Autopsy Prevalence of Tuberculosis and Other Potentially Treatable Infections among Adults with Advanced HIV Enrolled in Out-Patient Care in South Africa.
BACKGROUND
Early mortality among HIV-positive adults starting antiretroviral therapy (ART) remains high in resource-limited settings, with tuberculosis (TB) the leading cause of death. However, current methods to estimate TB-related deaths are inadequate and most autopsy studies do not adequately represent those attending primary health clinics (PHCs). This study aimed to determine the autopsy prevalence of TB and other infections in adults enrolled at South African PHCs in the context of a pragmatic trial of empiric TB treatment ("TB Fast Track").


RESULTS
Adults with CD4 ≤150 cells/μL, not on ART or TB treatment, were enrolled to TB Fast Track and followed up for at least six months. Minimally invasive autopsy (MIA) was conducted as soon as possible after death. Lungs, liver, and spleen were biopsied; blood, CSF, and urine aspirated; and bronchoalveolar lavage fluid obtained. Samples underwent mycobacterial, bacterial, and fungal culture; molecular testing (including Xpert® MTB/RIF); and histological examination. 34 MIAs were conducted: 18 (53%) decedents were female; median age was 39 (interquartile range 33-44) years; 25 (74%) deaths occurred in hospitals; median time from death to MIA was five (IQR 3-6) days. 16/34 (47%) had evidence of TB (14/16 [88%] with extrapulmonary disease; 6/16 [38%] not started on treatment antemortem); 23 (68%) had clinically important bacterial infections; four (12%) cryptococcal disease; three (9%) non-tuberculous mycobacterial disease; and two (6%) Pneumocystis pneumonia. Twenty decedents (59%) had evidence of two or more concurrent infections; 9/16 (56%) individuals with TB had evidence of bacterial disease and two (13%) cryptococcal disease.


CONCLUSIONS
TB, followed by bacterial infections, were the leading findings at autopsy among adults with advanced HIV enrolled from primary care clinics. To reduce mortality, strategies are needed to identify and direct those at highest risk into a structured pathway that includes expedited investigation and/or treatment of TB and other infections.
TB Centre, London School of Hygiene & Tropical Medicine, London, United Kingdom.
Aaron S
http://orcid.org/0000-0001-9643-664X
AS
Karat
Department of Anatomical Pathology, National Health Laboratory Service and University of the Witwatersrand, Johannesburg, South Africa.
Tanvier
T
Omar
Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.|School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Anne
A
von Gottberg
The Aurum Institute, Johannesburg, South Africa.
Mpho
M
Tlali
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
TB Centre, London School of Hygiene & Tropical Medicine, London, United Kingdom.|The Aurum Institute, Johannesburg, South Africa.|School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Gavin J
GJ
Churchyard
TB Centre, 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
Foundation for Professional Development, Pretoria, South Africa.
Suzanne
S
Johnson
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, Maryland, 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
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
Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.|School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Nicole
N
Wolter
Africa Health Research Institute, Durban, South Africa.|Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
Emily B
EB
Wong
The Aurum Institute, Johannesburg, South Africa.|School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Salome
S
Charalambous
TB Centre, 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, Durban, South Africa.|University of KwaZulu-Natal, Durban, South Africa.
Alison D
AD
Grant
D000328:Adult; D001344:Autopsy / Q000706:statistics & numerical data; D018791:CD4 Lymphocyte Count; D003453:Cryptococcosis / Q000453:epidemiology / Q000209:etiology; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000473:pathology; D008168:Lung / Q000473:pathology; D008297:Male; D011020:Pneumonia, Pneumocystis / Q000453:epidemiology / Q000209:etiology; D015995:Prevalence; D011320:Primary Health Care / Q000706:statistics & numerical data; D013019:South Africa / Q000453:epidemiology; D013154:Spleen / Q000473:pathology; D014397:Tuberculosis, Pulmonary / Q000453:epidemiology* / Q000209:etiology