Eva Netterlid

Quadrivalent Human Papillomavirus Vaccine Effectiveness: A Swedish National Cohort Study

Background Incidence of condyloma, or genital warts (GW), is the earliest possible disease outcome to measure when assessing the effectiveness of human papillomavirus (HPV) vaccination strategies. Efficacy trials that follow prespecified inclusion and exclusion criteria may not be fully generalizable to real-life HPV vaccination programs, which target a broader segment of the population. We assessed GW incidence after on-demand vaccination with quadrivalent HPV vaccine using individual-level data from the entire Swedish population. Methods An open cohort of girls and women aged 10 to 44 years living in Sweden between 2006 and 2010 (N > 2.2 million) was linked to multiple population registers to identify incident GW in relation to HPV vaccination. For vaccine effectiveness, incidence rate ratios of GW were estimated using time-to-event analyses with adjustment for attained age and parental education level, stratifying on age at first vaccination. Results A total of 124 000 girls and women were vaccinated between 2006 and 2010. Girls and women with at least one university-educated parent were 15 times more likely to be vaccinated before age 20 years than girls and women whose parents did not complete high school (relative risk ratio = 15.45, 95% confidence interval [CI] = 14.65 to 16.30). Among those aged older than 20 years, GW rates declined among the unvaccinated, suggesting that HPV vaccines were preferentially used by women at high risk of GW. Vaccination effectiveness was 76% (95% CI = 73% to 79%) among those who received three doses of the vaccine with their first dose before age 20 years. Vaccine effectiveness was highest in girls vaccinated before age 14 years (effectiveness = 93%, 95% CI = 73% to 98%). Conclusions Young age at first vaccination is imperative for maximizing quadrivalent HPV vaccine effectiveness.

Tracking parental attitudes on vaccination across European countries: The Vaccine Safety, Attitudes, Training and Communication Project (VACSATC)

The paper presents the first results from the European project VACSATC which aimed to track parental attitudes on vaccinations across several European countries. We compared five cross-sectional surveys of parents with children less than 3 years of age in England, Norway, Poland, Spain and Sweden carried out during 2008-2009. Data were collected from 6611 respondents. Two countries used face-to face interviews, one used telephone interviews, and two other countries used mail-in questionnaires. In all countries health professionals were indicated as the most important and trusted source of information on vaccination. The study results also show that parental attitudes on vaccinations in the childhood vaccination programs are generally positive. However, there were differences in attitudes on vaccination between the five countries, possibly reflecting different methods of sampling the respondents, context-specific differences (e.g. level of activity of governmental agencies), but also individual-level parental variation in demographic and socioeconomic status variables.

Association of Varying Number of Doses of Quadrivalent Human Papillomavirus Vaccine With Incidence of Condyloma

IMPORTANCE Determining vaccine dose-level protection is essential to minimize program costs and increase mass vaccination program feasibility. Currently, a 3-dose vaccination schedule is recommended for both the quadrivalent and bivalent human papillomavirus (HPV) vaccines. Although the primary goal of HPV vaccination programs is to prevent cervical cancer, condyloma related to HPV types 6 and 11 is also prevented with the quadrivalent vaccine and represents the earliest measurable preventable disease outcome for the HPV vaccine. OBJECTIVE To examine the association between quadrivalent HPV vaccination and first occurrence of condyloma in relation to vaccine dose in a population-based setting. DESIGN, SETTING, AND PARTICIPANTS An open cohort of all females aged 10 to 24 years living in Sweden (n = 1,045,165) was followed up between 2006 and 2010 for HPV vaccination and first occurrence of condyloma using the Swedish nationwide population-based health data registers. MAIN OUTCOMES AND MEASURES Incidence rate ratios (IRRs) and incidence rate differences (IRDs) of condyloma were estimated using Poisson regression with vaccine dose as a time-dependent exposure, adjusting for attained age and parental education, and stratified on age at first vaccination. To account for prevalent infections, models included a buffer period of delayed case counting. RESULTS A total of 20,383 incident cases of condyloma were identified during follow-up, including 322 cases after receipt of at least 1 dose of the vaccine. For individuals aged 10 to 16 years at first vaccination, receipt of 3 doses was associated with an IRR of 0.18 (95% CI, 0.15-0.22) for condyloma, whereas receipt of 2 doses was associated with an IRR of 0.29 (95% CI, 0.21-0.40). One dose was associated with an IRR of 0.31 (95% CI, 0.20-0.49), which corresponds to an IRD of 384 cases (95% CI, 305-464) per 100,000 person-years, compared with no vaccination. The corresponding IRDs for 2 doses were 400 cases (95% CI, 346-454) and for 3 doses, 459 cases (95% CI, 437-482). The number of prevented cases between 3 and 2 doses was 59 (95% CI, 2-117) per 100,000 person-years. CONCLUSIONS AND RELEVANCE Although maximum reduction in condyloma risk was seen after receipt of 3 doses of quadrivalent HPV vaccine, receipt of 2 vaccine doses was also associated with a considerable reduction in condyloma risk. The implications of these findings for the relationship between number of vaccine doses and cervical cancer risk require further investigation.

There is an association between contact allergy to aluminium and persistent subcutaneous nodules in children undergoing hyposensitization therapy.

Background:  The development of persistent itchy nodules at the injection site following hyposensitization therapy with aluminium‐precipitated antigen extract has been described in several reports. Occasionally, contact allergy to aluminium has been reported in individuals with such nodules.

The Participation of HPV-Vaccinated Women in a National Cervical Screening Program: Population-Based Cohort Study

Background Concerns have been raised that HPV-vaccination might affect women’s cervical screening behavior. We therefore investigated the association between opportunistic HPV-vaccination and attendance after invitation to cervical screening. Methods A cohort of all women resident in Sweden, born 1977-1987 (N=629,703), and invited to cervical screening, was followed October 2006 - December 2012. Invitations to screening were identified via the National Quality Register for Cervical Cancer Prevention, as was the primary outcome of a registered smear. Vaccination status was obtained from two nationwide health data registers. Hazard ratios (HR) were estimated using Cox regression adjusted for age, education level and income (HRadj). Women were individually followed for up to 6 years, of which the first and second screening rounds were analyzed separately. Results Screening attendance after three years of follow-up was 86% in vaccinated women (N=4,897) and 75% in unvaccinated women (N=625,804). The crude HR of screening attendance in vaccinated vs. unvaccinated women was 1.31 (95% CI 1.27-1.35) in the first screening round. Adjustment for education and income reduced but did not erase this difference (HRadj=1.09, 95% CI 1.05-1.13). In the second screening round, attendance was likewise higher in HPV-vaccinated women (crude HR=1.26, 95% CI 1.21-1.32; HRadj=1.15, 95% CI 1.10-1.20). Conclusions HPV-vaccination is so far associated with equal or higher attendance to cervical screening in Sweden in a cohort of opportunistically vaccinated young women. Most but not all of the difference in attendance was explained by socioeconomic differences between vaccinated and unvaccinated women. HPV vaccine effectiveness studies should consider screening attendance of HPV-vaccinated women when assessing incidence of screen-detected cervical lesions.

Does Allergen-specific Immunotherapy Induce Contact Allergy to Aluminium?

Persistent, itching nodules have been reported to appear at the injection site after allergen-specific immuno-therapy with aluminium-precipitated antigen extract, occasionally in conjunction with contact allergy to aluminium. This study aimed to quantify the development of contact allergy to aluminium during allergen-specific immunotherapy. A randomized, controlled, single-blind multicentre study of children and adults entering allergen-specific immunotherapy was performed using questionnaires and patch-testing. A total of 205 individuals completed the study. In the 3 study groups all subjects tested negative to aluminium before allergen-specific immunotherapy and 4 tested positive after therapy. In the control group 4 participants tested positive to aluminium. Six out of 8 who tested positive also had atopic dermatitis. Positive test results were found in 5/78 children and 3/127 adults. Allergen-specific immunotherapy was not shown to be a risk factor for contact allergy to aluminium. Among those who did develop aluminium allergy, children and those with atopic dermatitis were more highly represented.

Immunization site pain: Case definition and guidelines for collection, analysis, and presentation of immunization safety data

mmunization site pain: Case definition and guidelines for collection, analysis, nd presentation of immunization safety data ane F. Gidudua,∗, Gary A. Walcob, Anna Taddioc, William T. Zempskyd, Scott A. Halperine, ngela Calugara, Neville A. Gibbs f, Renald Hennigg, Milivoj Jovancevich, Eva Netterlid i, erri O’Connor j, James M. Oleskek, Frederick Varricchio l,1, Theodore F. Tsaim, Harry Seifertn, nne E. Schuindn, The Brighton Immunization Site Pain Working Group2

Surveillance of Vaccine Safety: Comparison of parental reports with routine surveillance and a clinical trial

One way to maintain confidence in vaccination programmes is to improve monitoring of immunisation safety. We studied active parental reporting of adverse events after a booster dose of diphtheria-tetanus toxoid (DT). 7193 children received the vaccine. Questionnaires were submitted by 84.2% of the parents, who reported reactions for 9.2% of the children. Four percent of events were classified as moderate/severe by interviews. Relative risk of redness and swelling reported was 0.24 (95% CI, 0.13-0.42) compared to a clinical trial, while it was 71.0 (44-114) compared to passive surveillance. Active surveillance by parental reports is a useful complement to passive surveillance of childhood immunisations to generate hypotheses for evaluation in controlled studies.

Highest Vaccine Uptake after School-Based Delivery - A County-Level Evaluation of the Implementation Strategies for HPV Catch-Up Vaccination in Sweden

Background The Swedish school-based vaccination programme offers HPV vaccine to girls born ≥1999 in 5-6th grade. In 2012, all counties introduced free-of-charge catch-up vaccination campaigns targeting girls born 1993–1998. Varying vaccine uptake in the catch-up group by December 2012 suggested that some implementation strategies were more successful than others. In order to inform future vaccination campaigns, we assessed the impact of different implementation strategies on the county-level catch-up vaccine uptake. Methods We conducted an ecological study including all Swedish counties (n = 21), asking regional health offices about the information channels they used and where vaccination of the catch-up target group took place in their counties. The uptake of ≥1 dose by 30 September 2014 was estimated using data from the voluntary national vaccination register. We investigated associations between counties’ catch-up vaccine uptake, information channels and vaccination settings by calculating incidence rate ratios (IRR) and 95% confidence intervals (CI), using negative binomial regression models. Results County level catch-up vaccine uptake varied between 49–84%. All counties offered vaccination through primary health care settings. Apart from this eight (34%) also offered the vaccine in some of their schools, four (19%) in all their schools, and two (10%) in other health care centres. The information channels most frequently used were: information at the national on-line health care consulting web-page (100%), letter/invitations (90%), and advertisement (81%). Counties offering vaccination to girls in all schools and counties offering vaccination in some of their schools, reached higher vaccine uptake compared to counties not offering vaccination in any of their schools (all schools adjusted IRR: 1.3, 95% CI: 1.1–1.5, some schools adjusted IRR: 1.2, 95% CI: 1.1–1.3). Conclusion Counties offering HPV vaccination to catch-up groups in schools reached the highest vaccine uptake. No information channel explained differences in county-level vaccine uptake. Our findings suggest that catch-up vaccination outside the national vaccination program can reach a high uptake at the population level if it is implemented primarily with an organized delivery (e.g. in schools).

Young individuals with atopic disease and asthma or rhinoconjunctivitis may have clinically relevant contact allergies.

BackgroundChildren and adolescents with atopic disease who have allergic asthma and/or rhinitis with and without atopic dermatitis may have hidden, clinically relevant contact allergies. ObjectiveThe objective of this study was to survey contact allergies in children and adolescents who had been offered allergen-specific immunotherapy and accepted (exposed)/not accepted (unexposed) such treatment. MethodsThirty-seven exposed and 24 unexposed individuals with atopic disease were patch tested with a standard series supplemented with aluminum chloride hexahydrate, an empty Finn Chamber, and 8 antigen preparations. ResultsIn the exposed group, 18 allergies were detected in 13 individuals with atopic disease when excluding reactions to aluminum and antigen preparations, whereas the corresponding figures for the unexposed group were 9 and 6, respectively (non–significant difference). Independent of the allergen-specific immunotherapy, significantly more (P = 0.013) individuals with atopic dermatitis had at least 1 contact allergy. Clinically relevant allergies were represented by sesquiterpene lactone mix, para–tertiary butylphenol-formaldehyde resin, tixocortol pivalate, and colophony. ConclusionsClinically relevant contact allergies are not uncommon in children and adolescents with atopic disease, which is why patch testing always should be considered in the management of dermatitis in individuals with atopic disease.