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Background Invasive meningococcal B disease (IMD-B) causes morbidity and mortality among infants and adolescents in the Netherlands. While multiple vaccines against IMD-B are licensed by the European Medicines Agency, none of them is currently part of the Dutch National Immunization Program (NIP). We evaluated the clinical impact and cost-effectiveness of different IMD-B vaccination strategies for Dutch infants and adolescents. Methods We developed a static, single-cohort Markov model to estimate the lifetime number of IMD-B cases and deaths prevented, as well as the incremental cost-effectiveness ratio (ICER), of vaccinating infants with 4CMenB (age 0; 2 + 1 schedule) or adolescents with 4CMenB, MenB-fHBp, or MenABCWY + MenB-fHBp (age 15; 1 + 1 schedule), compared with no IMD-B vaccination. The analysis adopted a societal perspective, including costs and quality-adjusted life years (QALYs) related to vaccination, adverse events, acute IMD-B, long-term sequelae, productivity losses of patients and caregivers, special education needs, and out-of-pocket expenses for patients and their families. We also conducted a threshold analysis for the incidence of IMD-B and a systematic uncertainty assessment. Results For infants, the use of 4CMenB would prevent 11.14 IMD-B cases and 0.85 IMD-B-related deaths in one birth cohort of 166,073 infants over a lifetime. For adolescents, IMD-B vaccination would prevent 7.24–8.57 cases and 0.25–0.29 deaths in a single cohort of 197,782 adolescents, depending on which vaccine is used. The ICER was €594,056/QALY for 4CMenB in infants, while for adolescents the ICER ranged between €717,287/QALY and €890,023/QALY, depending on the vaccine type used. These ICERs exceed the commonly used cost-effectiveness thresholds (€20,000 to €80,000/QALY gained) in the Netherlands, rendering vaccination not cost-effective. This outcome proved robust in deterministic and probabilistic sensitivity analyses, as well as in scenario analyses. The threshold analysis demonstrated that IMD-B vaccination may only become cost-effective at a €80,000/QALY threshold with more than a sixfold increase in incidence. Conclusions The modelled IMD-B vaccination programs resulted in the prevention of limited morbidity and mortality at a high financial burden. The inclusion of any of the evaluated vaccines in the Dutch NIP for infants or adolescents is not cost-effective in any target group at conventional Dutch cost-effectiveness thresholds given current IMD-B incidence levels.

Background New 15- and 20-valent pneumococcal vaccines (PCV15, PCV20) are available for both children and adults, while PCV21 for adults is in development. However, their cost-effectiveness for older adults, taking into account indirect protection and serotype replacement from a switch to PCV15 and PCV20 in childhood vaccination, remains unexamined. Methods We used a static model for the Netherlands to assess the cost-effectiveness of different strategies with 23-valent pneumococcal polysaccharide vaccine (PPV23), PCV15, PCV20, and PCV21 for a 65-year-old cohort from a societal perspective, over a 15-year time horizon. Childhood vaccination was varied from PCV10 to PCV13, PCV15, and PCV20. Indirect protection was assumed to reduce the incidence of vaccine serotypes in older adults by 80% (except for serotype 3, no effect), completely offset by an increase in non-vaccine serotype incidence due to serotype replacement. Results Indirect effects from childhood vaccination reduced the cost-effectiveness of vaccination of older adults, depending on the serotype overlap between the vaccines. With PCV10, PCV13, or PCV15 in children, PCV20 was more effective and less costly for older adults than PPV23 and PCV15. PCV20 costs approximately €10,000 per quality-adjusted life year (QALY) gained compared to no pneumococcal vaccination, which falls below the conventional Dutch €20,000/QALY gained threshold. However, with PCV20 in children, PCV20 was no longer considered cost-effective for older adults, costing €22,550/QALY gained. As indirect effects progressed over time, the cost-effectiveness of PCV20 for older adults further diminished for newly vaccinated cohorts. PPV23 was more cost-effective than PCV20 for cohorts vaccinated 3 years after the switch to PCV20 in children. PCV21 offered the most QALY gains, and its cost-effectiveness was minimally affected by indirect effects due to its coverage of 11 different serotypes compared to PCV20. Conclusions For long-term cost-effectiveness in the Netherlands, the pneumococcal vaccine for older adults should either include invasive serotypes not covered by childhood vaccination or become more affordable than its current pricing for individual use.

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.

COVID-19 control measures have resulted in a decline in invasive bacterial disease caused by Neisseria meningitidis (IMD), Streptococcus pneumoniae (IPD), and Haemophilus influenzae (Hi-D). These species comprise different serogroups and serotypes that impact transmissibility and virulence. We evaluated type- and pathogen-specific changes in invasive bacterial disease epidemiology in the Netherlands during the first year of the SARS-CoV-2 pandemic. Cases were based on nationwide surveillance for five bacterial species with either respiratory (IMD, IPD, Hi-D) or non-respiratory (controls) transmission routes and were compared from the pre-COVID period (April 2015–March 2020) to the first COVID-19 year (April 2020–March 2021). IMD, IPD, and Hi-D cases decreased by 78%, 67%, and 35%, respectively, in the first COVID-19 year compared to the pre-COVID period, although effects differed per age group. Serogroup B-IMD declined by 61%, while serogroup W and Y-IMD decreased >90%. IPD caused by serotypes 7F, 15A, 12F, 33F, and 8 showed the most pronounced decline (≥76%). In contrast to an overall decrease in Hi-D cases, vaccine-preventable serotype b (Hib) increased by 51%. COVID-19 control measures had pathogen- and type-specific effects related to invasive infections. Continued surveillance is critical to monitor potential rebound effects once restriction measures are lifted and transmission is resumed.

Background To guide decision-making on immunisation programmes for ageing adults in Europe, one of the aims of the Vaccines and InfecTious diseases in the Ageing popuLation (IMI2-VITAL) project is to assess the burden of disease (BoD) of (potentially) vaccine-preventable diseases ((P)VPD). We aimed to identify the available data sources to calculate the BoD of (P)VPD in participating VITAL countries and to pinpoint data gaps. Based on epidemiological criteria and vaccine availability, we prioritized (P) VPD caused by Extra-intestinal pathogenic Escherichia coli (ExPEC), norovirus, respiratory syncytial virus, Staphylococcus aureus , and pneumococcal pneumonia. Methods We conducted a survey on available data (e.g. incidence, mortality, disability-adjusted life years (DALY), quality-adjusted life years (QALY), sequelae, antimicrobial resistance (AMR), etc.) among national experts from European countries, and carried out five pathogen-specific literature reviews by searching MEDLINE for peer-reviewed publications published between 2009 and 2019. Results Morbidity and mortality data were generally available for all five diseases, while summary BoD estimates were mostly lacking. Available data were not always stratified by age and risk group, which is especially important when calculating BoD for ageing adults. AMR data were available in several countries for S. aureus and ExPEC. Conclusion This study provides an exhaustive overview of the available data sources and data gaps for the estimation of BoD of five (P) VPD in ageing adults in the EU/EAA, which is useful to guide pathogen-specific BoD studies and contribute to calculation of (P)VPDs BoD.

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.

We studied the secondary attack rate (SAR), risk factors, and precautionary practices of household transmission in a prospective, longitudinal study. We further compared transmission between the Alpha (B.1.1.7) variant and non-Variant of Concern (non-VOC) viruses. From May 2020 throughout April 2021, we recruited 70 confirmed COVID-19 cases with 146 household contacts. Participants donated biological samples eight times over 6 weeks and answered questionnaires. SARS-CoV-2 infection was detected by real-time RT-PCR. Whole genome sequencing and droplet digital PCR were used to establish virus variant and viral load. SARS-CoV-2 transmission occurred in 60% of the households, and the overall SAR for household contacts was 50%. The SAR was significantly higher for the Alpha variant (78%) compared with non-VOC viruses (43%) and was associated with a higher viral load. SAR was higher in household contacts aged ≥40 years (69%) than in younger contacts (40–47%), and for contacts of primary cases with loss of taste/smell. Children had lower viral loads and were more often asymptomatic than adults. Sleeping separately from the primary case reduced the risk of transmission. In conclusion, we found substantial household transmission, particularly for the Alpha variant. Precautionary practices seem to reduce SAR, but preventing household transmission may become difficult with more contagious variants, depending on vaccine use and effectiveness.

Objective: We aim to discuss whether preventive quarantine can mitigate the spread of Covid-19 during the pandemic. Design: We did a cross-sectional, observational study design in a mass-screening program in the enrolment to the Norwegian military during April 19-28th 2020 (COVID-NOR-MIL). Subjects: 1170 presumptively healthy young Norwegian conscripts. Setting: A structured interview encouraged the coming conscripts to a self-imposed preventive quarantine the last two weeks before enrolment. Main outcome measures: All conscripts underwent a PCR-based test with nasopharyngeal swabs at the day of enrolment. Results: Only two tested positive. The study discusses the predictive value of the RT-PCR test and the risk of false positive and false negative results, particularly when using the test in a low-prevalent cohort, even if the test properties of sensitivity and specificity is almost 100%. Further, the study discusses the challenge of whether a positive SARS-CoV-2 PCR-test represent viable and contagious virus or only viral remnants. Conclusion: The adherence to self-imposed preventive quarantine is a challenge and is a subject to further research. Implications: We want to draw the attention to the potential value of a thorough pre-screening processes and self-imposed preventive quarantine to minimize the potential spread of SARS-Cov-2.

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. 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. 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). 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.

Background Accurate estimates of SARS‐CoV‐2 infection in different population groups are important for the health authorities. In Norway, public infection control measures have successfully curbed the pandemic. However, military training and service are incompatible with these measures; therefore extended infection control measures were implemented in the Norwegian Armed Forces. We aimed to describe these measures, discuss their value, and investigate the polymerase chain reaction (PCR) prevalence and seroprevalence of SARS‐CoV‐2, as well as changes in antibody titer levels over the 6‐week military training period in a young, asymptomatic population of conscripts. Methods In April 2020, 1170 healthy conscripts (median age 20 years) enrolled in military training. Extended infection control measures included a pre‐enrollment telephone interview, self‐imposed quarantine, questionnaires, and serial SARS‐CoV‐2 testing. At enrollment, questionnaires were used to collect information on symptoms, and SARS‐CoV‐2 rapid antibody testing was conducted. Serial SARS‐CoV‐2 PCR and serology testing were used to estimate the prevalence of confirmed SARS‐CoV‐2 and monitor titer levels at enrollment, and 3 and 6 weeks thereafter. Results At enrollment, only 0.2% of conscripts were SARS‐CoV‐2 PCR‐positive, and seroprevalence was 0.6%. Serological titer levels increased nearly 5‐fold over the 6‐week observation period. Eighteen conscripts reported mild respiratory symptoms during the 2 weeks prior to enrollment (all were PCR‐negative; one was serology‐positive), whereas 17 conscripts reported respiratory symptoms and nine had fever at enrollment (all were PCR‐ and serology‐negative). Conclusions The prevalence of SARS‐CoV‐2 was less than 1% in our sample of healthy Norwegian conscripts. Testing of asymptomatic conscripts seems of no value in times of low COVID‐19 prevalence. SARS‐CoV‐2 antibody titer levels increased substantially over time in conscripts with mild symptoms.