Vaccine Update: Recent Progress With Novel Vaccines, and New Approaches to Safety Monitoring and Vaccine Shortage.

Vaccines are increasingly based on new constructs, new technologies, and new compounds. Novel immunization programs are rapidly implemented globally. In this article, we highlight selected hot topics of this highly dynamic and broad field of scientific and public health development. The first section focuses on novel vaccines including malaria, dengue, serogroup B meningococcal, and respiratory syncytial virus vaccines and antibodies. The second section is addressing emerging strategies and programmatic challenges including maternal immunization, integrated mother-child safety monitoring, and finally coping strategies with vaccine shortages.

Interpretation of primary care physicians' attitude regarding rotavirus immunisation using diffusion of innovation theories.

To evaluate primary care physicians' attitude towards implementation of rotavirus (RV) immunisation into the Swiss immunisation schedule, an eight-question internet-based questionnaire was sent to the 3799 subscribers of InfoVac, a nationwide web-based expert network on immunisation issues, which reaches >95% of paediatricians and smaller proportions of other primary care physicians. Five demographic variables were also inquired. Descriptive statistics and multivariate analyses for the main outcome "acceptance of routine RV immunisation" and other variables were performed. Diffusion of innovation theory was used for data assessment. Nine-hundred seventy-seven questionnaires were returned (26%). Fifty percent of participants were paediatricians. Routine RV immunisation was supported by 146 participants (15%; so called early adopters), dismissed by 620 (64%), leaving 211 (21%) undecided. However, when asked whether they would recommend RV vaccination to parents if it were officially recommended by the federal authorities and reimbursed, 467 (48.5%; so called early majority) agreed to recommend RV immunisation. Multivariate analysis revealed that physicians who would immunise their own child (OR: 5.1; 95% CI: 4.1-6.3), hospital-based physicians (OR: 1.6; 95% CI: 1.1-2.3) and physicians from the French (OR: 1.6; 95% CI: 1.2-2.3) and Italian speaking areas of Switzerland (OR: 2.5; 95% CI: 1.1-5.8) were more likely to support RV immunisation. Diffusion of innovation theory predicts a >80% implementation if approximately 50% of a given population support an innovation. Introduction of RV immunisation in Switzerland is likely to be successful, if (i) the federal authorities issue an official recommendation and (ii) costs are covered by basic health care insurance.

Rotavirus vaccines: considerations for successful implementation in Europe.

A group of European experts in infectious diseases and vaccinology has met on several occasions to assess the rationale for universal vaccination against rotavirus infection of infants in Europe. On the basis of the available data, we concluded that vaccination was the best approach to prevent severe rotavirus gastroenteritis, and that European countries should consider implementing rotavirus vaccination in their routine immunisation programmes. The main barrier to the implementation of rotavirus vaccination in Europe is a general lack of awareness of stakeholders, policymakers, health-care professionals, and parents about rotavirus disease and the advantages of vaccination. Further studies on the cost of the disease and the benefit of vaccination, together with raising awareness are necessary steps to ensure successful implementation of rotavirus vaccination in Europe.

Superior relative efficacy of live attenuated influenza vaccine compared with inactivated influenza vaccine in young children with recurrent respiratory tract infections.

BACKGROUND: Young children have a high incidence of influenza and influenza-related complications. This study compared the efficacy and safety of cold-adapted influenza vaccine, trivalent (CAIV-T) with trivalent inactivated influenza vaccine (TIV) in young children with a history of recurrent respiratory tract infections (RTIs). METHODS: Children 6 to 71 months of age were randomized to receive 2 doses of CAIV-T (n = 1101) or TIV (n = 1086), 35 +/- 7 days apart before the start of the 2002-2003 influenza season and were followed up for culture-confirmed influenza, effectiveness outcomes, reactogenicity, and adverse events. RESULTS: Overall, 52.7% (95% confidence interval [CI] = 21.6%-72.2%) fewer cases of influenza caused by virus strains antigenically similar to vaccine were observed in CAIV-T than in TIV recipients. Greater relative efficacy for CAIV-T was observed for the antigenically similar A/H1N1 (100.0%; 95% CI = 42.3%-100.0%) and B (68.0%; 95% CI = 37.3%-84.8%) strains but not for the antigenically similar A/H3N2 strains (-97.1%; 95% CI = -540.2% to 31.5%). Relative to TIV, CAIV-T reduced the number of RTI-related healthcare provider visits by 8.9% (90% CI = 1.5%-15.8%) and missed days of school, kindergarten, or day care by 16.2% (90% CI = 10.4%-21.6%). Rhinitis and rhinorrhea, otitis media, and decreased appetite were the only events that were reported more frequently in CAIV-T subjects. There was no difference between groups in the incidence of wheezing after vaccination. CONCLUSIONS: CAIV-T was well tolerated in these children with RTIs and demonstrated superior relative efficacy compared with TIV in preventing influenza illness.

Early appearance of bactericidal antibodies after polysaccharide challenge of toddlers primed with a group C meningococcal conjugate vaccine: what is its role in the maintenance of protection?

The contribution of memory responses after meningococcal vaccination to protection may depend on the rapidity of the response. Toddlers were challenged with a licensed polysaccharide (PS) vaccine 1 year after vaccination with a single dose of meningococcal group C-CRM(197) conjugate (MCC) vaccine at the age of 12 to 15 months. Bactericidal antibodies and immunoglobulin G (IgG) antibodies detected by an enzyme-linked immunosorbent assay (ELISA) were measured before challenge and 4, 7, 14, or 21 Days later ("Days" refer to treatment groups, "days" to sampling days). Among 281 subjects in the intent-to-treat population, 173 per-protocol (PP) subjects were challenged with 10 microg PS antigen and 103 others with a 50-microg PS vaccinating dose. Capsular PS-specific ELISA IgG titers were negligible in baseline samples and increased only twofold within 4 days of PS administration. In contrast, the proportion of PP subjects with serum bactericidal antibody (SBA) titers of >or=1:8 or >or=1:128 increased, respectively, from 41% and 16% before challenge to 84% and 74% at Day 4 and to 100% and 97% at Day 7. Recipients of 50 microg PS responded with similar kinetics but showed a trend toward higher antibody levels. Unexpectedly, 69% of subjects bled on days 2 to 3 already had achieved SBA titers of >or=1:8. The majority of toddlers previously immunized with MCC and challenged 1 year later with PS antigen mounted protective levels of bactericidal antibody within 2 to 4 days.

Seroprevalence of Varicella-Zoster virus IgG antibodies in Swiss children during the first 16 months of age.

QUESTION UNDER STUDY: To investigate the persistence of maternal IgG antibodies against Varicella-Zoster virus (VZV) in infants and young children. METHODS: Serum specimens of children aged 0-16 months who had been hospitalized in our institution between 1994 and 1999 were identified from our routine serum collection. Exclusion criteria were: preterm delivery (<37 gestational weeks); suspected varicella infection or presence of exanthema of unknown etiology at time of serum collection; transfusion of blood products during 6 months preceding serum collection; foreign born mother; and previous VZV immunization. Serotesting for IgG antibodies against VZV was performed by use of a commercially available ELISA kit. RESULTS: Two hundred and fifty three serum specimens from 240 patients were analyzed. Age distribution of patients at time of specimen collection was: 0-3 months: n=57; >3-6 months: n=47; >6-9 months: n=47; >9-12 months: n=48; >12-16 months: n=54. Seroprevalence rates for IgG antibodies against VZV in the different age groups were 90% (0-3 months), 38% (>3-6 months); 0% (>6-9 and >9-12 months); and 7% (>12-16 months). CONCLUSIONS: Our results demonstrate high levels of passively acquired humoral immunity against varicella in Swiss infants during the first 3 months of life. Beyond the first 3 months of life IgG antibodies against VZV are lacking in the majority of patients and between 6 and 12 months of age all specimens tested were negative. Beyond the first year of life antibodies against varicella were detected in four samples, probably due to previous VZV infection. In accordance with current recommendations, VZV vaccination should ideally be administered to children 9 months of age and older, although our data indicate that successful immunization may be possible at earlier age (6 months onwards) in certain circumstances.

How do physicians immunize their own children? Differences among pediatricians and nonpediatricians.

CONTEXT: Immunization has an essential impact on public health worldwide. Numerous studies have shown the efficacy of different vaccines to protect individuals from various diseases. However, some parents choose not to vaccinate their children for reasons such as, among others, doubts regarding their usefulness, concerns over safety or efficacy, etc. Physicians are known to exert a direct influence on immunization rates by answering questions and clarifying misconceptions. Yet, it is unknown how they immunize their own children. OBJECTIVE: We sought to assess how physicians interested in vaccination issues immunized, or would immunize, their own children. DESIGN, SETTING, AND PARTICIPANTS: An 11-question, Web-based survey with a total of 102 discrete answers was sent to 2070 Swiss physicians in October 2004. All physicians were subscribers to a nonprofit, Web-based expert network (InfoVac, www.infovac.ch) that distributes monthly newsletters and answers question within 2 days on immunization issues. The InfoVac network reaches > 95% of pediatricians in Switzerland but < 20% of general practitioners. All responses were anonymous, and no identifier could be used to trace the participants of the survey. Questions were divided into 2 parts: (1) physicians who were parents were asked which vaccines they gave to their own children and at what age, and (2) all physicians were asked which vaccines they would give to their own child and at what age if they had a newborn child in 2004. Vaccines available in Switzerland at the time of the survey were offered as possible replies, and recommended vaccines were considered as those noted in the Swiss federal immunization schedule issued yearly. One question compared their immunization practice between their own children and their patients. Sociodemographics, qualifying year, membership in different professional groups, and their type of practice were also requested. Statistics. Standard descriptive statistics were used for sociodemographic characteristics. Univariate statistical analyses were performed for each variable to determine its relationship to the dependent variable, being a pediatrician or nonpediatrician. Logistic-regression analysis was used to calculate the adjusted odds ratios (ORs) and 95% confidence intervals (CIs), controlling for any statistically significant demographic variables that might function as confounders (gender, parenthood, workplace, year of diploma, and type of practice). For all statistical tests, differences were considered significant at P < .05. MAIN OUTCOME MEASURE: We performed a comparison of past and projected immunization rates in the children of pediatricians and nonpediatricians. RESULTS: One thousand seventeen valid questionnaires were received (response rate: 49.1%; pediatricians: 53.3%). Nine hundred fifteen physicians (90%) had > or = 1 child. All physicians reported immunizing children in their practice. Pediatricians were more likely to be women and to work in private practice than nonpediatricians but less likely to belong to a self-reported alternative medicine association. Among the nonpediatricians, 317 were general practitioners, 144 were internists, and 95 were other specialists. Ninety-two percent of pediatricians followed the official immunization recommendations for their own children. In contrast, after controlling for gender, workplace, type of practice, and year of diploma, nonpediatricians were more likely not to have immunized their children against measles, mumps, hepatitis B, or Haemophilus influenzae type b. They more frequently postponed diphtheria-tetanus-pertussis (DTP) (OR: 4.5; 95% CI: 2.0-10.19) and measles-mumps-rubella (MMR) vaccination. Although projected immunization rates were higher than effective rates, 10% of nonpediatricians would still not follow the official immunization recommendations in 2004. They would more frequently refrain from using combination vaccines and postpone DTP and MMR immunization to later in life. Several comparisons confirmed the weaker use of the more recently licensed vaccines by nonpediatricians. In addition to vaccines currently recommended in Switzerland, both groups of physicians added hepatitis A, influenza, and varicella vaccines to the vaccination schedule of their own children. Pediatricians were more likely to give pneumococcal (OR: 2.26; 95% CI: 1.004-4.68) and meningococcal C (OR: 2.26; 95% CI: 1.62-3.17) vaccines to their own children. In contrast, they were less likely to give tick-borne encephalitis virus vaccine (OR: 0.65; 95% CI: 0.44-0.95). CONCLUSIONS: Ninety-three percent of the surveyed physicians agree with the current official vaccination recommendations and would apply them to their own children. However, the observation that 5% of nonpediatricians would not use Haemophilus influenzae type b vaccine if they had a child born in 2004 is unexpected and concerning. In contrast, both groups gave additional vaccines than those recommended to their own children. Among physicians in Switzerland interested in immunization, a significant proportion of nonpediatricians decline or delay the immunization of their own children with the recommended MMR- or DTP-based combination vaccines, which indicates that clarification of misconceptions such as fear of "immune overload" has not yet reached important targets among health care providers who thus are unlikely to answer parental concerns adequately.