Pre-vaccination care-seeking in females reporting severe adverse reactions to HPV vaccine. A registry based case-control study

BACKGROUND:Since 2013 the number of suspected adverse reactions to the quadrivalent human papillomavirus (HPV) vaccine reported to the Danish Medicines Agency (DMA) has increased. Due to the resulting public concerns about vaccine safety, the coverage of HPV vaccinations in the childhood vaccination programme has declined. The aim of the present study was to determine health care-seeking prior to the first HPV vaccination among females who suspected adverse reactions to HPV vaccine. METHODS:In this registry-based case-control study, we included as cases vaccinated females with reports to the DMA of suspected severe adverse reactions. We selected controls without reports of adverse reactions from the Danish vaccination registry and matched by year of vaccination, age of vaccination, and municipality, and obtained from the Danish National Patient Registry and The National Health Insurance Service Register the history of health care usage two years prior to the first vaccine. We analysed the data by logistic regression while adjusting for the matching variables. RESULTS:The study included 316 cases who received first HPV vaccine between 2006 and 2014. Age range of cases was 11 to 52 years, with a peak at 12 years, corresponding to the recommended age at vaccination, and another peak at 19 to 28 years, corresponding to a catch-up programme targeting young women. Compared with 163,910 controls, cases had increased care-seeking in the two years before receiving the first HPV vaccine. A multivariable model showed higher use of telephone/email consultations (OR 1.9; 95% CI 1.2-3.2), physiotherapy (OR 2.1; 95% CI 1.6-2.8) and psychologist/psychiatrist (OR 1.9; 95% CI 1.3-2.7). Cases were more likely to have a diagnosis in the ICD-10 chapters of diseases of the digestive system (OR 1.6; 95% CI 1.0-2.4), of the musculoskeletal system (OR 1.6; 95% CI 1.1-2.2), symptoms or signs not classified elsewhere (OR 1.8; 95% CI 1.3-2.5) as well as injuries (OR 1.5; 95% CI 1.2-1.9). CONCLUSION:Before receiving the first HPV vaccination, females who suspected adverse reactions has symptoms and a health care-seeking pattern that is different from the matched population. Pre-vaccination morbidity should be taken into account in the evaluation of vaccine safety signals

Magic squares: Latin, Semiclassical and Quantum

Quantum magic squares were recently introduced as a 'magical' combination of quantum measurements. In contrast to quantum measurements, they cannot be purified (i.e. dilated to a quantum permutation matrix) -- only the so-called semiclassical ones can. Purifying establishes a relation to an ideal world of fundamental theoretical and practical importance; the opposite of purifying is described by the matrix convex hull. In this work, we prove that semiclassical magic squares can be purified to quantum Latin squares, which are 'magical' combinations of orthonormal bases. Conversely, we prove that the matrix convex hull of quantum Latin squares is larger than the semiclassical ones. This tension is resolved by our third result: We prove that the quantum Latin squares that are semiclassical are precisely those constructed from a classical Latin square. Our work sheds light on the internal structure of quantum magic squares, on how this is affected by the matrix convex hull, and, more generally, on the nature of the 'magical' composition rule, both at the semiclassical and quantum level.Comment: v1: 17 pages, 5 figures. v2: contains Remark 16, pointed out to us by David Roberso

Written reminders increase vaccine coverage in Danish children - evaluation of a nationwide intervention using The Danish Vaccination Register, 2014 to 2015

We evaluated a national intervention of sending written reminders to parents of children lacking childhood vaccinations, using the Danish Vaccination Register (DDV). The intervention cohort included the full birth cohort of 124,189 children born in Denmark who reached the age of 2 and 6.5 years from 15 May 2014 to 14 May 2015. The reference cohort comprised 124,427 children who reached the age of 2 and 6.5 years from 15 May 2013 to 14 May 2014. Vaccination coverage was higher in the intervention cohort at 2.5 and 7 years of age. The differences were most pronounced for the second dose of the measles-mumps-rubella vaccine (MMR2) and the diphtheria-tetanus-pertussis-polio vaccine DTaP-IPV4 among the 7-year-olds, with 5.0 percentage points (95% confidence interval (CI): 4.5–5.4) and 6.4 percentage points (95% CI: 6.0–6.9), respectively. Among the 2.5 and 7-year-olds, the proportion of vaccinations in the preceding 6 months was 46% and three times higher, respectively, in the intervention cohort than the reference cohort. This study indicates a marked effect of personalised written reminders, highest for the vaccines given later in the schedule in the older cohort. In addition, the reminders increased awareness about correct registration of vaccinations in DDV.</jats:p

Acute myocardial infarctions and stroke triggered by laboratory-confirmed respiratory infections in Denmark, 2010 to 2016.

BackgroundSeveral studies have investigated a possible association between respiratory infection and acute myocardial infarction (MI). As both influenza and pneumococcal infections are vaccine preventable, understanding the populations affected by virus-induced cardiovascular complications is important to guide public health and clinical practice.AimThis observational study aimed to quantify the association between laboratory-confirmed respiratory bacteria or virus infections and risk of first MI or stroke, by using self-controlled case series (SCCS) analysis of anonymised linked electronic Danish health records.MethodsThe SCCS method was used to determine the relative incidence of the first event of MI and stroke occurring within 28 days after laboratory-confirmed respiratory infections compared with the baseline time period.ResultsIn the age and season adjusted analyses for first acute MI, the incidence ratios (IR) of a MI event occurring during the risk period were significantly elevated following a Streptococcus pneumoniae infection with values of 20.1, 11.0 and 4.9 during 1-3, 4-7 and 8-14 days, respectively and following respiratory virus infection with values of 15.2, 4.5 and 4.4 during 1-3, 8-14 and 15-28 days, respectively. The significantly elevated IRs for stroke following an S. pneumoniae infection were 25.5 and 6.3 during 1-3 and 8-14 days, respectively and following respiratory virus infection 8.3, 7.8 and 6.2 during 1-3, 4-7 and 8-14 days, respectively.ConclusionThis study suggested a significant cardiovascular event triggering effect following infection with S. pneumoniae and respiratory viruses (mainly influenza), indicating the importance of protection against vaccine-preventable respiratory infections

Sociodemographic predictors are associated with compliance to a vaccination-reminder in 9692 girls age 14, Denmark 2014–2015

We aimed to identify sociodemographic predictors of compliance after receiving a personalised reminder on lacking vaccinations against MMR (Measles, Mumps, Rubella) and/or HPV (Human Papilloma Virus) among parents of Danish adolescent girls.A nationwide register-based study, including all 14-year-old girls (15 May 2014–14 May 2015) lacking either MMR, HPV-vaccination or both. Vaccination-compliance following a postal reminder was modelled using multivariable logistic regression and included the following socio-demographic predictors: maternal age, education, employment and ethnicity. Birth order, number of siblings, family-structure, location of residence, and household income.The parents of 9692 girls received a reminder. Out of 4940 exclusively lacking an HPV-vaccine, 15.3% were subsequently vaccinated. Among 2026 only lacking an MMR vaccination, 8.5% were vaccinated. Among 2726 girls lacking both, 5% received an HPV, 4.4% an MMR and 5.4% received both vaccinations. We identified sociodemographic differences between reminderletter-compliers and non-compliers, also according to vaccination types. Non-western descendants were more likely to receive HPV-vaccination, although the association was only significant for those who only lacked HPV (OR 2.02, 95% 1.57–2.59). For girls only lacking an MMR, regional differences were identified. Among girls lacking both vaccines, girls of mothers with intermediate (OR 0.63, 0.42–0.95) or basic education (OR 0.43, 0.24–0.75) were less likely to be vaccinated compared to girls of higher educated mothers.Reminders were in particular effective in increasing HPV uptake among immigrants of non-Western ethnicity. We found reminders to be less effective among less educated mothers whose daughters lacked both vaccines. To increase the coverage in this group, additional interventions are needed. Keywords: Vaccination, Immunization, Socioeconomic factor

Community cohort study of rotavirus and other enteropathogens: are routine vaccinations associated with sex-differential incidence rates?

OBJECTIVE: Community studies in West Africa have demonstrated that routine vaccinations may have non-targeted effects, the female-male mortality ratio being reduced after administration of BCG and increased after diphtheria-tetanus-pertussis (DTP). We examined whether immunisation status was associated with infection with rotavirus and other enteropathogens. METHODS: We recruited 200 children shortly after birth and followed them until 2 years of age with weekly morbidity interviews and stool sampling. Vaccination status for each child was classified according to the most recent vaccination as documented by vaccination card. MAIN OUTCOME MEASURES: The female-male incidence rate ratios (IRR) of infection with an enteropathogen and of enteropathogen-associated diarrhoea were estimated for children according to whether they had received BCG or DTP as their last vaccination. RESULTS: For children who received BCG as their last vaccine, the adjusted female-male IRRs for primary rotavirus-infection and diarrhoea were 1.05 (95% CI: 0.21-5.28) and 0.0 (95% CI: 0-3.02), respectively. For children who received DTP as their last vaccine, the adjusted female-male IRRs were 1.93 (0.89-4.21) and 1.92 (0.70-5.32), respectively, for rotavirus-associated infection and diarrhoea. Restricted to the rotavirus season, the female-male IRRs for rotavirus infection and diarrhoea were 2.56 (1.17-5.63) and 2.63 (0.94-7.34), respectively. The female-male IRR for rotavirus-associated diarrhoea differed significantly among BCG and DTP recipients (p=0.02). Infections with enteropathogens not associated with diarrhoea were associated with lower female-male IRRs after BCG of 0.82 (0.55-1.23) and higher female-male IRRs after DTP vaccination of 1.32 (1.03-1.70) for primary infection (p=0.05). Though there were few infections with other diarrhoea-causing enteropathogens, these were also associated with a lower female-male IRR after BCG of 0.62 (0.26-1.52) and a higher female-male IRR after DTP vaccination of 1.51 (1.04-2.20) for all infection. CONCLUSION: Routine immunisations may affect morbidity for non-targeted infections. As in studies of infant mortality, BCG is associated with lower risk for girls, whereas, DTP is associated with higher risk for girls relative to boys

Laboratory Diagnostics of <i>Rickettsia</i> Infections in Denmark 2008–2015

Rickettsiosis is a vector-borne disease caused by bacterial species in the genus Rickettsia. Ticks in Scandinavia are reported to be infected with Rickettsia, yet only a few Scandinavian human cases are described, and rickettsiosis is poorly understood. The aim of this study was to determine the prevalence of rickettsiosis in Denmark based on laboratory findings. We found that in the Danish individuals who tested positive for Rickettsia by serology, the majority (86%; 484/561) of the infections belonged to the spotted fever group. In contrast, we could confirm 13 of 41 (32%) PCR-positive individuals by sequencing and identified all of these as R. africae, indicating infections after travel exposure. These 13 samples were collected from wound/skin material. In Denmark, approximately 85 individuals test positive for Rickettsia spp. annually, giving an estimated 26% (561/2147) annual prevalence among those suspected of rickettsiosis after tick bites. However, without clinical data and a history of travel exposure, a true estimation of rickettsiosis acquired endemically by tick bites cannot be made. Therefore, we recommend that both clinical data and specific travel exposure be included in a surveillance system of Rickettsia infections