Clinical trial NCT06047821: Enterics for Global Health (EFGH)
Official title: The Incidence and Burden of Shigella Diarrhea in Children Aged 6-35 Months: the Enterics for Global Health (EFGH) - Shigella Burden Study
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Shigella
Child
Diarrhea
Keywords: Epidemiology
Shigella
Diarrhea
Children
Enterics
Vaccine
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: Aga Khan University
name: International Centre for Diarrhoeal Disease Research, Bangladesh
name: University of Maryland, Baltimore
name: University of Virginia
name: Asociacion Benefica Prisma
name: Medical Research Council Unit, The Gambia
name: Kenya Medical Research Institute
name: Center for Vaccine Development - Mali
name: Malawi-Liverpool-Wellcome Trust Clinical Research Programme
name: Bill and Melinda Gates Foundation
First posted: 2023-09-21
Enrollment: 9800
Sex: ALL
Minimum age (years): 6
Maximum age (years): 35
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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).

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.

Eligibility criteria: 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

Primary outcomes:
measure: Shigella incidence
timeFrame: At enrollment in the study (cross-sectional)
Secondary outcomes:
measure: Antimicrobial susceptibility
timeFrame: At enrollment in the study (cross-sectional)
measure: Cost per episode treated
timeFrame: 3 months
measure: Death
timeFrame: 3 months
measure: Hospitalization
timeFrame: 3 months
measure: Persistent diarrhea (index episode)
timeFrame: 3 months
measure: Diarrhea/dysentery recurrence
timeFrame: 3 months
measure: Change in linear growth
timeFrame: 3 months
Other outcomes:
Locations:
city: Dhaka
country: Bangladesh
facility: Dhaka Medical College Hospital
city: Dhaka
country: Bangladesh
facility: EFGH Field Clinic
city: Dhaka
country: Bangladesh
facility: icddr,b Dhaka Hospital
city: Dhaka
country: Bangladesh
facility: Mugda Medical College Hospital
city: Dhaka
country: Bangladesh
facility: Sir Salimullah Medical College Hospital
city: Basse Santa Su
country: Gambia
facility: Basse Hospital
state: Upper River Region
city: Basse Santa Su
country: Gambia
facility: Gambisara Health Centre (HC)
state: Upper River Region
city: Siaya
country: Kenya
facility: Abidha Health Center
city: Siaya
country: Kenya
facility: Akala Health Center
city: Siaya
country: Kenya
facility: Bar Agulu Health Center
city: Siaya
country: Kenya
facility: Dienya Health Centre
city: Siaya
country: Kenya
facility: Lwak Mission Hospital
city: Siaya
country: Kenya
facility: Ongielo Health Centre
city: Siaya
country: Kenya
facility: Siaya County Referral Hospital
city: Siaya
country: Kenya
facility: Ting Wangi Health Center
city: Siaya
country: Kenya
facility: Wagai Health Center
city: Blantyre
country: Malawi
facility: Ndirande Health Centre
city: Bamako
country: Mali
facility: Asacodjeneka Cscom
city: Bamako
country: Mali
facility: Asacodjip Cscom
city: Bamako
country: Mali
facility: Banconi CSCOM (ASACOBA)
city: Bamako
country: Mali
facility: CSREF Commune 1
city: Karachi
country: Pakistan
facility: Abbasi Shaheed Hospital
city: Karachi
country: Pakistan
facility: Ali Akbar Shah Center
city: Karachi
country: Pakistan
facility: Bhains colony AKU site
city: Karachi
country: Pakistan
facility: Khidmat e Alam Medical Centre
city: Karachi
country: Pakistan
facility: Sindh Government Hospital, Ibrahim Hyderi
city: Karachi
country: Pakistan
facility: Sindh Government Hospital, Korangi
city: Iquitos
country: Peru
facility: America Health Post
state: Maynas
city: Iquitos
country: Peru
facility: Hospital de Apoloyo
state: Maynas
city: Iquitos
country: Peru
facility: Modelo Health Post
state: Maynas
city: Iquitos
country: Peru
facility: Progreso Health Post
state: Maynas
city: Iquitos
country: Peru
facility: San Juan Health Post
state: Maynas
city: Iquitos
country: Peru
facility: Santo Tomas Health Post
state: Maynas
Study officials:
affiliation: University of Washington
name: Patricia B Pavlinac, PhD
role: PRINCIPAL_INVESTIGATOR
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