Enterics for Global Health (EFGH) (EFGH)
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| ClinicalTrials.gov Identifier: NCT06047821 |
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Recruitment Status :
Recruiting
First Posted : September 21, 2023
Last Update Posted : November 7, 2023
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Sponsor:
University of Washington
Collaborators:
Aga Khan University
International Centre for Diarrhoeal Disease Research, Bangladesh
University of Maryland, Baltimore
University of Virginia
Asociacion Benefica Prisma
Medical Research Council Unit, The Gambia
Kenya Medical Research Institute
Center for Vaccine Development - Mali
Malawi-Liverpool-Wellcome Trust Clinical Research Programme
Bill and Melinda Gates Foundation
Information provided by (Responsible Party):
Patricia B Pavlinac, University of Washington
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Brief Summary:
Diarrhea remains a leading cause of death among young children, with the majority of diarrhea deaths occurring in low- and middle-income countries. Childhood diarrhea caused by a type of bacteria called "Shigella" is responsible for an estimated 60,000 deaths each year and may cause particularly severe illness among children. Currently, there are several promising vaccines to prevent Shigella diarrhea in development, but key information is still needed to inform future vaccine studies. The purpose of this study, titled Enterics for Global Health (or the "EFGH"), is to determine the number and rate of new cases of Shigella diarrhea among children 6 to 35 months of age presenting to health facilities with diarrhea or dysentery. Over a two-year period, the EFGH study will enroll 1,400 children from each of the seven countries: Peru, Pakistan, Bangladesh, Mali, Malawi, Kenya, and The Gambia (9,800 children total).
| Condition or disease |
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| Shigella Child Diarrhea |
In low- and middle-income countries, nearly one third of children experience at least one episode of Shigella-attributable diarrhea during their first 2 years of life. In addition to it being a leading cause of diarrhea, this enteric bacterium is also associated with linear growth faltering, a precursor to stunting. Stunting is a marker of vulnerability to childhood infection, decreased vaccine efficacy and lifelong morbidity. Currently, several promising Shigella vaccines are in development. Eventual Phase 2b/3 Shigella vaccine trials will require a consortium of potential vaccine trial sites in settings with a high incidence of Shigella-attributed medically-attended diarrhea, high participant retention, and the laboratory capacity to confirm Shigella infection. The Enterics for Global Health (EFGH) Shigella burden study will employ cross-sectional and longitudinal study designs to establish updated incidence rates and document consequences of Shigella diarrhea within 7 country sites in Africa, Asia, and Latin America. Over a two-year period, the EFGH study will enroll 9,800 children (1,400 per country site) between 6-35 months with medically-attended diarrhea. Through this multi-country surveillance network, selected EFGH sites will be ready to quickly implement rigorous and efficient vaccine trials and provide critical data to policy makers about the relative importance of this vaccine-preventable disease, accelerating the time to vaccine availability and uptake among children in high Shigella burden settings.
Primary Aims
1. Determine the incidence of Shigella-attributed medically-attended diarrhea in children 6 to 35 months of age in each of the EFGH country sites.
Secondary Aims
- Determine the incidence of Shigella medically-attended diarrhea by serotype, severity definition, laboratory method (culture vs. qPCR), age, and by season.
- Describe the prevalence of resistance to commonly used antibiotics in Shigella isolates in each EFGH country site.
- Determine the risk of death, hospitalization, persistent diarrhea, diarrhea recurrence, and linear growth faltering in the 3 months following an episode of Shigella medically-attended diarrhea.
- Compare various severity definitions in their ability to distinguish Shigella from non-Shigella attributable diarrhea and ability to predict risk of death or hospitalization in the subsequent 3 months.
- Quantify the cost incurred by families and health care systems due to Shigella morbidity and mortality.
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Identify optimal laboratory methods for Shigella culture by:
- comparing the isolation rate of Shigella between two transport media for rectal swabs (Cary-Blair and modified Buffered Glycerol Saline [BGS])
- comparing the isolation rate of Shigella between two fecal sample types (rectal swabs and whole stool) among the subset of children who produced whole stool in The Gambia and Bangladesh country sites.
| Study Type : | Observational |
| Estimated Enrollment : | 9800 participants |
| Observational Model: | Cohort |
| Time Perspective: | Prospective |
| Official Title: | The Incidence and Burden of Shigella Diarrhea in Children Aged 6-35 Months: the Enterics for Global Health (EFGH) - Shigella Burden Study |
| Actual Study Start Date : | August 25, 2022 |
| Estimated Primary Completion Date : | December 25, 2024 |
| Estimated Study Completion Date : | May 31, 2025 |
| Group/Cohort |
|---|
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Children with Shigella Diarrhea
Children with Shigella identified by culture or quantitative PCR
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Children without Shigella Diarrhea
Children without Shigella identified by culture or quantitative PCR
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Primary Outcome Measures :
- Shigella incidence [ Time Frame: At enrollment in the study (cross-sectional) ]The primary outcome measure is Shigella incidence, defined as incident diarrhea among children enrolled at health clinics attributable to Shigella by microbiological methods (culture or qPCR) divided by the estimated population living in the catchment area. Incidence will be reported as crude incidence as well as adjusted for healthcare seeking and the percentage of children who were enrolled.
Secondary Outcome Measures :
- Antimicrobial susceptibility [ Time Frame: At enrollment in the study (cross-sectional) ]Antimicrobial susceptibility will be computed separately for Ampicillin, Azithromycin, Ceftriaxone, Ciprofloxacin, Nalidixic Acid, Pivmecillinam, and Trimethoprim-Sulfamethoxazole and defined as intermediate or resistant according to the most recent Clinical and Laboratory Standards Institute (CLSI) interpretive standards at the time of data analysis.
- Cost per episode treated [ Time Frame: 3 months ]Cost per episode treated will be calculated using the direct and indirect financial costs and total economic costs of illness per outpatient and inpatient episode of Shigella-associated diarrhea from the household and, separately, payer perspectives.
- Death [ Time Frame: 3 months ]Death: all cause mortality during follow-up among enrolled children.
- Hospitalization [ Time Frame: 3 months ]Hospitalization will be defined as an overnight stay (child was on the ward from at least 12am to 6am) that occurs during follow-up among enrolled children
- Persistent diarrhea (index episode) [ Time Frame: 3 months ]Persistent diarrhea will be defined as 14 or more days of diarrhea (starting from the date at which the diarrhea first started (as opposed to date at presentation to an EFGH facility) and concluding at the last day of diarrhea prior to the two consecutive diarrhea-free days concluding the episode.
- Diarrhea/dysentery recurrence [ Time Frame: 3 months ]Diarrhea/dysentery recurrence will be defined as new diarrhea/dysentery episodes (>48 hours after a diarrhea-free period).
- Change in linear growth [ Time Frame: 3 months ]Change in mean length/height-for-age z-score (∆LAZ/∆HAZ) from enrollment to 3 months. The 2006 World Health Organization (WHO) reference population will be used to calculate HAZ from the average of two repeated length/height (cm) measures per child per time point
Biospecimen Retention: Samples With DNA
Shigella isolates, lactose fermenting sweep, and rectal swab/stool DNA; Specimens stored at -80 degrees Celsius at each respective country-site
Information from the National Library of Medicine
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| Ages Eligible for Study: | 6 Months to 35 Months (Child) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
| Sampling Method: | Non-Probability Sample |
Study Population
Children aged 6-35 months of age presenting with diarrhea at selected study health facilities in Bangladesh, Malawi, Kenya, Mali, the Gambia, Pakistan, and Peru.
Criteria
Inclusion Criteria:
- Child is 6-35 months of age
- Primary caregiver and child plan to remain at their current residence for at least the next 4 months
- Primary caregiver is able to provide informed consent (legal age or emancipated minor) and provides consent within a common language for which translations are available
- Child presents to health facility with diarrhea (≥3 abnormally loose or watery stools in the previous 24 hours) with or without the presence of blood
- Child resides within the pre-defined study area
- Fewer than 4 hours have passed since the child presented to a health facility
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Diarrhea episode is:
- Acute (onset within 7 days of study enrollment) and
- Represents a new episode (onset after at least 2 diarrhea-free days)
- Caregiver is willing to have child participate in follow-up visits at week 4 and month 3
- Willingness to have samples collected from the child (rectal swabs at enrollment)
- Site enrollment cap has not been met
- Child is not being referred to a non-EFGH facility at the time of screening
Exclusion Criteria:
- Child is < 6-35 months of age
- Child is > 6-35 months of age
- Primary caregiver and child do not plan to remain at their current residence for at least the next 4 months
- Primary caregiver is not able to provide informed consent (legal age or emancipated minor)
- Primary caregiver does not provide consent within a common language for which translations are available
- Child does not present to health facility with diarrhea (≥3 abnormally loose or watery stools in the previous 24 hours) with or without the presence of blood
- Child does not reside within the pre-defined study area
- 4 or more hours have passed since the child presented to a health facility
- Diarrhea episode is not Acute (onset within 7 days of study enrollment)
- Diarrhea episode does not represent a new episode (onset after at least 2 diarrhea-free days)
- Caregiver is unwilling to have child participate in follow-up visits at week 4 and month 3
- Unwillingness to have samples collected from the child (rectal swabs at enrollment)
- Site enrollment cap has been met
- Child is being referred to a non-EFGH facility at the time of screening
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06047821
Contacts
| Contact: Patricia B Pavlinac, PhD | 206-616-8326 | ppav@uw.edu | |
| Contact: Sean R Galagan, MSPH | sgalagan@uw.edu |
Locations
Show 33 study locations
Sponsors and Collaborators
University of Washington
Aga Khan University
International Centre for Diarrhoeal Disease Research, Bangladesh
University of Maryland, Baltimore
University of Virginia
Asociacion Benefica Prisma
Medical Research Council Unit, The Gambia
Kenya Medical Research Institute
Center for Vaccine Development - Mali
Malawi-Liverpool-Wellcome Trust Clinical Research Programme
Bill and Melinda Gates Foundation
Investigators
| Principal Investigator: | Patricia B Pavlinac, PhD | University of Washington |
Study Documents (Full-Text)
Documents provided by Patricia B Pavlinac, University of Washington:
Documents provided by Patricia B Pavlinac, University of Washington:
Statistical Analysis Plan [PDF] October 31, 2023
Publications:
| Responsible Party: | Patricia B Pavlinac, Associate Professor, University of Washington |
| ClinicalTrials.gov Identifier: | NCT06047821 |
| Other Study ID Numbers: |
INV-01665 |
| First Posted: | September 21, 2023 Key Record Dates |
| Last Update Posted: | November 7, 2023 |
| Last Verified: | November 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | The publicly available analytic de-identified datasets corresponding to each specific aim, along with corresponding analytic code in Stata or R, will be posted to Dataverse, which is a publicly available data repository. Data requests for data not included in the publicly available analytic datasets corresponding to each aim will be managed by the University of Washington and relevant EFGH site investigators. |
| Supporting Materials: |
Analytic Code |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Patricia B Pavlinac, University of Washington:
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Epidemiology Shigella Diarrhea |
Children Enterics Vaccine |
Additional relevant MeSH terms:
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Dysentery, Bacillary Diarrhea Signs and Symptoms, Digestive Enterobacteriaceae Infections Gram-Negative Bacterial Infections Bacterial Infections Bacterial Infections and Mycoses |
Infections Dysentery Gastroenteritis Gastrointestinal Diseases Digestive System Diseases Intestinal Diseases |