Vaccines for preventing typhoid fever

Background: Two typhoid vaccines are commercially available, Ty21a (oral) and Vi polysaccharide (parenteral), but neither is used routinely. Other vaccines, such as a new modified, conjugated Vi vaccine called Vi-rEPA, are in development. Objectives: To evaluate vaccines for preventing typhoid fever. Search strategy: In December 2006, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2006, Issue 3), MEDLINE, EMBASE, LILACS, and mRCT. We also searched relevant conference proceedings up to 2004 and scanned the reference lists of all included trials. Selection criteria: Randomized and quasi-randomized controlled trials (RCTs) comparing typhoid fever vaccines with other typhoid fever vaccines or an inactive agent (placebo or vaccine for a different disease). Data collection and analysis: Two authors independently applied inclusion criteria and extracted data. We computed vaccine efficacy per year of follow up and cumulative three-year efficacy, stratifying for vaccine type and dose. We calculated relative risks (RR) and efficacy (1-RR as a percentage) with 95% confidence intervals (CI). Main results: Of the 17 included RCTs, 10 evaluated efficacy (Ty21a: 5 trials; Vi polysaccharide: 4 trials, Vi-rEPA: 1 trial), and 11 reported on adverse events. Ty21a vaccine (3 doses). According to one trial (20,543 participants), this vaccine provided statistically significant protection in each of the first three years (one: 35%, 95% CI 8% to 54%; two: 58%, 95% CI 40% to 71%; three: 46%, 95% CI -6% to 72%), and the cumulative efficacy for 2.5 to 3 years was 48% (95% CI 34% to 58%). Four cluster-RCTs that did not adjust for clustering were not included in the meta-analyses. Compared with placebo, this vaccine was not associated with an increased rate of fever, vomiting, diarrhoea, nausea or abdominal pain, headache, or rash. Vi polysaccharide vaccine (1 dose). This vaccine provided protection in year one (68%, 95% CI 50% to 80%; 99,979 participants, 3 trials) and year two (60%, 95% CI 31% to 76%; 142,555 participants, 2 trials), but not in year three (11,384 participants, 1 trial). The three-year cumulative efficacy was 55% (95% CI 30% to 70%; 11,384 participants, 1 trial). Compared with placebo, there was no statistically significant difference in the incidence of fever or erythema, but local swelling was more common with the vaccine. Vi-rEPA vaccine (2 doses). In one trial of 12,008 participants, this vaccine provided protection in year one (94%, 95% CI 75% to 99%) and year two (87%, 95% CI 56% to 96%). Cumulative efficacy at 46 months (3.8 years) was 89% (95% CI 76% to 97%). No swelling or erythema occurred in the vaccine or placebo group; fever was more frequent in the vaccine group. Authors' conclusions: The licensed Ty21a and Vi polysaccharide vaccines are efficacious. The new and unlicensed Vi-rEPA vaccine is as efficacious and may confer longer immunity.