Treatment heterogeneity of water, sanitation, hygiene, and nutrition interventions on child growth by environmental enteric dysfunction and pathogen status for young children in Bangladesh.

Background: Water, sanitation, hygiene (WSH), nutrition (N), and combined (N+WSH) interventions are often implemented by global health organizations, but WSH interventions may insufficiently reduce pathogen exposure, and nutrition interventions may be modified by environmental enteric dysfunction (EED), a condition of increased intestinal permeability and inflammation. This study investigated the heterogeneity of these treatments' effects based on individual pathogen and EED biomarker status with respect to child linear growth.

Methods: We applied cross-validated targeted maximum likelihood estimation and super learner ensemble machine learning to assess the conditional treatment effects in subgroups defined by biomarker and pathogen status.

Use of a TaqMan Array Card for identification of enterotoxins and colonization factors directly from stool samples in an enterotoxigenic vaccine study.

Enterotoxigenic (ETEC) is a leading cause of childhood and travelers' diarrhea. The vaccine candidate ETVAX encompasses several ETEC colonization factors (CFs) with a hybrid LT (heat-labile toxin)/cholera toxin B subunit adjuvanted with a double-mutant LT. Stool samples from a Phase 2b ETVAX trial were tested by a PCR-based customized TaqMan Array Card (TAC), including three ETEC toxin genes (LT and heat-stable toxins, STh and STp) and 18 ETEC CFs.

Effect of biannual azithromycin on respiratory pathogens among symptomatic children: results from the randomised Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance (MORDOR) I trial.

Introduction: Biannual (ie, every 6 months) mass drug administration of azithromycin has reduced childhood mortality in Niger, but its effects on specific respiratory pathogens are not fully elucidated.

Methods: Across 2 years of the Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance (MORDOR) study in Niger, we evaluated 1468 nasopharyngeal swabs from children who presented for care with respiratory symptoms. Swabs were tested by quantitative PCR using a customised TaqMan Array Card that included assays for 19 respiratory pathogens.

Automated post-run analysis of arrayed quantitative PCR amplification curves using machine learning.

Background: The TaqMan Array Card (TAC) is an arrayed, high-throughput qPCR platform that can simultaneously detect multiple targets in a single reaction. However, the manual post-run analysis of TAC data is time consuming and subject to interpretation. We sought to automate the post-run analysis of TAC data using machine learning models.

TaqMan Array Card real-time polymerase chain reaction panel to detect pathogens in whole blood of febrile inpatients in northern Tanzania, 2016-2019.

Background: Acute febrile illness is a common reason for seeking healthcare in low- and middle-income countries. We describe the diagnostic utility of a TaqMan Array Card (TAC) real-time polymerase chain reaction (PCR) panel for pathogen detection in paediatric and adult inpatients admitted with febrile illness.

Methods: In this prospective cohort study, we screened medical admissions for a tympanic temperature ≥38.

Genomic Epidemiology of 2023-2024 Oropouche Outbreak in Iquitos, Peru reveals independent origin from a concurrent outbreak in Brazil.

Oropouche virus is an arbovirus endemic to the Americas. Periodic outbreaks have occurred since its description in 1955. In late 2023, an outbreak occurred in Peru, centered in and around Iquitos in the Eastern Peruvian Amazon.

Describing Biological Vulnerability in Small, Vulnerable Newborns in Urban Burkina Faso (DenBalo): Gut Microbiota, Immune System, and Breastmilk Assembly.

: Small vulnerable newborns (SVNs), including those born preterm, small for gestational age, or with low birth weight, are at higher risk of neonatal mortality and long-term health complications. Early exposure to maternal vaginal microbiota and breastfeeding plays a critical role in the development of the neonatal microbiota and immune system, especially in low-resource settings like Burkina Faso, where neonatal mortality rates remain high. : The DenBalo study aims to investigate the role of maternal and neonatal factors, such as vaginal and gut microbiota, immune development, and early nutrition, in shaping health outcomes in SVNs and healthy infants.

The impact of vaccines for diarrhoea on antibiotic use among children in five low-resource settings: a comparative simulation study.

Background: Vaccines for diarrhoea could have the ancillary benefit of preventing antibiotic use. We aimed to quantify and compare the expected impact of enteric vaccines on antibiotic use via Monte Carlo simulations.

Methods: We analysed data from a longitudinal birth cohort, which enrolled children from 2009 to 2012 from Bangladesh, India, Nepal, Pakistan, and Tanzania.

Epidemiologic and genomic characterization of an outbreak of Rift Valley fever among humans and dairy cattle in northern Tanzania.

Background: A peri-urban outbreak of Rift Valley fever virus (RVFV) among dairy cattle from May through August 2018 in northern Tanzania was detected through testing samples from prospective livestock abortion surveillance. We sought to identify concurrent human infections, their phylogeny, and epidemiologic characteristics in a cohort of febrile patients enrolled from 2016-2019 at hospitals serving the epizootic area.

Methods: From September 2016 through May 2019, we conducted a prospective cohort study that enrolled febrile patients hospitalized at two hospitals in Moshi, Tanzania.

Infectious etiology of intussusception in Indian children less than 2 years old: a matched case-control analysis.

Background: Enteric infections are hypothesized to be associated with intussusception in children. A small increase in intussusception following rotavirus vaccination has been seen in some settings. We conducted post-marketing surveillance for intussusception following rotavirus vaccine, Rotavac introduction in India and evaluated association of intussusception with enteric pathogens.

Enteric pathogens relationship with small bowel histologic features of environmental enteric dysfunction in a multicountry cohort study.

Background: Environmental Enteric Dysfunction (EED) is an acquired disorder of asymptomatic altered gut function, the etiology of which is unknown. EED is postulated to be a major contributor to growth faltering in early childhood in regions where early-life enteropathogenic carriage is prevalent. Few studies have examined the critical organ (the upper small bowel) with enteropathogens in the evolution of small bowel disease.

Prevalence and dynamics of antimalarial drug resistance mutations among the isolates in TAK Province, Thailand, during the period of 1998-2001.

Despite the overall decline in malaria cases in Thailand, continuous surveillance in endemic areas remains crucial. This retrospective analysis examined samples from Tak province, Thailand, collected in 1998, 1999, and 2001, to investigate the prevalence and evolution of antimalarial genotypic drug resistance. The study revealed a high prevalence of drug-resistant , particularly to mefloquine and sulfadoxine/pyrimethamine, with significant mutations in genes associated with resistance.

Lactoferrin and lysozyme to promote nutritional, clinical and enteric recovery: a protocol for a factorial, blinded, placebo-controlled randomised trial among children with diarrhoea and malnutrition (the Boresha Afya trial).

Introduction: Children with moderate or severe wasting are at particularly high risk of recurrent or persistent diarrhoea, nutritional deterioration and death following a diarrhoeal episode. Lactoferrin and lysozyme are nutritional supplements that may reduce the risk of recurrent diarrhoeal episodes and accelerate nutritional recovery by treating or preventing underlying enteric infections and/or improving enteric function.

Methods And Analysis: In this factorial, blinded, placebo-controlled randomised trial, we aim to determine the efficacy of lactoferrin and lysozyme supplementation in decreasing diarrhoea incidence and improving nutritional recovery in Kenyan children convalescing from comorbid diarrhoea and wasting.

Leveraging data from a longitudinal birth cohort to improve attribution of diarrhea etiology among children in low-resource settings.

Attributing infectious causes of diarrhea is critical to inform treatment and burden estimates. The attributable fraction (AF) approach based on the association between pathogen quantity and diarrhea has been frequently used but may underestimate incidence. We leveraged data from the multisite birth-cohort Malnutrition and Enteric Disease (MAL-ED) Study, where diarrheal and non-diarrheal stools were collected from 1,715 children from 0-2 years.

Growth and Cognitive Development in Tanzanian Children are Associated with Timing of Birth in Relation to Seasonal Malnutrition.

Objective: To evaluate in a rural Tanzanian birth cohort the association between birth timing in relation to the preharvest lean season and early-life growth and cognitive development.

Study Design: Children were enrolled within 14 days of birth and followed up for 18 months. Child anthropometry was measured every 3 months.

Assessment of Spillover of Antimicrobial Resistance to Untreated Children 7-12 Years Old After Mass Drug Administration of Azithromycin for Child Survival in Niger: A Secondary Analysis of the MORDOR Cluster-Randomized Trial.

Background: The risk of antibiotic resistance is complicated by the potential for spillover effects from one treated population to another. Azithromycin mass drug administration programs report higher rates of antibiotic resistance among treatment arms in targeted groups. This study aimed to understand the risk of spillover of antibiotic resistance to nontarget groups in these programs.

Clinical and nutritional correlates of bacterial diarrhoea aetiology in young children: a secondary cross-sectional analysis of the ABCD trial.

Objective: The objective was to assess the association between nutritional and clinical characteristics and quantitative PCR (qPCR)-diagnosis of bacterial diarrhoea in a multicentre cohort of children under 2 years of age with moderate to severe diarrhoea (MSD).

Design: A secondary cross-sectional analysis of baseline data collected from the AntiBiotics for Children with Diarrhoea trial (NCT03130114).

Patients: Children with MSD (defined as 3 loose stools within 24 hours and presenting with at least one of the following: some/severe dehydration, moderate acute malnutrition (MAM) or severe stunting) enrolled in the ABCD trial and collected stool sample.

Etiology of diarrheal hospitalizations following rotavirus vaccine implementation and association of enteric pathogens with malnutrition among under-five children in India.

Malnourished children are at higher risk of mortality and morbidity following diarrheal illness and certain enteropathogens have been associated with malnutrition in children. Very few studies have comprehensively looked at the etiology of diarrhea in malnourished children and most have used conventional diagnostic methods with suboptimal sensitivity. We used a highly sensitive molecular approach against a broad range of pathogens causing diarrhea and examined their association with malnutrition.

Treatment Heterogeneity of Water, Sanitation, Hygiene, and Nutrition Interventions on Child Growth by Environmental Enteric Dysfunction and Pathogen Status for Young Children in Bangladesh.

Background: Water, sanitation, hygiene (WSH), nutrition (N), and combined (N+WSH) interventions are often implemented by global health organizations, but WSH interventions may insufficiently reduce pathogen exposure, and nutrition interventions may be modified by environmental enteric dysfunction (EED), a condition of increased intestinal permeability and inflammation. This study investigated the heterogeneity of these treatments' effects based on individual pathogen and EED biomarker status with respect to child linear growth.

Methods: We applied cross-validated targeted maximum likelihood estimation and super learner ensemble machine learning to assess the conditional treatment effects in subgroups defined by biomarker and pathogen status.

Diarrhea Case Surveillance in the Enterics for Global Health Surveillance Study: Epidemiologic Methods.

Background: is a leading cause of acute watery diarrhea, dysentery, and diarrhea-attributed linear growth faltering, a precursor to stunting and lifelong morbidity. Several promising vaccines are in development and field efficacy trials will require a consortium of potential vaccine trial sites with up-to-date diarrhea incidence data.

Methods: The Enterics for Global Health (EFGH) surveillance study will employ facility-based enrollment of diarrhea cases aged 6-35 months with 3 months of follow-up to establish incidence rates and document clinical, anthropometric, and financial consequences of diarrhea at 7 country sites (Mali, Kenya, The Gambia, Malawi, Bangladesh, Pakistan, and Peru).