Minimally Invasive Tissue Sampling Research Articles

Experience on postmortem minimally invasive tissue sampling to ascertain the cause of death determination in South African children: A case for implementing as standard of care

Determining the death burden for prioritising public health interventions necessitates detailed data on the causal pathways to death. Postmortem minimally invasive tissue sampling (MITS), incorporating histology, molecular and microbial culture diagnostics, enhances cause-of-death attribution, particularly for infectious deaths. MITS proves a valid alternative to full diagnostic autopsies, especially in low- and middle-income countries. In Soweto, South Africa (SA), the Child Health and Mortality Prevention Surveillance (CHAMPS) programme has delineated over 1 000 child and stillbirth deaths since 2017. This SA CHAMPS site supports advocating for the use of postmortem MITS as routine practice, for more granular insights into under-5 mortality causes. This knowledge is crucial for SA’s pursuit of Sustainable Development Goal 3.2, targeting reduced neonatal and under-5 mortality rates. This commentary explores the public health advantages and ethicolegal considerations surrounding implementing MITS as standard of care for stillbirths, neonatal and paediatric deaths in SA. Furthermore, based on the data from CHAMPS, we present three pragmatic algorithmic approaches to the wide array of testing options for cost-effectiveness and scalability of postmortem MITS in South African state facilities.

Post-mortem investigation of deaths due to pneumonia in children aged 1–59 months in sub-Saharan Africa and South Asia from 2016 to 2022: an observational study

The Child Health and Mortality Prevention Surveillance (CHAMPS) Network programme undertakes post-mortem minimally invasive tissue sampling (MITS), together with collection of ante-mortem clinical information, to investigate causes of childhood deaths across multiple countries. We aimed to evaluate the overall contribution of pneumonia in the causal pathway to death and the causative pathogens of fatal pneumonia in children aged 1-59 months enrolled in the CHAMPS Network. In this observational study we analysed deaths occurring between Dec 16, 2016, and Dec 31, 2022, in the CHAMPS Network across six countries in sub-Saharan Africa (Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa) and one in South Asia (Bangladesh). A standardised approach of MITS was undertaken on decedents within 24-72 h of death. Diagnostic tests included blood culture, multi-organism targeted nucleic acid amplifications tests (NAATs) of blood and lung tissue, and histopathology examination of various organ tissue samples. An interdisciplinary expert panel at each site reviewed case data to attribute the cause of death and pathogenesis thereof on the basis of WHO-recommended reporting standards. Pneumonia was attributed in the causal pathway of death in 455 (40·6%) of 1120 decedents, with a median age at death of 9 (IQR 4-19) months. Causative pathogens were identified in 377 (82·9%) of 455 pneumonia deaths, and multiple pathogens were implicated in 218 (57·8%) of 377 deaths. 306 (67·3%) of 455 deaths occurred in the community or within 72 h of hospital admission (presumed to be community-acquired pneumonia), with the leading bacterial pathogens being Streptococcus pneumoniae (108 [35·3%]), Klebsiella pneumoniae (78 [25·5%]), and non-typeable Haemophilus influenzae (37 [12·1%]). 149 (32·7%) deaths occurred 72 h or more after hospital admission (presumed to be hospital-acquired pneumonia), with the most common pathogens being K pneumoniae (64 [43·0%]), Acinetobacter baumannii (19 [12·8%]), S pneumoniae (15 [10·1%]), and Pseudomonas aeruginosa (15 [10·1%]). Overall, viruses were implicated in 145 (31·9%) of 455 pneumonia-related deaths, including 54 (11·9%) of 455 attributed to cytomegalovirus and 29 (6·4%) of 455 attributed to respiratory syncytial virus. Pneumonia contributed to 40·6% of all childhood deaths in this analysis. The use of post-mortem MITS enabled biological ascertainment of the cause of death in the majority (82·9%) of childhood deaths attributed to pneumonia, with more than one pathogen being commonly implicated in the same case. The prominent role of K pneumoniae, non-typable H influenzae, and S pneumoniae highlight the need to review empirical management guidelines for management of very severe pneumonia in low-income and middle-income settings, and the need for research into new or improved vaccines against these pathogens. Bill & Melinda Gates Foundation.

Postmortem minimally invasive tissue sampling in communities: exploring perceptions of families, funeral workers, religious and community leaders and healthcare providers from Pakistan

BackgroundMinimally 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.MethodsA 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.ResultsIn 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.ConclusionThis 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.

A prospective observational study of nurses performing minimally invasive tissue sampling of brain, liver, and lung tissues among deceased neonates and stillbirths in Ethiopia.

With a neonatal mortality rate of 33 per 1,000 live births in 2019, Ethiopia is striving to attain the Sustainable Development Goal target of 12 deaths per 1,000 live births by 2030. A better understanding of the major causes of neonatal mortality is needed to effectively design and implement interventions to achieve this goal. Minimally Invasive Tissue Sampling (MITS), an alternative to conventional autopsy, requires fewer resources and through task-shifting of sample collection from pathologists to nurses, has the potential to support the expansion of pathology-based post-mortem examination and improve mortality data. This paper evaluates the accuracy and adequacy of MITS performed by nurses at a tertiary and general hospital and in the home of the deceased. Nurses in a tertiary and general hospital in Ethiopia were trained in MITS sample collection on neonatal deaths and stillbirths using standardized protocols. MITS sample collection was performed by both pathologists and nurses in the tertiary hospital and by nurses in the general hospital and home-setting. Agreement in the performance of MITS between pathologists and nurses was calculated for samples collected at the tertiary hospital. Samples collected by nurses in the general hospital and home-setting were evaluated for technical adequacy using preestablished criteria. One hundred thirty-nine MITS were done: 125 in hospitals and 14 inside homes. There was a perfect or almost perfect agreement between the pathologists and the nurses in the tertiary hospital using Gwet's agreement interpretation criteria. The adequacy of MITS samples collected by nurses in the general hospital was more than 72% when compared to the preset criteria. The adequacy of the MITS sampling yield ranged from 87% to 91% on liveborn neonatal deaths and 76% for the liver, right and left lungs and 55% for brain tissues in stillbirths. This study demonstrated that task-shifting MITS sample collection to nurses can be achieved with comparable accuracy and adequacy as pathologists. Our study showed that with standardized training and supportive supervision MITS sample collection can be conducted by nurses in a tertiary, general hospital and, at the home of the deceased. Future studies should validate and expand on this work by evaluating task-shifting of MITS sample collection to nurses within community settings and with larger sample sizes.

Community perceptions of postmortem examination and minimally invasive tissue sampling in neonates:a qualitative study in South India

BackgroundPostmortem examination is the gold standard for establishing the cause of death. Minimally Invasive Tissue Sampling (MITS) of organs is a novel approach that can be used as an alternative to postmortem examination. In this study, the community perceptions in two states in South India towards neonatal postmortem and the acceptance towards the MITS technique is studied.MethodsIn-depth interviews were conducted among the participants from Kerala and Karnataka to understand the perception towards postmortem and the acceptance of the novel MITS technique. The interviews were audio recorded, and a thematic analysis was done to identify the overarching themes and codes.ResultsThe knowledge and attitude of participants on conventional and MITS postmortem techniques, reasons for refusal, and the need for raising awareness were identified in the study. Participants favored the MITS techniques as it was less disfiguring and less time-consuming. The major concerns for refusal of conventional postmortem were that the procedure was disfiguring, time-consuming, and caused emotional stress to the parents.ConclusionsParticipants favored the MITS approach over conventional postmortem as it caused less disfigurement and was conducive to the religious practice of burial of the body.

Concordance between MITS and conventional autopsies for pathological and virological diagnoses

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.

Acceptability of minimally invasive autopsy by community members and healthcare workers in Siaya and Kisumu counties, western Kenya, 2017-2018.

Worldwide, nearly six million children under the age of five (<5s) die annually, a substantial proportion of which are due to preventable and treatable diseases. Efforts to reduce child mortality indicators in the most affected regions are often undermined by a lack of accurate cause of death data. To generate timely and more accurate causes of death data for <5s, the Child Health and Mortality Prevention Surveillance (CHAMPS) Network established mortality surveillance in multiple countries using Minimally Invasive Tissue Sampling (MITS) in <5 deaths. Here we present acceptability of MITS by community members and healthcare workers in Siaya and Kisumu counties, western Kenya. From April 2017 to February 2018, we conducted 40 in-depth interviews and five focus group discussions with healthcare workers and community members, before and during CHAMPS implementation. Participants were purposively selected. Field observations to understand traditional death-related practices were also performed. Interviews were transcribed into Nvivo 11.0 for data organization and management. Analysis was guided by the grounded theory approach. Facilitators of acceptability were desire to understand why death occurred, timely performance of MITS procedures, potential for MITS results in improving clinical practice and specific assistance provided to families by the CHAMPS program. However, cultural and religious beliefs highlighted important challenges to acceptability, including CHAMPS teams recruiting after a child's death, rumours and myths, unmet expectations from families, and fear by healthcare workers that some families could use MITS results to sue for negligence. Increasing MITS uptake requires sustained strategies to strengthen the identified facilitators of acceptability and simultaneously address the barriers. MITS acceptance will contribute to better characterization of causes of death and support the development of improved interventions aimed at reducing <5 mortality.

The PURPOSe cause of death study in stillbirths and neonatal deaths in India and Pakistan: A review.

The PURPOSe study was a prospective, observational study conducted in India and Pakistan to determine the cause of death for stillbirths and preterm neonatal deaths, using clinical data together with minimally invasive tissue sampling (MITS) and the histologic and polymerase chain reaction (PCR) evaluation of fetal/neonatal tissues and the placenta. After evaluating all available data, an independent panel chose a maternal, a placental and a fetal/neonatal cause of death. Here, we summarise the major results. Among the most important findings were that most stillbirths were caused by fetal asphyxia, often preceded by placental malperfusion, and clinically associated with pre-eclampsia, placental abruption and a small-for-gestational-age fetus. The preterm neonatal deaths were primarily caused by birth asphyxia, followed by various infections. An important finding was that many of the preterm neonatal deaths were caused by a nosocomial infection acquired after neonatal intensive care (NICU) admission; the most common organisms were Acinetobacter baumannii, followed by Klebsiella pneumoniae, Escherichia coli/Shigella and Haemophilus influenzae. Group B streptococcus was less commonly present in the placentas or internal organs of the neonatal deaths.

Causes of Death Among Infants and Children in the Child Health and Mortality Prevention Surveillance (CHAMPS) Network.

The number of deaths of children younger than 5 years has been steadily decreasing worldwide, from more than 17 million annual deaths in the 1970s to an estimated 5.3 million in 2019 (with 2.8 million deaths occurring in those aged 1-59 months [53% of all deaths in children aged <5 years]). More detailed characterization of childhood deaths could inform interventions to improve child survival. To describe causes of postneonatal child deaths across 7 mortality surveillance sentinel sites in Africa and Asia. The Child Health and Mortality Prevention Surveillance (CHAMPS) Network conducts childhood mortality surveillance in sub-Saharan Africa and South Asia using innovative postmortem minimally invasive tissue sampling (MITS). In this cross-sectional study, MITS was conducted in deceased children aged 1 to 59 months at 7 sites in sub-Saharan Africa and South Asia from December 3, 2016, to December 3, 2020. Data analysis was conducted between October and November 2021. The expert panel attributed underlying, intermediate, and immediate conditions in the chain of events leading to death, based on histopathologic analysis, microbiological diagnostics, clinical data, and verbal autopsies. In this study, MITS was performed in 632 deceased children (mean [SD] age at death, 1.3 [0.3] years; 342 [54.1%] male). The 6 most common underlying causes of death were malnutrition (104 [16.5%]), HIV (75 [11.9%]), malaria (71 [11.2%]), congenital birth defects (64 [10.1%]), lower respiratory tract infections (LRTIs; 53 [8.4%]), and diarrheal diseases (46 [7.2%]). When considering immediate causes only, sepsis (191 [36.7%]) and LRTI (129 [24.8%]) were the 2 dominant causes. An infection was present in the causal chain in 549 of 632 deaths (86.9%); pathogens most frequently contributing to infectious deaths included Klebsiella pneumoniae (155 of 549 infectious deaths [28.2%]; 127 [81.9%] considered nosocomial), Plasmodium falciparum (122 of 549 [22.2%]), and Streptococcus pneumoniae (109 of 549 [19.9%]). Other organisms, such as cytomegalovirus (57 [10.4%]) and Acinetobacter baumannii (39 [7.1%]; 35 of 39 [89.7%] considered nosocomial), also played important roles. For the top underlying causes of death, the median number of conditions in the chain of events leading to death was 3 for malnutrition, 3 for HIV, 1 for malaria, 3 for congenital birth defects, and 1 for LRTI. Expert panels considered 494 of 632 deaths (78.2%) preventable and 26 of 632 deaths (4.1%) preventable under certain conditions. In this cross-sectional study investigating causes of child mortality in the CHAMPS Network, results indicate that, in these high-mortality settings, infectious diseases continue to cause most deaths in infants and children, often in conjunction with malnutrition. These results also highlight opportunities for action to prevent deaths and reveal common interaction of various causes in the path toward death.

Data usefulness in determining cause of stillbirth in South Asia.

To evaluate the usefulness of data to determine cause of stillbirth in India and Pakistan. Prospective, observational study. Study hospitals in India and Pakistan. 200 fetal deaths with placental evaluation and minimally invasive tissue sampling (MITS) of internal organs and polymerase chain reaction (PCR) test for 75 pathogens. Data defined as useful to determine stillbirth causes. Placental pathology was the most useful to determine cause of stillbirth. Comparing placental and fetal weight with standard weights was useful in 44.5% and 48.5%, respectively. Lung histology was useful in 42.5%. Most of the other findings of internal organ histology were only occasionally useful. Signs of abruption, by maternal history or placental evaluation, were always deemed useful. Placenta, brain and cord blood PCR were also useful, but less often than histology. Based on this analysis, maternal clinical history, placental histology and fetal examination were most informative. Comparing the placental and fetal weights with recognised standards was useful in nearly half the cases. Fetal tissue histology and PCR were also informative. Of all the potential tests of MITS-obtained specimens, we would first recommend histological evaluation of the lungs, and using a multiplex PCR platform would determine pathogens in blood and brain/CSF. We recognise that this approach will not identify some causes, including some genetic and internal organ anomalies, but will confirm most common causes of stillbirth and most of the preventable causes of stillbirth in low- and middle-income countries.

Stillbirths and Neonatal Deaths Caused by Group B Streptococcus in Africa and South Asia Identified Through Child Health and Mortality Prevention Surveillance (CHAMPS).

Invasive Group B Streptococcus (GBS) is a common cause of early-onset neonatal sepsis and is also associated with stillbirth. This study aimed to determine the proportion of stillborn infants and infants who died between 0 and 90 days attributable to GBS using postmortem minimally invasive tissue sampling (MITS) in 7 low- and middle-income countries (LMICs) participating in Child Health and Mortality Prevention Surveillance (CHAMPS). Deaths that occurred between December 2016 and December 2021 were investigated with MITS, including culture for bacteria of blood and cerebrospinal fluid (CSF), multipathogen polymerase chain reaction on blood, CSF, and lung tissue and histopathology of lung, liver, and brain. Data collection included clinical record review and verbal autopsy. Expert panels reviewed all information and assigned causes of death. We evaluated 2966 deaths, including stillborn infants (n = 1322), infants who died during first day of life (0 to <24 hours, n = 597), early neonatal deaths (END) (1 day to <7 days; END; n = 593), and deaths from 7 to 90 days (n = 454). Group B Streptococcus was determined to be in the causal pathway of death for 2.7% of infants (79 of 2, 966; range, 0.3% in Sierra Leone to 7.2% in South Africa), including 2.3% (31 of 1322) of stillbirths, 4.7% (28 of 597) 0 to <24 hours, 1.9% (11 of 593) END, and 2.0% (9 of 454) of deaths from 7 to 90 days of age. Among deaths attributed to GBS with birth weight data available, 61.9% (39 of 63) of decedents weighed <2500 grams at birth. Group B Streptococcus sepsis was the postmortem diagnosis for 100% (31 of 31) of stillbirths. For deaths <90 days, postmortem diagnoses included GBS sepsis (83.3%, 40 of 48), GBS meningitis (4.2%, 2 of 48), and GBS pneumonia (2.1%, 1 of 48). Our study reveals significant heterogeneity in the contribution of invasive GBS disease to infant mortality across different countries, emphasizing the need for tailored prevention strategies. Moreover, our findings highlight the substantial impact of GBS on stillbirths, shedding light on a previously underestimated aspect in LMICs.

An approach to determining the most common causes of stillbirth in low and middle-income countries: A commentary.

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.

Experiences of parents and caretakers going through the consent process to perform minimally invasive tissue sampling (MITS) on their deceased children in Quelimane, Mozambique: A qualitative study.

In Mozambique, the Countrywide Mortality Surveillance for Action (COMSA) Program implemented a child mortality surveillance to strengthen vital events registration (pregnancies, births, and deaths) and investigate causes of death using verbal autopsies. In Quelimane district, in addition to the abovementioned cause of death determination approaches, minimally invasive tissue sampling (MITS) was performed on deceased children <5years of age. This study focused on understanding deceased children parents' and caretakers' experiences of the consent process to perform MITS in order to contribute to the improvement of approaches to cause of death investigation and inform efforts to maximize acceptability of mortality surveillance activities. A qualitative study was conducted in six urban and semi-urban communities in Quelimane district. A total of 40 semi-structured interviews with family members of deceased children and 50 non-participant observations of the consent process were conducted to explore their experience with informed consent request to perform MITS on their child. Data analysis of the interviews and observations was thematic, being initially deductive (predetermined codes) followed by the generation of new codes according to the data (inductive).The Consolidated criteria for reporting qualitative research (COREQ) guidelines for reporting qualitative studies were performed. Although most participants consented to the performance of MITS on their deceased child, some stated they had not fully understood the MITS procedure despite the informed consent process due to unclear information and their state of mind after their loss. Consenting to MITS and doing so with family members disagreeing were also identified as stress-enhancing factors. Participants also described dissatisfaction of family members, resulting from the condition of the body delivered after tissue collection. In addition, the waiting time to receive the body and resulting delays for the funeral were considered additional factors that may increase stress and compromise the acceptability of MITS. Family experiences were influenced by operational and logistical issues linked to the procedure itself and by it being in tension with social and cultural issues, which caused stress and discontentment on parents and caretakers of deceased children. The main factors that contributed to the experience of going through the MITS process were the state of mind after the death, complex decision making processes within the family, washing of the body for purification after MITS and seepage, and limited understanding of consent for MITS. When requesting consent for MITS, emphasis should be placed on transmitting clear and understandable information about MITS procedures to participants.

Neural tube defects as a cause of death among stillbirths, infants, and children younger than 5 years in sub-Saharan Africa and southeast Asia: an analysis of the CHAMPS network

Neural tube defects are common birth defects resulting in severe morbidity and mortality; they can largely be prevented with periconceptional maternal intake of folic acid. Understanding the occurrence of neural tube defects and their contribution to mortality in settings where their burden is highest could inform prevention and health-care policy. We aimed to estimate the mortality attributed to neural tube defects in seven countries in sub-Saharan Africa and southeast Asia. This analysis used data from the Child Health and Mortality Prevention Surveillance (CHAMPS) network and health and demographic surveillance systems from South Africa, Mozambique, Bangladesh, Kenya, Mali, Ethiopia, and Sierra Leone. All stillbirths and infants and children younger than 5 years who died, who were enrolled in CHAMPS, whose families consented to post-mortem minimally invasive tissue sampling (MITS) between Jan 1, 2017, and Dec 31, 2021, and who were assigned a cause of death by a determination of cause of death panel as of May 24, 2022, were included in this analysis, regardless the cause of death. MITS and advanced diagnostic methods were used to describe the frequency and characteristics of neural tube defects among eligible deaths, identify risk factors, and estimate the mortality fraction and mortality rate (per 10 000 births) by CHAMPS site. Causes of death were determined for 3232 stillbirths, infants, and children younger than 5 years, of whom 69 (2%) died with a neural tube defect. Most deaths with a neural tube defect were stillbirths (51 [74%]); 46 (67%) were neural tube defects incompatible with life (ie, anencephaly, craniorachischisis, or iniencephaly) and 22 (32%) were spina bifida. Deaths with a neural tube defect were more common in Ethiopia (adjusted odds ratio 8·09 [95% CI 2·84-23·02]), among female individuals (4·40 [2·44-7·93]), and among those whose mothers had no antenatal care (2·48 [1·12-5·51]). Ethiopia had the highest adjusted mortality fraction of deaths with neural tube defects (7·5% [6·7-8·4]) and the highest adjusted mortality rate attributed to neural tube defects (104·0 per 10 000 births [92·9-116·4]), 4-23 times greater than in any other site. CHAMPS identified neural tube defects, a largely preventable condition, as a common cause of death among stillbirths and neonatal deaths, especially in Ethiopia. Implementing interventions such as mandatory folic acid fortification could reduce mortality due to neural tube defects. Bill & Melinda Gates Foundation.

A Qualitative Assessment of Community Acceptability and Its Determinants in the Implementation of Minimally Invasive Tissue Sampling in Children in Quelimane City, Mozambique.

The Countrywide Mortality Surveillance for Action project aims to implement a child mortality surveillance program through strengthening vital registration event reporting (pregnancy, birth, and death) and investigating causes of death (CODs) based on verbal autopsies. In Quelimane (central Mozambique), Minimally Invasive Tissue Sampling (MITS) procedures were added to fine-tune the COD approaches. Before the implementation of MITS, an evaluation of the acceptability and ethical considerations of child mortality surveillance was considered fundamental. A socio-anthropological study was conducted in Quelimane, using observations, informal conversations, semi-structured interviews, and focus group discussions with healthcare providers, nharrubes (traditional authorities who handle bodies before the funeral), community and religious leaders, and traditional birth attendants to understand the locally relevant potential facilitators and barriers to the acceptability of MITS. Audio materials were transcribed, systematically coded, and analyzed using NVIVO12®. The desire to know the COD, intention to discharge the elders from accusations of witchcraft, involvement of leaders in disseminating project information, and provision of transport for bodies back to the community constitute potential facilitators for the acceptability of MITS implementation. In contrast, poor community mobilization, disagreement with Islamic religious practices, and local traditional beliefs were identified as potential barriers. MITS was considered a positive innovation to determine the COD, although community members remain skeptical about the procedure due to tensions with religion and tradition. Therefore, the implementation of MITS in Quelimane should prioritize the involvement of a variety of influential community and religious leaders.

Multi-Cause Calibration of Verbal Autopsy-Based Cause-Specific Mortality Estimates of Children and Neonates in Mozambique.

The Countrywide Mortality Surveillance for Action platform is collecting verbal autopsy (VA) records from a nationally representative sample in Mozambique. These records are used to estimate the national and subnational cause-specific mortality fractions (CSMFs) for children (1-59 months) and neonates (1-28 days). Cross-tabulation of VA-based cause-of-death (COD) determination against that from the minimally invasive tissue sampling (MITS) from the Child Health and Mortality Prevention project revealed important misclassification errors for all the VA algorithms, which if not accounted for will lead to bias in the estimates of CSMF from VA. A recently proposed Bayesian VA-calibration method is used that accounts for this misclassification bias and produces calibrated estimates of CSMF. Both the VA-COD and the MITS-COD can be multi-cause (i.e., suggest more than one probable COD for some of the records). To fully use this probabilistic COD data, we use the multi-cause VA calibration. Two different computer-coded VA algorithms are considered-InSilicoVA and EAVA-and the final CSMF estimates are obtained using an ensemble calibration that uses data from both the algorithms. The calibrated estimates consistently offer a better fit to the data and reveal important changes in the CSMF for both children and neonates in Mozambique after accounting for VA misclassification bias.

Child Health and Mortality Prevention Surveillance (CHAMPS): Manhiça site description, Mozambique

The Manhiça Health Research Centre (Manhiça HDSS) was established in 1996 in Manhiça, a rural district at Maputo Province in the southern part of Mozambique with approximately 49,000 inhabited households, a total population of 209.000 individuals, and an annual estimated birth cohort of about 5000 babies. Since 2016, Manhiça HDSS is implementing the Child Health and Mortality Prevention Surveillance (CHAMPS) program aiming to investigate causes of death (CoD) in stillbirths and children under the age of 5 years using, among other tools, the innovative post-mortem technique known as Minimally Invasive Tissue sampling (MITS). Both in-hospital and community pediatric deaths are investigated using MITS. For this, community-wide socio-demographic approaches (notification of community deaths by key informants, formative research involving several segments of the community, availability of free phone lines for notification of medical emergencies and deaths, etc.) are conducted alongside to foster community awareness, involvement and adherence as well as to compute mortality estimates and collect relevant information of health and mortality determinants. The main objective of this paper is to describe the Manhiça Health and Demographic Surveillance System (HDSS) site and the CHAMPS research environment in place including the local capacities among its reference hospital, laboratories, data center and other relevant areas involved in this ambitious surveillance and research project, whose ultimate aim is to improve child survival through public health actions derived from credible estimates and understanding of the major causes of childhood mortality in Mozambique.

Can Nurses Perform Minimally Invasive Tissue Sampling (MITS) Equally Well as Pathologists? An Observational Study to Evaluate Task-Shifting in the Determination of Cause of Death Among Neonates and Stillbirths in Ethiopia

Can Nurses Perform Minimally Invasive Tissue Sampling (MITS) Equally Well as Pathologists? An Observational Study to Evaluate Task-Shifting in the Determination of Cause of Death Among Neonates and Stillbirths in Ethiopia

Prioritizing Health Care Strategies to Reduce Childhood Mortality

Although child mortality trends have decreased worldwide, deaths among children younger than 5 years of age remain high and disproportionately circumscribed to sub-Saharan Africa and Southern Asia. Tailored and innovative approaches are needed to increase access, coverage, and quality of child health care services to reduce mortality, but an understanding of health system deficiencies that may have the greatest impact on mortality among children younger than 5 years is lacking. To investigate which health care and public health improvements could have prevented the most stillbirths and deaths in children younger than 5 years using data from the Child Health and Mortality Prevention Surveillance (CHAMPS) network. This cross-sectional study used longitudinal, population-based, and mortality surveillance data collected by CHAMPS to understand preventable causes of death. Overall, 3390 eligible deaths across all 7 CHAMPS sites (Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa) between December 9, 2016, and December 31, 2021 (1190 stillbirths, 1340 neonatal deaths, 860 infant and child deaths), were included. Deaths were investigated using minimally invasive tissue sampling (MITS), a postmortem approach using biopsy needles for sampling key organs and fluids. For each death, an expert multidisciplinary panel reviewed case data to determine the plausible pathway and causes of death. If the death was deemed preventable, the panel identified which of 10 predetermined health system gaps could have prevented the death. The health system improvements that could have prevented the most deaths were evaluated for each age group: stillbirths, neonatal deaths (aged <28 days), and infant and child deaths (aged 1 month to <5 years). Of 3390 deaths, 1505 (44.4%) were female and 1880 (55.5%) were male; sex was not recorded for 5 deaths. Of all deaths, 3045 (89.8%) occurred in a healthcare facility and 344 (11.9%) in the community. Overall, 2607 (76.9%) were deemed potentially preventable: 883 of 1190 stillbirths (74.2%), 1010 of 1340 neonatal deaths (75.4%), and 714 of 860 infant and child deaths (83.0%). Recommended measures to prevent deaths were improvements in antenatal and obstetric care (recommended for 588 of 1190 stillbirths [49.4%], 496 of 1340 neonatal deaths [37.0%]), clinical management and quality of care (stillbirths, 280 [23.5%]; neonates, 498 [37.2%]; infants and children, 393 of 860 [45.7%]), health-seeking behavior (infants and children, 237 [27.6%]), and health education (infants and children, 262 [30.5%]). In this cross-sectional study, interventions prioritizing antenatal, intrapartum, and postnatal care could have prevented the most deaths among children younger than 5 years because 75% of deaths among children younger than 5 were stillbirths and neonatal deaths. Measures to reduce mortality in this population should prioritize improving existing systems, such as better access to antenatal care, implementation of standardized clinical protocols, and public education campaigns.

Primary motivations for and experiences with paediatric minimally invasive tissue sampling (MITS) participation in Malawi: a qualitative study

ObjectiveTo understand family member consent decision-making influences and experiences in Malawi in order to inform future minimally invasive tissue sampling (MITS) studies.DesignQualitative study.SettingQueen Elizabeth Central Hospital (QECH) in Blantyre, Malawi,...