Progress in vaccines against typhoid fever.

The widely available heat-phenol-inactivated whole cell typhoid vaccine, which provides approximately 65% protection, has limited usefulness because of the adverse reactions it evokes. In contrast, several new typhoid vaccines promise protection without reactogenicity. Attenuated oral vaccine Ty21a has been evaluated in three field trials of efficacy in Santiago, Chile, involving 530,000 schoolchildren. Three doses of Ty21a in an enteric-coated formulation given within one week provided 69% efficacy for at least four years. Fewer doses conferred less protection, while adding a fourth dose significantly enhanced protection; increasing the interval between doses did not improve protection. Large-scale vaccination with Ty21a appeared to cause a herd-immunity effect. Ty21a has reached the stage of being a practical tool for public health. With respect to other vaccines, the safety and immunogenicity of an auxotrophic (Aro-,Pur-) Salmonella typhi mutant (strain 541Ty) has recently been evaluated. Lastly, parenteral purified Vi polysaccharide of S. typhi was safe and immunogenic and provided 64%-72% protection (for at least 17-21 months) in controlled field trials in Nepal and South Africa.