Noninferior immunogenic responses to all 4 human papillomavirus types in the quadrivalent vaccine permit the bridging of efficacy data that were generated in young women to girls. The results in boys lend support for the implementation of gender-neutral human papillomavirus vaccination programs. This vaccine generally was well tolerated.

No abstract

Summary of study A multi-country randomized, placebo-controlled trial of the safety, immunogenicity and efficacy of respiratory syncytial virus (RSV) F-protein nanoparticle vaccine was undertaken in 4,636 pregnant women and their infants. RSV F-protein vaccine was safe and immunogenic in the pregnant women inducing anti-F IgG, palivizumab-competing antibodies and RSV neutralizing antibodies that were transferred to the fetus. Although the primary endpoint of prevention of RSV-specific medically-significant lower respiratory tract infection (MS-LRTI) was not met per protocol criteria for efficacy (i.e. 97.52% lower bound >30%), vaccine efficacy was 39.4% (97.52% CI: -1.0, 63.7%; p=0.0278) in infants 0-90 days age. Furthermore, there was a 58.8% (95% CI 31.9, 75.0%) lower rate of RSV LRTI with severe hypoxemia (secondary endpoint) through to 90 days of age in the expanded intent-to-treat analysis. The number of women needed to be vaccinated to prevent RSV-specific MS-LRTI or LRTI with severe hypoxemia in their infants through to 180 days of life were 88 and 82, respectively. Background RSV is the dominant cause of severe lower respiratory tract infection (LRTI) in infants, with most severe disease concentrated in younger-age infants. Methods Healthy, pregnant women between 28 and 36 weeks gestation, with expected delivery near the start of the RSV season, were randomized to a single intramuscular dose of nanoparticle RSV F-protein vaccine, or placebo in a 2:1 ratio. Their infants were followed for 180 days for medically-significant LRTI (MS-LRTI), LRTI with severe hypoxemia and/or LRTI- hospitalization. RSV detection was performed centrally by PCR. Safety evaluation continued until 364 days age. Results 4,636 women were randomized, with 4,579 live births. Over the first 90 days of life, efficacy against RSV-MS-LRTI was 39.4% (97.52%CI: -1.0, 63.7%; p=0.0278) and 41.4% (95%CI: 5.3, 61.2%) in the per protocol and expanded intent-to-treat (eITT) analyses, respectively. There was a lower rate (efficacy 58.8%; 95%CI 31.9, 75.0% in eITT analysis; not adjusted for multiplicity) of RSV-LRTI with severe hypoxemia in infants of vaccinees through 90 days age. Pneumonia reported as a serious adverse events was 49.4% less common in infants of vaccinees (2.6%) than placebo-recipients through 364 days age. Conclusions Maternal vaccination with RSV F-nanoparticle vaccine was safe and immunogenic. The prespecified primary endpoint success criterion (efficacy 97.5% lower bound ≥30%) was not achieved. However, maternal immunization was associated with reduced risk of RSV-confirmed MS-LRTI and LRTI with severe hypoxemia in early infancy. Trial Registration Number ClinicalTrials.Gov: NCT02624947. Funding statement Funded by Novavax, with supporting grant from the Bill and Melinda Gates Foundation.

Objectives -To determine the prevalence of asthma in the past 12 months in Melbourne schoolchildren aged 7, 12, and 15 years and to compare the prevalence of a history of asthma with that of 26 years ago.Design -A questionnaire on respiratory symptoms was distributed to children for completion by parents and return to the school. Subjects were selected by a stratified cluster design.Setting-Government and non-government schools in the greater Melbourne area, Australia.Subjects Conclusions-The current prevalence of asthma in Melbourne schoolchildren is high and has risen substantially over the past 26 years.

The usefulness of surveys for measuring the severity of asthma in school-age children depends on the availability of reliable and valid questionnaires. The aim of this study was to develop a measure of functional severity of asthma over the previous 12 mo, for use in population studies and in investigating treatment regimens. Of 10,198 children surveyed, 9,192 (90%) in school Years 2, 7, and 10 (mean ages 8, 13, and 16 yr) in Melbourne were screened for wheeze. The parents of the 1,267 children with wheeze were interviewed. Symptoms and restriction of activity due to asthma were analyzed using factor analysis and the partial credit version of the item response theory measurement model. The result was a continuous severity scale that was highly consistent with the data, and with goodness of fit statistics indicating the severity of 97% of children was well described by the scale. The scale correlated significantly with school absence due to wheeze (r = 0.35), functional impairment during the 2 wk before interview (Functional Status II-R [FSII-R], r = 0.30), visits to medical care for wheeze (r = 0.22), and amount of medication (r = 0.36). For descriptive purposes, a simple index with four bands of severity was developed from the continuous severity scale: low severity (47% of children with wheeze), moderate (30%), mild (18%), and high (5%). The scale and index facilitate standardized description of the impact of asthma on daily life on the basis of responses to six survey questions.

HE DISEASE BURDEN OF SEAsonal influenza in the pediatric population is generally attributed to a combination of immunologic naivety, prolonged virus shedding, and enhanced transmission opportunity in child-care and educational institutions. 1 Consistent with this experience, initial reports of the introduction and indigenous transmission of 2009 influenza A(H1N1) infection in many countries have largely involved children, 2 often attending day or boarding schools. [3][4][5] Serosurveys have demonstrated little or no cross-reactivity of the pediatric sera sample to the new virus strain, under-Context In the ongoing influenza pandemic, a safe and effective vaccine against 2009 influenza A(H1N1) is needed for infants and children.Objective To assess the immunogenicity and safety of a 2009 influenza A(H1N1) vaccine in children.Design, Setting, and Participants Randomized, observer-blind, age-stratified, parallel group study assessing 2 doses of an inactivated, split-virus 2009 influenza A(H1N1) vaccine in 370 healthy infants and children aged 6 months to less than 9 years living in Australia.Intervention Intramuscular injection of 15 µg or 30 µg of hemagglutinin antigen dose of monovalent, unadjuvanted 2009 influenza A(H1N1) vaccine in a 2-dose regimen, administered 21 days apart.Main Outcome Measures Hemagglutination inhibition assay to estimate the proportion of participants with antibody titers of 1:40 or greater, seroconversion, or a significant antibody titer increase, and factor increase in geometric mean titer. Assessments of solicited adverse events during 7 days and unsolicited adverse events for 21 days after each vaccination. ResultsFollowing the first dose of vaccine, antibody titers of 1:40 or greater were observed in 161 of 174 infants and children in the 15-µg group (92.5%; 95% confidence interval [CI], 87.6%-95.6%) and in 168 of 172 infants and children in the 30-µg group (97.7%; 95% CI, 94.2%-99.1%). Corresponding seroconversion rates were 86.8% (95% CI, 80.9%-91.0%) and 94.2% (95% CI, 89.6%-96.8%), and factor increases in geometric mean titer were 13.6 (95% CI,). All participants demonstrated antibody titers of 1:40 or greater after the second vaccine dose. Immune responses were robust regardless of age, baseline serostatus, or seasonal influenza vaccination status. The majority of adverse events were mild to moderate in severity. ConclusionOne 15-µg dose of vaccine was immunogenic in infants and children starting at 6 months of age and vaccine-associated reactions were mild to moderate in severity. Trial Registration clinicaltrials.gov Identifier: NCT00940108

BackgroundMaintaining high levels of childhood vaccinations is important for public health. Success requires better understanding of parents' perceptions of diseases and consequent decisions about vaccinations, however few studies have considered this from the theoretical perspectives of risk perception and decision-making under uncertainty. The aim of this study was to examine the utility of subjective risk perception and decision-making theories to provide a better understanding of the differences between immunisers' and non-immunisers' health beliefs and behaviours.MethodsIn a qualitative study we conducted semi-structured in-depth interviews with 45 Australian parents exploring their experiences and perceptions of disease severity and susceptibility. Using scenarios about 'a new strain of flu' we explored how risk information was interpreted.ResultsWe found that concepts of dread, unfamiliarity, and uncontrollability from the subjective perception of risk and ambiguity, optimistic control and omission bias from explanatory theories of decision-making under uncertainty were useful in understanding why immunisers, incomplete immunisers and non-immunisers interpreted severity and susceptibility to diseases and vaccine risk differently. Immunisers dreaded unfamiliar diseases whilst non-immunisers dreaded unknown, long term side effects of vaccines. Participants believed that the risks of diseases and complications from diseases are not equally spread throughout the community, therefore, when listening to reports of epidemics, it is not the number of people who are affected but the familiarity or unfamiliarity of the disease and the characteristics of those who have had the disease that prompts them to take preventive action. Almost all believed they themselves would not be at serious risk of the 'new strain of flu' but were less willing to take risks with their children's health.ConclusionThis study has found that health messages about the risks of disease which are communicated as though there is equality of risk in the population may be unproductive as these messages are perceived as unbelievable or irrelevant. The findings from this study have implications beyond the issue of childhood vaccinations as we grapple with communicating risks of new epidemics, and indeed may usefully contribute to the current debate especially in the UK of how these theories of risk and decision-making can be used to 'nudge' other health behaviours.

This study investigated mothers' perceptions of vaccine‐preventable diseases and associated vaccines in terms of perceived susceptibility, severity, benefits and barriers. A purposive sampling strategy was used to choose mothers whose only or youngest child was completely, incompletely (behind the recommended immunisation schedule) or partially (parents chose or advised not to have a specific immunisation) immunised or had no immunisations. Semi‐structured interviews found that complete immunisers believed the risk of vaccines was lower than the risk from disease and that the likelihood of contracting many of these diseases was low. Incomplete immunisers perceived vaccines to be less effective in preventing disease and were often confused about which diseases the vaccines would protect against. Non‐immunisers were more concerned about unknown, long‐term side effects of vaccines than the diseases. Many mothers who did immunise believed that preventing diseases was not always possible and for diseases such as measles, mumps and rubella, it was not always necessary nor desirable. Vaccines were perceived as placing stress on the immune system rather than strengthening it. Important themes relating to barriers to the decision to immunise were a lack of ‘balanced’, detailed information and poor communication between health providers and parents. The major barrier to timely, age‐appropriate immunisations was the occurrence of minor illnesses in the target child or the family. This study found that many mothers were balancing the risks of immunising with the risks of not immunising and this must be taken into account, along with factors such as difficulties in obtaining immunisations.