Clinical trial NCT04838587: An Epidemiological Surveillance Study to Determine the Incidence of ETEC in Children and Infants in Lusaka
Official title: An Epidemiological Surveillance Study to Determine the Incidence of ETEC in Children and Infants in Lusaka.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Diarrhea Toddlers
Escherichia Coli Diarrhea
Keywords: Incidence
Epidemiology
Lead sponsor: Centre for Infectious Disease Research in Zambia
Sponsor class: OTHER
Collaborators: name: European and Developing Countries Clinical Trials Partnership (EDCTP)
name: Scandinavian Biopharma AB
name: Göteborg University
First posted: 2021-04-09
Enrollment: 6828
Sex: ALL
Maximum age (years): 36
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: This study is a multi-site longitudinal observation study, to be conducted at Matero First Level Hospital, Chawama First Level Hospital, George Clinic, Kanyama First Level Hospital and Chainda clinic in Lusaka. The facilities are situated in a typical peri-urban settlement area of Lusaka and serves a community with a combined population of about 1 million. We assume that all sites have similar incidence of ETEC diarrhoea, therefore, each of the 5 sites will enroll 1350 children bringing our total sample size for the study to 6,750 participants.

Brief summary: Diarrhoea is the one of the top five leading causes of death among children below the age of five years, globally. It is estimated that one in ten deaths in children under five is attributed to diarrhoea. Enterotoxigenic E.coli (ETEC) is one of the major causative agents of moderate-to-severe (MSD) diarrhoea among children both globally and in Zambia.

The overall aim of this study is to document the burden of ETEC associated diarrhoea in Zambian children under 3 years of age.

Detailed description: This study seeks to determine diarrhoea aetiology, calculate the incidence of moderate-to-severe ETEC-associated diarrhea, and describe the frequency of ETEC colonization factors and enterotoxin types in children under 3 years old in Zambia.

These data are required for the design of an anticipated phase 3 trial of the leading ETEC vaccine (ETVAX®) that will be evaluated in Zambia from 2021 onwards.

The following are the research questions that this study seeks to answer:

1. What is the incidence of MSD with confirmed ETEC aetiology in children under three years old in Zambia?
2. What are the prevalent colonization toxins and factors (CFs) in diarrhoeagenic isolates of ETEC infections in children in Zambia?
3. What are the other common pathogens causing diarrhoea in Zambian children?

This prospective, observational, longitudinal study is proposed at five health facilities in Lusaka. The proposed study sites are Chawama, George, Kanyama, Chainda, and Matero Health Facilities. These facilities are located within typical peri-urban settlements of Lusaka and serves communities with a cumulative total population of over 1 million people. The study will be done in two stages beginning with a household census in the study catchment area of the participating health facilities and then followed by the passive diarrhoea surveillance stage. A surveillance system for passive case detection of diarrhoea will be set up at each facility for the 12-months of the project to detect any seasonal variations of disease burden. Prior to commencement, several community sensitization activities will be conducted within the catchment areas of the health facility.

A stool sample will be collected from each participant who presents to the health facility and is eligible for enrollment. All research samples will be collected at the study site and laboratory assays will be performed as per written SOPs and will be a part of the study documentation. All the samples will be processed in Zambia using the Novodiag® platform. The Novodiag® (Mobidiag Ltd, Finland) is a novel multiplex molecular platform that is based on real-time PCR and microarray technology and can identify various gastroenteritis causing bacteria, parasites and viruses as well as carry out antimicrobial resistance gene testing of organisms.

Eligibility criteria: Inclusion Criteria:

* A child \< 36 months old at the time of enrolment.
* A child presenting with diarrhoea (i.e. \> 3 episodes of looser than normal stools in 24 hours) at a health facility within the study catchment area and in possession of a study ID number.
* Parents of eligible children, able to understand the study information and give informed consent by signature or thumbprint. (NB. illiterate participants will be able to give consent in the presence of an impartial witness)
* Children living within the study catchment area served by each participating health facility and in possession of a study ID number
* The parent/s who is willing to comply with all stipulated study procedures.
* Parents who are willing to allow their child to submit a stool sample for testing.

Exclusion Criteria:

* Children presenting to the health facility without a study ID number
* Any child born after the Census has taken place
* Any child currently participating in the OEV124 study

Primary outcomes:
measure: Incidence of MSD ETEC diarrhoea in Zambia.
timeFrame: 12 months
Secondary outcomes:
measure: Virulence factors of ETEC isolates
timeFrame: 12 months
measure: The common pathogens causing MSD in children less than 3 years
timeFrame: 12 months
measure: Seasonality of ETEC diarrhoea
timeFrame: 12 months
measure: Antimicrobial resistance pattern of ETEC
timeFrame: 12 months
Other outcomes:
Locations:
city: Lusaka
country: Zambia
facility: Chawama First level hospital
city: Lusaka
country: Zambia
facility: George Clinic
city: Lusaka
country: Zambia
facility: Kanyama First Level Hospital
city: Lusaka
country: Zambia
facility: Matero Clinical Research Site, Chainda South CRS
Study officials:
affiliation: Centre for Infectious Disease Research in Zambia
name: Roma Chilengi, MBChB
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre for Infectious Disease Research in Zambia
name: Monde Muyoyeta, MBChB
role: PRINCIPAL_INVESTIGATOR
References: