Prevention of Typhoid Fever in Nepal with the VI Capsular Polysaccharide ofSalmonella Typhi

Abstract

We conducted a pilot study followed by a large clinical trial in Nepal of the use of the capsular polysaccharide of Salmonella typhi (Vi) as a vaccine to prevent typhoid fever. In the pilot study, involving 274 Nepalese, there were no significant side effects of the Vi vaccine; about 75 percent responded with a rise in serum antibodies of fourfold or more. In the clinical trial, residents of five villages were given intramuscular injections of either Vi or, as a control, pneumococcus vaccine dispensed in coded, randomly arranged, single-dose syringes. There were 6907 participants, of whom 6438 were members of the target population (5 to 44 years of age); each was visited every two days. Those with temperatures of 37.8 degrees C or higher for three consecutive days were examined and asked to give blood for culture. Typhoid was diagnosed as either blood culture-positive or clinically suspected on the basis of bradycardia, splenomegaly, and fever, with a negative blood culture. Seventeen months after vaccination, the codes were broken for the 71 patients meeting the criteria for either culture-positive or clinically suspected typhoid. The attack rate of typhoid was 16.2 per 1000 among the controls and 4.1 per 1000 among those immunized with Vi (P less than 0.00001). The efficacy of Vi was 72 percent in the culture-positive cases, 80 percent in the clinically suspected cases, and 75 percent in the two groups combined. These data provide evidence that Vi antibodies confer protection against typhoid. Surveillance continues to determine the duration of Vi-induced immunity.

Host adapted serotypes of Salmonella enterica

“…The expression of a capsular polysaccharide, the Vi antigen, appears to be crucial for Typhi to survive in mouse and human macrophage cell lines and to resist to lysis by serum complement [65][66][67], whereas it does not appear to be necessary for epithelial cell invasion [68]. This antigen is also known to be associated with the virulence of the organism in i o and to confer immunity against typhoid fever, when injected alone, in areas with a high incidence of this disease [69,70]. This virulence factor is not uniquely found in Typhi but also in Paratyphi C and rarely, in Dublin and Citrobacter freundii, suggesting that horizontal gene transfer have occurred in the evolution of these bacteria [15,[71][72][73].…”

Vaccines based on the cell surface carbohydrates of pathogenic bacteria

“…Processing of zwitterionic capsular polysaccharides by an MHC II pathway has very recently been suggested (Cobb et al 2004). (Acharya et al 1987, Yang et al 2001. Vaccines containing two (Groups A and C), three (Groups A, C and W135) or four meningococcal (Groups A, C, Y and W135) CPSs are licensed.…”

Vaccines against typhoid fever

“…Previous exposure to S. Typhi does not seem to influence the immune response [21,22,23]. The efficacy of the Vi polysaccharide was assessed in the late 1980s in field trials in typhoid-endemic areas in Nepal and South Africa.…”

“…In South Africa, the vaccine was given to more than 11,000 children 6-14 years of age and exhibited a protective efficacy of 64% during the first 21 months after vaccination and an efficacy of 55% over three years [22,24]. In Nepal, the vaccine was tested in 6,900 individuals 5-44 years of age and resulted in 72% protective efficacy over 17 months [21,25]. Two weeks after immunization, about 80% of vaccinees exhibit a fourfold rise in antibody titres [20].…”