Diarrhea Infectious

The overall objective of the RESTORATiVE303 study is to evaluate the safety and the Clostridioides difficile infection (CDI) recurrence rate at Week 8 in participants who receive a 14-day course of VE303 or matching placebo. The objectives and endpoints are identical for Stage 1 (recurrent CDI) and Stage 2 (high-risk primary CDI).

Diarrheal disease remains a leading cause of morbidity and mortality for children under 5 globally. Accepted best practice for managing diarrhea in the absence of blood or suspicion of cholera is rehydration, however in resource poor areas antibiotics are still prescribed at high rates due to pressures such as financial incentives, caregiver expectations, and diagnostic uncertainty. Informal healthcare providers often serve as first point of care for pediatric diarrhea patients in low- and middle- income countries (LMICs) and commonly prescribe antibiotics for pediatric diarrhea at high frequencies. In this pilot before-after feasibility trial informally trained healthcare providers will use a mobile phone-based application (Accessible Diarrhea Etiology Prediction Tool, ADEPT) which will allow for the exploration of the acceptability, feasibility, and utility of the tool, as well as ADEPTs ability to decrease inappropriate antibiotic prescribing practices.

The findings from previous recent randomized controlled trials of The Cholera Hospital Based Intervention for 7 Days (CHoBI7) demonstrated that this intervention was effective in significantly reducing symptomatic cholera infections, diarrheal disease, and stunting among young children in intervention households, and had significant sustained impacts on handwashing with soap behaviors and improved water quality 12 months post intervention. Therefore, the investigators next step in the transition to scale is to: (1) To tailor the CHoBI7 program for delivery in rural health facilities and market test the CHoBI7 Program to determine the feasibility of providing a modified water, sanitation, and hygiene (WASH) package with only a soapy water bottle and chlorine tablets in both urban and rural settings through formative research and engagement of key stakeholders (Formative Research Phase); and (2) To evaluate the effectiveness of delivering the CHoBI7 program in district hospitals and sub-district health complexes in rural areas in terms of increases in WASH behaviors and decreases in diarrheal disease by conducting a randomized controlled trial (RCT) (Intervention Implementation and Evaluation Phase).

The purpose of this study is to evaluate whether antibiotic treatment of non-dysentery Shigella associated watery diarrhea (NDSD) cases improves clinical outcomes and growth in children. Children with NDSD seeking care for diarrhea at the study hospitals in Bangladesh and Zambia will be enrolled and randomized to receive Azithromycin or placebo (a look-alike substance that contains no drug). Enrolled children will be followed for three months with household visits. The investigators will determine whether antibiotic treatment of NDSD reduces the duration of diarrhea and time to microbiological cure (shedding of Shigella in stool), and whether it improves growth in children compared with the placebo group.

The first objective of our study is to develop a theory-driven evidence-based targeted water, sanitation, and hygiene (WASH) intervention for household members of diarrhea patients in South Kivu, Democratic Republic of the Congo (DRC) through formative research and community engagement. The second objective is to conduct a randomized controlled trial of 2,320 household members of 580 severe diarrhea patients to evaluate the effectiveness of the developed targeted WASH intervention in terms of: 1. reducing diarrheal diseases household members of cholera and severe diarrhea patients; and 2. increasing WASH behaviors.

Malnutrition in women of reproductive age remains a public health concern in Sub-Saharan Africa (SSA). Malnutrition during pregnancy affects foetal growth with a tendency of the exposed infants to also develop it. The interaction of the mother with the infant shapes the seeding and the trajectory of the infant intestinal microbiota which is crucial for development of a healthy immune system Malnutrition has been associated with intestinal inflammation, intestinal leakage and reduced calorie absorption. Early life malnutrition and environmental enteric dysfunction (EED) immunopathology remains poorly described in the context of mother-infant dyads. This is essential as malnutrition, poor water, sanitation and hygiene (WASH), including the presence of infectious diseases limit the developmental potential of the exposed infants in SSA, including Zimbabwe. In addition, maternal stress and poor mental health may also affect standard hygiene practices, including how a mother cares for her baby, potentially aggravating EED and the risk of the infant being malnourished. Primary outcomes 1. Infant malnutrition and recovery. 2. Gut dysfunction (gut inflammation, leaky gut, malabsorption, dysbiosis) 3. Diarrhea episodes, defined as any episode of acute diarrhoea (≥3 passages of loose stool within 24 hours as reported by the mother) occurring before the next study visit. Definition of malnutrition outcomes to be assessed in babies born to malnourished women, is a mid- upper arm circumference (MUAC) \<23cm; * MUAC for age: Malnourished defined as those below -2 standard (SD) of the World Health Organisation (WHO) reference * Weight-for-age: Underweight defined as those below -2SD WHO reference * Weight-for-height: Wasted defined as those below -2SD WHO reference * Height-for-age: Stunted defined as those below -2SD WHO reference * Z-scores (as they are i.e. a continuous variable, taking age of infants into account) * A composite variable, any of malnourished, underweight, wasted or stunted.