Childhood Tuberculosis
Launch of the Centre for International Child Health
29th January 2016
James Seddon
Clinical Lecturer
Imperial College London
Introduction
• Paediatric tuberculosis fascinating topic• Quite a challenging field to work in• Exciting times
• More funding• More research• More interest
• Opportunity • Advance field• Make a significant difference to some of the most vulnerable and
marginalised children
Child with symptoms
Identification of host response to organism
Identification of organism
Phenotypic identification of
organism
Genotypic identification of
organism
Making a diagnosis
Phenotypic identification or
resistance
Genotypic identification of
resistance
The impact of Bacillus Calmette–Guérin
vaccination on tuberculin skin test responses in
children is age-dependent: evidence to be
considered when screening children for
tuberculosis infection
NIKS study team. Thorax. Under review
Child with symptoms
Identification of host response to organism
Identification of organism
Phenotypic identification of
organism
Genotypic identification of
organism
Making a diagnosis
Phenotypic identification or
resistance
Genotypic identification of
resistance
Smear status
Smearpositive
Smearnegative Xpert MTB/RIF
GeneXpertpositive
GeneXpertnegative
Culture
Culturepositive
Culturenegative
Why understanding the epidemiology important?
• Who, where, when• Targeting resources• Discrepancies• Sentinel event• Market assessment• Advocacy
Challenges
• Few cases confirmed• Difficult to obtain specimens• Paucibacillary disease• Limited laboratory capability• Greatest challenge in youngest
children
• Under-reporting• Previously only sputum smear-
positive cases reported• Private sector frequently not
reported
All children with TB
Children who are diagnosed
with TB
Children with TB who are reported to
WHO
Children with TB who present to health services
0
25
50
75
AFR AMR EMR EUR SEA WPR GLOBAL
WHO region
% o
f inc
iden
t MD
R−T
B in
chi
ldre
n
MDR type
DS
FQR
SLR
XDR
0
25
50
75
100
AFR AMR EMR EUR SEA WPR GLOBAL
WHO region
% o
f in
ciden
t T
B in
child
ren
DR type
S
INH
RIF
MDR
DST S INH RIF MDR FQR SLR XDR
Disease 753,096 40,289 6,156 18,603 2,566 2,731 1,988
Infection 57,305,870 3,088,543 452,635 1,413,608 201,005 228,580 167,223
Burden of drug-resistant tuberculosis
Dodd et al. In prep
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0.01
0.10
1.00
0 10 20 30
Months on ART
Incid
ence r
ate
ra
tio (
log s
ca
le)
First author, Year
●
●
●
●
●
●
●
●
●
●
Auld, 2014
Bakeera−Kitaka, 2011
Braitstein, 2009
Brennan, 2014
Crook, 2016
Curtis, 2012
De Beaudrap, 2013
Edmonds, 2009
Li, 2013
Walters, 2014
Author/Year
Berggren Palme, 2001
Bhat, 1993
Chintu, 1993
Chintu, 1995
Luo, 1994
Mukadi, 1997
Rose, 2012
Yassin, 2011
RE summary
HIV in
TB
(n/N)
47 / 377
36 / 96
88 / 237
42 / 61
67 / 110
31 / 160
18 / 33
14 / 141
OR [95 % CI]
HIV in
controls
(n/N)
2 / 122
18 / 134
26 / 242
15 / 160
16 / 167
0 / 161
22 / 93
3 / 153
7.9 [ 4.5 −13.7]
1.0 5.0 20.0 100.0
Odds Ratio (log scale)
Relationship between HIV and tuberculosis in children
Dodd et al. In prep
0 10000 20000 30000 40000 50000 60000 70000 80000
AFR
AMR
EMR
EUR
SEA
WPR
DeathsinchildrenduetoTB
Ontx(HIV-)
Offtx(HIV-)
Ontx(HIV+)
Offtx(HIV+)
Mortality in children due to tuberculosis
Child TB mortality
(absolute numbers)
0 to 524
524 to 1,978
1,978 to 6,080
6,080 to 18,080
18,080 to 42,332
No data
Dodd et al. In prep
Treatment of MDR-TB disease
Treatment of MDR-TB infection
Treatment of DS-TB disease
Treatment of DR-TB
infection
Treatment of TB Meningitis
New Drugs
Children < 5 years
(aged 1-5 years TST positive or < 12 months regardless of TST)with known MDR-TB adult contact in the household
N=988 households
Randomise (1:1)
INTERVENTION ARM
Treatment Phase:6 months daily dosing of
levofloxacin
Follow-up phase:18 months post-treatment
CONTROL ARM
Treatment Phase:6 months daily dosing of
placebo
Follow-up phase:18 months post-treatment
Conclusions
• Childhood TB big problem globally• Important problem in the UK
• After a long period of little investigation lots of work now being done on paediatric TB
• Lots being done at Imperial
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