Higher-valency pneumococcal conjugate vaccines in older adults, taking into account indirect effects from childhood vaccination: a cost-effectiveness study for the Netherlands.

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.

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.

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.

European data sources for computing burden of (potential) vaccine-preventable diseases in ageing adults.

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.

Pre-screening and preventive quarantine likely explains the low SARS-CoV-2 prevalence among Norwegian conscripts.

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.

Increase in invasive disease caused by Haemophilus influenzae b, the Netherlands, 2020 to 2021.

The incidence of most respiratory-transmitted diseases decreased during the COVID-19 pandemic as a result of containment measures. In contrast, in the Netherlands we noted an increase in invasive disease caused by Haemophilus influenzae b (Hib) (from < 0.3/100,000 before 2019 to 0.39 and 0.33/100,000 in 2020 and 2021) in vaccinated and unvaccinated age groups. We did not find a change in vaccine effectiveness against Hib invasive disease (effectiveness > 90%). We discuss factors that may have contributed to this rise.

Poor self-reported adherence to COVID-19-related quarantine/isolation requests, Norway, April to July 2020.

To limit SARS-CoV-2 spread, quarantine and isolation are obligatory in several situations in Norway. We found low self-reported adherence to requested measures among 1,704 individuals (42%; 95% confidence interval: 37-48). Adherence was lower in May-June-July (33-38%) compared with April (66%), and higher among those experiencing COVID-19-compatible symptoms (71%) compared with those without (28%). These findings suggest that consideration is required of strategies to improve people's adherence to quarantine and isolation.

COVID-19 cases reported to the Norwegian Institute of Public Health in the first six weeks of the epidemic. / Covid-19 rapportert til Folkehelseinstituttet de første seks ukene av epidemien.

BACKGROUND: The first case of SARS-CoV-2 infection in Norway was confirmed on 26 February 2020. Following sharpened advice on general infection control measures at the beginning of the outbreak, extensive national control measures were implemented on 12 March, and testing was focused on those with severe illness. We describe the first six weeks of the outbreak in Norway, viewed in light of testing criteria and control measures. MATERIAL AND METHOD: We described all laboratory-confirmed cases of COVID-19 reported to three different surveillance systems under the Norwegian Institute of Public Health up to 5 April 2020, and compared cases reported up to 12 March with those reported from 13 March. RESULTS: By 12 March, 1 128 cases had been reported. Their median age was 47 years, 64 % were male, 66 % had travelled abroad, 6 % were hospitalised at the time of reporting, and < 1 % had died. The median age of the 4 742 cases reported from 13 March was 48 years, 47 % were male, 18 % had travelled abroad, 15 % were hospitalised, and 3 % died. INTERPETATION: The distribution of COVID-19 cases before and after 12 March reflects different phases of the outbreak. However, findings must be interpreted in the light of criteria for testing, testing activity, control measures and characteristics of surveillance systems.

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.

What are the most important infectious diseases among those ≥65 years: a comprehensive analysis on notifiable diseases, Norway, 1993-2011.

BACKGROUND: As the population ages, the burden on the healthcare system might increase and require changed public health priorities. As infections are often more severe at older age, we rank notifiable infectious diseases (ID) and describe trends of ID among the general population aged ≥65 years in Norway in order to inform public health priorities for the aging population. METHODS: We included all eligible cases of the 58 IDs notified between 1993 and 2011 (n = 223,758; 12% ≥65 years) and determined annual notification rates as the number of notified cases divided by the number of inhabitants of the corresponding year. We ranked diseases using their average annual notification rate for 2007-2011. Trends in notification rates from 1993 onwards were determined with a non-parametric test for trend. Using notification rate ratios (NRR), we compared results in those aged ≥65 years to those aged 20-64 years. RESULTS: Invasive pneumococcal disease was the most common ID among the population ≥65 years (notification rate 58/100,000), followed by pertussis (54/100,000) and campylobacteriosis (30/100,000). Most ID notification rates did not change over time, though the notification rate of symptomatic MRSA infections increased from 1/100,000 in 1995 (first year of notification) to 14/100,000 in 2011.Overall, fewer cases were notified among the population ≥65 years compared to 20-64 year olds (NRR = 0.73). The NRR of each of the invasive bacterial diseases and antibiotic-resistant infections were above 1.5 (i.e. more common in ≥65), while the NRR of each food- and waterborne disease, blood-borne disease/STI and (non-invasive) vaccine preventable disease was below 1. CONCLUSIONS: Based on our results, we emphasise the importance of focusing public health efforts for those ≥65 years on preventing invasive bacterial infections. This can be achieved by increasing pneumococcal and influenza vaccine uptake, and risk communication including encouraging those aged ≥65 years and their caretakers to seek healthcare at signs of systemic infection. Furthermore, good compliance to infection control measures, screening of the at-risk population, and careful use of antibiotics may prevent further increase in antibiotic-resistant infections.

Association between human papillomavirus vaccine uptake and cervical cancer screening in the Netherlands: implications for future impact on prevention.

Several countries recently added human papillomavirus (HPV) vaccination to cervical cancer screening in the effort to prevent cervical cancer. They include the Netherlands, where both programs are free. To estimate their combined future impact on cancer prevention, information is needed on the association between participation in vaccination now and in screening in the future and on what groups are at risk for nonparticipation. We studied the association between participation in screening by mothers and in vaccination by their daughters. Girls' vaccination status was matched by house-address with their mothers' screening participation. We estimated the effect on cancer incidence by means of computer simulation. We investigated risk groups for nonparticipation using multivariable multilevel logistic regression and calculated population-attributable fractions. Our results, based on 89% of girls invited for vaccination in 2009 (n = 337,368), show that vaccination status was significantly associated with mothers' screening participation (odds ratio: 1.54 [95% confidence interval: 1.51-1.57]). If a mother's screening is taken as proxy of a girl's future screening, only 13% of the girls will not participate in either program compared to 23% if screening alone is available. The positive association between vaccination and screening resulted in slightly lower model estimates of the impact of vaccination on cancer incidence, compared to estimates assuming no association. Girls with nonwestern ethnicities, with young mothers, who live in urban areas with low socioeconomic status, are at risk for nonparticipation. A significant part of potential nonscreeners may be reached through HPV vaccination. Estimates made before vaccination was introduced only slightly overestimated its impact on cervical cancer incidence.

The burden of invasive meningococcal disease in the Netherlands, 2011-2020.

INTRODUCTION: Representative information on disease course and outcome of invasive meningococcal disease (IMD) is important because of the shift in meningococcal epidemiology that recently occurred in the Netherlands. With this study, we update earlier research on the burden of IMD in the Netherlands. MATERIAL AND METHODS: We performed a retrospective study using Dutch surveillance data on IMD from July 2011 to May 2020. Clinical information was collected from hospital records. The effect of age, serogroup, and clinical manifestation on disease course and outcome was assessed in multivariable logistic regression analyses. Grouping of infecting isolates was performed by Ouchterlony gel diffusion or by PCR. RESULTS: Clinical information was collected for 278 IMD cases of which the majority had IMD-B (55%), followed by IMD-W (27%), IMD-Y (13%), and IMD-C (5%). Most patients presented with meningitis (32%) or sepsis (30%). Hospitalisation for ≥ 10 days was most frequent among 24-64 year olds (67%). ICU admission was highest among 24-64 year olds (60%), and in case of sepsis (70%), or sepsis plus meningitis (61%). Sequelae at discharge was lower for patients with mild meningococcaemia compared to patients with sepsis plus meningitis (OR: 0.19, 95% CI: 0.07-0.51). The overall case fatality rate was 7%, and was highest for IMD-Y (14%) and IMD-W (13%) patients. CONCLUSIONS: IMD remains a disease with high morbidity and mortality. Sepsis (with or without meningitis) is associated with a more severe disease course and outcome compared to other clinical manifestations. The high disease burden can be partly prevented by meningococcal vaccination.

Pathogen- and Type-Specific Changes in Invasive Bacterial Disease Epidemiology during the First Year of the COVID-19 Pandemic in The Netherlands.

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.

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.

Age-dependent patterns of infection and severity explaining the low impact of 2009 influenza A (H1N1): evidence from serial serologic surveys in the Netherlands.

Despite considerable research efforts in specific subpopulations, reliable estimates of the infection attack rates and severity of 2009 influenza A (H1N1) in the general population remain scarce. Such estimates are essential to the tailoring of future control strategies. Therefore, 2 serial population-based serologic surveys were conducted, before and after the 2009 influenza A (H1N1) epidemic, in the Netherlands. Random age-stratified samples were obtained using a 2-stage cluster design. Participants donated blood and completed a questionnaire. Data on sentinel general practitioner-attended influenza-like illness and nationwide hospitalization and mortality were used to assess the severity of infection. The estimated infection attack rates were low in the general population (7.6%, 95% confidence interval: 3.6, 11) but high in children aged 5-19 years (35%, 95% confidence interval: 25, 45). The estimated hospitalization and mortality rates per infection increased significantly with age (5-19 years: 0.042% and 0.00094%, respectively; 20-39 years: 0.12% and 0.0025%; 40-59 years: 0.68% and 0.032%; 60-75 years: >0.81% and >0.068%). The high infection attack rate in children and the very low attack rate in older adults, together with the low severity of illness per infection in children but substantial severity in older adults, produced an epidemic with a low overall impact.

Effectiveness of a MF-59™-adjuvanted pandemic influenza vaccine to prevent 2009 A/H1N1 influenza-related hospitalisation; a matched case-control study.

BACKGROUND: During the 2009 influenza A/H1N1 pandemic, adjuvanted influenza vaccines were used for the first time on a large scale. Results on the effectiveness of the vaccines in preventing 2009 influenza A/H1N1-related hospitalisation are scanty and varying. METHODS: We conducted a matched case-control study in individuals with an indication for vaccination due to underlying medical conditions and/or age ≥ 60 years in The Netherlands. Cases were patients hospitalised with laboratory-confirmed 2009 A/H1N1 influenza infection between November 16, 2009 and January 15, 2010. Controls were matched to cases on age, sex and type of underlying medical condition(s) and drawn from an extensive general practitioner network. Conditional logistic regression was used to estimate the vaccine effectiveness (VE = 1 - OR). Different sensitivity analyses were used to assess confounding by severity of underlying medical condition(s) and the effect of different assumptions for missing dates of vaccination. RESULTS: 149 cases and 28,238 matched controls were included. It was estimated that 22% of the cases and 28% of the controls received vaccination more than 7 days before the date of onset of symptoms in cases. A significant number of breakthrough infections were observed. The VE was estimated at 19% (95%CI -28-49). After restricting the analysis to cases with controls suffering from severe underlying medical conditions, the VE was 49% (95% CI 16-69). CONCLUSIONS: The number of breakthrough infections, resulting in modest VE estimates, suggests that the MF-59™ adjuvanted vaccine may have had only a limited impact on preventing 2009 influenza A/H1N1-related hospitalisation in this setting. As the main aim of influenza vaccination programmes is to reduce severe influenza-related morbidity and mortality from influenza in persons at high risk of complications, a more effective vaccine, or additional preventive measures, 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.

Household Transmission of SARS-CoV-2: A Prospective Longitudinal Study Showing Higher Viral Load and Increased Transmissibility of the Alpha Variant Compared to Previous Strains.

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.

Severe acute respiratory syndrome coronavirus 2 prevalence in 1170 asymptomatic Norwegian conscripts.

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.