Typhoid fever is caused by Salmonella Typhi, a highly virulent and invasive enteric bacterium. Only humans are affected, usually following ingestion of contaminated food or water. The symptoms of the disease include fever, headache, abdominal pain, and fatigue. Severe forms of typhoid fever may cause cerebral dysfunction, delirium and shock, and occasionally intestinal perforation and hemorrhages. Approximately 1-4% of patients continue to carry S. Typhi in their intestinal tract and gall bladder for months or years ("asymptomatic carriers"). Immunocompromised people are susceptible to lower infectious doses of S. Typhi and are at increased risk of severe disease. Multidrug resistant strains of S. Typhi have continued to emerge since the 1970s, providing a key rationale for the introduction of typhoid fever vaccination in high-risk areas for typhoid fever.
Typhoid Fever Vaccines
Two new-generation two typhoid vaccines of demonstrated safety and efficacy are available on the international market, the Vi polysaccharide vaccine which is administrated by injection and the live attenuated Ty21a vaccine which is given orally. The Vi polysaccharide vaccine is composed of purified Vi capsular polysaccharide from the Ty2 S. Typhi strain. It is administered subcutaneously or intramuscularly. The Ty21a oral vaccine is based on an attenuated Ty2 strain in which multiple genes, including the genes responsible for the production of the Vi polysaccharide, have been mutated. The oral Ty21a vaccine is available as enteric-coated capsules or a liquid suspension. The whole-cell heat-phenol or acetone inactivated vaccine is still available in several developing countries. However, given its relatively high reactogenicity, this vaccine should be replaced by the Vi polysaccharide vaccine or the Ty21a vaccine.
Typhoid Vaccine Standardization
WHO requirements for typhoid vaccine formulated in 1966 describe the production and control of the whole-cell vaccines. These vaccines have been almost completely replaced by the Vi polysaccharide and attenuated vaccines. Requirements for the production and quality control of Vi polysaccharide typhoid vaccine were adopted in 1992.
Typhoid polysaccharide vaccine, Title: Requirements for Vi Polysaccharide Typhoid Vaccine; Adopted 1992, TRS No 840, Annex 1
Typhoid vaccine, Requirements for Typhoid Vaccine; Adopted 1966, TRS No 361, Annex 4
Live attenuated vaccines:
WHO recommendations for the production and quality control of the Ty21a attenuated oral vaccine were adopted by the ECBS in 1983.
Typhoid vaccine, live attenuated, Requirements for Typhoid Vaccine (Live, attenuated, Ty 21a, Oral); Adopted at ECBS 1983. TRS No 700, Annex 3
Typhoid Conjugate Vaccines
WHO Guidelines on the quality, safety and efficacy of typhoid conjugate vaccines were adopted by the ECBS in 2013.
WHO reference materials for the whole-cell typhoid parenteral vaccines (acetone and heat-phenol-inactivated) are available to qualified applicants: