Background
Typhoid fever and paratyphoid fever continue to be important causes of illness and death, particularly among children and adolescents in south‐central and southeast Asia. Two typhoid vaccines are widely available, Ty21a (oral) and Vi polysaccharide (parenteral). Newer typhoid conjugate vaccines are at varying stages of development and use. The World Health Organization has recently recommended a Vi tetanus toxoid (Vi‐TT) conjugate vaccine, Typbar‐TCV, as the preferred vaccine for all ages.
Objectives
To assess the effects of vaccines for preventing typhoid fever.
Search methods
In February 2018, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, and
m
RCT. We also searched 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 with an inactive agent (placebo or vaccine for a different disease) in adults and children. Human challenge studies were not eligible.
Data collection and analysis
Two review authors independently applied inclusion criteria and extracted data, and assessed the certainty of the evidence using the GRADE approach. We computed vaccine efficacy per year of follow‐up and cumulative three‐year efficacy, stratifying for vaccine type and dose. The outcome addressed was typhoid fever, defined as isolation of
Salmonella enterica
serovar Typhi in blood. We calculated risk ratios (RRs) and efficacy (1 − RR as a percentage) with 95% confidence intervals (CIs).
Main results
In total, 18 RCTs contributed to the quantitative analysis in this review: 13 evaluated efficacy (Ty21a: 5 trials; Vi polysaccharide: 6 trials; Vi‐rEPA: 1 trial; Vi‐TT: 1 trial), and 9 reported on adverse events. All trials but one took place in typhoid‐endemic countries. There was no information on vaccination in adults aged over 55 years of age, pregnant women, or travellers. Only one trial included data on children under two years of age.
Ty21a vaccine (oral vaccine, three doses)
A three‐dose schedule of Ty21a vaccine probably prevents around half of typhoid cases during the first three years after vaccination (cumulative efficacy 2.5 to 3 years: 50%, 95% CI 35% to 61%, 4 trials, 235,239 participants, moderate‐certainty evidence). These data include patients aged 3 to 44 years.
Compared with placebo, this vaccine probably does not cause more vomiting, diarrhoea, nausea or abdominal pain (2 trials, 2066 participants; moderate‐certainty evidence), headache, or rash (1 trial, 1190 participants; moderate‐certainty evidence); however, fever (2 trials, 2066 participants; moderate‐certainty evidence) is probably more common following vaccination.
Vi polysaccharide vaccine (...
