Complete Diagnostic Autopsy Research Articles

Determination of causes of adult deaths using minimally invasive tissue sampling in Gandaki province of Nepal: a multicenter hospital-based study

BackgroundMinimally Invasive Tissue Sampling (MITS) has been successfully used to establish the cause of death in low- and middle-income countries, mostly in stillbirths and neonates. The objective of this study was to determine the causes of death among adults using MITS in the Gandaki province of Nepal and to find out the contribution of MITS to identify the causes of death.MethodsA multicentric hospital-based pilot study was conducted to enroll 100 cases of adult deaths. The specimens of cerebrospinal fluid, blood, brain, lungs, and liver tissue were collected utilizing MITS. These specimens underwent standard histopathological, serological, and microbiological analyses. The findings from MITS, and if available, clinical records and forensic autopsy findings were compiled and the cause of death panel identified the causes of death. The final cause of death allocated to each case was based on the WHO International Medical Certificate of Death.ResultsAmong a total of 100 cases enrolled during the study period, infectious cause attributed to the immediate cause of death in 77 (77%), cardiovascular in 10 (10%), neurological in 8 (8%), malignancy in two (2%), and gastrointestinal and hepatobiliary cause in one (1%) case. The mean age of the cases was 50.8 ± 15.9 years and 76 (76%) were males. MITS established the cause of death in the causal chain of events in 81(81%) cases and identified the cause of death significantly more with infectious than non-infectious causes (p < 0.001).ConclusionsMITS was useful in establishing the cause of death in the majority of adult deaths and the most common cause was infectious disease. Our findings suggest that MITS can be a valuable and alternative tool for mortality surveillance in low-resource settings, where complete diagnostic autopsies are less accepted or less prioritized.

MINIMALLY INVASIVE AUTOPSY - AN ADVANCED TECHNIQUE IN DETERMINING THE CAUSE OF DEATH

Complete diagnostic autopsy (CDA) is the gold standard in determining the cause of death. However, according to the statistics of the World Health Organization, the practice of CDA has been on a dramatic decline in high - income countries or has not been recorded consistently in low - and middle - income countries, including Vietnam, for the last few decades. This is due to capacity and resource issues as well as cultural and religious factors regarding management of corpses. As a result, the development of quick, less invasive procedures becomes necessary in order to improve the statistics of cause of death worldwide. One such procedure that has the potential to serve as an alternative to complete diagnostic autopsy is minimally invasive autopsy (MIA). This procedure involves using hollow needles to take samples from different tissues and fluids from key organs before combining histology and microbiology to determine the cause of death. This paper aims to explore this novel procedure as well as its potential in becoming the dominant post - mortem examination, especially in the context of infectious causes of death.

Knowledge and attitudes toward complete diagnostic autopsy and minimally invasive autopsy: A cross-sectional survey in Hanoi, Vietnam.

Knowing the cause of death (CoD) plays an important role in developing strategies and interventions to prevent early mortality. In Vietnam, the CoD of the majority of patients who acquired infectious diseases remains unknown. While there are challenges that hinder the use of complete diagnostic autopsy (CDA) in practice, minimally invasive autopsy (MIA) might be a promising alternative to establish CoD in Vietnam. The current study aims to explore knowledge of and attitudes toward CDA and MIA in the wider population in Vietnam. The study was cross-sectional, using structured questionnaires that were disseminated electronically via several websites and as paper-based forms in a national level hospital in Vietnam. Descriptive analyses were performed and where appropriate, comparisons between the healthcare workers and the general public were performed. We included 394 questionnaires in the analysis. The majority of participants were under age 40, living in major cities and currently practicing no religion. 76.6% of respondents were aware of CDA and among them, 98% acknowledged its importance in medicine. However, most participants thought that CDA should only be performed when the CoD was suspicious or unconfirmed because of its the invasive nature. For MIA, only 22% were aware of the method and there was no difference in knowledge of MIA between healthcare workers and the wider public. The questionnaire results showed that there are socio-cultural barriers that hinder the implementation of CDA in practice. While the awareness of MIA among participants was low, the minimally invasive nature of the method is promising for implementation in Vietnam. A qualitative study is needed to further explore the ethical, socio-cultural and/or religious barriers that might hinder the implementation of MIA in Vietnam.

Postmortem high-dimensional immune profiling of severe COVID-19 patients reveals distinct patterns of immunosuppression and immunoactivation

A complete diagnostic autopsy is the gold-standard to gain insight into Coronavirus disease 2019 (COVID-19) pathogenesis. To delineate the in situ immune responses to SARS-CoV-2 viral infection, here we perform comprehensive high-dimensional transcriptional and spatial immune profiling in 22 COVID-19 decedents from Wuhan, China. We find TIM-3-mediated and PD-1-mediated immunosuppression as a hallmark of severe COVID-19, particularly in men, with PD-1+ cells being proximal rather than distal to TIM-3+ cells. Concurrently, lymphocytes are distal, while activated myeloid cells are proximal, to SARS-CoV-2 viral antigens, consistent with prevalent SARS-CoV-2 infection of myeloid cells in multiple organs. Finally, viral load positively correlates with specific immunosuppression and dendritic cell markers. In summary, our data show that SARS-CoV-2 viral infection induces lymphocyte suppression yet myeloid activation in severe COVID-19, so these two cell types likely have distinct functions in severe COVID-19 disease progression, and should be targeted differently for therapy.

Ultrasound-Guided Minimally Invasive Tissue Sampling: A Minimally Invasive Autopsy Strategy During the COVID-19 Pandemic in Brazil, 2020.

BackgroundMinimally invasive autopsies, also known as minimally invasive tissue sampling (MITS), have proven to be an alternative to complete diagnostic autopsies (CDAs) in places or situations where this procedure cannot be performed. During the coronavirus disease 2019 (COVID-19) pandemic, CDAs were suspended by March 2020 in Brazil to reduce biohazard. To contribute to the understanding of COVID-19 pathology, we have conducted ultrasound (US)–guided MITS as a strategy.MethodsThis case series study includes 80 autopsies performed in patients with COVID-19 confirmed by laboratorial tests. Different organs were sampled using a standardized MITS protocol. Tissues were submitted to histopathological analysis as well as immunohistochemical and molecular analysis and electron microscopy in selected cases.ResultsUS-guided MITS proved to be a safe and highly accurate procedure; none of the personnel were infected, and accuracy ranged from 69.1% for kidney, up to 90.1% for lungs, and reaching 98.7% and 97.5% for liver and heart, respectively. US-guided MITS provided a systemic view of the disease, describing the most common pathological findings and identifying viral and other infectious agents using ancillary techniques, and also allowed COVID-19 diagnosis confirmation in 5% of the cases that were negative in premortem and postmortem nasopharyngeal/oropharyngeal swab real-time reverse-transcription polymerase chain reaction.ConclusionsOur data showed that US-guided MITS has the capacity similar to CDA not only to identify but also to characterize emergent diseases.

Lung Findings in Minimally Invasive Tissue Sampling (MITS) Examinations of Fetal and Preterm Neonatal Deaths: A Report From the PURPOSe Study.

Complete diagnostic autopsy (CDA) is considered to be the gold-standard procedure that aids in determination of cause of death in stillbirths and neonatal deaths. However, CDA is not routinely practiced in South Asian countries due to religious beliefs, lack of expertise, and lack of resources. Minimally invasive tissue sampling (MITS) has been recommended as a less mutilating and less expensive alternative to CDA for obtaining tissues for analysis. The present study aims to evaluate the yield of lung tissue and histological findings using MITS as part of a cause of death analysis for stillborns and preterm neonatal deaths. Data were collected during an observational multicenter prospective study called the Project to Understand and Research Preterm birth and Stillbirth (PURPOSe) conducted in India and Pakistan. After obtaining written informed consent from parents, the eligible stillbirths and neonatal deaths were subjected to MITS using a standard protocol. The tissues were obtained from both lungs for histological and microbiological analysis. At both sites, a total of 453 stillbirths and 352 neonatal deaths underwent MITS. For stillbirths and neonatal deaths, the yield of lung tissue using MITS was high (92%). Intrauterine fetal distress and respiratory distress syndrome were the leading lung pathologies reported in stillbirths and neonatal deaths, respectively. MITS appears to be a reasonable alternative to CDA in obtaining and evaluating lung tissue to inform accurate cause of death analysis in stillbirth and preterm deaths.

Cause of Death in Neonates With Neurological Insults in the Neonatal Intensive Care Unit: Insights From A MITS Pilot Study.

BackgroundMinimally invasive tissue sampling (MITS) of organs has been used as an alternative to complete diagnostic autopsy in countries where refusal for autopsy in newborns is common for sociocultural reasons. There is a paucity of literature regarding the diagnostic utility of MITS of the brain after death in neonates with neurological insults, especially in India.MethodsThis was a prospective, preliminary single-center tertiary care hospital study in India, focused specifically on MITS of the brain after neonatal death as a diagnostic tool to identify the various neurological insults. All neonatal deaths with neurological symptoms occurring within the first 30 days of life were enrolled, irrespective of the suspected clinical diagnosis.ResultsSixteen neonates were enrolled after death for MITS of the brain, performed for diagnostic purposes, during the study period from February 2020 to March 2021. Their gestational ages ranged from 26 to 38 weeks. All neonates had either a history of seizures and/or respiratory distress or clinical evidence of sepsis and were on ventilator support. Histopathology in all 16 neonates showed evidence of anoxia, with or without reactive astrogliosis or microgliosis. In 5 neonates with cranial ultrasound evidence of brain hemorrhage, MITS of the brain showed intraventricular hemorrhage, subdural hemorrhage, or intraparenchymal white matter microhemorrhages. Premortem blood culture–proven sepsis was seen in 9 neonates. In all cases (100%), MITS had a good diagnostic yield and was useful to establish the neurological insult in the brain.ConclusionsMITS of the brain provides an accurate and adequate diagnosis and can be an alternative to complete diagnostic autopsy for establishing the cause of death due to neurological insults, especially in low-resource settings where obtaining consent for more invasive procedure is often challenging.

Minimally Invasive Tissue Sampling as an Alternative to Complete Diagnostic Autopsies in the Context of Epidemic Outbreaks and Pandemics: The Example of Coronavirus Disease 2019 (COVID-19).

BackgroundInfectious diseases’ outbreak investigation requires, by definition, conducting a thorough epidemiological assessment while simultaneously obtaining biological samples for an adequate screening of potential responsible pathogens. Complete autopsies remain the gold-standard approach for cause-of-death evaluation and characterization of emerging diseases. However, for highly transmissible infections with a significant associated lethality, such as COVID-19, complete autopsies are seldom performed due to biosafety challenges, especially in low-resource settings. Minimally invasive tissue sampling (MITS) is a validated new approach based on obtaining postmortem samples from key organs and body fluids, a procedure that does not require advanced biosafety measures or a special autopsy room.MethodsWe aimed to review the use of MITS or similar procedures for outbreak investigation up to 27 March 2021 and their performance for evaluating COVID-19 deaths.ResultsAfter a literature review, we analyzed in detail the results of 20 studies conducted at international sites, whereby 216 COVID-19–related deaths were investigated. MITS provided a general and more granular understanding of the pathophysiological changes secondary to the infection and high-quality samples where the extent and degree of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–related damage could be evaluated.ConclusionsMITS is a useful addition in the investigation and surveillance of infections occurring in outbreaks or epidemics. Its less invasive nature makes the tool more acceptable and feasible and reduces the risk of procedure-associated contagion, using basic biosafety measures. Standardized approaches protocolizing which samples should be collected—and under which exact biosafety measures—are necessary to facilitate and expand its use globally.

Building Global Capacity to Conduct Pathology-Based Postmortem Examination: Establishing a New Training Hub for Minimally Invasive Tissue Sampling.

BackgroundMinimally invasive tissue sampling (MITS), an alternative to complete diagnostic autopsy, is a pathology-based postmortem examination that has been validated in low- and middle-income countries (LMICs) and can provide accurate cause of death information when used with other data. The MITS Surveillance Alliance was established in 2017 with the goal to expand MITS globally by increasing training capacity, accessibility, and availability in LMICs. Between January 2019 and May 2020, the MITS Surveillance Alliance convened a multidisciplinary team of technical advisors to attain this goal.MethodsThis article describes the process used to develop criteria and identify an optimal location for a MITS training hub, establish a cadre of LMIC-based trainers, refine standardized MITS sample collection protocols, develop a training program, and release a telepathology platform for quality assessment of MITS histological samples.ResultsResults include the creation of a training hub and curriculum, with a total of 9 pathologists and technicians trained as part of the training of the trainers. Those trainers trained 15 participants from seven MITS projects representing 6 LMICs trained in MITS sample collection. The 15 participants have gone on to train more than 50 project-level staff in MITS sample collection.ConclusionsLessons learned include an appreciation for using an iterative process for establishing standardized procedures, creating opportunities for all stakeholders to deliver critical feedback, and highlighting the importance of complementing in-person trainings with ongoing technical assistance.

Validating a Minimally Invasive Tissue Sampling (MITS) Method in Determining Cause of Death in Stillbirths and Neonates.

Complete diagnostic autopsy (CDA) remains the gold standard and a valuable technique for determining cause of death. It is a source of health statistics that can be used to measure health care services’ quality, unraveling important information on disease processes, particularly in emerging and unknown diseases. It can also be a vital tool for medical education and biomedical research. However, autopsy rates have been declining globally. There is an urgent need to develop and validate alternative methods in different settings to provide reliable information on cause of death. In this study, we aimed to determine cause of death (KazCoDe) in neonates and infants using minimally invasive tissue sampling (MITS), and to compare these results with those of CDA. We conducted MITS and CDA sequentially on 24 deceased children at the Pathological Bureau of the Akimat of the city of Nur-Sultan. Clinical data of the study subjects were extracted from their clinical records. During both procedures, brain, liver and lung tissues were collected for pathological diagnosis. Fifteen (62.5%) and nine (37.5%) were stillbirths and neonates, respectively. Eight (33.3%) were females and 16 (66.7%) were males. MITS diagnosis of cause of death was concordant with CDA diagnosis in 83.3% out of the 24 cases when considering the immediate and underlying causes of death and reviewing all the clinical and laboratory test results as part of the diagnostic evaluation to arrive at a cause of death (ICD-PM). We concluded that MITS is a valuable and reliable method for cause of death diagnosis in stillbirths and neonates, which can contribute vital mortality statistics in children in the absence of CDA.

Consent to minimally invasive tissue sampling procedures in children in Mozambique: A mixed-methods study.

Minimally invasive tissue sampling (MITS), also named minimally invasive autopsy is a post-mortem method shown to be an acceptable proxy of the complete diagnostic autopsy. MITS improves the knowledge of causes of death (CoD) in resource-limited settings. Its implementation requires understanding the components of acceptability, including facilitators and barriers in real-case scenarios. We undertook a mixed-methods analysis comparing anticipated (hypothetical scenario) and experienced (real-case scenario) acceptability of MITS among relatives of deceased children in Mozambique. Anticipated acceptability information was obtained from 15 interviews with relatives of deceased children. The interview focus was on whether and why they would allow the procedure on their dead child in a hypothetical scenario. Experienced acceptability data were obtained from outcomes of consent requested to relatives of 114 deceased children during MITS implementation, recorded through observations, clinical records abstraction and follow-up informal conversations with health care professionals and semi-structured interviews with relatives. Ninety-three percent of relatives indicated that they would hypothetically accept MITS on their deceased child. A key reason was knowing the CoD to take preventive actions; whereas the need to conform with the norm of immediate child burial, the secrecy of perinatal deaths, the decision-making complexity, the misalignment between MITS' purpose and traditional values, lack of a credible reason to investigate CoD, and the impotency to resuscitate the deceased were identified as potential points of hesitancy for acceptance. The only refusing respondent linked MITS to a perception that sharing results would constitute a breach of confidentiality and the lack of value attached to CoD determination. Experienced acceptability revealed four different components: actual acceptance, health professionals' hesitancy, relatives' hesitancy and actual refusal, which resulted in 82% of approached relatives to agree with MITS and 79% of cases to undergo MITS. Barriers to acceptability included, among others, health professionals' and facilities' unpreparedness to perform MITS, the threat of not burying the child immediately, financial burden of delays, decision-making complexities and misalignment of MITS' objectives with family values. MITS showed high anticipated and experienced acceptability driven by the opportunity to prevent further deaths. Anticipated acceptability identified secrecy, confidentiality and complex decision-making processes as barriers, while experienced acceptability revealed family- and health facility-level logistics and practical aspects as barriers. Health-system and logistical impediments must also be considered before MITS implementation. Additionally, the multiple components of acceptability must be taken into account to make it more consistent and transferrable.

Perceptions of family, community and religious leaders and acceptability for minimal invasive tissue sampling to identify the cause of death in under-five deaths and stillbirths in North India: a qualitative study

BackgroundMinimal invasive tissue sampling (MITS) has emerged as a suitable alternative to complete diagnostic autopsy (CDA) for determination of the cause of death (CoD), due to feasibility and acceptability issues. A formative research was conducted to document the perceptions of parents, community and religious leaders on acceptability of MITS.MethodsThis qualitative study was conducted at and around the Safdarjung Hospital, Delhi, India. Participants for in-depth interview included the parents who had either child or neonatal death or stillbirth and the key community and religious representatives. The focus group discussions (FGDs) involved community members. Process of obtaining consent for MITS was observed. Data were analyzed inductively manually for emerging themes and codes.ResultsA total of 104 interviews (parents of deceased children, neonates or stillbirths, n = 93; community members, n = 8 and religious leaders, n = 7), 8 FGDs (n = 72) were conducted and process of obtaining consent for MITS (n = 27) was observed. The participants were positive and expressed willingness to accept MITS. The key determinants for acceptance of MITS were: (1) understanding and willingness to know the cause of death or stillbirth, (2) experience of the healthcare received and trust, (3) the religious and sociocultural norms. Parents and community favored for MITS over CDA when needed, especially where in cases with past stillbirths and child deaths. The experience of treatment, attitude and communication from healthcare providers emerged as important for consent. The decision making process was collective involving the elders and family. No religious leader was against the procedure, as both, the respect for the deceased and need for medical care were satisfied.ConclusionsLargely, MITS appeared to be acceptable for identifying the causes of child deaths and stillbirths, if the parents and family are counseled appropriately considering the sociocultural and religious aspects. They perceived the quality of care, attitude and communication by the healthcare providers as critical factors for acceptance of MITS.

Limitations to current methods to estimate cause of death: a validation study of a verbal autopsy model.

Background: Accurate information on causes of death (CoD) is essential to estimate burden of disease, track global progress, prioritize cost-effective interventions, and inform policies to reduce mortality. In low-income settings, where a significant proportion of deaths take place at home or in poorly-resourced peripheral health facilities, data on CoD often relies on verbal autopsies (VAs). Validations of VAs have been performed against clinical diagnosis, but never before against an acceptable gold standard: the complete diagnostic autopsy (CDA). Methods: We have validated a computer-coded verbal autopsy method -the InterVA- using individual and population metrics to determine CoD against the CDA, in 316 deceased patients of different age groups who died in a tertiary-level hospital in Maputo, Mozambique between 2013 and 2015. Results: We found a low agreement of the model across all age groups at the individual (kappa statistic ranging from -0.030 to 0.232, lowest in stillbirths and highest in adults) and population levels (chance-corrected cause-specific mortality fraction accuracy ranging from -1.00 to 0.62, lowest in stillbirths, highest in children). The sensitivity in identifying infectious diseases was low (0% for tuberculosis, diarrhea, and disseminated infections, 32% for HIV-related infections, 33% for malaria and 36% for pneumonia). Of maternal deaths, 26 were assigned to eclampsia but only four patients actually died of eclampsia. Conclusions: These findings do not lead to building confidence in current estimates of CoD. They also call to the need to implement autopsy methods where they may be feasible, and to improve the quality and performance of current VA techniques.

Limitations to current methods to estimate cause of death: a validation study of a verbal autopsy model.

Background: Accurate information on causes of death (CoD) is essential to estimate burden of disease, track global progress, prioritize cost-effective interventions, and inform policies to reduce mortality. In low-income settings, where a significant proportion of deaths take place at home or in poorly-resourced peripheral health facilities, data on CoD often relies on verbal autopsies (VAs). Validations of VAs have been performed against clinical diagnosis, but never before against an acceptable gold standard: the complete diagnostic autopsy (CDA). Methods: We have validated a computer-coded verbal autopsy method -the InterVA- using individual and population metrics to determine CoD against the CDA, in 316 deceased patients of different age groups who died in a tertiary-level hospital in Maputo, Mozambique between 2013 and 2015. Results: We found a low agreement of the model across all age groups at the individual (kappa statistic ranging from -0.030 to 0.232, lowest in stillbirths and highest in adults) and population levels (chance-corrected cause-specific mortality fraction accuracy ranging from -1.00 to 0.62, lowest in stillbirths, highest in children). The sensitivity in identifying infectious diseases was low (0% for tuberculosis, diarrhea, and disseminated infections, 32% for HIV-related infections, 33% for malaria and 36% for pneumonia). Of maternal deaths, 26 were assigned to eclampsia but only four patients actually died of eclampsia. Conclusions: These findings do not lead to building confidence in current estimates of CoD. They also call to the need to implement autopsy methods where they may be feasible, and to improve the quality and performance of current VA techniques.

Rumor surveillance in support of minimally invasive tissue sampling for diagnosing the cause of child death in low-income countries: A qualitative study.

In low-and middle-income countries, determining the cause of death of any given individual is impaired by poor access to healthcare systems, resource-poor diagnostic facilities, and limited acceptance of complete diagnostic autopsies. Minimally invasive tissue sampling (MITS), an innovative post-mortem procedure based on obtaining tissue specimens using fine needle biopsies suitable for laboratory analysis, is an acceptable proxy of the complete diagnostic autopsy, and thus could reduce the uncertainty of cause of death. This study describes rumor surveillance activities developed and implemented in Bangladesh, Mali, and Mozambique to identify, track and understand rumors about the MITS procedure. Our surveillance activities included observations and interviews with stakeholders to understand how rumors are developed and spread and to anticipate rumors in the program areas. We also engaged young volunteers, local stakeholders, community leaders, and study staff to report rumors being spread in the community after MITS launch. Through community meetings, we also managed and responded to rumors. When a rumor was reported, the field team purposively conducted interviews and group discussions to track, verify and understand the rumor. From July 2016 through April 2018, the surveillance identified several rumors including suspicions of organs being harvested or transplanted; MITS having been performed on a living child, and concerns related to disrespecting the body and mistrust related to the study purpose. These rumors, concerns, and cues of mistrust were passed by word of mouth. We managed the rumors by modifying the consent protocol and giving additional information and support to the bereaved family and to the community members. Rumor surveillance was critical for anticipating and readily identifying rumors and managing them. Setting up rumor surveillance by engaging community residents, stakeholders, and volunteers could be an essential part of any public health program where there is a need to identify and react in real-time to public concern.

Limitations to current methods to estimate cause of death: a validation study of a verbal autopsy model

Background: Accurate information on causes of death (CoD) is essential to estimate burden of disease, track global progress, prioritize cost-effective interventions, and inform policies to reduce mortality. In low-income settings, where a significant proportion of deaths take place at home or in poorly-resourced peripheral health facilities, data on CoD often relies on verbal autopsies (VAs). Validations of VAs have been performed against clinical diagnosis, but never before against an acceptable gold standard: the complete diagnostic autopsy (CDA). Methods: We have validated a computer-coded verbal autopsy method –the InterVA- using individual and population metrics to determine CoD against the CDA, in 316 deceased patients of different age groups who died in a tertiary-level hospital in Maputo, Mozambique between 2013 and 2015. Results: We found a low agreement of the model across all age groups at the individual (kappa statistic ranging from -0.030 to 0.232, lowest in stillbirths and highest in adults) and population levels (chance-corrected cause-specific mortality fraction accuracy ranging from -1.00 to 0.62, lowest in stillbirths, highest in children). The sensitivity in identifying infectious diseases was low (0% for tuberculosis, diarrhea, and disseminated infections, 32% for HIV-related infections, 33% for malaria and 36% for pneumonia). Of maternal deaths, 26 were assigned to eclampsia but only four patients actually died of eclampsia. Conclusions: These findings do not lead to building confidence in current estimates of CoD. They also call to the need to implement autopsy methods where they may be feasible, and to improve the quality and performance of current VA techniques.

An In-Depth Examination of Reasons for Autopsy Acceptance and Refusal in Northern Tanzania.

Uncertainty about the causes of death (COD) in low- and middle-income countries (LMICs) has been recognized as a constraint to global health and development. Although complete diagnostic autopsy (CDA) is the best way to assess COD, it is uncommon in LMICs because of low investment priority and assumptions about poor acceptability. Social science research was conducted from May 2016 through July 2017 to examine issues related to acceptability of CDAs in northern Tanzania where autopsy was being offered in two referral hospitals to assess COD associated with febrile illness. Initial formative research entailed 29 key informant interviews, seven observations of burial practices, and four group discussions. In-depth interviews were conducted with families of deceased, including nine families that accepted and 11 families that refused CDA. The formative research identified concepts related to death, understandings of CDA, and cultural practices and psychosocial considerations associated with death that informed the authorization process. Most families who accepted CDA cited the desire to get clarity regarding the COD as a primary reason for acceptance. An unexpected finding was that CDA is perceived as a means to determine witchcraft involvement, a common explanation for COD and a common reason for postmortem acceptance. Death resulting from chronic illness or conditions presumed to have a clinical diagnosis were reasons for CDA to be viewed as unnecessary. The timing, way families were approached, and content of information shared during authorization influenced acceptance and refusal of CDA. Findings show that CDAs can be acceptable in settings where traditional disease models prevail.

Performance of the Xpert MTB/RIF Ultra Assay for Determining Cause of Death by TB in Tissue Samples Obtained by Minimally Invasive Autopsies

Performance of the Xpert MTB/RIF Ultra Assay for Determining Cause of Death by TB in Tissue Samples Obtained by Minimally Invasive Autopsies

Quality of care and maternal mortality in a tertiary-level hospital in Mozambique: a retrospective study of clinicopathological discrepancies

SummaryBackgroundAlthough an increasing number of pregnant women in resource-limited areas deliver in health-care facilities, maternal mortality remains high in these settings. Inadequate diagnosis and management of common life-threatening conditions is an important determinant of maternal mortality. We analysed the clinicopathological discrepancies in a series of maternal deaths from Mozambique and assessed changes over 10 years in the diagnostic process. We aimed to provide data on clinical diagnostic accuracy to be used for improving quality of care and reducing maternal mortality.MethodsWe did a retrospective analysis of clinicopathological discrepancies in 91 maternal deaths occurring from Nov 1, 2013, to March 31, 2015 (17 month-long period), at a tertiary-level hospital in Mozambique, using complete diagnostic autopsies as the gold standard to ascertain cause of death. We estimated the performance of the clinical diagnosis and classified clinicopathological discrepancies as major and minor errors. We compared the findings of this analysis with those of a similar study done in the same setting 10 years earlier.FindingsWe identified a clinicopathological discrepancy in 35 (38%) of 91 women. All diagnostic errors observed were classified as major discrepancies. The sensitivity of the clinical diagnosis for puerperal infections was 17% and the positive predictive value was 50%. The sensitivity for non-obstetric infections was 48%. The sensitivity for eclampsia was 100% but the positive predictive value was 33%. Over the 10-year period, the performance of clinical diagnosis did not improve, and worsened for some diagnoses, such as puerperal infection.InterpretationDecreasing maternal mortality requires improvement of the pre-mortem diagnostic process and avoidance of clinical errors by refining clinical skills and increasing the availability and quality of diagnostic tests. Comparison of post-mortem information with clinical diagnosis will help monitor the reduction of clinical errors and thus improve the quality of care.FundingBill & Melinda Gates Foundation and Instituto de Salud Carlos III.

Limitations to current methods to estimate cause of death: a validation study of a verbal autopsy model.

Background: Accurate information on causes of death (CoD) is essential to estimate burden of disease, track global progress, prioritize cost-effective interventions, and inform policies to reduce mortality. In low-income settings, where a significant proportion of deaths take place at home or in poorly-resourced peripheral health facilities, data on CoD often relies on verbal autopsies (VAs). Validations of VAs have been performed against clinical diagnosis, but never before against an acceptable gold standard: the complete diagnostic autopsy (CDA). Methods: We have validated a computer-coded verbal autopsy method -the InterVA- using individual and population metrics to determine CoD against the CDA, in 316 deceased patients of different age groups who died in a tertiary-level hospital in Maputo, Mozambique between 2013 and 2015. Results: We found a low agreement of the model across all age groups at the individual (kappa statistic ranging from -0.030 to 0.232, lowest in stillbirths and highest in adults) and population levels (chance-corrected cause-specific mortality fraction accuracy ranging from -1.00 to 0.62, lowest in stillbirths, highest in children). The sensitivity in identifying infectious diseases was low (0% for tuberculosis, diarrhea, and disseminated infections, 32% for HIV-related infections, 33% for malaria and 36% for pneumonia). Of maternal deaths, 26 were assigned to eclampsia but only four patients actually died of eclampsia. Conclusions: These findings do not lead to building confidence in current estimates of CoD. They also call to the need to implement autopsy methods where they may be feasible, and to improve the quality and performance of current VA techniques.