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Karat, Aaron S.; Omar, Tanvier; von Gottberg, Anne; Tlali, Mpho; Chihota, Violet N.; Churchyard, Gavin J.; Fielding, Katherine L.; Johnson, Suzanne; Martinson, Neil A.; McCarthy, Kerrigan; Wolter, Nicole; Wong, Emily B.; Charalambous, Salome; Grant, Alison D. (2016)
Publisher: Public Library of Science
Journal: PLoS ONE
Languages: English
Types: Article
Subjects: Microbial Pathogens, Research Article, Bacteria, Anatomy, Infectious Diseases, Pathology and Laboratory Medicine, Mycobacterium Tuberculosis, Human Cytomegalovirus, Histology, Pathogens, Herpesviruses, Actinobacteria, Viruses, Surgical and Invasive Medical Procedures, Biology and Life Sciences, DNA viruses, Tuberculosis, Microbiology, Physiology, Medicine, Tropical Diseases, Bacterial Pathogens, Body Fluids, Bacterial Diseases, Q, Medical Microbiology, Viral Pathogens, R, Nervous System, Science, Cerebrospinal Fluid, Organisms, Medicine and Health Sciences, Autopsy
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”). Methods and Findings 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.

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