Tuberculosis in Pediatric Antiretroviral Therapy Programs in Low- and Middle-Income Countries: Diagnosis and Screening Practices

Ballif, Marie; Renner, Lorna; Dusingize, Jean Claude; Leroy, Valériane; Ayaya, Samuel; Wools‐Kaloustian, Kara; Cortés, Claudia; McGowan, Catherine C.; Graber, Claire; Mandalakas, Anna M.; Mofenson, Lynne; Egger, Matthias; Wati, Ketut Dewi Kumara; Nallusamy, Revathy; Reubenson, Gary; Davies, Mary‐Ann; Fenner, Lukas

doi:10.1093/jpids/piu020

Cited by 15 publications

(10 citation statements)

References 25 publications

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“…Similarly, in 2012 we conducted a site-level survey of pediatric ART programs in six IeDEA regions and found that NAAT was available at about one-third of sites; and, among 146 children who developed TB, AFB smear was utilized for 52%, mycobacterial culture for 17%, and NAAT for only 8%. 19 Among the many impediments to TB diagnosis in children is obtaining diagnostic respiratory specimens. Performing early morning gastric aspirates can improve diagnostic yield, but requires hospitalization, which is often not practical in LMIC.…”

Section: Discussionmentioning

confidence: 99%

“…Limited availability of diagnostics, challenges with obtaining sputum, and paucibacillary disease which may be more pronounced in HIV/TB co-infected children may result in many children being diagnosed with TB on clinical criteria alone (without microbiologic confirmation with NAAT, acid-fast bacilli [AFB] culture, and/or AFB smear). 12,16-19 Despite studies demonstrating low risk for ethambutol associated ocular toxicity, 13,14 some practitioners still opt to prescribe a three-drug IP regimen lacking ethambutol for preverbal children. Similarly, some providers delay ART initiation beyond the recommended eight weeks after ATT initiation to avoid immune reconstitution inflammatory syndrome (IRIS), which is uncommon among children.…”

Section: Introductionmentioning

confidence: 99%

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Tuberculosis Treatment Outcomes Among HIV/TB-Coinfected Children in the International Epidemiology Databases to Evaluate AIDS (IeDEA) Network

Carlucci

Peratikos

Kipp

et al. 2017

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Introduction Management of tuberculosis (TB) is challenging in HIV/TB co-infected children. The World Health Organization (WHO) recommends nucleic acid amplification tests for TB diagnosis, a four-drug regimen including ethambutol during intensive phase of treatment (IP), and initiation of antiretroviral therapy (ART) within eight weeks of TB diagnosis. We investigated TB treatment outcomes by diagnostic modality, IP regimen, and ART status. Methods We conducted a retrospective cohort study among HIV/TB co-infected children enrolled at International Epidemiology Databases to Evaluate AIDS treatment sites from 2012-2014. We modeled TB outcome using multivariable logistic regression including diagnostic modality, IP regimen, and ART status. Results Among 386 HIV-infected children diagnosed with TB, 20% had microbiological confirmation of TB, and 20% had unfavorable TB outcomes. During IP, 78% were treated with a four-drug regimen. Thirty-one percent were receiving ART at the time of TB diagnosis, and 32% were started on ART within eight weeks of TB diagnosis. Incidence of ART initiation within eight weeks of TB diagnosis was higher for those with favorable TB outcomes (64%) compared to those with unfavorable outcomes (40%) (p=0.04). Neither diagnostic modality (OR 1.77; 95%CI 0.86-3.65) nor IP regimen (OR 0.88; 95%CI 0.43-1.80) were associated with TB outcome. Discussion In this multinational study of HIV/TB co-infected children, many were not managed per WHO guidelines. Children with favorable TB outcomes initiated ART sooner than children with unfavorable outcomes. These findings highlight the importance of early ART for children with HIV/TB co-infection, and reinforce the need for implementation research to improve pediatric TB management.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Tuberculosis Treatment Outcomes Among HIV/TB-Coinfected Children in the International Epidemiology Databases to Evaluate AIDS (IeDEA) Network

Carlucci

Peratikos

Kipp

et al. 2017

JAIDS Journal of Acquired Immune Deficiency Syndromes

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“…For example, a study compared the characteristics and comprehensiveness of adult HIV care and treatment programmes in sub-Saharan Africa with programmes in the Americas and Asia-Pacific region [7]. Other studies examined the management of mental health and substance use disorders [8], or the diagnostic and screening practices for (drug resistant) tuberculosis in adult and paediatric patients [9][10][11]. Furthermore, the routine data collected by participating sites have been enriched in some countries by linking the routine HIV databases to cancer registries [12,13], vital registries [14] or administrative databases [15].…”

Section: Data Collection At Individual and Site Levelmentioning

confidence: 99%

Cohort profile: The International epidemiology Databases to Evaluate AIDS (IeDEA) in sub-Saharan Africa, 2012-2019

Chammartin

Ostinelli

Anastos

et al. 2019

Preprint

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Purpose: The objectives of the International epidemiology Databases to Evaluate AIDS (IeDEA) are to (i) evaluate the delivery of combination antiretroviral therapy (ART) in children, adolescents and adults in sub-Saharan Africa, (ii) to describe ART regimen effectiveness, durability and tolerability, (iii) to examine HIV-related comorbidities and co-infections, and (iv) to examine the pregnancy- and HIV-related outcomes of women on ART and their infants exposed to HIV or antiretroviral therapy in utero or via breastmilk. Participants: IeDEA is organized in four regions (Central, East, Southern and West Africa), with 240 treatment and care sites, six data centres at African, European and US universities, and almost 1.4 million children, adolescents and adult people living with HIV (PLWHIV) enrolled. Findings to date: The data include socio-demographic characteristics, clinical outcomes, opportunistic events, treatment regimens, clinic visits and laboratory measurements. They have been used to analyse outcomes in people living with HIV-1 or HIV-2 who initiate ART, including determinants of mortality, of switching to second-line and third-line ART, drug resistance, loss to follow-up and the immunological and virological response to different ART regimens. Programme-level estimates of mortality have been corrected for loss to follow-up. We examined the impact of co-infection with hepatitis B and C, and the epidemiology of different cancers and of (multi-drug resistant) tuberculosis, renal disease and of mental illness. The adoption of 'Treat All', making ART available to all PLWHIV regardless of CD4+ cell count or clinical stage was another important research topic. Future plans: IeDEA has formulated several research priorities for the 'Treat All' era in sub-Saharan Africa. It recently obtained funding to set up sentinel sites where additional data are prospectively collected on cardiometabolic risks factors as well as mental health and liver diseases, and is planning to create a drug resistance database.

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“…Finally, there have been missed opportunities to correctly diagnose and treat children with TB in programs focused on other health problems of children who also are at risk for TB. 4,5 …”

Section: Why Has Childhood Tb Been Neglected?mentioning

confidence: 99%

“…Unfortunately, a recently published survey of pediatric antiretroviral treatment programs in Africa, Asia, the Caribbean, and Central and South America documented a low utilization of TB diagnostic and screening services in these programs. 4 Although sputum microscopy and chest radiography were available in all programs, among the 146 children diagnosed with TB during the study period, chest radiography was used in 86%, sputum microscopy in 52%, induced sputum microscopy in 26%, culture in 17%, and Xpert MTB/ RIF in 8% of children. Only 86% of the sites provided treatment of TB disease, and 30% never provided isoniazid preventive therapy to HIV-infected children.…”

Section: Childhood Tb and Hiv Infectionmentioning

confidence: 99%

Improving Tuberculosis Care for Children in High-Burden Settings

Starke

2014

Pediatrics

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Tuberculosis in Pediatric Antiretroviral Therapy Programs in Low- and Middle-Income Countries: Diagnosis and Screening Practices

Cited by 15 publications

References 25 publications

Tuberculosis Treatment Outcomes Among HIV/TB-Coinfected Children in the International Epidemiology Databases to Evaluate AIDS (IeDEA) Network

Tuberculosis Treatment Outcomes Among HIV/TB-Coinfected Children in the International Epidemiology Databases to Evaluate AIDS (IeDEA) Network

Cohort profile: The International epidemiology Databases to Evaluate AIDS (IeDEA) in sub-Saharan Africa, 2012-2019

Improving Tuberculosis Care for Children in High-Burden Settings

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