Unmasking the hidden tuberculosis mortality burden in a large postmortem study in Maputo Central Hospital, Mozambique

Sensitive tools are needed to accurately establish the diagnosis of tuberculosis (TB) at death, especially in low-income countries. The objective of this study was to evaluate the burden of TB in a series of patients who died in a tertiary referral hospital in sub-Saharan Africa using an in-house real time PCR (TB-PCR) and the Xpert MTB/RIF Ultra (Xpert Ultra) assay.Complete diagnostic autopsies were performed in a series of 223 deaths (56.5% being HIV-positive), including 54 children, 57 maternal deaths and 112 other adults occurring at the Maputo Central Hospital, Mozambique. TB-PCR was performed in all lung, cerebrospinal fluid and central nervous system samples in HIV-positive patients. All samples positive for TB-PCR or showing histological findings suggestive of TB were analysed with the Xpert Ultra assay.TB was identified as the cause of death in 31 patients: 3/54 (6%) children, 5/57 (9%) maternal deaths and 23/112 (21%) other adults. The sensitivity of the main clinical diagnosis to detect TB as the cause of death was 19.4% (95% CI: 7.5-37.5) and the specificity was 97.4% (94.0-99.1) compared to autopsy findings. Concomitant TB (TB disease in a patient dying of other causes) was found in 31 additional cases. Xpert Ultra helped to identify 15 cases of concomitant TB. In 18 patients, " - " DNA was identified by TB-PCR and Xpert Ultra in the absence of histological TB lesions. Overall, 62 cases (27.8%) had TB disease at death and 80 (35.9%) had TB findings.The use of highly sensitive, easy to perform molecular tests in complete diagnostic autopsies may contribute to identifying TB cases at death that would have otherwise been missed. Routine use of these tools in certain diagnostic algorithms for hospitalised patients needs to be considered. Clinical diagnosis showed poor sensitivity for the diagnosis of TB at death

High within-host diversity found from direct genotyping on post-mortem tuberculosis specimens in a high-burden setting

Objectives: To characterize the clonal complexity in Mycobacterium tuberculosis (MTB) infections considering factors that help maximize the detection of coexisting strains/variants. Methods: Genotypic analysis by Mycobacterial Interspersed Repetitive-Unit-Variable-Number Tandem-Repeats (MIRU-VNTR) was performed directly on 70 biopsy specimens from two or more different tissues involving 28 tuberculosis cases diagnosed post-mortem in Mozambique, a country with a high tuberculosis burden. Results: Genotypic data from isolates collected from two or more tissues were obtained for 23 of the 28 cases (82.1%), allowing the analysis of within-patient diversity. MIRU-VNTR analysis revealed clonal diversity in ten cases (35.7%). Five cases showed allelic differences in three or more loci, suggesting mixed infection with two different strains. In half of the cases showing within-host diversity, one of the specimens associated with clonal heterogeneity was brain tissue. Conclusions: Direct MTB genotyping from post-mortem tissue samples revealed a frequent within-host Mycobacterium tuberculosis diversity, including mixed and polyclonal infections. Most of this diversity would have been overlooked if only standard analysis of respiratory specimens had been performed

Contribution of the clinical information to the accuracy of the minimally invasive and the complete diagnostic autopsy

Although autopsy diagnosis includes routinely, a thorough evaluation of all available pathological results and also of any available clinical data, the contribution of this clinical information to the diagnostic yield of the autopsy has not been analyzed. We aimed to determine to which degree the use of clinical data improves the diagnostic accuracy of the complete diagnostic autopsy (CDA) and the minimally invasive autopsy (MIA), a simplified pathological postmortem procedure designed for low-income sites. 264 coupled MIA and CDA procedures (112 adults, 57 maternal deaths, 54 children and 41 neonates) were performed at the Maputo hospital, Mozambique. We compared the diagnoses obtained by the MIA blind to clinical data (MIAb), the MIA adding the clinical information (MIAc), and the CDA blind to clinical information (CDAb), with the results of the gold standard, the CDA with clinical data, by comparing the ICD-10 codes and the main diagnostic classes obtained with each evaluation strategy (MIAb, MIAc, CDAb, CDAc). The clinical data increased diagnostic coincidence to the MIAb with the gold standard in 30/264 (11%) cases and modified the CDAb diagnosis in 20/264 (8%) cases. The increase in concordance between MIAb and MIAc with the gold standard was significant in neonatal deaths (kappa increasing from 0.404 to 0.618, P=.0271), adult deaths (kappa increasing from 0.732 to 0.813, P=.0221) and maternal deaths (kappa increasing from 0.485 to 0.836, P<.0001). In conclusion, the use of clinical information increases the precision of MIA and CDA and may strengthen the performance of the MIA in resource-limited settings

Postmortem Interval and Diagnostic Performance of the Autopsy Methods

Postmortem studies, including the complete diagnostic autopsy (CDA) and the minimally invasive autopsy (MIA), an innovative approach to post-mortem sampling and cause of death investigation, are commonly performed within 24 hours after death because the quality of the tissues deteriorates over time. This short timeframe may hamper the feasibility of the procedure. In this study, we compared the diagnostic performance of the two postmortem procedures when carried out earlier and later than 24 hours after death, as well as the impact of increasing postmortem intervals (PMIs) on the results of the microbiological tests in a series of 282 coupled MIA/CDA procedures performed at the Maputo Central Hospital in Mozambique between 2013 and 2015. 214 procedures were conducted within 24 hours of death (early autopsies), and 68 after 24 hours of death (late autopsies). No significant differences were observed in the number of non-conclusive diagnoses (2/214 [1%] vs. 1/68 [1%] p = 0.5645 for the CDA; 27/214 [13%] vs. 5/68 [7%] p = 0.2332 for the MIA). However, increasing PMIs were associated with a raise in the number of bacteria identified (rate: 1.014 per hour [95%CI: 1.002-1.026]; p = 0.0228). This increase was mainly due to rising numbers of bacteria of the Enterobacteriaceae family and Pseudomonas genus strains. Thus, performing MIA or CDA more than 24 hours after death can still render reliable diagnostic results, not only for non-infectious conditions but also for many infectious diseases, although, the contribution of Enterobacteriaceae and Pseudomonas spp. as etiological agents of infections leading to death may be overestimated

Validity of a Minimally Invasive Autopsy for Cause of Death Determination in Adults in Mozambique: An Observational Study

Background There is an urgent need to identify tools able to provide reliable information on the cause of death in low-income regions, since current methods (verbal autopsy, clinical records, and complete autopsies) are either inaccurate, not feasible, or poorly accepted. We aimed to compare the performance of a standardized minimally invasive autopsy (MIA) approach with that of the gold standard, the complete diagnostic autopsy (CDA), in a series of adults who died at Maputo Central Hospital in Mozambique. Methods and Findings In this observational study, coupled MIAs and CDAs were performed in 112 deceased patients. The MIA analyses were done blindly, without knowledge of the clinical data or the results of the CDA. We compared the MIA diagnosis with the CDA diagnosis of cause of death. CDA diagnoses comprised infectious diseases (80; 71.4%), malignant tumors (16; 14.3%), and other diseases, including non-infectious cardiovascular, gastrointestinal, kidney, and lung diseases (16; 14.3%). A MIA diagnosis was obtained in 100/112 (89.2%) cases. The overall concordance between the MIA diagnosis and CDA diagnosis was 75.9% (85/112). The concordance was higher for infectious diseases and malignant tumors (63/80 [78.8%] and 13/16 [81.3%], respectively) than for other diseases (9/16; 56.2%). The specific microorganisms causing death were identified in the MIA in 62/74 (83.8%) of the infectious disease deaths with a recognized cause. The main limitation of the analysis is that both the MIA and the CDA include some degree of expert subjective interpretation. Conclusions A simple MIA procedure can identify the cause of death in many adult deaths in Mozambique. This tool could have a major role in improving the understanding and surveillance of causes of death in areas where infectious diseases are a common cause of mortality

Malacoplakia of the Uterine Cervix: A Case Report

Malacoplakia is an uncommon chronic granulomatous inflammation that rarely affects the female genital tract. A case of a 78-year-old woman with malacoplakia involving the uterine cervix and the vagina is described. The patient complained of vaginal bleeding. Clinically, a 13-mm mass was detected in the cervix, which was confirmed by ultrasound scan and magnetic resonance imaging. Histological examination showed a dense histiocytic infiltrate with abundant Michaelis–Gutmann bodies involving the uterine cervix and the upper vagina. The presence of Escherichia coli was confirmed in the lesion by immunohistochemistry and polymerase chain reaction. Only 12 cases of cervical malacoplakia have been reported to date. This condition should be included in the differential diagnosis of cervical tumors

Contribution of the clinical information to the accuracy of the minimally invasive and the complete diagnostic autopsy

Although autopsy diagnosis includes routinely, a thorough evaluation of all available pathological results and also of any available clinical data, the contribution of this clinical information to the diagnostic yield of the autopsy has not been analyzed. We aimed to determine to which degree the use of clinical data improves the diagnostic accuracy of the complete diagnostic autopsy (CDA) and the minimally invasive autopsy (MIA), a simplified pathological postmortem procedure designed for low-income sites. 264 coupled MIA and CDA procedures (112 adults, 57 maternal deaths, 54 children and 41 neonates) were performed at the Maputo hospital, Mozambique. We compared the diagnoses obtained by the MIA blind to clinical data (MIAb), the MIA adding the clinical information (MIAc), and the CDA blind to clinical information (CDAb), with the results of the gold standard, the CDA with clinical data, by comparing the ICD-10 codes and the main diagnostic classes obtained with each evaluation strategy (MIAb, MIAc, CDAb, CDAc). The clinical data increased diagnostic coincidence to the MIAb with the gold standard in 30/264 (11%) cases and modified the CDAb diagnosis in 20/264 (8%) cases. The increase in concordance between MIAb and MIAc with the gold standard was significant in neonatal deaths (kappa increasing from 0.404 to 0.618, P=.0271), adult deaths (kappa increasing from 0.732 to 0.813, P=.0221) and maternal deaths (kappa increasing from 0.485 to 0.836, P<.0001). In conclusion, the use of clinical information increases the precision of MIA and CDA and may strengthen the performance of the MIA in resource-limited settings.Sin financiación2.735 JCR (2019) Q2, 27/78 Pathology1.193 SJR (2019) Q1, 34/209 Pathology and Forensic MedicineNo data IDR 2019UE

Malacoplakia of the Uterine Cervix: A Case Report

Malacoplakia is an uncommon chronic granulomatous inflammation that rarely affects the female genital tract. A case of a 78-year-old woman with malacoplakia involving the uterine cervix and the vagina is described. The patient complained of vaginal bleeding. Clinically, a 13-mm mass was detected in the cervix, which was confirmed by ultrasound scan and magnetic resonance imaging. Histological examination showed a dense histiocytic infiltrate with abundant Michaelis-Gutmann bodies involving the uterine cervix and the upper vagina. The presence of Escherichia coli was confirmed in the lesion by immunohistochemistry and polymerase chain reaction. Only 12 cases of cervical malacoplakia have been reported to date. This condition should be included in the differential diagnosis of cervical tumors

Pathological Methods Applied to the Investigation of Causes of Death in Developing Countries: Minimally Invasive Autopsy Approach.

Complete diagnostic autopsies (CDA) remain the gold standard in the determination of cause of death (CoD). However, performing CDAs in developing countries is challenging due to limited facilities and human resources, and poor acceptability. We aimed to develop and test a simplified minimally invasive autopsy (MIA) procedure involving organ-directed sampling with microbiology and pathology analyses implementable by trained technicians in low- income settings.A standardized scheme for the MIA has been developed and tested in a series of 30 autopsies performed at the Maputo Central Hospital, Mozambique. The procedure involves the collection of 20 mL of blood and cerebrospinal fluid (CSF) and puncture of liver, lungs, heart, spleen, kidneys, bone marrow and brain in all cases plus uterus in women of childbearing age, using biopsy needles.The sampling success ranged from 67% for the kidney to 100% for blood, CSF, lung, liver and brain. The amount of tissue obtained in the procedure varied from less than 10 mm2 for the lung, spleen and kidney, to over 35 mm2 for the liver and brain. A CoD was identified in the histological and/or the microbiological analysis in 83% of the MIAs.A simplified MIA technique allows obtaining adequate material from body fluids and major organs leading to accurate diagnoses. This procedure could improve the determination of CoD in developing countries