Clinical Research Directory

Single Dose Azithromycin to Prevent Cholera in Children

This study aims to determine whether single-dose azithromycin is effective in preventing cholera in children who are at extremely high risk of infection. The study will also determine the effect of this intervention on the development of antibiotic resistant bacteria. The results will inform future strategies to prevent cholera in children, and improve overall understanding of the impact of azithromycin on antibiotic resistance.

Cholera Control by Case-area Targeted Interventions (CATIs)

To evaluate the effectiveness of the CATI approach among household contacts in the reduction of cumulative incidence of cholera and explore the genome analysis and immune response of V. cholerae antigen from different hotspots in Dhaka city, cholera cases will be enrolled by rapid diagnostic test (RDT) from the diarrhoeal patients coming to icddr,b Dhaka hospital. Hotspots will be defined as the households (HHs) surrounding the RDT-positive cholera case (around 20-40m radius). The 'Case area targeted interventions' (CATI) will be given by administrating Oral Cholera Vaccine (OCV) with either one dose or two doses of OCV 1 month apart among household contacts (≥1-year age and non-pregnant women) and contacts of the contacts residing in the adjacent HHs. The passive surveillance for cholera will be followed using the icddr,b hospital, and other health facilities. Data on each individual's states of the clusters (e.g., susceptible, exposed, infectious, or recovered) will be tracked throughout the 3 years study follow-up.

Assessment of a Novel Fixed-dose Combination (FDC) Drug VR-AD-1005 for the Treatment of Acute Watery Diarrhea in Cholera

Cholera still remains a global public health concern affecting both children and adults, and patients can succumb in quick time if remain untreated. Cholera is a secretory diarrhea and is generally treated with oral or intravenous rehydration therapy to compensate for the fluid loss. However, antimicrobial treatment is given to patients with moderate to severe diarrhea. The consistent emergence of multidrug-resistant bacteria is a major concern for the management of infectious diseases including cholera. No antisecretory drug has so far been proven successful. In a phase II clinical trial, the investigators will assess the effectiveness of a novel antisecretory drug VR-AD-1005 for treating cholera. Changes in stool volume and rehydration therapy will be assessed for VR-AD-1005 in comparison with placebo. If successful, this will be a huge advance in managing cholera and other secretory diarrhea. The introduction of the antisecretory drug can minimize the hospital stay and reduce antibiotic use, which in turn can reduce the emergence of antibiotic resistance among pathogens

Testing a Scalable Model of the Cholera Hospital-Based Intervention for 7 Days (CHoBI7)

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).

Next Generation ORS: Comparing ORS With Calcium vs Standard ORS in Reducing Severity of Acute Watery Diarrhea

Diarrhea remains a leading killer of children in need of better treatments.

Vaccine- and Infection-derived Correlates of Protection for Cholera

Background: Vibrio cholerae causes millions of cholera cases and thousands of deaths annually. Vaccines are in short supply. There is no agreement on how to introduce new vaccines or evaluate their effectiveness, and the lack of 'correlates of protection' (CoPs) against cholera is a major obstacle to vaccine development. CoPs are markers of effective immune response to vaccination. While other infectious diseases have well established CoPs, none are widely accepted for cholera. Relevance: Lack of accepted CoPs impedes development of cholera vaccines, limiting progress toward improved vaccines, slowing the licensure of new vaccines, and contributing to the current vaccine shortage; an immediate obstacle to achieving reductions in cholera-related illness and deaths. The identification of new CoPs will speed the development of improved cholera vaccines and provide a pathway to their licensure and use. Hypothesis: The investigators hypothesize that some individuals who receive inactivated oral cholera vaccine (OCV) will develop antibody responses which predict protection against V. cholerae infection and that specific immune responses distinguish individuals who are protected against cholera by prior natural infection from those who are protected from OCVs. Objectives: The investigators will administer an OCV or typhoid vaccine (TCV) control and monitor antibody responses to identify better CoPs for cholera following both vaccination and natural infection. Methods: The investigators will randomize 1219 participants; 554 participants will receive an inactivated bivalent OCV, 665 participants will receive a TCV control. The investigators will collect 12 blood samples over two-years following vaccination to measure antibodies against V. cholerae and to monitor for re-infection. Outcome measures/variables: The endpoint of interest is V. cholerae infection after vaccination. The investigators define infection as positive culture or PCR for V. cholerae or seroconversion events observed over the 2-year follow up period.

Preventative Intervention for Cholera for 7 Days

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.

Cholera-Hospital-Based-Intervention-for-7-Days (CHoBI7) Water, Sanitation, and Hygiene (WASH) Case Area Targeted Intervention (CATI)

Objective: The investigators objective is to develop and evaluate the effectiveness of a case area targeted water, sanitation, and hygiene (WASH) intervention in reducing cholera infections and increasing sustained WASH behaviors in transmission hotspots in a ring around cholera cases.

Impact Study of Cholera Vaccination in Endemic Areas - Clinical Surveillance

This project aims to fill this essential knowledge gap by assessing the impact of oral cholera vaccine mass campaigns in 2 sites (urban and rural) in DRC, described in this protocol. The evidence generated from this project will be key to develop future strategies regarding cholera vaccine use in endemic settings, including places with higher burden in terms of cholera mortality.