Effectiveness of a Typhoid Conjugate Vaccine in DRC

Study Overview
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Brief Summary
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This is a prospective cohort evaluation of vaccine effectiveness of a single dose of Typbar-TCV® against symptomatic blood culture-confirmed typhoid fever when administered through a mass vaccination campaign to children 9 months to <16 years of age in Kisantu, DRC.

Detailed Description
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This study is conducted in Kisantu, DRC and is comprised of a mass vaccination campaign of children aged 9 months to <16 years with a single dose of Typbar-TCV® and a concomitant surveillance study to assess the incidence of culture-confirmed typhoid fever in the population during a period of three years following vaccination. Safety events will be monitored for 30 minutes following vaccination for all participants. In a subset of age-eligible participants living in the study area, the investigators will assess local and systemic solicited adverse events/adverse reactions and unsolicited adverse events occurring within the first 7 days post-vaccination and unsolicited and serious adverse events within 28 days post-vaccination. A population census will be conducted at baseline to enumerate and characterize the population under study and demographic information will be collected to allow for minimization of potential sources of bias during analysis. An interim censuses and a census at study closure will be carried out to update population information. The investigators hypothesize that the Typbar-TCV® vaccine is effective in large scale vaccination campaigns, thereby lowering the incidence of blood-culture confirmed typhoid fever in children. Lessons and experiences on vaccination feasibility and uptake will be important for informing TCV introduction across the African continent.

Official Title
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An Open-label Effectiveness Study of a Typhoid Conjugate Vaccine in Kisantu, Democratic Republic of Congo (TyVECO) - Step 2: Typhoid Conjugate Vaccine (TCV) Mass-vaccination Campaign

Conditions
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Typhoid Fever

Intervention / Treatment
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* Biological: Vi-TT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Parent/guardian willing and able to provide informed consent; assent will be sought for participants between 12 and <16 years of age Resident of the defined study area, Kisantu Health Zone at the time of vaccination Age between 9 months and <16 years (i.e., ≤15 years and 364 days) on the day of vaccination Exclusion Criteria: The participant has a known allergy to any of the vaccine components, Any medical reason perceived to increase risk to health posed by vaccination as judged by a medical professional Self-reported pregnancy in females greater or equal to 11 years of age who have reported menarche

Ages Eligible for Study
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Minimum Age: 9 Months
Maximum Age: 15 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vi-TT<br>Single dose of Vi-TT to children 9 months to <16 years of age | Biological: Vi-TT<br>* Single dose of vaccine administered through a mass vaccine campaign to children between 9 months and <16 years of age. The campaign will emulate vaccine delivery as would be administered in a local mass vaccination campaign.<br>* Other names: Typbar TCV;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Direct vaccine effectiveness of Typbar-TCV® | Comparison of incidence of blood culture confirmed Salmonella Typhi infection in participants 9 months to <16 years of age vaccinated with a single dose of Typbar-TCV® delivered through a mass vaccination campaign and unvaccinated participants 9 months to <16 years of ageSalmonella Typhi isolated from blood specimens using conventional microbiological techniques | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall vaccine effectiveness of Typbar-TCV® | Comparison of incidence of blood culture confirmed Salmonella Typhi infection in all individuals 9 months to <16 years of age residing in clusters with lowest vaccine coverage (delineated virtually using GIS data) and all individuals 9 months to <16 years of age residing in clusters with highest vaccine coverage | 3 years | 
| Total vaccine effectiveness of Typbar-TCV® | Comparison of the incidence of blood culture confirmed Salmonella Typhi infection in vaccinated individuals 9 months to <16 years of age residing in clusters with highest vaccine coverage (delineated virtually using GIS data) versus unvaccinated individuals 9 months to <16 years of age residing in clusters with lowest vaccine coverage | 3 years | 
| Indirect vaccine effectiveness of Typbar-TCV® | Comparison of the incidence of blood culture confirmed Salmonella Typhi infection in unvaccinated individuals 9 months to <16 years residing in clusters with lowest levels of vaccine coverage (delineated virtually using GIS data) versus unvaccinated individuals 9 months to <16 years of age residing in clusters with highest levels of vaccine coverage | 3 years | 
| Safety profile of Typbar-TCV® | Proportion of participants developing local and systemic solicited adverse events/adverse reactions and unsolicited adverse events within the first 7 days post-vaccination in a subset of vaccinees and unsolicited and serious adverse events within 28 days post-vaccination | 28 days | 
| Feasibility of a single-dose Typbar-TCV® mass campaign in Kisantu, DRC | Descriptive report assessing both the scientific feasibility, including the ability of the study team to measure the above-named objectives, and operational feasibility, focusing on logistical aspects of the study conduct | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Typhoid conjugate vaccine, Vaccine effectiveness, Mass vaccination campaign, Democratic Republic of Congo (DRC)