Enterics for Global Health (EFGH) (EFGH)

November 2, 2023 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

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

  1. Determine the incidence of Shigella medically-attended diarrhea by serotype, severity definition, laboratory method (culture vs. qPCR), age, and by season.
  2. Describe the prevalence of resistance to commonly used antibiotics in Shigella isolates in each EFGH country site.
  3. 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.
  4. 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.
  5. Quantify the cost incurred by families and health care systems due to Shigella morbidity and mortality.

  6. 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 Contact

  • Name: Patricia B Pavlinac, PhD
  • Phone Number: 206-616-8326
  • Email: ppav@uw.edu

Study Contact Backup

Study Locations

  • Bangladesh
      • Dhaka, Bangladesh
        • Recruiting
        • icddr,b Dhaka Hospital
        • Contact:
        • Principal Investigator:
          • Firdausi Qadri, PhD
      • Dhaka, Bangladesh
        • Recruiting
        • Dhaka Medical College Hospital
        • Contact:
        • Principal Investigator:
          • Firdausi Qadri, PhD
      • Dhaka, Bangladesh
        • Recruiting
        • EFGH Field Clinic
        • Contact:
        • Principal Investigator:
          • Firdausi Qadri, PhD
      • Dhaka, Bangladesh
        • Recruiting
        • Mugda Medical College Hospital
        • Contact:
        • Principal Investigator:
          • Firdausi Qadri, PhD
      • Dhaka, Bangladesh
        • Recruiting
        • Sir Salimullah Medical College Hospital
        • Contact:
        • Principal Investigator:
          • Firdausi Qadri, PhD
  • Gambia
    • Upper River Region
      • Basse Santa Su, Upper River Region, Gambia
      • Basse Santa Su, Upper River Region, Gambia
        • Recruiting
        • Gambisara Health Centre (HC)
        • Contact:
        • Principal Investigator:
          • Jahangir Hossain, MD
  • Kenya
      • Siaya, Kenya
        • Recruiting
        • Abidha Health Center
        • Contact:
        • Principal Investigator:
          • Richard Omore, PhD
      • Siaya, Kenya
        • Recruiting
        • Akala Health Center
        • Contact:
        • Principal Investigator:
          • Richard Omore, PhD
      • Siaya, Kenya
        • Recruiting
        • Bar Agulu Health Center
        • Contact:
        • Principal Investigator:
          • Richard Omore, PhD
      • Siaya, Kenya
        • Recruiting
        • Dienya Health Centre
        • Contact:
        • Principal Investigator:
          • Richard Omore, PhD
      • Siaya, Kenya
        • Recruiting
        • Lwak Mission Hospital
        • Contact:
        • Principal Investigator:
          • Richard Omore, PhD
      • Siaya, Kenya
        • Recruiting
        • Ongielo Health Centre
        • Contact:
        • Principal Investigator:
          • Richard Omore, PhD
      • Siaya, Kenya
        • Recruiting
        • Siaya County Referral Hospital
        • Contact:
        • Principal Investigator:
          • Richard Omore, PhD
      • Siaya, Kenya
        • Recruiting
        • Ting Wangi Health Center
        • Contact:
        • Principal Investigator:
          • Richard Omore, PhD
      • Siaya, Kenya
        • Recruiting
        • Wagai Health Center
        • Contact:
        • Principal Investigator:
          • Richard Omore, PhD
  • Malawi
      • Blantyre, Malawi
        • Recruiting
        • Ndirande Health Centre
        • Contact:
        • Principal Investigator:
          • Khuzwayo Jere, PhD
        • Principal Investigator:
          • Jennifer Cornick, PhD
        • Principal Investigator:
          • Nigel Cunliffe, PhD
  • Mali
      • Bamako, Mali
        • Recruiting
        • Asacodjeneka Cscom
        • Principal Investigator:
          • Samba Sow, MD
        • Contact:
        • Principal Investigator:
          • Karen Kotloff, MD
      • Bamako, Mali
        • Recruiting
        • Asacodjip Cscom
        • Principal Investigator:
          • Samba Sow, MD
        • Contact:
        • Principal Investigator:
          • Karen Kotloff, MD
      • Bamako, Mali
        • Recruiting
        • Banconi CSCOM (ASACOBA)
        • Principal Investigator:
          • Samba Sow, MD
        • Contact:
        • Principal Investigator:
          • Karen Kotloff, MD
      • Bamako, Mali
        • Recruiting
        • CSREF Commune 1
        • Principal Investigator:
          • Samba Sow, MD
        • Contact:
        • Principal Investigator:
          • Karen Kotloff, MD
  • Pakistan
      • Karachi, Pakistan
        • Recruiting
        • Abbasi Shaheed Hospital
        • Contact:
        • Principal Investigator:
          • Farah Qamar, MBBS
      • Karachi, Pakistan
        • Recruiting
        • Ali Akbar Shah Center
        • Contact:
        • Principal Investigator:
          • Farah Qamar, MBBS
      • Karachi, Pakistan
        • Recruiting
        • Bhains colony AKU site
        • Contact:
        • Principal Investigator:
          • Farah Qamar, MBBS
      • Karachi, Pakistan
        • Recruiting
        • Khidmat e Alam Medical Centre
        • Contact:
        • Principal Investigator:
          • Farah Qamar, MBBS
      • Karachi, Pakistan
        • Recruiting
        • Sindh Government Hospital, Ibrahim Hyderi
        • Contact:
        • Principal Investigator:
          • Farah Qamar, MBBS
      • Karachi, Pakistan
        • Recruiting
        • Sindh Government Hospital, Korangi
        • Contact:
        • Principal Investigator:
          • Farah Qamar, MBBS
  • Peru
    • Maynas
      • Iquitos, Maynas, Peru
        • Recruiting
        • America Health Post
        • Contact:
        • Principal Investigator:
          • Maribel Paredes Olortegui, MPH
        • Principal Investigator:
          • Margaret Kosek, MD
      • Iquitos, Maynas, Peru
        • Recruiting
        • Hospital de Apoloyo
        • Contact:
        • Principal Investigator:
          • Maribel Paredes Olortegui, MPH
        • Principal Investigator:
          • Margaret Kosek, MD
      • Iquitos, Maynas, Peru
        • Recruiting
        • Modelo Health Post
        • Contact:
        • Principal Investigator:
          • Maribel Paredes Olortegui, MPH
        • Principal Investigator:
          • Margaret Kosek, MD
      • Iquitos, Maynas, Peru
        • Recruiting
        • Progreso Health Post
        • Contact:
        • Principal Investigator:
          • Maribel Paredes Olortegui, MPH
        • Principal Investigator:
          • Margaret Kosek, MD
      • Iquitos, Maynas, Peru
        • Recruiting
        • San Juan Health Post
        • Contact:
        • Principal Investigator:
          • Maribel Paredes Olortegui, MPH
        • Principal Investigator:
          • Margaret Kosek, MD
      • Iquitos, Maynas, Peru
        • Recruiting
        • Santo Tomas Health Post
        • Contact:
        • Principal Investigator:
          • Maribel Paredes Olortegui, MPH
        • Principal Investigator:
          • Margaret Kosek, MD

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

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.

Description

Inclusion Criteria:

  1. Child is 6-35 months of age
  2. Primary caregiver and child plan to remain at their current residence for at least the next 4 months
  3. 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
  4. 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
  5. Child resides within the pre-defined study area
  6. Fewer than 4 hours have passed since the child presented to a health facility

  7. Diarrhea episode is:

    • Acute (onset within 7 days of study enrollment) and
    • Represents a new episode (onset after at least 2 diarrhea-free days)
  8. Caregiver is willing to have child participate in follow-up visits at week 4 and month 3
  9. Willingness to have samples collected from the child (rectal swabs at enrollment)
  10. Site enrollment cap has not been met
  11. 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

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 (Estimated)

December 25, 2024

Study Completion (Estimated)

May 31, 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)

November 7, 2023

Last Update Submitted That Met QC Criteria

November 2, 2023

Last Verified

November 1, 2023

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

No

Studies a U.S. FDA-regulated device product

No

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.

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