Minimally invasive postmortem intestinal tissue sampling in malnourished and acutely ill children is feasible and informative

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\u27 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 \u3e90% 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

Minimally invasive postmortem intestinal tissue sampling in malnourished and acutely ill children is feasible and informative

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\u27 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 \u3e90% 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

Data Management in Multicountry Consortium Studies: The Enterics For Global Health (EFGH) Shigella Surveillance Study Example

Background: Rigorous data management systems and planning are essential to successful research projects, especially for large, multicountry consortium studies involving partnerships across multiple institutions. Here we describe the development and implementation of data management systems and procedures for the Enterics For Global Health (EFGH) Shigella surveillance study—a 7-country diarrhea surveillance study that will conduct facility-based surveillance concurrent with population-based enumeration and a health care utilization survey to estimate the incidence of Shigella­-associated diarrhea in children 6 to 35 months old. Methods: The goals of EFGH data management are to utilize the knowledge and experience of consortium members to collect high-quality data and ensure equity in access and decision-making. During the planning phase before study initiation, a working group of representatives from each EFGH country site, the coordination team, and other partners met regularly to develop the data management systems for the study. Results: This resulted in the Data Management Plan, which included selecting REDCap and SurveyCTO as the primary database systems. Consequently, we laid out procedures for data processing and storage, study monitoring and reporting, data quality control and assurance activities, and data access. The data management system and associated real-time visualizations allow for rapid data cleaning activities and progress monitoring and will enable quicker time to analysis. Conclusions: Experiences from this study will contribute toward enriching the sparse landscape of data management methods publications and serve as a case study for future studies seeking to collect and manage data consistently and rigorously while maintaining equitable access to and control of data

Population Enumeration and Household Utilization Survey Methods in the Enterics for Global Health (EFGH): Shigella Surveillance Study

Background: Accurate estimation of diarrhea incidence from facility-based surveillance requires estimating the population at risk and accounting for case patients who do not seek care. The Enterics for Global Health (EFGH) Shigella surveillance study will characterize population denominators and healthcare-seeking behavior proportions to calculate incidence rates of Shigella diarrhea in children aged 6–35 months across 7 sites in Africa, Asia, and Latin America. Methods: The Enterics for Global Health (EFGH) Shigella surveillance study will use a hybrid surveillance design, supplementing facility-based surveillance with population-based surveys to estimate population size and the proportion of children with diarrhea brought for care at EFGH health facilities. Continuous data collection over a 24 month period captures seasonality and ensures representative sampling of the population at risk during the period of facility-based enrollments. Study catchment areas are broken into randomized clusters, each sized to be feasibly enumerated by individual field teams. Conclusions: The methods presented herein aim to minimize the challenges associated with hybrid surveillance, such as poor parity between survey area coverage and facility coverage, population fluctuations, seasonal variability, and adjustments to care-seeking behavior

Postmortem Intestinal Sampling in Malawi

Thesis (Master's)--University of Washington, 2020Background In LMICs, undernutrition is the leading underlying cause of child mortality, which remains unacceptably high. Environmental enteric dysfunction (EED), a prevalent condition in areas with lack of access to hygiene and safe sanitation could be a significant contributor to undernutrition. To better understand the role of EED in child undernutrition and mortality, accurate cause of death ascertainment is crucial. Minimally invasive tissue sampling (MITS) is a validated technique for assigning cause of death, but the current procedure lacks gastrointestinal interrogation. We aimed to assess the utility of postmortem endoscopically obtained intestinal biopsies, as autolysis may preclude its usefulness, and to adapt an EED histopathologic scoring system to assess upper intestinal disease severity and an inflammatory bowel histopathologic disease scoring system to measure lower intestinal disease severity. Methods MITS in Malawi (MiM) recruited children who died during inpatient admission at Queen Elizabeth Central Hospital in Blantyre, Malawi. Eligibility criteria included age (1 week-59 months) and admission diagnosis (acute illness or malnutrition). Upon death, the standard MITS procedure was conducted after upper and lower endoscopies to collect three duodenal and one colonic and one rectal sample, respectively. These were formalin fixed, prepared into paraffin blocks, sectioned, and stained with hematoxylin and eosin (H&E). Two independent pathologists assessed degree of autolysis on each H&E slide and a gastrointestinal pathologist applied the 11-parameter upper and 4-parameter lower intestinal histopathologic scoring system to measure intestinal disease severity. Results Twenty-eight post-mortem endoscopic procedures were completed. We were able to obtain duodenal, colonic, and rectal samples in 25, 6, and 25 cases. Some degree of autolysis was found in nearly all intestinal samples (n=99 (98%)), though complete autolysis was rare (n=11 (11%)). We found increasing tissue autolysis in more distally located intestinal tissues. Tissue autolysis in the rectum was negatively associated with age (PR=0.991; 95%CI: 0.987, 0.995). We found no associations between tissue autolysis and any other variables of interest, including postmortem time interval and body refrigeration time. Chronic inflammation was prevalent in both the upper and lower intestinal tissues (average scores: 1.9 and 2.0, respectively), although acute inflammation was not present in any of the tissues. We also identified a low density of Paneth and goblet cells in the upper intestine (average scores: 2.5 and 2.2 respectively). Conclusions Postmortem endoscopic biopsy is feasible, despite high levels of autolysis. Autolysis was not found to be dependent on body refrigeration or postmortem time interval, but did vary based on intestinal site, possibly related to increasing microbial colonization in more distal segments of the intestinal tract. We identified duodenal chronic inflammation and reduced Paneth and goblet cell densities, which are features of EED. Severe rectal chronic inflammation was also seen, including in children as young as 6 weeks old. These data warrant further investigation and confirmation but point to the utility of including intestinal sampling as part of the MITS procedure

Data management in multicounty consortium studies: The enterics for gobal health (EFGH) Shigella surveillance study example

Background: Rigorous data management systems and planning are essential to successful research projects, especially for large, multicountry consortium studies involving partnerships across multiple institutions. Here we describe the development and implementation of data management systems and procedures for the Enterics For Global Health (EFGH) Shigella surveillance study-a 7-country diarrhea surveillance study that will conduct facility-based surveillance concurrent with population-based enumeration and a health care utilization survey to estimate the incidence of Shigella--associated diarrhea in children 6 to 35 months old.Methods: The goals of EFGH data management are to utilize the knowledge and experience of consortium members to collect high-quality data and ensure equity in access and decision-making. During the planning phase before study initiation, a working group of representatives from each EFGH country site, the coordination team, and other partners met regularly to develop the data management systems for the study.Results: This resulted in the Data Management Plan, which included selecting REDCap and SurveyCTO as the primary database systems. Consequently, we laid out procedures for data processing and storage, study monitoring and reporting, data quality control and assurance activities, and data access. The data management system and associated real-time visualizations allow for rapid data cleaning activities and progress monitoring and will enable quicker time to analysis.Conclusions: Experiences from this study will contribute toward enriching the sparse landscape of data management methods publications and serve as a case study for future studies seeking to collect and manage data consistently and rigorously while maintaining equitable access to and control of data

Intimate partner violence and adherence to PrEP and ART among Ugandan HIV serodifferent couples.

BackgroundIntimate partner violence (IPV) is associated with increased risk of HIV acquisition and reduced engagement in HIV care. There is limited understanding of the ways in which IPV exposure and other maladaptive relationship dynamics may influence adherence to antiretroviral treatment (ART) and pre-exposure prophylaxis (PrEP) for individuals in committed, HIV serodifferent partnerships.MethodsWe used binomial generalized linear mixed effect regression models to evaluate the association between IPV exposure and ART/PrEP adherence among members of serodifferent couples in Uganda. Secondarily, we assessed the association between relationship powerlessness and ART/PrEP adherence.ResultsWe enrolled and followed both partners in 149 heterosexual serodifferent couples. The partner living with HIV was female in 64% of couples. IPV exposure was associated with low ART adherence (15% vs. 5% in quarters with no IPV, odds ratio [OR]: 4.78, 95% confidence interval [CI] 1.48 - 15.42) but not low PrEP adherence (33% vs. 36%, p=0.69). Among HIV-negative individuals, those reporting moderate relationship powerlessness were less likely to have poor PrEP adherence compared to those with low relationship powerlessness (20% vs. 30%, OR: 0.57, 95% CI 0.36 - 0.90). We observed no association between relationship powerlessness and ART adherence.ConclusionsWe found that IPV exposure was associated with low adherence to ART and that relationship powerlessness was associated with good adherence to PrEP. These findings contribute to the evidence base outlining the influence of IPV and relationship power on ART/PrEP adherence for individuals in HIV serodifferent unions

Minimally invasive postmortem intestinal tissue sampling in malnourished and acutely ill children is feasible and informative

No abstract available

Quantifying the Cost of <i>Shigella</i> Diarrhea in the Enterics for Global Health (EFGH) <i>Shigella</i> Surveillance Study.

BackgroundComparative costs of public health interventions provide valuable data for decision making. However, the availability of comprehensive and context-specific costs is often limited. The Enterics for Global Health (EFGH) Shigella surveillance study-a facility-based diarrhea surveillance study across 7 countries-aims to generate evidence on health system and household costs associated with medically attended Shigella diarrhea in children.MethodsEFGH working groups comprising representatives from each country (Bangladesh, Kenya, Malawi, Mali, Pakistan, Peru, and The Gambia) developed the study methods. Over a 24-month surveillance period, facility-based surveys will collect data on resource use for the medical treatment of an estimated 9800 children aged 6-35 months with diarrhea. Through these surveys, we will describe and quantify medical resources used in the treatment of diarrhea (eg, medication, supplies, and provider salaries), nonmedical resources (eg, travel costs to the facility), and the amount of caregiver time lost from work to care for their sick child. To assign costs to each identified resource, we will use a combination of caregiver interviews, national medical price lists, and databases from the World Health Organization and the International Labor Organization. Our primary outcome will be the estimated cost per inpatient and outpatient episode of medically attended Shigella diarrhea treatment across countries, levels of care, and illness severity. We will conduct sensitivity and scenario analysis to determine how unit costs vary across scenarios.ConclusionsResults from this study will contribute to the existing body of literature on diarrhea costing and inform future policy decisions related to investments in preventive strategies for Shigella