Chapter 62 - Typhoid Fever Vaccines

Abstract

Typhoid fever is an acute systemic infection of organs of the mononuclear phagocyte system (spleen, liver, bone marrow) and the gallbladder that is restricted to human hosts. In the pre-antibiotic era, the case fatality rate of acute typhoid was ~10-20%. In 1948, chloramphenicol was shown to reduce the typhoid case fatality to ~1% and this antibiotic became the main tool globally to control the typhoid mortality burden. However, the emergence of resistance to chloramphenicol in the early 1970s led to other antimicrobials replacing chloramphenicol as first line agents to treat acute typhoid fever. By the 1980s, two new typhoid vaccines also came on the scene including purified unconjugated S. Typhi Vi capsular polysaccharide administered parenterally and live oral vaccine strain Ty21a. When multidrug-resistant (MDR) S. Typhi became prevalent ~1989/1990 in Asia, limitations of the Vi polysaccharide and Ty21a vaccines stimulated the development of further improved typhoid vaccines including Vi conjugates in which the Vi polysaccharide is covalently linked to carrier proteins such as tetanus toxoid, mutant diphtheria toxin CRM197 and diphtheria toxoid. Extensively drug-resistant (XDR) S. Typhi explosively appeared in 2016, causing a large outbreak of typhoid fever in Pakistan and rapidly spreading to many countries over the next five years. This XDR strain, susceptible to only one oral antibiotic and to one expensive parenteral antibiotic, galvanized a global effort to complete the development of candidate Vi conjugate vaccines and to demonstrate their safety, immunogenicity, efficacy and effectiveness as a new tool to prevent typhoid fever.This chapter reviews the efficacy of Vi polysaccharide and oral Ty21a vaccines (still widely used to prevent typhoid fever among travelers from industrialized countries) and provides extensive new data on the safety, immunogenicity, and efficacy of several Vi conjugate vaccines that are licensed by various national regulatory agencies and are prequalified and recommended for use by the World Health Organization. The properties of these various typhoid vaccines are reviewed in this chapter.