During the 5 month-study period 290 patients died on the study ward. An autopsy was requested in 158 (54%) and performed in 59 (37%) of them. In this paper we present the autopsy data of 53 patients; 66% HIV-positive, 21% HIV-negative and 13% patients with an unknown serological status (, ). Details of the entire study cohort including those that did not consent to autopsy were previously described 
. Six patients (3 HIV-positive patients, none on ART) were left out of the analysis due to incomplete postmortem data.
On admission 16 (30%) of the 53 patients were unaware of their HIV serological status. Six (38%) tested HIV-positive and 4 (25%) HIV-negative during hospitalization. One patient tested HIV-negative according to the medical chart, however according to the relatives he was HIV-positive. He was classified as a patient with unknown serological status for the analysis. All patients, except one, with an unknown HIV serological status died within 48 hours after admission. The median duration of hospitalization before death was 5 days (range <1–30 days). According to relatives, 61% of patients had symptoms of the current illness for more than one month. Ninety-one percent of patients had sought medical care prior to admission and 55% had done so 30 days or more before admission. Of the 16 patients with unknown HIV serological status on admission, 88% had sought medical care prior to admission.
A CD4 T-cell count was available for 13 (36%) HIV-positive patients. Their mean CD4 T-cell count was 50 cells/mm3 (95% CI 14–87). Ten (27%) patients were reported to be on ART before they died. Six patients had been on ART for less than 2 months; the other 4 were on ART for 8, 12, 36 and 48 months respectively. All were on a NNRTI-based regimen. No patient was started on ART during the admission in Mulago Hospital. For 6 of the patients on ART, CD4 T-cell counts were known. In one patient on ART for 12 months, the CD4 T-cell count was only 29 cells/mm3. In another patient on ART for 36 months the CD4 T-cell count was only 26 cells/mm3. In 4 patients who started ART less than 2 months before admission, the CD4 T-cell count pre-ART ranged from 2 to 82 cells/mm3. No pre-death ascertainment of HIV viral loads was available to assess non-adherence or viral failure. Of the 30 patients aware of their HIV-positive serological status on admission, 93% were on cotrimoxazole prophylactic treatment.
Overall, 83% of the HIV-positive patients died as a result of infectious diseases (). The leading cause of death was tuberculosis (TB), which accounted for 37% of all deaths (n
13) (). Another 9% of patients had TB infection that was not considered their cause of death (n
3). In all TB patients, the disease was disseminated beyond the lung parenchyma. The most frequently infected organs were the spleen (81%), liver (69%), lymph nodes (69%) and lungs (56%). The second most common cause of death was a Cryptococcus neoformans
infection that accounted for 20% of deaths (n
7). One additional patient had disseminated Cryptococcus neoformans
infection but died of pulmonary haemorrhage due to disseminated Kaposi's sarcoma (KS). In all but one patient, the cryptococcal infection was located in the meninges (88%). Other organs involved included the spleen (50%), the liver (38%), the lungs (38%), the kidneys (38%) and the lymph nodes (38%). Disseminated KS was the only identified malignancy and caused death in 3 patients (9%) who all had widespread involvement including the gastrointestinal tract (67%), the lungs (67%) and the peri- and myocardium (33%) (). Other less common causes of death included bacterial meningitis (9%), progressive multifocal leucoencephalopathy (3%), Pneumocystis jiroveci
pneumonia (PJP) (3%) and disseminated cytomegalovirus infection (). The latter was a patient who was tested HIV-positive on admission and who was not on cotrimoxazole prophylaxis. Pneumonia was found in 14% of patients, but considered to be the cause of death in only 6%. Chronic renal damage suggestive of HIV-associated nephropathy (HIVAN) was found in 9%. Dual infections were common and identified in 26% of the patients (, ).
Causes of death and contributory findings according to HIV-serological status.
Spectrum of host response to mycobacterial infection in HIV-infected patients.
Dual infections among HIV-infected patients.
HIV-positive patients on ART: At least 8 of the 10 patients on ART died of HIV-related conditions; 50% died of disseminated TB, 20% of disseminated Cryptococcus neoformans infection and 10% of disseminated KS. A 32-year-old female that started treatment with tenofovir, emtricitabine and efavirenz 6 weeks prior to admission possibly died of ART-induced liver failure. Liver sections showed an eosinophilic infiltration against a background of cirrhosis. She had a concurrent clinical undiagnosed TB infection in the lymph nodes. One patient died of pneumonia with Pseudomonas aeruginosa.
HIV- negative patients: The leading causes of death in HIV-negative patients were non-infectious and accounted for 73% of all deaths. Only one patient had TB, which was disseminated to liver, spleen, meninges and kidneys. One patient died of decompensated alcoholic liver cirrhosis. Two patients died of variceal bleeding secondary to liver cirrhosis: one of alcoholic origin and the other of unknown origin. One patient died of cardiac failure, but also had secondary chronic liver congestion leading to cirrhosis. A patient that died of pulmonary thromboembolism also had underlying sickle cell disease.
Patients with unknown HIV serological status: Non-infectious diseases accounted for 71% of all deaths. Gastrointestinal bleeding was the cause of death in 3 patients: one patient had a variceal bleeding secondary to liver cirrhosis due to disseminated Schistosoma mansoni infection, in the others no bleeding focus was identified. An accidental finding was an Ancylostoma duodenale in the small gut of one of these two patients. One patient died of a perforated chronic duodenal ulcer. The infectious causes of death were bacterial meningitis and disseminated candidiasis.
Comparison between clinical diagnoses and autopsy findings
Overall, 49 postmortem diagnoses were made. Of these 12% were clinically confirmed, 27% highly suspected, 16% considered and 45% not considered. The 6 confirmed diagnoses were cryptococcal meningitis with a positive Indian ink in 5 patients and disseminated TB with a positive Ziehl-Neelsen (ZN) stain of sputum and liver tissue obtained with a liver biopsy in 1 patient. The 13 highly suspected clinical diagnoses consisted of TB in 8 patients: 3 patients were referred while on anti-TB treatment, one patient had a suggestive chest x-ray, 3 patients a suggestive abdominal ultrasound and one patient had both a suggestive chest x-ray and abdominal ultrasound. The other highly suspected diagnoses were disseminated KS (n
2), liver failure on the basis of laboratory results (n
2) and a cerebral abscess on the basis of a computer tomography of the head. The 8 autopsy diagnoses that were clinically considered were bacterial meningitis (n
3), cryptococcal meningitis (n
2), disseminated TB (n
2) and pneumonia (n
1). No diagnostic work-up had been done except in two patients: one patient with disseminated cryptococal infection had a negative serum cryptococcal antigen and another patient with disseminated TB had 3 negative ZN sputum smears, high protein in cerebrospinal fluid without a ZN performed and a normal abdominal ultrasound.
The 22 diagnoses that were clinically not considered consisted mainly of TB (23%) and bacterial pneumonia (18%) together accounting for 9 unconsidered diagnoses. Of these, 4 patients appeared to have two postmortem diagnoses: TB and liver failure, TB and bacterial meningitis, pneumonia and TB, pneumonia and cryptococcal meningitis. In all 4 patients, the second diagnosis was either highly suspected (n
2) or considered (n
2). Three patients diagnosed postmortem with disseminated TB without cerebral or meningeal involvement, presented with central nervous system symptoms. One patient with postmortem pneumonia presented with diarrhea and a CD4 cell count of 1 cell/mm3
. Another patient with postmortem bilateral bronchopneumonia was clinically highly suspected for TB based on a chest x-ray.
When considering only cause of death, 14% had a confirmed diagnosis, 34% a highly suspected diagnosis, 20% a considered diagnosis and 31% of diagnoses were not considered.
IRIS: The ward doctors reported a clinical suspicion of TB-associated immune reconstitution inflammatory syndrome (IRIS) in 4 patients. Three of them started anti-TB treatment 1–4 months and ART 2 weeks–3 months prior to admission. One patient started ART 2 weeks before and anti-TB treatment 1 week after admission. The autopsy revealed disseminated TB in 3 of them and disseminated cryptococcal infection in one. No signs of IRIS (e.g. granuloma formation) were identified in any of the postmortem specimens.
HIV-negative patients: Of the 12 autopsy diagnoses, none were clinically confirmed, 17% highly suspected, 42% considered and 42% not considered. TB was highly suspected on the basis of a chest x-ray and liver cirrhosis on the basis of an abdominal ultrasound. The clinically considered diagnoses were all based on the clinical presentation without investigations done. Five diagnoses were clinically not considered: small cell type bronchogenic carcinoma in a patient with a productive cough since 3 months clinically suspected of pulmonary TB, pulmonary embolism in a patient with sickle cell disease presenting with back pain clinically suspected of a sickle cell crisis, ischemic cardiac failure and liver cirrhosis with variceal bleeding and malaria in a 19-year-old male admitted with fever and jaundice diagnosed clinically as hepatic failure of unknown origin. No malaria testing was performed during admission.
Patients with unknown HIV serological status: Of the 9 autopsy diagnoses, none were clinically confirmed or highly suspected, 67% considered and 33% not considered. The clinically considered diagnoses were all based on clinical presentation. The following diagnoses were clinically not considered: cardiac failure in an 80-year old female with a second postmortem diagnosis of upper gastro-intestinal bleeding probably of vascular origin and disseminated candidiasis and liver cirrhosis of unknown etiology in a 32 year old male with a discrepant HIV serostatus according to the medical chart and the relatives.
Pathology of the central nervous system: The brain was eviscerated and sampled in all 53 of the autopsies. In 15 patients (28%), there was evidence of an infectious pathogen. Thirteen of the 15 patients (80%) were HIV infected. Cryptococcal meningitis was present in 6 patients, bacterial meningitis in 4, TB in 2, candidiasis, cerebral abscess and PML each in one patient (). In all of them, the brain pathology was considered the cause of death except in one patient where cryptococcosis was considered as ‘significant other pathology contributing to death’ in a patient who died of disseminated KS. Brain pathology had been clinically suspected in 14 of the 15 patients (93%).
Central nervous system infections.