HTRA1 and typhoid fever: Examples of carrier vaccines in which pleiotropic deletion mutations resulted in clinically acceptable attenuated vaccine candidates include deletions of phoP/phoQ (Ty1033, [8]), ssaV (TSB7, [11]), and htrA (CVD 908-htrA; [7,67,68]); all of these attenuated strains can no longer establish systemic infections within the host, which eventually leads to the classic pyrogenic state typical of typhoid fever.