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A Highly Effective Typhoid Vaccine at Last?

The 16 to 33 million cases of typhoid fever that occur each year, principally in Southeast Asia, result in approximately 600,000 deaths. Currently licensed typhoid vaccines are only about 70 percent effective in older children and adults and fail to protect young children; consequently, routine immunization programs don't include typhoid vaccine. NIH and Vietnamese investigators report that a new Salmonella typhi conjugate vaccine, constructed analogously to Haemophilus influenzae vaccine, has high protective efficacy in young children.

This double-blind, randomized, NIH- and manufacturer-supported trial was designed to evaluate a new typhoid vaccine comprising the capsular polysaccharide of S. typhi, Vi, conjugated to nontoxic recombinant Pseudomonas aeruginosa exotoxin A (Vi-rEPA). Active surveillance of 11,091 children, 2 to 5 years old, residing in the typhoid-endemic Mekong Delta of Vietnam, lasted for 27 months. Four of 5525 children who received 2 injections of Vi-rEPA (6 weeks apart) in 1998 developed blood-culture-positive typhoid fever, compared with 47 of 5566 placebo-inoculated children (efficacy, 91.5 percent). One of 388 children who received 1 vaccine injection developed typhoid fever, compared with 8 of 383 placebo recipients (efficacy, 87.7 percent). All 21 children requiring hospitalization were placebo recipients. No serious vaccine-associated adverse effects occurred; 20 Vi-rEPA recipients had arm swelling of more than 5 cm after their second injection. All 36 children studied serologically developed at least 10-fold rises in serum IgG Vi antibodies 4 weeks after their second injection of Vi-rEPA. Serologic responses persisted for at least 2 years in vaccinees.

Comment: Vi-rEPA is a highly effective vaccine in young children, representing a major advance in potential control of typhoid fever. The antibody levels it induces strongly suggest that it would also be highly protective in older children and adults, including travelers, laboratory workers, and military populations. If Vi-rEPA also proves immunogenic and safe for infants, it should be added to WHO global immunization programs.

— N Blacklow

Published in Journal Watch Infectious Diseases May 10, 2001

Citation(s):

Lin FY et al. The efficacy of a Salmonella typhi Vi conjugate vaccine in two-to-five- year-old children. N Engl J Med 2001 Apr 26 344 1263-1269.

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Guerrant RL and Kosek M. Polysaccharide conjugate typhoid vaccine. N Engl J Med 2001 Apr 26 344 1322-1323.

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