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Abstract Background Malaria contributes substantially to the persistent burden of child deaths in sub-Saharan Africa. Accurate and comprehensive malaria mortality data are crucial to monitor the progress in reducing malaria incidence and mortality. Verbal Autopsy (VA) ascertains the cause of death despite its limitations leading to misclassification errors. Minimally Invasive Tissue Sampling (MITS) is being conducted in some settings as an alternative to Complete Diagnostic Autopsy (CDA). The present study examines the validity of malaria-related deaths comparing VA diagnoses with those obtained through MITS and/or CDA. Methods A comprehensive literature search for original studies in English language using Ovid MEDLINE, Ovid Embase, CINAHL via EBSCO, Scopus, The Cochrane Library via Wiley, Google Scholar and searching the MITS Surveillance Alliance papers was carried out. The reference period was January 1, 1990–March 31, 2024. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were adopted. Results Among 71 articles identified in the databases, 21 matched the eligibility criteria. Qualitative syntheses showed that malaria Cause Specific Mortality Fractions (CSMFs) across various studies ranged from 2 to 31%. Plasmodium falciparum was mostly responsible for these deaths and the most common complications were anaemia and cerebral malaria. The sensitivity and specificity of the VA validation studies ranged from 18.4% to 33% and from 86.6% to 97%, respectively, and there was a high level of misclassification for both InSilico and Expert Algorithm VA for malaria compared to MITS. The overall concordance rates between MITS and CDA diagnoses ranged from 68 to 90%, with the highest concordance seen in deaths due to infectious diseases and malignant tumours. Clinical data increased diagnostic coincidence between MITS blind to clinical data and the gold standard CDA by 11%. Conclusions The comprehensive review finds that MITS demonstrated better accuracy compared to VA in diagnosing malaria-attributed deaths, particularly in hospital settings. The high specificity of malaria in VA diagnosis suggests population-based estimates of the proportion of deaths due to malaria are broadly plausible.

Background: Malaria contributes substantially to the persistent burden of child deaths in sub-Saharan Africa. Accurate and comprehensive malaria mortality data are crucial to monitor the progress in reducing malaria incidence and mortality. Verbal Autopsy (VA) ascertains the cause of death despite its limitations leading to misclassification errors. Minimally Invasive Tissue Sampling (MITS) is being conducted in some settings as an alternative to Complete Diagnostic Autopsy (CDA). The present study examines the validity of malaria-related deaths comparing VA diagnoses with those obtained through MITS and/or CDA. Methods: A comprehensive literature search for original studies in English language using Ovid MEDLINE, Ovid Embase, CINAHL via EBSCO, Scopus, The Cochrane Library via Wiley, Google Scholar and searching the MITS Surveillance Alliance papers was carried out. The reference period was January 1, 1990–March 31, 2024. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were adopted. Results: Among 71 articles identified in the databases, 21 matched the eligibility criteria. Qualitative syntheses showed that malaria Cause Specific Mortality Fractions (CSMFs) across various studies ranged from 2 to 31%. Plasmodium falciparum was mostly responsible for these deaths and the most common complications were anaemia and cerebral malaria. The sensitivity and specificity of the VA validation studies ranged from 18.4% to 33% and from 86.6% to 97%, respectively, and there was a high level of misclassification for both InSilico and Expert Algorithm VA for malaria compared to MITS. The overall concordance rates between MITS and CDA diagnoses ranged from 68 to 90%, with the highest concordance seen in deaths due to infectious diseases and malignant tumours. Clinical data increased diagnostic coincidence between MITS blind to clinical data and the gold standard CDA by 11%. Conclusions: The comprehensive review finds that MITS demonstrated better accuracy compared to VA in diagnosing malaria-attributed deaths, particularly in hospital settings. The high specificity of malaria in VA diagnosis suggests population-based estimates of the proportion of deaths due to malaria are broadly plausible. [ABSTRACT FROM AUTHOR]

The exact aetiology of the cause of death (COD) remains unknown for a high proportion of deaths caused by infectious diseases. Complete diagnostic autopsy (CDA) is considered the gold standard to determine COD, but it is often not used in low and middle-income countries (LMIC), including Vietnam, for a variety of reasons. One alternative is minimally invasive tissue sampling (MITS). This study was part of a larger project to explore the perceptions of MITS in Vietnam to provide recommendations for its potential implementation. We collected in-depth interviews and focus group discussions that explored MITS acceptability from 96 participants, including key informants, healthcare workers, community stakeholders, and people who had family members pass away recently. Participants highlighted the minimally invasive nature as the most considerable strength of MITS that could make it acceptable in Vietnam compared with CDA. However, participants still had concerns including the accuracy of the technique, the potential damage on the body, and the potential conflicts MITS results could have with original clinical diagnoses. Overall, the hypothetical acceptability of MITS was not clear-cut. It is imperative to consider acceptability before implementing new medical procedures into a given context, especially when it revolves around death, dying and the body.

Abstract Background Diagnostic autopsy is the most reliable approach to definitively ascertain the cause of death and evaluate the accuracy of antemortem clinical diagnoses. Identifying diagnostic discrepancies is vital to understanding common gaps in antemortem clinical diagnoses and modifying antemortem diagnostic approaches to increase the accuracy of clinical diagnosis. The objective of this study was to determine the frequency of diagnostic discrepancies between antemortem clinical diagnoses and postmortem autopsies on lung pathologies and to understand the reasons for diagnostic discrepancies among cases included in Child Health and Mortality Prevention Surveillance (CHAMPS) in Ethiopia. Methods A clinical case series study of deaths among children under-five in the CHAMPS study at three sites in Ethiopia between October 2019 and April 2022 was conducted. The antemortem clinical diagnoses and postmortem pathological diagnoses of the lung were compared for each case. Two senior physicians assessed the findings for both agreement and disagreement. McNemar’s test was used to assess for statistically significant differences between antemortem and postmortem diagnoses. Results Seventy-five cases were included (73.3% male). Over half (54.7%) died between the 1st and 7th day of life. Sepsis (66.7%), pneumonia (6.7%), and meconium aspiration syndrome (5.0%) were the most common immediate causes of death. Half (52%) of cases were correctly diagnosed antemortem. The magnitude of diagnostic discrepancy was 35% (95% CI: 20-47%). The most common contributing factors to diagnostic discrepancy were gaps in knowledge (22/75, 35.5%) and problems in consultation and teamwork (22/75, 35.5%). Conclusions Misdiagnoses were common among young children who died with positive lung pathology findings. In-service education initiatives and multidisciplinary collaboration are needed to mitigate high rates of diagnostic discrepancies among young children to potentially prevent future deaths.

Background: Diagnostic autopsy is the most reliable approach to definitively ascertain the cause of death and evaluate the accuracy of antemortem clinical diagnoses. Identifying diagnostic discrepancies is vital to understanding common gaps in antemortem clinical diagnoses and modifying antemortem diagnostic approaches to increase the accuracy of clinical diagnosis. The objective of this study was to determine the frequency of diagnostic discrepancies between antemortem clinical diagnoses and postmortem autopsies on lung pathologies and to understand the reasons for diagnostic discrepancies among cases included in Child Health and Mortality Prevention Surveillance (CHAMPS) in Ethiopia. Methods: A clinical case series study of deaths among children under-five in the CHAMPS study at three sites in Ethiopia between October 2019 and April 2022 was conducted. The antemortem clinical diagnoses and postmortem pathological diagnoses of the lung were compared for each case. Two senior physicians assessed the findings for both agreement and disagreement. McNemar's test was used to assess for statistically significant differences between antemortem and postmortem diagnoses. Results: Seventy-five cases were included (73.3% male). Over half (54.7%) died between the 1st and 7th day of life. Sepsis (66.7%), pneumonia (6.7%), and meconium aspiration syndrome (5.0%) were the most common immediate causes of death. Half (52%) of cases were correctly diagnosed antemortem. The magnitude of diagnostic discrepancy was 35% (95% CI: 20-47%). The most common contributing factors to diagnostic discrepancy were gaps in knowledge (22/75, 35.5%) and problems in consultation and teamwork (22/75, 35.5%). Conclusions: Misdiagnoses were common among young children who died with positive lung pathology findings. In-service education initiatives and multidisciplinary collaboration are needed to mitigate high rates of diagnostic discrepancies among young children to potentially prevent future deaths. [ABSTRACT FROM AUTHOR]

Minimally invasive tissue sampling of the brain in newborns using the Bard Monopty needle helps to diagnose various neurological conditions by obtaining relevant brain cores. We designed a modified procedure to provide maximum diagnostic utility in brain tissue biopsies. Twenty newborns underwent postmortem minimally invasive tissue sampling of the brain through the anterior fontanelle and posterior approach, using the engraved lines on the needle labeled from mark 0 to 13. The cores were correlated with conventional autopsy findings. Meninges were best obtained at marks 0 and 1 from the anterior fontanelle and mark 1 from posterior fontenelle in 85% of cases. Periventricular brain parenchyma was best obtained from mark 3 and mark 1 from anterior and posterior fontanel, respectively in 90% cases. The sampling success in obtaining brain cores was 100%. This modified technique increases the yield of meninges and brain tissue in newborns and aids in diagnosis. [ABSTRACT FROM AUTHOR]

In pandemics or to further study highly contagious infectious diseases, new strategies are needed for the collection of post-mortem tissue samples to identify the pathogen as well as its morphological impact. In this study, an ultrasound-guided minimally invasive tissue sampling (MITS) protocol was developed and validated for post-mortem use. The histological and microbiological qualities of post-mortem specimens were evaluated and compared between MITS and conventional autopsy (CA) in a series of COVID-19 deaths. Thirty-six ultrasound-guided MITS were performed. In five cases more, specimens for histological and virological examination were also obtained and compared during the subsequently performed CA. Summary statistics and qualitative interpretations (positive, negative) were calculated for each organ tissue sample from MITS and CA, and target genes were determined for both human cell count (beta-globin) and virus (SARS-CoV-2 specific E gene). There are no significant differences between MITS and CA with respect to the detectability of viral load in individual organs, which is why MITS can be of utmost importance and an useful alternative, especially during outbreaks of infectious diseases. [ABSTRACT FROM AUTHOR]

The exact aetiology of the cause of death (COD) remains unknown for a high proportion of deaths caused by infectious diseases. Complete diagnostic autopsy (CDA) is considered the gold standard to determine COD, but it is often not used in low and middle-income countries (LMIC), including Vietnam, for a variety of reasons. One alternative is minimally invasive tissue sampling (MITS). This study was part of a larger project to explore the perceptions of MITS in Vietnam to provide recommendations for its potential implementation. We collected in-depth interviews and focus group discussions that explored MITS acceptability from 96 participants, including key informants, healthcare workers, community stakeholders, and people who had family members pass away recently. Participants highlighted the minimally invasive nature as the most considerable strength of MITS that could make it acceptable in Vietnam compared with CDA. However, participants still had concerns including the accuracy of the technique, the potential damage on the body, and the potential conflicts MITS results could have with original clinical diagnoses. Overall, the hypothetical acceptability of MITS was not clear-cut. It is imperative to consider acceptability before implementing new medical procedures into a given context, especially when it revolves around death, dying and the body. [ABSTRACT FROM AUTHOR]

Abstract Background Minimally invasive tissue sampling (MITS) has increasingly been used to improve the diagnosis of disease and identification of the cause of death, particularly in underserved areas. However, there are multiple barriers to accessing those who die within the community, our study aimed to explore the perceptions and insights of community members and healthcare providers regarding the feasibility of implementing MITS in community settings. Methods A qualitative exploratory study was conducted. A total of twenty one in-depth interviews were conducted with deceased infants’ parents, elders of the family, religious leaders, community leaders, and funeral workers. Focus group discussions were conducted with health care providers (n = 14) in two peri-urban slum areas of Karachi, Pakistan. The duration of this study was from August to October 2020. Data was analyzed using thematic analysis and was coded and merged into categories forming eight major themes. Results In general, participants viewed minimally invasive tissue sampling (MITS) as beneficial for improving child health, though some had concerns about disrespecting the deceased during sample collection. Misinformation, fear of needles, and medical procedures were major barriers to MITS implementation. To enhance acceptance, community and religious leaders suggested using religious rulings, obtaining parental consent, ensuring confidentiality, and increasing efforts of community engagement. Community healthcare providers, along with funeral workers, recommended providing community members with grief counseling to increase study participation. Besides concerns about sampling interfering with respect for the decease, community members also raised concerns about misinformation. Further, participants provided feedback on the design and appearance of the mobile van used to collect MITS samples from children under the age of five. Conclusion This study is critical for understanding the challenges associated with implementation of community-based MITS sampling in Pakistan. Integrating the use of a mobile van for sample collection, grief counseling along with community engagement sessions and advocacy will help address community-based misinformation and develop community trust.

Abstract Background Minimally 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. Methods A 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. Results Among 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

Background: Minimally invasive tissue sampling (MITS) has increasingly been used to improve the diagnosis of disease and identification of the cause of death, particularly in underserved areas. However, there are multiple barriers to accessing those who die within the community, our study aimed to explore the perceptions and insights of community members and healthcare providers regarding the feasibility of implementing MITS in community settings. Methods: A qualitative exploratory study was conducted. A total of twenty one in-depth interviews were conducted with deceased infants' parents, elders of the family, religious leaders, community leaders, and funeral workers. Focus group discussions were conducted with health care providers (n = 14) in two peri-urban slum areas of Karachi, Pakistan. The duration of this study was from August to October 2020. Data was analyzed using thematic analysis and was coded and merged into categories forming eight major themes. Results: In general, participants viewed minimally invasive tissue sampling (MITS) as beneficial for improving child health, though some had concerns about disrespecting the deceased during sample collection. Misinformation, fear of needles, and medical procedures were major barriers to MITS implementation. To enhance acceptance, community and religious leaders suggested using religious rulings, obtaining parental consent, ensuring confidentiality, and increasing efforts of community engagement. Community healthcare providers, along with funeral workers, recommended providing community members with grief counseling to increase study participation. Besides concerns about sampling interfering with respect for the decease, community members also raised concerns about misinformation. Further, participants provided feedback on the design and appearance of the mobile van used to collect MITS samples from children under the age of five. Conclusion: This study is critical for understanding the challenges associated with implementation of community-based MITS sampling in Pakistan. Integrating the use of a mobile van for sample collection, grief counseling along with community engagement sessions and advocacy will help address community-based misinformation and develop community trust. [ABSTRACT FROM AUTHOR]

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Background: Minimally 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. Methods: A 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. Results: Among 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). Conclusions: MITS 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. [ABSTRACT FROM AUTHOR]

Stillbirth, one of the most common adverse pregnancy outcomes, is especially prevalent in low and middle-income countries (LMICs). Understanding the causes of stillbirth is crucial to developing effective interventions. In this commentary, investigators working across several LMICs discuss the most useful investigations to determine causes of stillbirths in LMICs. Useful data were defined as 1) feasible to obtain accurately and 2) informative to determine or help eliminate a cause of death. Recently, new tools for LMIC settings to determine cause of death in stillbirths, including minimally invasive tissue sampling (MITS) – a method using needle biopsies to obtain internal organ tissue from deceased fetuses for histology and pathogen identification in those tissues have become available. While placental histology has been available for some time, the development of the Amsterdam Criteria in 2016 has provided a useful framework to categorize placental lesions. The authors recommend focusing on the clinical history, the placental evaluation, the external examination of the fetus, and, when available, fetal tissue obtained by MITS, especially of the lung (focused on histology and microbiology) and brain/cerebral spinal fluid (CSF) and fetal blood (focused on microbiological analysis). The authors recognize that this approach may not identify some causes of stillbirth, including some genetic abnormalities and internal organ anomalies, but believe it will identify the most common causes of stillbirth, and most of the preventable causes.

Global health practitioners and policymakers have become increasingly vocal about the complex challenges of identifying and quantifying the causes of death of the world's poorest people. To address this cause-of-death uncertainty and to minimise longstanding sensitivities about full autopsies, the Bill and Melinda Gates Foundation have been one of the foremost advocates of minimally invasive autopsy technology (MIA). MIA involves using biopsy needles to collect samples from key organs and body fluids; as such, it is touted as potentially more acceptable and less invasive than a complete autopsy, which requires opening the cadaver. In addition, MIA is considered a good means of collecting accurate bodily samples and can provide the crucial information needed to address cause-of-death uncertainty. In this paper, we employ qualitative data to demonstrate that while MIA technology has been introduced as a solution to the enduring cause-of-death uncertainty, the development and deployment of technologies such as these always constitute interventions in complex social and moral worlds; in this respect, they are both the solutions to and the causes of new kinds of uncertainties. We deconstruct the ways in which those new dimensions of uncertainty operate at different levels in the global health context. [ABSTRACT FROM AUTHOR]

The role of meningitis in causing deaths and in children under 5 is unclear, especially since widespread use of vaccines to prevent common causes of meningitis. Child Health and Mortality Prevention Surveillance (CHAMPS) uses post-mortem minimally invasive tissue sampling (MITS) and ante-mortem data to explore death causes. We aimed to assess meningitis's contribution to mortality and identify causative pathogens in children under 5 within CHAMPS Network sites. In this observational study, we analyzed deaths in live-born children <5 years of age that occurred between December 16, 2016, and December 31, 2023, in CHAMPS catchments in six sub-Saharan African countries (Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, South Africa) and Bangladesh. MITS was conducted within 24–72 h of death, including blood and cerebrospinal fluid (CSF) culture, multi-organism targeted nucleic acid amplification tests on blood, CSF and lung tissue, and histopathology of lung, liver and brain. Expert panels at each site reviewed data to attribute causes of death following ICD-10 standards. Meningitis was in the causal pathway for 7.0% (270/3857) of deaths; in 4.8% (13/270) meningitis was considered the underlying condition. Neonates accounted for 65.9% (178/270) and infants or children 34.1% (92/270). Among neonatal meningitis deaths, 55.6% (99/178) occurred ≥72 h post-hospital admission; and common pathogens were Acinetobacter baumannii (49.5%, 49/99; mainly from South Africa) and Klebsiella pneumoniae (40.4%, 40/99). Forty-four percent (79/178) of neonatal meningitis deaths were community-associated, primarily due to K. pneumoniae (35.4%, 28/79) and Escherichia coli (13.9%, 11/79). Among infant and child meningitis deaths, 43.5% (40/92) occurred ≥72 h post-admission; and common pathogens were K. pneumoniae (42.5%,17/40) and A. baumannii (17.5%, 7/40). Among community-associated meningitis deaths in infants and children (56.5%, 52/92), Streptococcus pneumoniae (34.6%, 18/52) and K. pneumoniae (19.2%, 10/52) were common pathogens. Pathogen prevalence varied by region. Our study highlights meningitis as a significant contributor to under-5 mortality in low-middle-income countries. The prominent role of K. pneumoniae and A. baumannii, particularly in healthcare settings and specific regions, highlights the need for better infection control, targeted interventions, and more effective treatment strategies. • Meningitis was found to be one of the leading causes of U5 deaths in the CHAMPS network, exceeding the WHO's estimated rate. • This discrepancy suggests current estimates may underestimate meningitis cases by not considering all contributing factors. • High rates of resistant organisms like K pneumoniae and A baumannii increase mortality risk if antibiotics aren't used. • Vaccination has reduced S. pneumoniae cases, it remains a significant pathogen for community-acquired meningitis. [ABSTRACT FROM AUTHOR]

Global health practitioners and policymakers have become increasingly vocal about the complex challenges of identifying and quantifying the causes of death of the world’s poorest people. To address this cause-of-death uncertainty and to minimise longstanding sensitivities about full autopsies, the Bill and Melinda Gates Foundation have been one of the foremost advocates of minimally invasive autopsy technology (MIA). MIA involves using biopsy needles to collect samples from key organs and body fluids; as such, it is touted as potentially more acceptable and less invasive than a complete autopsy, which requires opening the cadaver. In addition, MIA is considered a good means of collecting accurate bodily samples and can provide the crucial information needed to address cause-of-death uncertainty. In this paper, we employ qualitative data to demonstrate that while MIA technology has been introduced as a solution to the enduring cause-of-death uncertainty, the development and deployment of technologies such as these always constitute interventions in complex social and moral worlds; in this respect, they are both the solutions to and the causes of new kinds of uncertainties. We deconstruct the ways in which those new dimensions of uncertainty operate at different levels in the global health context.

Belson Rugwizangoga,1,2 Jean Berchmans Niyibizi,3 Marie Claire Ndayisaba,2 Emile Musoni,1,2 Felix Manirakiza,1,2 Annette Uwineza,1,2 Lisine Tuyisenge,4 Martin Nyundo,5 Theobald Hategekimana,5 Gervais Ntakirutimana2 1Department of Clinical Biology, University of Rwanda, Kigali, Rwanda; 2Department of Pathology, University Teaching Hospital of Kigali, Kigali, Rwanda; 3Department of Public Health, University of Rwanda, Kigali, Rwanda; 4Department of Pediatrics, University Teaching Hospital of Kigali, Kigali, Rwanda; 5Department of Surgery, University Teaching Hospital of Kigali, Kigali, RwandaCorrespondence: Belson Rugwizangoga PO Box 655, Kigali, Rwanda, Tel +250-78-854-6597Email b.rugwizangoga@ur.ac.rw; belson777@gmail.comPurpose: In most low- and lower middle-income countries (LMICs), minimally invasive tissue sampling (MITS) is a relatively new procedure for identifying the cause of death (CoD). This study aimed to explore perceptions and acceptance of bereaved families and health-care professionals regarding MITS in the context of MITS initiation in Rwanda as an alternative to clinical autopsy.Methods: This was a qualitative phenomenological study with thematic analysis. Participants were bereaved relatives (individual interviews) and health-care professionals (focus-group discussions) involved in MITS implementation. It was conducted in the largest referral and teaching hospital in Rwanda.Results: Motivators of MITS acceptance included eagerness to know the CoD, noninvasiveness of MITS, trust in medics, and the fact that it was free. Barriers to consent to MITS included inadequate explanations from health-care professionals, high socioeconomic status, lack of power to make decisions, and lack of trust in medics. Health-care professionals perceived both conventional autopsy and MITS as gold-standard procedures in CoD determination. They recommended including MITS among hospital services and commended the post-MITS multidisciplinary discussion panel in CoD determination. They pointed out that there might be reticence in approaching bereaved relatives to obtain consent for MITS. Both groups of participants highlighted the issue of delay in releasing MITS results.Conclusion: Both health-care professionals and bereaved relatives appreciate that MITS is an acceptable procedure to include in routine hospital services. Dealing with barriers met by either group is to be considered in the eventual next phases of MITS implementation in Rwanda and similar sociocultural contexts.Keywords: minimally invasive tissue sampling, perceptions, acceptance, low- and lower middle–income countries

Objectives: To describe and compare liver mitochondrial and peroxisomal histopathology by nutritional status in children who died following hospitalization for acute illness in Malawi., Methods: Liver tissue was collected using Minimally Invasive Tissue Sampling from eleven children under-five years old who died during hospitalization and were either non-wasted ( n = 4), severely wasted ( n = 4) or had edematous malnutrition ( n = 3). Histology was assessed on hematoxylin and eosin stained slides. Mitochondrial and peroxisomal ultrastructural features were characterized using electron microscopy (EM) and immunofluorescence (IF)., Results: Hepatic steatosis was present in 50 % of non-wasted and severely wasted children and all children with edematous malnutrition. Edematous malnutrition was associated with 56 % and 45 % fewer mitochondria than severe wasting ( p < 0.001) and no wasting ( p = 0.006), respectively, and abnormal mitochondrial morphology compared to severe wasting ( p = 0.002) and no wasting ( p = 0.035). Peroxisomal abundance was reduced in edematous malnutrition compared to severe wasting ( p = 0.005), but did not differ from no-wasting., Conclusion: Edematous malnutrition is associated with reduced abundance and altered morphology of hepatic mitochondria and peroxisomes. Interventions targeting improvements in hepatic metabolic function may be beneficial in improving metabolism and reducing mortality in children with severe malnutrition, particularly in those with nutritional edema., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Inc.)

Background Although much has been learned about the pathophysiology of coronavirus disease 2019 (COVID-19) infections, pathology data from patients who have died of COVID-19 in low- and middle-income country settings remain sparse. We integrated minimally invasive tissue sampling (MITS) into an ongoing postmortem surveillance study of COVID-19 in deceased individuals of all ages in Lusaka, Zambia. Methods We enrolled deceased subjects from the University Teaching Hospital Morgue in Lusaka, Zambia within 48 hours of death. We collected clinical and demographic information, a nasopharyngeal swab, and core tissue biopsies from the lung, liver, and kidneys for pathologic analysis. Individuals were considered eligible for MITS if they had a respiratory syndrome prior to death or a COVID-19+ polymerase chain reaction (PCR) nasopharyngeal swab specimen. Samples were retested using quantitative reverse transcriptase PCR. Results From June to September 2020 we performed MITS on 29 deceased individuals. PCR results were available for 28/29 (96.5%) cases. Three had a COVID-19+ diagnosis antemortem, and 5 more were identified postmortem using the recommended cycle threshold cut-point <40. When expanding the PCR threshold to 40 ≤ cycle threshold (Ct) ≤ 45, we identified 1 additional case. Most cases were male and occurred in the community The median age at death was 47 years (range 40–64). Human immunodeficiency virus (HIV)/AIDS, tuberculosis, and diabetes were more common among the COVID-19+ cases. Diffuse alveolar damage and interstitial pneumonitis were common among COVID-19+ cases; nonspecific findings of hepatic steatosis and acute kidney injury were also prevalent in the COVID-19+ group. Vascular thrombi were rarely detected. Conclusions Lung abnormalities typical of viral pneumonias were common among deceased COVID-19+ individuals, as were nonspecific findings in the liver and kidneys. Pulmonary vascular thrombi were rarely detected, which could be a limitation of the MITS technique. Nonetheless, MITS offers a valuable alternative to open autopsy for understanding pathological changes due to COVID-19. [ABSTRACT FROM AUTHOR]

Background We used postmortem minimally invasive tissue sampling (MITS) to assess the effect of time since death on molecular detection of pathogens among respiratory illness–associated deaths. Methods Samples were collected from 20 deceased children (aged 1–59 months) hospitalized with respiratory illness from May 2018 through February 2019. Serial lung and/or liver and blood samples were collected using MITS starting soon after death and every 6 hours thereafter for up to 72 hours. Bodies were stored in the mortuary refrigerator for the duration of the study. All specimens were analyzed using customized multipathogen TaqMan® array cards (TACs). Results We identified a median of 3 pathogens in each child's lung tissue (range, 1–8; n = 20), 3 pathogens in each child's liver tissue (range, 1–4; n = 5), and 2 pathogens in each child's blood specimen (range, 0–4; n = 5). Pathogens were not consistently detected across all collection time points; there was no association between postmortem interval and the number of pathogens detected (P  = .43) and no change in TAC cycle threshold value over time for pathogens detected in lung tissue. Human ribonucleoprotein values indicated that specimens collected were suitable for testing throughout the study period. Conclusions Results suggest that lung, liver, and blood specimens can be collected using MITS procedures up to 4 days after death in adequately preserved bodies. However, inconsistent pathogen detection in samples needs careful consideration before drawing definitive conclusions on the etiologic causes of death. [ABSTRACT FROM AUTHOR]

Background Minimally 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. Methods This 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. Results US-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. Conclusions Our data showed that US-guided MITS has the capacity similar to CDA not only to identify but also to characterize emergent diseases. [ABSTRACT FROM AUTHOR]

Minimally invasive tissue sampling (MITS) is increasingly being used to better understand causes of death in low-resource settings. Undernutrition (eg, wasting, stunting) is prevalent among children globally and yet not consistently coded or uniformly included on death certificates in MITS studies when present. Consistent and accurate attribution of undernutrition is fundamental to understanding its contribution to child deaths. In May 2020, members of the MITS Alliance Cause of Death Technical Working Group convened a panel of experts in public health, child health, nutrition, infectious diseases, and MITS to develop guidance for systematic integration of undernutrition, as assessed by anthropometry, in cause of death coding, including as part of the causal chain or as a contributing condition, in children <5 years of age. The guidance presented here will support MITS and other researchers, public health practitioners, and clinicians with a systematic approach to assigning and interpreting undernutrition in death certification. [ABSTRACT FROM AUTHOR]

Background Intestinal disorders such as environmental enteric dysfunction (EED) are prevalent in low- and middle-income countries (LMICs) and important contributors to childhood undernutrition and mortality. Autopsies are rarely performed in LMICs but minimally invasive tissue sampling is increasingly deployed as a more feasible and acceptable procedure, although protocols have been devoid of intestinal sampling to date. We sought to determine (1) the feasibility of postmortem intestinal sampling, (2) whether autolysis precludes enteric biopsies' utility, and (3) histopathologic features among children who died during hospitalization with acute illness or undernutrition. Methods Transabdominal needle and endoscopic forceps upper and lower intestinal sampling were conducted among children aged 1 week to 59 months who died while hospitalized in Blantyre, Malawi. Autolysis ratings were determined for each hematoxylin and eosin slide, and upper and lower intestinal scoring systems were adapted to assess histopathologic features and their severity. Results Endoscopic and transabdominal sampling procedures were attempted in 28 and 14 cases, respectively, with >90% success obtaining targeted tissue. Varying degrees of autolysis were present in all samples and precluded histopathologic scoring of 6% of 122 biopsies. Greater autolysis in duodenal samples was seen with longer postmortem interval (Beta = 0.06, 95% confidence interval, 0.02–0.11). Histopathologic features identified included duodenal Paneth and goblet cell depletion. Acute inflammation was absent but chronic inflammation was prevalent in both upper and lower enteric samples. Severe chronic rectal inflammation was identified in children as young as 5.5 weeks. Conclusions Minimally invasive postmortem intestinal sampling is feasible and identifies histopathology that can inform mortality contributors. [ABSTRACT FROM AUTHOR]

Background Precise determination of the causal chain that leads to community deaths in children in low- and middle-income countries is critical to estimating all causes of mortality accurately and to planning preemptive strategies for targeted allocation of resources to reduce this scourge. Methods An active surveillance population-based study that combined minimally invasive tissue sampling (MITS) and verbal autopsies (VA) among children under 5 was conducted in Buenos Aires, Argentina, from September 2018 to December 2020 to define the burden of all causes of community deaths. Results Among 90 cases enrolled (86% of parental acceptance), 81 had complete MITS, 15.6% were neonates, 65.6% were post-neonatal infants, and 18.9% were children aged 1–5 years. Lung infections were the most common cause of death (CoD) in all age groups (57.8%). Among all cases of lung infections, acute bronchiolitis was the most common CoD in infants aged <12 months (23 of 36, 63.9%), and bacterial pneumonia was the most common cause in children aged >12 months (8 of 11, 72.7%). The most common comorbid condition in all age groups was undernutrition in 18 of 90 (20%). It was possible to find an immediate CoD in 78 of 81 subjects where MITS could be done. With this combined approach, we were able to determine that sudden infant death syndrome was overestimated in state reports. Conclusions CoD determination by a combination of MITS and VA provides an accurate estimation of the chain of events that leads to death, emphasizing possible interventions to prevent mortality in children. [ABSTRACT FROM AUTHOR]

Background Minimally invasive tissue sampling (MITS) is a noninvasive technique used to determine the cause of deaths. Very little is known about the factors that affect MITS acceptance or refusal. We present findings from a prospective study conducted in Southeast Asia on the reasons for accepting or refusing MITS. Methods This substudy was conducted in India and Pakistan to determine the acceptability of MITS in women who had a stillbirth or preterm live birth who later died. A formal questionnaire was used to gather observations during the consent for MITS, such as reasons for acceptance or refusal of MITS, as well as which family members were involved in the decision process. Results In Pakistan, the MITS acceptability forms were completed for 470 of 477 women (98.5%) with an eligible stillbirth for this substudy, and 334 of 337 (99.1%) with an eligible preterm neonatal death. In India, MITS acceptability forms were completed in 219 of 305 women (71.8%) with an eligible stillbirth and 260 of 264 (98.4%) with an eligible preterm neonatal death. In India, the most common reasons for MITS refusal for both stillbirths and preterm neonatal deaths were cultural concerns, while in Pakistan, the most common reason for MITS refusal was a potential delay in the funeral. The primary reason for accepting MITS was that the parents wanted to understand the cause of death. At both sites, fathers, mothers, and relatives, often in consultation, choose whether or not to accept MITS to determine the cause of death in stillbirths and preterm neonatal deaths. Conclusions MITS was more commonly accepted in India than in Pakistan. Cultural concerns in India and funeral delays in Pakistan were common reasons for refusal. Parents from both sites were curious to know the cause of stillbirths and preterm neonatal deaths. The father, mother, and relatives were key decision makers for consenting to or declining MITS. [ABSTRACT FROM AUTHOR]

Background Minimally 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. Methods This 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. Results Sixteen 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. Conclusions MITS 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. [ABSTRACT FROM AUTHOR]

Background Minimally invasive tissue sampling (MITS) is a useful tool to determine cause of death in low- and middle-income countries (LMICs). In 2019 the MITS Surveillance Alliance supported the implementation of small-scale postmortem studies using MITS in several LMICs. Methods In this article we describe the preparations, challenges, and lessons learned as part of implementing MITS across 4 study sites in 3 countries: Nepal, Rwanda, and Tanzania. We describe the process for building capacity to conduct MITS, which consisted of training in MITS sample collection, individual site assessment to determine readiness and gaps prior to implementation, site visits as sites began implementation of MITS, and feedback based on remote evaluation of histology slides via an online portal. Results The 4 study sites each conducted 100 MITS, for a total of 400. All 4 sites lacked sufficient infrastructure and facilities to conduct MITS, and upgrades were required. Common challenges faced by sites included that clinical autopsies were neither routinely conducted nor widely accepted. Limited clinical records made cause of death determination more difficult. Lessons learned included the importance of sensitization of the community and medical staff to MITS to enhance understanding and increase consent. Conclusions The study sites accomplished MITS and utilized the available support systems to overcome the challenges. The quality of the procedures was satisfactory and was facilitated through the organized capacity-building programs. [ABSTRACT FROM AUTHOR]

Background Available information on the causes of death among people living with human immunodeficiency virus (PLHIV) in low- and middle-income countries (LMICs) remains scarce. We aimed to provide data on causes of death in PLHIV from two LMICs, Brazil and Mozambique, to assess the impact of clinical misdiagnosis on mortality rates and to evaluate the accuracy of minimally invasive tissue sampling (MITS) in determining the cause of death in PLHIV. Methods We performed coupled MITS and complete autopsy on 164 deceased PLHIV (18 children, 36 maternal deaths, and 110 adults). HIV antibody levels and HIV RNA viral loads were determined from postmortem serum samples. Results Tuberculosis (22.7%), toxoplasmosis (13.9%), bacterial infections (13.9%), and cryptococcosis (10.9%) were the leading causes of death in adults. In maternal deaths, tuberculosis (13.9%), bacterial infections (13.9%), cryptococcosis (11.1%), and cerebral malaria (8.3%) were the most frequent infections, whereas viral infections, particularly cytomegalovirus (38.9%), bacterial infections (27.8%), pneumocystosis (11.1%), and HIV-associated malignant neoplasms (11.1%) were the leading cause among children. Agreement between the MITS and the complete autopsy was 100% in children, 91% in adults, and 78% in maternal deaths. The MITS correctly identified the microorganism causing death in 89% of cases. Conclusions Postmortem studies provide highly granular data on the causes of death in PLHIV. The inaccuracy of clinical diagnosis may play a significant role in the high mortality rates observed among PLHIV in LMICs. MITS might be helpful in monitoring the causes of death in PLHIV and in highlighting the gaps in the management of the infections. [ABSTRACT FROM AUTHOR]

Background Minimally invasive tissue sampling (MITS), a postmortem procedure that uses core needle biopsy samples and does not require opening the body, may be a valid alternative to complete autopsy (CA) in highly infectious diseases such as coronavirus disease-19 (COVID-19). This study aimed to (1) compare the performance of MITS and CA in a series of COVID-19 deaths and (2) evaluate the safety of the procedure. Methods From October 2020 to February 2021, MITS was conducted in 12 adults who tested positive before death for COVID-19, in a standard, well-ventilated autopsy room, where personnel used reinforced personal protective equipment. In 9 cases, a CA was performed after MITS. A thorough histological evaluation was conducted, and the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was evaluated by real-time reverse-transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. Results The diagnoses provided by MITS and CA matched almost perfectly. In 9 patients, COVID-19 was in the chain of events leading to death, being responsible for diffuse alveolar damage and mononuclear T-cell inflammatory response in the lungs. No specific COVID-19 features were identified. Three deaths were not related to COVID-19. All personnel involved in MITS repeatedly tested negative for COVID-19. SARS-CoV-2 was identified by RT-PCR and immunohistochemistry in the MITS samples, particularly in the lungs. Conclusions MITS is useful for evaluating COVID-19–related deaths in settings where a CA is not feasible. The results of this simplified and safer technique are comparable to those of CA. [ABSTRACT FROM AUTHOR]

Background Minimally invasive tissue sampling (MITS) is an alternative to complete autopsy for determining causes of death. Multiplex molecular testing performed on MITS specimens poses challenges of interpretation, due to high sensitivity and indiscriminate detection of pathogenic, commensal, or contaminating microorganisms. Methods MITS was performed on 20 deceased children with respiratory illness, at 10 timepoints up to 88 hours postmortem. Samples were evaluated by multiplex molecular testing on fresh tissues by TaqMan® Array Card (TAC) and by histopathology, special stains, immunohistochemistry (IHC), and molecular testing (PCR) on formalin-fixed, paraffin-embedded (FFPE) tissues. Results were correlated to determine overall pathologic and etiologic diagnoses and to guide interpretation of TAC results. Results MITS specimens collected up to 3 days postmortem were adequate for histopathologic evaluation and testing. Seven different etiologic agents were detected by TAC in 10 cases. Three cases had etiologic agents detected by FFPE or other methods and not TAC; 2 were agents not present on TAC, and 2 were streptococci that may have been species other than those present on TAC. Result agreement was 43% for TAC and IHC or PCR, and 69% for IHC and PCR. Extraneous TAC results were common, especially when aspiration was present. Conclusions TAC can be performed on MITS up to 3 days after death with refrigeration and provides a sensitive method for detection of pathogens but requires careful interpretation in the context of clinicoepidemiologic and histopathologic findings. Interpretation of all diagnostic tests in aggregate to establish overall case diagnoses maximizes the utility of TAC in MITS. [ABSTRACT FROM AUTHOR]

Background Minimally 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. Methods This 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. Results Results 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. Conclusions Lessons 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. [ABSTRACT FROM AUTHOR]

Background Infectious 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. Methods We 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. Results After 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. Conclusions MITS 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. [ABSTRACT FROM AUTHOR]

Abstract Background Around 5.4 million under-five deaths occur globally annually. Over 2.5 million neonatal deaths and an equivalent stillbirths also occur annually worldwide. India is largest contributor to these under-five deaths and stillbirths. To meet the National Health Policy goals aligned with sustainable development targets, adoption of specific strategy and interventions based on exact causes of death and stillbirths are essential. The current cause of death (CoD) labelling process is verbal autopsy based and subject to related limitations. In view of rare diagnostic autopsies, the minimally invasive tissue sampling (MITS) has emerged as a suitable alternate with comparable efficiency to determine CoD. But there is no experience on perception and acceptance for MITS in north Indian context. This formative research is exploring the perceptions and view of families, communities and healthcare providers regarding MITS to determine the acceptability and feasibility. Methods The cross-sectional study adopts exploratory qualitative research design. The study will be conducted in New Delhi linked to deaths and stillbirths occurring at a tertiary care hospital. The data from multiple stakeholders will be collected through 53–60 key-informant in-depth interviews (IDIs), 8 focus group discussions (FGDs) and 8–10 death or stillbirth event observations. The IDIs will be done with the parents, family members, community representatives, religious priests, burial site representatives and different health care providers. The FGDs will be conducted with the fathers, mothers, and elderly family members in the community. The data collection will focus on death, post-death rituals, religious practices, willingness to know CoD, acceptability of MITS and decision making dynamics. Data will be analysed following free listing, open coding, selective coding and theme identification. Subsequently 8–10 parents will be approached for consent to conduct MITS using the communication package to be developed using the findings. Discussion The study will provide in-depth understanding of the cultural, social, religious practices related to child death and stillbirth and factors that potentially determine acceptance of MITS. The findings will guide development of communication and counselling package and strategies for obtaining consent for MITS. The pilot experience on obtaining consent for MITS will inform suitable refinement and future practice.

Postmortem studies are crucial for providing insight into emergent diseases. However, a complete autopsy is frequently not feasible in highly transmissible diseases due to biohazard challenges. Minimally invasive autopsy (MIA) is a needle-based approach aimed at collecting samples of key organs without opening the body, which may be a valid alternative in these cases. We aimed to: (a) provide biosafety guidelines for conducting MIAs in COVID-19 cases, (b) compare the performance of MIA versus complete autopsy, and (c) evaluate the safety of the procedure. Between October and December 2020, MIAs were conducted in six deceased patients with PCR-confirmed COVID-19, in a basic autopsy room, with reinforced personal protective equipment. Samples from the lungs and key organs were successfully obtained in all cases. A complete autopsy was performed on the same body immediately after the MIA. The diagnoses of the MIA matched those of the complete autopsy. In four patients, COVID-19 was the main cause of death, being responsible for the different stages of diffuse alveolar damage. No COVID-19 infection was detected in the personnel performing the MIAs or complete autopsies. In conclusion, MIA might be a feasible, adequate and safe alternative for cause of death investigation in COVID-19 cases.

Background Current estimates for causes of childhood deaths are mainly premised on modeling of vital registration and limited verbal autopsy data and generally only characterize the underlying cause of death (CoD). We investigated the potential of minimally invasive tissue sampling (MITS) for ascertaining the underlying and immediate CoD in children 1 month to 14 years of age. Methods MITS included postmortem tissue biopsies of brain, liver, and lung for histopathology examination; microbial culture of blood, cerebrospinal fluid (CSF), liver, and lung samples; and molecular microbial testing on blood, CSF, lung, and rectal swabs. Each case was individually adjudicated for underlying, antecedent, and immediate CoD by an international multidisciplinary team of medical experts and coded using the International Classification of Diseases , Tenth Revision (ICD-10). Results An underlying CoD was determined for 99% of 127 cases, leading causes being congenital malformations (18.9%), complications of prematurity (14.2%), human immunodeficiency virus/AIDS (12.6%), diarrheal disease (8.7%), acute respiratory infections (7.9%), injuries (7.9%), and malignancies (7.1%). The main immediate CoD was pneumonia, sepsis, and diarrhea in 33.9%, 19.7%, and 10.2% of cases, respectively. Infection-related deaths were either an underlying or immediate CoD in 78.0% of cases. Community-acquired pneumonia deaths (n = 32) were attributed to respiratory syncytial virus (21.9%), Pneumocystis jirovecii (18.8%), cytomegalovirus (15.6%), Klebsiella pneumoniae (15.6%), and Streptococcus pneumoniae (12.5%). Seventy-one percent of 24 sepsis deaths were hospital-acquired, mainly due to Acinetobacter baumannii (47.1%) and K. pneumoniae (35.3%). Sixty-two percent of cases were malnourished. Conclusions MITS, coupled with antemortem clinical information, provides detailed insight into causes of childhood deaths that could be informative for prioritization of strategies aimed at reducing under-5 mortality. [ABSTRACT FROM AUTHOR]

Background: Around 5.4 million under-five deaths occur globally annually. Over 2.5 million neonatal deaths and an equivalent stillbirths also occur annually worldwide. India is largest contributor to these under-five deaths and stillbirths. To meet the National Health Policy goals aligned with sustainable development targets, adoption of specific strategy and interventions based on exact causes of death and stillbirths are essential. The current cause of death (CoD) labelling process is verbal autopsy based and subject to related limitations. In view of rare diagnostic autopsies, the minimally invasive tissue sampling (MITS) has emerged as a suitable alternate with comparable efficiency to determine CoD. But there is no experience on perception and acceptance for MITS in north Indian context. This formative research is exploring the perceptions and view of families, communities and healthcare providers regarding MITS to determine the acceptability and feasibility. Methods: The cross-sectional study adopts exploratory qualitative research design. The study will be conducted in New Delhi linked to deaths and stillbirths occurring at a tertiary care hospital. The data from multiple stakeholders will be collected through 53–60 key-informant in-depth interviews (IDIs), 8 focus group discussions (FGDs) and 8–10 death or stillbirth event observations. The IDIs will be done with the parents, family members, community representatives, religious priests, burial site representatives and different health care providers. The FGDs will be conducted with the fathers, mothers, and elderly family members in the community. The data collection will focus on death, post-death rituals, religious practices, willingness to know CoD, acceptability of MITS and decision making dynamics. Data will be analysed following free listing, open coding, selective coding and theme identification. Subsequently 8–10 parents will be approached for consent to conduct MITS using the communication package to be developed using the findings. Discussion: The study will provide in-depth understanding of the cultural, social, religious practices related to child death and stillbirth and factors that potentially determine acceptance of MITS. The findings will guide development of communication and counselling package and strategies for obtaining consent for MITS. The pilot experience on obtaining consent for MITS will inform suitable refinement and future practice. [ABSTRACT FROM AUTHOR]

In this feasibility study, we carried out in an interdisciplinary team standardised, ultrasound-guided, minimally invasive autopsy (US-MIA) directly at the bedside of patients who died of COVID-19 in the intensive care unit of the Rechts der Isar Hospital of the Technical University Munich (TUM). The aim of the study was to verify the feasibility, time efficiency and infection hygiene aspects of the process, as well as the quality of the tissue samples. Our results show that bedside US-MIA is suitable for obtaining tissue samples before the onset of postmortem autolysis, and that it can also be carried out quickly and safely. The potential of US-MIA, which has gained little recognition so far, deserves special attention in the context of postmortem diagnosis, research and quality assurance. In the future, these strengths of US-MIA could help to lead postmortem diagnosis into the modern age of pathological deep analytics ("omics")., (© 2023. The Author(s).)

One of the most common indications for endoscopic ultrasound (EUS)-guided tissue sampling is to diagnose the etiology of suspicious lymphadenopathy. Although most cases of lymphadenopathy are benign and self-limiting, patients with deep-seated lymph nodes living in tuberculosis endemic areas or with suspected malignancy require tissue diagnosis to guide treatment. Fine-needle aspirate and fine-needle biopsy systems have excellent reliability for evaluating both benign and malignant lymph node diseases. The advent of new technologies and addition of ancillary molecular diagnostics have improved the diagnostic potential obtained by fine-needle sampling. In turn, the clinical applications of EUS tissue sampling have evolved and further expanded to include granulomatous diseases and lymphoma. Optimizing tissue acquisition to obtain high-quality specimens is of utmost importance and may be achieved with operative strategies unique to lymph node sampling. This chapter discusses the powerful clinical impact of EUS-guided lymph node sampling and technical considerations of optimizing diagnostic yield. [ABSTRACT FROM AUTHOR]

Stillbirth, one of the most common adverse pregnancy outcomes, is especially prevalent in low and middle-income countries (LMICs). Understanding the causes of stillbirth is crucial to developing effective interventions. In this commentary, investigators working across several LMICs discuss the most useful investigations to determine causes of stillbirths in LMICs. Useful data were defined as 1) feasible to obtain accurately and 2) informative to determine or help eliminate a cause of death. Recently, new tools for LMIC settings to determine cause of death in stillbirths, including minimally invasive tissue sampling (MITS) - a method using needle biopsies to obtain internal organ tissue from deceased fetuses for histology and pathogen identification in those tissues have become available. While placental histology has been available for some time, the development of the Amsterdam Criteria in 2016 has provided a useful framework to categorize placental lesions. The authors recommend focusing on the clinical history, the placental evaluation, the external examination of the fetus, and, when available, fetal tissue obtained by MITS, especially of the lung (focused on histology and microbiology) and brain/cerebral spinal fluid (CSF) and fetal blood (focused on microbiological analysis). The authors recognize that this approach may not identify some causes of stillbirth, including some genetic abnormalities and internal organ anomalies, but believe it will identify the most common causes of stillbirth, and most of the preventable causes., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 Goldenberg RL et al.)

Current understanding of the causes of under-5 childhood deaths in low- and middle-income countries relies heavily on country-level vital registration data and verbal autopsies. Reliable data on specific causes of deaths are crucial to target interventions more effectively and achieve rapid reductions in under-5 mortality. The Child Health and Mortality Prevention Surveillance (CHAMPS) network aims to systematically describe causes of child death and stillbirth in low- and middle-income countries using minimally invasive tissue sampling. The articles in this supplement introduce the set of foundational epidemiologic, demographic surveillance, social behavioral science, and laboratory methods. Undergirding the CHAMPS surveillance system designed to determine causes of child mortality. [ABSTRACT FROM AUTHOR]