ZyVac-TCV Bangladesh Study
brief summary
This is a prospective closed cohort, open-label, phase III effectiveness study using a test-negative design of a typhoid conjugate vaccine, ZyVac® TCV (purified Vi capsular polysaccharide of Salmonella Typhi conjugated to tetanus toxoid as carrier protein), manufactured by Zydus Lifesciences Limited. The study will be conducted in a closed cohort population among children aged 6 months to 15 years residing in wards 5, 6, 7, 48, 49, 50, 63, 71, and 72 of Dhaka South City Corporation (DSCC). The targeted number of age-eligible children in the study area is \~92,000 among them \~60,000 will be vaccinated. A subset of the first 600 consenting participants will be selected by age strata (6 months to \<2 years, 2-4 years, 5-15 years) for enrollment in the immunogenicity study with an additional three follow-up visits. Diary cards will be used to collect adverse events (AEs) following immunization (AEFI) data up to day 7 for a subset of active follow-up of the first 600 vaccinated participants. Participants not in this subset will be encouraged to go to the 'Adverse Event Monitoring Cell' at the Maniknagar field office. Data on serious adverse events (SAEs) will be reported for six months after vaccination. All study updates including AEs and SAEs will be reported to the data safety and monitoring board (DSMB) and sponsor. Passive surveillance for typhoid fever will be carried out in the Maniknagar field office and Mugda Medical College and Hospital in the catchment area among the age-eligible children.
detailed description
This will be a phase III effectiveness study of the typhoid conjugate vaccine (Vi-TCV) (ZyVac® TCV). The study will be conducted in a closed cohort population of children aged 6 months to 15 years residing in a selected geographical catchment area in Dhaka, Bangladesh using a test-negative design (TND). The TND is a particular type of case-control study including controls who present themselves with similar signs and symptoms (to those of the cases) in the same healthcare facilities. Individuals with the disease of interest are tested with a laboratory assay where test-positive and test-negative individuals are considered cases and controls, respectively.
Hypothesis:
The typhoid Vi-polysaccharide conjugate vaccine will be effective in preventing typhoid fever among Bangladeshi children.
Specific Objectives
Primary objective:
To evaluate the effectiveness of typhoid conjugate vaccine (TCV) against blood culture-confirmed typhoid fever using the test-negative design
Secondary objective:
To evaluate the effectiveness of typhoid conjugate vaccine (TCV) against blood culture-confirmed typhoid fever stratified by age groups (6 months to \<2 years, 2 to 4 years, 5 to 15 years) To evaluate the effectiveness of typhoid conjugate vaccine (TCV) against blood culture-confirmed typhoid fever stratified by the period of follow-up (first and second six months) after vaccination To determine the immunogenicity of TCV in a subset of participants, stratified by age groups (6 months to \<2 years, 2 to 4 years, 5 to 15 years)
Study area The study will be conducted in wards 5, 6, 7, 48, 49, 50, 63, 71, and 72 of Dhaka South City Corporation, covering an area of \~10.33 km2. No TCV campaigns have been conducted in this area. According to the Population and Housing Census 2022, the total population within the selected geographical catchment area is \~465,000 with households of \~122,000. The proportion of males is 54 percent and the average household size is \~3.8 people. Assuming \~20% of the population is from the 6-month to 15-year age group, the expected number of age-eligible children is \~92,000.
Baseline mapping A map of the study area will be created based on open-source georeferenced satellite images (source: Esri, Maxar, Earthstar Geographics, and the geographical information system (GIS) user community). The satellite image of the study area will be printed by separating it into several small pieces and provided to the field team for data collection. In this process field team will visit the entire area according to the map and draw the structure/building, road, and other salient geographic features in the printed images. A unique geographical information system (GIS) identification number will be assigned for all the buildings/structures, and submitted to the GIS team to develop the digital vector data (point, line, and polygon feature). The digital data of structure/building (polygon feature) centroid x and y coordinates will be used to represent real-world coordinate values or global positioning system (GPS) values.
official title
Evaluation of Typhoid Conjugate Vaccine (TCV) Effectiveness Among Bangladeshi Children Using the Test-negative Design