Social contact patterns during the early COVID-19 pandemic in Norway: insights from a panel study, April to September 2020.

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.

Effectiveness of 10 and 13-valent pneumococcal conjugate vaccines against invasive pneumococcal disease in European children: SpIDnet observational multicentre study.

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.

Evolution of Bordetella pertussis in the acellular vaccine era in Norway, 1996 to 2019.

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.

Global spatial dynamics and vaccine-induced fitness changes of Bordetella pertussis.

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.

Invasive group A streptococcal disease in pregnant women and young children: a systematic review and meta-analysis.

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 I2. 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; I2=100%). Invasive GAS incidence was 0·04 per 1000 livebirths (0·03 to 0·05; I2=100%; 11 studies) for neonates, 0·13 per 1000 livebirths (0·10 to 0·16; I2=100%; ten studies) for infants, and 0·09 per 1000 person-years (95% CI 0·07 to 0·10; I2=100%; nine studies) for children worldwide; 0·12 per 1000 livebirths (95% CI 0·00 to 0·24; I2=100%; three studies) in neonates, 0·33 per 1000 livebirths (-0·22 to 0·88; I2=100%; two studies) in infants, and 0·22 per 1000 person-years (0·13 to 0·31; I2=100%; two studies) in children in LMICs; and 0·02 per 1000 livebirths (0·00 to 0·03; I2=100%; eight studies) in neonates, 0·08 per 1000 livebirths (0·05 to 0·11; I2=100%; eight studies) in infants, and 0·05 per 1000 person-years (0·03 to 0·06; I2=100%; seven studies) in children for HICs. Case fatality risks were high, particularly among neonates in LMICs (61% [95% CI 33 to 89]; I2=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.

Serotype Replacement after Introduction of 10-Valent and 13-Valent Pneumococcal Conjugate Vaccines in 10 Countries, Europe.

We evaluated invasive pneumococcal disease (IPD) during 8 years of infant pneumococcal conjugate vaccine (PCV) programs using 10-valent (PCV10) and 13-valent (PCV13) vaccines in 10 countries in Europe. IPD incidence declined during 2011-2014 but increased during 2015-2018 in all age groups. From the 7-valent PCV period to 2018, IPD incidence declined by 42% in children <5 years of age, 32% in persons 5-64 years of age, and 7% in persons >65 years of age; non-PCV13 serotype incidence increased by 111%, 63%, and 84%, respectively, for these groups. Trends were similar in countries using PCV13 or PCV10, despite different serotype distribution. In 2018, serotypes in the 15-valent and 20-valent PCVs represented one third of cases in children <5 years of age and two thirds of cases in persons >65 years of age. Non-PCV13 serotype increases reduced the overall effect of childhood PCV10/PCV13 programs on IPD. New vaccines providing broader serotype protection are needed.

Antimicrobial susceptibility and clonality of Streptococcus pneumoniae isolates recovered from invasive disease cases during a period with changes in pneumococcal childhood vaccination, Norway, 2004-2016.

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.

High overall confidence in childhood vaccination in Norway, slightly lower among the unemployed and those with a lower level of education.

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.

Impact of narrow-spectrum penicillin V on the oral and faecal resistome in a young child treated for otitis media.

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.

Indirect Effects of Pneumococcal Childhood Vaccination in Individuals Treated With Immunosuppressive Drugs in Ambulatory Care: A Case-cohort Study.

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.

Effect of childhood pneumococcal conjugate vaccination on invasive disease in older adults of 10 European countries: implications for adult vaccination.

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.

Draft Genome Sequence of a Potentially Novel Streptococcus Species Belonging to the Streptococcus mitis Group.

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.

Surveillance of Circulating Bordetella pertussis Strains in Europe during 1998 to 2015.

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.

External Quality Assurance for Laboratory Identification and Capsular Typing of Streptococcus pneumoniae.

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.

Effect of high-valency pneumococcal conjugate vaccines on invasive pneumococcal disease in children in SpIDnet countries: an observational multicentre study.

BACKGROUND: The Streptococcus pneumoniae Invasive Disease network (SpIDnet) actively monitors populations in nine sites in seven European countries for invasive pneumococcal disease. Five sites use 13-valent pneumococcal conjugate vaccine (PCV13) alone and four use the ten-valent PCV (PCV10) and PCV13. Vaccination uptake is greater than 90% in six sites and 67-78% in three sites. We measured the effects of introducing high-valency PCVs on the incidence of invasive pneumococcal disease in children younger than 5 years. METHODS: We compared the incidence of invasive pneumococcal disease in each of the 4 years after the introduction of PCV13 alone or PCV10 and PCV13 with the average incidence during the preceding period of heptavalent PCV (PCV7) use, overall and by serotype category. We calculated incidence rate ratios (IRRs) and 95% CIs for each year and pooled the values for all sites in a random effects meta-analysis. FINDINGS: 4 years after the introduction of PCV13 alone or PCV10 and PCV13, the pooled IRR was 0·53 (95% CI 0·43-0·65) for invasive pneumococcal disease in children younger than 5 years caused by any serotype, 0·16 (0·07-0·40) for disease caused by PCV7 serotypes, 0·17 (0·07-0·42) for disease caused by 1, 5, and 7F serotypes, and 0·41 (0·25-0·69) for that caused by 3, 6A and 19A serotypes. We saw a similar pattern when we restricted the analysis to sites where only PCV13 was used. The pooled IRR for invasive pneumococcal disease caused by non-PCV13 serotypes was 1·62 (1·09-2·42). INTERPRETATION: The incidence of invasive pneumococcal disease caused by all serotypes decreased due to a decline in the incidence of vaccine serotypes. By contrast, that of invasive pneumococcal disease caused by non-PCV13 serotypes increased, which suggests serotype replacement. Long-term surveillance will be crucial to monitor the further effects of PCV10 and PCV13 vaccination programmes in young children. FUNDING: European Centre for Disease Prevention and Control, Czech National Institute of Public Health, French National Agency for Public Health, Irish Health Services Executive, Norwegian Institute of Public Health, Public Health Agency of Catalonia, Public Health Department of Community of Madrid, Navarra Hospital Complex, Public Health Institute of Navarra, CIBER Epidemiology and Public Health, Institute of Health Carlos III, Public Health Agency of Sweden, and NHS Scotland.

In vitro and in vivo comparison of transport media for detecting nasopharyngeal carriage of Streptococcus pneumoniae.

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.

Epidemiology and outcome of sepsis in adult patients with Streptococcus pneumoniae infection in a Norwegian county 1993-2011: an observational study.

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.

Geographical differences in seroprevalence of Borrelia burgdorferi antibodies in Norway, 2011-2013.

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.

Decreased Carriage and Genetic Shifts in the Streptococcus pneumoniae Population After Changing the Seven-valent to the Thirteen-valent Pneumococcal Vaccine in Norway.

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.