Typhoid is spread by infected human waste, so safe food, clean water, improved sanitation, and good hygiene practices are key to preventing the disease. But they cannot do the job alone. Because of the significant burden of typhoid and the growing threat of drug resistance, the role of vaccines alongside safe water, sanitation, and hygiene 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
Two typhoid vaccines are currently recommended by the World Health Organization (WHO) and are commercially available, but neither is used routinely in any country.
|Name||Ty21a||Vi capsular polysaccharide vaccine (ViCPS)|
|Tradename(s) (Manufacturer)||Vivotif® (PaxVax)||Typhim Vi® (Sanofi Pasteur)
|Administration||Oral capsules||Intramuscular injection|
|Age||>6 years of age
(>2 years of age in some countries)
|>2 years of age|
|Number of doses||3 to 4 doses||1 dose with boosters every 2 to 3 years|
|Duration of protection||7 years||2 years|
|Effectiveness||50% to 80%||50% to 80%|
Uptake of the current vaccines in typhoid-endemic countries has been low. The Ty21a vaccine requires numerous doses, and the Vi capsular polysaccharide (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, the Vaccine Alliance does not provide funding for Ty21a or ViCPS vaccines.
Typhoid conjugate vaccines
New typhoid Vi conjugate vaccines (TCVs) have great potential to address the limitations of the existing vaccines. TCVs strengthen the immunogenic properties of the ViCPS vaccine and have been found to elicit strong, long-lived immune responses in both infants and children. These vaccines are of particular interest to the global health community because, unlike the existing vaccines, they could be delivered to children younger than two years as part of routine childhood immunization programs. In November 2017, Gavi announced a US$85 million funding window to support the introduction of typhoid conjugate vaccines in developing countries in 2019 and 2020.
The leading TCV candidate, Typbar-TCV®, is manufactured by Bharat Biotech. It is administered in a single dose. Approved for children six months of age and older, Typbar-TCV is currently licensed in India and Nepal. As of early 2018, the vaccine is undergoing two phase IV post-licensure trials. Typbar-TCV was prequalified by WHO in late 2017.
Another advanced TCV candidate is called PedaTyph™, which is manufactured by Bio-Med and is licensed in India for children three months of age and older. Efficacy trials of PedaTyph have found more than 90 percent efficacy against typhoid. However, it has not been submitted for WHO prequalification. Nine other TCV candidates are in various stages of development.
World Health Organization recommendations
The latest WHO position paper on typhoid vaccines, published in 2008, states:
Although the Vi and the Ty21a vaccines provide appreciable levels of protection and have a good record of safety, improved vaccines against typhoid fever are desirable. Such vaccines should confer higher levels and more durable protective immunity in all age groups, including those aged <2 years, preferably without the need for booster doses. While several new candidate vaccines show considerable promise, they are unlikely to be on the market within the next several years. In the meantime, endemic countries should consider how best to make use of the Vi and the Ty21a vaccines in children aged >2 years old.
With TCVs joining the market, being licensed in countries, securing Gavi funding, and achieving prequalification, an updated WHO position paper on typhoid vaccines is expected soon.
Photo: PATH/Gabe Bienczycki