Impact of Rotaviral Diarrhea on Child Growth in Sub-Saharan Africa and South Asia in the Global Enteric Multicenter Study.

Rotavirus is the leading cause of dehydrating diarrhea among children in developing countries. The impact of rotaviral diarrhea on nutritional status is not well understood. We aimed to determine the association between rotavirus-positive moderate-to-severe diarrhea and nutrition in children under 5 years of age. We analyzed data from the Global Enteric Multicenter Study on children 0-59 months old from South Asia and sub-Saharan Africa. The relationships between explanatory variables and outcome variables were assessed using multiple linear regression; the explanatory variable was the presence of rotavirus in the stool sample, and the outcome variables were z scores [length/height-for-age (LAZ/HAZ), weight-for-age (WAZ), and weight-for-length/height (WLZ/WHZ)] at follow-up (∼60 days). The prevalence of rotaviral diarrhea was 17.3% (905/5,219) in South Asia and 19.95% (842/4,220) in sub-Saharan Africa. Rotavirus was associated with higher LAZ/HAZ (ß: 0.19; 95% CI: 0.12, 0.26; P <0.001) and WAZ (ß: 0.15; 95% CI: 0.79, 0.22; P <0.001) in sub-Saharan Africa and with lower WLZ/WHZ (ß coefficient: -0.08; 95% CI: -0.15, -0.009; P = 0.027) in South Asia. Our study indicates that rotaviral diarrhea is positively associated with nutritional status in sub-Saharan Africa and is negatively associated with nutritional status in South Asia. An expedited implementation policy of ongoing preventive and control strategies, including vaccination against rotavirus, is necessary to reduce the burden of rotaviral diarrhea, which may further help to reduce the potential nutritional ramifications.

Symptomatic and Asymptomatic Campylobacter Infections and Child Growth in South Asia: Analyzing Data from the Global Enteric Multicenter Study.

Campylobacter is a major cause of food-borne gastrointestinal illnesses worldwide, predominantly affecting children under 5 years of age. This study examined potential associations of symptomatic (with diarrhea) and asymptomatic (without diarrhea) Campylobacter infections with child growth among children under 5 years of age in South Asia. The Global Enteric Multicenter Study was conducted from 2007 to 2011 with a case-control design. Children were followed for 60 days after enrollment. Stool culture was performed to isolate Campylobacter spp. Among the 22,567 enrolled children, 9,439 were symptomatic, with 786 (8.28%) testing positive for Campylobacter. Conversely, 13,128 asymptomatic healthy controls were included, with 1,057 (8.05%) testing positive for Campylobacter. Growth faltering was observed in the symptomatic group, particularly among children aged 0-11 months (-0.19 height-for-age z score [HAZ]; 95% CI: -0.36, -0.03; P = 0.018) and 24-59 months (-0.16 HAZ; 95% CI: -0.28, -0.04; P = 0.010). However, in the asymptomatic group, growth faltering was observed only in the 24- to 59-month age group, in terms of HAZ (-0.15 HAZ; 95% CI: -0.24, -0.05; P = 0.002) and weight-for-height z score (-0.16; 95% CI: -0.26, -0.06; P = 0.001). These findings underscore the importance of immediate and enhanced introduction of preventive modalities to reduce the burden of Campylobacter infections and reduce their long-term sequelae.

Vibrio cholerae in rural and urban Bangladesh, findings from hospital-based surveillance, 2000-2021.

With more than 100,000 cases estimated each year, Bangladesh is one of the countries with the highest number of people at risk for cholera. Moreover, Bangladesh is formulating a countrywide cholera-control plan to satisfy the GTFCC (The Global Task Force on Cholera Control) Roadmap's goals. With a particular focus on cholera trends, variance in baseline and clinical characteristics of cholera cases, and trends in antibiotic susceptibility among clinical isolates of Vibrio cholerae, we used data from facility-based surveillance systems from icddr,b's Dhaka, and Matlab Hospitals from years 2000 to 2021. Female patients comprised 3,553 (43%) in urban and 1,099 (51.6%) in rural sites. Of the cases and most patients 5,236 (63.7%) in urban and 1,208 (56.7%) in the rural site were aged 15 years and more. More than 50% of the families belonged to the poor and lower-middle-class; in 2009 (24.4%) were in urban and in 1,791 (84.2%) were in rural sites. In the urban site, 2,446 (30%) of households used untreated drinking water, and 702 (9%) of families disposed of waste in their courtyard. In the multiple logistic regression analysis, the risk of cholera has significantly increased due to waste disposal in the courtyard and the boiling of water has a protective effect against cholera. Rotavirus (9.7%) was the most prevalent co-pathogen among the under-5 children in both sites. In urban sites, the percentage of V. cholerae along with co-existing ETEC and Campylobacter is changing in the last 20 years; Campylobacter (8.36%) and Enterotoxigenic Escherichia coli (ETEC) (7.15%) were the second and third most prevalent co-pathogens. Shigella (1.64%) was the second most common co-pathogen in the rural site. Azithromycin susceptibility increased slowly from 265 (8%) in 2006-2010 to 1485 (47.8%) in 2016-2021, and erythromycin susceptibility dropped substantially over 20 years period from 2,155 (98.4%) to 21 (0.9%). Tetracycline susceptibility decreased in the urban site from 2051 (45.9%) to 186 (4.2%) and ciprofloxacin susceptibility decreased from 2,581 (31.6%) to 1,360 (16.6%) until 2015, then increased 1,009 (22.6%) and 1,490 (18.2%) in 2016-2021, respectively. Since 2016, doxycycline showed 902 (100%) susceptibility. Clinicians need access to up-to-date information on antimicrobial susceptibility for treating hospitalized patients. To achieve the WHO-backed objective of eliminating cholera by 2030, the health systems need to be put under a proper surveillance system that may help to improve water and sanitation practices and deploy oral cholera vaccines strategically.

Citrulline and kynurenine to tryptophan ratio: potential EED (environmental enteric dysfunction) biomarkers in acute watery diarrhea among children in Bangladesh.

Two emerging biomarkers of environmental enteric dysfunction (EED) include plasma citrulline (CIT), and the kynurenine (KYN): tryptophan (TRP)/ (KT) ratio. We sought to investigate the plasma concentration of CIT and KT ratio among the children having dehydrating diarrhea and examine associations between concentrations of CIT and KT ratio with concurrent factors. For this analysis, we used cross-sectional data from a total of 102, 6-36 months old male children who suffered from non-cholera acute watery diarrhea and had some dehydration admitted to an urban diarrheal hospital, in Bangladesh. CIT, TRP, and KYN concentrations were determined at enrollment from plasma samples using ELIZA. At enrollment, the mean plasma CIT concentration was 864.48 ± 388.55 µmol/L. The mean plasma kynurenine, tryptophan concentrations, and the KT ratio (× 1000) were 6.93 ± 3.08 µmol/L, 33.44 ± 16.39 µmol/L, and 12.12 ± 18.10, respectively. With increasing child age, KYN concentration decreased (coefficient: - 0.26; 95%CI: - 0.49, - 0.04; p = 0.021); with increasing lymphocyte count, CIT concentration decreased (coef.: - 0.01; 95% CI: - 0.02,0.001, p = 0.004); the wasted child had decreased KT ratio (coef.: - 0.6; 95% CI: - 1.18, - 0.02; p = 0.042) after adjusting for potential covariates. The CIT concentration was associated with blood neutrophils (coef.: 0.02; 95% CI: 0.01, 0.03; p < 0.001), lymphocytes (coef.: - 0.02; 95% CI: - 0.03, - 0.02; p < 0.001) and monocyte (coef.: 0.06; 95% CI: 0.01, 0.11; p = 0.021); KYN concentration was negatively associated with basophil (coef.: - 0.62; 95% CI: - 1.23, - 0.01; p = 0.048) after adjusting for age. In addition, total stool output (gm) increased (coef.: 793.84; 95% CI: 187.16, 1400.52; p = 0.011) and also increased duration of hospital stay (hour) (coef.: 22.89; 95% CI: 10.24, 35.54; p = 0.001) with increasing CIT concentration. The morphological changes associated with EED may increase the risk of enteric infection and diarrheal disease among children. Further research is critically needed to better understand the complex mechanisms by which EED biomarkers may impact susceptibility to dehydrating diarrhea in children.

A double-blind clinical trial to compare the efficacy and safety of a multiple amino acid-based ORS with the standard WHO-ORS in the management of non-cholera acute watery diarrhea in infants and young children: "VS002A" trial protocol.

BACKGROUND: Diarrhea is the second deadliest disease for under-five children globally and the situation is more serious in developing countries. Oral rehydration solution (ORS) is being used as a standard treatment for acute watery diarrhea for a long time. Our objective is to compare the efficacy of amino acid-based ORS "VS002A" compared to standard glucose-based WHO-ORS in infants and young children suffering from acute non-cholera watery diarrhea. METHODS: It is a randomized, double-blind, two-cell clinical trial at Dhaka Hospital of icddr,b. A total of 312 male children aged 6-36 months old with acute non-bloody watery diarrhea are included in this study. Intervention arm participants get amino acid-based ORS (VS002A) and the control arm gets standard glucose-based WHO-ORS. The primary efficacy endpoint is the duration of diarrhea in the hospital. DISCUSSION: Oral rehydration therapy (ORT) with the present ORS formulation has certain limitations - it does not reduce the volume, frequency, or duration of diarrhea. Additionally, the failure of present standard ORS to significantly reduce stool output likely contributes to the relatively limited use of ORS by mothers as they do not feel that ORS is helping their child recover from the episode of diarrhea. Certain neutral amino acids (e.g., glycine, L-alanine, L-glutamine) can enhance the absorption of sodium ions and water from the gut. By using this concept, a shelf-stable, sugar-free amino acid-based hydration medicinal food named 'VS002A' that effectively rehydrates, and improves the barrier function of the bowel following infections targeting the gastrointestinal tract has been developed. If the trial shows significant benefits of VS002A use, this may provide evidence to support consideration of the use of VS002A in the present WHO diarrhea management guidelines. Conversely, if there is no evidence of benefit, these results will reaffirm the current guidelines. TRIAL REGISTRATION: ClinicalTrials.gov NCT04677296 . Registered on December 21, 2020.