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Objectives: Studies have shown temporal changes in post-acute sequelae of COVID-19 (PASC) prevalence for early SARS-CoV-2 variants, although often lacking controls. This prospective study assesses the prevalence of symptoms in Delta- and Omicron-infected cases up to 12 months compared with population controls., Methods: Adult participants filled out surveys every 3 months (T0-T12) between July 2021 and August 2023. Cases were recruited with a positive SARS-CoV-2 test during the Delta or Omicron domination. Population controls were randomly invited from the Dutch Personal Records Database. Participants indicated the presence of 13 PASC-associated symptoms, and severity scores of fatigue, cognitive impairment, dyspnea, and pain. PASC prevalence was defined as the excess prevalence of havingat least one PASC-associated symptom in cases compared with population controls., Results: PASC prevalence was 34.3% at T3 and decreased to 21.7% at T12 for Delta and decreased from 18.7% at T3 to 16.7% at T12 for Omicron. At T12, the difference between Delta and Omicron was not significant. Delta cases generally had higher excess symptom scores for fatigue, dyspnea, and cognitive impairment than Omicron., Conclusions: In the first 9 months after infection, PASC prevalence was higher for Delta than Omicron, but the difference reduced over time and approximated after 12 months., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Understanding the impact of different types of social interactions is key to improving epidemic models. Here, we use extensive registry data-including PCR test results and population-level networks-to investigate the impact of school, family, and other social contacts on SARS-CoV-2 transmission in the Netherlands (June 2020-October 2021). We isolate and compare different contexts of potential SARS-CoV-2 transmission by matching pairs of students based on their attendance at the same or different primary school (in 2020) and secondary school (in 2021) and their geographic proximity. We then calculate the probability of temporally associated infections-i.e. the probability of both students testing positive within a 14-day period. Our results highlight the relative importance of household and family transmission in the spread of SARS-CoV-2 compared to school settings. The probability of temporally associated infections for siblings and parent-child pairs living in the same household ranged from 22.6-23.2%. Interestingly, a high probability (4.7-7.9%) was found even when family members lived in different households, underscoring the persistent risk of transmission within family networks. In contrast, the probability of temporally associated infections was 0.52% for pairs of students living nearby but not attending the same primary or secondary school, 0.66% for pairs attending different secondary schools but having attended the same primary school, and 1.65% for pairs attending the same secondary school. It is worth noting, however, that even small increases in school-related infection probabilities can trigger large-scale outbreaks due to the dense network of interactions in these settings. Finally, we used multilevel regression analyses to examine how individual, school, and geographic factors contribute to transmission risk. We found that the largest differences in transmission probabilities were due to unobserved individual (60%) and school-level (35%) factors. Only a small proportion (3%) could be attributed to geographic proximity of students or to school size, denomination, or the median income of the school area., Competing Interests: Declarations. Ethical statement: Data is collected by Statistics Netherlands (CBS) and the National Institute for Public Health and the Environment (RIVM), and made available to researchers for well-defined projects and statistical analysis. Researchers need to be pre-approved before accessing the data, and all data is pseudoanomyzied, and available in a secure research environment. The data is safeguarded under the stringent privacy regulations set by the Statistics Netherlands Act (“Wet op het Centraal bureau voor de statistiek”) and the European Union’s General Data Protection Regulation, guaranteeing that individual personal information is not revealed during the analysis. All methods were carried out in accordance with relevant guidelines and regulations. Competing interests: The authors declare no competing interests. Declaration of generative AI and AI-assisted technologies in the writing process: During the preparation of this work the author(s) used https://www.deepl.com/write for copyediting and to improve readability. After using this tool/service, the author(s) reviewed and edited the content as needed and take(s) full responsibility for the content of the publication., (© 2024. The Author(s).)

Competing Interests: We declare no competing interests. During the preparation of this manuscript, the author used OpenAI GPT-4 using GPT “Academic Assistant Pro” to generate an initial sketch draft based on an extended outline with relevant topics in bullet points produced by the main author. After using this tool/service, the authors substantially reworked and edited the content and then performed an AI check for grammar and spelling of a near final version. The authors take full responsibility for the content of the publication.

Objectives: Different SARS-CoV-2 variants can differentially affect the prevalence of Post Covid-19 Condition (PCC). This prospective study assesses prevalence and severity of symptoms three months after an Omicron infection, compared to Delta, test-negative and population controls. This study also assesses symptomology after reinfection and breakthrough infections., Methods: After a positive SARS-CoV-2 test, cases were classified as Omicron or Delta based on ≥ 85% surveillance prevalence. Three months after enrolment, participants indicated point prevalence for 41 symptoms and severity, using validated questionnaires for four symptoms. PCC prevalence was estimated as the difference in prevalence of at least one significantly elevated symptom, identified by permutation test, in cases compared to population controls., Results: At three months follow-up, five symptoms and severe dyspnea were significantly elevated in Omicron cases (n = 4138) compared to test-negative (n = 1672) and population controls (n = 2762). PCC prevalence was 10·4% for Omicron cases and 17·7% for Delta cases (n = 6855). In Omicron cases, severe fatigue and dyspnea were more prevalent in reinfected than primary infected, while severity of symptoms did not significantly differ between cases with a booster or primary vaccination course., Conclusions: Prevalence of PCC is 41% lower after Omicron than Delta at three months. Reinfection seems associated with more severe long-term symptoms compared to first infection., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objectives: We describe health-related quality of life during the COVID-19 pandemic in the general Dutch population and correlations with restrictive measures., Methods: Data were obtained from 18-85 year-old participants of two population-based cohort studies (February 2021-July 2022): PIENTER Corona (n = 8,019) and VASCO (n = 45,413). Per cohort, mean scores of mental and physical health and health utility from the SF-12 were calculated by age group, sex and presence of a medical risk condition. Spearman correlations with stringency of measures were calculated., Results: Both cohorts showed comparable results. Participants <30 years had lowest health utility and mental health score, and highest physical health score. Health utility and mental health score increased with age (up to 79 years), while physical health score decreased with age. Women and participants with a medical risk condition scored lower than their counterparts. Fluctuations were small over time but most pronounced among participants <60 years, and correlated weakly, but mostly positively with measure stringency., Conclusions: During the Dutch COVID-19 epidemic, health utility and mental health scores were lower and fluctuated strongest among young adults compared to older adults. In our study population, age, sex and presence of a medical risk condition seemed to have more impact on health scores than stringency of COVID-19 non-pharmaceutical interventions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 van Hagen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., (© 2024. The Author(s).)

Measuring the severity of the disease of SARS-CoV-2 is complicated by the lack of valid estimations for the prevalence of infection. Self-administered rapid antigen diagnostic tests (Ag-RDTs) were available in the Netherlands since March 2021, requiring confirmation by reverse-transcription polymerase chain reaction (RT-PCR) for positive results. We explored the possibility of utilizing the positive predictive value (PPV) of Ag-RDTs to estimate SARS-CoV-2 prevalence. We used data from all Public Health service testing facilities between 3 May 2021 and 10 April 2022. The PPV was calculated by dividing the number of positive RT-PCR results by the total number of confirmation tests performed, and used to estimate the prevalence and compared with the number of COVID-19 hospital admissions. In total 3,599,894 cases were included. The overall PPV was 91.8% and 88.8% were symptomatic. During our study period, the estimated prevalence ranged between 2-22% in symptomatic individuals and 2-14% in asymptomatic individuals, with a correlation between the estimated prevalence and hospital admissions two weeks later (r = 0.68 (p<0.01) and r = 0.60 (p<0.01) for symptomatic/asymptomatic individuals). The PPV of Ag-RDTs can help estimate changes in SARS-CoV-2 prevalence, especially when used in conjunction with other surveillance systems. However, the used method probably overestimated the true prevalence because of unmonitored differences in test propensity between individuals., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Gorgels et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The Dutch national open database on COVID-19 has been incrementally expanded since its start on 30 April 2020 and now includes datasets on symptoms, tests performed, individual-level positive cases and deaths, cases and deaths among vulnerable populations, settings of transmission, hospital and ICU admissions, SARS-CoV-2 variants, viral loads in sewage, vaccinations and the effective reproduction number. This data is collected by municipal health services, laboratories, hospitals, sewage treatment plants, vaccination providers and citizens and is cleaned, analysed and published, mostly daily, by the National Institute for Public Health and the Environment (RIVM) in the Netherlands, using automated scripts. Because these datasets cover the key aspects of the pandemic and are available at detailed geographical level, they are essential to gain a thorough understanding of the past and current COVID-19 epidemiology in the Netherlands. Future purposes of these datasets include country-level comparative analysis on the effect of non-pharmaceutical interventions against COVID-19 in different contexts, such as different cultural values or levels of socio-economic disparity, and studies on COVID-19 and weather factors., (© 2023. The Author(s).)

Background: Children play a key role in the transmission of many infectious diseases. They have many of their close social encounters at home or at school. We hypothesized that most of the transmission of respiratory infections among children occur in these two settings and that transmission patterns can be predicted by a bipartite network of schools and households., Aim and Methods: To confirm transmission over a school-household network, SARS-CoV-2 transmission pairs in children aged 4-17 years were analyzed by study year and primary/secondary school. Cases with symptom onset between 1 March 2021 and 4 April 2021 identified by source and contact-tracing in the Netherlands were included. In this period, primary schools were open and secondary school students attended class at least once per week. Within pairs, spatial distance between the postcodes was calculated as the Euclidean distance., Results: A total of 4059 transmission pairs were identified; 51.9% between primary schoolers; 19.6% between primary and secondary schoolers; 28.5% between secondary schoolers. Most (68.5%) of the transmission for children in the same study year occurred at school. In contrast, most of the transmission of children from different study years (64.3%) and most primary-secondary transmission (81.7%) occurred at home. The average spatial distance between infections was 1.2 km (median 0.4) for primary school pairs, 1.6 km (median 0) for primary-secondary school pairs and 4.1 km (median 1.2) for secondary school pairs., Conclusion: The results provide evidence of transmission on a bipartite school-household network. Schools play an important role in transmission within study years, and households play an important role in transmission between study years and between primary and secondary schools. Spatial distance between infections in a transmission pair reflects the smaller school catchment area of primary schools versus secondary schools. Many of these observed patterns likely hold for other respiratory pathogens., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: Economic evaluations of vaccines should accurately represent all relevant economic and health consequences of vaccination, including losses due to adverse events following immunization (AEFI). We investigated to what extent economic evaluations of pediatric vaccines account for AEFI, which methods are used to do so and whether inclusion of AEFI is associated with study characteristics and the vaccine's safety profile., Methods: A systematic literature search (MEDLINE, EMBASE, Cochrane Systematic Reviews and Trials, Database of the Centre for Reviews and Dissemination of the University of York, EconPapers, Paediatric Economic Database Evaluation, Tufts New England Cost-Effectiveness Analysis Registry, Tufts New England Global Health CEA, International Network of Agencies for Health Technology Assessment Database) was performed for economic evaluations published between 2014 and 29 April 2021 (date of search) pertaining to the five groups of pediatric vaccines licensed in Europe and the United States since 1998: the human papillomavirus (HPV) vaccines, the meningococcal vaccines (MCV), the measles-mumps-rubella-varicella (MMRV) combination vaccines, the pneumococcal conjugate vaccines (PCV) and the rotavirus vaccines (RV). Rates of accounting for AEFI were calculated, stratified by study characteristics (e.g., region, publication year, journal impact factor, level of industry involvement) and triangulated with the vaccine's safety profile (Advisory Committee on Immunization Practices [ACIP] recommendations and information on safety-related product label changes). The studies accounting for AEFI were analyzed in terms of the methods used to account for both cost and effect implications of AEFI., Results: We identified 112 economic evaluations, of which 28 (25%) accounted for AEFI. This proportion was significantly higher for MMRV (80%, four out of five evaluations), MCV (61%, 11 out of 18 evaluations) and RV (60%, nine out of 15 evaluations) compared to HPV (6%, three out of 53 evaluations) and PCV (5%, one out of 21 evaluations). No other study characteristics were associated with a study's likelihood of accounting for AEFI. Vaccines for which AEFI were more frequently accounted for also had a higher frequency of label changes and a higher level of attention to AEFI in ACIP recommendations. Nine studies accounted for both the cost and health implications of AEFI, 18 studies considered only costs and one only health outcomes. While the cost impact was usually estimated based on routine billing data, the adverse health impact of AEFI was usually estimated based on assumptions., Discussion: Although (mild) AEFI were demonstrated for all five studied vaccines, only a quarter of reviewed studies accounted for these, mostly in an incomplete and inaccurate manner. We provide guidance on which methods to use to better quantify the impact of AEFI on both costs and health outcomes. Policymakers should be aware that the impact of AEFI on cost-effectiveness is likely to be underestimated in the majority of economic evaluations., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: This prospective study assesses symptoms 3 months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection compared to test-negative and population controls, and the effect of vaccination prior to infection., Methods: Participants enrolled after a positive (cases) or negative (test-negative controls) SARS-CoV-2 test, or after invitation from the general population (population controls). After 3 months, participants indicated presence of 41 symptoms and severity of 4 symptoms. Permutation tests were used to select symptoms significantly elevated in cases compared to controls and to compare symptoms between cases that were vaccinated or unvaccinated prior to infection., Results: In total, 9166 cases, 1698 symptomatic but test-negative controls, and 3708 population controls enrolled. At 3 months, 13 symptoms, and severity of fatigue, cognitive impairment, and dyspnea were significantly elevated incases compared to controls. Of cases, 48.5% reported ≥1 significantly elevated symptom compared to 29.8% of test-negative controls and 26.0% of population controls. Effect of vaccination could be determined for cases aged <65 years, and was significantly protective for loss of smell and taste but not for other symptoms., Discussion: Three months after SARS-CoV-2 infection, almost half of cases report symptoms, which was higher than background prevalence and test-negative prevalence. Vaccination prior to infection was protective against loss of smell and taste in cases aged <65 years., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

BackgroundSince the roll-out of COVID-19 vaccines in late 2020 and throughout 2021, European governments have relied on mathematical modelling to inform policy decisions about COVID-19 vaccination.AimWe present a scenario-based modelling analysis in the Netherlands during summer 2021, to inform whether to extend vaccination to adolescents (12-17-year-olds) and children (5-11-year-olds).MethodsWe developed a deterministic, age-structured susceptible-exposed-infectious-recovered (SEIR) model and compared modelled incidences of infections, hospital and intensive care admissions, and deaths per 100,000 people across vaccination scenarios, before the emergence of the Omicron variant.ResultsOur model projections showed that, on average, upon the release of all non-pharmaceutical control measures on 1 November 2021, a large COVID-19 wave may occur in winter 2021/22, followed by a smaller, second wave in spring 2022, regardless of the vaccination scenario. The model projected reductions in infections/severe disease outcomes when vaccination was extended to adolescents and further reductions when vaccination was extended to all people over 5 years-old. When examining projected disease outcomes by age group, individuals benefitting most from extending vaccination were adolescents and children themselves. We also observed reductions in disease outcomes in older age groups, particularly of parent age (30-49 years), when children and adolescents were vaccinated, suggesting some prevention of onward transmission from younger to older age groups.ConclusionsWhile our scenarios could not anticipate the emergence/consequences of SARS-CoV-2 Omicron variant, we illustrate how our approach can assist decision making. This could be useful when considering to provide booster doses or intervening against future infection waves.

For the measles-mumps-rubella (MMR) vaccine, the World Health Organization-recommended coverage for herd protection is 95% for measles and 80% for rubella and mumps. However, a national vaccine coverage does not reflect social clustering of unvaccinated children, e.g. in schools of Orthodox Protestant or Anthroposophic identity in The Netherlands. To fully characterise this clustering, we estimated one-dose MMR vaccination coverages at all schools in the Netherlands. By combining postcode catchment areas of schools and school feeder data, each child in the Netherlands was characterised by residential postcode, primary and secondary school (referred to as school career). Postcode-level vaccination data were used to estimate vaccination coverages per school career. These were translated to coverages per school, stratified by school identity. Most schools had vaccine coverages over 99%, but major exceptions were Orthodox Protestant schools (63% in primary and 58% in secondary schools) and Anthroposophic schools (67% and 78%). School-level vaccine coverage estimates reveal strong clustering of unvaccinated children. The school feeder data reveal strongly connected Orthodox Protestant and Anthroposophic communities, but separated from one another. This suggests that even at a national one-dose MMR coverage of 97.5%, thousands of children per cohort are not protected by herd immunity.

Introduction: A substantial proportion of individuals infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), report persisting symptoms weeks and months following acute infection. Estimates on prevalence vary due to differences in study designs, populations, heterogeneity of symptoms and the way symptoms are measured. Common symptoms include fatigue, cognitive impairment and dyspnoea. However, knowledge regarding the nature and risk factors for developing persisting symptoms is still limited. Hence, in this study, we aim to determine the prevalence, severity, risk factors and impact on quality of life of persisting symptoms in the first year following acute SARS-CoV-2 infection., Methods and Analysis: The LongCOVID-study is both a prospective and retrospective cohort study being conducted in the Netherlands, with a one year follow-up. Participants aged 5 years and above, with self-reported positive or negative tests for SARS-CoV-2 will be included in the study. The primary outcome is the prevalence and severity of persistent symptoms in participants that tested positive for SARS-CoV-2 compared with controls. Symptom severity will be assessed for fatigue (Checklist Individual Strength (CIS subscale fatigue severity)), pain (Rand-36/SF-36 subscale bodily pain), dyspnoea (Medical Research Council (mMRC)) and cognitive impairment (Cognitive Failure Questionnaire (CFQ)). Secondary outcomes include effect of vaccination prior to infection on persistent symptoms, loss of health-related quality of life (HRQoL) and risk factors for persisting symptoms following infection with SARS-CoV-2., Ethics and Dissemination: The Utrecht Medical Ethics Committee (METC) declared in February 2021 that the Medical Research Involving Human Subjects Act (WMO) does not apply to this study (METC protocol number 21-124/C). Informed consent is required prior to participation in the study. Results of this study will be submitted for publication in a peer-reviewed journal., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Infants are at highest risk of pneumococcal disease. Their added protection through herd effects is a key part in the considerations on optimal pneumococcal vaccination strategies. Yet, little is currently known about the main transmission pathways to this vulnerable age group. Hence, this study investigates pneumococcal transmission routes to infants in the coastal city of Nha Trang, Vietnam., Methods and Findings: In October 2018, we conducted a nested cross-sectional contact and pneumococcal carriage survey in randomly selected 4- to 11-month-old infants across all 27 communes of Nha Trang. Bayesian logistic regression models were used to estimate age specific carriage prevalence in the population, a proxy for the probability that a contact of a given age could lead to pneumococcal exposure for the infant. We used another Bayesian logistic regression model to estimate the correlation between infant carriage and the probability that at least one of their reported contacts carried pneumococci, controlling for age and locality. In total, 1,583 infants between 4 and 13 months old participated, with 7,428 contacts reported. Few infants (5%, or 86 infants) attended day care, and carriage prevalence was 22% (353 infants). Most infants (61%, or 966 infants) had less than a 25% probability to have had close contact with a pneumococcal carrier on the surveyed day. Pneumococcal infection risk and contact behaviour were highly correlated: If adjusted for age and locality, the odds of an infant's carriage increased by 22% (95% confidence interval (CI): 15 to 29) per 10 percentage points increase in the probability to have had close contact with at least 1 pneumococcal carrier. Moreover, 2- to 6-year-old children contributed 51% (95% CI: 39 to 63) to the total direct pneumococcal exposure risks to infants in this setting. The main limitation of this study is that exposure risk was assessed indirectly by the age-dependent propensity for carriage of a contact and not by assessing carriage of such contacts directly., Conclusions: In this study, we observed that cross-sectional contact and infection studies could help identify pneumococcal transmission routes and that preschool-age children may be the largest reservoir for pneumococcal transmission to infants in Nha Trang, Vietnam., Competing Interests: CS is Lead investigator on a Merck Investigator Studies Program grant funded by MSD on pneumococcal serotype epidemiology in children with empyema. CS is Investigator on a clinical research collaboration on PCV vaccination in Mongolia.

Objectives: We aimed to identify populations at a high risk for SARS-CoV-2 infection but who are less likely to present for testing, by determining which sociodemographic and household factors are associated with a lower propensity to be tested and, if tested, with a higher risk of a positive test result., Design and Setting: Internet-based participatory surveillance data from the general population of the Netherlands., Participants: Weekly survey data collected over a 5-month period (17 November 2020 to 18 April 2021) from a total of 12 026 participants who had contributed at least 2 weekly surveys was analysed., Methods: Multivariable analyses using generalised estimating equations for binomial outcomes were conducted to estimate the adjusted ORs of testing and of test positivity associated with participant and household characteristics., Results: Male sex (adjusted OR for testing (OR t ): 0.92; adjusted OR for positivity (OR p ): 1.30, age groups<20 (OR t : 0.89; OR p : 1.27), 50-64 years (OR t : 0.94; OR p : 1.06) and 65+ years (OR t : 0.78; OR p : 1.24), diabetics (OR t : 0.97; OR p : 1.06) and sales/administrative employees (OR t : 0.93; OR p : 1.90) were distinguished as lower test propensity/higher test positivity factors., Conclusions: The factors identified using this approach can help identify potential target groups for improving communication and encouraging testing among those with symptoms, and thus increase the effectiveness of testing, which is essential for the response to the COVID-19 pandemic and for public health strategies in the longer term., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Higher incidence of and risk of hospitalisation and death from Influenza A(H1N1)pdm09 during the 2009 pandemic was reported in ethnic minority groups in many high-income settings including in the United Kingdom (UK). Many of these studies rely on geographical and temporal aggregation of cases and can be difficult to interpret due to the spatial and temporal factors in outbreak spread. Further, it can be challenging to distinguish between disparities in health outcomes caused by variation in transmission risk or disease severity., Methods: We used anonymised laboratory confirmed and suspected case data, classified by ethnicity and deprivation status, to evaluate how disparities in risk between socio-economic and ethnic groups vary over the early stages of the 2009 Influenza A(H1N1)pdm09 epidemic in Birmingham and London, two key cities in the emergence of the UK epidemic. We evaluated the relative risk of infection in key ethnic minority groups and by national and city level deprivation rank., Results: We calculated higher incidence in more deprived areas and in people of South Asian ethnicity in both Birmingham and London, although the magnitude of these disparities reduced with time. The clearest disparities existed in school-aged children in Birmingham, where the most deprived fifth of the population was 2.8 times more likely to be infected than the most affluent fifth of the population., Conclusions: Our analysis shows that although disparities in reported cases were present in the early phase of the Influenza A(H1N1)pdm09 outbreak in both Birmingham and London, they vary substantially depending on the period over which they are measured. Further, the development of disparities suggest that clustering of social groups play a key part as the outbreak appears to move from one ethnic and socio-demographic group to another. Finally, high incidence and large disparities between children indicate that they may hold an important role in driving inequalities., (© 2021. The Author(s).)

Objectives: Pre-exposure prophylaxis (PrEP) users are routinely tested four times a year (3 monthly) for asymptomatic Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections on three anatomical locations. Given the high costs of this testing to the PrEP programme, we assessed the impact of 3 monthly screening(current practice), compared with 6 monthly on the disease burden. We quantified the difference in impact of these two testing frequencies on the prevalence of CT and NG among all men who have sex with men (MSM) who are at risk of an STI, and explored the cost-effectiveness of 3-monthly screening compared with a baseline scenario of 6-monthly screening., Methods: A dynamic infection model was developed to simulate the transmission of CT and NG among sexually active MSM (6500 MSM on PrEP and 29 531 MSM not on PrEP), and the impact of two different test frequencies over a 10-year period. The difference in number of averted infections was used to calculate incremental costs and quality-adjusted life-years (QALY) as well as an incremental cost-effectiveness ratio (ICER) from a societal perspective., Results: Compared with 6-monthly screening, 3-monthly screening of PrEP users for CT and NG cost an additional €46.8 million over a period of 10 years. Both screening frequencies would significantly reduce the prevalence of CT and NG, but 3-monthly screening would avert and extra ~18 250 CT and NG infections compared with 6-monthly screening, resulting in a gain of ~81 QALYs. The corresponding ICER was ~€430 000 per QALY gained, which exceeded the cost-effectiveness threshold of €20 000 per QALY., Conclusions: Three-monthly screening for CT and NG among MSM on PrEP is not cost-effective compared with 6-monthly screening. The ICER becomes more favourable when a smaller fraction of all MSM at risk for an STI are screened. Reducing the screening frequency could be considered when the PrEP programme is established and the prevalence of CT and NG decline., Competing Interests: Competing interests: EH obtained advisory board fees and a research grant from Gilead Sciences; both of which were paid to her institute., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To assess the cost-effectiveness of a preexposure prophylaxis (PrEP) programme offering a choice of daily and event-driven PrEP for men who have sex with men (MSM) in the Netherlands., Methods: We used an agent-based transmission model and an economic model to simulate a programme offering only daily PrEP and a programme offering daily and event-driven PrEP. Use of PrEP medication and preference for daily versus event-driven PrEP were estimated from the Amsterdam PrEP Demonstration Project (AMPrEP). We calculated costs, quality-adjusted life-years (QALY), and incremental cost-effectiveness ratios (ICER), over 2018-2027. An ICER less than €20 000 per QALY gained was considered cost-effective., Results: Using AMPrEP data, we estimated that 27% of PrEP users chose event-driven PrEP with a median of 12 pills per month; daily PrEP users used a median of 30 pills per month. With PrEP, 3740 HIV infections were averted and 1482 QALYs were gained over 2018-2027, compared to the scenario without PrEP. The probability of the PrEP programme being cost-effective (compared to not having a PrEP programme) increased from 91% with daily PrEP to 94% with a choice of daily and event-driven PrEP. The probability of being cost-saving increased from 42% with only daily PrEP to 48% with choice of daily and event-driven PrEP., Conclusions: A daily PrEP programme for MSM would be cost-effective. Providing a choice of daily and event-driven PrEP can result in savings and is more likely to be cost-effective and cost-saving, compared to a programme offering only daily PrEP., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

During the first wave of the severe acute respiratory syndrome-coronavirus-2 epidemic in the Netherlands, notifications consisted mostly of patients with relatively severe disease. To enable real-time monitoring of the incidence of mild coronavirus disease 2019 (COVID-19) - for which medical consultation might not be required - the Infectieradar web-based syndromic surveillance system was launched in mid-March 2020. Our aim was to quantify associations between Infectieradar participant characteristics and the incidence of self-reported COVID-19-like illness. Recruitment for this cohort study was via a web announcement. After registering, participants completed weekly questionnaires, reporting the occurrence of a set of symptoms. The incidence rate of COVID-19-like illness was estimated and multivariable Poisson regression used to estimate the relative risks associated with sociodemographic variables, lifestyle factors and pre-existing medical conditions. Between 17 March and 24 May 2020, 25 663 active participants were identified, who reported 7060 episodes of COVID-19-like illness over 131 404 person-weeks of follow-up. The incidence rate declined over the analysis period, consistent with the decline in notified cases. Male sex, age 65+ years and higher education were associated with a significantly lower COVID-19-like illness incidence rate (adjusted rate ratios (RRs) of 0.80 (95% CI 0.76-0.84), 0.77 (0.70-0.85), 0.84 (0.80-0.88), respectively) and the baseline characteristics ever-smoker, asthma, allergies, diabetes, chronic lung disease, cardiovascular disease and children in the household were associated with a higher incidence (RRs of 1.11 (1.04-1.19) to 1.69 (1.50-1.90)). Web-based syndromic surveillance has proven useful for monitoring the temporal trends in, and risk factors associated with, the incidence of mild disease. Increased relative risks observed for several patient factors could reflect a combination of exposure risk, susceptibility to infection and propensity to report symptoms.

In early 2020 many countries closed schools to mitigate the spread of SARS-CoV-2. Since then, governments have sought to relax the closures, engendering a need to understand associated risks. Using address records, we construct a network of schools in England connected through pupils who share households. We evaluate the risk of transmission between schools under different reopening scenarios. We show that whilst reopening select year-groups causes low risk of large-scale transmission, reopening secondary schools could result in outbreaks affecting up to 2.5 million households if unmitigated, highlighting the importance of careful monitoring and within-school infection control to avoid further school closures or other restrictions.

Objectives: Cost-effectiveness analyses (CEA) are based on the value judgment that health outcomes (eg, quantified in quality-adjusted life-years; QALYs) are all equally valuable irrespective of their context. Whereas most published CEAs perform extensive sensitivity analysis on various parameters and assumptions, only rarely is the influence of the QALY-equivalence assumption on cost-effectiveness results investigated. We illustrate how the integration of alternative social value judgments in CEA can be a useful form of sensitivity analysis., Methods: Because varicella-zoster virus (VZV) vaccination affects 2 distinct diseases (varicella zoster and herpes zoster) and likely redistributes infections across different age groups, the program has an important equity dimension. We used a cost-effectiveness model and disentangled the share of direct protection and herd immunity within the total projected QALYs resulting from a 50-year childhood VZV program in the UK. We use the UK population's preferences for QALYs in the vaccine context to revalue QALYs accordingly., Results: Revaluing different types of QALYs for different age groups in line with public preferences leads to a 98% change in the projected net impact of the program. The QALYs gained among children through direct varicella protection become more important, whereas the QALYs lost indirectly through zoster in adults diminish in value. Weighting of vaccine-related side effects made a large difference., Conclusions: Our study shows that a sensitivity analysis in which alternative social value judgments about the value of health outcomes are integrated into CEA of vaccines is relatively straightforward and provides important additional information for decision makers to interpret cost-effectiveness results., (Copyright © 2020 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Objective: To estimate the economic burden to the health service of surgical site infection following caesarean section and to identify potential savings achievable through implementation of a surveillance programme., Design: Economic model to evaluate the costs and benefits of surveillance from community and hospital healthcare providers' perspective., Setting: England., Participants: Women undergoing caesarean section in National Health Service hospitals., Main Outcome Measure: Costs attributable to treatment and management of surgical site infection following caesarean section., Results: The costs (2010) for a hospital carrying out 800 caesarean sections a year based on infection risk of 9.6% were estimated at £18 914 (95% CI 11 521 to 29 499) with 28% accounted for by community care (£5370). With inflation to 2019 prices, this equates to an estimated cost of £5.0 m for all caesarean sections performed annually in England 2018-2019, approximately £1866 and £93 per infection managed in hospital and community, respectively. The cost of surveillance for a hospital for one calendar quarter was estimated as £3747 (2010 costs). Modelling a decrease in risk of infection of 30%, 20% or 10% between successive surveillance periods indicated that a variable intermittent surveillance strategy achieved higher or similar net savings than continuous surveillance. Breakeven was reached sooner with the variable surveillance strategy than continuous surveillance when the baseline risk of infection was 10% or 15% and smaller loses with a baseline risk of 5%., Conclusion: Surveillance of surgical site infections after caesarean section with feedback of data to surgical teams offers a potentially effective means to reduce infection risk, improve patient experience and save money for the health service., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: To optimize the focus of future public information campaigns in The Netherlands promoting the uptake of vaccines among adults and children, we quantified the contribution of several attributes to the vaccination decision., Method: We performed a discrete choice experiment (DCE) among Dutch adults including six attributes, i.e. vaccine effectiveness, vaccine-preventable burden of disease (specified in severity and frequency), accessibility of vaccination in terms of co-payment and prescription requirements, frequency of mild side-effects, population-level vaccination coverage and local vaccination coverage among family and friends. Participants answered the DCE from their own perspective ('oneself' group) or with regard to a vaccine decision for their youngest child ('child' group). The data was analysed by means of panel mixed logit models., Results: We included 1547 adult participants (825 'oneself' and 722 'child'). Vaccine effectiveness was the most important attribute in the 'oneself' group, followed by burden of disease (relative importance (RI) 78%) and accessibility (RI 76%). In the 'child' group, burden of disease was most important, but tied closely with vaccine effectiveness (RI 97%). Of less importance was the risk of mild vaccine-related side-effects and both population and local vaccination coverage. Interestingly, participants were more willing to vaccinate when uptake among the population or family and friends was high, indicating that social influence and social norms plays a role., Conclusions: Vaccine effectiveness and disease severity are key attributes in vaccination decision-making for adults making a decision for themselves and for parents who decide for their children. Hence, public information campaigns for both adult and child vaccination should primarily focus on these two attributes. In addition, reinforcing social norms may be considered.

In Hong Kong, universal varicella vaccination was introduced in July 2014 with a two-dose schedule but the vaccines had been available in the private market since 1996. With data from varicella notification and surveys on immunization coverage, we used the screening method to estimate dose-specific varicella vaccine effectiveness (VE) among preschool children in Hong Kong before universal vaccination. We estimated the VE of one- and two-dose varicella vaccination against all notified varicella as 69.4% (95% confidence interval (95% CI) 69.5-71.2) and 93.4% (95% CI 91.7-94.7), respectively. We found that VE did not decrease with time since receipt. Varicella vaccine was more effective against complications (85.4% [95% CI 48.8-95.8] for one dose and 100% [95% CI -Inf to 100] for two doses) and against hospital admission (75.2% [95% CI 53.4-86.8] for one dose and 93.1% [95% CI 47.1-99.1] for two doses). Lower protection of one-dose varicella vaccine resulted in breakthrough varicella. Under universal vaccination, second-dose varicella vaccine (given as combined measles, mumps, rubella and varicella vaccine) was first scheduled for children when they reach primary one (about 6 years of age) and was recently advanced to 18 months of age. Shortening the interval between the first dose and second dose of varicella vaccination should reduce breakthrough varicella and outbreaks in preschool.

Background: The present study aims to assess the cost-effectiveness of an influenza vaccination program for children in the Netherlands. This requires an evaluation of the long-term impact of such a program on the burden of influenza across all age groups, using a transmission model that accounts for the seasonal variability in vaccine effectiveness and the shorter duration of protection following vaccination as compared to natural infection., Methods: We performed a cost-effectiveness analysis based on a stochastic dynamic transmission model that has been calibrated to reported GP visits with influenza-like illness in the Netherlands over 11 seasons (2003/2004 to 2014/2015). We analyzed the costs and effects of extending the current program with vaccination of children aged 2-16 years at 50% coverage over 20 consecutive seasons. We measured the effects in quality-adjusted life-years (QALYs) and we adopted a societal perspective., Results: The childhood vaccination program is estimated to have an average incremental cost-effectiveness ratio (ICER) of €3944 per QALY gained and is cost-effective in the general population (across 1000 simulations; conventional Dutch threshold of €20,000 per QALY gained). The childhood vaccination program is not estimated to be cost-effective for the target-group itself with an average ICER of €57,054 per QALY gained. Uncertainty analyses reveal that these ICERs hide a wide range of outcomes. Even though introduction of a childhood vaccination program decreases the number of infections, it tends to lead to larger epidemics: in 23.3% of 1000 simulations, the childhood vaccination program results in an increase in seasons with a symptomatic attack rate larger than 5%, which is expected to cause serious strain on the health care system. In 6.4% of 1000 simulations, the childhood vaccination program leads to a net loss of QALYs. These findings are robust across different targeted age groups and vaccination coverages., Conclusions: Modeling indicates that childhood influenza vaccination is cost-effective in the Netherlands. However, childhood influenza vaccination is not cost-effective when only outcomes for the children themselves are considered. In approximately a quarter of the simulations, the introduction of a childhood vaccination program increases the frequency of seasons with a symptomatic attack rate larger than 5%. The possibility of an overall health loss cannot be excluded.

Background: In children aged <5 years in whom severe respiratory syncytial virus (RSV) episodes predominantly occur, there are currently no appropriate standardised instruments to estimate quality of life years (QALY) loss., Objectives: We estimated the age-specific QALY loss due to RSV by developing a regression model which predicts the QALY loss without the use of standardised instruments., Methods: We conducted a surveillance study which targeted confirmed RSV episodes in children aged <5 years (confirmed cases) and their household members who experienced symptoms of RSV during the same time (suspected cases). All participants were asked to complete questions regarding their health during the infection, with the suspected cases additionally providing health-related quality of life (HR-QoL) loss estimates by completing EQ-5D-3L-Y or EQ-5D-3L instruments. We used the responses from the suspected cases to calibrate a regression model which estimates the HR-QoL and QALY loss due to infection., Findings: For confirmed RSV cases in children under 5 years of age who sought health care, our model predicted a QALY loss per RSV episode of 3.823 × 10 -3 (95% CI 0.492-12.766 × 10 -3 ), compared with 3.024 × 10 -3 (95% CI 0.329-10.098 × 10 -3 ) for under fives who did not seek health care. Quality of life years loss per episode was less for older children and adults, estimated as 1.950 × 10 -3 (0.185-9.578 × 10 -3 ) and 1.543 × 10 -3 (0.136-6.406 × 10 -3 ) for those who seek or do not seek health care, respectively., Conclusion: Evaluations of potential RSV vaccination programmes should consider their impact across the whole population, not just young child children., (© 2019 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Objectives: To assess the cost-effectiveness of increased consistent HIV testing among MSM in the Netherlands., Methods: Among MSM testing at sexually transmitted infection clinics in the Netherlands in 2014-2015, approximately 20% tested consistently every 6 months. We examined four scenarios with increased percentage of MSM testing every 6 months: a small and a moderate increase among all MSM; a small and a moderate increase only among MSM with at least 10 partners in the preceding 6 months. We used an agent-based model to calculate numbers of HIV infections and AIDS cases prevented with increased HIV testing. These numbers were used in an economic model to calculate costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) due to increased testing, over 2018-2027, taking a healthcare payer perspective., Results: A small increase in the percentage testing every 6 months among all MSM resulted in 490 averted HIV infections and an average ICER of &OV0556;27 900/QALY gained. A moderate increase among all MSM, resulted in 1380 averted HIV infections and an average ICER of &OV0556;36 700/QALY gained. Both were not cost-effective, with a &OV0556;20 000 willingness-to-pay threshold. Increasing the percentage testing every 6 months only among MSM with at least 10 partners in the preceding 6 months resulted in less averted HIV infections than increased testing among all MSM, but was on average cost-saving., Conclusion: Increased HIV testing can prevent considerable numbers of new HIV infections among MSM, but may be cost-effective only if targeted at high-risk individuals, such as those with many partners.

Objectives: Reliable and timely HIV care cost estimates are important for policy option appraisals of HIV treatment and prevention strategies. As HIV clinical management and outcomes have changed, we aimed to update profiles of antiretroviral (ARV) usage pattern, patent/market exclusivity details and management costs in adults (≥ 18 years old) accessing HIV specialist care in England., Methods: The data reported quarterly to the HIV and AIDS Reporting System in England was used to identify ARV usage pattern, and were combined with British National Formulary (BNF) prices, non-ARV care costs and patent/market exclusivity information to generate average survival-adjusted lifetime care costs. The cumulative budget impact from 2018 to the year in which all current ARVs were expected to lose market exclusivity was calculated for a hypothetical 85 000 (± 5000) person cohort, which provided an illustration of potential financial savings afforded by bioequivalent generic switches. Price scenarios explored BNF70 (September 2015) prices and generics at 10/20/30/50% of proprietary prices. The analyses took National Health Service (NHS) England's perspective (as the payer), and results are presented in 2016/2017 British pounds., Results: By 2033, most currently available ARVs would lose market exclusivity; that is, generics could be available. Average per person lifetime HIV cost was ~£200 000 (3.5% annual discount) or ~£400 000 (undiscounted), reducing to ~£70 000 (3.5% annual discount; ~£120 000 undiscounted) with the use of generics (assuming that generics cost 10% of proprietary prices). The cumulative budget to cover 85 000 (± 5000) persons for 16 years (2018-2033) was £10.5 (± 0.6) billion, reducing to £3.6 (± 0.2) billion with the use of generics., Conclusions: HIV management costs are high but financial efficiency could be improved by optimizing generic use for treatment and prevention to mitigate the high cost of lifelong HIV treatment. Earlier implementation of generics as they become available offers the potential to maximize the scale of the financial savings., (© 2019 British HIV Association.)

Vaccination programs generate direct protection, herd protection and, occasionally, side effects, distributed over different age groups. This study elicits the general public's view on how to balance these outcomes in funding decisions for vaccines. We performed an optimal design discrete choice experiment with partial profiles in a representative sample (N = 1499) of the population in the United Kingdom in November 2016. Using a panel mixed logit model, we quantified, for four different types of infectious disease, the importance of a person's age during disease, how disease was prevented-via direct vaccine protection or herd protection-and whether the vaccine induced side effects. Our study shows clear patterns in how the public values vaccination programs. These diverge from the assumptions made in public health and cost-effectiveness models that inform decision-making. We found that side effects and infections in newborns and children were of primary importance to the perceived value of a vaccination program. Averting side effects was, in any age group, weighted three times as important as preventing an identical natural infection in a child whereas the latter was weighted six times as important as preventing the same infection in elderly aged 65-75 years. These findings were independent of the length or severity of the disease, and were robust across respondents' backgrounds. We summarize these patterns in a set of preference weights that can be incorporated into future models. Although the normative significance of these weights remains a matter open for debate, our study can, hopefully, contribute to the evaluation of vaccination programs beyond cost-effectiveness., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: In many regions of the world, vaccine hesitancy has become an important concern to public health. A key part of any effective solution to it is to gain an in-depth understanding of the problem: its scope, who holds hesitant views and for which reasons., Methods: We adapt the original 10-item Vaccine Hesitancy Scale (VHS), which targets parental attitudes, to a more generic version that captures general attitudes to vaccination. We use this adapted VHS in a sample of 1402 British citizens, selected from a large online panel (N > 1,000,000) based on quota for age, gender, educational attainment and region (response rate 43%). The existence of VHS subscales is evaluated via exploratory and confirmatory factor analysis. We describe the extent of vaccine hesitancy in the sample, and use simple and multiple regression analysis to examine associations between respondent characteristics and vaccine hesitancy., Results: Despite ambiguities in defining hesitancy, we found that a substantial part of our sample held hesitant views about vaccination, particularly for those items reflecting aversion to risks of side effects. Four percent responded in a hesitant way to all ten items and ninety to at least one of the ten items. In line with recent studies in other populations, we identified two subscales within the VHS: lack of confidence in the need for vaccines and aversion to the risk of side effects. We found significant associations between hesitancy and various respondent characteristics but the predictive power of these associations remained limited., Conclusion: Our study suggests that whereas a substantial percentage of the British population is vaccine hesitant, these views are not clustered in typical demographic features. The small but important adaptation of the VHS to target general attitudes seems to result in highly similar psychometric characteristics as the original scale that exclusively targets parents. We provide suggestions for further validation of the VHS., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: The newly registered adjuvanted herpes zoster subunit vaccine (HZ/su) has a higher efficacy than the available live-attenuated vaccine (ZVL). National decision-makers soon need to decide whether to introduce HZ/su or to prefer HZ/su above ZVL., Methods: Using a Markov model with a decision tree, we conducted a cost-effectiveness analysis of vaccination with HZ/su (two doses within 2 months) or zoster vaccine live (ZVL) (single dose, or single dose with a booster after 10 years) for cohorts of 50-, 60-, 70- or 80-year-olds in the Netherlands. The model was parameterized using vaccine efficacy data from randomized clinical trials and up-to-date incidence, costs and health-related quality of life data from national datasets. We used a time horizon of 15 years, and the analysis was conducted from the societal perspective., Results: At a coverage of 50%, vaccination with two doses of HZ/su was estimated to prevent 4335 to 10,896 HZ cases, depending on the cohort age. In comparison, this reduction was estimated at 400-4877 for ZVL and 427-6466 for ZVL with a booster. The maximum vaccine cost per series of HZ/su to remain cost-effective to a willingness-to-pay threshold of €20,000 per quality-adjusted life year (QALY) gained ranged from €109.09 for 70-year-olds to €63.68 for 50-year-olds. The cost-effectiveness of ZVL changed considerably by age, with corresponding maximum vaccine cost per dose ranging from €51.37 for 60-year-olds to €0.73 for 80-year-olds. Adding a ZVL booster after 10 years would require a substantial reduction of the maximum cost per dose to remain cost-effective as compared to ZVL single dose. Sensitivity analyses on the vaccine cost demonstrated that there were scenarios in which vaccination with either HZ/su (two doses), ZVL single dose or ZVL + booster could be the most cost-effective strategy., Conclusions: A strategy with two doses of HZ/su was superior in reducing the burden of HZ as compared to a single dose or single dose + booster of ZVL. Both vaccines could potentially be cost-effective to a conventional Dutch willingness-to-pay threshold for preventive interventions. However, whether HZ/su or ZVL would be the most cost-effective alternative depends largely on the vaccine cost.

Objective: To quantify inequalities in zoster vaccine uptake by determining its association with socio-demographic factors: age, gender, ethnicity, immigration status, deprivation (at Lower-layer Super Output Area-level), care home residence and living arrangements., Method: This population-based cohort study utilised anonymised primary care electronic health records from England (Clinical Practice Research Datalink) linked to deprivation and hospitalisation data. Data from 35,333 individuals from 277 general practices in England and eligible for zoster vaccination during the two-year period (2013-2015) after vaccine introduction were analysed. Logistic regression was used to obtain adjusted odds ratios (aOR) for the association of socio-demographic factors with zoster vaccine uptake for adults aged 70 years (main target group) and adults aged 79 years (catch-up group)., Results: Amongst those eligible for vaccination, 52.4% (n = 18,499) received the vaccine. Socio-demographic factors independently associated with lower zoster vaccine uptake in multivariable analyses were: being older (catch-up group: aged 79 years) aOR = 0.89 (95% confidence interval (CI):0.85-0.93), care home residence (aOR = 0.64 (95%CI: 0.57-0.73)) and living alone (aOR = 0.85 (95%CI: 0.81-0.90)). Uptake decreased with increasing levels of deprivation (p-value for trend<0.0001; aOR most deprived versus least deprived areas = 0.69 (95%CI: 0.64-0.75)). Uptake was also lower amongst those of non-White ethnicities (for example, Black versus White ethnicity: aOR = 0.61 (95%CI: 0.49-0.75)) but was not lower among immigrants after adjusting for ethnicity. Lower uptake was also seen amongst females compared to men in the catch-up group., Conclusions: Inequalities in zoster vaccine uptake exist in England; with lower uptake among those of non-White ethnicities, and among those living alone, in a care home and in more deprived areas. Tailored interventions to increase uptake in these social groups should assist in realising the aim of mitigating vaccination inequalities. As care home residents are also at higher risk of zoster, improving the uptake of zoster vaccination in this group will also mitigate inequalities in zoster burden., Competing Interests: The authors have declared that no competing interests exist.

Background: Chronic infection with hepatitis B or C virus (HBV/HCV) can progress to cirrhosis, liver cancer, and even death. In a low endemic country as the Netherlands, migrants are a key risk group and could benefit from early diagnosis and antiviral treatment. We assessed the cost-effectiveness of screening foreign-born migrants for chronic HBV and/or HCV using a societal perspective., Methods: The cost-effectiveness was evaluated using a Markov model. Estimates on prevalence, screening programme costs, participation and treatment uptake, transition probabilities, healthcare costs, productivity losses and utilities were derived from the literature. The cost per Quality Adjusted Life Year (QALY) gained was estimated and sensitivity analyses were performed., Results: For most migrant groups with an expected high number of chronically infected cases in the Netherlands combined screening is cost-effective, with incremental cost-effectiveness ratios (ICERs) ranging from €4,962/QALY gained for migrants originating from the Former Soviet Union and Vietnam to €9,375/QALY gained for Polish migrants. HBV and HCV screening proved to be cost-effective for migrants from countries with chronic HBV or HCV prevalence of ≥0.41% and ≥0.22%, with ICERs below the Dutch cost-effectiveness reference value of €20,000/QALY gained. Sensitivity analysis showed that treatment costs influenced the ICER for both infections., Conclusions: For most migrant populations in a low-endemic country offering combined HBV and HCV screening is cost-effective. Implementation of targeted HBV and HCV screening programmes to increase early diagnosis and treatment is important to reduce the burden of chronic hepatitis B and C among migrants., Competing Interests: The authors have declared that no competing interests exist.

Background: Social and cultural disparities in infectious disease burden are caused by systematic differences between communities. Some differences have a direct and proportional impact on disease burden, such as health-seeking behaviour and severity of infection. Other differences-such as contact rates and susceptibility-affect the risk of transmission, where the impact on disease burden is indirect and remains unclear. Furthermore, the concomitant impact of vaccination on such inequalities is not well understood., Methods: To quantify the role of differences in transmission on inequalities and the subsequent impact of vaccination, we developed a novel mathematical framework that integrates a mechanistic model of disease transmission with a demographic model of social structure, calibrated to epidemiologic and empirical social contact data., Results: Our model suggests realistic differences in two key factors contributing to the rates of transmission-contact rate and susceptibility-between two social groups can lead to twice the risk of infection in the high-risk population group relative to the low-risk population group. The more isolated the high-risk group, the greater this disease inequality. Vaccination amplified this inequality further: equal vaccine uptake across the two population groups led to up to seven times the risk of infection in the high-risk group. To mitigate these inequalities, the high-risk population group would require disproportionately high vaccination uptake., Conclusion: Our results suggest that differences in contact rate and susceptibility can play an important role in explaining observed inequalities in infectious diseases. Importantly, we demonstrate that, contrary to social policy intentions, promoting an equal vaccine uptake across population groups may magnify inequalities in infectious disease risk.

Some 50 years ago, Edgar Hope-Simpson published his hypothesis regarding the interactions between varicella and herpes zoster. As part of this hypothesis, Hope-Simpson postulated that reactivation of varicella zoster virus (VZV) was under immunological control, and that this immunological control could be boosted "endogenously" due to reactivation of latent VZV, and "exogenously" due to exposure to varicella. This hypothesis has important policy implications and remains a source of debate today; namely, does reducing VZV circulation through effective pediatric varicella vaccination programs lead to unintended increases in herpes zoster (HZ) incidence? This article provides 2 very different perspectives on this issue. The first perspective (Rafael Harpaz: Evidence Against an Effect) highlights the empiric experience of the United States, with its population of >300 million, a highly effective national varicella vaccination program lasting >20 years, and with several credible sources of data regarding HZ incidence. The US data have shown an increase in HZ incidence that preceded the availability of varicella vaccination by decades; indeed, HZ rates appear to have plateaued among older adults since varicella vaccination was introduced. Furthermore, HZ rates are not different in states having higher vs lower preschool varicella vaccination rates. The second perspective (Albert J. van Hoek: Evidence for an Effect) cites data that persons with close exposure to children appear to be at lower risk of HZ before universal VZV vaccination, but not so thereafter. Due to historic demographic changes, exogenous boosting could play a role in explaining the observed increase in HZ before varicella vaccination. Thus, it might be difficult to separate declines in exogenous boosting due to demographic changes from those caused by the varicella vaccination program. Additional data will be needed to conclusively rule out an impact of varicella vaccination on HZ.

Background: Men who have sex with men require special attention for human papillomavirus vaccination given elevated infection risks and the development of, in particular, anal cancer., Objective: Our purpose was to review the cost effectiveness of human papillomavirus vaccination for both currently vaccine-eligible and non-eligible individuals, particularly the men-who-have-sex-with-men population, and synthesize the available evidence., Methods: We systematically searched for published articles in two main databases (PubMed and EMBASE). Screening and data extraction were performed by two independent reviewers. The risk of bias was assessed using a validated instrument (Bias in Economic Evaluation, ECOBIAS). Methodological aspects, study results, and sensitivity analyses were extracted and synthesized to generate a consistent overview of the cost effectiveness of human papillomavirus vaccination in the men-who-have-sex-with-men population., Results: From 770 identified articles, four met the inclusion criteria. Across the studies, human papillomavirus vaccination showed incremental cost-effectiveness ratios ranging from dominant to US$96,146 and US$14,000 to US$18,200 for tertiary prevention and primary prevention, respectively. The incremental cost-effectiveness ratio seemed most sensitive to vaccine efficacy, vaccine costs, and the incidence of anal cancer in the selected target populations., Conclusion: This review presents the human papillomavirus vaccine, both as a primary and adjuvant (tertiary) vaccination, as a potentially cost-effective strategy for preventing mainly-but not limited to only-anal cancer in men-who-have-sex-with-men populations.

Background: In April 2010, 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7 in the infant immunisation schedule in England and Wales. Despite limited serotype replacement in invasive pneumococcal disease (IPD) during the first four post-PCV13 years, non-vaccine type (NVT) IPD increased substantially in 2014/15. We undertook a carriage study in 2015/16 to help understand the reasons for this increase., Methods and Findings: Families with a child aged <5 years attending a participating general practice in Gloucestershire or Hertfordshire were invited to provide nasopharyngeal swabs from all consenting members. Swabs from 650 individuals (293 under five, 73 five to twenty and 284 >twenty years) were cultured and serotyped for Streptococcus pneumoniae. Results were compared with those from three previous household studies conducted in the same populations between 2001 to 2013, and with the serotypes causing IPD to estimate case-carrier ratios (CCRs). Overall carriage prevalence did not differ between the four carriage studies with reductions in vaccine-type carriage offset by increases in NVT carriage. While no individual NVT serotype showed an increase in CCR from 2012/13, the composition of the serotypes comprising the NVT group differed such that the overall CCR of the NVT group had significantly increased since 2012/13. Carriage of two PCV13 serotypes, 3 and 19A, was found in 2015/16 (3/650 = 0.5% and 2/650 = 0.3% respectively) with no overall reduction in carriage prevalence of PCV13-7 serotypes since 2012/13, though 6C prevalence, a vaccine-related serotype, had reduced from 1.8% in 2012/13 to 2/648 (0.3%) in 2015/16, p = 0.013., Conclusions: There was continuing evolution in carried NVTs six years after PCV13 introduction which, in addition to being vaccine-driven, could also reflect natural secular changes in certain NVTs. This poses challenges in predicting future trends in IPD. Elimination of carriage and disease due to serotypes 3 and 19A may not be achieved by PCV13., Competing Interests: The authors have declared that no competing interests exist.

In Hong Kong, universal varicella vaccination started in July 2014. Before this, children could receive varicella vaccine via the private market. We analysed the epidemiology of varicella and zoster before universal vaccination. We estimated varicella vaccination coverage through surveys in preschool children. We estimated the burden of varicella and zoster with varicella notifications from 1999/00 to 2013/14, Accident and Emergency Department (A&E) attendance and inpatient admissions to public hospitals from 2004/05 to 2013/14. We fitted a catalytic model to serological data on antibodies against varicella-zoster virus to estimate the force of infection. We found that varicella vaccination coverage gradually increased to about 50% before programme inception. In children younger than 5 years, the annual rate of varicella notifications, varicella admission and zoster A&E attendance generally declined. The annual notification, A&E attendance and hospitalisation rate of varicella and zoster generally increased for individuals between 10 and 59 years old. Varicella serology indicated an age shift during the study period towards a higher proportion of infections in slightly older individuals, but the change was most notable before vaccine licensure. In conclusion, we observed a shift in the burden of varicella to slightly older age groups with a corresponding increase in incidence but it cannot necessarily be attributed to private market vaccine coverage alone. Increasing varicella vaccination uptake in the private market might affect varicella transmission and epidemiology, but not to the level of interrupting transmission.