Tropical Gastroenterology & Nutrition group

Environmental enteric dysfunction (EED) is an asymptomatic acquired disorder characterized by upper small bowel inflammation, villus blunting, and gut permeability. It is a major contributor to poor growth in childhood as well as other highly consequential outcomes such as delayed neuorcognitive development. After decades of intermittent interest in this entity, we are now seeing a resurgence in the field of EED. However, recent studies have been hampered by a lack of investigation of the target tissue—the upper small bowel. In 2016, the EEDBI (Environmental Enteric Dysfunction Biopsy Initiative) Consortium was established as a common scientific platform across 3 independent EED biopsy cohort studies in Bangladesh, Pakistan, and Zambia. Two centers in the United States recruited comparison groups of children undergoing endoscopy for clinical indications. The EEDBI Consortium goal was to augment the contributions of the individual centers and answer high-level questions amenable to analysis and interpretation across the studies. Here, we describe the Consortium and its cohorts and recruitment procedures across studies. We also offer details applicable to all papers in this supplement, which describe EED mucosal histology, morphometry, immunohistochemistry, and transcriptomics as well as histology relationship to pathogens and biomarkers.

There is a knowledge gap on the epidemiology of inflammatory bowel disease in Africa. To begin to address this issue, we formed a case reporting network of practitioners with an interest in inflammatory bowel disease across sub-Saharan Africa. Here, we report a series of 175 cases from 12 countries over 2 years.

Abstract Background and Aims Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is an idiopathic, chronic, and frequently disabling inflammatory disorder of the intestines characterized by a dysregulated mucosal immune response. The pathophysiology of the disease remains incompletely understood. Genetic factors affecting disease are under investigation, however, genetic studies in non-European populations are scarce and it is an urgent scientific, social, and ethical requirement that research in under-studied populations is prioritized. The objective of this study is to understand the genetics of IBD in sub-Saharan African ancestry populations and to identify genetic factors that affect pathogenesis of IBD in this region. Methodology A case-control study will be conducted from January 2024 to December 2025. Consecutive eligible subjects with IBD and controls will be invited to take part in the study. Data will be collected through chart review, structured interviews, and collection of saliva samples for genotyping using the H3Africa chip in the first instance. Genome-wide imputation and replication analysis will be done. Single-marker association analyses will be performed using the Cochran Armitage trend and logistic regression test after correction for population structure. We will look at known European ancestry and African American (AA) IBD-associated variants as well as variants that are unique to our populations (we will be able to look at local admixture in the AA population to see if these variants are replicated). Anticipated Impact This study will contribute significantly to knowledge of genetic risk factors for IBD in sub-Saharan Africa. It may also help to identify potential complications of treatments such as thiopurines which have been commonly used in European populations but where experience of use in sub-Saharan Africa is lacking.

Children with linear growth faltering refractory to nutritional management show evidence of environmental enteropathy, which may compromise nutrient availability. Protein could be particularly affected, due to the possibility of sub-optimal digestibility and/or increase in requirement for immune response. This increase in protein requirement along with poor intake could potentially lead to increased breakdown of body protein sources and in turn a depleted protein state. The present review focuses on protein status in children at risk of linear growth faltering and environmental enteropathy. One pig study is also presented. There is consistent evidence of low circulating essential and conditionally essential amino acids, in children. One study showed no difference in protein synthesis/breakdown, and fat free mass (FFM) in children at risk of linear growth faltering and environmental enteropathy. Weanling pigs exposed to nutrient deprivation showed a decrease in plasma albumin, with a slower rate of weight and length accretion, and a lower FFM. These findings emphasize the need for improving intake of high-quality protein in children living in regions with a high prevalence of environmental enteropathy, with careful studies of the effect on growth rate and protein status.

Background: Tenofovir regimens remain the preferred formulations in the HIV guidelines for adolescents and young adults in Zambia and globally. However, some adolescents and young adults are maintained on abacavir by clinicians because of anxiety about possible proximal tubular dysfunction from tenofovir. We assessed the effect of two regimens on proximal tubular function in adolescents and young adults living with HIV. Methods: This was a cross-sectional study involving 180 participants with HIV receiving either tenofovir or abacavir for ≥12 months at the largest tertiary teaching hospital. Two first-morning urine and blood specimens were collected and analyzed for proximal tubular markers, glomerular function, electrolytes, and routine monitoring tests. Proximal tubular function was determined by measuring the fractional excretion of phosphate (FePO4). Proximal tubular dysfunction was defined by FePO4 ≥20% regardless of serum phosphate and FePO4 ≥10-20% when serum phosphate was below 0.81mmol/L. Results: The prevalence of proximal tubular dysfunction was 6% and was higher in the tenofovir group than the abacavir (10% vs. 2%, p<0.058). However, after adjusting for potential confounders, tenofovir was not associated with worse proximal tubular function. Age, urine b2-microglobulin: creatinine ratio, C-reactive protein, and urine protein: creatinine ratio was all associated with worsening proximal tubular dysfunction. Reduced estimated glomelurar filtration rate (eGFR) was found in four (2.2%) participants; three of which were on tenofovir. Conclusions: Proximal tubular dysfunction defined by FePO4 was more prevalent in the tenofovir group than the abacavir group, but not after adjusting for age. Our findings should be interpreted with caution as age differences between the two groups confounded the results.

The exact prevalence of gastric cancer in Zambia is unknown. The aim of this study was to determine the proportion of gastric cancer cases seen at the largest hospital in Zambia, whose records were included in the Zambia National Cancer Registry (ZNCR). We reviewed gastric cancer records between January 2015 and December 2017 from the University Teaching Hospital, Cancer Diseases Hospital and ZNCR. Statistical analysis was done using Stata version 15. We reviewed 94 patient records (42 were females) with a mean age of 59 years (standard deviation, 14.9). Histologically, the majority of the cases were adenocarcinoma (84%). Of the reviewed records, only 39/94 (42%) had their data included in the ZNCR. Median time to from endoscopic diagnosis to histopathological confirmation was 11 days (inter-quartile range; 7-20). Median time from histological confirmation to the Cancer Diseases Hospital for therapy was 8 days (IQR 2-19). Overall median survival time for gastric cancer patients was 290 days (CI 95%, 112 - 1225). Data on gastric cancer reported in the ZNCR are an underestimate of the true disease burden and there is need to strengthen data collection strategies for gastric cancer in Zambia.

La guerra en Ucrania provocada por el liderazgo de Vladimir Putin se está perfilando como el evento más tenso no visto desde la Crisis de los Misiles de 1962 en Cuba. Sin embargo, la invasión rusa ha ya trastocado las fronteras terrestres de todos sus vecinos en Eurasia, los países nórdicos, los miembros de la OTAN y de manera ejemplar ha ahogado los esfuerzos de una salida negociada y diplomática hasta el momento de escribir estas líneas en el seno de la Organización de las Naciones Unidas. Asimismo, se están dislocando las cadenas de suministro de energía, gas, petróleo y de seguridad bancaria que están orillando al límite la interdependencia de Europa y Estados Unidos con Rusia y el resto de los mercados energéticos en el mundo; lo cual es en sí, un polvorín.

Environmental enteropathy (EE) is a subclinical condition of the small intestine that is highly prevalent in low- and middle-income countries. It is thought to be a key contributing factor to childhood malnutrition, growth stunting, and diminished oral vaccine responses. Although EE has been shown to be the by-product of a recurrent enteric infection, its full pathophysiology remains unclear. Here, we mapped the cellular and molecular correlates of EE by performing high-throughput, single-cell RNA-sequencing on 33 small intestinal biopsies from 11 adults with EE in Lusaka, Zambia (eight HIV-negative and three HIV-positive), six adults without EE in Boston, United States, and two adults in Durban, South Africa, which we complemented with published data from three additional individuals from the same clinical site. We analyzed previously defined bulk-transcriptomic signatures of reduced villus height and decreased microbial translocation in EE and showed that these signatures may be driven by an increased abundance of surface mucosal cells-a gastric-like subset previously implicated in epithelial repair in the gastrointestinal tract. In addition, we determined cell subsets whose fractional abundances associate with EE severity, small intestinal region, and HIV infection. Furthermore, by comparing duodenal EE samples with those from three control cohorts, we identified dysregulated WNT and MAPK signaling in the EE epithelium and increased proinflammatory cytokine gene expression in a T cell subset highly expressing a transcriptional signature of tissue-resident memory cells in the EE cohort. Together, our work elucidates epithelial and immune correlates of EE and nominates cellular and molecular targets for intervention.

Using survey data obtained through semi-structured questionnaires which were administered using a multi-stage random sampling process, this study sought to undertake an experimental application of the Benefit Incidence Analysis (BIA) socio-economic evaluation tool on 117 rural farming households in Chongwe District of Zambia. The sampled households were receiving agricultural support through the Government-financed Farmer Input Support Programme (FISP). Specifically, this experimental study of the usage of BIA on agriculture-related spending in Zambia was aimed at proving possible replication of the usage of BIA for evaluating socio-economic and distributional impacts of financing for Climate Smart Agricultural (CSA) practices. Results prove that BIA assessment variables such as income/expenditure quintiles, education status, gender and age are also applicable to and essential in evaluating CSA initiatives. Despite this study proving applicability to CSA assessments, undertaking a BIA is highly technical and data intensive. Such an undertaking would heavily rely on the timely availability of complementary economic and financial data and an intermediate to advanced level of technical capacity in order to administer the analysis.