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TB and HIV in children

TB and HIV in children. Pope Kosalaraksa, M.D. Department of Pediatrics Faculty of Medicine Khon Kaen University. TB/HIV: Outline. Epidemiologic consideration Clinical manifestation Diagnosis Antiretroviral therapy Disease prevention. Epidemiologic consideration.

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TB and HIV in children

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  1. TB and HIV in children Pope Kosalaraksa, M.D. Department of Pediatrics Faculty of Medicine Khon Kaen University

  2. TB/HIV: Outline • Epidemiologic consideration • Clinical manifestation • Diagnosis • Antiretroviral therapy • Disease prevention

  3. Epidemiologic consideration • TB-disease: high in countries with high prevalence of concomitant HIV and/or drug resistant TB • Huge programmatic gaps • WHO report estimated : 10.4 million episodes of TB during 2007 • Among 9.3 million incident cases of TB : 1.4 million (15%) had HIV co-infection : Africa 79%, SEA 11% Marais BJ, et al. Int J Tuberc Lung dis 2005;9:1305–13.

  4. Epidemiologic consideration • TB : commonest causes of morbidity and the leading cause of death in HIV-infected adults • Optimal integration of TB and HIV care : Big challenge

  5. TB in children • Underappreciated TB disease burden • Accurate quantification of childhood TB disease burden is difficult • Childhood TB: approximately 50% of adult TB in poor epidemic control area • TB in children results from recent transmission • Burden of pediatric disease reflects the level of TB control achieved within community Marais BJ, et al. Int J Tuberc Lung dis 2005;9:1305–13.

  6. High disease rates among HIV children • Increased MTB exposure : parent to very young child • Increased vulnerability to develop active disease • Age and immune status: most important : risk of TB in CD4%<15% = 4X baseline HIV RNA> 100,000 = 3X : 20X increase in TB incidence compared to HIV-uninfected infants Elenga N, et al. Pediatr Infect Dis J 2005;24:1077–82.

  7. TB in HIV-infected children • Increase risk for TB in HIV-infected adult and children • Unlike other AIDS-related OIs : CD4 is not sufficient indicator of increase risk Guideline for the prevention and treatment of opportunisitic infections among HIV-exposed and HIV-infected children. MMWR 2009;58,No.RR-11.

  8. TB in children • Infected from adults • Progress from primary infection more than reactivation • Identify and treat source person Bakshi SS, et al Am J Dis Child 1993;147:320-4.

  9. Clinical manifestations • TB/HIV: more likely to be symptomatic : fever, cough • Extrapulmonary disease (>25%) : lymph nodes, blood, CNS, bone : pericardium, peritoneum • Children < 4 yearsor HIV-infected children : once infected >> active TB disease : increase rate of miliary TB, meningitis

  10. Diagnosis: difficult • Tuberculin skin test (TST) : latent TB • Ex vivo assay : IFN-gamma : QuantiFERON-TB Gold, T-SPOT • Sputum, gastric content : AFB, culture : Nucleic acid amplification Guideline for the prevention and treatment of opportunisitic infections among HIV-exposed and HIV-infected children. MMWR 2009;58,No.RR-11.

  11. Diagnosis: children/HIV • Difficult to obtain specimen • Pre-existed or coincidental fever : LIP, bacterial pneumonia • Link to adult • High index of suspicion • Strenuous efforts to obtain diagnostic specimen • Mainly use: clinical, exposure history, CXR

  12. Pulmonary TB: CXR Children • localized alveolar infiltration • pneumonitis • hilar/mediastinal adenopathy +/- atelectasis Children with HIV • multilobar • diffuse interstitial • miliary

  13. Treatment • Empiric TB therapy : suspected case : continue until – rule out : use directly observed therapy • HIV-infected children : minimum 6-9 months : 12 months for bone, joint, meningitis, miliary • 2-month intensive phase

  14. Antituberculous treatment in HIV/TB • Rifampicin : critical role – bactericidal : potent induction of CYP3A – NNRTI, PI : overlap toxicities • Many pills : > 7 drugs : adherence Guideline for the prevention and treatment of opportunisitic infections among HIV-exposed and HIV-infected children. MMWR 2009;58,No.RR-11.

  15. ARV-naïve: HIV/TB • Optimal treatment both TB and HIV • Anti-TB: immediately • HAART Low CD4 : start ARV within 2-8 wks after anti-TB : severe immunocompromised – within 2 wks High CD4 : deferred ARV

  16. Drug resistant TB • Minimum 3 drugs • Bactericidal > 2 • 3-6 drug regimen • Duration 9-24 months Guideline for the prevention and treatment of opportunisitic infections among HIV-exposed and HIV-infected children. MMWR 2009;58,No.RR-11.

  17. Disease prevention • Early detection and rapid cure of infectious cases • ‘‘Three I’s’’ prevention strategy (WHO) : intensified case finding : infection control : isoniazid preventive

  18. Strategies for prevention, diagnosis and treatment of TB in HIV-infected children Marais BJ, et al. Paediatr Respir Rev 2011;12:39-45.

  19. ART and TB risk • ART in adults : significant reduce risk – TB • Immune recovery after HAART : reduce > 50% TB risk • Greatest benefit : early HIV diagnosis and treatment • Early diagnosis and treatment : increase survival and reduce TB Violari A, et al. N Engl J Med 2008;359:2233–44.

  20. Drug interaction • WHO guideline : ART should be initiated as soon as possible (preferably within the first 2-8 weeks of TB therapy) in all HIV-infected individuals diagnosed with TB • Rifampicin: drug interaction : NRTI – compatible : NNRTI – NVP > EFV : PIs - all

  21. Recommend ART with Anti-TB • 2NRTIs + EFV • 2 NRTIs + NVP (dose at upper end) • 3 NRTIs (VL < 100,000 copies/ml) • 2 NRTIs + LPV/RTV (mg-mg parity of LPV) Marais BJ, et al. Paediatr Respir Rev 2011;12:39-45.

  22. Immune reconstitution inflammatory syndrome (IRIS) • Transient worsening symptoms : fever, lymphadenopathy, intracranial granuloma, pleural or pericardial effusion • After HAART initiation in severely immunocompromised host • IRIS : unmasking : paradoxical

  23. IRIS Prospective survey : 152 Thai children, low CD4 (<15%), • IRIS (19%), usually within 4 wks of ART • Majority: atypical mycobacteria TB (3/14), BCG (2/14) Experience in Africa • young infants: M. bovis BCG • older children: TB Puthanakit T, et al. Pediatr Infect Dis J 2006;25:53–8.

  24. Higher TB mortality rate • co-infections with other pathogens • poorer absorption or penetration into affected areas of TB drugs • misdiagnosis in children with other HIV-related lung disease • poor treatment adherence due to chronic illness, death of the parent, high pill burden • advanced immunosuppression and severe malnutrition Marais BJ, et al. Paediatr Respir Rev 2011;12:39-45.

  25. TB in HIV-infected children: summary • Common • Has effect to each other • History of exposure: important • Specimen, lab diagnosis: difficult • Established system : TB contact history, CXR • Treatment: early, drug interaction • Adherence

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