Ida Laake

Do parental education and income matter? A nationwide register-based study on HPV vaccine uptake in the school-based immunisation programme in Norway

Objective Vaccine against human papillomavirus (HPV) has been offered free of charge to all 12-year-old girls in Norway since 2009. Nevertheless, the uptake of HPV vaccine is lower than for other childhood vaccines. The aim of this study was to examine whether parental education and income are associated with initiation and completion of HPV vaccination. Design Nationwide register-based study. Setting Publicly funded childhood immunisation programme in Norway. Participants 91 405 girls born between 1997 and 1999 and registered in the Norwegian Central Population Registry were offered HPV vaccine during the first 3 programme years. Of these, 84 139 had complete information on all variables and were included in the study. Measurements Information on HPV-vaccination status was obtained from the Norwegian Immunisation Registry. Data on socioeconomic factors were extracted from Statistics Norway. Risk differences (RDs) and CIs were estimated with Poisson regression. Results In the study sample, 78.3% received at least one dose of HPV vaccine and 73.6% received all three doses. High maternal education was significantly associated with lower probability of initiating HPV vaccination (multivariable RD=−5.5% (95% CI −7.0% to −4.0%) for highest compared with lowest education level). In contrast, high maternal income was significantly associated with higher probability of initiating vaccination (multivariable RD=10.1% (95% CI 9.0% to 11.3%) for highest compared with lowest quintile). Paternal education and income showed similar, but weaker, associations. The negative association between education and initiation was only seen for incomes below the median value. Conclusions In spite of the presumably equal access to HPV vaccine in Norway, we found socioeconomic disparities in vaccine uptake. More studies are needed to explain the underlying factors responsible for the observed socioeconomic differences. Insight into these factors is necessary to target information and increase vaccination coverage to ultimately reduce HPV-related disease across socioeconomic barriers.

HPV vaccination and risk of chronic fatigue syndrome/myalgic encephalomyelitis: A nationwide register-based study from Norway

BACKGROUND Vaccination has been suggested to be involved in the aetiology of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). HPV vaccine was introduced in the Norwegian Childhood Immunisation Programme and offered 12year old girls from 2009. We studied the association between HPV vaccination and risk of CFS/ME and also assessed medical history in relation to both risk of CFS/ME and HPV vaccine uptake. METHODS Individual data from national registries, including the Norwegian Population Registry, the Norwegian Patient Registry and the Norwegian Immunisation Registry were linked using the unique personal identification number. Yearly incidence rates of CFS/ME for 2009-2014 were calculated among the 824,133 boys and girls, aged 10-17 living in Norway during these 6years. A total of 176,453 girls born 1997-2002 were eligible for HPV vaccination and included in further analyses. Hazard ratios (HRs) of CFS/ME were estimated using Cox regression. Risk differences (RDs) of vaccine uptake were estimated with binomial regression. RESULTS A similar yearly increase in incidence rate of CFS/ME was observed among girls and boys, IRR=1.15 (95% confidence interval (CI) 1.10-1.19) and 1.15 (95% CI 1.09-1.22), respectively. HPV vaccination was not associated with CFS/ME, HR=0.86 (95% CI 0.69-1.08) for the entire follow-up period and 0.96 (95% CI 0.64-1.43) for the first two years after vaccination. The risk of CFS/ME increased with increasing number of previous hospital contacts, HR=5.23 (95% CI 3.66-7.49) for 7 or more contacts as compared to no contacts. Girls with 7 or more hospital contacts were less likely to be vaccinated than girls with no previous hospital contacts, RD=-5.5% (95% CI -6.7% to -4.2%). CONCLUSIONS No indication of increased risk of CFS/ME following HPV vaccination was observed among girls in the first 6 birth cohorts offered HPV vaccine through the national immunisation programme in Norway.

Risk of Pertussis in Relation to Degree of Prematurity in Children Less Than 2 Years of Age

BACKGROUND A few previous studies reported increased risk of pertussis in children with birth weight < 2500g. The risk of pertussis by degree of prematurity has not been determined in a cohort study. The vaccine effectiveness (VE) against reported pertussis in preterm infants is unknown. METHODS Data were obtained from the Medical Birth Registry of Norway (1998-2010) and linked to other national registries. In total, 713,166 children were included in our study and followed until 2 years of age. Incidence rate ratios (IRRs) and confidence intervals (CIs) were estimated with Poisson regression. RESULTS We identified 999 reported cases of pertussis. We observed a higher rate of reported pertussis in preterm than in full-term infants, IRR = 1.65 (95% CI 1.32-2.07). Compared to full-term infants, the risk of reported pertussis in infants born at gestational age (GA) 35-36 weeks, GA 32-34 weeks and GA 23-27 weeks was higher (IRRs = 1.49 (95% CI 1.11-2.01), 1.63 (95% CI 1.06-2.51), and 4.49 (95% CI 2.33-8.67), respectively). Moreover, preterm infants had a higher rate of pertussis-related hospitalisation than full-term infants (IRR = 1.99 (95% CI 1.47-2.71)). The VE against reported pertussis for the 3rd dose was 88.8% (95% CI 84.3-92.0) in full-term infants and 93.0% (95% CI 85.8-96.5) in preterm infants. CONCLUSIONS In this cohort study preterm infants, including those born at GA 35 and 36 weeks had increased risk of reported pertussis. The VE was similar in preterm and full-term infants.Background: A few previous studies reported increased risk of pertussis in children with birth weight less than 2500 g. The risk of pertussis by degree of prematurity has not been determined in a cohort study. The vaccine effectiveness (VE) against reported pertussis in preterm infants is unknown. Methods: Data were obtained from the Medical Birth Registry of Norway (1998–2010) and linked to other national registries. In total, 713,166 children were included in our study and followed until 2 years of age. Incidence rate ratios (IRRs) and confidence intervals (CIs) were estimated with Poisson regression. Results: We identified 999 reported cases of pertussis. We observed a higher rate of reported pertussis in preterm than in full-term infants, IRR = 1.65 (95% CI: 1.32–2.07). Compared to full-term infants, the risk of reported pertussis in infants born at gestational age (GA) 35–36, 32–34 and 23–27 weeks were higher [IRRs = 1.49 (95% CI: 1.11–2.01), 1.63 (95% CI: 1.06–2.51) and 4.49 (95% CI: 2.33–8.67), respectively]. Moreover, preterm infants had a higher rate of pertussis-related hospitalization than full-term infants [IRR = 1.99 (95% CI: 1.47–2.71)]. The VE against reported pertussis for the third dose was 88.8% (95% CI: 84.3–92.0) in full-term infants and 93.0% (95% CI: 85.8–96.5) in preterm infants. Conclusions: In this cohort study, preterm infants including those born at GA 35 and 36 weeks had increased risk of reported pertussis. The VE was similar in preterm and full-term infants.

Substantial Decline in Prevalence of Vaccine-Type and Nonvaccine-Type Human Papillomavirus (HPV) in Vaccinated and Unvaccinated Girls 5 Years After Implementing HPV Vaccine in Norway

High HPV vaccine uptake in a single-cohort program aimed at largely HPV-naive girls reduced vaccine types by 90% in vaccinated and 54% in unvaccinated girls. Indication of cross-protection in both vaccinated and unvaccinated girls was also observed.

Distinct T and NK cell populations may serve as immune correlates of protection against symptomatic pandemic influenza A(H1N1) virus infection during pregnancy

Maternal influenza infection during pregnancy is associated with increased risk of morbidity and mortality. However, the link between the anti-influenza immune responses and health-related risks during infection is not well understood. We have analyzed memory T and NK cell mediated immunity (CMI) responses in pandemic influenza A(H1N1)pdm09 (pdm09) virus infected non-vaccinated pregnant women participating in the Norwegian Influenza Pregnancy Cohort (NorFlu). The cohort includes information on immunization, self-reported health and disease status, and biological samples (plasma and PBMC). Infected cases (N = 75) were defined by having a serum hemagglutination inhibition (HI) titer > = 20 to influenza pdm09 virus at the time of delivery, while controls (N = 75) were randomly selected among non-infected pregnant women (HI titer <10). In ELISpot assays cases had higher frequencies of IFNγ+ CD8+ T cells responding to pdm09 virus or conserved CD8 T cell-restricted influenza A virus epitopes, compared to controls. Within this T cell population, frequencies of CD95+ late effector (CD45RA+CCR7-) and naive (CD45RA+CCR7+) CD8+ memory T cells correlated inversely with self-reported influenza illness (ILI) symptoms. ILI symptoms in infected women were also associated with lower numbers of poly-functional (IFNγ+TNFα+, IL2+IFNγ+, IL2+IFNγ+TNFα+) CD4+ T cells and increased frequencies of IFNγ+CD3-CD7+ NK cells compared to asymptomatic cases, or controls, after stimulation with the pdm09 virus. Taken together, virus specific and functionally distinct T and NK cell populations may serve as cellular immune correlates of clinical outcomes of pandemic influenza disease in pregnant women. Our results may provide information important for future universal influenza vaccine design.

Human papillomavirus prevalence and type distribution in urine samples from Norwegian women aged 17 and 21 years: A nationwide cross-sectional study of three non-vaccinated birth cohorts

Background The aim of the current study was to assess the HPV prevalence in unscreened and unvaccinated young women living in Norway, to provide important baseline data for early estimation of the impact of the HPV vaccination program. Methods A total of 13,129 self-sampled urine samples from two complete birth-cohorts of 17-year old women born in 1994 and 1996 and one third of a birth-cohort of 21-year old women born in 1990, were analysed for the presence of 37 HPV types using PCR and a DNA hybridization technique. Results In the two birth cohorts of 17-year old women, HPV was detected in 19.9% (95% CI 18.8–20.9) and 15.4% (95% CI 14.5–16.3), respectively. High-risk HPV types were detected in 11.2% (95% CI 10.3–12.0) and 7.6% (95% CI 6.9–8.2), respectively, while vaccine types were detected in 7.4% (95% CI 6.7–8.1) and 6.0% (95% CI 5.4–6.6), respectively. Among the 21-year old women HPV was detected in 45.4% (95% CI 42.9–47.8), whereas high-risk types were detected in 29.8% (95% CI 27.5–32.0). Vaccine types (HPV 6, 11, 16, 18) were detected in 16.2% (95% CI 14.4–18.1). Conclusion This large population based study confirms that HPV testing in urine samples is easy and highly feasible for epidemiological studies and vaccine surveillance in young women. HPV was very common and a broad spectrum of HPV types was identified. Differences in HPV prevalence was seen both between age groups and between the two birth cohorts of 17-year old women.

Do selective immunisation against tuberculosis and hepatitis B reach the targeted populations? A nationwide register-based study evaluating the recommendations in the Norwegian Childhood Immunisation Programme.

BACKGROUND Selective immunisation is an alternative to universal vaccination if children at increased risk of disease can be identified. Within the Norwegian Childhood Immunisation Programme, BCG vaccine against tuberculosis and vaccine against hepatitis B virus (HBV) are offered only to children with parents from countries with high burden of the respective disease. We wanted to study whether this selective immunisation policy reaches the targeted groups. METHODS The study population was identified through the Norwegian Central Population Registry and consisted of all children born in Norway 2007-2010 and residing in Norway until their second birthday, in total 240,484 children. Information on vaccinations from the Norwegian Immunisation Registry, and on parental country of birth from Statistics Norway, was linked to the population registry by personal identifiers. The coverage of BCG and HBV vaccine was compared with the coverage of vaccines in the universal programme. RESULTS Among the study population, 16.1% and 15.9% belonged to the target groups for BCG and HBV vaccine, respectively. Among children in the BCG target group the BCG vaccine coverage was lower than the coverage of pertussis and measles vaccine (83.6% vs. 98.6% and 92.3%, respectively). Likewise, the HBV vaccine coverage was lower than the coverage of pertussis and measles vaccine in the HBV target group (90.0% vs. 98.6% and 92.3%, respectively). The coverage of the targeted vaccines was highest among children with parents from South Asia and Sub-Saharan Africa. The coverage of vaccines in the universal programme was similar in targeted and non-targeted groups. CONCLUSIONS Children targeted by selective vaccination had lower coverage of the target vaccines than of vaccines in the universal programme, indicating that selective vaccination is challenging. Improved routines for identifying eligible children and delivering the target vaccines are needed. Universal vaccination of all children with these vaccines could be considered.