Typhoid

Typhoid fever is a severe systemic infection caused by the human-adapted Salmonella enterica serovar Typhi (S. Typhi). Paratyphoid fever is indistinguishable from typhoid fever in its clinical presentation but is associated with other typhoidal Salmonella serovars, including the human-adapted S. enterica serovars Paratyphi A, Paratyphi B, Paratyphi C, or Sendai. Although eradicated in most developed countries, these illnesses continue to be a major contributor to morbidity and mortality worldwide, and the emergence of antibiotic resistance is beginning to limit treatment options. Sanitation of drinking water is effective in reducing transmission of typhoid and paratyphoid fever, but eradication of these diseases also requires management of human carriers. Typhoidal Salmonella serovars are closely related genetically to nontyphoidal Salmonella serovars, which are associated with a localized gastroenteritis in humans. Recent studies suggest that differences in the clinical presentation of typhoid fever and gastroenteritis can be attributed to virulence mechanisms that enable typhoidal Salmonella serovars to evade innate immunity but that are absent from nontyphoidal Salmonella serovars. One such factor is the virulence capsular polysaccharide (Vi antigen) of S. Typhi and S. Paratyphi C. Studies on immunity to typhoid fever have resulted in licensing of a killed whole-cell parenteral typhoid vaccine, a live-attenuated oral typhoid vaccine, and a parenteral vaccine consisting of purified Vi antigen. Our entry will review basic and applied research on this enigmatic human disease.