Understanding the burden of enteric fever in Africa and Asia: a study of transmission and antibiotic resistance to improve diagnostics and inform vaccine strategies

• Register: ISRCTN
• Last refreshed on: 21 February 2022
• Main ID: ISRCTN12131979
• Date of registration: 20/10/2016
• Prospective Registration: No
• Primary sponsor: University of Oxford
• Public title: Understanding the burden of enteric fever in Africa and Asia: a study of transmission and antibiotic resistance to improve diagnostics and inform vaccine strategies
• Scientific title: Prospective, epidemiological, clinical and laboratory programme to plan and evaluate strategies to control enteric fever in different settings in Africa and Asia
• Date of first enrolment: 29/05/2016
• Target sample size: 100000
• Recruitment status: Completed
• URL: https://www.isrctn.com/ISRCTN12131979
• Study type: Observational
• Study design: Prospective epidemiological clinical and laboratory programme (Diagnostic)
• Phase: Not Applicable

Countries of recruitment

Bangladesh, Malawi, Nepal

Contacts

• Name: Andrew Pollard

• Name: Sarah Kelly

Key inclusion & exclusion criteria

Inclusion criteria:
Census study, WASH and HUS survey:
Census participants will be the population (n =100,000, all ages) residing in a demarcated geographic area that is a known catchment population for each of the 3 typhoid surveillance sites. Participants will be recruited and consented as households.
1. Head of household / key informant is willing and competent to give informed consent for participation of the household in the study
2. Head of household / key informant is Male or Female, aged 18 years or above
3. Household is within the census area

Passive surveillance:
This component will include all patients presenting at any of the clinical surveillance sites in each country with a history of subjective fever >72 hours with or without objective fever on presentation.
1. Individual willing and competent to give informed consent if =18 years or the parent/legal guardian if participant <18 years;
2. Able to comply with study requirements
3. In addition those considered index cases (for the household contact component) must be resident in a household enrolled in the census survey

Household contacts (index cases):
From each site at least 73 households with index cases identified by the hospital surveillance component will be visited and all individual members of the household enrolled for the household contact study.
(Resident in same household as index case (identified from passive surveillance study) in whom enteric fever has been confirmed by a positive blood culture for S. Typhi or S. Paratyphi;
1. Individual willing and competent to give informed consent if =18 years or the parent/legal guardian if participant <18 years
2. Able to comply with study requirements

Serosurveillance:
Individual, age stratified participants (0-4 years, 5-9 years, 10-14 years >14 years) will be randomly selected from the census population.
1. Individual willing and competent to give informed consent if =18 years or the parent/legal guardian if participant <18 years
2. Male or female
3. Able to comply with study requirements
4. Resident in census area

Household contacts (of suspected chronic carriers identified in serosurvey):
Individuals resident in 50 households of suspected chronic carriers will be approached to request blood and stool samples in order to assess risk of infection in this group.
1. Resident in the same household as suspected chronic carrier identified in the serosurvey;
2. Individual willing and competent to give informed consent if =18 years or the parent/legal guardian if participant <18 years;
3. Able to comply with study requirements.

Exclusion criteria:
Census study, WASH and HUS survey:
1. Head of household/key informant not willing for household to participate
2. Unable to identify Head of household/key informant

Passive surveillance:
1. Previous enrolment into this component (e.g. from previous attendance at healthcare facility with persistent fever)
2. Other underlying disease which can be rapidly diagnosed such as Malaria in children (Blantyre)

Household contacts (index cases):
1. Not a resident of household of index case at time of his/her primary illness
2. Fever at presentation in index case confirmed not due to S. Typhi or Paratyphi fever
3. Deemed clinically unsuitable by the survey team (e.g. terminally ill)

Serosurveillance:
1. Not resident in the census area
2. Deemed clinically unsuitable by the survey team (e.g. terminally ill)

Household contacts (of suspected chronic carriers identified in serosurvey):
1. Not a resident of household of suspected chronic carrier at time of the visit
2. Deemed clinically unsuitable by the survey team (e.g. terminally ill)


Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Enteric fever
Infections and Infestations

Intervention(s)

?1. A population census of ~100,000 individuals to establish baseline demographic data on a per household basis; to be updated at regular intervals with migration, births and deaths during the study period. Approximately 20,000 households at each site will be visited by study staff and consent sought from the head of the household or key informant. With their assistance a brief questionnaire will be completed by researchers to provide data such as age, sex and relationship structure of those resident within the household.

2. Water sanitation and hygiene (WASH) and healthcare utilisation (HUS) surveys in households included in the census. Study staff will gather information from the consenting head/key informant of >700 randomly selected households from within the site census area. This will include data describing the actual and hypothetical usage of healthcare facilities for febrile illness episodes.

3. Passive surveillance performed at serving healthcare centres for cases of febrile illness and identification of culture-positive enteric fever illness. All individuals presenting at local health care facilities serving the census populations with a history of fever >72 hours will be eligible. Census identifier and screening information, including area of residence and clinical symptoms will be recorded following consent. Blood, stool, and other clinical samples will be collected for confirmation of diagnosis and development of diagnostic and serosurveillance tools. Patients with blood culture confirmed invasive Salmonella disease (S. Typhi, S. Paratyphi A or Non-Typhoidal Salmonellae) whose household is included in the census will be considered as index cases for further investigation (see 5, below). Research teams wil

Primary Outcome(s)

The burden of enteric fever (typhoid and paratyphoid) in Africa and Asia, within the census populations, over a 2-year observation period, as determined by:
1. The number of new cases confirmed by blood culture
2. The rate of carriage per 1000 head of population
3. The infection rate amongst household contacts of confirmed cases

Secondary Outcome(s)

Antibody detection rates per 1000 head of population during the 2-year observation period to determine:
1. Rate of chronic carriage
2. Incidence of non-clinical typhoid
3. Rates of infection arising from close contact with confirmed enteric fever and chronic carriers

Secondary ID(s)

OVG 2015/04

Source(s) of Monetary Support

Wellcome Trust, Bill and Melinda Gates Foundation

Secondary Sponsor(s)

International Centre for Diarhoea and Diarrhoeal Research, Bangladesh

Unviersity of Liverpool

Ethics review

Status:
Approval date:
Contact:

1. Oxford, United Kingdom: Tropical Research Ethics Committee, 13/10/2015, ref: 39-15 2. Dhaka, Bangladesh: icddr,b Research Review Committee, 23/02/2016, ref: PR-15119 3. Blantyre, Malawi: National Health Sciences Research Committee, 19/05/2016, ref: 15/5/1599 4. Patan, Nepal: Nepal Health Research Council, 20/01/2016, ref: 306/2015

Results

• Results available: Yes
• Date Completed: 31/12/2020