Primary prevention

Enteric fever can be effectively prevented through sanitation and hygiene. In high-income countries the disease was efficiently controlled through improvement of water and food sanitation. However, in low-income countries the construction of a new, effective infrastructure is unlikely to occur in the near future, especially not in slum areas.

Among travelers, a strict observance of hygiene rules (i.e., avoiding contaminated food and water, handwashing) has always been stressed. However, the efficacy of these precautions is known to be poor, if judged according to their failure in preventing traveler's diarrhea. Thus, vaccines can play a major role in prevention and typhoid vaccination is recommended for travelers visiting areas where there is risk for exposure.​[40]

To date, three types of typhoid vaccines exist: live attenuated oral vaccine, Vi capsular polysaccharide vaccine, and the newer Vi conjugated vaccines.

  • The live oral vaccine is an attenuated Salmonella typhi strain, Ty21a, which is a mutant of Ty2 with a uridine diphosphogalactose 4-epimerase defect. It is avirulent (lacking the Vi antigen) but contains immunogenic cell wall polysaccharides. Primary vaccination consists of 1 enteric-coated capsule or lyophilized sachet on alternate days for 3 to 4 doses. It works by eliciting serum and mucosal antibodies to S typhi O, S typhi H, and other antigens, and by stimulating an array of cell-mediated immune responses (including cytotoxic T cells). Efficacy is about 50% to 78% and duration of protection is 3 to 4 years.[41] The disadvantage of the vaccine is that concurrent use of antibiotics or antimalarials may interfere with the antibody response. The vaccine also needs to be refrigerated, cannot be given to children under 6 years of age, and relies on the recipient to complete the 3 to 4 required doses.[42][43] In addition, being live-attenuated, the vaccine is contraindicated in pregnancy and in those with cell-mediated immunosuppression.

  • The Vi vaccine contains the purified capsular polysaccharide antigen. The Vi antigen is the so-called virulence antigen that allows S typhi to survive in blood and cause septicemia. The Vi vaccine contains only the Vi component of S typhi and gives a rapid brisk seroconversion following 1 dose.[12][44] It is safe to be coadministered with other travel vaccines, including antimalarials, with no diminution in antibody response. It can be administered from the age of 2 years upward. The duration of protection appears to be between 2 and 3 years, with efficacy of 50% to 67%,[41] although in one study performed in Pakistan the vaccine did not confer any statistically significant protection to children ages 2 to 5 years.[45] Despite the fact that it is a polysaccharide vaccine, a Chinese study has shown that revaccination did give a boosting effect, with geometric mean antibody titer slightly lower (but difference was nonsignificant) than primary vaccination.[46] The vaccine is available combined with hepatitis A vaccine.[47]

  • The newer S typhi Vi conjugate vaccines have been developed by conjugating Vi to a carrier protein (similar to the conjugated pneumococcal and meningococcal vaccines). This has the advantage of increasing immunogenicity, and therefore efficacy (about 90%) and protection time, and it can be given to infants as well.[48][49]​​ Two typhoid conjugate vaccines are currently licensed, and both consist of Vi polysaccharide linked to tetanus toxoid (Vi-TT). The World Health Organization recommends 1 dose of a Vi-TT vaccine (Typbar-TCV®) for infants ages from 6 months and adults up to 45 years in typhoid-endemic regions.​[1]

One Cochrane review of typhoid vaccines found that the Ty21a vaccine and the Vi polysaccharide vaccine are effective for the prevention of enteric fever in children ages 2 years or older and in young adults living in typhoid-endemic regions.[50] Phase 3 randomized controlled trials evaluating the efficacy of typhoid conjugate vaccines in Nepal, Bangladesh, and Malawi found a vaccine efficacy of around 80% in all age groups.[51][52][53]

An important caveat in all estimates of vaccine efficacy is that most are derived from studies on local populations. These groups may have a degree of pre-existing immunity and are likely to have more repeated exposure, and therefore immune enhancement, than travelers, among whom vaccine efficacy has never been clearly established. In one human-model challenge, 112 volunteers in the UK ingested inoculum of S typhiafter vaccination with either the regular Vi polysaccharide vaccine or the conjugate vaccine (Vi-TT), and the efficacy in both vaccines was about 50%.[54]

The live oral vaccine (Ty21a) should not be given during pregnancy. No data on the safety of the Vi vaccine during pregnancy exist; however, there is no theoretical safety concern.[1][55]​​

A major disadvantage of all the above-mentioned vaccines is the lack of protection against S paratyphi organisms. Purified Vi vaccine protects by eliciting serum antibodies against Vi, an antigen that exists only in S typhi strains. In contrast, the attenuated S typhi Ty21a, which does not express Vi, but rather mediates protection by eliciting a vigorous secretory immunoglobulin A (IgA) and cell-mediated response, might give some protection against S paratyphi organisms. In fact, an Israeli study demonstrated that Vi vaccine gave better protection against S typhi among travelers to India while Ty21a gave better protection against S paratyphi A.[14] A retrospective analysis of pooled data from Ty21a vaccine studies in Chile showed some protection of this vaccine against paratyphoid B infection only (efficacy of 49%).[56]

Use of this content is subject to our disclaimer