Typhoid fever is a systemic infection caused by Salmonella Typhi, usually through ingestion of contaminated food or water. The acute illness is characterized by prolonged fever, headache, nausea, loss of appetite, and constipation or sometimes diarrhoea. Symptoms are often non-specific and clinically non-distinguishable from other febrile illnesses. However, clinical severity varies and severe cases may lead to serious complications or even death. It occurs predominantly in association with poor sanitation and lack of clean drinking water. An estimated 9 million cases and 110 000 typhoid-related deaths occur annually worldwide (2019 estimates). A similar but often less severe disease, paratyphoid fever, is caused by Salmonella Paratyphi A and B (or uncommonly Paratyphi C).

Three typhoid vaccines are currently recommended by WHO for control of endemic and epidemic typhoid fever:

• an injectable typhoid conjugate vaccine (TCV), consisting of Vi polysaccharide antigen linked to a carrier protein licensed for children from 6 months of age and adults up to 45 years or 65 years of age (depending on the specific vaccine);
• an injectable unconjugated polysaccharide vaccine based on the purified Vi antigen (known as Vi-PS vaccine) for persons aged two years and above; and
• an oral live attenuated Ty21a vaccine in capsule formulation for those over six years of age.

Among the available typhoid vaccines, TCV is preferred at all ages for routine programmatic use in view of its improved immunological properties, suitability for use in younger children and expected longer duration of protection. WHO further recommends that all typhoid fever vaccination programmes should be implemented in the context of other efforts to control the disease, including health education, water quality and sanitation improvements, and training of health professionals in diagnosis and treatment.

Gavi, the Vaccine Alliance announced in November 2017 funding support to eligible countries for programmatic use of TCV starting from 2019. There are currently two WHO prequalified TCV products available on the global market. Reviews of the available safety data for TCV by the Global Advisory Committee on Vaccine Safety (GACVS) concluded that the safety profile of the vaccine is reassuring, there are no signals of serious adverse events to date, and no theoretical safety concerns for TCV use.

Phase IV randomized control trials have been conducted in Bangladesh, Nepal and Malawi led by the Typhoid Vaccine Acceleration Consortium. They report a protective efficacy of a single dose of TCV, against blood-culture confirmed typhoid fever in children aged 9 months to 16 years, ranging between 79 to 88% after approximately 18 to 24 months of follow up. These results support the existing recommendations for TCV use, which were based on immunogenicity data and results from a controlled human infection trial. Additionally, safety data reported from these studies support the earlier GACVS conclusions and provide further reassuring evidence for TCV use in typhoid endemic settings.

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