Condition category
Infections and Infestations
Date applied
26/03/2020
Date assigned
06/05/2020
Last edited
25/06/2020
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Enteric fever forms a significant portion of the burden of infectious diseases in developing countries. Caused by Salmonella species (bacteria), it is transmitted through the consumption of food or water contaminated by the excrement of individuals carrying these organisms. Those infected, display symptoms such as fever, weakness, stomach pains, diarrhea or constipation, and rashes. Enteric fever may even be fatal, if left untreated.
In India, this disease still poses a major health risk to the public. Planning measures for its control requires reliable, India-specific epidemiological data on the disease, which is currently lacking. The current study will help fill in such knowledge gaps by estimating the incidence rate and burden of enteric fever occurring at secondary care hospitals in 6 sites across India, over a 24 month period.

Who can participate?
Any patient that has been hospitalized at a healthcare facility involved with the study, who has a fever, and is greater than 6 months of age, irrespective of their gender, may participate. Patients at the study associated healthcare facilities hospitalized with non-traumatic ileal perforations may also participate.

What does the study involve?
At each study hospital. hospitalized patients (> 6 months of age) with a fever or non-traumatic ileal perforations are asked to participate. All participants receive a blood culture. Those whose culture tests positive for either S, Typhi or S. Paratyphi (enteric fever positive) as well as those with ileal perforations, are followed up until the 30th day after their study enrollment to record details such as their treatment, costs and outcomes. The total enteric fever cases that are encountered at each site is then used to calculate the site-specific incidence of the disease. Such surveillance activities will go on for 2 years.
A survey is conducted within clearly demarcated areas at each site. Socio-demographic data as well as details about illnesses/deaths that have occurred in the surveyed households are collected. This survey will be used to calculate the proportion of those patients who require hospitalization and have a fever but choose non-study hospitals for admission which will in turn be used to adjust the incidence rates for each site.

What are the possible risks and benefits of participating?
The participants will not receive any immediate benefit by taking part in this study. However, the results of this study may help policymakers and researchers better understand how enteric fever can be controlled and therefore lead to its reduction. The participants face no risks by taking part.

Where is the study run from?
1. Rural Development Trust Hospital, Bathalapalli, Andhra Pradesh (India)
2. Post Graduate Institute of Medical Education and Research, Chandigarh (India)
3. Lady Willingdon Hospital, Manali (India)
4. Makunda Christian Leprosy and General Hospital, Bazaricherra (India)
5. Chinchpada Christian Hospital, Navapur (India)
6. Duncan Hospital, Raxaul (India)

When is the study starting and how long is it expected to run for?
February 2018 to April 2020 (updated 25/06/2020, previously: May 2020)

Who is funding the study?
Bill and Melinda Gates Foundation (USA)

Who is the main contact?
Dr Jacob John
jacob@nssefi.org

Trial website

Contact information

Type

Public

Primary contact

Dr Jacob John

ORCID ID

Contact details

Community Health Training Center
Department of Community Health and Development
Christian Medical College
Bagayam
Vellore
632002
India
+91 9442631628
jacob@nssefi.org

Type

Scientific

Additional contact

Dr Jacob John

ORCID ID

Contact details

Community Health Training Center
Department of Community Health and Development
Christian Medical College
Bagayam
Vellore
632002
India
+91 9442631628
jacob@nssefi.org

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

Tier2v211072019

Study information

Scientific title

Surveillance for Enteric Fever in India (SEFI), tier 2 - a hybrid surveillance approach to estimate the burden and incidence of enteric (typhoid) fever in India

Acronym

SEFI

Study hypothesis

This study aims to estimate the incidence and burden of severe enteric fever in six different settings across India. Such data will enable policymakers to plan suitable control measures against the disease in the country.

Ethics approval

1. Approved 06/12/2017, Postgraduate Institute of Medical Education and Research Institutional Ethics Committee (Room number 6006, 6th floor, Research block B, Post Graduate Institute of Medical Education and Research, Sector 12, Chandigarh, India, 160012; +91 172 2755266; iecpgi@gmail.com), ref: PGI/IEC/2018/000017
2. Approved 15/12/2017, Rural Development Trust Hospital Institutional Ethics Committee (Rural Development Trust Hospital, Bathalapalli, Anantapur, Andhra Pradesh, India, 515661;+91 9177155517; hariharanadha.sarma@gmail.com), ref: RDTHBTP/CERT/ETHICS/2018/002
3. Approved 09/03/2018, Lady Willingdon Hospital Institutional Review Board (Manali, Himachal Pradesh, India, 175131; +91 9816033110; philalex1@gmail.com), ref: LWH/IRB/CL/2018/01
4. Approved 17/11/2017, Emmanuel Hospital Association Institutional Ethics Committee (Emmanuel Hospital Association, 808/92, Deepali Building, Nehru Place, New Delhi, India, 110019; +91 8527747395; jameelageorge@eha-health.org), ref: Protocol Number - 170, Version 2; Protocol number – 168, Version 2; Protocol Number 173, Version 2

Study design

Prospective observational multi-center hybrid surveillance study

Primary study design

Observational

Secondary study design

Hybrid model - hospital based disease surveillance paired with a community based healthcare utilization survey

Trial setting

Hospitals

Trial type

Screening

Patient information sheet

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

Condition

Enteric fever

Intervention

The site-specific incidence of enteric fever will be estimated through a hybrid approach - hospital-based surveillance combined with a healthcare utilization survey. Surveillance for enteric fever will be carried out at the designated hospital in each of the six chosen sites, which are the preferred healthcare facilities among their catchment area populations for providing inpatient care for febrile illnesses. All febrile hospitalizations and non-traumatic ileal perforations that occur at these facilities are recruited into the study after collecting informed consent from the patient/patient's parents or guardian. Next, a blood culture is performed and all those recruited patients with a culture positive for either S. Typhi or S. Paratyphi, as well as those who present with a non-traumatic ileal perforation, are followed up until the 30th day after enrollment to document treatment received, costs incurred, and outcome at discharge.

A healthcare utilization study is also carried out in a clearly demarcated catchment area for each of the study hospitals in order to estimate the proportion of febrile patients seeking inpatient care at non-study hospitals. This survey collects data such as socio-demographic characteristics, illness in the past two weeks, and details of hospitalizations and deaths based on a 12-month recall, from approximately 5,000 households (25,000 individuals) in each site's catchment area, via a questionnaire.

Intervention type

Other

Phase

Drug names

Primary outcome measure

Incidence of enteric fever in each of the study sites over the 24 months of surveillance measured by dividing the number of blood culture-confirmed enteric fever cases with the product of the hospital's catchment population and time period of surveillance. This crude incidence shall then be adjusted for the proportion of febrile patients from the catchment population seeking inpatient healthcare at other facilities, compliance to the study protocol, the sensitivity of blood culture and the probability of enteric fever patients being hospitalized.

Secondary outcome measures

1. Characterization of the clinical spectrum of enteric fever presenting at smaller (<350 beds) hospitals over the 24 months of surveillance- determined through estimating the prevalence of enteric fever among those hospitalized with a febrile illness, the prevalence of complications and severe disease among those presenting to surveillance facilities with enteric fever, and prevalence of antimicrobial resistance among S. Typhi/S. Paratyphi isolates
2. Estimates of the cost of treatment and productivity loss associated with a severe enteric fever over the 24 month period of surveillance- determined through calculating direct and indirect cost-of-illness for severe enteric fever and indebtedness directly attributable to the severe enteric fever illness episodes

Overall trial start date

25/04/2017

Overall trial end date

22/04/2020

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

For the hospital-based surveillance:
1. Age: greater than six months of age
2. Gender: Both
3. Patients presenting with fever who are hospitalized irrespective of the duration of fever or temperature
4. Patients with non-traumatic ileal perforation irrespective of history of fever or culture confirmation of typhoid

For the healthcare utilization survey:
1. All those who normally reside and are present in the household during the entire period of survey – from the first day of survey to the last day of survey (both days inclusive).
2. All those who were known to be normally residing and had actually stayed in the household during a part of the survey (from the first day of survey to the last day of survey) but were not present at the time of visit of the interviewer.
3. All those who were known to be normally residing in the household and were not present at the time of visit of the enumerator but are expected to return by the last day of survey.
4. Age: all
5. Gender: both

Participant type

Patient

Age group

Mixed

Gender

Both

Target number of participants

150,000

Participant exclusion criteria

For the hospital-based surveillance:
1. Patients who are not Indian citizens

For the healthcare utilization survey:
1. Visitors to the household

Recruitment start date

26/02/2018

Recruitment end date

07/04/2020

Locations

Countries of recruitment

India

Trial participating centre

Rural Development Trust Hospital
Kadiri Road Anantapuramu district
Bathalapalli
515661
India

Trial participating centre

Post Graduate Institute of Medical Education and Research
Sector-12
Chandigarh
160012
India

Trial participating centre

Lady Willingdon Hospital
Kullu district
Manali
175131
India

Trial participating centre

Makunda Christian Leprosy and General Hospital
Karimganj District
Bazaricherra
788727
India

Trial participating centre

Chinchpada Christian Hospital
Chinchapads Nandurbar District
Taluka Navapur
425417
India

Trial participating centre

Duncan Hospital
East Champaran District
Raxaul
845305
India

Sponsor information

Organisation

Vellore Christian Medical College Foundation

Sponsor details

Ida Scudder Road
Vellore
632004
India
+91 04162282052
wellcome@cmcvellore.ac.in

Sponsor type

University/education

Website

https://www.vellorecmc.org/

Funders

Funder type

Charity

Funder name

Bill and Melinda Gates Foundation

Alternative name(s)

बिल एंड मिलिंडा गेट्स फाउंडेशन, Bill & Melinda Gates Foundation, Gates Foundation, 比尔及梅琳达·盖茨基金会, BMGF, B&MGF

Funding Body Type

private sector organisation

Funding Body Subtype

Trusts, charities, foundations (both public and private)

Location

United States of America

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer-reviewed journal.

IPD sharing statement:
The datasets generated during and/or analysed during the current study are available from the corresponding author, Dr Jacob John (jacob@nssefi.org), 6 months after the final participant is enrolled into the study. Any requesting party with an analysis plan for the data will be given access. Data analysed as part of the primary results paper shall be made available along with the publication. All data shall be anonymized prior to analysis/sharing. Consent is obtained from all participants.

Intention to publish date

01/09/2020

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

25/06/2020: The following changes were made to the trial record: 1. The overall end date was changed from 17/05/2020 to 22/04/2020. 2. The recruitment end date was changed from 10/05/2020 to 07/04/2020. 3. The plain English summary was updated to reflect these changes. 07/04/2020: Trial’s existence confirmed by Lady Willingdon Hospital Institutional Review Board.