Vaccines for preventing typhoid fever

Abstract

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 (...

Travel-Related Typhoid Fever: Narrative Review of the Scientific Literature

“…Two-year post-vaccination effectiveness was87% [36,43]. A single randomized trial in Indian children aged between six months and 12 years did not clarify the efficacy of two doses of Vi-TT vaccine one year after administration [40].A real-life survey in Germany described an adverse event rate of 28.6% (fatigue, pain, headache, pyrexia, myalgia, and swelling), increased after concomitant immunization with other vaccines(i.e., rabies, typhoid, and yellow fever vaccines) [44].A US military study showed more adverse events in individuals exposed to the polysaccharide Vi vaccine in comparison with those exposed to the oral vaccine, although rash and diarrhea were more incident in the latter group [45].Fever and pain at the injection site were incident using parenteral vaccines [40].…”

“…Ty21a live attenuated vaccine, developed from attenuated Ty2 strains of S. typhi, does not confer protection after a single dose; three doses administered in alternate days in persons living in endemic countries and four doses in travelers are usually recommended to elicit adapted mucosal immunity (IgA antibodies), whose duration lasts~7 years in 60-70% of the vaccinated cases [38,39]. Half of typhoid fever cases could be prevented until three years after vaccination [40].…”

“…Primary prevention based on the available vaccines cannot be implemented in youngest children: the purified Vi capsular polysaccharide vaccine is not recommended in children aged <2 years for its poor immunogenicity; the live attenuated oral vaccine Ty21a is not well tolerated in children aged under five years [47].A recent review on the efficacy of the currently available vaccines confirmed that Ty21a and Vi polysaccharide vaccines can reduce the incidence of infections in adults and children aged >2 years [40].…”

Conservation of the OmpC Porin Among Typhoidal and Non-Typhoidal Salmonella Serovars

“…Furthermore, invasive NTS bacteremia (iNTS) is a common complication observed in immunocompromised adults and in young children with severe malaria and malnutrition (4). The current available licensed vaccines against Salmonella are the oral live attenuated Ty21a, the Vi capsular polysaccharide (Vi CPS), and the Vi-tetanus toxoid conjugate (Vi-TT), which only target the Typhi serovar, and have shown variable efficacy; 50% (95% CI 35-61%) for Ty21a, 55% (95% CI 30-70%) for Vi-CPS, and 54.6% (95% CI 26.8-71.8%) for Vi-TT (5,6), while no licensed vaccines against iNTS are currently available (7). Although cross-reactivity through vaccination with the Ty21a vaccine can be induced against Paratyphi A, B, and Enteritidis serovars (8,9), cross-protection has been reported only against Paratyphi B (10).…”

Factors influencing participation in controlled human infection models: a pooled analysis from six enteric fever studies

“…It remains a considerable global health challenge, causing an estimated 14.3 million (12•5-16•3) infections and 136 000 deaths annually 1 . Until recently 2 , licensed vaccines for S. Typhi were only moderately efficacious 3 and could not be used in young children. There are currently no licensed vaccines for S. Paratyphi 4 .…”