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Volume 344:1263-1269 April 26, 2001 Number 17 Next

	Full Text PDF Editorial by Guerrant, R. L. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Typhoid fever is common in developing countries. The licensed typhoid vaccines confer only about 70 percent immunity, do not protect young children, and are not used for routine vaccination. A newly devised conjugate of the capsular polysaccharide of Salmonella typhi, Vi, bound to nontoxic recombinant Pseudomonas aeruginosa exotoxin A (rEPA), has enhanced immunogenicity in adults and in children 5 to 14 years old and has elicited a booster response in children 2 to 4 years old.

Methods In a double-blind, randomized trial, we evaluated the safety, immunogenicity, and efficacy of the Vi-rEPA vaccine in children two to five years old in 16 communes in Dong Thap Province, Vietnam. Each of the 11,091 children received two injections six weeks apart of either Vi-rEPA or a saline placebo. Cases of typhoid, diagnosed by the isolation of S. typhi from blood cultures after 3 or more days of fever (a temperature of 37.5°C or higher), were identified by active surveillance over a period of 27 months. We estimated efficacy by comparing the attack rate of typhoid in the vaccine group with that in the placebo group.

Results S. typhi was isolated from 4 of the 5525 children who were fully vaccinated with Vi-rEPA and from 47 of the 5566 children who received both injections of placebo (efficacy, 91.5 percent; 95 percent confidence interval, 77.1 to 96.6 percent; P<0.001). Among the 771 children who received only one injection, there was 1 case of typhoid in the vaccine group and 8 cases in the placebo group. Cases were distributed evenly among all age groups and throughout the study period. No serious adverse reactions were observed. In all 36 children studied four weeks after the second injection of the vaccine, levels of serum IgG Vi antibodies had increased by a factor of 10 or more.

Conclusions The Vi-rEPA conjugate typhoid vaccine is safe and immunogenic and has more than 90 percent efficacy in children two to five years old. The antibody responses and the efficacy suggest that this vaccine should be at least as protective in persons who are more than five years old.

Source Information

From the National Institute of Child Health and Human Development (F.Y.C.L., Z.K., D.A.B., J.B.R., R.S., S.C.S.), and the National Institute of Diabetes and Digestive and Kidney Diseases (J.S.), National Institutes of Health, Bethesda, Md.; and Dong Thap Provincial Hospital, Cao Lânh (V.A.H., P.V.B.), the Pasteur Institute, Ho Chi Minh City (H.B.K., T.C.T.), and the National Institute of Hygiene and Epidemiology, Hanoi (D.D.T.) — all in Vietnam.

Address reprint requests to Dr. Lin at the National Institute of Child Health and Human Development, Rm. 7B03, 6100 Executive Blvd., Bethesda, MD 20892-7510, or at link{at}exchange.nih.gov.

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