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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

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Tuberculosis in children and young adults l.jpg

Tuberculosis in Children and Young Adults

Clydette Powell, MD, MPH

USAID/Washington

CCIH, May 2004


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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


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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


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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


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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


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Leading Infectious Disease Causes of Death, 1998

3.5

2.3

2.2

1.5

1.1

0.9

WHO Report 2000


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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


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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?

700

600

500

400

300

200

100

0

Male

Female

Per 100,000 population

<11-45-910-1415-1920-2425-2930-3435-3940-4445-4950-54

Age (years)


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Childhood TB diagnosed by:

  • Combination of :

    • Contact with infectious adult case

    • Symptoms and signs

    • Positive tuberculin skin test

    • Suspicious CXR

    • Bacteriological confirmation

    • Serology


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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


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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


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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


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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


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Challenges for Surveillance

  • Difficult diagnosis of childhood TB

  • Lack of standard case definition

  • Increased extrapulmonary disease

  • Low public health priority of childhood TB


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WHO Estimated Total Cases by Age, 2000


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WHO Estimated Total Cases by Age, 2000


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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.


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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.


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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


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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.


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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


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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


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Clinical and immunopathological course of HIV associated TB


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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?


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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


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