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Background: Acute otitis media (AOM) is the most common reason for antimicrobial use, and tympanostomy tube placement (TTP) is the most common reason for surgery requiring general anesthesia in children. Ten-valent pneumococcal conjugate vaccine (PCV10) was introduced in Finland in 2010 for infants. We evaluated the indirect impact of PCV10 on these surrogate otitis outcomes in unvaccinated children., Methods: Using before-after design, unvaccinated children ineligible for National Vaccination Program (born January 2006 to May 2010) were followed-up during 2012-2016 (target cohort, age 1.5-7 years). The target cohort was compared with an age- and season-matched unvaccinated reference cohort (born January 2000 to May 2004) during 2006-2010. Antimicrobial purchase data were obtained from the Social Insurance Institution of Finland benefits register. We assessed the relative reduction by generalized Cox regression for outpatient purchases of antibiotics recommended for treatment of AOM in the Finnish guidelines. Data on all TTP procedures were obtained from national hospital discharge register and Social Insurance Institution benefits register., Results: The rate of outpatient purchases of antimicrobials recommended for AOM was 51 in the unvaccinated reference cohort and 44/100 person-years in the unvaccinated target cohort; relative rate reduction was 14.7% [95% confidence interval: 14.0-15.3] and absolute rate reduction 7/100 person-years. The rates of TTP in the reference and target cohorts were 1.66/100 and 1.61/100 person-years, respectively. The relative rate reduction was 3.6% (0.7-6.5)., Conclusions: Antimicrobial use and TTP procedures reduced in unvaccinated children after PCV10 introduction in infants. These indirect effects contribute to the savings in health care resource use for otitis and may also help in combating antimicrobial resistance.

Narcolepsy type 1, likely an immune-mediated disease, is characterized by excessive daytime sleepiness and cataplexy. The disease is strongly associated with human leukocyte antigen (HLA) DQB1∗06:02. A significant increase in the incidence of childhood and adolescent narcolepsy was observed after a vaccination campaign with AS03-adjuvanted Pandemrix influenza vaccine in Nordic and several other countries in 2010 and 2011. Previously, it has been suggested that a surface-exposed region of influenza A nucleoprotein, a structural component of the Pandemrix vaccine, shares amino acid residues with the first extracellular domain of the human OX 2 orexin/hypocretin receptor eliciting the development of autoantibodies. Here, we analyzed, whether H1N1pdm09 infection or Pandemrix vaccination contributed to the development of autoantibodies to the orexin precursor protein or the OX 1 or OX 2 receptors. The analysis was based on the presence or absence of autoantibody responses against analyzed proteins. Entire OX 1 and OX 2 receptors or just their extracellular N-termini were transiently expressed in HuH7 cells to determine specific antibody responses in human sera. Based on our immunofluorescence analysis, none of the 56 Pandemrix-vaccinated narcoleptic patients, 28 patients who suffered from a laboratory-confirmed H1N1pdm09 infection or 19 Pandemrix-vaccinated controls showed specific autoantibody responses to prepro-orexin, orexin receptors or the isolated extracellular N-termini of orexin receptors. We also did not find any evidence for cell-mediated immunity against the N-terminal epitopes of OX 2 . Our findings do not support the hypothesis that the surface-exposed region of the influenza nucleoprotein A would elicit the development of an immune response against orexin receptors., Competing Interests: The authors declare that they have no competing interests., (© 2020 The Authors.)

Background: Otitis media in young children is associated with major resource use including antimicrobial consumption and tympanostomy tube placements (TTPs). We evaluated the impact of 10-valent pneumococcal conjugate vaccine (PCV10) introduction into the Finnish National Vaccination Programme (NVP) against these outcomes in vaccine-eligible children., Methods: PCV10-NVP began September 2010 with a 2 + 1 schedule; uptake in 2012 was estimated at 92%. The relative and absolute reduction in the NVP-eligible target cohort was compared with a season and age-matched (3-54 months) cohort before NVP introduction. Outpatient antimicrobial purchase data were collected from the Social Insurance Institution register. Data on purchases of antimicrobials recommended for treatment of acute otitis media by the Finnish Current Care Guidelines (amoxicillin with/without enzyme inhibitor, cefuroxime, cefaclor, clarithromycin, azithromycin) were collected, but full data on penicillin and sulfadiazine/trimethoprim were not available. Data on all TTP procedures were obtained from national hospital discharge register and Social Insurance Institution benefits register. Generalized Cox regression was used in the analysis., Results: The incidence rates of antimicrobial purchases in the reference and target cohorts were 1.09 and 0.89 per person-year, respectively. The relative rate reduction was 17.5% (95% confidence interval: 17.0-18.1) and the absolute rate reduction 0.20 per person-year. The rates of TTP in the reference and target cohorts were 5.41/100 and 4.56/100 person-years, respectively. The relative rate reduction was 14.8% (95% confidence interval: 13.1-16.5) and the absolute rate reduction 0.86/100 person-years., Conclusions: Use of antimicrobials and TTPs reduced after PCV10 was introduced into a routine vaccination program. This suggests considerable savings in health care resource use.

The USA has a long-standing paediatric influenza vaccination programme, including use of live attenuated influenza vaccine (LAIV). Following US evidence of apparent lack of vaccine effectiveness (VE) of LAIV in 2015/2016, particularly against A(H1N1)pdm09, the USA suspended the use of LAIV in the 2016/2017 season. The UK introduced LAIV for children in 2013/2014 and Finland in 2015/2016. Both countries have since been closely monitoring programme performance. In 2015/2016, the UK and Finland, unlike the USA, found evidence of significant VE of LAIV against laboratory-confirmed influenza. Several studies, however, reported relatively lower VE of LAIV against A(H1N1)pdm09 infection compared with inactivated influenza vaccine, although not for A(H3N2) or B. The reasons for these apparent differences remain under investigation. Both the UK and Finland continue to recommend the use of LAIV in children for the 2017/2018 season and are intensifying further monitoring of their childhood programmes against a range of end-points., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Pneumococcal conjugate vaccines (PCVs) have demonstrated efficacy against childhood pneumococcal disease in several regions globally. We demonstrate how spatial epidemiological analysis of a PCV trial can assist in developing vaccination strategies that target specific geographic subpopulations at greater risk for pneumococcal pneumonia. We conducted a secondary analysis of a randomized, placebo-controlled, double-blind vaccine trial that examined the efficacy of an 11-valent PCV among children less than 2 y of age in Bohol, Philippines. Trial data were linked to the residential location of each participant using a geographic information system. We use spatial interpolation methods to create smoothed surface maps of vaccination rates and local-level vaccine efficacy across the study area. We then measure the relationship between distance to the main study hospital and local-level vaccine efficacy, controlling for ecological factors, using spatial autoregressive models with spatial autoregressive disturbances. We find a significant amount of spatial variation in vaccination rates across the study area. For the primary study endpoint vaccine efficacy increased with distance from the main study hospital from -14% for children living less than 1.5 km from Bohol Regional Hospital (BRH) to 55% for children living greater than 8.5 km from BRH. Spatial regression models indicated that after adjustment for ecological factors, distance to the main study hospital was positively related to vaccine efficacy, increasing at a rate of 4.5% per kilometer distance. Because areas with poor access to care have significantly higher VE, targeted vaccination of children in these areas might allow for a more effective implementation of global programs.

Background: Numerous studies evaluating the efficacy of conjugate pneumococcal vaccines are being conducted or planned throughout the world. Some of these studies are evaluating the effect of vaccine on nasopharyngeal (NP) carriage., Methods: The World Health Organization established a Working Group comprised of representatives from these trials and other NP colonization experts to establish core, standardized methods for the study of pneumococcal NP colonization that could be used in these trials. The intent was to reduce or eliminate variability in key methods which themselves could contribute to variability of observed pneumococcal NP colonization. In this way variability of vaccine effects between trials on NP colonization could more easily be analyzed for population or vaccine differences without the confounding effect caused by differences in study methodology., Results: This paper presents the evidence base supporting the need for standardized NP colonization study methods, the methods themselves (Core Consensus Methods), including collection techniques, culture media, equipment, serotyping, storage of specimens and transport of isolates agreed on by the Working Group as well as a discussion of research priorities., Conclusions: The Core Consensus Methods provide a common methodology to conduct pneumococcal NP colonization studies with minimum interstudy method variability. The intention is to allow more meaningful comparisons of study results from conjugate pneumococcal vaccine trials.