Evaluation of Typhoid Conjugate Vaccine Effectiveness in Ghana
Evaluation of Typhoid Conjugate Vaccine Effectiveness in Ghana
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.
Inclusion Criteria: In order to be eligible to participate in this study, an individual
 must meet the following criteria:

 -  Healthy participants aged 9 months to <16 years (i.e., ≤15 years and 364 days) of age
 at the time of vaccination

 -  Participants/Parents/legally authorized representative (LAR) who have voluntarily
 given informed assent (sought from participants aged 12 years to <16 years) and
 informed consent

 -  Participants/Parents/LAR living within study target area at the time of vaccination
 and willing to follow the study procedures and be available for the entire duration of
 the study

 Exclusion Criteria: An individual who meets any of the following criteria will be excluded
 from participation in this study:

 -  Known allergy to any vaccine component

 -  Self-reported ongoing acute and/or chronic illness

 -  Any self-reported coagulopathies

 -  Any medical or social compelling reasons in the judgment of a clinical physician

 -  Self-reported pregnancy/Positive urine pregnancy test or lactating

 -  Previous typhoid vaccination in the last 5 years (proven by the presentation of a
 vaccine card or self-reporting).

 Temporary exclusion criteria

 -  Self-reported fever (elevated tympanic (≥38°C) or axillary temperature (≥37.5°C))
 within 24 hours of vaccination

 -  Self-reported use of antipyretics within 4hours prior to vaccination

 -  Any other vaccination during the last 4 weeks (proven by the presentation of a vaccine
 card or self-reporting)

 -  Girls ≥11 years of age with self-reported irregular menstruation or who do not know
 their last menstruation date