Measuring mortality due to HIV-associated tuberculosis among adults in South Africa: Comparing verbal autopsy, minimally-invasive autopsy, and research data
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Date
2017-03-23Author
Karat, Aaron S.
Tlali, Mpho
Fielding, Katherine L.
Charalambous, Salome
Chihota, Violet N.
Churchyard, Gavin J.
Hanifa, Yasmeen
Johnson, Suzanne
McCarthy, Kerrigan
Martinson, Neil A.
Omar, Tanvier
Kahn, Kathleen
Chandramohan, Daniel
Grant, Alison D.
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Karat, A. S., Tlali, M., Fielding, K. L., Charalambous, S., Chihota, V. N., Churchyard, G. J., Hanifa, Y., Johnson, S., McCarthy, K., Martinson, N. A., Omar, T., Kahn, K., Chandramohan, D. & Grant, A. D. (2017) Measuring mortality due to HIV-associated tuberculosis among adults in South Africa: Comparing verbal autopsy, minimally-invasive autopsy, and research data. PLOS One, 12(3).
Abstract
Background
The World Health Organization (WHO) aims to reduce tuberculosis (TB) deaths by 95% by
2035; tracking progress requires accurate measurement of TB mortality. International Classification of Diseases (ICD) codes do not differentiate between HIV-associated TB and HIV
more generally. Verbal autopsy (VA) is used to estimate cause of death (CoD) patterns but
has mostly been validated against a suboptimal gold standard for HIV and TB. This study,
conducted among HIV-positive adults, aimed to estimate the accuracy of VA in ascertaining
TB and HIV CoD when compared to a reference standard derived from a variety of clinical
sources including, in some, minimally-invasive autopsy (MIA). Methods and findings
Decedents were enrolled into a trial of empirical TB treatment or a cohort exploring diagnostic
algorithms for TB in South Africa. The WHO 2012 instrument was used; VA CoD were assigned using physician-certified VA (PCVA), InterVA-4, and SmartVA-Analyze. Reference
CoD were assigned using MIA, research, and health facility data, as available. 259
VAs were completed: 147 (57%) decedents were female; median age was 39 (interquartile
range [IQR] 33±47) years and CD4 count 51 (IQR 22±102) cells/μL. Compared to reference
CoD that included MIA (n = 34), VA underestimated mortality due to HIV/AIDS (94% reference,
74% PCVA, 47% InterVA-4, and 41% SmartVA-Analyze; chance-corrected concordance
[CCC] 0.71, 0.42, and 0.31, respectively) and HIV-associated TB (41% reference,
32% PCVA; CCC 0.23). For individual decedents, all VA methods agreed poorly with reference
CoD that did not include MIA (n = 259; overall CCC 0.14, 0.06, and 0.15 for PCVA,
InterVA-4, and SmartVA-Analyze); agreement was better at population level (cause-specific
mortality fraction accuracy 0.78, 0.61, and 0.57, for the three methods, respectively). Conclusions
Current VA methods underestimate mortality due to HIV-associated TB. ICD and VA methods
need modifications that allow for more specific evaluation of HIV-related deaths and
direct estimation of mortality due to HIV-associated TB.