Flagellar serotypes of Salmonella typhi in Indonesia: relationships among motility, invasiveness, and clinical illness.

While the H1-d flagellar serotype of Salmonella typhi has been found worldwide, the H1-j serotype occurs only in Indonesia. A cross-sectional survey in Indonesia compared epidemiologic, clinical, and pathogenetic characteristics of these two serotypes. S. typhi isolates were collected from patients with acute typhoid fever in four Indonesian cities. Flagellar serotype was determined by polymerase chain reaction amplification of the fliC locus of the flg gene. Of 321 isolates, 51 (15.9%) were H1-j. Patients with H1-j infection were older than those with H1-d (P < .001). Among 30 patients with known clinical outcomes, H1-j infection was associated with milder clinical illness than H1-d (P = .06). In vitro, H1-j isolates were both less motile on semi-solid agar plates (P = .004) and less invasive of HEp-2 cells (P = .002) than H1-d isolates. The association of decreased severity of illness with decreased motility and invasiveness suggests that flagellar properties are a component of S. typhi's virulence.

Oral immunisation against typhoid fever in Indonesia with Ty21a vaccine.

When tested under conditions of moderate transmission of typhoid fever, a liquid formulation of the oral typhoid fever vaccine Ty21a had a protective efficacy of 96% in Egypt, and an enteric coated capsule formulation had an efficacy of 67% in Chile. We compared the two formulations under conditions of intense transmission of typhoid fever in Indonesia in a randomised, double-blind trial. 20,543 subjects (age range 3-44 years) received either three doses of enteric coated capsules containing placebo or live Ty21a, or three doses of lyophilised placebo or live Ty21a reconstituted with phosphate buffer. During 30 months of follow-up, the rate of blood-culture-positive typhoid fever among controls was 810/100,000 per year. Rates of typhoid fever were 379/100,000 per year for subjects who received the liquid formulation of vaccine and 468/100,000 per year for subjects who received enteric coated capsules. The protective efficacies of the liquid and enteric coated formulations were 53% and 42%, respectively. Neither formulation protected against infection with Salmonella paratyphi A. No major side-effects were noted, but the overall incidence of side-effects was greater in the vaccine groups. Under conditions of intense transmission, Ty21a protected against typhoid fever; however, because Ty21a will not protect all individuals, there is a need for additional approaches to prevent the disease.

PIP: When tested under conditions of moderate transmission of typhoid fever, a liquid formulation of the oral typhoid fever vaccine, Ty21a, had a protective efficacy of 96% in Egypt, and an enteric coated capsule formulation had an efficacy of 67% in Chile. The authors compared the 2 formulations under conditions of intense transmission of typhoid fever in Indonesia in a randomized, double blind trial. 20,543 subjects (age range 3-44 years) received either 3 doses of enteric-coated capsules containing placebo or live Ty21a, or 3 doses of lyophilized placebo or live Ty21a reconstituted with phosphate buffer. During 30 months of followup, the rate of blood-culture-positive typhoid fever among controls was 810/100,000/year. Rates of typhoid fever were 379/100,000/year for subjects who received the liquid formulation of vaccine and 468/100,000/year for subjects who received enteric coated capsules. The protective efficacies of the liquid and enteric coated formulations were 53% and 42%, respectively. Neither formulation protected against infection with Salmonella paratyphi A. No major side effects were noted, but the overall incidence of side effects was greater in the vaccine groups. Under conditions of intense transmission, Ty21a protected against typhoid fever; however since it will not protect all individuals, there is a need for additional approaches in prevention of the disease.

Immunogenicity of Vibrio cholerae O1 toxin-coregulated pili in experimental and clinical cholera.

A functional tcpA gene, encoding the major subunit of toxin-coregulated pili (TCP), is necessary for Vibrio cholerae O1 Ogawa strain 395 to colonize the human intestine and confer protective immunity to virulent challenge. The immunogenicity of TCP and other antigens in experimental and naturally acquired cholera was determined. Seroconversion to cholera toxin (CT), whole cell preparations, and to Ogawa lipopolysaccharide but not to purified native TCP or to a TcpA mimiotope was found in volunteers. Local intestinal secretory immunoglobulin A from volunteers showed conversions to cholera toxin and lipopolysaccharide but not to TCP. Cholera patients in Indonesia showed a seroconversion rate to TCP of 3 of 6 and a seroconversion to a TcpA mimiotope of 1 of 6. Volunteer and patient sera showed similar vibriocidal seroconversions when assayed against either TCP-positive and TCP-negative V. cholerae O1 strains, suggesting that TCP do not contribute demonstrably to the vibriocidal antigen. We conclude that although seroconversion to TCP can occur in naturally acquired cholera, solid long-term protection can be engendered in the absence of a detectable anti-TCP immune response.