh thn kinh, ic, cc bt thng v tim nh cn ng ng mch, thng lin tht, thng lin nh..... 5. Chn on phng th nghim: Chn on phng th nghim ch yu da vo phn ng huyt thanh hc tm khng th c hiu. Tm s hin din ca khng th IgM ch im nhim trng mi y, hoc s tng hiu gi IgG 4 ln mu huyt thanh ly vo giai on lnh bnh so vi mu huyt thanh ly trong giai on bnh cp. Phn lp virus t cc bnh phm cht tit h hp, nc tiu, mu, dch no ty trn nui cy t bo, nhng bin php ny t c thc hin do quy trnh phn lp kh phc tp. K thut RT-PCR nhm xc nh ARN ca virus trong cc dch c th. 6. Phng nga Cch phng nga tt nht l dng vaccine, Hoa k vaccine gim c chng RA27/3 c s dng cho tr vo lc tr 12 -15 thng v liu tim nhc vo lc tr 4-6 tui.

III. HANTAVIRUS
Hantavirus l mt ging thuc h Bunyamviridae, nhng virus ny khng truyn bnh qua cn trng tit tc m qua ng h hp do ht cht tit ng h hp, nc tiu, nc bt ca chut. 1. Tnh cht virus Virus c hnh cu ng knh 100nm, bao ngoi l hai lp lipid v trn b mt c cc gai glycoprotein (G1 v G2) di khong 5-10 nm, nucleocapsid cha 3 on ARN c kch thc khc nhau, on ln khong 6530-6550 nucleotid m ha cho enzyme sao chp ca virus, on trung bnh 3613-3707 nt m ha cho cc glycoprotein ca virus, on nh 1696-2083 nt m ha cho cc protein ca nucleocapsid.

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Hnh 2. Cu to Hantavirus Virus b bt hot bi nhit, cc cht c hot tnh b mt, cc dung mi hu c v dung dich thuc ty. Hantavirus pht trin trn nhiu t bo nui cy nh t bo vero, cc t bo lai, t bo ni mc tnh mch. Trn cc nui cy ny virus khng gy hiu ng t bo bnh l. 2. Tnh cht gy bnh 2.1. Dch t hc Hantavirus gy nhim trng chut m khng c biu hin bnh r rng, chut b nhim virus chm tng cn, nhng khng nh hng g n kh nng sng v sinh sn ca chng. Khi nhim trng chut, virus c thi ra trong cht tit nh nc tiu, phn, nc bt. Ngi khng phi l tc ch t nhin ca Hantavirus, ngi b nhim virus ny qua ng h hp do ht khng kh c mang cc ht bi cha virus c thi ra t chut b nhim trng, ngoi ra nhim trng do chut cn khi tip xc trc tip nh by chut, hay nui chut trong phng th nghim.. Bnh nhim trng Hantavirus gp khp ni trn th gii, bnh c bo co xy ra nhiu nc thuc chu u, chu , chu M. chu bnh xy ra nhiu nc nh Nht bn, Hn quc, Thi lan, Trung quc. cc nc chu nng nghip bnh xy ra thng lin h n ma trng trt hay ma gt. mt s nc chu u bnh xy ra vo cc thng 10 khi chut tm ch c tr cc nh kho. 2.2. Bnh ngi Hantavirrus gy nhim trng ngi t khng triu chng, nhim trng nh n cc th lm sng nng, hai th lm sng nng hay gp l st xut huyt km theo hi chng suy thn v nhim trng hantavirus km hi chng h hp. Vi hi chng h hp thng khi u vi st, nhc u, au c, bnh tin trin nhanh n suy h hp c trng vi ph phi khng do suy tim, v h huyt p. Bnh c t l t vong cao, trong mt s bo co n 50%. St Hantavirus vi suy thn biu hin vi st, au c ko di 3-7 ngy, tip theo giai on gim tiu cu, gim huyt p v xut huyt. Giai on v niu bt u khi huyt p bt u tr v bnh thng, v niu c th ko di 3-7 ngy, sau l giai on a niu v hi phc. Vi th ny t l t vong 5-10% xy ra trong giai on h huyt p hoc giai on v niu. 3. Chn on phng th nghim Phn lp virus t cc mu nghim lm sng ln nui cy t bo thng kh khn, trong giai on u cn tim vo chut phng th nghim, sau nui cy ln t bo. Quy trnh phn lp thnh cng mt nhiu tun, do vy y khng phi l quy trnh thch hp chn on. Chn on nhanh bng k thut khuch i gen

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RT-PCR xc nh ARN ca virus mu nghim mu hay tng ph. Cc th nghim huyt thanh hc thng c dng gm min dch hunh quang xc nh c IgM v IgG, th nghim min dch lin kt enzyme xc nh IgM chn on nhim trng cp. 4. Phng v iu tr Phng bnh chung bng dit chut, hn ch tip xc vi chut, chn nui chut trong phng th nghim cn nui trong cc bung nui ng quy nh m o an ton.. Cha c vaccine c chp nhn dng ngi Hin nay cng cha c thuc khng virus c hiu vi Hantavirus, cc th bnh nng ch yu l dng bin php h tr.

TI LIU THAM KHO

1. B mn Vi sinh vt Trng i hc Y khoa H Ni (1982), Vi sinh vt y hc , Nh xut bn Y hc, H Ni, Tp I v II. 2. B mn Vi sinh vt Trng i hc Y H Ni (2001), Vi sinh y hc, Nh xut bn Y hc, H ni. 3. B mn Vi sinh vt Trng i hc Y khoa Hu (2004), Bi ging vi sinh y hc. 4. Nguyn Ln Dng, Nguyn nh Quyn, Phm Vn Ty (1997), Vi sinh vt hc, Nh xut bn Gio dc. 5. Phm Vn Ty (2005), Virut hc, Nh xut bn Gio dc. 6. Balley and Scotts (1994), Diagnostic Microbiology, 9e edition, Mosby. 7. Burrows (1981), Textbook of microbiology, twenty - first edition, W.B. Saundrers company. 8. Albert Balows, William J. Hauler (1991), Manual of clinical Microbiology, ASM, 5e edition. 9. Fields BN (1995), Fields' Virology, 3th ed, Lippincott Williams & Wilkin, Philadelphia. 10. Freeman BA (1979), Burrows Textbook of Microbiology, WB Saunders company, philadelphia.

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11. Hatheway CL (1990), Toxigenic Clostridia, Clinical Microbiology Reviews, American society for microbiology, 66-98. 12. Katzung BG (1989), Basic and clinical pharmacology, 4th ed, Appleton & Lange, USA, 545-610. 13. Mandell GL, Bennett JE and Dolin R; Mandell (1995), Douglas and Bennett's Principles and practice of infectious diseases, 4th ed, Churchill Livingstone, pp. 2-28. 14. Turner TB (1965), The Spirochetes, in Bacterial and mucotic infections of man, 4th ed, Lippincott Co, Philadelphia, 573- 609. 15. Collection Azay (1997), Bacteriologie mdicale, Presses universitaire de Lyon. 16. Jean Freney, Francois Renaud,Willy Hansen et Claud Bollet (2000), Prcis de bacteriologie clinique, Edition ESKA. 17. Mammette A. (2002), Virologie mdicale, Presses Universitaire de Lyon.