Typhoid Vaccines

Typhoid is spread by infected human waste, so safe food, clean water, improved sanitation, and good hygiene (WASH) practices are key to preventing the disease. Because of the significant burden of typhoid and the growing threat of drug resistance, the role of vaccines alongside WASH interventions is critical in high-risk, typhoid-endemic areas. This is especially important among rural and hard-to-reach communities where progress in medical services, infrastructure, and development may be slow. Additionally, typhoid vaccines are valuable for travelers, food workers (including street vendors), household contacts of typhoid carriers, and laboratory workers.

Currently available typhoid vaccines

Three classes of typhoid vaccines are currently recommended by the World Health Organization (WHO).

Name Typhoid conjugate vaccines (TCV) Ty21a Vi capsular polysaccharide vaccines (ViCPS)
Tradename(s) (Manufacturer) Typbar TCV® (Bharat Biotech)
TYPHIBEV® (Biological E)
Vivotif® (PaxVax) Typhim Vi® (Sanofi Pasteur) Typherix® (GlaxoSmithKline)
Administration Intramuscular injection Oral capsules Intramuscular injection
Age >6 months of age >6 years of age >2 years of age
Number of doses 1 dose 3 to 4 doses 1 dose with boosters every 2 to 3 years
Duration of protection >2 years*
*Studies currently underway with Typbar TCV
7 years 2 years
Effectiveness 79% to 85%
Data from TyVAC efficacy studies in Bangaldesh, Malawi, and Nepal with Typbar TCV
50% to 80% 50% to 80%

Typhoid conjugate vaccines (TCVs) are of particular interest to the global health community because they have the potential to overcome many of the challenges that impeded uptake of earlier vaccines. TCVs are more effective and may provide longer-lasting protection*, require one dose, and are suitable for children younger than two years of age, allowing for inclusion in routine childhood immunization programs. Two TCVs are WHO prequalified and available with Gavi, the Vaccine Alliance support, and many more are under development.

Typbar TCV, manufactured by Bharat Biotech Ltd., was prequalified by WHO in late 2017 and recommended by WHO in 2018. It is administered in a single dose and approved for children six months of age and older. Large Phase 3 efficacy studies conducted in Bangladesh, Malawi, and Nepal show that Typbar TCV is safe and highly effective, preventing 85%, 84%, and 79% of typhoid cases in vaccinated children, respectively. Additionally, more than 36 million children have also safely received Typbar TCV through country introduction campaigns. This vaccine can also be safely co-administered with other routine childhood vaccines including measles-rubella, yellow fever, and meningococcal A vaccines.

TYPHIBEV, manufactured by Biological E, was prequalified by WHO in late 2020. It is administered in a single dose and approved for children over six months of age. Clinical studies show that it is safe when given at 9 months of age concurrently with measles vaccine, and its immune response profile is similar to that of Typbar TCV.

Uptake of the Ty21a and ViCPS vaccines in typhoid-endemic countries has been low. The Ty21a vaccine requires numerous doses, and the ViCPS vaccine has short-lived protection. Additionally, neither vaccine is amenable to use in children younger than two years of age, which limits the potential health benefits and prevents use in routine childhood vaccination programs. Gavi does not provide funding for Ty21a or ViCPS vaccines.

World Health Organization recommendations and Gavi support

The WHO position paper on typhoid vaccines, published in 2018, states:

WHO recommends programmatic use of typhoid vaccines for the control of typhoid fever. […] Among the available typhoid vaccines, TCV is preferred at all ages in view of its improved immunological properties, suitability for use in younger children and expected longer duration of protection. Countries may also consider the routine use of ViPS vaccine in individuals aged 2 years and older, and Ty21a vaccine for individuals aged more than 6 years. In choosing a typhoid vaccine, the costs, programmatic issues and duration of protection should be considered.

WHO recommends the introduction of TCV to be prioritized in countries with the highest burden of typhoid
disease or a high burden of antimicrobial resistant S. Typhi. Decisions on the age of TCV administration, target population and delivery strategy for routine and catch-up vaccination should be based on the local epidemiology of typhoid fever, including antimicrobial resistance patterns, and programmatic considerations
of the routine childhood immunization programme.

Gavi has provided financial support for eligible countries to introduce TCVs since 2018. Applications for TCV introduction support are available now.

Outbreak response and country introductions

TCV has been used safely and effectively as part of outbreak response efforts, both in Pakistan to control an extensively drug-resistant typhoid outbreak that began in 2016 and in Zimbabwe. Following Pakistan’s outbreak response TCV campaign, they became the first country to introduce TCVs into their routine childhood immunization program with the launch of a phased introduction beginning in Sindh Province in November 2019, followed by Punjab Province and Islamabad in 2021. The remaining provinces plan to introduce TCV in 2022.

Liberia was the first African country to introduce TCV into its national routine immunization schedule in April 2021, and Zimbabwe introduced TCV into its national routine immunization schedule in May 2021. Nepal and Malawi are planning to introduce TCV in 2022.

Samoa was the first country to introduce TCV without Gavi support in August 2021.

*Data from TyVAC studies indicate protection greater than two years.

Photo: PATH/Gabe Bienczycki