Un cas de

Tuberculose du Vietnam

Dr. TRAN Thi Trang Anh

 Motif dhospitalisation

Une fille de 6 ans hospitalise lhpital

national de Pdiatrie du Vietnam le
23/01/2017 pour :

Fivres et convulsion
 HISTOIRE DE LA MALADIE
10j avant hospitalisation, la fille prsente une fivre persistante avec douleurs
abdominales.
J1 , elle a consult dans un cabinet priv, mais il ny pas dinformation sur le
diagnostic et le traitement.
J2, la fivre reste 39-40 oC , elle est hospitalise lhpital local : Sp
appendicite et transfert lhpital de la rgion.
J9 de la surveillance (pas dinfo prcise) , fivre trs frquente et trouble de
conscience (les rponses sont plus lentes), ne tousse pas , pas de
convulsion , pas de vomissement, on a fait LP, CT crbral et diagnostic
mningite. ( LP : 225 leuco, N 20%, L 80% ; Pandy + ; CT scan : dme
crbral lger)
La fille est transfere lhpital National de Pdiatrie,mais sur la chemin du
transport, elle a une crise convulsive gnralise, hypertonique pendant 6-7
mins.Aprs la crise, elle est somnolente, perte du tonus des sphincters (perte
urines et selles), pas de paralysie.
 Antecedents
ATCD personnel : Aucun antcdent
Accouchement voie basse 39 SA; le seul
enfant ; PN = 3900 g
Grossesse spontane de droulement normal
Dveloppement mental normal
Nutrition normale, pas perte de poids
rcemment
Vaccination jour.
Pas de voyage rcent
ATCD familial : toux chez son grand pre sans
diagnostic:
Pas de notion de contage
 Examen clinique dentree
FC 110/min, saturation 98% en air
ambiant, T 37C.
Sur le plan neurologique : Somnolent,
V/AVPU, syndrome mning : raideur de
nuque (+), pas de vomissement, constipation
(+), Kernig (+);pas de signes neuro de
focalisation
Sur le plan cardiovasculaire -pulmonaire :
normal
Pouls : bien frapps. Extrmits : chaudes
Abdomen : plat, souple, pas de douleurs
le reste de l'examen clinique est sans
particularit
 DIAGNOSTIC?

-Mningite bactrienne
-Mningite Tuberculeuse
 Examens complementaires
BC NEU LYM Hb TC
23/1 19,94 83,1 8,1 108 367
25/1 20,97 77,4 10,3 110 264
CRP 0,71 Procalcitonin 27,38
Na/ K= 125,8/2,8 Ca = 2,12 G = 5,6
URE 4,58 CRE 44 GOT/GPT 97,7/91,2
Lactat 3,13
BiL TP: 149,9 GT 56,4 TT 93,5 Amoniac 53
HbsAg (-)
 Examens complementaires
PL : liquide claire, normal pressure,
protines 2.28 g/L, glucose 1.81 mmol/L,
leucocytes 40 /mm3, Pandy ++
PCR TB de LCR (+) 25/1, MODS TB (+) 03/02
AFB, PCR TB Liquide gastrique 3 flacons (-)
Radiographie thoracique normale
IRM : dilatation des ventricules bilatrale
 Diagnostics & Traitement
Diagnostics : Mningite tuberculeuse
Traitement :
ATB : Rocephin + Vancomycine --> Protocol
2RHZE+10RH (25/01)
Traitement pour mningite
 Evolution

Fivre 38,5- 390C

Convulsions hypertoniques (24/01)
25/01 Coma P/AVPU, G 6, rflexe pupillaire
faible, bilatral 3 mm, pas de contrle de
transit
TDM dilatation des ventricules et pression
intracrnienne augmente
Opration pour drivation ventriculaire
externe 26/01
Au decours: Squelles mentales et physiques, G
8, hypertonique et fivre persistante -->
mauvais pronostic
TUBERCULOSE
 TB is an infectious disease caused by the bacillus
Mycobacterium tuberculosis.
It typically affects the lungs (pulmonary TB) but can
affect other sites as well (extrapulmonary TB).
The disease is spread in the air when people who are
sick with pulmonary TB expel bacteria, for example by
coughing.
Overall, a relatively small proportion (515%) of the
estimated 23 billion people infected with M. tuberculosis
will develop TB disease during their lifetime. However,
the probability of developing TB is much higher among
people infected with HIV.
 PIDMIOLOGIE - Mondial
Selon lOrganisation mondiale de la sant (OMS), on estime 10,4
millions le nombre de nouveaux cas de tuberculose dans le monde
en 2015
lAfrique (275 cas/105 habi- tants) et lAsie du Sud-Est (246 cas/105)
concentrant le plus gros fardeau de la maladie.
une baisse particulirement marque dans les 31 pays de lUnion
europenne (UE) / Espace conomique europen (EEE), ou le taux
de dclaration tait de 11,7 cas/105 habitants en 2015
PIDMIOLOGIE - Mondial
 PIDMIOLOGIE - Mondial
TB in children
Estimating the global burden of tuberculosis (TB) disease in children is
challenging due to the lack of a standard case definition, the difficulty in
establishing a definitive diagnosis, the frequency of extrapulmonary
disease in young children, and the relatively low public health priority given
to TB in children relative to adults
In 2014 report, the WHO estimates that, of the nine million incident cases
of TB in 2013, approximately 550,000 occurred among children under age
15
Approximately 75 percent of these cases occurred in the 22 highest TB-
burden countries
Most children are infected by household contacts with TB disease,
particularly parents or other caretakers. Even in circumstances when adult
index cases are sputum smear negative, transmission to children has been
documented in 30 to 40 percent of households
 PIDMIOLOGIE - France
Le nombre de cas de tuberculose maladie dclar en France en
2015 tait de 4 741, dont 3 422 cas avec une localisation
pulmonaire, soit des taux de 7,1 cas pour 105 habitants et de
5,1/105 pour les formes pulmonaires.
 PIDMIOLOGIE - France
Les taux de dclaration de la maladie les plus levs taient observs dans
trois rgions (Mayotte : 25,9/105, Guyane : 18,3/105 et Ile-de-France :
14,5/105), ainsi que chez certaines popu- lations spci ques : personnes
sans domicile xe (166,8/105), personnes incarcres (91,3/105) et
personnes nes ltranger (35,1/105)
 PIDMIOLOGIE - France
Les enfants de moins de 5 ans reprsentaient 2,5% des cas
dclars (n=121), soit un taux de dclaration de 3,1/105
Le nombre annuel de cas de tuberculose maladie chez les enfants
ns aprs 2006 diminuait en Ile-de-France et augmentait en France
mtropolitaine hors Ile-de-France.
Le nombre de cas de tuberculoses svres chez les enfants ns
aprs 2006 tait en moyenne de 2,2 mningites et de 1,3 miliaire
par an entre 2007 et 2015.
PIDMIOLOGIE - France
 PIDMIOLOGIE - Vietnam
Vietnam is a middle-income country that is ranked eleventh in TB
burden among the high-prevalence countries.
A national survey in 2006 estimated that the prevalence of TB was 307
bacteriologically proven cases per 100,000 adults (95% CI, 249 to 366
per 100,000 persons aged 15 and over) [7].
In Viet Nam, the proportion of children aged 0-14 is 24% of the
population (87.6 million), equivalent to 21 million children (GSO 2011)
Every year, the number of new cases of children in Vietnam is
approximately 351000, but until now there isnt any official report about
the prevalence rates of TB of Vietnamese childrens
80% of TB case if type TB pulmonary and mainly AFB (-)
According to Program of national Strategies in Vietnam, the rates of
children infected with TB was decteted and enregisted for treatment in
2010 and 2014 is 1,2% and 1,37%, which means Viet nam can only
diagnose 10% the number of new cases every year.
 Symptmes
Pulmonary tuberculosis
Pulmonary disease and associated intrathoracic adenopathy are the most
frequent presentations of tuberculosis (TB) in children Common symptoms
of pulmonary TB in children include
- Chronic, unremitting cough that is not improving and has been present for
more than three weeks
- Fever of more than 38C for at least two weeks, other common causes
having been excluded
- Weight loss or failure to thrive (based on child's growth chart)

However, these symptoms are fairly nonspecific.

 Symptmes
Extrapulmonary tuberculosis : In regions where the incidence rates are low,
such as North America and Western Europe, extrapulmonary manifestations of
diseases are seen primarily in adults with reactivation infection, and the
dominant form of CNS disease is meningitis.
Tuberculous meningitis accounts for about 1 percent of all cases of tuberculosis
(TB) and 5 percent of all extrapulmonary disease in immunocompetent individuals
Typically, patients with tuberculous meningitis present with a subacute febrile
illness that progresses through three discernible phases :

- The prodromal phase, lasting two to three weeks, is characterized by the

insidious onset of malaise, lassitude, headache, low-grade fever, and
personality change.
- The meningitic phase follows with more pronounced neurologic features, such
as meningismus, protracted headache, vomiting, lethargy, confusion, and
varying degrees of cranial nerve and long-tract signs.
- The paralytic phase supervenes as the pace of illness accelerates rapidly;
confusion gives way to stupor and coma, seizures, and often hemiparesis. For
the majority of untreated patients, death ensues within five to eight weeks of
the onset of illness.
DIAGNOSTICS

CLINIQUE Examen direct +

culture

Screening test
L'intradermo-raction la .PCR
tuberculine (IDR)
.....
Test immunologique de
production dinterfron gamma
+/- Image radiologique
(cicatrice du foyer infectieux)
 DIAGNOSTIC
Tuberculosis (TB) in children is often diagnosed clinically. Because pulmonary TB in children
typically presents with paucibacillary, noncavitary pulmonary disease, bacteriologic
confirmation is achievable in less than 50 percent of children and 75 percent of infants; in
such cases, pulmonary TB is diagnosed by other clinical criteria

For diagnosis of extrapulmonary TB, specimens for culture should be collected from any site where
infection is suspected. Each specimen should be cultured regardless of acid-fast bacilli (AFB) smear
results

The approach outlined by the World Health Organization (WHO) for evaluation of a child
suspected of having TB includes :
Careful history (including history of TB contact and symptoms consistent with TB)
Clinical examination (including growth assessment)
TST and/or IGRA (both tests, if available, to increase sensitivity)
Bacteriological confirmation whenever possible
Investigations relevant for suspected pulmonary and extrapulmonary TB
HIV testing (eg, in high HIV-prevalence areas)
 DIAGNOSTIC
Diagnostics and laboratory strengthening
The most common method for diagnosing TB worldwide remains sputum
smear microscopy (developed more than 100 years ago), in which bacteria
are observed in sputum samples examined under a microscope.
However, developments in TB diagnostics in the last few years mean that
the use of rapid molecular tests to diagnose TB and drug-resistant TB is
increasing, and some countries are phasing out use of smear microscopy
for diagnostic (as opposed to treatment monitoring) purposes.
In countries with more developed laboratory capacity, cases of TB are also
diagnosed via culture methods (the current reference standard)
 DIAGNOSTIC
Diagnostics and laboratory strengthening
The use of the rapid test Xpert MTB/RIF has expanded substantially since
2010, when WHO first recommended its use.
In all, 4.8 million test cartridges were procured in 2014 by 116 low- and
middle-income countries at conces- sional prices, up from 550 000 in 2011.
By 2015, 69% of countries recommended using Xpert MTB/RIF as the initial
diagnostic test for people at risk of drug-resistant TB, and 60% recommended
it as the initial diagnostic test for people living with HIV.
While the Xpert MTB/RIF test appears to be highly specific, its sensitivity for
sputum smear negative TB in children remains low. Therefore, it cannot
replace current methods used to suspect and diagnose TB in infants and
children.
The Xpert MTB/RIF test is meant to be a rapid diagnostic test that may take
the place of sputum microscopy but not mycobacterial culture . A negative
Xpert MTB/RIF test should be interpreted in the context of the child's clinical
and radiographic findings
 TRAITEMENT & MANAGEMENT
Les outils majeurs pour maitriser la tuberculose restent lidentication
rapide des cas et leur prise en charge prcoce et adquate, qui vise
gurir le patient et permet de limiter la transmission du bacille
dans la communaut ainsi que le dveloppement de la rsistance
aux antituberculeux
 TRAITEMENT & MANAGEMENT
Effective drug treatments were first developed in the 1940s.
The most effective first line anti-TB drug,rifampicin,became available in
the 1960s.
The currently recommended treatment for new cases of drug-susceptible TB
is a six-month regimen of four first-line drugs: isoniazid, rifampicin,
ethambutol and pyrazinamide.
Treatment success rates of 85% or more for new cases are regularly reported
to WHO by its Member States.
Treatment for multidrug-resistant TB (MDR-TB), defined as resistance to
isoniazid and rifampicin (the two most powerful anti-TB drugs) is longer,
and requires more expensive and more toxic drugs.
For most patients with MDR-TB, the current regimens recommended by WHO
last 20 months, and treatment success rates are much lower.
 TRAITEMENT & MANAGEMENT
The pediatric treatment regimens outlined by the WHO are comparable
with the adult regimens
 TRAITEMENT & MANAGEMENT
Mningite TB
Patients with hydrocephalus may require surgical decompression of the
ventricular system in order to effectively manage the complications of raised
intracranial pressure.
In such patients with clinical stage II disease, the combination of serial
lumbar puncture and steroid therapy may suffice while judging the early
response to chemotherapy.
However, surgical intervention should not be delayed in patients with stupor
and coma or when the clinical course of therapy is marked by progressive
neurologic impairment
 TRAITEMENT & MANAGEMENT
Vaccination
Bacille Calmette-Gurin (BCG) is a live strain of Mycobacterium bovis developed by Calmette
and Gurin for use as an attenuated vaccine to prevent tuberculosis and other mycobacterial
infections.
The vaccine was first administered to humans in 1921 and remains the only vaccine against
tuberculosis in general use.
Bacillus Calmette-Gurin vaccine is the most widely administered vaccine in the world; it has
been given to over three billion individuals, principally in the setting of routine newborn
immunization
A widely cited meta-analysis suggests that BCG vaccination reduces the risk of active TB by
about 50 percent, although this figure does not reflect the important differences in efficacy in
different age groups
Primary vaccination of newborns and infants appears to confer protection in about 80 percent
of cases, whereas primary vaccination of older children and adults is considerably less effective
.
The greatest benefit of BCG appears to be diminished risk of tuberculous meningitis and
disseminated disease in children (75 to 86 percent efficacy) However, studies that have
evaluated these outcomes are limited by biases in design and/or inadequate statistical power.
 TRAITEMENT & MANAGEMENT
Vaccination
La vaccination BCG du nourrisson a t obligatoire jusquen 2005 en France et
effectue trs majoritairement par voie percutane
Cette politique etait justiee par le constat de linduction par le BCG dune protection
denviron 85% contre les formes extrapulmonaires de tuberculose et denviron 50%
contre les formes pulmonaires

En janvier 2006, le vaccin par multipuncture (Monovax) a t retir du march et

remplac par le vaccin BCG SSI administrable par voie intradermique, ce qui a
conduit une baisse immdiate de la couverture vaccinale
En juillet 2007, faisant suite une expertise francaise qui estimait que la
vaccination des seuls enfants risque (moins de 15% des enfants) pouvait viter
les trois quarts des cas de tuberculose jusque-l vits par le BCG.
lobligation de vaccination des enfants par le BCG a t remplace par une
recommandation de vaccination des enfants les plus exposs la tuberculose,
notamment les enfants nes, ou dont au moins lun des parents etait ne en zone de
forte endemie tuberculeuse, et tous les enfants residant en Ile-de-France ou en
Guyane
 TRAITEMENT & MANAGEMENT

Cet article fait le point sur lpidmiologie de la tuberculose en France en

2015, en faisant un focus sur les enfants ns aprs 2006 a fin de juger de
limpact des modi cations des modalits vaccinales sur lincidence de la
tuberculose de lenfant.

Le nombre annuel de cas de tuberculose maladie chez les enfants ns aprs 2006 diminuait en Ile-de-
France et augmentait en France mtropolitaine hors Ile-de-France. Le nombre de cas de tuberculoses
svres chez les enfants ns aprs 2006 tait en moyenne de 2,2 mningites et de 1,3 miliaire par an
entre 2007 et 2015.
Ces donnes montrent une poursuite de la baisse du nombre de cas de tuberculose dclars en France.
Les donnes chez lenfant nindiquent pas dimpact des nouvelles modalits de vaccination par le BCG
au-dela de ce qui tait attendu. Il convient cependant de continuer suivre attentivement lvolution de
lincidence de la tuberculose, notamment dans les nouvelles gnrations denfants, surtout dans la
situation dinquitude actuelle provoque par les incertitudes concernant lapprovisionnement en vaccin
BCG.
 TRAITEMENT & MANAGEMENT
Drug rsistance TB
Drug-resistant TB continues to threaten global TB control and remains a major
public health concern in many countries.
Globally, an estimated 3.3% of new TB cases and 20% of previously treated
cases have MDR-TB, a level that has changed little in recent years.
In 2014, an estimated 190 000 people died of MDR-TB

Globally, only 50% of MDR-TB patients were successfully treated. However,

the 2015 treatment success target of 75% for MDR-TB patients was reached
by 43 of the 127 countries and territories that reported outcomes for the
2012 cohort, including three high MDR-TB burden countries (Estonia, Ethiopia
and Myanmar).

Extensively drug-resistant TB (XDR-TB) had been reported by 105 countries

by 2015. An estimated 9.7% of people with MDR-TB have XDR-TB.
 TRAITEMENT & MANAGEMENT
Eastern European and central Asian countries continue to have the highest levels of
MDR-TB.
 TRAITEMENT & MANAGEMENT
En France en 2009, environ 6% des souches rsistantes lisoniazide Souche MDR
1,4% (favorise par traitements mal conduits)
.
 TRAITEMENT & MANAGEMENT
Without treatment,
the death rate is high

lidentication rapide des cas

leur prise en charge prcoce et
adquate
TRAITEMENT & MANAGEMENT
 TRAITEMENT & MANAGEMENT
In the diagnostics pipeline, tests based on molecular tech- nologies are
the most advanced.
" A diagnostic platform called the GeneXpert Omni is in development. It
is intended for point-of-care testing for TB and rifampicin-resistant TB
using Xpert MTB/RIF cartridges. The device is expected to be smaller,
lighter and less expensive than currently available platforms for point-of-
care nucleic acid detection and will come with a built-in, 4-hour battery.
" A next-generation cartridge called Xpert Ultra is also in development. It
is intended to replace the Xpert MTB/RIF cartridge and could potentially
replace conventional culture as the primary diagnostic tool for TB.
 TRAITEMENT & MANAGEMENT
" Eight new or repurposed anti-TB drugs are in advanced phases of
clinical development. For the first time in six years, an anti-TB drug
candidate (TBA-354) is in Phase I testing.
Recent observational studies of the effectiveness of short treatment
regimens for MDR-TB in Niger and Cameroon found that a 12-month
regimen was effective and well-tol- erated in patients not previously
exposed to second-line drugs. At least 16 countries in Africa and Asia
have intro- duced shorter regimens as part of trials or observational
studies under operational research conditions, and WHO will reassess
current guidance on their use in 2016.
" Fifteen vaccine candidates are in clinical trials. Their emphasis has
shifted from children to adolescents and adults.
" New diagnostics, drugs and vaccines will be needed to achieve the
targets set in the End TB Strategy.