Study Overview

A Phase III Randomized, Double-Blind, Controlled Trial of the Clinical Efficacy of Typhoid Conjugate Vaccine (Vi-TCV) Among Children Age 9 Months Through 12 Years in Blantyre, Malawi.

Study Description

This study is a double-blind, individually randomized, controlled, clinical efficacy trial with two vaccine groups: Vi-TCV (Typhoid conjugate) and MCV-A (meningococcal group A conjugate). This study will take place in Blantyre, Malawi, Africa. Participants (up to 30,000) will be randomized in a 1:1 ratio. Children 9 months through 12 in the Blantyre area who meet the inclusion criteria will be eligible for enrollment.

Study Results

Between Feb 21, 2018, and Sept 27, 2018, 28 130 children were vaccinated; 14 069 were assigned to receive Vi-TT and 14 061 to receive MenA. After a median follow-up of 4·3 years (IQR 4·2–4·5), 24 (39·7 cases per 100 000 person-years) children in the Vi-TT group and 110 (182·7 cases per 100 000 person-years) children in the MenA group were diagnosed with a first episode of blood culture-confirmed typhoid fever. In the intention-to-treat population, the efficacy of Vi-TT was 78·3% (95% CI 66·3–86·1), and 163 (129–222) children needed to be vaccinated to prevent one case. Efficacies by age group were 70·6% (6·4–93·0) for children aged nine months to 2 years; 79·6% (45·8–93·9) for children aged 2–4 years; and 79·3% (63·5–89·0) for children aged 5–12 years.

Study Interpretation

A single dose of Vi-TT is durably efficacious for at least four years among children aged nine months to 12 years and shows efficacy in all age groups, including children younger than two years. These results support current WHO recommendations in typhoid-endemic areas for mass campaigns among children aged nine months to 15 years, followed by routine introduction in the first two years of life.