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Background: Live oral cholera vaccine CVD 103-HgR is well-tolerated and immunogenic when administered to adults, school age children and preschool children in a single 5 x 10(9) colony-forming unit dose. Because elicitation of immune responses after administration of a single dose is exceptional for any oral vaccine in any age group, CVD 103-HgR was used as a probe to investigate the clinical acceptability, practicality and immunogenicity of this vaccine in infants and toddlers 3 to 17 months of age., Methods: The study was undertaken successively in 12- to 17-month-olds (n = 104), 7- to 11-month-olds (n = 106) and 3- to 5-month-olds (n = 102). One-half of the subjects were randomly allocated to receive vaccine and the other one-half to receive placebo, in double blind fashion. After 2 weeks of double blind follow-up, all subjects received a dose of vaccine. Vibriocidal antibody titers were measured on coded sera collected at baseline and 2 weeks after each dosing. The buffered vaccine "cocktail" had a volume of 100 ml; subjects who ingested > or =70 ml were considered fully vaccinated., Findings: Only 37% of subjects overall (25% of 3- to 5-month-olds) ingested > or =70 ml of the cocktail. The vaccine was well-tolerated with no significant differences in the rate or severity of adverse reactions after ingestion of vaccine vs. placebo. Seroconversion after ingestion of a single dose of CVD 103-HgR was similar in fully vaccinated subjects (66%) and in those who ingested a smaller fraction of the vaccine cocktail (63%). Of subjects who ingested two doses, 5 of 118 excreted vaccine organisms on Day 7 after the first dose vs. 0 of 118 after the second dose., Interpretation: Single dose oral CVD 103-HgR is well-tolerated and immunogenic in infants even when a partial dose is ingested. The buffered vaccine cocktail that is readily imbibed by older children is not appealing to young infants, and improved vaccine formulations and delivery vehicles for immunizing infants must be sought.

Background: The cost of Haemophilus influenzae type b (Hib) conjugate vaccines has limited their use in non-industrialised countries. To identify more economical vaccination schedules, we carried out a randomised trial of the immunogenicity of alternative regimens to the standard three-dose series., Methods: 627 Chilean infants were randomly allocated to one of four regimens with either Hib polysaccharide-tetanus toxoid conjugate vaccine (PRP-T) or Hib oligosaccharide-diphtheria mutant toxoid conjugate vaccine (PRP-CRM197), for a total of eight groups. All infants receive diphtheria-tetanus-pertussis (DTP) vaccine at ages 2, 4, and 6 months. The regimens included three full doses, three fractional doses consisting of one half or one third of the full dose, and a regimen of two full doses (at age 4 and 6 months). The primary outcome was the proportion of infants with serum anti-polyribosylribitol phosphate (PRP, the type b capsular polysaccharide) concentrations of 0.15 microg/mL or more at age 8 months., Findings: 93% (95% CI 85-98) of infants vaccinated with three full doses of PRP-T or PRP-CRM197 (95% CI 84-98) achieved anti-PRP concentrations of 0.15 microg/mL or more at age 8 months, compared with 91% (83-96) to 100% (95-100) of infants immunised with any fractional-dose regimen. Of the infants vaccinated with two doses of PRP-T or PRP-CRM197, 99% (93-100) and 87% (77-93) developed anti-PRP concentrations of 0.15 microg/mL or more, respectively., Interpretation: 91% (83-96) to 100% (95-100) of infants immunised with one-half or one-third of a full dose of Hib conjugate developed protective antibody concentrations. Carrier priming with DTP may make two-dose schedules an option in some places. These alternative regimens could bring the cost of Hib vaccines within reach of countries that currently cannot afford them.

To assess whether combining a Haemophilus influenzae type b conjugate vaccine (PRP-T) and diphtheria-tetanus toxoid-pertussis (DTP) vaccine in a single syringe would impact adversely the antibody response and clinical protection conferred by pertussis vaccine, surveillance and a nested serosurvey were conducted among infants in a large-scale evaluation of PRP-T in Santiago. Infants received either combined PRP-T/DTP or DTP only at 2, 4, and 6 months of age. At 8 months, pertussis agglutinin, anti-pertussis toxin, and anti-filamentous hemagglutinin antibody levels in the PRP-T/DTP (137.7, 23.1, and 12.2, respectively) and DTP (142.9, 20.6, and 13.0, respectively) groups were comparable. The incidence of pertussis was similar among infants assigned to health centers administering combined PRP-T/DTP and those administering DTP alone (13.1 vs. 12.2 cases/10(5) child-years). Combined PRP-T/DTP vaccine did not diminish protection against pertussis.

Persons of blood group O are at increased risk of developing cholera gravis. In a randomized, placebo-controlled, double-blind safety-immunogenicity trial of live oral cholera vaccine CVD 103-HgR in 5- to 9-year-old Chilean children, vibriocidal antibody seroconversion (74% overall) did not differ by blood group. However, the reciprocal geometric mean titer (GMT) in blood group O vaccines (GMT = 486) was higher than that in non-O vaccines (GMT = 179) (P < 0.02).

CVD 103-HgR is an attenuated, AB+, live, recombinant vaccine strain, developed by deletion of the toxA gen in a virulent Vibrio cholerae 01, Inada classical strain (569B). In phase II studies conducted to date, CVD 103-HgR has been well tolerated and immunogenic in volunteers from both industrialized countries and cholera-endemic areas. In this study of safety, immunogenicity and excretion, 81 Chilean adults were randomly allocated to receive, in a double blind fashion, a single oral dose of 5 x 10(9) FU of CVD 103-HgR or placebo, (5 x 10(9) heat-killed E. Coli K12 organisms), in 100 ml of buffered water. Side effects were assessed by daily visits to the participants. Immunogenicity, (vibriocidal seroconversion), was investigated in blood drawn before and on days 8 and 28 after immunization, while stool cultures to assess excretion of the vaccine strain were performed on specimens obtained on days 1 and 7. None of the participants, (40 vaccinees and 41 placebo recipients), experienced untoward effects during 30 minutes of close surveillance after ingestion of the preparation; upon follow up, neither adverse events were more frequently reported by the vaccinees. 34/40 vaccinees, and 2/41 participants receiving placebo had a significant raise, (> = fourfold), in their vibriocidal titers; (85 vs 2%, p < 0.001). The peak postimmunization geometric mean titer, (222), was ten fold higher than the baseline vibriocidal titer. The vaccine strain was recovered in stool cultures from 8 participants, one of them excreted the strain in both specimens. We conclude that CVD-103-HgR is safe and immunogenic in Chilean adults.

An enzyme-linked immunosorbent assay (ELISA) measuring, in serum, immunoglobulin G (IgG), IgM, and IgA to Vi capsular polysaccharide antigen that was tyraminated (Vi-Tyr) to increase its binding efficiency to microtiter plates was compared with the standard passive hemagglutination assay (PHA) as a screening test for chronic Salmonella typhi carriers. Initially, three populations were evaluated: 22 healthy U.S. adults, 17 young Chilean adults with acute typhoid fever, and 51 Chileans who had bacteriologically confirmed S. typhi chronic carriage. IgG-specific Vi-Tyr antibodies were preferentially present in the S. typhi chronic carrier state. A total of 44 of 51 (81%) chronic carriers, 0 of 22 (0%) healthy U.S. adults, and 2 of 17 (12%) Chileans with acute typhoid fever had reciprocal IgG Vi-Tyr ELISA antibody titers in serum of greater than or equal to 200. The IgG Vi-Tyr ELISA was then compared with the PHA as a screening test for chronic carriers in 141 Chilean female food handlers. One woman was serologically incriminated as a carrier by both the IgG ELISA and PHA; her coprocultures were positive for S. typhi. One other woman, identified as a carrier by PHA, was negative by culture and IgG ELISA. The IgG Vi-Tyr ELISA is as sensitive as the PHA (86 versus 76%) and as specific (95 versus 95%) in screening for chronic carriers.