Gates-funded program aims to accelerate introduction of under-used typhoid vaccines

Pilot immunization of students to demonstrate feasibility of mass vaccination

The Bill & Melinda Gates Foundation has recently awarded the International Vaccine Institute (IVI) a $14 million, five-year grant to advance the use of typhoid vaccines for children in countries where typhoid fever still poses a serious public health threat.

Despite the existence since the late 1980s of two new-generation, safe and effective typhoid vaccines – the injectable, single-dose Vi polysaccharide vaccine, and the oral live 3-4 dose Ty21a – few countries have introduced them into their immunization programs. As a result, typhoid fever continues to exact a considerable toll each year – resulting in an estimated 21 million cases and more than 200,000 deaths world-wide.

The Vi-based Vaccines for Asia (VIVA) Initiative will address the under-use of typhoid vaccines in endemic countries in a number of ways – by conducting pilot vaccine introduction programs for school children in two typhoid-endemic countries to demonstrate the feasibility and impact of large-scale typhoid immunization; by assisting with technology transfer of Vi to vaccine producers in developing countries to increase the world-wide availability of affordable vaccine; by developing and field testing a Vi-conjugate vaccine that can be incorporated into the infant immunization schedule; and by developing an “investment case” and advocacy strategy to help ensure support for the introduction of typhoid vaccines by national governments and the donor community.

This Initiative comes at a critical time. The World Health Organization has issued an updated Position Paper on Typhoid Vaccines that includes new recommendations on the use of new-generation typhoid vaccines for the control of both endemic and epidemic typhoid (learn more).  The  WHO Regional Offices in Asia and the Eastern Mediterranean region have been directed to discuss these recommendations with countries in their regions, so that realistic plans for their implementation can be developed.

“Successful large-scale vaccine demonstration projects, along with an increased supply of existing vaccines, the arrival of a new typhoid vaccine for use in infants and a convincing investment case will pave the way for making these recommendations a reality in typhoid-endemic countries,” said Dr. John Clemens, IVI’s Director-General.

Through the VIVA Initiative, school children in Karachi, Pakistan and Jakarta, Indonesia will receive Vi vaccination delivered through schools by the national and local government immunization programs. These large-scale pilot vaccine introduction projects will determine the feasibility and acceptability of school-based typhoid immunization in high-incidence, impoverished settings and measure their impact on disease incidence (through case-control studies and studies of secular trends of typhoid incidence).

Designed as a first step towards the broader introduction of typhoid vaccines in other high-risk areas in these countries, such as urban slums, these pilot projects will provide important evidence to policymakers in these countries and to the global health community on how school-based typhoid vaccination can be a practical and effective way to control this disease. The pilot projects will also test an innovative means of financing typhoid vaccination for the longer term. Children in private schools in both areas will be offered typhoid vaccine for a reasonable user fee, to be used to subsidize free vaccination of public school students, who come from poorer families.

If typhoid vaccines are to be used more broadly in typhoid-endemic countries, there needs to be a sufficient supply of high-quality vaccine that is affordable for developing countries. To help ensure this, VIVA is helping with the technology transfer of Vi vaccine to high-quality producers in India and Indonesia.

Another major goal of the VIVA Initiative is to further develop, test and bring to licensure a Vi-diphtheria toxoid (DT) conjugate vaccine. Unlike Vi and Ty21a, the conjugate vaccine may be effective in children under two years of age, allowing it to be administered to infants through routine infant immunization programs. Studies by the Disease of the Most Impoverished (DOMI), coordinated by the IVI and funded by the Gates Foundation, have found that pre-schoolers in several highly-endemic countries had high rates of typhoid fever, dispelling the conventional wisdom that typhoid has little impact on young children. “Hence, this vaccine, developed in IVI’s laboratories in collaboration with the U.S. National Institutes of Health, could be important to controlling typhoid fever in certain highly-endemic countries,” Dr. Clemens commented.

VIVA will transfer the production technology of the Vi-DT vaccine and quality control tests to a producer in a country with a WHO-approved national regulatory authority, where it will undergo clinical trials. By the end of VIVA, this vaccine should be licensed in the country of production and be under consideration by WHO for pre-qualification to allow its purchase by UN agencies.

Finally, to generate support for typhoid vaccination from governments and donors, VIVA will prepare a comprehensive investment case, which will use data from the field to determine the feasibility, potential impact, costs and cost-effectiveness of typhoid vaccination targeted for high-risk areas and populations in countries still plagued by this disease.