Safety and efficacy of the pentavalent human-bovine (WC3) reassortant rotavirus vaccine in healthy premature infants

BACKGROUND: Premature infants seem to be at greater risk of hospitalization from rotavirus gastroenteritis than term infants. Safety and efficacy of the pentavalent human-bovine (WC3) reassortant rotavirus vaccine were assessed in premature infants enrolled in the large-scale, blinded, placebo-controlled rotavirus efficacy and safety trial (REST). METHODS: Healthy infants 6-12 weeks of chronologic age at study entry were randomized to receive 3 oral doses of pentavalent rotavirus vaccine or placebo at 4- to 10-week intervals. Infants born at < or =36 weeks of gestational age were eligible if thriving at the time of enrollment. Safety and efficacy were retrospectively assessed in these premature infants comparing vaccine with placebo recipients. Cases of rotavirus gastroenteritis were defined as forceful vomiting and/or > or =3 watery or looser-than-normal stools within a 24-hour period, accompanied by detection of rotavirus antigen in the stool. RESULTS: A total of 2070 infants between 25 and 36 gestational weeks received at least 1 dose of vaccine or placebo; 1005 vaccine recipients and 1061 placebo recipients were evaluable for safety. Serious adverse events occurred in 55 vaccine recipients (5.5%) and 62 placebo recipients (5.8%). In a nested substudy of 308 premature infants evaluable for detailed safety (154 in each group), the frequencies of fever, diarrhea, vomiting, and irritability were comparable between vaccine and placebo recipients. Overall, 3 doses of the pentavalent vaccine reduced the rate of hospitalizations and emergency department visits in premature infants due to rotavirus gastroenteritis by 100% (95% CI: 82.2-100) compared with placebo. The vaccine also prevented 73.0% (95% CI: -2.2-95.2) of rotavirus gastroenteritis cases of any severity. CONCLUSIONS: In this post hoc analysis of healthy premature infants, the pentavalent rotavirus vaccine was generally well-tolerated and substantially reduced rotavirus-attributable hospitalizations and emergency department visits compared with placebo. Overall, vaccine safety and efficacy seemed to be generally comparable to the results in the REST study population as a whole. These results support vaccinating healthy premature infants on the same schedule as term infants.     

Cost of influenza hospitalization at a tertiary care children's hospital and its impact on the cost-benefit analysis of the recommendation for universal influenza immunization in children age 6 to 23 months

OBJECTIVE: To calculate the costs of influenza hospitalization at a tertiary care children's hospital as the basis of a cost-benefit analysis of the new influenza vaccine recommendation for children age 6 to 23 months. STUDY DESIGN: We reviewed the medical records of all patients admitted to Children's Memorial Hospital (CMH) in 2002 diagnosed with influenza. Total hospital costs were obtained from the Business Development Office. RESULTS: Thirty-five charts were analyzed. Both of the 2 patients requiring mechanical ventilation and 4 of 6 patients admitted to the intensive care unit had high-risk underlying medical conditions. Nine children were age 6 to 23 months; 4 of these 9 had no preexisting medical conditions. Had all 18 high-risk children over age 6 months been protected from influenza, approximately $350,000 in hospital charges could have been saved. CONCLUSIONS: Preventing the additional 4 hospitalizations in the otherwise low-risk children age 6 to 23 months for whom vaccine is currently recommended would have cost approximately $281,000 ($46/child) more than the hospital charges saved. When all children age 6 to 23 months are considered, influenza vaccination is less costly than other prophylactic measures. Addition of indirect costs, deaths, outpatient costs, and the cost of secondary cases would favor the cost:benefit ratio for influenza vaccination of all children age 6 to 23 months.     

Safety, immunogenicity and efficacy in healthy infants of G1 and G2 human reassortant rotavirus vaccine in a new stabilizer/buffer liquid formulation

BACKGROUND: A refrigerator-stable rotavirus (RV) vaccine that withstands gastric acid is anticipated to permit more widespread use of RV vaccine. OBJECTIVE: We investigated for the first time in infants an oral, liquid formulation of G1 and G2 human bovine reassortant rotavirus vaccine (HRRV) with a new stabilizer/buffer (S/B) containing sucrose, sodium phosphate and sodium citrate. METHODS: During 1997 through 1998, 731 healthy infants approximately 2 to 4 months of age were enrolled at 19 US sites to receive 3 HRRV or placebo doses approximately 6 to 8 weeks apart in a partially double blinded study. Infants were randomized to: (1) HRRV with no S/B but with prefeeding; (2) HRRV plus 1 of 3 different concentrations/volumes of S/B; or (3) placebo. RESULTS: No serious vaccine-related adverse experiences or intussusception cases were reported. No statistically significant differences were observed between vaccine and placebo recipients for fever (> or =38.1 degrees C) 0 to 7 days after any dose, irritability, vomiting or diarrhea incidence 0 to 42 days after any dose. Vaccine virus shedding among vaccine recipients was uncommon. Among S/B vaccine groups, proportions of infants with a > or =3-fold titer rise from baseline to Postdose 3 for G1 serum-neutralizing antibody (SNA), G2 SNA, WC3 SNA, serum anti-RV IgA, serum anti-RV IgG and stool anti-RV IgA were generally similar to those of the prefed non-S/B group. CONCLUSIONS: HRRV with a new S/B was generally well-tolerated; immunogenicity was generally similar to the prefed non-S/B group. No intussusception cases were reported, but the small sample size precluded a definitive conclusion. A large international clinical study is under way to address safety and efficacy of an S/B formulation of a pentavalent version of HRRV.     

Influenza vaccine effectiveness in healthy 6- to 21-month-old children during the 2003-2004 season

OBJECTIVE: To assess the clinical effectiveness of influenza vaccine in preventing influenza-like illness (ILI) office visits. STUDY DESIGN: We analyzed billing and immunization registry data for healthy 6- to 21-month-olds from 5 Denver, Colorado pediatric practices (n = 5193). ILI and pneumonia/influenza (a subset of ILI) were defined from International Classification of Diseases, Ninth Revision, Clinical Modification codes for office visits occurring during peak influenza season. Partially vaccinated (PV) and fully vaccinated (FV) patients were defined as having 1 shot and 2 shots, respectively, more than 14 days before the first ILI visit. The likelihood of an ILI visit was determined using a Cox proportional hazards model accounting for patient characteristics, practice site, and immunization status. RESULTS: A total of 28% of the patients had an ILI office visit, and 5% had a pneumonia/influenza visit. Hazard ratios (HRs) for FV versus UV were 0.31 (95% confidence interval [CI] = 0.3 to 0.4) for ILI and 0.13 (95% CI = 0.1 to 0.2) for pneumonia/influenza, corresponding to a vaccine effectiveness (1 - HR x 100) of 69% for ILI and 87% for pneumonia/influenza. The corresponding HRs for PV versus UV were 1.0 (95% CI = 0.9 to 1.2) and 1.1 (95% CI = 0.8 to 1.5). CONCLUSIONS: Although 2 doses of vaccine were 69% effective against ILI office visits and 87% effective against pneumonia/influenza office visits, 1 dose did not prevent office visits during the 2003-2004 influenza season.