Typhoid fever vaccines: a meta-analysis of studies on efficacy and toxicity

Abstract

Objective: To estimate the efficacy and toxicity of typhoid fever vaccines. Design: Meta-analysis of randomised efficacy trials and both randomised and non-randomised toxicity studies of the parenteral whole cell, oral Ty21a, and parenteral Vi vaccines. Subjects: 1 866 951 subjects in 17 efficacy trials; 11 204 subjects in 20 toxicity studies. Main outcome measures: Pooled estimates of three year cumulative efficacy, year specific efficacy, and incidence of adverse events. Results: Three year cumulative efficacy was 73% (95% confidence interval 65% to 80%) for two doses of whole cell vaccines (based on seven trials); 51% (35% to 63%) for three doses of Ty21a vaccine (four trials); and 55% (30% to 71%) for one dose of Vi vaccine (one trial). For whole cell and Ty21a vaccines, regimens of fewer doses were less effective. Efficacy was shown to be significant for five years for whole cell vaccines, four years for Ty21a vaccine, and two years for Vi vaccine. Neither the age of vaccine recipient nor the incidence of typhoid fever in the control group (varying from 6 to 810 cases per 100 000 person years) affected the efficacy of the whole cell or Ty21a vaccines. After vaccination, fever occurred in 15.7% (11.5% to 21.2%) of whole cell vaccine recipients, 2.0% (0.7% to 5.3%) of Ty21a vaccine recipients, and 1.1% (0.1% to 12.3%) of Vi vaccine recipients. Conclusions: Whole cell vaccines are more effective than the Ty21a and Vi vaccines but are more frequently associated with adverse events. Whether the added efficacy of the whole cell vaccines outweighs their toxicity will depend on the setting in which vaccination is used. Typhoid fever is an important public health problem in the developing world, but the efficacy of currently available vaccines has remained uncertain This meta-analysis of 17 vaccine efficacy trials and 20 toxicity studies of the whole cell, Ty21a, and Vi typhoid vaccines showed that whole cell vaccines probably offer the greatest protection for the longest time These vaccines, however, were associated with higher toxicity than the Ty21a and Vi vaccines The decision about whether to vaccinate against typhoid fever—and which vaccine to use—depends on the individual setting Efficacy trials of vaccines should use standardised trial designs and methods of reporting