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Background: During the COVID-19 pandemic, many countries adopted social distance measures and lockdowns of varying strictness. Social contact patterns are essential in driving the spread of respiratory infections, and country-specific measurements are needed. This study aimed to gain insights into changes in social contacts and behaviour during the early pandemic phase in Norway., Methods: We conducted an online panel study among a nationally representative sample of Norwegian adults by age and gender. The panel study included six data collections waves between April and September 2020, and 2017 survey data from a random sample of the Norwegian population (including children < 18 years old) were used as baseline. The market research company Ipsos was responsible for carrying out the 2020 surveys. We calculated mean daily contacts, and estimated age-stratified contact matrices during the study period employing imputation of child-to-child contacts. We used the next-generation method to assess the relative reduction of R0 and compared the results to reproduction numbers estimated for Norway during the 2020 study period., Results: Over the six waves in 2020, 5 938 observations/responses were registered from 1 718 individuals who reported data on 22 074 contacts. The mean daily number of contacts among adults varied between 3.2 (95%CI 3.0-3.4) to 3.9 (95%CI 3.6-4.2) across the data collection waves, representing a 67-73% decline compared to pre-pandemic levels (baseline). Fewer contacts in the community setting largely drove the reduction; the drop was most prominent among younger adults. Despite gradual easing of social distance measures during the survey period, the estimated population contact matrices remained relatively stable and displayed more inter-age group mixing than at baseline. Contacts within households and the community outside schools and workplaces contributed most to social encounters. Using the next-generation method R0 was found to be roughly 25% of pre-pandemic levels during the study period, suggesting controlled transmission., Conclusion: Social contacts declined significantly in the months following the March 2020 lockdown, aligning with implementation of stringent social distancing measures. These findings contribute valuable empirical information into the social behaviour in Norway during the early pandemic, which can be used to enhance policy-relevant models for addressing future crises when mitigation measures might be implemented., (© 2024. The Author(s).)

Between 2016 and 2019, a catch-up human papillomavirus (HPV) vaccination took place in Norway for women born between 1991 and 1996. The aim of this study was to identify sociodemographic determinants of complete vaccination (3 doses) and partial vaccination (1-2 doses). A random sample of 10,000 women who were offered catch-up HPV vaccination were invited. We assessed the association between sociodemographic characteristics and vaccination completion using univariable and multivariable multinomial logistic regression.Of 4,967 respondents, 3,464 (63%) received complete vaccination and 298 (7%) received partial vaccination. 30% did not receive any vaccination and functioned as reference group. Compared with having Norwegian caregivers, having a caregiver from non-western countries decreased the odds of partial and complete vaccination (aOR = 0.57; 95%CI = 0.35-0.95 and aOR = 0.57; 95%CI = 0.44-0.74). Having a caregiver from other western countries decreased the odds of complete vaccination (aOR = 0.72; 95%CI = 0.52-0.98). Residing in Norway for 10 years or longer significantly increased the odds of complete vaccination (aOR = 2.65; 95%CI = 1.58-4.43). Being in a relationship significantly increased the odds of partial vaccination compared with being single (aOR = 1.50; 95%CI = 1.02-2.21). Being married (aOR = 0.66; 95%CI = 0.50-0.86) and having children (aOR = 0.53; 95%CI = 0.42-0.68) decreased the odds of complete vaccination. Having university education increased the odds of both partial and complete vaccination (aOR = 2.19; 95%CI = 1.47-3.25 and aOR = 4.11; 95%CI = 3.33-5.06).Having a caregiver born outside of Norway, having children and being married decreased the odds of receiving complete HPV vaccination. This highlights the need to target communication around HPV vaccination toward different ethnic communities and include more specific messaging that having children and being married does not necessarily prevent HPV infections.

Between September and October 2019, the Norwegian Institute for Public Health (NIPH) surveyed women born between 1991 and 1996 who were offered catch-up vaccination for human papilloma virus (HPV). The aim was to identify determinants of vaccine schedule adherence. A random sample of 10,000 women who were offered catch-up vaccination were invited to participate in the survey. We defined adherence as receiving all three doses. Determinants of HPV vaccination adherence were investigated using descriptive, univariable and multivariable logistic regression analyses providing adjusted odds ratios (aOR). Data from 3,762 respondents who received at least one dose were included. Overall, 92.1% (95% CI = 89.3-91.9) of those initiating vaccination adhered to the complete schedule. The following factors were significantly associated with HPV vaccination adherence compared to non-adherence: country of origin (aOR = 0.43; 95% CI = 0.47-0.97), having children (aOR = 0.51; 95% CI = 0.35-0.73), ease of finding out where to get vaccinated (aOR = 1.94; 95% CI = 1.69-2.23), preference for receiving information from health authorities (aOR = 1.37; 95% CI = 1.04-1.81) and vaccination being readily available (aOR = 2.28; 95% CI = 1.50-3.37). Information from NIPH via SMS and social media were negatively associated for Norwegians (aOR = 0.68, 95% CI = 0.46-1.01) and positively associated for those whose country of origin was not Norway (aOR = 1.48, 95% CI = 0.69-3.14; not significant). Those who did not adhere to the full vaccination schedule reported that they had forgotten (40.4%; 95% CI = 33.5-47.8) or had no time (32.9%; 95% CI = 26.2-40.4). Despite NIPH's targeted communication campaign, the main barriers for HPV vaccination adherence were difficulty to find out where to get the vaccine, forgetting to take the vaccine or not having time to complete the schedule.

Background: The incidence of invasive disease caused by group A streptococcus (GAS) has increased in multiple countries in the past 15 years. However, despite these reports, to the best of our knowledge, no systematic reviews and combined estimates of the incidence of invasive GAS have been done in key high-risk groups. To address this, we estimated the incidence of invasive GAS disease, including death and disability outcomes, among two high-risk groups-namely, pregnant women and children younger than 5 years., Methods: We did a systematic review and meta-analyses on invasive GAS outcomes, including incidence, case fatality risks, and neurodevelopmental impairment risk, among pregnant women, neonates (younger than 28 days), infants (younger than 1 year), and children (younger than 5 years) worldwide and by income region. We searched several databases for articles published from Jan 1, 2000, to June 3, 2020, for publications that reported invasive GAS outcomes, and we sought unpublished data from an investigator group of collaborators. We included studies with data on invasive GAS cases, defined as laboratory isolation of Streptococcus pyogenes from any normally sterile site, or isolation of S pyogenes from a non-sterile site in a patient with necrotising fasciitis or streptococcal toxic shock syndrome. For inclusion in pooled incidence estimates, studies had to report a population denominator, and for inclusion in pooled estimates of case fatality risk, studies had to report aggregate data on the outcome of interest and the total number of cases included as a denominator. We excluded studies focusing on groups at very high risk (eg, only preterm infants). We assessed heterogeneity with I 2 ., Findings: Of the 950 published articles and 29 unpublished datasets identified, 20 studies (seven unpublished; 3829 cases of invasive GAS) from 12 countries provided sufficient data to be included in pooled estimates of outcomes. We did not identify studies reporting invasive GAS incidence among pregnant women in low-income and middle-income countries (LMICs) nor any reporting neurodevelopmental impairment after invasive GAS in LMICs. In nine studies from high-income countries (HICs) that reported invasive GAS in pregnancy and the post-partum period, invasive GAS incidence was 0·12 per 1000 livebirths (95% CI 0·11 to 0·14; I 2 =100%). Invasive GAS incidence was 0·04 per 1000 livebirths (0·03 to 0·05; I 2 =100%; 11 studies) for neonates, 0·13 per 1000 livebirths (0·10 to 0·16; I 2 =100%; ten studies) for infants, and 0·09 per 1000 person-years (95% CI 0·07 to 0·10; I 2 =100%; nine studies) for children worldwide; 0·12 per 1000 livebirths (95% CI 0·00 to 0·24; I 2 =100%; three studies) in neonates, 0·33 per 1000 livebirths (-0·22 to 0·88; I 2 =100%; two studies) in infants, and 0·22 per 1000 person-years (0·13 to 0·31; I 2 =100%; two studies) in children in LMICs; and 0·02 per 1000 livebirths (0·00 to 0·03; I 2 =100%; eight studies) in neonates, 0·08 per 1000 livebirths (0·05 to 0·11; I 2 =100%; eight studies) in infants, and 0·05 per 1000 person-years (0·03 to 0·06; I 2 =100%; seven studies) in children for HICs. Case fatality risks were high, particularly among neonates in LMICs (61% [95% CI 33 to 89]; I 2 =54%; two studies)., Interpretation: We found a substantial burden of invasive GAS among young children. In LMICs, little data were available for neonates and children and no data were available for pregnant women. Incidences of invasive GAS are likely to be underestimates, particularly in LMICs, due to low GAS surveillance. It is essential to improve available data to inform development of prevention and management strategies for invasive GAS., Funding: Wellcome Trust., Competing Interests: Declaration of interests We declare no competing interests., (Crown Copyright © 2022 Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.)

Background: Pneumococcal conjugate vaccines covering 10 (PCV10) and 13 (PCV13) serotypes have been introduced in the infant immunization schedule of most European countries in 2010-11. To provide additional real-life data, we measured the effectiveness of PCV10 and PCV13 against invasive pneumococcal disease (IPD) in children of 12 European sites (SpIDnet)., Methods: We compared the vaccination status of PCV10 and PCV13 serotype IPD (cases) to that of nonPCV13 serotype IPD (controls) reported in 2012-2018. We calculated pooled effectiveness as (1-vaccination odds ratio)*100, and measured effectiveness over time since booster dose., Results: The PCV13 and PCV10 studies included 2522 IPD cases from ten sites and 486 cases from four sites, respectively. The effectiveness of ≥ 1 PCV13 dose was 84.2% (95 %CI: 79.0-88.1) against PCV13 serotypes (n = 2353) and decreased from 93.1% (87.8-96.1) < 12 months to 85.1% (72.0-92.1) ≥ 24 months after booster dose. PCV13 effectiveness of ≥ 1 dose was 84.7% (55.7-94.7) against fatal PCV13 IPD, 64.5% (43.7-77.6), 83.2% (73.7-89.3) and 85.1% (67.6-93.1) against top serotypes 3, 19A and 1, respectively, and 85.4% (62.3-94.4) against 6C. Serotype 3 and 19A effectiveness declined more rapidly. PCV10 effectiveness of ≥ 1 dose was 84.8% (69.4-92.5) against PCV10 serotypes (n = 370), 27.2% (-187.6 to 81.6) and 85.3% (35.2-96.7) against top serotypes 1 and 7F, 32.5% (-28.3 to 64.5) and -14.4% (-526.5 to 79.1) against vaccine-related serotypes 19A and 6C, respectively., Conclusions: PCV10 and PCV13 provide similar protection against IPD due to the respective vaccine serotype groups but serotype-specific effectiveness varies by serotype and vaccine. PCV13 provided individual protection against serotype 3 and vaccine-related serotype 6C IPD. PCV10 effectiveness was not significant against vaccine-related serotypes 19A and 6C. PCV13 effectiveness declined with time after booster vaccination. This multinational study enabled measuring serotype-specific vaccine effectiveness with a precision rarely possible at the national level. Such large networks are crucial for the post-licensure evaluation of vaccines., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

We described the population structure of Bordetella pertussis (B. pertussis) in Norway from 1996 to 2019 and determined if there were evolutionary shifts and whether these correlated with changes in the childhood immunization program. We selected 180 B. pertussis isolates, 22 from the whole cell vaccine (WCV) era (1996-1997) and 158 from the acellular vaccine (ACV) era (1998-2019). We conducted whole genome sequencing and determined the distribution and frequency of allelic variants and temporal changes of ACV genes. Norwegian B. pertussis isolates were evenly distributed across a phylogenetic tree that included global strains. We identified seven different allelic profiles of ACV genes (A-F), in which profiles A1, A2, and B dominated (89%), all having pertussis toxin (ptxA) allele 1, pertussis toxin promoter (ptxP) allele 3, and pertactin (prn) allele 2 present. Isolates with ptxP1 and prn1 were not detected after 2007, whereas the prn2 allele likely emerged prior to 1972, and ptxP3 before the early 1980s. Allele conversions of ACV genes all occurred prior to the introduction of ACV. Sixteen percent of our isolates showed mutations within the prn gene. ACV and its booster doses (implemented for children in 2007 and adolescents in 2013) might have contributed to evolvement of a more uniform B. pertussis population, with recent circulating strains having ptxA1, ptxP3, and prn2 present, and an increasing number of prn mutations. These strains clearly deviate from ACV strains (ptxA1, ptxP1, prn1), and this could have implications for vaccine efficiency and, therefore, prevention and control of pertussis., (© 2022. The Author(s).)

As with other pathogens, competitive interactions between Bordetella pertussis strains drive infection risk. Vaccines are thought to perturb strain diversity through shifts in immune pressures; however, this has rarely been measured because of inadequate data and analytical tools. We used 3344 sequences from 23 countries to show that, on average, there are 28.1 transmission chains circulating within a subnational region, with the number of chains strongly associated with host population size. It took 5 to 10 years for B. pertussis to be homogeneously distributed throughout Europe, with the same time frame required for the United States. Increased fitness of pertactin-deficient strains after implementation of acellular vaccines, but reduced fitness otherwise, can explain long-term genotype dynamics. These findings highlight the role of vaccine policy in shifting local diversity of a pathogen that is responsible for 160,000 deaths annually.

Background: Pneumococcal disease outbreaks of vaccine preventable serotype 4 sequence type (ST)801 in shipyards have been reported in several countries. We aimed to use genomics to establish any international links between them., Methods: Sequence data from ST801-related outbreak isolates from Norway (n = 17), Finland (n = 11) and Northern Ireland (n = 2) were combined with invasive pneumococcal disease surveillance from the respective countries, and ST801-related genomes from an international collection (n = 41 of > 40,000), totalling 106 genomes. Raw data were mapped and recombination excluded before phylogenetic dating., Results: Outbreak isolates were relatively diverse, with up to 100 SNPs (single nucleotide polymorphisms) and a common ancestor estimated around the year 2000. However, 19 Norwegian and Finnish isolates were nearly indistinguishable (0-2 SNPs) with the common ancestor dated around 2017., Conclusion: The total diversity of ST801 within the outbreaks could not be explained by recent transmission alone, suggesting that harsh environmental and associated living conditions reported in the shipyards may facilitate invasion of colonising pneumococci. However, near identical strains in the Norwegian and Finnish outbreaks does suggest that transmission between international shipyards also contributed to those outbreaks. This indicates the need for improved preventative measures in this working population including pneumococcal vaccination., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [R.A.G received a PhD stipend from Pfizer 2009–2011. L.S is a co-investigator in an unrelated study, for which THL has received research funding from GlaxoSmithKline Vaccines. S.C.C: acts as principal investigator on studies conducted on behalf of University Hospital Southampton NHS Foundation Trust/University of Southampton that are sponsored by vaccine manufacturers but receives no personal payments from them. S.C.C. has participated in advisory boards for vaccine manufacturers but receives no personal payments for this work. S.C.C. has received financial assistance from vaccine manufacturers to attend conferences. All grants and honoraria are paid into accounts within the respective NHS Trusts or Universities, or to independent charities. N.K.F, C.L.S The Immunisation and Countermeasures Division, Public Health England - National Infection Service, London, UK provides vaccine manufacturers with post-marketing surveillance reports, which the Marketing Authorization Holders are required to submit to the UK Licensing authority in compliance with their Risk Management Strategy. A cost recovery charge is made for these reports. N.K.F and C.S. conduct contract research funded by vaccine manufacturers (including GlaxoSmithKline and Pfizer) on behalf of Public Health England. No personal remuneration is received. M.T reports grants from GlaxoSmithKline and Pfizer to the Finnish Institute for Health and Welfare for unrelated research projects in which she is a co-investigator. All remaining authors report no conflicts of interest.]., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The elderly and adults with medical risk conditions remain at high risk of invasive pneumococcal disease (IPD), highlighting the importance of adequate preventive efforts. In an observational population-based study in Norway (pop ≥ 5 years, 2009-2017) covering six years post-PCV13 implementation, we explored the incidence and risk of IPD associated with age and comorbidities. We obtained the data on 5535 IPD cases from the Norwegian Surveillance System for Communicable Diseases and the population data from Statistics Norway. To define comorbidities, we obtained ICD-10 codes from the Norwegian Patient Registry for the cases and the Norwegian population. The average annual decrease in PCV13 IPD incidence was significant in all risk groups and decreased post-PCV13 introduction by 16-20% per risk group, implying a nondifferential indirect protection from the childhood vaccination. The IPD incidence remained high in the medical risk groups. The relative importance of medical risk conditions was 2.8 to 6 times higher in those aged 5-64 versus ≥65 years for all types of IPD, since age itself is a risk factor for IPD. In groups without medical risk, the risk of IPD was eight times higher in those aged ≥65 compared to those 5-64 years (RR 8.3 (95% CI 7.3-9.5)). Our results underscore the need for age- and risk-group-based prevention strategies.

Reported incidence of pertussis in the European Union (EU) and the European Economic Area (EEA) varies and may not reflect the real situation, while vaccine-induced protection against diphtheria and tetanus seems sufficient. We aimed to determine the seroprevalence of DTP antibodies in EU/EEA countries within the age groups of 40-49 and 50-59 years. Eighteen countries collected around 500 samples between 2015 and 2018 (N = 10,302) which were analysed for IgG-DTP specific antibodies. The proportion of sera with pertussis toxin antibody levels ≥100 IU/mL, indicative of recent exposure to pertussis was comparable for 13/18 countries, ranging between 2.7-5.8%. For diphtheria the proportion of sera lacking the protective level (<0.1 IU/mL) varied between 22.8-82.0%. For tetanus the protection was sufficient. Here, we report that the seroprevalence of pertussis in these age groups indicates circulation of B. pertussis across EU/EEA while the lack of vaccine-induced seroprotection against diphtheria is of concern and deserves further attention.

Serotype-specific surveillance for invasive pneumococcal disease (IPD) is essential for assessing the impact of 10- and 13-valent pneumococcal conjugate vaccines (PCV10/13). The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project aimed to evaluate the global evidence to estimate the impact of PCV10/13 by age, product, schedule, and syndrome. Here we systematically characterize and summarize the global landscape of routine serotype-specific IPD surveillance in PCV10/13-using countries and describe the subset that are included in PSERENADE. Of 138 countries using PCV10/13 as of 2018, we identified 109 with IPD surveillance systems, 76 of which met PSERENADE data collection eligibility criteria. PSERENADE received data from most (n = 63, 82.9%), yielding 240,639 post-PCV10/13 introduction IPD cases. Pediatric and adult surveillance was represented from all geographic regions but was limited from lower income and high-burden countries. In PSERENADE, 18 sites evaluated PCV10, 42 PCV13, and 17 both; 17 sites used a 3 + 0 schedule, 38 used 2 + 1, 13 used 3 + 1, and 9 used mixed schedules. With such a sizeable and generally representative dataset, PSERENADE will be able to conduct robust analyses to estimate PCV impact and inform policy at national and global levels regarding adult immunization, schedule, and product choice, including for higher valency PCVs on the horizon.

Changes in pneumococcal antimicrobial resistance (AMR) have been reported following use of pneumococcal conjugate vaccines (PCVs) in childhood vaccination programmes. We describe AMR trends and clonality in Norway during 2004-2016; we studied 10,239 invasive pneumococcal disease (IPD) isolates in terms of serotypes, antimicrobial susceptibility, and for a systematically collected subset of 2473 isolates, multilocus sequence types (ST). The IPD cases were notified to the Norwegian Surveillance System for Communicable Diseases and pneumococcal isolates were collected through the National Reference Laboratory for Pneumococci. The cases are sourced from the entire Norwegian population. We supplemented the IPD isolates with isolates from carriage studies in children attending day-care, performed in 2006 (before mass childhood vaccination with PCV7), 2008 (2 years after PCV7 introduction), 2013 (2 years after the transition to PCV13), and 2015. IPD cases were 0-102 years old; median 64 years. Carriage study participants were typically aged 1-5 years. Overall, AMR was low; a maximum of 7% of IPD isolates were resistant, depending on the antimicrobial. Erythromycin and trimethoprim/sulfamethoxazole resistant IPD (ERY-R and SXT-R, respectively) decreased in the PCV7 period (2006-2010). In the PCV13 period (2011-2016) however, we saw an indication of increased non-susceptibility among IPD isolates. This increase was mainly due to non-vaccine serotypes 15A-ST63 (multidrug resistant), 24F-ST162 (SXT-R), 23B-ST2372 (penicillin non-susceptible and SXT-R) and 33F (ERY-R and clindamycin resistant). Resistant or non-susceptible IPD isolates were often clones introduced into Norway during the study period. The exception was ERY-R isolates; initially, these largely consisted of an established serotype 14-ST9 clone, which disappeared after introducing PCV7. The carriage study results mostly resembled the changes seen in IPD with a maximum of 9% of the participants per study carrying resistant pneumococci. As actual PCVs are not fully limiting AMR, higher-valency vaccines and prudent use of antimicrobials are still needed to temper pneumococcal AMR., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Lotta Siira is a co-investigator in an unrelated study, for which the National Institute for Health and Welfare, Finland, has received research funding from GlaxoSmithKline Biologicals SA. The other authors report no conflicts of interests., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The study aimed to assess whether gastrointestinal (GI) symptoms at admission are associated with increased short-term mortality in patients with invasive pneumococcal disease (IPD)., Methods: We included all patients with IPD at Aker University Hospital in Oslo, Norway, from 1993 to 2008. Clinical data were registered. Survival data were retrieved from official registries. We used Cox regression and Kaplan-Meier curve to compare mortality within 28 days of admission in patients with and without GI symptoms., Results: Four hundred sixteen patients were included. Of these, 108 patients (26%) presented with GI symptoms, and 47 patients (11%) with GI symptoms only. Patients with GI symptoms were younger (p < 0.001) and had less cardiovascular disease (p < 0.001), pulmonary disease (p = 0.048), and cancer (p = 0.035) and received appropriate antibiotic treatment later. After adjusting for risk factors, we found an increased hazard ratio of 2.28 (95% CI 1.31-3.97) in patients presenting with GI symptoms. In patients with GI symptoms only there was an increased hazard ratio of 2.24 (95% CI 1.20-4.19) in univariate analysis, which increased to 4.20 (95% CI 2.11-8.39) after multivariate adjustment. Fewer patients with GI symptoms only received antibiotics upon admission., Conclusions: A large proportion of IPD patients present with GI symptoms only or in combination with other symptoms. GI symptoms in IPD are associated with increased short-term mortality.

In Norway, childhood immunisation is offered on voluntary basis, free of charge and is delivered through trained nurses at > 650 child health centres and school health services. Maintaining high confidence in the vaccination programme is key to sustaining high vaccine uptake. We aimed to investigate confidence in childhood vaccination in the general population and to identify determinants for lower confidence. In 2017 and 2018, Statistics Norway asked questions on confidence in childhood vaccination (to all respondents) and children's vaccination history (to parents) in their routine cross-sectional survey. Respondents reported their level of agreement on a five-point Likert scale. Using a weighted analysis we calculated proportions agreeing [95% confidence interval] by respondent characteristics. Overall, 2169 individuals participated (54% response). 95.8% [94.8-96.7] answered that vaccination is important, 93.4% [92.2-94.4] thought that vaccines are safe, 96.0% [95.0-96.8] thought that vaccines are effective and for 93.4% [92.2-94.4] vaccination was compatible with their basic values. Those with lower level of education expressed lower confidence in vaccination due to conflict with their basic values (88.2% [84.7-91.0] answered positively). Those unemployed expressed lower confidence due to conflict with their basic values (81.9% [71.8-88.9]) and because of concerns about vaccines' safety (83.5% [73.7-90.1]). 96.3% [94.3-97.6] of parents (n = 580) had their children fully vaccinated, despite that one fifth answered that they at least once have had doubts on whether or not to vaccinate their children. There is high confidence in childhood vaccination in Norway. Those with a lower level of education and the unemployed reported comparatively lower confidence. To maintain high confidence in childhood vaccination, we recommend maintaining the well-informed system with easily accessible vaccinations. Furthermore, we recommend maintaining surveillance of vaccine confidence, supplemented with targeted studies on subgroups who are less confident, express doubts and/or oppose vaccination. Those studies should inform communication strategies tailored to subgroups., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Adult vaccination is high on the agenda in many countries. Two different vaccines are available for the prevention of pneumococcal disease in adults: a 23-valent polysaccharide vaccine (PPV23), and a 13-valent conjugated vaccine (PCV13). The objective of this review is to update the evidence base for vaccine efficacy and effectiveness of PPV23 and PCV13 against invasive pneumococcal disease and pneumonia among an unselected elderly population. We systematically searched for clinical trials and observational studies published between January 1 2016 and April 17 2019 in Pubmed, Embase, Cinahl, Web of Science, Epistemonikos and Cochrane databases. Risk of bias was assessed using Cochrane Risk of Bias tool for and the Newcastle-Ottawa Scale. Results were stratified by vaccine type and outcome. We identified nine studies on PCV13 and six on PPV23. No new randomized clinical trials were identified. Due to different outcomes, it was not possible to do a meta-analysis. New high-quality observational studies indicate protective vaccine effectiveness for both vaccines against vaccine type pneumonia. Our estimates for the protective vaccine efficacy and effectiveness (VE) of PPV23 on pneumonia and pneumococcal pneumonia overlap with results from previously published reviews. Some of the results indicate that the effectiveness of the PPV23 is best in younger age groups, and that it decreases over time.

Objectives: Antibiotic overuse has led to the global emergence of antimicrobial-resistant bacteria, and children are among the most frequent users of antibiotics. Most studies with broad-spectrum antibiotics show a severe impact on resistome development in patients. Although narrow-spectrum antibiotics are believed to have fewer side effects, their impact on the microbiome and resistome is mostly unknown. The aim of this study was to investigate the impact of the narrow-spectrum antibiotic phenoxymethylpenicillin (penicillin V) on the microbiome and resistome of a child treated for acute otitis media., Methods: Oral and faecal samples were collected from a 1-year-old child before (Day 0) and after (Days 5 and 30) receiving penicillin V for otitis media. Metagenomic sequencing data were analysed to determine taxonomic profiling using Kraken and Bracken software, and resistance profiling using KMA in combination with the ResFinder database., Results: In the oral samples, antimicrobial resistance genes (ARGs) belonging to four classes were identified at baseline. At Day 5, the abundance of some ARGs was increased, whereas some remained unchanged and others could no longer be detected. At Day 30, most ARGs had returned to baseline levels or lower. In the faecal samples, seven ARGs were observed at baseline and five at Day 5. At Day 30, the number of ARGs had increased to 21., Conclusions: Following penicillin V, we observed a remarkable enrichment of the aecal resistome, indicating that even narrow-spectrum antibiotics may have important consequences in selecting for a more resistant microbiome., (Copyright © 2019 International Society for Antimicrobial Chemotherapy. Published by Elsevier Ltd. All rights reserved.)

Background: Streptococcus pneumoniae carriage is often asymptomatic but can cause invasive pneumococcal disease. Pneumococcal carriage is a prerequisite for disease, with children as main reservoir and transmitters. Childhood carriage can therefore be used to determine which serotypes circulate in the population and which may cause disease in the non-vaccinated population. In 2006, a pneumococcal conjugate vaccine (PCV7) was introduced into the Norwegian Childhood Immunisation Programme, which was replaced by the more valent PCV13 in 2011. We investigated changes in pneumococcal carriage prevalence 4 years after switching to PCV13 compared to three previous surveys, and analysed factors associated with carriage in children., Methods: We conducted a cross-sectional study in Norway, autumn 2015, among children attending day-care centres. We collected questionnaire data and nasopharyngeal swabs to identify pneumococcal serotypes. We compared the carriage prevalence in 2015 with surveys conducted in the same setting performed before widespread vaccination (2006; n = 610), 2 years after PCV7 introduction (2008; n = 600), and 2 years after switching to PCV13 (2013; n = 874). Using multilevel logistic regression we determined the association between pneumococcal carriage and previously associated factors., Results: In 2015, 896 children participated, with age ranging from 8 to 80 months. The overall carriage prevalence was 48/100 children [95%CI 44-53] in 2015, 38% [29-46] lower than in 2006 pre-PCV7, and 23% [12-32] lower than in 2013, 2 years after switching to PCV13. The PCV13 carriage prevalence was 2.8/100 children [1.9-4.2] in 2015. Increasing age (p < 0.001), recent antimicrobial use (odds ratio = 0.42 [0.21-0.57]) and being vaccinated (odds ratio = 0.37 [0.29-0.47]) were negatively associated with carriage., Conclusions: Our study showed a continued decrease in overall pneumococcal carriage, mainly fuelled by the decline in vaccine serotypes after vaccine introduction. Childhood vaccination with PCV13 should be continued to keep low PCV13 carriage, transmission and disease. Furthermore, the low prevalence of PCV13-type carriage in children endorse the choice of not recommending PCV13 in addition to the 23-valent pneumococcal polysaccharide vaccine to most medical risk groups in Norway, as little disease caused by these serotypes can be expected.

Background: Pneumococcal conjugate vaccines (PCVs) have the potential to prevent pneumococcal disease through direct and indirect protection. This multicentre European study estimated the indirect effects of 5-year childhood PCV10 and/or PCV13 programmes on invasive pneumococcal disease (IPD) in older adults across 13 sites in 10 European countries, to support decision-making on pneumococcal vaccination policies., Methods: For each site we calculated IPD incidence rate ratios (IRR) in people aged ≥65 years by serotype for each PCV10/13 year (2011-2015) compared with 2009 (pre-PCV10/13). We calculated pooled IRR and 95% CI using random-effects meta-analysis and PCV10/13 effect as (1 - IRR)*100., Results: After five PCV10/13 years, the incidence of IPD caused by all types, PCV7 and additional PCV13 serotypes declined 9% (95% CI -4% to 19%), 77% (95% CI 67% to 84%) and 38% (95% CI 19% to 53%), respectively, while the incidence of non-PCV13 serotypes increased 63% (95% CI 39% to 91%). The incidence of serotypes included in PCV13 and not in PCV10 decreased 37% (95% CI 22% to 50%) in six PCV13 sites and increased by 50% (95% CI -8% to 146%) in the four sites using PCV10 (alone or with PCV13). In 2015, PCV13 serotypes represented 20-29% and 32-53% of IPD cases in PCV13 and PCV10 sites, respectively., Conclusion: Overall IPD incidence in older adults decreased moderately after five childhood PCV10/13 years in 13 European sites. Large declines in PCV10/13 serotype IPD, due to the indirect effect of childhood vaccination, were countered by increases in non-PCV13 IPD, but these declines varied according to the childhood vaccine used. Decision-making on pneumococcal vaccination for older adults must consider the indirect effects of childhood PCV programmes. Sustained monitoring of IPD epidemiology is imperative., Competing Interests: Competing interests: The following authors report funding for research projects, travels or consultancy outside the submitted work: H-CS (project sponsored by Pfizer); ZH (travel grant from Pfizer), SNL (research including GSK, Pfizer, Sanofi Pasteur on behalf of St George’s University of London and Public Health England (PHE)); NKF (employed by PHE Respiratory and Vaccine Preventable Bacteria Reference Unit and PHE Immunisation that provided serotype surveillance reports to Affinivax, Pfizer and GSK); HR-K and JJ (employed by the National Institute for Health and Welfare that received research funding from GSK for the conduct of a trial of PCV10); AvdE (Pfizer grant for an investigator initiated project, consultancy fees from GSK, participation in the Pfizer Scientific Advisory board); CM-A (fees from GSK and grants from Pfizer); EV (Pfizer grants and personal fees); MC (Pfizer grants and personal fees); HH (research funding from Pfizer and Astellas)., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The extent to which iatrogenically-immunosuppressed individuals benefit from indirect effects of childhood vaccination with pneumococcal conjugate vaccines (PCVs) is unknown. We determined how the sequential introduction of PCV7 (2006) and PCV13 (2011) in the Norwegian childhood vaccination program has affected the epidemiology of invasive pneumococcal disease (IPD) in individuals treated with immunosuppressants in ambulatory care., Methods: We conducted a case-cohort study comprising 7926 IPD cases reported to the Norwegian Surveillance System for Communicable Diseases in 2005-2014 and 249998 individuals randomly selected from the National Registry in 2012. We defined immunosuppressive treatment groups based on dispensed prescriptions retrieved from the Norwegian Prescription Database. Incidences and age-adjusted relative risks (RR) were estimated., Results: IPD incidences decreased in all groups. The PCV13 incidence decreased by 5-12% across groups. The non-PCV13 incidence increased by 4-10%, mostly in individuals on chemotherapy (overlapping 95% confidence intervals). In the PCV13 era, the RR for IPD was highest (significant) and the percentage of cases caused by the polysaccharide vaccine PPV23 serotypes lowest (numerical) in individuals on chemotherapy (RR = 20.4, PPV23 = 52%), followed by individuals on corticosteroids (RR = 6.2, PPV23 = 64%), other immunosuppressants (RR = 5.6, PPV23 = 68%), and no immunosuppressants (RR = 1 [reference], PPV23 = 74%)., Conclusions: IPD incidences declined after PCV introduction in both immunocompetent and iatrogenically-immunosuppressed individuals, underscoring the benefit of childhood vaccination for the entire population. Still, individuals treated with immunosuppressants in ambulatory care are at increased risk of IPD caused by a more diverse group of serotypes., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objectives: Burden of pneumococcal disease depends on the prevalence and invasive disease potential of serotypes. We aimed to estimate the invasive disease potential of serotypes in children under 5 years of age by combining data from different settings with routine immunisation with pneumococcal conjugate vaccines (PCV)., Methods: We conducted a systematic review, supplemented by unpublished data, to identify data on the frequency of pneumococcal serotypes in carriage and invasive pneumococcal disease (IPD). We estimated the invasive disease potential of serotypes as the ratio of IPD in relation to carriage (odds ratio and 95%CI) compared with 19A (reference serotype) by meta-analysis. We report results based on a random effects model for children aged 0-23, 24-29, and 0-59 months and by invasive clinical syndromes., Results: In comparison with 19A, serotypes 1, 7F, and 12F had a significantly higher invasive disease potential in children aged 0-23 and 0-59 months for all IPD and clinical syndromes (OR > 5). Several non-vaccine types (NVTs) (6C, 15A, 15BC, 16F, 23B, in these two age groups) had a lower invasive disease potential than 19A (OR 0.1-0.3). NVTs 8, 12F, 24F, and 33F were at the upper end of the invasiveness spectrum., Conclusions: There is substantial variation among pneumococcal serotypes in their potential to cause IPD and disease presentation, which is influenced by age and time after PCV introduction. Surveillance of IPD and carriage is critical to understand the expected effectiveness of current PCVs (in the longer term) and guide the development of future vaccines., (Copyright © 2018 The British Infection Association. All rights reserved.)

We report here the draft genome sequence of a Streptococcus species belonging to the S. mitis group. While a clear species identification cannot be made for the isolate, it appears that its most recent common ancestor is the species S. pseudopneumoniae ., (Copyright © 2018 Kirkeleite et al.)

One reason for increased pertussis incidence is the adaptation of Bordetella pertussis to vaccine-induced immunity by modulating its genomic structure. This study, EUpert IV, includes 265 isolates collected from nine European countries during 2012 to 2015 ( n = 265) and compares the results to previous EUpert I to III studies (1998 to 2009). The analyses included genotyping, serotyping, pulsed-field gel electrophoresis (PFGE), and multilocus variable-number tandem-repeat analysis (MLVA). Genotyping results showed only small variations among the common virulence genes of B. pertussis The frequencies of serotypes Fim2 and Fim3 varied among the four collections. Genomic analyses showed that MLVA type 27 increased to 80% between the periods of 1998 to 2001 and 2012 to 2015. Two PFGE profiles, BpSR3 (29.4%) and BpSR10 (27.2%), constituted more than 50% of the circulating isolates in the present collection. Our study indicates that the European B. pertussis population is changing and became more homogenous after the introduction of acellular pertussis vaccines., (Copyright © 2018 American Society for Microbiology.)

An external quality assessment (EQA) scheme for pneumococcal serotype identification has been performed over a period of 11 years, by a network of European pneumococcal reference laboratories. We report the results from the EQA, and present an assessment of the acceptability and utility of the EQA scheme. Reports from 22 EQA panels distributed in 2005-2016 were analysed. Each EQA panel consisted of seven isolates. A questionnaire including seven questions related to the acceptability and utility of the EQA scheme was distributed to all participating laboratories. Altogether, 154 pneumococcal isolates were tested. Of the 92 serologically distinct serotypes currently defined, 49 serotypes were included in the rounds. Discrepant results were observed in eight EQA rounds, involving 11 isolates (7.1%, 95% CI: 4% to 12%). All participating laboratories reported that the EQA scheme was useful for quality assurance purposes. Our results show that comparable serotyping data can be obtained in different laboratories. The EQA participation helps to keep the typing procedures at a high standard and provides data for accreditation purposes. The EQA is helpful when new technologies are introduced, and reveal limitations of both genotypic and phenotypic methods. Continuation of the presented EQA scheme is planned.

Objectives: We studied if patients surviving hospitalization for invasive pneumococcal disease (IPD) have an increased long-term mortality., Methods: In this population-based case-control study, we assessed adults discharged from Aker University Hospital in Oslo, Norway, from 1993 to 2008 after surviving IPD. Mortality among the study population was compared to the general Norwegian population using standardized mortality ratios (SMR). Median follow-up time was 7.2 years (range 5 days to 21.1 years). Associated factors were also investigated., Results: We assessed 372 patients of whom 184 patients died during the observation period. Mortality was increased for 10 years after surviving hospitalization for IPD. Patients aged 18-64 years had a one-year SMR of 18.8 (95% CI: 10.0-32.1) and a 10-year SMR of 6·0 (95% CI: 4.4-8.0). SMR for the first five years among patients with and without underlying conditions were 10.7 (95% CI: 7.0-15.5) and 2.8 (95% CI: 0.9-6.4), respectively. Patients older than 65 years had a one-year SMR of 1·8 (95% CI: 1.2-2.7) and a 10-year SMR of 1.6 (95% CI: 1.4-1.9)., Conclusions: Patients surviving IPD had an increased long-term mortality compared to the general population. This was particularly pronounced in patients with known underlying conditions. These findings suggest that IPD is a negative prognostic marker, and that a closer follow-up of patients who have suffered IPD is warranted.

Background: As a standard method for pneumococcal carriage studies, the World Health Organization recommends nasopharyngeal swabs be transported and stored at cool temperatures in a medium containing skim-milk, tryptone, glucose and glycerol (STGG). An enrichment broth used for transport at room temperature in three carriage studies performed in Norway may have a higher sensitivity than STGG. We therefore compared the media in vitro and in vivo., Methods: For the in vitro component, three strains (serotype 4, 19F and 3) were suspended in STGG and enrichment broth. Recovery was compared using latex agglutination, quantification of bacterial loads by real-time PCR of the lytA gene, and counting colonies from incubated plates. For the in vivo comparison, paired swabs were obtained from 100 children and transported in STGG at cool temperatures or in enrichment broth at room temperature. Carriage was identified by latex agglutination and confirmed by Quellung reaction., Results: In vitro, the cycle threshold values obtained by PCR did not differ between the two media (p = 0.853) and no clear difference in colony counts was apparent after incubation (p = 0.593). In vivo, pneumococci were recovered in 46% of swabs transported in STGG and 51% of those transported in enrichment broth (Kappa statistic 0.90, p = 0.063)., Discussion: Overall, no statistical differences in sensitivity were found between STGG and enrichment broth. Nevertheless, some serotype differences were observed and STGG appeared slightly less sensitive than enrichment broth for detection of nasopharyngeal carriage of pneumococci by culturing. We recommend the continued use of STGG for transport and storage of nasopharyngeal swabs in pneumococcal carriage studies for the benefit of comparability between studies and settings, including more resource-limited settings., Competing Interests: The authors declare there are no competing interests.

Background: The approach to surveillance of Lyme borreliosis varies between countries, depending on the purpose of the surveillance system and the notification criteria used, which prevents direct comparison of national data. In Norway, Lyme borreliosis is notifiable to the Surveillance System for Communicable Diseases (MSIS). The current notification criteria include a combination of clinical and laboratory results for borrelia infection (excluding Erythema migrans) but there are indications that these criteria are not followed consistently by clinicians and by laboratories. Therefore, an evaluation of Lyme borreliosis surveillance in Norway was conducted to describe the purpose of the system and to assess the suitability of the current notification criteria in order to identify areas for improvement., Methods: The CDC Guidelines for Evaluation of Surveillance Systems were used to develop the assessment of the data quality, representativeness and acceptability of MSIS for surveillance of Lyme borreliosis. Data quality was assessed through a review of data from 1996 to 2013 in MSIS and a linkage of MSIS data from 2008 to 2012 with data from the Norwegian Patient Registry (NPR). Representativeness and acceptability were assessed through a survey sent to 23 diagnostic laboratories., Results: Completeness of key variables for cases reported to MSIS was high, except for geographical location of exposureThe NPR-MSIS linkage identified 1047 cases in both registries, while 363 were only reported to MSIS and 3914 were only recorded in NPR. A higher proportion of cases found in both registries were recorded as neuroborreliosis in MSIS (84.4 %) than those cases found only in MSIS (20.1 %). The trend (average yearly increase or decrease in reported cases) of neuroborreliosis in MSIS was not significantly different from the trend for all other clinical manifestations recorded in MSIS in negative binomial regression (p = 0.3). The 16 surveyed laboratories (response proportion 70 %) indicated differences in testing practices and low acceptability of the notification criteria., Conclusions: Given the challenges associated with diagnosing Lyme borreliosis, the selected notification criteria should be closely linked with the purpose of the surveillance system. Restricting reportable Lyme borreliosis to neuroborreliosis may increase validity, while a more sensitive case definition (potentially including erythema migrans) may better reflect the true burden of disease. We recommend revising the current notification criteria in Norway to ensure that they are unambiguous for clinicians and laboratories.

Detection of specific antibodies against Borrelia burgdorferi sensu lato is a useful aid for the diagnosis of Lyme borreliosis. However, antibodies are present in the general population. The seroprevalence increase with age, and varies according to the prevalence of infected ticks. We performed a seroprevalence study of IgM and IgG antibody reactivity against B. burgdorferi sensu lato in Norway by age-groups and geography, in order to provide a reference set of seroprevalence to inform the interpretation of positive test results. We used two commercially available enzyme immuno assays (EIA) and a multiplexed bead assay to detect Borrelia IgG antibodies in a convenience sample of 3057 sera collected from clinical chemistry laboratories in 10 of 19 counties in Norway between December 2011 and January 2013. We estimated seroprevalence by age and county by a logistic regression model. IgM antibodies were detected by two commercially available EIAs and a multiplexed bead assay. The overall seroprevalence of Borrelia IgG was 4.0% (95% CI: 2.4-6.6%) and 4.2% (2.6-6.8%) by the two EIAs, respectively. The seroprevalence increased by age, and by geography from north to south. The IgG assays showed a good agreement for positive test results. All sera positive for IgG in the multiplexed bead assay reacted with the VlsE antigen, and also had high antibody levels by EIA. The Borrelia seroprevalence varied by geography and increased by age. The results indicate regional differences in pre-test probabilities for positive test results, and can inform the interpretation of laboratory results., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

We investigated a nationwide outbreak of Salmonella Coeln in Norway, including 26 cases identified between 20 October 2013 and 4 January 2014. We performed a matched case-control study, environmental investigation and detailed traceback of food purchases to identify the source of the outbreak. In the case-control study, cases were found to be more likely than controls to have consumed a ready-to-eat salad mix (matched odds ratio 20, 95% confidence interval 2·7-∞). By traceback of purchases one brand of ready-to-eat salad was indicated, but all environmental samples were negative for Salmonella. This outbreak underlines that pre-washed and bagged salads carry a risk of infection despite thorough cleaning procedures by the importer. To further reduce the risk of infection by consumption of ready-to-eat salads product quality should be ensured by importers. Outbreaks linked to salads reinforce the importance of implementation of appropriate food safety management systems, including good practices in lettuce production.

Background: Invasive pneumococcal disease (IPD) is responsible for significant mortality and morbidity worldwide. There are however few longitudinal studies on the changes in case fatality rate of IPD in recent years. We carried out a prospective observational study of patients with IPD in Nord Trøndelag county in Norway from 1993 to 2011 to study the clinical variables and disease outcome. The main outcome was all-cause mortality after 30 and 90 days., Methods: Patients with positive blood cultures were registered prospectively by the microbiology laboratory and clinical variables were registered retrospectively from patients' hospital records. The severity of sepsis was assigned according to the 2001 International Sepsis Definition Conference criteria. The association between mortality and predictive factors was studied using a logistic regression model., Results: The total number of patients was 414 with mean age of 67 years and 53 % were male. Comorbidity was assessed by the Charlson Comorbidity Index (CCI). A CCI-score of 0 was registered in 144 patients (34.8 %), whereas 190 had a score of 1-2 (45.9 %) and 80 (19.3 %) had a score ≥3. 68.8 % of the patients received appropriate antibiotics within the first 6 h. The 30-day mortality risk increased by age and was 3-fold higher for patients aged ≥80 years (24.9, 95 % CI 16.4-33.4 %) compared to patients aged <70 (8.0, 95 % CI 3.5-12.4 %). 110 patients, (26.6 %) had severe sepsis and 37 (8.9 %) had septic shock. The 30 day all-cause mortality risk for those with sepsis without organ failure was 5.4 % (95 % CI 2.7-8.0 %), 20.2 % (95 % CI 13.5-27.4 %) for those with severe sepsis and 35.0 % (95 % CI 21.6-49.0 %) for those with septic shock. The mortality risk did not differ between the first and the second halves of the study period with a 30-day mortality risk of 13.5 % (95 % CI 7.9-19.2 %) for 1993-2002 versus 11.8 % (95 % CI 8.2-15.3 %) for 2003-2011., Conclusion: IPD carries a high mortality despite early and appropriate antibiotics in most cases. We found no substantial decrease in case fatality rate during the study period of 18 years. Older age and higher severity of disease were important risk factors for death in IPD.

Background: Shifts in the pneumococcal population colonizing healthy children are expected after switching from a 7-valent pneumococcal conjugate vaccine (PCV7) to a 13-valent (PCV13) in the childhood immunization program. We assessed effects of the switch by comparing pneumococcal carriage and serotype and genetic diversity of pneumococci carried by children in the PCV13-era with those carried in the prevaccination-era and PCV7-era., Methods: Nasopharyngeal swabs were obtained in autumn 2013 from children attending day-care centers (874 swabs, 583 isolates). Serotyping, multilocus sequence typing and antimicrobial susceptibility testing were performed on all isolates. Results were compared with samples from 2006 (610 swabs, 538 isolates) and 2008 (600 swabs, 562 isolates)., Results: The carriage prevalence in 2013 was 62 of 100 children (95% confidence intervals: 58-66), a significant decrease from 2006 and 2008. PCV13 serotypes accounted for 7% of isolates in 2013. Non-PCV13 prevalence increased from 2006 to 2008 [prevalence ratio: 1.73 (1.40-2.15)] but remained stable in 2013 [0.99 (0.88-1.12)]. Still, non-PCV13 serotypes 21, 23B, 23A and 22F had increased. In 2013, the serotype and genetic diversity had decreased slightly, and distinct serotype and genetic profiles clustered more within day-care centers compared with the earlier samples. Serotype switch was uncommon. Overall, antimicrobial resistance was limited., Conclusions: Carriage of PCV13 serotypes has decreased without a coinciding increase in non-PCV13 serotypes. The serotype and genetic shifts among non-PCV13 serotypes suggest that a new equilibrium has not yet been reached. As the few non-PCV13 serotypes that increased have generally a lower invasive capacity than vaccine serotypes, direct and indirect protection of PCV13 on invasive pneumococcal disease can be expected to continue.

Mycoplasma pneumoniae outbreaks cause increased use of macrolides and tetracyclines. We aimed to investigate whether drug use data, in addition to laboratory data, could improve understanding of the spread of M. pneumoniae epidemics. Number of users of Mycoplasma antibiotics (erythromycin, doxycycline, clarithromycin) per week and county of residence in an indicator age group (6-12 years) was retrieved from the Norwegian prescription database for the epidemic season 2011-2012 and compared to non-epidemic seasons. In 2011, increased use of Mycoplasma antibiotics was first observed in September on the west coast of Norway. The Norwegian laboratory-based surveillance system showed the first increase in positive tests in August 2011 and an epidemic was announced on 25 October 2011. At that time the use of Mycoplasma antibiotics had already exceeded three times the use in non-epidemic periods. Data for three counties from the regional microbiological laboratories showed that the increase in number of positive samples coincided in time with the increase in prescription data. Laboratory data cannot accurately determine the extent of an epidemic, and drug use data cannot identify the cause. Establishing a systematic interaction between the two monitoring systems will enhance surveillance and probably contribute to improved infection control and prudent antibiotic prescribing.

Two different vaccines, a 23-valent polysaccharide vaccine (PPV23) and a 13-valent conjugate vaccine (PCV13), are available for prevention of invasive pneumococcal disease (IPD) in the population aged 65 years and older (65+). The IPD epidemiology in the 65+ is undergoing change due to indirect effects of childhood immunisation. Vaccine recommendations for the 65+ must take into account these trends in epidemiology. We therefore explored the preventive potential of vaccination strategies to prevent IPD in the 65+, including PPV23, PCV13 or PCV13 + PPV23 in 2014-2019. Quasi-Poisson regression models were fitted to 2004-2014 population-wide surveillance data and used to predict incidences for vaccine-type and non-vaccine type IPD. We determined the number of people needed to be vaccinated to prevent one case per season (NNV) for each strategy and estimated the public health impact on the IPD case counts from increasing the vaccine uptake to 28-45%. Our results indicate that PCV13-IPD will decrease by 71% from 58 (95% prediction interval 55-61) cases in 2014/15 to 17 (6-52) in 2018/19 and PPV23-IPD by 32% from 168 (162-175) to 115 (49-313) cases. The NNV will increase over time for all strategies because of a decreasing vaccine-type IPD incidence. In 2018/19, the PCV13-NNV will be 5.3 times higher than the PPV23-NNV. Increasing the vaccine uptake will lead to a larger public health impact for all scenarios. Combining PCV13 and PPV23 is most effective, but the additional effect of PCV13 will decrease and is only marginal in 2018/19. Our study demonstrates the importance of increasing PPV23 uptake and of developing vaccines that confer broader immunity., (Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.)

Despite more than 50 years of vaccination, pertussis is still an endemic disease, with regular epidemic outbreaks. With the exception of Poland, European countries have replaced whole-cell vaccines (WCVs) by acellular vaccines (ACVs) in the 1990s. Worldwide, antigenic divergence in vaccine antigens has been found between vaccine strains and circulating strains. In this work, 466 Bordetella pertussis isolates collected in the period 1998-2012 from 13 European countries were characterised by multi-locus antigen sequence typing (MAST) of the pertussis toxin promoter (ptxP) and of the genes coding for proteins used in the ACVs: pertussis toxin (Ptx), pertactin (Prn), type 2 fimbriae (Fim2) and type 3 fimbriae (Fim3). Isolates were further characterised by fimbrial serotyping, multi-locus variable-number tandem repeat analysis (MLVA) and pulsed-field gel electrophoresis (PFGE). The results showed a very similar B. pertussis population for 12 countries using ACVs, while Poland, which uses a WCV, was quite distinct, suggesting that ACVs and WCVs select for different B. pertussis populations. This study forms a baseline for future studies on the effect of vaccination programmes on B. pertussis populations.

For decades, vaccination with the 23-valent polysaccharide pneumococcal vaccine (PPV23) has been available for risk groups aged ⩾2 years to prevent invasive pneumococcal disease (IPD). Recently, a 13-valent pneumococcal conjugated vaccine (PCV13) has been licensed for use in all age groups. PCV13 may induce better protection than PPV23 because of different immunogenic properties. This called for a revision of vaccine recommendations for risk groups. We therefore reviewed literature on risk groups for IPD, and effectiveness and safety of pneumococcal vaccines and supplemented that with information from public health institutes, expert consultations and data on IPD epidemiology. We included 187 articles. We discuss the implications of the heterogenic vulnerability for IPD within and between risk groups, large indirect effects of childhood immunization, and limited knowledge on additional clinical benefits of PCV13 in combination with PPV23 for the Norwegian recommendations. These are now step-wise and consider the need for vaccination, choice of pneumococcal vaccines, and re-vaccination interval by risk group.

Pathogen adaptation has been proposed to contribute to the resurgence of pertussis. A striking recent example is the emergence of isolates deficient in the vaccine component pertactin (Prn). This study explores the emergence of such Prn-deficient isolates in six European countries. During 2007 to 2009, 0/83 isolates from the Netherlands, 0/18 from the United Kingdom, 0/17 Finland, 0/23 Denmark, 4/99 Sweden and 5/20 from Norway of the isolates collected were Prn-deficient. In the Netherlands and Sweden, respectively 4/146 and 1/8 were observed in a later period (2010–12). The Prn-deficient isolates were genetically diverse and different mutations were found to inactivate the prn gene. These are indications that Prn-deficiency is subject to positive selective pressure. We hypothesise that the switch from whole cell to acellular pertussis vaccines has affected the balance between ‘costs and benefits’ of Prn production by Bordetella pertussis to the extent that isolates that do not produce Prn are able to expand. The absence of Prn-deficient isolates in some countries may point to ways to prevent or delay the spread of Prn-deficient strains. In order to substantiate this hypothesis, trends in the European B. pertussis population should be monitored continuously.

The introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in the childhood immunisation programme in Norway in 2006 substantially decreased the incidence of vaccine-type (VT) invasive pneumococcal disease (IPD) in all age groups. Additionally, a slight increase in the non-vaccine (NVT) serotype IPD incidence (serotype replacement) was observed. After replacing PCV7 with PCV13 in 2011, a further decrease in IPD incidence is expected. However, the protection by the six additional serotypes opens new nasopharyngeal niches for colonisation, which favours conditions for serotype replacement. Close monitoring of IPD therefore remains important in order to quickly detect changes. In this observational retrospective population-based cohort study we used data notified nationally between 1 January 2004 and 31 December 2012 to determine the VT- and NVT-IPD incidences. The diversity in serotype distribution per year was analysed using the Simpson's index of diversity. Immunisation history of young children was obtained from the Norwegian Vaccination Registry to determine vaccine failure. The incidence of VT-IPD decreased in the targeted (<5 years) and non-targeted (≥5) age groups since PCV7 introduction and further decreased after the replacement with PCV13. Only two cases of vaccine failure were identified. This indicates very high effectiveness of the 2+1 schedules with PCV7 or PCV13 and suggests that non-vaccinated individuals profit through indirect protection. The decrease in incidence of PCV7-IPD in non-targeted age groups became larger in later years, indicating a lag phase for the indirect effects, and suggests that the indirect protection of PCV13 will increase in coming years. The incidence of some NVT, specifically serotypes 23B and 15A, increased after PCV13 introduction. This coincided with an increased Simpson's index of diversity in the targeted age group. As this suggests that serotype replacement is again occurring, continues monitoring of IPD is important so that adaptations to vaccine recommendations can be promptly issued., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

In October and November 2013, four cases of wound botulism were confirmed in people who inject drugs (PWID) in Norway. Two additional cases are suspected. Because of the international distribution pathways for heroin – the likely source of the outbreak – healthcare workers and public health authorities in other countries should remain vigilant for wound botulism in PWID. This outbreak serves as a reminder that countries should ensure access to botulinum antitoxin in case of outbreak situations.

Viable Bordetella pertussis isolates are essential for surveillance purposes. We performed culture of 223 PCR-positive nasopharyngeal samples. B. pertussis was recovered from 45 (20.2%) of the samples. Growth was associated with a high bacterial load, as determined by PCR. Culture from PCR-positive samples is a feasible approach to recover B. pertussis isolates, and culture can be limited to samples with a high bacterial load.

Background: The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced into the Norwegian Childhood Immunization Program in 2006. A substantial effectiveness of PCV7 immunization against invasive pneumococcal disease has been demonstrated, whereas evidence of its impact on respiratory tract infections are less consistent., Methods: This study included children participating in the Norwegian Mother and Child Cohort Study, which recruited pregnant women between 1999 and 2008. Maternal report of acute otitis media (AOM), lower respiratory tract infections (LRTIs) and asthma in the child was compared by PCV7 immunization status, as obtained from the Norwegian Immunization Registry. Generalized linear models with the log-link function were used to report adjusted relative risks (RRs) and 95% confidence intervals (CIs)., Results: For children who had received 3 or more PCV7 immunizations by 12 months of age, the adjusted RRs of AOM and LRTIs between 12 and 18 months were 0.86 (95% CI: 0.81, 0.91) and 0.78 (95% CI: 0.70, 0.87) respectively, when compared with nonimmunized children. A reduced risk of AOM, RR 0.92 (95% CI: 0.90, 0.94), and LRTIs, RR 0.75 (95% CI: 0.71, 0.80), between 18 and 36 months of age was also identified among children who had received 3 or more immunizations by 18 months of age. No association was seen between PCV7 immunization and asthma at 36 months of age., Conclusion: Reduced incidences of AOM and LRTIs before 36 months of age were observed among children immunized with PCV7 through the childhood immunization program.

Serotype replacement in invasive pneumococcal disease has been observed after widespread use of the 7-valent pneumococcal conjugate vaccine (PCV7). Replacement is dominated by penicillin-nonsusceptible serotype 19A in several countries. Antibiotic selection pressure has been proposed to interact with immunization, leading to rapid replacement. In Norway, where prescription of antibiotics is limited, post-PCV7 replacement by serotype 19A is dominated by penicillin-susceptible clones. Hence, serotype 19A replacement occurs, although it is not driven by antibiotic selection pressure.

Epidemics of Mycoplasma pneumoniae have recently been reported from England and Wales and from Denmark. A similar increase in M. pneumoniae infections was noted in Norway late autumn 2011.The epidemic has resulted in shortage of erythromycin and the use of alternative antibiotics has been recommended.

Genetic diversity in the species Streptococcus pneumoniae is mainly driven by horizontal gene transfer. S. pneumoniae is naturally competent for transformation. Competence is induced by a pheromone termed competence stimulating peptide (CSP) by a quorum-sensing mechanism. Two CSP pherotypes predominate amongst clinical isolates of S. pneumoniae, CSP-1 and CSP-2, with ability to trigger competence in bacteria of the homologue pherotype. Opposing theories on the effect of pherotypes on speciation have been proposed, either as a barrier for intra-pherotype gene transfer, or as a mechanism for fratricide resulting in lysis of non-competent bacterial cells. The aim of the present study was to determine pherotype distribution in strains of S. pneumococci isolated from the nasopharynges of healthy children. We sequenced the locus encoding CSP, comC, in sets of strains obtained from children colonised by multiple pneumococcal strains simultaneously. The impact of pherotype on co-colonisation was determined by comparing the observed distribution of pherotypes in co-colonising strains with the estimated pair-wise probability based on the overall pherotype distribution in the sample set. Five distinct comC alleles were identified, encoding CSP belonging to the two dominating pherotypes, CSP-1 (62.7%) and CSP-2 (37.3%). The observed distribution of pherotypes in sets of co-colonising pneumococcal strains did not differ from the probability estimate. Thus, co-colonisation of S. pneumoniae in healthy children is not restricted by pherotype., (Copyright © 2011 Elsevier B.V. All rights reserved.)