Prevalence of tuberculosis in post-mortem studies of HIV-infected adults and children in resource-limited settings

Abstract

Objectives:Tuberculosis (TB) is estimated to be the leading cause of HIV-related deaths globally. However, since HIV-associated TB frequently remains unascertained, we systematically reviewed autopsy studies to determine the true burden of TB at death.Methods:We systematically searched Medline and Embase databases (to end 2013) for literature reporting on health facility-based autopsy studies of HIV-infected adults and/or children in resource-limited settings. Using forest plots and random-effects meta-analysis, we summarized the TB prevalence found at autopsy and used meta-regression to explore variables associated with autopsy TB prevalence.Results:We included 36 eligible studies, reporting on 3237 autopsies. Autopsy TB prevalence was extremely heterogeneous (range 0–64.4%), but was markedly higher in adults [pooled prevalence 39.7%, 95% confidence interval (CI) 32.4–47.0%] compared to children (pooled prevalence 4.5%, 95% CI 1.7–7.4%). Post-mortem TB prevalence varied by world region, with pooled estimates in adults of 63.2% (95% CI 57.7–68.7%) in South Asia (n = 2 studies); 43.2% (95% CI 38.0–48.3) in sub-Saharan Africa (n = 9 studies); and 27.1% (95% CI 16.0–38.1%) in the Americas (n = 5 studies). Autopsy prevalence positively correlated with contemporary estimates of national TB prevalence. TB in adults was disseminated in 87.9% (82.2–93.7%) of cases and was considered the cause of death in 91.4% (95% CI 85.8–97.0%) of TB cases. Overall, TB was the cause of death in 37.2% (95% CI 25.7–48.7%) of adult HIV/AIDS-related deaths. TB remained undiagnosed at death in 45.8% (95% CI 32.6–59.1%) of TB cases.Conclusions:In resource-limited settings, TB accounts for approximately 40% of facility-based HIV/AIDS-related adult deaths. Almost half of this disease remains undiagnosed at the time of death. These findings highlight the critical need to improve the prevention, diagnosis and treatment of HIV-associated TB globally.

Empirical tuberculosis therapy versus isoniazid in adult outpatients with advanced HIV initiating antiretroviral therapy (REMEMBER): a multicountry open-label randomised controlled trial

“…The conduct of the study in multiple sites where early mortality rates are high and TB is endemic is a major strength, but the results may not be generalizable to settings where systematic TB screening is not performed or where limited resources prevent close follow-up and early TB diagnosis after ART initiation. In addition, the results from this study among outpatients initiating ART may be not be generalizable to sicker inpatient populations with higher mortality rates, where the prevalence of TB at autopsy has approached 50% 6 . However, randomized trials of empiric TB therapy in highly advanced patients in inpatient settings would address a different research question, and may have different concerns regarding equipoise.…”

“…Numerous studies done pre- and post-mortem have identified TB as the major cause of mortality in those with advanced HIV disease who are initiating ART in sub-Saharan Africa, India, Haiti and parts of South America, where our study took place 2, 6 . An additional hypothesized effect of empiric TB therapy relates to a potentially more durable TB preventive impact of isoniazid and rifampin compared to isoniazid alone 16 .…”

Implementation and Operational Research: Population-Based Active Tuberculosis Case Finding During Large-Scale Mobile HIV Testing Campaigns in Rural Uganda

“…1 In East Africa, TB remains a major cause of death despite effective antibiotics, due in part to diagnostic delay and under-diagnosis. 1–4 Late or non-presentation to health facilities is one major cause of under-diagnosis that contributes to ongoing transmission and persistently high mortality rates. 5,6 Shifting TB screening out of health facilities and into communities, or “active” case finding, may reduce delays in TB diagnosis and undiagnosed disease.…”

Can antiretrovirals curb southern Africa's HIV-associated TB epidemic?

“…1,2 There is evidence that antiretroviral therapy (ART) reduces the risk of acquiring TB among PLHIV even at higher CD4 cell counts, 3 and modeling using data from nine sub-Saharan African countries suggests that immediate ART will avert over a third of new TB cases by 2050. 4 A study from Zimbabwe in this edition of Public Health Action adds to the case for expanded ART coverage as a way to reduce the burden of TB.…”