Condition category
Infections and Infestations
Date applied
10/10/2016
Date assigned
20/10/2016
Last edited
05/07/2017
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Enteric fever is a generalised illness which can cause a variety of symptoms including fever, tiredness, headache, stomach pain, diarrhoea and constipation due to infection with certain types of bacteria (for example, Salmonella). These bacteria are passed between humans and infection occurs after ingesting them in contaminated food or water. In certain parts of the world where enteric fever is common, there are many other illnesses that can cause similar symptoms. Finding out to what degree enteric fever affects a population is important, as this information is needed to determine how and when to use prevention methods, including vaccines. For enteric fever, this is made more complicated as many people don't come to hospital when they are sick or only have a mild illness. Some people can also carry the bacteria for a long period of time without becoming sick at all. Identifying these individuals is likely to be important for reducing the amount of enteric fever in these areas. The overall aim of this study is to collect together information needed to determine how a vaccine may help in controlling enteric fever.

Who can participate?
Participants who live in specific study areas with known high levels of enteric fever cases, irrespective of age or sex.

What does the study involve?
This study involves running a number of population surveys and surveillance studies, collecting, for example, general information on households (age and gender of people in households and also relationships), information on the usage of healthcare facilities (such as water sanitation and hygiene services), information on cases of enteric fever reported by healthcare centres and immunity testing for antigens that cause enteric fever.

What are the possible benefits and risks of participating?
There are no immediate benefits to taking part in the study, although it is believed that these studies will help researchers to understand how to prevent the disease and therefore reduce the number of cases that occur. There are no risks to taking part.

Where is the study run from?
The study is run from Oxford University in the United Kingdom. Recruitment to the study and the census areas of interest are located in Malawi in Africa and Nepal and Bangladesh in South Asia.

When is the study starting and how long is it expected to run for?
June 2015 to January 2019

Who is funding the study?
1. Wellcome Trust
2. Bill and Melinda Gates Foundation

Who is the main contact?
1. Prof. Andrew J Pollard (scientific)
2. Ms Susan Tonks (public)

Trial website

Contact information

Type

Scientific

Primary contact

Prof Andrew Pollard

ORCID ID

Contact details

University of Oxford
Room 02-46-07
Childrens Hospital
John Radcliffe
Oxford
OX3 9DU
United Kingdom

Type

Public

Additional contact

Ms Susan Tonks

ORCID ID

Contact details

Centre for Clinical Vaccinology and Tropical Medicine
Churchill Hospital
Old Road
Headington
Oxford
OX3 7LE
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

OVG 2015/04

Study information

Scientific title

Prospective, epidemiological, clinical and laboratory programme to plan and evaluate strategies to control enteric fever in different settings in Africa and Asia

Acronym

STRATAA: STRAtegic Typhoid alliance across Africa and Asia

Study hypothesis

The overall aim of this research is to provide the science to underpin the implementation of new vaccines for the control of invasive Salmonella diseases in different epidemiological settings in Africa and Asia by:
1. Providing missing data on disease burden, antibiotic resistance and transmission needed to support and implement conjugate vaccines for enteric fever and NTS, using epidemiological data collection and application of knowledge from typhoid and paratyphoid human challenge models
2. Establishing the host-factors that determine susceptibility to enteric fever and NTS, to inform vaccine implementation strategies
3. Providing a comprehensive approach to diagnostics to allow a more accurate assessment of disease burden, vaccine impact and to inform epidemiological models
4. Investigating the mechanisms of natural and vaccine-induced protection in human challenge models (UK), test in human-to-mouse studies, and validate in field settings (Nepal, Bangladesh and Malawi) and to develop correlates of protection to drive vaccine implementation
5. Model disease dynamics and the balance between direct and indirect vaccine impact in different settings using the biological and epidemiological data emerging from the programme
6. Strengthen research capacity in enteric fever endemic regions of the world and provide the data for vaccine implementation advocacy

The study will employ field sites with different patterns of disease, co-morbidities, force of infection, transmission and carriage and integrate expertise from different scientific disciplines to provide the essential data required to achieve a measurable impact on disease through introduction of conjugate typhoid vaccines.

Ethics approval

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

Study design

Prospective epidemiological clinical and laboratory programme

Primary study design

Observational

Secondary study design

Cohort study

Trial setting

Community

Trial type

Diagnostic

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

Enteric fever

Intervention


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 will collect further clinical information from index cases at day 8 and, with addition of further samples, at months 1, 6 and in some cases 12 months at the relevant health care facility.

4. Population serosurveillance study including ~10,000 individuals at each census site selected by age-stratification, to look for subclinical and/or background immunising exposure to typhoidal Salmonella antigens in addition to identifying recent exposure and chronic carriers. Members of the research teams will collect blood samples from consenting participants. Serological assays for (immunoglobulin G) antibody to typhoid Virulence factor (Vi) will be performed on all samples; if raised this antibody can be used as an indicator of chronic typhoid carriage. Those with ‘high’ titres will have further blood and stool samples collected 6 and 12 months after the initial visit.

5. Household contact tracing of individuals presenting in the passive surveillance study (index cases) and identified as being chronic carriers in the serosurveillance study. Researchers will visit ≥73 households of cases identified by passive surveillance to enrol members as household contacts. Following consent procedures, blood and stool samples will be collected at the first visit and 1 month later. If a participant is found to have elevated anti-Vi IgG antibody levels, two further stool samples (collected at least 48 hours apart) will be collected at a six 6 month visit and the participant will be treated according to local and national guidelines. Further stool samples will be collected at 12 months to ensure treatment has been successful. Household contacts of suspected chronic carriers, identified during the serosurvey, will be approached by researchers (in an opportunistic sampling strategy) at the six-month follow-up visit to the household. Blood and stool samples will be collected with individual consent. No attempts will be made to carry out repeat visits to contact members of the household not present at the initial visit.

Intervention type

Other

Phase

Drug names

Primary outcome measures

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 measures

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

Overall trial start date

22/06/2015

Overall trial end date

01/01/2019

Reason abandoned

Eligibility

Participant 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.

Participant type

All

Age group

All

Gender

Both

Target number of participants

Census: 100,000 at 3 sites. Other surveys (passive surveillance, WASH, HUS, serosurvey and contact tracing) performed within this.

Participant 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)

Recruitment start date

29/05/2016

Recruitment end date

01/11/2018

Locations

Countries of recruitment

Bangladesh, Malawi, Nepal

Trial participating centre

International Centre for Diarrhoea Research, Bangladesh
68, ShaheedTajuddin Ahmed Sarani Mohakhali
Dhaka
1212
Bangladesh

Trial participating centre

Malawi-Liverpool-Wellcome Trust
Queen Elizabeth Central Hospital College of Medicine P.O. Box 30096 Chichiri
Blantyre
3
Malawi

Trial participating centre

Oxford University Clinical Research Unit - Nepal
Patan Academy of Health Sciences Lagankhel
Lalitpur
26500
Nepal

Sponsor information

Organisation

University of Oxford

Sponsor details

Clinical Trials and Research Governance
Joint Research Office
Block 60
Churchill Hospital
Oxford
OX3 7LJ
United Kingdom

Sponsor type

University/education

Website

https://www.admin.ox.ac.uk/researchsupport/ctrg/

Organisation

International Centre for Diarhoea and Diarrhoeal Research, Bangladesh

Sponsor details

68
ShaheedTajuddin Ahmed Sarani
Mohakhali
Dhaka
1212
Bangladesh

Sponsor type

Research organisation

Website

http://www.icddrb.org

Organisation

Unviersity of Liverpool

Sponsor details

Research Support Office
2nd Floor Block D Waterhouse Building
3 Brownlow street
Liverpool
L69 3GL
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Charity

Funder name

Wellcome Trust

Alternative name(s)

Wellcome

Funding Body Type

private sector organisation

Funding Body Subtype

international

Location

United Kingdom

Funder name

Bill and Melinda Gates Foundation

Alternative name(s)

Bill & Melinda Gates Foundation

Funding Body Type

private sector organisation

Funding Body Subtype

foundation

Location

United States of America

Results and Publications

Publication and dissemination plan

Intention to publish date

01/01/2020

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

2017 protocol in: https://www.ncbi.nlm.nih.gov/pubmed/28674145

Publication citations

Additional files

Editorial Notes

05/07/2017: Publication reference added.