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
Three types of typhoid vaccines of demonstrated safety and efficacy are available on the international market:- a conjugated vaccine in which the Vi polysaccharide vaccine is bound to a carrier protein, a non-conjugated Vi polysaccharide vaccine, and a live attenuated Ty21a vaccine. The two Vi polysaccharide-containing vaccines include the purified Vi capsular polysaccharide from the Ty2 S. Typhi strain. They are administered subcutaneously or intramuscularly. The Ty21a vaccine is administered orally and 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. A fourth type of typhoid vaccine, which is a whole-cell heat-phenol or acetone inactivated, is still available in several developing countries; however, given its relatively high reactogenicity, this vaccine should be replaced by the typhoid conjugate vaccine, the Vi polysaccharide vaccine or the Ty21a oral vaccine. Only the typhoid conjugate and the Vi polysaccharide vaccines are available through the WHO prequalification programme.
Typhoid Vaccine Standardization
Written Standards
Typhoid Conjugate Vaccines
WHO Guidelines on the quality, safety and efficacy of typhoid conjugate vaccines were first adopted by the ECBS in October 2013. Since that time, there were several major developments including the establishment of new WHO international standards, publication of SAGE recommendations on the use of typhoid conjugate vaccines in those aged 6 months to 45 years, and the WHO prequalification of typhoid conjugate vaccines. In light of these advances, the Guidelines were updated and adopted by ECBS in the Seventy-second meeting, 19–23 October 2020.
Recommendations to assure the quality, safety and efficacy of typhoid conjugate vaccines, Annex 2, TRS No 1030
Vi polysaccharide vaccines:
Requirements for the production and quality control of Vi polysaccharide typhoid vaccine were adopted in 1992.
Typhoid polysaccharide vaccine: Requirements for Vi Polysaccharide Typhoid Vaccine; Adopted 1992, TRS No 840, Annex 1
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
Whole cell vaccines:
WHO Requirements for typhoid vaccine formulated in 1966 describe the production and control of the whole-cell vaccines. Due to their reactogenicity these vaccines are no longer recommended and have been almost completely replaced by the typhoid conjugate, Vi polysaccharide and attenuated vaccines.
Reference materials
WHO international standards for Vi antigens and Vi antibodies (human) are available to qualified applicants. Reference materials for the whole-cell typhoid parenteral vaccines (acetone and heat-phenol-inactivated) are also available:
International Reference Preparations catalogue
