Autopsy Prevalence of Tuberculosis and Other Potentially Treatable Infections among Adults with Advanced HIV Enrolled in Out-Patient Care in South Africa

• Published in: PloS one Vol. 11; no. 11; p. e0166158
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 09.11.2016; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; Adult; Adults; AIDS; Alveoli; Ambulatory care facilities; Antiretroviral agents; Antiretroviral therapy; Autopsies; Autopsy - statistics & numerical data; Bacteria; Bacterial infections; Bacteriology; Biology and Life Sciences; Bronchus; CD4 antigen; CD4 Lymphocyte Count; Cell culture; Cryptococcosis - epidemiology; Cryptococcosis - etiology; Cryptococcus; Death; Disease; Drug therapy; Fatalities; Female; Forensic pathology; Health care; Health sciences; Highly active antiretroviral therapy; HIV; HIV Infections - complications; HIV Infections - pathology; Human immunodeficiency virus; Humans; Hygiene; Infections; Laboratories; Lentivirus; Liver; Liver - pathology; Lung - pathology; Lungs; Male; Medical research; Medical treatment; Medicine; Medicine and Health Sciences; Meningitis; Missing in action; Mortality; Mycobacterium; Pneumocystis; Pneumonia; Pneumonia, Pneumocystis - epidemiology; Pneumonia, Pneumocystis - etiology; Prevalence; Prevalence studies (Epidemiology); Primary Health Care - statistics & numerical data; Public health; Respiratory diseases; Retroviridae; South Africa - epidemiology; Spleen; Spleen - pathology; Tuberculosis; Tuberculosis, Pulmonary - epidemiology; Tuberculosis, Pulmonary - etiology; Urine; South Africa
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0166158

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"). 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. 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.