Vellore Typhoid Vaccine Impact Trial

Study Overview
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Brief Summary
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This cluster randomised trial will examine the impact of introducing TyphiBEV, a typhoid conjugate vaccine licensed in India, on the incidence of typhoid fever in a high burden urban setting in South India.

Detailed Description
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TyphiBEV®, a typhoid conjugate vaccine from Biological E, has been licensed by the Central Drugs Standard Control Organaisation in India based on immunogenicity and safety data. A similar typhoid conjugate vaccine has been demonstrated in large clinical trials to provide 80% vaccine efficacy in Nepal and Bangladesh. The TyphiBEV® has not been similarly evaluated. The demonstration of the impact of a city-scale typhoid conjugate vaccine introduction on the burden of typhoid will aid policy decisions on the use of typhoid conjugate vaccines in the national immunisation program. After written informed consent, the investigators will establish stimulated passive surveillance in 72,000 individuals between 1 and 30 years of age within the Vellore Demographic Surveillance System to determine the incidence of blood-culture confirmed typhoid fever. Thirty-six thousand surveillance participants between 1 year and 30 years residing in the 30 clusters (areas) randomised to receive the vaccine will receive the vaccine at the beginning of the trial. Those in other areas will receive the same at the end of two years. Using a stimulated passive surveillance approach, those with acute febrile illness will be encouraged to visit study surveillance hospitals. Participants will be evaluated for blood-culture confirmed typhoid fever if they are eligible. The incidence of typhoid among those living in areas assigned to vaccination compared to those whose residence is in areas not designated for vaccination will be used to calculate the impact of the vaccine on disease burden.

Official Title
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Vellore Typhoid Vaccine Impact Trial

Conditions
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Typhoid Fever

Intervention / Treatment
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* Biological: Typhoid conjugate Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Consent For adults, 18 years and over - they must be willing and competent to provide informed consent For those aged under 18 years, the parent/guardian is willing and competent to provide informed consent, and if the participant is 11 to 18 years of age, informed assent will also be sought, Age: Between 1 and 30 years (i.e., up to 29 years 364 days) at time of recruitment into the surveillance Currently living within the study catchment area with no plans to leave the study area in the next 24 months Exclusion Criteria: For fever surveillance o Medical reasons that prevent the participant from complying with study requirements including follow up and testing during illness For vaccination Has received a typhoid vaccine in the previous three years Is known to have an allergy to any vaccine component Nursing mothers, Pregnancy or planning pregnancy around vaccination Receipt of any other vaccine in the past 30 days (temporary exclusion) Febrile illness in the 24 hours before vaccination (temporary exclusion)

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vaccinated arm<br>Typhoid Conjugate Vaccine (TyphiBEV) 0.5 ml as a single dose given intramuscularly to consenting, eligible residents of vaccine clusters | Biological: Typhoid conjugate Vaccine<br>* TyphiBEV is a clear colourless monovalent vaccine containing 25 µg of Typhoid Vi polysaccharide manufactured using the Citrobacter freundii sensu lato3056 (Vi) and is conjugated to CRM 197 as a carrier protein. Sodium chloride and Phosphate buffer are used as a buffering agent in the vaccine formulation with 2-Phenoxyethanol as a preservative.<br>* Other names: TyphiBEV;|
| No Intervention: Control arm<br>No vaccination in the control clusters | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total effect | Number of blood culture confirmed typhoid fever episodes in vaccinated participants from vaccine clusters compared to the number of blood culture confirmed typhoid fever episodes in unvaccinated participants from non-vaccine clusters | at 24 months of follow up beginning 28 days after vaccine introduction in vaccine clusters. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall effect | The number of blood culture confirmed typhoid fever episodes in participants from vaccine clusters compared to the number of blood culture confirmed typhoid fever episodes in participants from non-vaccine clusters | at 24 months of follow up beginning 28 days after vaccine introduction in vaccine clusters. | 
| Effect in children 1 to 14 years | The number of blood culture confirmed typhoid fever episodes in vaccinated children between 1 year and 14 years and 364 days from vaccine clusters compared to the number of blood culture confirmed typhoid fever episodes in unvaccinated children between 1 year and 14 years and 364 days from non-vaccine clusters | at 24 months of follow up beginning 28 days after vaccine introduction in vaccine clusters. | 
| Effect on all febrile illness requiring healthcare visits | The number of febrile illness episodes where healthcare is sought among vaccinated participants from vaccine clusters compared to unvaccinated participants from non-vaccine clusters | at 24 months of follow up beginning 28 days after vaccine introduction in vaccine clusters. | 
| Safety outcomes | The number and description of solicited and non-solicited adverse events reported within the first seven days after vaccination in the safety subset of vaccine recipients | Seven days after vaccine receipt | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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typhoid conjugate vaccine, cluster randomised trial, Enteric Fever