Infectious Events Among Unvaccinated Participants in the Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE)

Abstract

Background. STRIVE is a trial of a candidate Ebola vaccine among healthcare and frontline Ebola workers. Participants were randomized to immediate or deferred vaccination; no placebo was used. Little was known about background medical conditions in Sierra Leone or adverse events (AEs) expected in the trial. Infection events reported through STRIVE's safety reporting mechanism by participants in the deferred vaccination arm during their unvaccinated period are described. Methods. STRIVE monitored AEs by three methods: (1) surveillance monitor contact for all participants monthly, (2) a dedicated telephone hotline for participants to report medical events, and (3) a safety sub-study with a 30-day symptom diary and frequent follow-up calls. All AEs reported through any of these systems were triaged by study nurses. Participants were referred to a study physician immediately if a serious AE (SAE) was suspected or later if the participant did not improve. STRIVE covered the cost of medical care for acute events assessed and treated by study nurses and physicians. Data for MedDRA System Organ Class and Preferred Term codes for Infections and Infestations are reported. Results. Of the 4327 deferred arm participants that remained unvaccinated during the deferral period, 60.6% were male, and 5.2% were enrolled in the safety sub-study. Median (IQR) age was 31 (26-39) years. In all, 3129 AEs were reported by 1026 (23.7%) participants; of these 212 (6.8%) AEs reported by 185 participants were infectious. The most commonly reported infectious events were nasopharyngitis (118 events, 114 participants), malaria (32 events, 31 participants) and skin/soft tissue infections (SSTI) (27 events, 27 participants). Among 35 SAEs, 7 were infectious (3 SSTI, 2 malaria, 1 typhoid, 1 tuberculosis) and all 7 led to hospitalization; the tuberculosis case was fatal. Conclusion. In Sierra Leone, as elsewhere, infectious events were a substantial minority of AEs. Nasopharyngitis, malaria, and SSTIs were the most commonly reported infections, while SSTIs and malaria were the most common infectious causes of hospitalization. The unvaccinated STRIVE arm provides prospectively collected information on an understudied population that may serve as a baseline for future clinical trials.