DENGUE VIRUS

4 serotypes in man

All ages are affected especially children

Increase infection during rainy seasin
Pathogenesis: not clear, skin bit & spreads thru the lymph nodes as portal of entry, multiplies
producing viremia may persist for 3 days
Maybe immune mediated, occur with passively acquired maternal antibodies or circulating
antibodies from previous

Dengue infection upon subsequent exposure, immune complexes are formed resulting to:

1) Immune enhancement attachment of immune complexes to macrophages and other immune

cells resulting to increase number of virus that infect the cells
2) Immune complexes may activate the C system which leads to increase capillary permeability and
DIC (disseminated IV coagulation)
- Serotype 2 most common type though all serotypes will cause hemorrhagic manifestations
- Clinical infection: dengue infection most important arthropod borne infection
- Transmission: Aedes aegypti efficient vector, Aedes albopictus higher biting frequency than
aedes aegypti

Clinical manifestations:

1) Asymptomatic
2) Classical dengue virus
a. Mild case 4 days incubation, fever, maculopapular rash, rapid recovery
b. Sever case sudden onset of high fever 39C, persist 5-6 days, headache, pain in the
muscles
Flushing of the face, puffiness of the eyelids, suffusion of the conjunctival
capillaries, maculopapular rashes (upper & lower) extremities with occasional
purplish, itchy
Hepatomegaly, 5-10 days illness acute symptoms disappear
3) Dengue HF start acute with high grade fever & after a day or 2, hemorrhagic manifestations
appear as petechia, GI bleeding, drowsiness, letharygy, appears on the third day
Vascular permeability
Abnormal hemeotasis as fever subsides, circulatory insufficiency & bleeding (signs of
shock), may have a right sided pleural effusion and ascites
4) Dengue shock syndrome progression of DHF, generalized vasculitis, rapid poor pulses,
hypotension, cold extremities, restlessness
 DHF/DSS most likely to develop in immunocompromised patient, mild infection in
healthy people aged 7-12, can develop in infants born to immune mothers, is rare after
15 years old

Diagnosis as suggested by WHO:

Clinical fever, hemorrhagic manifestations, (+ tourniquet test), enlarged liver, shock (high pulse rate,
narrow pulse pressure to 20 mmHg or less), hypotension

Laboratory measures:

Thrombocytopenia less than 100,000/cumm

Patient start to bleed if platelet count is 50,000/cumm or below

Increasing hematocrit hemoconcentration, 20% above baseline

Acute dengue illness anorexia, nausea, vomiting

Laboratory parameters: low total WBC and absolute neutrophil, low absolute monocyte count,
higher liver enzymes in DHF patients
Treatment:
1) Improve oxygen delivery to the tissues
2) Restore intravascular volume, support circulation with vaso-active amine
dopamine
3) Correction of metabolic abnormalities
Rabies Virus

Only significant human pathogen in the group

Biochemical properties, mechanism of replication 7 genetics has been studied largely in
vesicular stomatitis
Typically found in horses & cattles but occasionally found in human
Since several rhadovirus replicate in arthropods and mammals they were classified as arbovirus
or robovirus

Structure: bullet shaped enveloped, viral particle is rounded at one end and flat at the other, minus
strand RNA which helical symmetry, ssRNA, surface is covered by regularly spaced projections with knob
like structures

Replication is confined to the cytoplasm od host cell:

1) After adsorption and coating, the virus RNA is transcribed by the virion RNA-dependent RNA
polymerase (transcriptase)
2) Plus strand mRNA then serves as a template for further RNA synthesis via a new polymerase
activity (the replicase) & serves as a messenger for viral protein synthesis
Rabies causes encephalitis resulting neuronal degeneration of the brain & spinal cord in
man, always fatal:
1. Antigenicity single immunologic type
a) Fixed virus (a virus form that is yielded by serial passage in lab animals) and
street virus (freshly isolated from an infect animal) are immunologically
indistinguishable
b) Antibodies directed against the surface glycoprotein projections are
responsible for neutralization
c) Antibodies against the nucleocapsid are recognized by complement fixation
but little role in protection

2. Pathogenesis virus is introduced in the body through a break or abrasion of

the skin, usually a bite by a rabid animal, respiratory tract by mean of aerosol by
a dense population of rabid bats either by:
a) Virus replicates in muscle & connective tissue, where it may remain for
days or months
b) Infection progresses along the axoplasm of peripheral nerves to the ganglia
of CNS where it multiplies causing severe encephalitis
c) 3-8 weeks incubation period but as short as 6 days
d) Symptoms develop in prodromal period, irritability, abnormal sensation at
the wounded site
e) Apparent symptoms with change in muscle tone leading to difficulty in
swallowing
f) Negri bodies (cytoplasmic inclusion in affected neurons) most diagnostic
microscopic characteristic
Types:

1) Street virus fresh from laboratory

21-60 days incubation period, long & variable, long period of excitement & viciousness,
virus in the salivary glands and CNS
2) Fixed virus serial brain to brain passage such as rabbits, short incubation period, rapid
multiplication, negri bodies difficult to see
3) Flurry stain modified virus, serial passage in chick embryo, nonpathogenic, virus for vaccine

Transmission:

1) Animal bite most common, virus in the saliva thru a bite or scratch of a broken skin, basis of
transmission is done by:
a. Adequate saliva that contains virus
b. Susceptible bitten animal
c. Site of inoculation bites in the head & neck are likely to cause disease earlier than
bites at areas more peripheral to the CNS
2) Aerosol transmission occurs in highly contaminated areas like caves or laboratory accidents
3) Human to human transmission rare
4) Corneal transplant some reported cases

Incubation period depends:

Amount of inoculum
Severity of lacerations
Distance virus travel from entry to brain
Shorter incubation if bitten in the face
Common symptoms: fever, headache, nausea, agitation, anxiety, confusion,
hyperactivity, difficulty swallowing, excessive salivation, fear of water, hallucinations,
insomnia, partial paralysis

Treatment:

No specific treatment
Small number of people who survived rabies but it is fatal
Bitten from a rabid animal, series of rabies shots are given to prevent virus from infecting you:
Fast acting shot, rabies immune globulin
Given near the bitten area as soon as possible, four injections for 14 days
Considerations:
1) If your bitten from a healthy animal, observed for 10 days then, no shots give, however,
consult medical help for further advisory
2) If bitten by a stray animal, rabies shot must be given immediately
Clinical findings:

1) Rabies in dogs 3-8 weeks incubation, as early as 10 days

3 phases:
a. Prodromal fever, change in temperament, if aggressive it will become affectionate, if
docile it will become irritable
b. Excitative around 3 to 7 days, restless, irritable, nervous high tendency to bite,
difficulty in swallowing, convulsive seizures then paralysis
c. Paralysis leads to come 7 death
2) Rabies in man 2 to 16 weeks, average of 2-3 weeks, shorter in children than in adults

Clinical course:

1) Asymptomatic: 2-8 weeks incubation period, extreme is 7 days or 1 year

2) Prodromal period sensation or itchiness, burning or pain
3) Encephalitic:
Anxiety, depression, behavioral changes
As it progress, painful spasms occur especially muscles of the deglutition hydrophobia
Hyperactive with extreme sensitivity to light, noise, touch and air currents, sweating
dysfunction, increase salivation, paralysis, convulsion, coma death
Rare recovery but permanent immunity

Laboratory diagnosis:

Rabies antigen detection from brain cells or cornea

Negri bodies inclusion bodies in an infected cells stained with Sellers stain
Virus inoculation use of lab animals like mice injected with the virus, later examined for negri
bodies

Prevention/control:

Post exposure alms to prevent or lessen the virus from reaching the brain
Observe the dog
Thorough cleaning of the wound with soap & water
Passive immunization: anti rabies serum (EQUINE) 40 IU/kg, rabies immune globulin (HUMAN)
21 IU/kg, given intramuscular
Active immunization:
1) Nerve tissue vaccine made from sheep, goat, mouse brain cells cause sensitization to
nerve tissue resulting to post vaccination encephalitis
2) Duck embryo vaccine (LYSSAVAC) virus grown in embryonated duck eggs
3) Human diploid cell vaccine (HDCV) killed virus grown in human fibroblast
Para influenza viruses 1,2,3,4

Para-myxovirus pleomorphic, enveloped ssRNA virus, (2) glycoprotein in the envelope namely
HN (haemagglutinin/neuraminidase) & F (fusion)
Inner helical core that protects ssRNA, haemagglutinin binds & agglutinates RBC
Epidemiology: cause respiratory tract infection, first infection occurs in children, poor immunity
& re-infections
Virus may shed up to 3 weeks & asymptomatic patients: serves as reservoir to infect again
Transmission: respiratory droplets, fomites
Clinical syndromes: acute laryngeo-tracheo bronchitis (Croup), bronchiolitis, pneumonia, re-
infections cause common cold symptoms

Rotavirus

Rota wheel
Wheel like appearance under an electron microscope
No enveloped, double shelled
Genome is composed of 11 segments double stranded RNA, 5 nonstructural proteins
Stable in the environment
Symptoms: 3-8 days of vomiting & watery diarrhea, frequent fever & abdominal pain,
dehydration, loss of appetite, decrease urination, dry mouth & throat, feeling dizzy when
standing up, (2) days incubation period
Epidemiology: fecal-oral route thru contaminated water/food, contact with contaminated
surfaces
Diagnosis: rapid detection in stool; detected thru EIA and reverse PCR
Treatment: healthy people self limited last for a few days
Vaccination: effective in getting the infection
CDC recommendation:
a) RotaTeq (RVS) licensed in 2006, given 3 doses at ages 2months, 4 months, 6 months
b) Rotarix (RV I) licensed 2008, given in 2 doses at ages 2 month, 4 month
c) All are given orally

Norovirus (Norwalk virus)

Virus that contain RNA surrounded by protein coating

Positive sense RNA genome encoding the major structural protein (VP 1) and major capsid
protein (VP2)
Amorphous surface using the electron microscopy
Norovirus most common cause of acute gastroenteritis, illness spreads easily
Known as stomach flu or viral gastroenteritis
Spread thru contaminated food, water, develops 24-48 hrs after exposure
Abrupt or gradual onset yet short lived, lasted 24-72 hours
Contaminated food from shellfish, ready to eat food processed from infected food handlers
 Symptoms: watery & non bloody diarrhea (common among adults)
Nausea & profuse non bloody vomiting
Stomach pain, abdominal cramps
Headaches, low grade fever, myalgias, malaise

Treatment & prevention: plenty of fluids, clean & disinfect contaminated surfaces/linens, washing of
fruits & vegetables prior to eating/cooking

Laboratory procedures:

Immune electron microscopy immune serum is used to aggregate virus in stool to aid
detection, aid in gastroenteritis diagnosis
Antigen detection immunoassay high sensitivity, low specificity due to reactivity with antigenic
variants
Nucleic acid amplification highly sensitive & specific

Adenovirus

Non-enveloped with icosahedral ds DNA

Double stranded DNA genome
First isolated from human adenois
Causes respiratory to multi-organ disease for those weakened immune system
Represents the largest non-enveloped viruses
Has a unique spike or fiber on its capsid that attached to the host cell

Classification & syndromes/target organ

A = GIT

B = pharynx, lungs, conjunctive, urinary tract

C = pharynx

D = eye (keratoconjunctivitis)

E = upper respiratory tract, eye

F = GIT

Epidemiology not seasonal, highly resistant to inactivation & may remain in the environment,
nosocomial infection due to pediatric ICUs

Transmission thru respiratory droplets, fomites and ingestion

Clinical features: infect those listed in the target organs, local lymph nodes (enlarged & tender),
asymptomatic (acute & self limiting)
Syndromes:

1) Asymptomatic infection isolated from the respiratory tract & stools of healthy people,
persistent silent infection on the tonsils
2) Acute pharyngitis with fever causes of acute sore throat
3) Pharyngoconjunctival fever acute conjunctivitis (pink eye) together with sore throat & fever
4) Acute follicular conjunctivitis pink eye highly infectious non purulent conjunctivitis
5) Epidemic kerato-conjunctivitis (shipyard eye) mild trauma to the eye resulting to infection of
the cornea like shared towels
6) Pneumonia/ pneumonitis seen in young babies following measles, seen in ICUs babies on
ventilators with artificial airways are at risk
7) Epidemic acute respiratory disease lower respiratory infection seen in military camps, has
been prevented by a live vaccine subtypes 4 & 7
8) Gastroenteritis diarrhea among children, subtypes 40-41 causes this leading to dehydration
and death
9) Mesenteric adenitis children has abdominal pain due to enlarged tender mesenteric lymph
nodes
10) Immunocompromised host in transplant, AIDS patients etc. causes hemorrhagic cystitis

Astrovirus

Causes outbreak in gastroenteritis in 1975

Small single stranded RNA
Non-enveloped virus, round with an unbroken surface
Contains (3) structural proteins, sequenced genome
Epidemiology endemic, mainly in children less than 7 years old
Transmission person to person via fecal oral route, outbreaks due to fecal contamination of
seafood/water

Diagnosis:

1) Electron microscopy useful as seen large amounts in stool

2) Immunofluorescence microscopy detects serotypes
3) ELIZA, PCR
Incubation period: 1-4 days
Symptoms: watery diarrhea, abdominal cramps, headache, nausea, low grade fever

Enterovirus