Typhoid fever vaccines: a meta-analysis of studies on efficacy and toxicity

Abstract

Objective: To estimate the efficacy and toxicity of typhoid fever vaccines. Design: Meta-analysis of randomised efficacy trials and both randomised and non-randomised toxicity studies of the parenteral whole cell, oral Ty21a, and parenteral Vi vaccines. Subjects: 1 866 951 subjects in 17 efficacy trials; 11 204 subjects in 20 toxicity studies. Main outcome measures: Pooled estimates of three year cumulative efficacy, year specific efficacy, and incidence of adverse events. Results: Three year cumulative efficacy was 73% (95% confidence interval 65% to 80%) for two doses of whole cell vaccines (based on seven trials); 51% (35% to 63%) for three doses of Ty21a vaccine (four trials); and 55% (30% to 71%) for one dose of Vi vaccine (one trial). For whole cell and Ty21a vaccines, regimens of fewer doses were less effective. Efficacy was shown to be significant for five years for whole cell vaccines, four years for Ty21a vaccine, and two years for Vi vaccine. Neither the age of vaccine recipient nor the incidence of typhoid fever in the control group (varying from 6 to 810 cases per 100 000 person years) affected the efficacy of the whole cell or Ty21a vaccines. After vaccination, fever occurred in 15.7% (11.5% to 21.2%) of whole cell vaccine recipients, 2.0% (0.7% to 5.3%) of Ty21a vaccine recipients, and 1.1% (0.1% to 12.3%) of Vi vaccine recipients. Conclusions: Whole cell vaccines are more effective than the Ty21a and Vi vaccines but are more frequently associated with adverse events. Whether the added efficacy of the whole cell vaccines outweighs their toxicity will depend on the setting in which vaccination is used.

Cell-mediated immune responses in humans after immunization with one or two doses of oral live attenuated typhoid vaccine CVD 909

“…Taken together, these observations, as well as those recently published [21], add further support to the contention that CVD 909 appears to be as immunogenic after one or two doses as the parent strain (CVD 908htrA) or the licensed Ty21a vaccine, which confers moderate protection in subjects following 3-4 doses of the lyophilized formulation in enteric-coated capsules [2,12,14,15,[36][37][38]. These results support the notion that expression of the capsule did not interfere with the ability of CVD 909 to elicit a wide array of CMI responses, and provide additional impetus for the continuing evaluation of CVD 909 as a leading oral typhoid vaccine candidate.…”

“…Vi polysaccharide is a parenteral vaccine that cannot stimulate CMI and fails to elicit responses to purified polysaccharides in children under 2 years of age [12,13]. Concerning Ty21a , this vaccine does not elicit anti-Vi antibodies (because it does not make Vi capsule) and is modestly immunogenic, requiring three or four doses to evoke protective immunity in ~47% to 96%, depending on the number of doses and formulations used and the time of surveillance [12,14,15].…”

Antibodies in Action: Role of Human Opsonins in Killing Salmonella enterica Serovar Typhi

“…Although typhoid fever vaccines have been available for over a century, they have ranged greatly in efficacy and reactogenicity (13,14). There are currently two safe and effective vaccines, Ty21a and Vi polysaccharide (Vi) vaccines, licensed in 56 and 92 countries, respectively (13,14,23,24,49).…”

Vaccines against typhoid fever

“…These studies demonstrated the efficacy of vaccines consisting of S. Typhi inactivated by heat and phenol or by acetone ranged from 51% to 88% in children and young adults and protection persisted for up to 7 years [10,11,12]. Although these early parenteral vaccines were clearly able to confer protection against typhoid fever, their global use as public health tools for routine vaccination was undermined by their high reactogenicity: the parenteral whole cell vaccines caused fever (6-30% of the recipients), headache (10%) and severe local pain (up to 35%) [13,14]. Furthermore, up to 10% of the vaccinees missed work or school owing to the vaccination [14].…”

“…Although these early parenteral vaccines were clearly able to confer protection against typhoid fever, their global use as public health tools for routine vaccination was undermined by their high reactogenicity: the parenteral whole cell vaccines caused fever (6-30% of the recipients), headache (10%) and severe local pain (up to 35%) [13,14]. Furthermore, up to 10% of the vaccinees missed work or school owing to the vaccination [14]. Consequently, the whole cell vaccines have been replaced by the well-tolerated Vi-based parenteral subunit vaccine and the oral attenuated live bacterial vaccine Ty21a.…”