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Background: Information on causes of death in HIV-infected patients in Sub-Saharan Africa is mainly derived from observational cohort and verbal autopsy studies. Autopsy is the gold standard to ascertain cause of death. We conducted an autopsy study to describe and compare the clinical and autopsy causes of death and contributory findings in hospitalized HIV-infected and HIV-uninfected patients in Uganda. Methods: Between May and September 2009 a complete autopsy was performed on patients that died on a combined infectious diseases gastroenterology ward in Mulago Hospital in Kampala, Uganda. Autopsy cause of death and contributing findings were based on the macro- and microscopic post-mortem findings combined with clinical information. Clinical diagnoses were reported by the ward doctor and classified as confirmed, highly suspected, considered or not considered, based on information derived from the medical chart. Results are reported according to HIV serostatus. Results: Fifty-three complete autopsies were performed in 66% HIV-positive, 21% HIV-negative and 13% patients with an unknown HIV serological status. Infectious diseases caused death in 83% of HIV-positive patients, with disseminated TB as the main diagnosis causing 37% of deaths. The spectrum of illness and causes of death were substantially different between HIV-positive and HIV-negative patients. In HIV-positive patients 12% of postmortem diagnoses were clinically confirmed, 27% highly suspected, 16% considered and 45% not considered. In HIV-negative patients 17% of postmortem diagnoses were clinically highly suspected, 42% considered and 42% not considered. Conclusion: Autopsy examination remains an important tool to ascertain causes of death particularly in settings with limited access to diagnostic testing during life. HIV-positive patients continue to die from treatable and clinically undiagnosed infectious diseases. Until rapid-point of care testing is available to confirm common infections, empiric treatment should be further investigated.
Mulago National Tertiary Referral Hospital is located in Kampala, Uganda and is a university teaching centre. Over the last 10 years, approximately 6800 patients died annually in Mulago Hospital including maternal and child deaths. Based on data from the mortuary, the autopsy rate in Mulago Hospital over the past decade has been stable at 5%. This study was conducted on a combined infectious diseases and gastroenterology ward. The study team included clinical doctors and pathologists. Next of kin of all patients that died on weekdays in the period from May–September 2009 on the study ward were asked for written informed consent to participate in the study. Both verbal and written information about the research and the autopsy procedure was provided in English and Luganda, the main local language. If needed, a translator was asked to assist. Clinical information was collected by interviewing the next of kin using a standardized questionnaire and by reviewing the medical chart of the deceased. After informed consent was obtained, the autopsy was performed within 12 hours. The body was embalmed free of charge afterwards. Patients that died without an available adult relative were excluded from the study. The doctor on the ward was asked for the clinical cause of death and any contributory condition(s). Afterwards the study team reviewed all medical charts to collect diagnostic evidence. Four groups of clinical diagnoses were defined: HIV status was abstracted from the medical chart. For those unaware of their serological status on admission, provider-initiated, free, opt-out HIV testing had been offered according to the hospital guidelines. The algorithm for rapid testing involved 3 sequential HIV tests: Determine TM (Abbot Laboratories by Abbot Japan CO. LTD, Minato-KU, Tokyo, Japan), HIV 1/2 Stat-Pak (Chembio Diagnostics Systems, 3661 Horseblock Road, Med Ford, New York, 11763, USA) and Unigold TM (Trinity Biotech PLC, IDA Business Park, Bray, Cowicklow, Ireland). After informed consent was obtained, a complete autopsy examination was performed, eviscerating all organs including the brain. Standard tissue sections were taken from every organ and from any macroscopically detected lesion. All samples were fixed in 10% formalin solution. Fixed tissue samples were processed for routine hematoxylin and eosin stain (H&E) following standard protocols. The H&E stained slides were examined by light microscopy by three experienced pathologists (R. Lukande, E. Van Marck and A. Nelson). When indicated, special stains for organisms were done including Ziehl-Neelsen (ZN), Grocott-Methenamine Silver, Brown-Hopps Gram, Periodic-Acid Schiff and mucicarmine. Acid fast bacilli seen after ZN staining were classified as mycobacterium tuberculosis, taking into account possible errors due to mycobacterial infections caused by other mycobacteria. When indicated we confirmed the diagnosis of Kaposi’s sarcoma and cytomegalovirus infection by immunohistochemistry using commercially available mouse monoclonal antibodies; LANA1 for HHV8, Cell Marque (reference number 265M-18) and CMV antibody, clone DDG9/CCH2, Ventana (reference number 760-2638). The cause of death and contributing findings were formulated based on the clinical information combined with the macro- and microscopic post-mortem findings. The study received ethical approval from the Makerere University Research and Ethics Committee, the Mulago Internal Review Board and the Infectious Diseases Institute Scientific Review Committee. The study received final approval and registration by the Uganda National Council of Science and Technology (ADM 154/212/01). Data were analyzed using STATA version 11.0 (Stat Corp., College Station, TX, Texas, USA). Data are expressed as mean with a 95% confidence interval (95% CI) or as median with a range.
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