Needle Autopsy to Establish the Cause of Death in HIV-Infected Hospitalized Adults in Uganda

Cox, Janneke; Lukande, Robert; Kalungi, Sam; Marck, Eric Van; Vijver, Koen Van de; Kambugu, Andrew; Nelson, Ann Marie; Manabe, Yukari C.; Colebunders, Robert

doi:10.1097/qai.0000000000000290

Cited by 32 publications

(35 citation statements)

References 26 publications

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“…Those who had MIA and those who did not were largely similar with regard to characteristics at enrolment and during follow up, although those with MIA were more likely to have been treated for TB between enrolment and death. This, together with the likelihood that MIA will miss some cases that may be identified by full autopsy [18], suggests that the prevalence of TB at death among the entire population of decedents in TB Fast Track may have been even higher than the almost 50% found in this sample. Nearly 90% of those with evidence of TB had disease in at least one extrapulmonary site and 38% were not on TB treatment at the time of death.…”

Section: Discussionmentioning

confidence: 99%

“…Full pathological autopsy with visualisation and sampling of all organs remains the gold standard for assigning cause of death [17,18], but it is expensive, time consuming, and not well accepted by families, who are often required to provide consent [19]. There is growing evidence that minimally invasive autopsy (MIA) can provide useful information relevant to cause of death, particularly with regards to TB and other infectious diseases [20,21]; one study, involving 96 HIV-positive adults in Uganda, compared histology from MIA to that from full autopsy and found that MIA was 71% sensitive and 100% specific in detecting TB [18].…”

Section: Introductionmentioning

confidence: 99%

“…There is growing evidence that minimally invasive autopsy (MIA) can provide useful information relevant to cause of death, particularly with regards to TB and other infectious diseases [20,21]; one study, involving 96 HIV-positive adults in Uganda, compared histology from MIA to that from full autopsy and found that MIA was 71% sensitive and 100% specific in detecting TB [18]. Adding culture and/or other bacteriological modalities to MIA would likely improve its sensitivity in this regard.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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BackgroundEarly 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 FindingsAdults 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.ConclusionsTB, 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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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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“…This technique enabled the diagnosis of 92% of cryptococcal brain infections in a post‐mortem study performed at Mulago hospital in Kampala, Uganda (Cox et al . ), and trained nurses could perform such a procedure in a village shortly after a child dies.…”

Section: What Type Of Research Needs To Be Undertaken?mentioning

confidence: 99%

Nodding syndrome since 2012: recent progress, challenges and recommendations for future research

Colebunders

Post

O‘Neill

et al. 2014

Tropical Med Int Health

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We aim to review the current epidemiology of nodding syndrome (NS) and discuss relevant gaps in research. NS and convulsive epilepsy of unknown aetiology are clustered within the same villages and families in onchocerciasis-endemic areas. They are therefore potentially different clinical expressions of the same disease. It has been difficult to perform full autopsies on NS patients who die in remote villages. Adequate fixation of tissue immediately after death is critical for the examination of brain tissue. Therefore, post-mortem transsphenoidal brain biopsies, performed immediately after death by trained nurses, will provide the best option for obtaining tissue for analysis. We suspect that certain blackflies in onchocerciasis-endemic areas may transmit a novel pathogen that could cause NS and epilepsy. This is supported by a recent drop in the number of new NS cases coinciding with vector control activities aimed at reducing blackfly populations in northern Uganda. We propose that metagenomic studies of human samples, blackflies and microfilariae are conducted to screen for pathogens, and that a clinical trial is planned to evaluate the impact of larviciding against NS and epilepsy epidemics.

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“…This study was a substudy of an autopsy study that is described in detail elsewhere (20). In brief, we included HIV-infected adults (Ͼ18 years old) who died in one of the medicine wards of Mulago Hospital, Kampala, Uganda, during the period from February to June 2013.…”

Section: Methodsmentioning

confidence: 99%

Accuracy of Lipoarabinomannan and Xpert MTB/RIF Testing in Cerebrospinal Fluid To Diagnose Tuberculous Meningitis in an Autopsy Cohort of HIV-Infected Adults

et al. 2015

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i Point-of-care tests for tuberculous meningitis (TBM) are needed. We studied the diagnostic accuracy of the lipoarabinomannan (LAM) lateral flow assay (LFA), LAM enzyme-linked immunosorbent assay (ELISA), and Xpert MTB/RIF in cerebrospinal fluid (CSF) in an autopsy cohort of Ugandan HIV-infected adults. We obtained written informed consent postmortem from the next of kin. A complete autopsy was done and CSF obtained. We performed LAM LFA (on unprepared and supernatant CSF after heating and spinning), LAM ELISA, and Xpert MTB/RIF on the CSF samples. Accuracy parameters were calculated for histopathological TBM and also for the composite standard, including Xpert MTB/RIF-positive cases. We tested CSF of 91 patients. LAM LFA had a sensitivity of 75% for definite histopathological TBM, ELISA a sensitivity of 43%, and Xpert MTB/RIF a sensitivity of 100% and specificities of 87%, 91%, and 87%, respectively. LAM LFA had a sensitivity of 50% for definite and probable histopathological TBM, ELISA a sensitivity of 38%, and Xpert MTB/RIF a sensitivity of 86% and specificities of 70%, 91%, and 87%, respectively. LAM LFA had a sensitivity of 68% for the composite standard and ELISA a sensitivity of 48% and specificities of 78% and 98%, respectively. The rapid diagnostic tests detected TBM in 22% to 78% of patients not on anti-TB treatment. Pointof-care tests have high accuracy in diagnosis of TBM in deceased HIV-infected adults. LAM LFA in CSF is a useful additional diagnostic tool.

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Needle Autopsy to Establish the Cause of Death in HIV-Infected Hospitalized Adults in Uganda

Cited by 32 publications

References 26 publications

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

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

Nodding syndrome since 2012: recent progress, challenges and recommendations for future research

Accuracy of Lipoarabinomannan and Xpert MTB/RIF Testing in Cerebrospinal Fluid To Diagnose Tuberculous Meningitis in an Autopsy Cohort of HIV-Infected Adults

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