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.

Cost-utility analysis of the universal pneumococcal vaccination programme for older adults in Norway.

The aim of this study was to establish whether the universal pneumococcal vaccination for older adults in Norway is likely to be cost-effective from the perspective of the health care provider. A decision tree model developed by the Public Health Agency of Sweden was adapted to the Norwegian setting. Two cohorts, consisting of 65-year-olds and 75-year-olds grouped into vaccinated and unvaccinated, were followed over a 5-year time horizon. In the base case, the 23-valent polysaccharide vaccine (PPV23) was used while the 13-valent pneumococcal conjugate vaccine (PCV13) was included in scenario analyses only. The costs and health benefits (measured in quality adjusted life years (QALY) gained) were compared in the two cohorts between the vaccinated and unvaccinated groups. The impact of indirect effects of the vaccine, such as herd immunity and serotype replacement, were not investigated. The relative importance of change in price was assessed by performing one-way sensitivity analyses. Under base-case assumptions, the programme for the 75-year-old cohort is expected to be dominant (cost-effective) from the health care perspective at the current maximal pharmacy retail price and at 75% vaccination coverage. In comparison, for the 65-year-old cohort the cost per QALY gained is approximately NOK 601,784 (EUR 61,281) under the base-case assumptions. A reduction in the cost of the vaccine to one quarter of its current level also brings the cost per QALY gained within the acceptable ranges in a Norwegian context for both the 65- and 75-year-old cohorts. There is no exact cost-effectiveness threshold in Norway. However, introducing a vaccination programme against pneumococcal disease for 65-year-olds in Norway is likely to fall within the acceptable range while for the 75-year-old cohort the universal programme appears to be dominant (cost-effective).

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.

Pertussis epidemiology including direct and indirect effects of the childhood pertussis booster vaccinations, Norway, 1998-2019.

BACKGROUND: The acellular pertussis vaccine has been used in the Norwegian national immunisation program since 1998. Following an increase in pertussis incidence in all age groups, booster doses were introduced for 7-8-year-olds in 2006, and for 15-16-year-olds in 2013. We assessed the effects of the booster doses on pertussis incidence in different age groups to inform potential changes in vaccination policy. METHODS: We included all pertussis cases notified to the Norwegian Surveillance System for Communicable Diseases in 1998-2019. We calculated annual incidence rates (IR, per 100,000 inhabitants) by age group. We estimated average annual changes in IRs (incidence rate ratios, IRR) for each age group for 2006-2012 and 2013-2019 using Poisson regression. RESULTS: In 1998-2019, 74,675 cases of pertussis were notified. Coinciding with booster introduction, between 2006 and 2012 the IR decreased among 8-15-year-olds (from 433 to 199/100,000, IRR 0.89 [95% confidence interval 0.88-0.90]). A similar decrease was seen between 2013 and 2019 among 16-19-year-olds (from 171 to 77/100,000, IRR 0.84 [0.82-0.86]). There was no significant change in IRs among children < 1 year of age between 2006 and 2012 (IRR 0.99 [0.95-1.04]) or 2013-2019 (IRR 0.96 [0.91-1.02]). The IR decreased in both periods among adults aged 20-39 and 40+ (IRR 0.94 [0.93-0.95] and 0.92 [0.91-0.92] in 2006-2012; IRR 0.97 [0.96-0.99] and 0.97 [0.96-0.99] in 2013-2019, respectively). Despite steady, high vaccination coverage, in 2013-2019, there was an increase in the IR among children aged 1-7 (63 to 86/100,000, IRR 1.05 [1.03-1.07]) and 8-15 years (88 to 122/100,000, IRR 1.08 [1.06-1.10]). CONCLUSIONS: Pertussis booster doses have offered direct protection in the targeted age groups. Our findings suggest indirect protection in adults, while the incidence in infants hasn't changed. The recent increase in IRs among 1-15-year-olds warrants close monitoring and further evaluation of the vaccination schedule.

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.

Phylogenetic Structure and Comparative Genomics of Multi-National Invasive Haemophilus influenzae Serotype a Isolates.

Recent reports have indicated a rise of invasive disease caused by Haemophilus influenzae serotype a (Hia) in North America and some European countries. The whole-genome sequences for a total of 410 invasive Hia isolates were obtained from 12 countries spanning the years of 1998 to 2019 and underwent phylogenetic and comparative genomic analysis in order to characterize the major strains causing disease and the genetic variation present among factors contributing to virulence and antimicrobial resistance. Among 410 isolate sequences received, 408 passed our quality control and underwent genomic analysis. Phylogenetic analysis revealed that the Hia isolates formed four genetically distinct clades: clade 1 (n = 336), clade 2 (n = 13), clade 3 (n = 3) and clade 4 (n = 56). A low diversity subclade 1.1 was found in clade 1 and contained almost exclusively North American isolates. The predominant sequence types in the Hia collection were ST-56 (n = 125), ST-23 (n = 98) and ST-576 (n = 51), which belonged to clade 1, and ST-62 (n = 54), which belonged to clade 4. Clades 1 and 4 contained predominantly North American isolates, and clades 2 and 3 predominantly contained European isolates. Evidence of the presence of capsule duplication was detected in clade 1 and 2 isolates. Seven of the virulence genes involved in endotoxin biosynthesis were absent from all Hia isolates. In general, the presence of known factors contributing to ß-lactam antibiotic resistance was low among Hia isolates. Further tests for virulence and antibiotic susceptibility would be required to determine the impact of these variations among the isolates.

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.

Health communication in and out of public health emergencies: to persuade or to inform?

Much health communication during the COVID-19 pandemic has been designed to persuade people more than to inform them. For example, messages like "masks save lives" are intended to compel people to wear face masks, not to enable them to make an informed decision about whether to wear a face mask or to understand the justification for a mask mandate. Both persuading people and informing them are reasonable goals for health communication. However, those goals can sometimes be in conflict. In this article, we discuss potential conflicts between seeking to persuade or to inform people, the use of spin to persuade people, the ethics of persuasion, and implications for health communication in the context of the pandemic and generally. Decisions to persuade people rather than enable them to make an informed choice may be justified, but the basis for those decisions should be transparent and the evidence should not be distorted. We suggest nine principles to guide decisions by health authorities about whether to try to persuade people.

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.

The Risk of Invasive Pneumococcal Disease Differs between Risk Groups in Norway Following Widespread Use of the 13-Valent Pneumococcal Vaccine in Children.

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.

Circulation of pertussis and poor protection against diphtheria among middle-aged adults in 18 European countries.

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.

Antimicrobial resistance profile and multidrug resistance patterns of Streptococcus pneumoniae isolates from patients suspected of pneumococcal infections in Ethiopia.

BACKGROUND: Antimicrobial-resistant strains of Streptococcus pneumoniae have become one of the greatest challenges to global public health today and inappropriate use of antibiotics and high level of antibiotic use is probably the main factor driving the emergence of resistance worldwide. The aim of this study is, therefore, to assess the antimicrobial resistance profiles and multidrug resistance patterns of S. pneumoniae isolates from patients suspected of pneumococcal infections in Ethiopia. METHODS: A hospital-based prospective study was conducted from January 2018 to December 2019 at Addis Ababa city and Amhara National Region State Referral Hospitals. Antimicrobial resistance tests were performed from isolates of S. pneumoniae that were collected from pediatric and adult patients. Samples (cerebrospinal fluid, blood, sputum, eye discharge, ear discharge, and pleural and peritoneal fluids) from all collection sites were initially cultured on 5% sheep blood agar plates and incubated overnight at 37 °C in a 5% CO2 atmosphere. Streptococcus pneumoniae was identified and confirmed by typical colony morphology, alpha-hemolysis, Gram staining, optochin susceptibility, and bile solubility test. Drug resistance testing was performed using the E-test method according to recommendations of the Clinical and Laboratory Standards Institute. RESULTS: Of the 57 isolates, 17.5% were fully resistant to penicillin. The corresponding value for both cefotaxime and ceftriaxone was 1.8%. Resistance rates to erythromycin, clindamycin, tetracycline, chloramphenicol and trimethoprim-sulfamethoxazole were 59.6%, 17.5%, 38.6%, 17.5 and 24.6%, respectively. Multidrug resistance (MDR) was seen in 33.3% isolates. The most common pattern was co-resistance to penicillin, erythromycin, clindamycin, and tetracycline. CONCLUSIONS: Most S. pneumoniae isolates were susceptible to ceftriaxone and cefotaxime. Penicillin has been used as a drug of choice for treating S. pneumoniae infection. However, antimicrobial resistance including multidrug resistance was observed to several commonly used antibiotics including penicillin. Hence, it is important to periodically monitor the antimicrobial resistance patterns to select empirical treatments for better management of pneumococcal infection.

Gastrointestinal symptoms in invasive pneumococcal disease: a cohort study.

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.

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.

A Systematic Review of Studies Published between 2016 and 2019 on the Effectiveness and Efficacy of Pneumococcal Vaccination on Pneumonia and Invasive Pneumococcal Disease in an Elderly Population.

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.

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.