- IVI-NICED study published by New England Journal of Medicine
- Vaccine primarily used for travelers may have major impact on morbidity and mortality in poorest populations

A setting in Kolkata, India where typhoid fever is endemic.
Typhoid fever is a waterborne and foodborne infection.

A new study has found that a currently available yet underused vaccine against typhoid fever is highly effective in young children and protects unvaccinated neighbors of vaccinees.

The study, conducted by the IVI in collaboration with the National Institute of Cholera and Enteric Diseases (NICED) in Kolkata, India, was published in the July 23rd  issue of The New England Journal of Medicine (NEJM).

Typhoid fever remains an important cause of illness and death in the developing world, killing an estimated 216,000 to 600,000 people annually. Multidrug-resistant Salmonella Typhi has spread to many parts of the world, limiting the ability to treat typhoid fever with available antibiotics. Typhoid is both a waterborne and foodborne gastrointestinal infection, with incidence approaching one percent of the population annually in certain endemic areas. Experts say that in the absence of affordable programs to assure safe water and better sanitation, short and medium-term efforts need to be directed towards prevention through vaccines.

This data from the IVI´s Diseases of the Most Impoverished (DOMI) program
suggests a high incidence of typhoid fever among populations in
endemic areas. (Ochiai et al. 2008 Bulletin of WHO)

Safe and effective vaccines against typhoid fever exist but they are used primarily for affluent travelers to developing countries, rather than for the poor residing in these countries, who account for the majority of the global burden of typhoid morbidity and mortality. One of these vaccines, Vi polysaccharide, is ideally suited for use in developing countries because it is cheap (about $0.50 per dose) and requires only a single dose.

Despite a recommendation by the World Health Organization for use of Vi vaccines in developing countries, its use has been limited, partly because of doubts about Vi’s ability to protect pre-school age children. This age group is at exceptionally high risk in the poorest settings.  There were also doubts about Vi’s ability to confer “herd protection,” or protection of unvaccinated residents living in highly vaccinated areas. 

To address these uncertainties, the IVI, in collaboration with NICED, conducted a Phase IV cluster-randomized effectiveness vaccine trial, which randomized 80 geographic clusters of an urban Kolkata slum to either the Vi vaccine or control vaccine.  Over two years of follow-up, the Vi group was shown to have 61 percent fewer episodes of typhoid than the control group. Protection of children under five years of age by Vi was even higher at 80 percent. Interestingly, unvaccinated neighbors of Vi vaccinated persons had a 44 percent lower risk of typhoid, indicating that Vi vaccine conferred substantial herd protection. The overall level of protection among all residents of the Vi clusters, regardless of whether they were vaccinated or not, was 57 percent.  Since the coverage of residents of the Vi clusters was about 60 percent, this observation indicates that the Vi vaccine prevented as many cases of typhoid in the total population as a vaccine that was nearly 100 percent protective in vaccinated persons.

“The protection of children under the age of five years is important because this age group has been shown to be at high risk for typhoid fever in many areas where the disease is endemic,” said Dr. John Clemens, Director-General of the IVI and an international expert in vaccine evaluation. In a separate IVI study conducted in five Asian countries and supported by the Bill and Melinda Gates Foundation, children less than five years of age were found to have high rates of typhoid in Kolkata, India; Jakarta, Indonesia; and Karachi, Pakistan, confirming that the disease is not limited to school-aged children and adults.

The IVI-NICED study, which was supported by the Gates Foundation and the governments of Korea, Sweden, and Kuwait, also revealed that delivering the low-cost Vi typhoid vaccine is logistically and programmatically possible. “The fact that the level of overall protection (57 percent) of all residents was similar to the protection of vaccinees (61 percent), despite vaccine coverage of only about 60 percent of the subjects, underscores the importance of herd protection by the Vi vaccine,” said Dr. Clemens, a co-author of the study. “It also suggests the need for consideration of herd protective effects in future deliberations about the use of this vaccine in developing countries.”

Meanwhile, in a separate vaccine development project, IVI laboratories have more than tripled the manufacturing yield of Vi polysaccharide, which is expected to further reduce the vaccine’s production cost, thus making it more accessible for developing countries. The production technology for the high-yield Vi polysaccharide is being transferred to high-quality producers in developing countries.