A cluster-randomised controlled Phase IV trial (cRCT) assessing the impact of a Vi-Polysaccharide conjugate vaccine in preventing typhoid infection in Asante Akim, Ghana (TyVEGHA) with a primary endpoint of determining the total protection conferred by single-dose vaccination with Vi-TT against blood culture-confirmed symptomatic S. Typhi infection in the intervention vaccine clusters, compared with the control vaccine clusters.
Typhoid fever remains a significant health problem in sub-Saharan Africa, with incidence rates \>100 cases per 100,000 person-years of observation. Despite the prequalification of safe and effective typhoid conjugate vaccines (TCV), the uptake of these vaccines in African countries has remained low. Real-life effectiveness data, which inform public health programs on the impact of TCVs in reducing typhoid-related mortality and morbidity, are critical to enhancing the introduction of TCVs in high-burden settings. Here we describe a cluster-randomized trial to investigate population-level protection of TCV against blood culture-confirmed typhoid fever. A total of 80 geographically distinct clusters have been delineated within the Agogo district of the Asante Akim region in Ghana. Clusters will be randomized to the intervention arm receiving TCV or a control arm receiving the meningococcal A conjugate vaccine. The primary study endpoint is the overall protection of TCV against blood culture-confirmed typhoid fever. Total, direct, and indirect protection will be measured as secondary outcomes. Blood culture-based enhanced surveillance will enable the estimation of incidence rates in the intervention and control clusters. Evaluation of the real-world impact of TCVs will improve uptake of prequalified/licensed safe and effective typhoid vaccines in public health programs of high burden settings.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
23,000
Single-dose V-TT administered to children and adolescents between the ages of 9 months to 15 years.
Single-dose of MCV-A vaccine (a meningococcal vaccine)
Kwame Nkrumah University of Science and Technology
Kumasi, Ashanti Region, Ghana
RECRUITINGTotal Protection
The incidence of blood culture-confirmed symptomatic TF in all vaccine recipients of the intervention clusters, compared with control clusters.
Time frame: 3 years
Safety Assessment
1\) Proportion of adverse events in participants receiving Vi-TT compared with MCV-A, measured by: * The proportion of participants in each group of a sub-sample of the cohort developing adverse events/adverse reactions within the first 7 days post-vaccination. * The proportion of participants in each group of the cohort developing serious adverse events during the entire study period, as determined by self-reporting at follow-up contact.
Time frame: 3 years
Overall protection
The incidence of blood culture-confirmed symptomatic TF in all residents of the intervention clusters compared with that in all residents of control clusters
Time frame: 3 years
Total protection against severe typhoid.
The incidence of severe TF in vaccinated individuals in intervention clusters compared to control clusters
Time frame: 3 years
Total protection against clinical typhoid.
The incidence of clinical typhoid fever cases, defined as persistent fever (tympanic (≥38.0℃) or axillary temperature (≥37.5℃) or reported fever for ≥3 consecutive days) with abdominal complaints at a study surveillance site in vaccinated individuals in intervention clusters compared to control clusters.
Time frame: 3 years
Overall protection against clinical typhoid.
The incidence of clinical typhoid fever cases presenting at a study surveillance site among all residents of the Vi-TT clusters compared to the control vaccine clusters.
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Time frame: 3 years
Indirect Protection aganist Blood Culture Confirmed Typhoid.
The incidence of blood culture-confirmed symptomatic TF in non-vaccinees of the intervention clusters compared with control clusters.
Time frame: 3 years
Seroconversion rates
The seroconversion rates as measured by enzyme linked immunosorbent assay (anti-Vi IgM and IgG) for S. Typhi and iNTS at defined time points in a age-stratified subset of intervention and control vaccinees.
Time frame: 3 years
Geometric mean titers
The antibody concentration as measured by enzyme linked immunosorbent assay (anti-Vi IgM and IgG) for S. Typhi and iNTS at defined time points in a age-stratified subset of intervention and control vaccinees.
Time frame: 3 years