TYPHOID-FEVER VACCINES - A METAANALYSIS OF STUDIES ON EFFICACY AND TOXICITY

Objective: To estimate the efficacy and toxicity of typhoid fever vacc ines. Design: Meta-analysis of randomised efficacy trials and both ran domised and non-randomised toxicity studies of the parenteral whole ce ll, oral Ty21a, and parenteral Vi vaccines. Subjects: 1 866 951 subjec ts 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: Thre e year cumulative efficacy was 73% (95% confidence interval 65% to 80% ) for two doses of whole cell vaccines (based on seven trials); 51% (3 5% 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 T y21a vaccines, regimens of fewer doses were less effective. Efficacy w as shown to be significant for five years for whole cell vaccines, fou r years for Ty21a vaccine, and two years for Vi vaccine. Neither the a ge of vaccine recipient nor the incidence of typhoid fever in the cont rol group (varying from 6 to 810 cases per 100 000 person years) affec ted the efficacy of the whole cell or Ty21a vaccines. After vaccinatio n, fever occurred in 15.7% (11.5% to 21.2%) of whole cell vaccine reci pients, 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 freque ntly associated with adverse events. Whether the added efficacy of the whole cell vaccines outweighs their toxicity will depend on the setti ng in which vaccination is used.