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Tuberculosis in
Children and
Young Adults
Clydette Powell, MD, MPH
USAID/Washington
CCIH, May 2004
Objectives
• Overview global epidemiology
• Review available surveillance data
and epidemiologic studies
• Review TB and HIV association
• Assess data limitations
• Provide recommendations for future
data collection and research
Tuberculosis
A Global Emergency
• One third of the world’s population is infected
• TB kills 5,000 people a day – 2-3 million each
year
• HIV and TB co-infection is producing explosive
epidemics
• Hundreds of thousands of children will become
TB orphans this year
• MDR threatens global TB control
Background
• Tuberculosis (TB) is increasing
among adults in many areas
• TB is major cause of childhood
morbidity and mortality worldwide
• Limited information on epidemiology
of TB in children
Childhood TB
•
Why neglected?
– Not considered important in global program
or contributing to immediate transmission
– Not regarded as public health risk
– Difficult to diagnose
•
Why is it important?
– Health problem in children
– May later contribute to epidemic
4
3.5
3
2.3
Under age 5
Over age 5
2.2
2
1.5
1.1
1
0.9
WHO Report 2000
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Death in millions
Leading Infectious Disease
Causes of Death, 1998
TB in Children
• WHO estimate of TB in children
– 1.3 million annual cases
– 450,000 deaths
• 15% of TB in low-income countries
children vs. 6% in United States
Childhood TB as Sentinel Event
• Indicates recent transmission in a
community
• Rapid progression from infection to
disease
“A deterioration in the control of TB thus
immediately hurts the youngest generation”
(Rieder, 1997)
• Children are future reservoir of disease
Rieder H. Anales Nestle, 1997
Per 100,000 population
700
Male
Female
600
500
400
300
200
100
0
<1
1-4
5-9
10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54
Age (years)
Effect of HIV?
Childhood TB diagnosed by:
Combination of :
 Contact with infectious adult case
 Symptoms and signs
 Positive tuberculin skin test
 Suspicious CXR
 Bacteriological confirmation
 Serology
Risk factors : infection to disease
HIV
Malnutrition
Recent exposure
Young age
Short incubation period
More severe
Highest risk
More difficult to diagnose
Host factors
Effect of HIV?
Risk Factors for TB - U.S.
• Racial/ethnic minorities
• Foreign-born children or children of
•
•
•
•
immigrant families
Internationally adopted children
Children traveling overseas
Poverty and crowding
Contact with infectious adult case
Tuberculous Infection Among Children by Type of
Contact and Bacteriologic Status of Index Case,
British Columbia and Saskatchewan, 1966-1971
Percent infected
40
35
Close
30
25
20
15
10
Casual
5
Close
Casual
0
Smear +
Smear -
Grzybowski S, et al. Bull Int Union Tuberc 1975;50:90-106
Risk of Progression to Disease
• Age
– 43% in infants (children < 1year)
– 25% in children aged one to five years
– 15% in adolescents
– 10% in adults
• Recent Infection
• Malnutrition
• Immunosuppression, particularly HIV
Miller, 1963
Challenges for Surveillance
•
•
•
•
Difficult diagnosis of childhood TB
Lack of standard case definition
Increased extrapulmonary disease
Low public health priority of
childhood TB
WHO Estimated Total Cases
by Age, 2000
Country
Total Cases
Cases <15 yrs
% in Children
India
1,815,740
185,233
10.2
China
1,645,703
86,978
5.3
Indonesia
581,918
15,691
2.7
Bangladesh
325,110
33,166
10.2
Nigeria
261,404
32,310
12.4
Pakistan
244,736
61,905
25.3
Philippines
230,217
12,167
5.3
South Africa
220,486
35,449
16.1
Russian Fed.
183,373
7,778
4.2
Ethiopia
178,349
28,675
16.1
Dem. Rep. Congo
148,598
24,052
16.1
WHO Estimated Total Cases
by Age, 2000
Country
Total Cases
Cases < 15 yrs
% in Children
Viet Nam
143,023
7,559
5.3
Kenya
137,603
22,124
16.1
Tanzania
117,489
18,890
16.1
Brazil
113,528
23,520
20.7
Thailand
85,928
2,317
2.7
Myanmar
78,489
8,007
10.2
Zimbabwe
76,296
12,267
16.1
Uganda
75,250
12,099
16.1
Cambodia
75,045
3,966
5.3
Afghanistan
69,342
17,540
25.3
Mozambique
47,909
7,703
16.1
6,856,537
659,397
9.6
TOTAL
Childhood TB in Malawi
• Retrospective study of 43 hospitals using
•
•
National TB Data from 1998
2739 cases in children (11.9%)
– 1.3% smear-positive, 21.3% smearnegative, 15.9% extrapulmonary
Poor outcomes
– 45% completed treatment
– 17% died
– 13% default
– 21% unknown
Harries AD et al.
Int J Tuberc Lung Dis. 2002; 6: 424-31.
Active Case Finding of TB Meningitis
• South Africa study among children
< 15 years
• Only 56% of cases were registered
• 16% of all cases in register contained
errors
– Incorrect diagnosis, double notification,
clerical error
Berman et al. Tubercle. 1992; 73: 349-55.
Extrapulmonary TB in Children
• Proportion in a given country could
be used as measure of case
detection
– 25-44% of all childhood TB in Ugandan
study
– 43% of children in Ethiopian study
– 21.3% of childhood TB using US
surveillance data
TB and BCG Vaccination
• Efficacy for adult pulmonary TB 080% in randomized clinical trials
• Best efficacy against serious
childhood disease
– 64% protection against TB meningitis
– 78% protection effect against
disseminated TB
• BCG important for young children,
inadequate as single strategy
Colditz GA et al. JAMA 1994; 271: 698-702.
Relationship between TB and HIV
Estimated TB incidence
(per 100 000 population)
What about children?
800
600
400
200
0
0.1
0.2
0.3
HIV prevalence adults 15- 49 years
0.4
TB/HIV Coinfection in Children
• 11-64% of children with TB are coinfected
•
•
•
with HIV in published studies
1-12% of children with AIDS in autopsy
studies found to have TB
Other lung disease in children with HIV
common
Difficulty of confirming TB in HIV-infected
children may result in overdiagnosis and
overreporting
Clinical and immunopathological course of
HIV associated TB
Treatment questions
• Difficult to evaluate true cure
• Recommended same length of treatment as
adults
• HIV & length of treatment??
• Many uncertainties eg pharmakokinetics,
treatment of MDR-TB
• Relapse/re-infection in HIV positive children
• Mortality?
Conclusions
• Data on trends in childhood TB are
•
•
•
•
limited
Consensus needed on common
definitions
Few epidemiologic studies in children
worldwide
Additional studies are needed
Childhood TB needs to become a priority