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.
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.
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.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Over 5 million stillbirths and neonatal deaths occur annually. Limited and imprecise information on the cause of these deaths hampers progress in achieving global health targets. Complete diagnostic ...autopsies (CDAs)-the gold standard for cause of death determination-are difficult to perform in most high-burden settings. Therefore, validation of simpler and more feasible methods is needed.
In this observational study, the validity of a minimally invasive autopsy (MIA) method in determining the cause of death was assessed in 18 stillbirths and 41 neonatal deaths by comparing the results of the MIA with those of the CDA. Concordance between the categories of diseases obtained by the 2 methods was assessed by the Kappa statistic, and the sensitivity, specificity, positive, and negative predictive values of the MIA diagnoses were calculated. A cause of death was identified in 16/18 (89%) and 15/18 (83%) stillborn babies in the CDA and the MIA, respectively. Fetal growth restriction accounted for 39%, infectious diseases for 22%, intrapartum hypoxia for 17%, and intrauterine hypoxia for 11% of stillborn babies. Overall, the MIA showed in this group a substantial concordance with the CDA (Kappa = 0.78, 95% CI 0.56-0.99). A cause of death was identified in all (100%) and 35/41 (85%) neonatal deaths in the CDA and the MIA, respectively. In this group, the majority of deaths were due to infectious diseases (66%). The overall concordance of the MIA with the CDA in neonates was moderate (Kappa = 0.40, 95% CI 0.18-0.63). A high percentage of accuracy was observed for the MIA in all the diagnostic categories in both stillbirths and neonates (>75%). The main limitation of this study is that some degree of subjective interpretation is inherent to cause-of-death attribution in both the MIA and the CDA; this is especially so in stillbirths and in relation to fetal growth restriction.
The MIA could be a useful tool for cause-of-death determination in stillbirths and neonatal deaths. These findings may help to accelerate progress towards meeting global health targets by obtaining more accurate information on the causes of death in these age groups, which is essential in guiding the design of new interventions and increasing the effectiveness of those already implemented.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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: three out of 54 (6%) children, five out of 57 (9%)maternal deaths and 23 out of 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 (27.8%) cases 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.
Two pathways have been described for vulvar squamous cell carcinomas (VSCC), one associated with human papillomavirus (HPV), and the other HPV‐independent. We compared the etiopathogenic features of ...a series of VSCC from Mozambique, a sub‐Saharan country with high prevalence of HPV and HIV, with those of Spain, a European country with low prevalence of HPV and HIV. All VSCC diagnosed at the two institutions from January 2018 to December 2020 were included (n = 35 and n = 41, respectively). HPV DNA detection and genotyping, and immunohistochemistry for p16 and p53 were performed. Tumors showing p16 positive staining and/or HPV DNA positivity were considered HPV‐associated. 34/35 tumors (97%) from Mozambique and 8/41 (19%) from Spain were HPV‐associated (P < .001). Mean age of the patients from Mozambique and Spain was 45 ± 12 and 72 ± 14, respectively (P < .001). No differences were found in terms of HPV genotypes or multiple HPV infection rates. 1/35 tumors (3%) from Mozambique and 29/41 (70%) from Spain showed abnormal p53 immunostaining (P < .001). In contrast with the predominance of HPV‐independent VSCC affecting old women in Europe, most VSCC in sub‐Saharan Africa are HPV‐associated and arise in young women. This data may have important consequences for primary prevention of VSCC worldwide.
Vulvar squamous cell carcinoma (VSCC) can arise from HPV or non‐HPV causes, and that affects prognosis. Here, the authors compared VSCC samples from a population in Mozambique, where HPV prevalence is high, with those from Spain, where it is low. In Mozambique, 97% of VSCC were HPV‐associated, based on p16 staining and HPV DNA positivity, compared with only 19% of VSCC in Spain. Mean age of patients in Mozambique was 45, vs 72 in Spain. Vaccination programs, the authors suggest, could therefore help prevent the majority of VSCC in sub‐Saharan Africa.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract In developing countries, the knowledge of the microorganisms causing fatal infections is critical and could help designing and implementing more effective preventive interventions and ...treatment guidelines. We aimed to develop and validate protocols for microbiological analysis in post-mortem samples obtained during minimally invasive autopsy (MIA) procedures and to assess their performance. Thirty MIAs performed in adults at Maputo Central Hospital in Southern Mozambique were included in the analysis. Microbiological tests included a universal screening for HIV, hepatitis B and C viruses, Plasmodium falciparum , and bacterial/fungal culture. In addition, a variety of molecular microbiology assays guided by the histological results were performed in blood, cerebrospinal fluid and a variety of tissue samples including liver, lung and central nervous system. The combination of culture-based methods together with molecular microbiological assays led to the identification of 17 out of 19 (89.5%) of the infectious deaths. Microorganisms identified included Mycobacterium tuberculosis , Toxoplasma gondii , Pneumocystis jiroveci , Cryptococcus neoformans , hepatitis B virus, human herpesvirus 8, cytomegalovirus, Streptococcus pneumoniae , Streptococcus dysgalactiae , Ryzopus oryzae , and Acinetobacter baumannii . The combination of classical cultures, serological tests and molecular assays performed in samples obtained through MIA allows the identification of most infectious agents causing death.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Despite global health efforts to reduce maternal mortality, rates continue to be unacceptably high in large parts of the world. Feasible, acceptable, and accurate postmortem sampling methods could ...provide the necessary evidence to improve the understanding of the real causes of maternal mortality, guiding the design of interventions to reduce this burden.
The validity of a minimally invasive autopsy (MIA) method in determining the cause of death was assessed in an observational study in 57 maternal deaths by comparing the results of the MIA with those of the gold standard (complete diagnostic autopsy CDA, which includes any available clinical information). Concordance between the MIA and the gold standard diagnostic categories was assessed by the kappa statistic, and the sensitivity, specificity, positive and negative predictive values and their 95% confidence intervals (95% CI) to identify the categories of diagnoses were estimated. The main limitation of the study is that both the MIA and the CDA include some degree of subjective interpretation in the attribution of cause of death. A cause of death was identified in the CDA in 98% (56/57) of cases, with indirect obstetric conditions accounting for 32 (56%) deaths and direct obstetric complications for 24 (42%) deaths. Nonobstetric infectious diseases (22/32, 69%) and obstetric hemorrhage (13/24, 54%) were the most common causes of death among indirect and direct obstetric conditions, respectively. Thirty-six (63%) women were HIV positive, and HIV-related conditions accounted for 16 (28%) of all deaths. Cerebral malaria caused 4 (7%) deaths. The MIA identified a cause of death in 86% of women. The overall concordance of the MIA with the CDA was moderate (kappa = 0.48, 95% CI: 0.31-0.66). Both methods agreed in 68% of the diagnostic categories and the agreement was higher for indirect (91%) than for direct obstetric causes (38%). All HIV infections and cerebral malaria cases were identified in the MIA. The main limitation of the technique is its relatively low performance for identifying obstetric causes of death in the absence of clinical information.
The MIA procedure could be a valuable tool to determine the causes of maternal death, especially for indirect obstetric conditions, most of which are infectious diseases. The information provided by the MIA could help to prioritize interventions to reduce maternal mortality and to monitor progress towards achieving global health targets.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Clinico-pathological discrepancies are more frequent in settings in which limited diagnostic techniques are available, but there is little information on their actual impact.
We assessed the accuracy ...of the clinical diagnoses in a tertiary referral hospital in sub-Saharan Africa by comparison with post-mortem findings. We also identified potential risk factors for misdiagnoses.
One hundred and twelve complete autopsy procedures were performed at the Maputo Central Hospital (Mozambique), from November 2013 to March 2015. We reviewed the clinical records. Major clinico-pathological discrepancies were assessed using a modified version of the Goldman and Battle classification.
Major diagnostic discrepancies were detected in 65/112 cases (58%) and were particularly frequent in infection-related deaths (56/80 70% major discrepancies). The sensitivity of the clinical diagnosis for toxoplasmosis was 0% (95% CI: 0-37), 18% (95% CI: 2-52) for invasive fungal infections, 25% (95% CI: 5-57) for bacterial sepsis, 34% (95% CI: 16-57), for tuberculosis, and 46% (95% CI: 19-75) for bacterial pneumonia. Major discrepancies were more frequent in HIV-positive than in HIV-negative patients (48/73 66% vs. 17/39 44%; p = 0.0236).
Major clinico-pathological discrepancies are still frequent in resource constrained settings. Increasing the level of suspicion for infectious diseases and expanding the availability of diagnostic tests could significantly improve the recognition of common life-threatening infections, and thereby reduce the mortality associated with these diseases. The high frequency of clinico-pathological discrepancies questions the validity of mortality reports based on clinical data or verbal autopsy.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Gigantomastia is a rare disease defined by an extreme and rapid enlargement of the breast, generally bilateral. The majority of cases are reported in pregnant women. Ninety-eight cases of gestational ...gigantomastia have been identified in electronic databases, and those with fatal outcomes comprised only 2 cases (2%). Despite its benign nature, it can lead to severe complications and even death. Its etiology has not been fully elucidated, but it has been speculated that a hormonal component may play a role in the pathogenesis. Currently, treatment options are limited, and surgery is gaining importance, but it is often not feasible in low-resource settings. Herein, we describe a case of a 30-year-old HIVpositive female with no relevant past medical history, who died due to the complications of gestational gigantomastia at the Maputo Central Hospital, in Mozambique.
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. A total of 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 International Classification of Diseases, Tenth Revision 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 (11%) of 264 cases and modified the CDAb diagnosis in 20 (8%) of 264 cases. The increase in concordance between MIAb and MIAc with the gold standard was significant in neonatal deaths (κ increasing from 0.404 to 0.618, P = .0271), adult deaths (κ increasing from 0.732 to 0.813, P = .0221), and maternal deaths (κ increasing from 0.485 to 0.836, 0.;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.
•The addition of clinical data increases the diagnostic accuracy of the minimally invasive autopsy (MIA) and complete diagnostic autopsy in 12% and 8% of the cases, respectively.•The increase in concordance from MIA blind to clinical data to MIA enhanced with clinical data was significant in neonatal, adult, and maternal deaths and was also evident in children, although it did not reach statistical significance.•The use of clinical data may improve the diagnostic precision of the MIA in resource-limited settings.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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