Tuberculosis in Children and

Young Adults

Clydette Powell, MD, MPHUSAID/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

Leading Infectious Disease Causes of Death, 1998

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WHO Report 2000

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

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Effect of HIV?Effect of HIV?

Childhood TB diagnosed by:

Combination of :Combination of : Contact with infectious adult caseContact with infectious adult case Symptoms and signsSymptoms and signs Positive tuberculin skin testPositive tuberculin skin test Suspicious CXRSuspicious CXR Bacteriological confirmationBacteriological confirmation Serology Serology

Risk factors : infection to diseaseRisk factors : infection to disease

HIVHIVMalnutritionMalnutritionRecent exposureRecent exposureYoung age Young age

Short incubation periodShort incubation periodMore severeMore severeHighest riskHighest riskMore difficult to diagnoseMore difficult to diagnose

Host factorsHost factors

Effect of HIV?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 ofTuberculous Infection Among Children by Type ofContact and Bacteriologic Status of Index Case,Contact and Bacteriologic Status of Index Case,British Columbia and Saskatchewan, 1966-1971British Columbia and Saskatchewan, 1966-1971

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Grzybowski S, et al. Bull Int Union Tuberc 1975;50:90-106

Close

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Casual

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

TOTAL 6,856,537 659,397 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% 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.

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 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.

Relationship between TB and HIV Relationship between TB and HIV

200200

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00 0.10.1 0.20.2 0.30.3 0.40.4

HIV prevalence adults 15HIV prevalence adults 15- 49 years- 49 years

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What about children?What about children?

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 Clinical and immunopathological course of HIV associated TBHIV 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