Field Effectiveness of Vi Polysaccharide

To the Editor—Field investigations in the People’s Republic of China to determine the protective efficacy of typhoid Vi polysaccharide vaccine (Vi vaccine) were done among students attending a middle school [1]. Vi vaccine was offered to students even during an outbreak of typhoid fever. The efficacy was 73% among those immunized before the outbreak and 71% among vaccine recipients during the outbreak. Many vaccine failures during the vaccine efficacy trials might have been caused by infection with Salmonella serotype Typhi strains that were lacking the Vi antigen. Vi-negative Salmonella Typhi cause a disease indistinguishable from that caused by a Vi-positive strain [2]. On their entry to an intracellular niche, Vi-negative Salmonella Typhi are protected from the Vi antibody [3]. Since Vi vaccines would not elicit any cellular immunity, they would not stop intracellular replication of Salmonella Typhi. Vi-negative Salmonella Typhi selected during a slide agglutination test with Vi typing antiserum have been known for several decades. Salmonella Typhi isolates that lacked the ViaB genetic sequences were responsible for an epidemic of multidrug-resistant typhoid fever in Calcutta, India [4]. The role of Vi-negative Salmonella Typhi infections in the People’s Republic of China should be determined immediately, and bacterial field isolates should be characterized fully in a reference laboratory. A high molarity affects the expression of the Vi antigen, rendering an otherwise Vi-positive isolate into an apparently negative one. Genotyping investigations for ViaB sequences on isolates would indicate the role of Vi-negative Salmonella Typhi in any failures with Vi vaccine, in locally produced batches of vaccine [1] and in the conjugated Vi vaccine bound to nontoxic recombinant Pseudomonas aeruginosa exotoxin A [5]. Establishment of ViaB genotyping facilities in the People’s Republic of China would be cost effective, and characterization of Salmonella Typhi isolates would be an asset to antityphoid strategies. Genotyping would indicate the contribution of Vi-negative Salmonella Typhi in partial failures [1, 5] of Vi vaccines.