Tuberculosis in Children and Young Adults

1. Tuberculosis in Children and Young Adults Clydette Powell, MD, MPH USAID/Washington CCIH, May 2004

2. 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

3. 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

4. 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

5. 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

6. Leading Infectious Disease Causes of Death, 1998 3.5 2.3 2.2 1.5 1.1 0.9 WHO Report 2000

7. 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

8. 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

9. Effect of HIV? 700 600 500 400 300 200 100 0 Male Female Per 100,000 population <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)

10. Childhood TB diagnosed by: • Combination of : • Contact with infectious adult case • Symptoms and signs • Positive tuberculin skin test • Suspicious CXR • Bacteriological confirmation • Serology

11. Host factors Effect of HIV? Risk factors : infection to disease HIV Malnutrition Recent exposure Young age Short incubation period More severe Highest risk More difficult to diagnose

12. 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

13. Tuberculous Infection Among Children by Type of Contact and Bacteriologic Status of Index Case, British Columbia and Saskatchewan, 1966-1971 Close Percent infected Close Casual Casual Grzybowski S, et al. Bull Int Union Tuberc 1975;50:90-106

14. 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

15. Challenges for Surveillance • Difficult diagnosis of childhood TB • Lack of standard case definition • Increased extrapulmonary disease • Low public health priority of childhood TB

16. WHO Estimated Total Cases by Age, 2000

17. WHO Estimated Total Cases by Age, 2000

18. 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% smear-negative, 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.

19. 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.

20. 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

21. TB and BCG Vaccination • Efficacy for adult pulmonary TB 0-80% 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.

22. Relationship between TB and HIV What about children? 800 800 600 600 Estimated TB incidence (per 100 000 population) 400 400 200 200 0 0.1 0.2 0.3 0.4 0 0.1 0.2 0.3 0.4 HIV prevalence adults 15- 49 years

23. 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

24. Clinical and immunopathological course of HIV associated TB

25. 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?

26. 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