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


RESULTS
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.
Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, United Kingdom.
Aaron S
http://orcid.org/0000-0001-9643-664X
AS
Karat
The Aurum Institute, Johannesburg, South Africa.
Mpho
M
Tlali
Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, United Kingdom.|School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Katherine L
KL
Fielding
The Aurum Institute, Johannesburg, South Africa.|School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Salome
S
Charalambous
The Aurum Institute, Johannesburg, South Africa.|School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Violet N
VN
Chihota
The Aurum Institute, Johannesburg, South Africa.|Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, United Kingdom.|School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Gavin J
GJ
Churchyard
Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, United Kingdom.
Yasmeen
Y
Hanifa
Foundation for Professional Development, Pretoria, South Africa.
Suzanne
S
Johnson
The Aurum Institute, Johannesburg, South Africa.|School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.|Division of Public Health, Surveillance and Response, National Institute for Communicable Disease of the National Health Laboratory Service, Johannesburg, South Africa.
Kerrigan
K
McCarthy
Perinatal HIV Research Unit, and Medical Research Council Soweto Matlosana Collaborating Centre for HIV/AIDS and TB, University of the Witwatersrand, Johannesburg, South Africa.|Johns Hopkins University Center for TB Research, Baltimore, United States of America.|Department of Science and Technology / National Research Foundation Centre of Excellence for Biomedical TB Research, University of the Witwatersrand, Johannesburg, South Africa.
Neil A
NA
Martinson
Department of Anatomical Pathology, National Health Laboratory Service and University of the Witwatersrand, Johannesburg, South Africa.
Tanvier
T
Omar
MRC/Wits Rural Public Health and Health Transitions Research Unit (Agincourt), School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.|INDEPTH Network, Accra, Ghana.|Epidemiology and Global Health Unit, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
Kathleen
K
Kahn
Department of Disease Control, London School of Hygiene & Tropical Medicine, London, United Kingdom.
Daniel
D
Chandramohan
Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, United Kingdom.|School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.|Africa Health Research Institute, School of Nursing and Public Health, University of KwaZulu-Natal, Durban, South Africa.
Alison D
AD
Grant
D000328:Adult; D001344:Autopsy / Q000379:methods; D002423:Cause of Death; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D019060:Minimally Invasive Surgical Procedures; D013019:South Africa / Q000453:epidemiology; D014397:Tuberculosis, Pulmonary / Q000209:etiology / Q000401:mortality*