Enterics for Global Health (EFGH) (EFGH)

January 10, 2025 updated by: Patricia B Pavlinac, University of Washington

The Incidence and Burden of Shigella Diarrhea in Children Aged 6-35 Months: the Enterics for Global Health (EFGH) - Shigella Burden Study

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).

Study Overview

Status

Active, not recruiting

Conditions

Detailed Description

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.
Identify optimal laboratory methods for Shigella culture by:
1. comparing the isolation rate of Shigella between two transport media for rectal swabs (Cary-Blair and modified Buffered Glycerol Saline [BGS])
2. 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

Enrollment (Estimated)

9800

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Bangladesh
- - Dhaka, Bangladesh
    - icddr,b Dhaka hospital
  - Dhaka, Bangladesh
    - Dhaka Medical College Hospital
  - Dhaka, Bangladesh
    - EFGH Field Clinic
  - Dhaka, Bangladesh
    - Mugda Medical College Hospital
  - Dhaka, Bangladesh
    - Sir Salimullah Medical College Hospital
Gambia
- Upper River Region
  - Basse Santa Su, Upper River Region, Gambia
    - Basse Hospital
  - Basse Santa Su, Upper River Region, Gambia
    - Gambisara Health Centre (HC)
Kenya
- - Siaya, Kenya
    - Siaya County Referral Hospital
  - Siaya, Kenya
    - Ongielo Health Centre
  - Siaya, Kenya
    - Abidha Health Center
  - Siaya, Kenya
    - Akala Health Center
  - Siaya, Kenya
    - Bar Agulu Health Center
  - Siaya, Kenya
    - Dienya Health Centre
  - Siaya, Kenya
    - Lwak Mission Hospital
  - Siaya, Kenya
    - Ting Wangi Health Center
  - Siaya, Kenya
    - Wagai Health Center
Malawi
- - Blantyre, Malawi
    - Ndirande Health Centre
Mali
- - Bamako, Mali
    - Asacodjeneka Cscom
  - Bamako, Mali
    - Asacodjip Cscom
  - Bamako, Mali
    - Banconi CSCOM (ASACOBA)
  - Bamako, Mali
    - CSREF Commune 1
Pakistan
- - Karachi, Pakistan
    - Abbasi Shaheed Hospital
  - Karachi, Pakistan
    - Ali Akbar Shah Center
  - Karachi, Pakistan
    - Bhains colony AKU site
  - Karachi, Pakistan
    - Khidmat e Alam Medical Centre
  - Karachi, Pakistan
    - Sindh Government Hospital, Ibrahim Hyderi
  - Karachi, Pakistan
    - Sindh Government Hospital, Korangi
Peru
- Maynas
  - Iquitos, Maynas, Peru
    - America Health Post
  - Iquitos, Maynas, Peru
    - Hospital de Apoloyo
  - Iquitos, Maynas, Peru
    - Modelo Health Post
  - Iquitos, Maynas, Peru
    - Progreso Health Post
  - Iquitos, Maynas, Peru
    - San Juan Health Post
  - Iquitos, Maynas, Peru
    - Santo Tomas Health Post

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

Child

Accepts Healthy Volunteers

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.

Description

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
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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Number of groups / cohorts

Cohorts and Interventions

Group / Cohort
Children with Shigella Diarrhea Children with Shigella identified by culture or quantitative PCR
Children without Shigella Diarrhea Children without Shigella identified by culture or quantitative PCR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	At enrollment in the study (cross-sectional)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	At enrollment in the study (cross-sectional)
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.	3 months
Death Time Frame: 3 months	Death: all cause mortality during follow-up among enrolled children.	3 months
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	3 months
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.	3 months
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).	3 months
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	3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Washington

Collaborators

University of Maryland, Baltimore

Bill and Melinda Gates Foundation

Aga Khan University

University of Virginia

International Centre for Diarrhoeal Disease Research, Bangladesh

Medical Research Council Unit, The Gambia

Kenya Medical Research Institute

Malawi-Liverpool-Wellcome Trust Clinical Research Programme

Center for Vaccine Development - Mali

Asociacion Benefica Prisma

Investigators

Principal Investigator: Patricia B Pavlinac, PhD, University of Washington

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 25, 2022

Primary Completion (Actual)

August 17, 2024

Study Completion (Estimated)

April 30, 2025

Study Registration Dates

First Submitted

September 12, 2023

First Submitted That Met QC Criteria

September 18, 2023

First Posted (Actual)

September 21, 2023

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

January 10, 2025

Last Verified

January 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

INV-01665

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD 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.

IPD Sharing Supporting Information Type

ANALYTIC_CODE

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Studies a U.S. FDA-regulated device product

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.