Jaana Joensuu

BACKGROUND: Human caliciviruses (HuCV) cause outbreaks of gastroenteritis, but their role in sporadic diarrhea in young children is not well-established. METHODS: Children (n = 2398) participating in a trial of oral rhesus-human reassortant rotavirus tetravalent (RRV-TV) vaccine were evaluated from 2 months to 2 years of age. Stool specimens from 1477 episodes of acute gastroenteritis (788 in a placebo and 689 in a RRV-TV vaccine recipient group) were tested for human calicivirus (HuCV) by reverse transcriptase-PCR with the use of broadly reactive primers, and positive results were confirmed by Southern hybridization with probes specific for main genetic clusters of Genogroups I and II of HuCV. RESULTS: HuCV were detected in 158 (20%) and 155 (22%) cases of gastroenteritis in the placebo and RRV-TV vaccine groups, respectively. According to hybridization results, 8% of HuCV were of Genogroup I and 92% were of Genogroup II. The peak season of HuCV gastroenteritis was from November to February. Of the 148 patients with pure HuCV infection in the placebo group, 89% had vomiting, 79% had watery diarrhea, 21% had fever, 28% needed oral rehydration and 1.4% were hospitalized. The diarrhea in HuCV gastroenteritis was much less severe than that in rotavirus gastroenteritis, but vomiting was equally severe. There was no effect of RRV-TV vaccine on the frequency or clinical severity of HuCV gastroenteritis. CONCLUSION: HuCVs are second in frequency to rotaviruses as causative agents in acute gastroenteritis in young children in the community.

BACKGROUND: Development is ongoing to increase the serotype coverage of pneumococcal conjugate vaccines. We report here the immunogenicity and safety of a new 11-valent pneumococcal conjugate vaccine (Pn-PD) in infants. METHODS: In a randomized, single blind study, 154 Finnish infants received 1 of 3 regimens: 4 doses of Pn-PD at 2, 4, 6 and 12-15 months; 3 doses of the Pn-PD at 2, 4 and 6 months and 1 dose of 23-valent polysaccharide vaccine (PncPS) at 12-15 months; or 3 doses of the hepatitis B vaccine at 2, 4 and 6 months and Pn-PD at 12-15 months. Serum IgG antibodies to vaccine serotypes 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F were measured with an enzyme immunoassay at the ages of 2, 7 and 12-15 months and at 4 or 28 days after the last vaccination. Local and systemic reactions were recorded by parents during 8 days after each dose. Serious adverse reactions were recorded during the entire study period. RESULTS: There was a significant increase in the IgG concentrations to vaccine serotypes after 3 doses of Pn-PD. Antibody concentrations after the primary series varied between 1.26 and 4.92 microg/ml depending on the serotype and study group. PncPS vaccine induced a better booster response than the Pn-PD, measured at 28 days after the fourth dose. IgG concentrations after the Pn-PD booster ranged between 1.60 and 9.63 microg/ml and after the PncPS booster between 4.24 and 40.54 microg/ml, depending on the serotype. The antibody concentrations after the first dose of Pn-PD administered at 12-15 months increased significantly but were lower than after the fourth dose at the same age. No significant antibody increase was measured 4 days after the vaccinations at 12-15 months. The safety profile of the vaccine was acceptable. CONCLUSIONS: The Pn-PD we tested was immunogenic and safe in infants.

The cost-benefit ratio of tetravalent rhesus rotavirus vaccine (RRV-TV) in Finland for prevention of rotavirus gastroenteritis was assessed in a randomized, double-blind, placebo-controlled trial. Costs related to vaccination, side effects, and gastroenteritis were identified. Children received RRV-TV (n = 1,191) or placebo (n = 1,207) at 2, 3, and 5 months of age with other infant vaccinations. Prospective follow-up averaged 1.0 years per child. An intention-to-treat analysis was performed from the perspective of society. Nine cases of severe rotavirus gastroenteritis occurred in the RRV-TV group, versus 100 in the placebo group (P < .0001); mean cost per vaccinated child was 4 Finnish marks (FIM) in the RRV-TV group, versus 203 FIM in the placebo group. Side effects with related costs occurred after 11% and 7% of doses in the RRV-TV group and placebo group, respectively (P < .001); mean cost per child was 89 FIM vs. 75 FIM. The break-even cost (i.e., net benefit, excluding cost of vaccine) of RRV-TV in prevention of severe rotavirus gastroenteritis was 109 FIM (U.S. $19.60) per child.