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 worlds 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

Leading Infectious Disease Causes of Death, 1998

Death in millions 4 3 2 1 0
3.5 2.3 2.2 1.5

Under age 5 Over age 5

1.1 0.9

AR I

AI DS

TB

ia ar al M M

he a

rr

WHO Report 2000

Di a

ea

sl

es

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

700

Per 100,000 population

600 500 400 300 200 100

Male Female

0 <1 1-4 5-9 10-1415-19

Effect of HIV?

20-2425-29 30-3435-3940-44 Age (years)

45-49

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
40 35 30

Close

Percent infected

25 20 15 10 5 0 Smear +

Casual

Smear -

Close Casual

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 India China Indonesia Bangladesh Nigeria Pakistan Philippines South Africa Russian Fed. Ethiopia Dem. Rep. Congo Total Cases 1,815,740 1,645,703 581,918 325,110 261,404 244,736 230,217 220,486 183,373 178,349 148,598 Cases <15 yrs 185,233 86,978 15,691 33,166 32,310 61,905 12,167 35,449 7,778 28,675 24,052 % in Children 10.2 5.3 2.7 10.2 12.4 25.3 5.3 16.1 4.2 16.1 16.1

WHO Estimated Total Cases by Age, 2000

Country Viet Nam Kenya Tanzania Brazil Thailand Myanmar Zimbabwe Uganda Cambodia Afghanistan Mozambique TOTAL Total Cases 143,023 137,603 117,489 113,528 85,928 78,489 76,296 75,250 75,045 69,342 47,909 6,856,537 Cases < 15 yrs 7,559 22,124 18,890 23,520 2,317 8,007 12,267 12,099 3,966 17,540 7,703 659,397 % in Children 5.3 16.1 16.1 20.7 2.7 10.2 16.1 16.1 5.3 25.3 16.1 9.6

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

What about children?
Estimated TB incidence (per 100 000 population)
800 800 600 600

400 400

200 200

0.1

0.2

0.3

0.4

HIV prevalence adults 15- 49 years

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