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Measuring mortality due to HIV-associated tuberculosis among adults in South Africa: Comparing verbal autopsy, minimally-invasive autopsy, and research data.

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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Karat AS, Tlali M, Fielding KL, Charalambous S, Chihota VN, Churchyard GJ, Hanifa Y, Johnson S, McCarthy K, Martinson NA, Omar T, Kahn K, Chandramohan D, Grant AD,


Karat AS, Tlali M, Fielding KL, Charalambous S, Chihota VN, Churchyard GJ, Hanifa Y, Johnson S, McCarthy K, Martinson NA, Omar T, Kahn K, Chandramohan D, Grant AD, (click to view)

Karat AS, Tlali M, Fielding KL, Charalambous S, Chihota VN, Churchyard GJ, Hanifa Y, Johnson S, McCarthy K, Martinson NA, Omar T, Kahn K, Chandramohan D, Grant AD,

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PloS one 2017 03 2312(3) e0174097 doi 10.1371/journal.pone.0174097

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.

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