Although the global burden of typhoid fever remains high, the global community has yet to coalesce around a comprehensive global policy or strategy for the management of the illness.
World Health Organization
In 2003, the World Health Organization (WHO) published Background Document: The Diagnosis, Treatment and Prevention of Typhoid Fever. Although this report is not intended as policy guidance, it outlines key prevention tools—including safe water, food safety, sanitation, and health education, alongside vaccines—as elements of a comprehensive prevention approach. The report identifies appropriate antibiotics as the proper course of treatment for typhoid fever, and it acknowledges antibiotic resistance as a growing issue. WHO partners with national governments during an outbreak to set forth specific guidelines to curb escalation.
In 2008, WHO published its first position paper for typhoid, which acknowledged the international public health impact of the disease. Designed for national public health officials and immunization program managers, the position paper on typhoid fever and typhoid vaccines serves as the framework in which typhoid interventions are considered. The 2008 paper considered the high burden of typhoid fever and increasing drug resistance in relation to the safety, efficacy, feasibility, and affordability of two vaccines licensed at the time (Vi and Ty21A). It stated that “countries should consider the programmatic use of typhoid vaccines for controlling endemic disease.” For most countries, control efforts will focus on vaccinating high-risk groups and populations. The paper also acknowledged the epidemic potential of typhoid fever and recommends using vaccines as a method for outbreak control. Additionally, the 2008 recommendation stated 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.”
In October 2017, the Strategic Advisory Group of Experts (SAGE) on Immunization, an advisory body to WHO, recommended typhoid conjugate vaccines (TCVs) for routine use in infants and children over six months of age in typhoid endemic countries. They also recommended prioritizing TCV introduction in countries with the highest burden of disease and/or a growing burden of drug-resistant typhoid, and in response to confirmed outbreaks. In December 2017, WHO prequalified Typbar-TCV®, signifying that the vaccine meets international standards for quality, safety, and efficacy, and allowing UN agencies, including UNICEF, and Gavi, the Vaccine Alliance to procure the vaccine for use in low- and middle-income countries. Typbar-TCV is the first TCV to be prequalified, but several others are in various stages of development.
In March 2018, WHO published a new position paper that formally recommends preferential programmatic use of prequalified typhoid conjugate vaccine (TCV) for all ages, “in view of its improved immunological properties, suitability for use in younger children and expected longer duration of protection.” The paper states that countries may also consider the routine use of ViPS vaccine in individuals aged 2 years and older and Ty21a vaccine for individuals aged 6 years and older, but that the costs, programmatic issues, and duration of protection should be considered. WHO recommends that the introduction of TCV should be prioritized in countries with the highest burden of typhoid disease or a high burden of drug-resistant S. Typhi. The paper also reemphasizes the importance of an integrated approach to typhoid prevention and control, including vaccines alongside water, sanitation, and hygiene interventions.
Gavi, the Vaccine Alliance
Every five years, Gavi, the Vaccine Alliance develops the Vaccine Investment Strategy (VIS) to determine which vaccines will be available through Gavi’s support programs. In 2008, Gavi prioritized typhoid vaccines for inclusion in the portfolio. However, since licensed polysaccharide typhoid vaccines are not suitable for infants and TCVs were thought to be on the horizon, no financial commitment was made at that time.
Following the SAGE recommendation for TCVs, the Gavi Board in November 2017 approved US$85 million in funding to support TCV introduction in developing countries. Applications for country support opened in 2018, with introductions anticipated in 2019 and 2020.
Photo: PATH/Rocky Prajapati