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Direct replication, that is, analysis of new data with the same study protocol, has a purpose in checking the reliability of earlier research findings. However, using a case study we show that direct replication can have an additional function. We find that identical numerical replication results can be the result of differential effects of biases across different data sources and we draw attention to the risk of asymmetric evaluation in such cases. We then show how exact replications have the important function to bring into focus the contextualities inherent in the generation of research findings. Understanding the contextuality allows for a better and richer understanding of what the results imply. •Direct replication studies are thought to assess reliability.•However, a numerical replication success can be more apparent than real.•A direct replication also allows to uncover important contextualities.•Replication studies can therefore lead to a richer understanding.

Previous research suggested that the inactivated influenza vaccine (IIV) may protect against SARS-CoV-2 infection or a severe course of COVID-19. These findings were however based on cohort studies, that are prone to confounding by indication. We examined the association between IIV and SARS-Cov-2 infection in a Dutch population using a test-negative design. This test-negative case-control study was conducted in adults (≥60) who tested because of COVID-19 like symptoms at community SARS-CoV-2 testing locations in the Netherlands during the period of November 8th 2021-March 11th 2022. Information on receipt of IIV in October-November 2021 was routinely collected at each visit. Logistic regression was used to calculate unadjusted, partially (sex, age, education level) and fully adjusted (COVID-19 vaccination, IIV 2020) odds ratios (ORs) for receipt of IIV in SARS-CoV-2 positive versus negative subjects. Differential effects on SARS-CoV-2 risk by time since IIV were investigated by including an interaction term for calendar time: November 2021-January 2022 vs February-March 2022. In total, 1,832 participants were included in the main analysis, of whom 336 (18.3 %) had a positive SARS-CoV-2 test. No significant association between IIV and SARS-CoV-2 infection was found; fully adjusted OR of 1.07 (95 % CI: 0.78–1.49). The interaction term for time periods was not significant (1.04 [95 % CI: 0.51–2.15], p = 0.91). Results were robust in sensitivity analyses. While earlier observational studies suggested a protective non-specific effect of IIV and SARS-CoV-2 infections, this smaller, but well controlled test-negative design study does not suggest an effect, either positive or negative. Larger test-negative design studies, or alternative designs such as the self-controlled case series design are needed to confirm these findings and provide more definite answers on the topic.

Knowledge on the molecular epidemiology of Escherichia coli causing E. coli bacteremia (ECB) in the Netherlands is mostly based on extended-spectrum beta-lactamase-producing E. coli (ESBL-Ec). We determined differences in clonality and resistance and virulence gene (VG) content between non-ESBL-producing E. coli (non-ESBL-Ec) and ESBL-Ec isolates from ECB episodes with different epidemiological characteristics. A random selection of non-ESBL-Ec isolates as well as all available ESBL-Ec blood isolates was obtained from two Dutch hospitals between 2014 and 2016. Whole genome sequencing was performed to infer sequence types (STs), serotypes, acquired antibiotic resistance genes and VG scores, based on presence of 49 predefined putative pathogenic VG. ST73 was most prevalent among the 212 non-ESBL-Ec (N = 26, 12.3%) and ST131 among the 69 ESBL-Ec (N = 30, 43.5%). Prevalence of ST131 among non-ESBL-Ec was 10.4% (N = 22, P value < .001 compared to ESBL-Ec). O25:H4 was the most common serotype in both non-ESBL-Ec and ESBL-Ec. Median acquired resistance gene counts were 1 (IQR 1-6) and 7 (IQR 4-9) for non-ESBL-Ec and ESBL-Ec, respectively (P value < .001). Among non-ESBL-Ec, acquired resistance gene count was highest among blood isolates from a primary gastro-intestinal focus (median 4, IQR 1-8). Median VG scores were 13 (IQR 9-20) and 12 (IQR 8-14) for non-ESBL-Ec and ESBL-Ec, respectively (P value = .002). VG scores among non-ESBL-Ec from a primary urinary focus (median 15, IQR 11-21) were higher compared to non-ESBL-Ec from a primary gastro-intestinal (median 10, IQR 5-13) or hepatic-biliary focus (median 11, IQR 5-18) (P values = .007 and .04, respectively). VG content varied between different E. coli STs. Non-ESBL-Ec and ESBL-Ec blood isolates from two Dutch hospitals differed in clonal distribution, resistance gene and VG content. Also, resistance gene and VG content differed between non-ESBL-Ec from different primary foci of ECB.

•Parental preferences and expected coverage may guide the introduction of rotavirus vaccines.•Vaccination decisions of parents were mostly driven by vaccine related out-of-pocket costs.•Highest coverage is expected for a vaccine with high effectiveness and protection duration.•Highest coverage can only be realized if the vaccine is implemented within the current NIP. This study aimed to identify characteristics that affect parental decisions about rotavirus vaccination, to determine the relative importance of those characteristics and subsequently to estimate vaccination coverage for different implementation strategies. A Discrete choice experiment (DCE) questionnaire was sent to the parents of 1250 newborns aged 6 weeks (response rate 37.3%). Mixed-logit models were used to estimate the relative importance of the five included rotavirus vaccine and implementation characteristics; vaccine effectiveness, frequency of severe side effects, protection duration, the healthcare facility that administrates vaccination and out-of-pocket costs. Based on the utility functions of the mixed-logit model, the potential vaccination coverage was estimated for different vaccine scenarios and implementation strategies. All characteristics, except for healthcare facility that administrates vaccination, influenced parental willingness to vaccinate their newborn against rotavirus. Parents were willing to trade 20.2 percentage points vaccine effectiveness for the lowest frequency of severe side effects (i.e., 1 in 1,000,000) or 20.8 percentage points for a higher protection duration. Potential vaccination coverage ranged between 22.7 and 86.2%, depending on vaccine scenario (i.e., vaccine effectiveness and protection duration) and implementation strategy (i.e., out-of-pocket costs and healthcare facility that administrates vaccination). When deciding about vaccination against rotavirus, parents are mostly driven by the out-of-pocket costs, vaccine effectiveness, protection duration, and frequency of severe side effects. The highest vaccination coverage is expected for a vaccine with high effectiveness and protection duration that is implemented within the current National Immunization Program context. Implementation of the same rotavirus vaccine in the free market will result in lowest coverage.

•5 years after PCV10 replaced PCV7 in the Netherlands, PCV10 has contributed to:•A reduction in pneumonia-bronchitis incidence in children and adults.•A reduction in sinusitis incidence in some adult age-groups.•The impact on otitis media incidence is not consistently observed in two analysis types and therefore uncertain.•This study supports evidence of direct and indirect effect of the switch from PCV7 to PCV10 on primary care attended infections. In 2011, 10-valent pneumococcal conjugate vaccine (PCV10) replaced PCV7 in The Netherlands. We aimed to assess the impact of this switch on non-invasive pneumococcal disease in primary care across various age-groups, including pneumonia-bronchitis, otitis media (OM) and sinusitis with and without considering pre-PCV10 secular trends. Electronic records of 397,441 individuals included in a regional primary care database from July 2006 to June 2016 were extracted (2,408,762 person-years). We fitted interrupted time-series on annual incidence rates (IR) of primary care diagnosed pneumonia-bronchitis, OM and sinusitis episodes per age-group. We performed these two types of analyses, comparing; 1) the post-PCV10 observed versus expected trend if PCV10 had not been implemented and pre-PCV10 secular trends had continued 2), the pre- versus post-PCV10 observed, model fitted trend. The latter assumes no secular trend. Incidence rate ratios (IRR) were calculated using both methods. We found significant reductions following PCV10 introduction with both analysis methods for pneumonia-bronchitis in the pediatric and adult age-groups, for sinusitis in the age-group 20–50 years and for OM, the effect across various age-groups are uncertain given contradictory results. For other outcomes and age-groups, the effect estimates were not consistent across the two-method used and heavily depended on the strength of the underlying trend. No consistent effects were observed in the elderly population, considering the two methods used. Our study supports some direct and indirect-effect of PCV10 introduction on non-IPD, mainly on pneumonia-bronchitis, but estimates heavily depend on the method of analysis used. Estimates from the two different approaches may differ substantially if underlying trends are strong.

The role of school-based contacts in the epidemiology of SARS-CoV-2 is incompletely understood. We use an age-structured transmission model fitted to age-specific seroprevalence and hospital admission data to assess the effects of school-based measures at different time points during the COVID-19 pandemic in the Netherlands. Our analyses suggest that the impact of measures reducing school-based contacts depends on the remaining opportunities to reduce non-school-based contacts. If opportunities to reduce the effective reproduction number ( R e ) with non-school-based measures are exhausted or undesired and R e is still close to 1, the additional benefit of school-based measures may be considerable, particularly among older school children. As two examples, we demonstrate that keeping schools closed after the summer holidays in 2020, in the absence of other measures, would not have prevented the second pandemic wave in autumn 2020 but closing schools in November 2020 could have reduced R e below 1, with unchanged non-school-based contacts. The role of school-based contacts in the epidemiology of SARS-CoV-2 is incompletely understood. Here, the authors use an age-structured transmission model fitted to age-specific seroprevalence and hospital admission data to assess the effects of school-based measures during the COVID-19 pandemic in the Netherlands.

Households are important sites for transmission of SARS-CoV-2 and preventive measures are recommended. This study aimed to 1) investigate the impact of living with a person infected with SARS-CoV-2; 2) understand how household members implemented infection control recommendations in their home; and 3) identify the information and support needs of household members. For this observational mixed-methods study, households with a person with confirmed SARS-CoV-2 infection were recruited via drive-through testing sites of Municipal Health Services, healthcare worker screening or hospital emergency visits in the University Medical Centre Utrecht, the Netherlands and via primary care physicians, hospital emergency visits or preoperative screening in the University Hospital of Antwerp, Belgium. We recorded household characteristics, including characteristics of all household members, together with their views on prevention measures. In a subset of households one adult household member was asked to participate in an interview investigating their views on preventive measures. Survey data were analysed using descriptive statistics and interview data by rapid framework analysis. A triangulation protocol was used to integrate findings. Thirty-four households (120 household members) were included in the quantitative survey. Twenty-two households were invited to be interviewed, of which 18 completed an interview (response 81.8%). Survey data showed that almost all households implemented some preventive measures, the use of face masks being least frequently reported. Measures taken depended on what was physically possible, the perceived severity of illness of the index patient and to what extent household members were willing to limit social interaction. Respondents did not believe in the effectiveness of wearing face masks within the house, and from the interviews this was explained by media coverage of face masks, impracticality and the stigma associated with wearing masks. Interviewees reported that quarantine had a high emotional burden and wished to have more information about the exact duration of quarantine, their own COVID-19 status, symptoms and when to seek medical help. People were willing to implement prevention measures, however actual adherence depended on perceived severity of illness and the perceived risk of becoming infected. Homes are social environments and recommendations for infection prevention should account for this context. Incorporating our findings into policy making could provide households with more relevant and actionable advice.

BackgroundThe incidence of childhood overweight and obesity is rising. It is hypothesized that infections in early childhood are associated with being overweight. This study investigated the association between the number of symptomatic infections or antibiotic prescriptions in the first 3 years of life and body mass index (BMI) in adolescence.SubjectsThe current study is part of the Prevention and Incidence of Asthma and Mite Allergy population-based birth cohort study. Weight and height were measured by trained research staff at ages 12 and 16 years. The 3015 active participants at age 18 years were asked for informed consent for general practitioner (GP) data collection and 1519 gave written informed consent. Studied exposures include (1) GP-diagnosed infections, (2) antibiotic prescriptions, and (3) parent-reported infections in the first 3 years of life. Generalized estimating equation analysis was used to determine the association between each of these exposures and BMI z-score.ResultsExposure data and BMI measurement in adolescence were available for 622 participants. The frequencies of GP-diagnosed infections and antibiotic prescriptions were not associated with BMI z-score in adolescence with estimates being 0.14 (95% CI −0.09–0.37) and 0.10 (95% CI −0.14–0.34) for the highest exposure categories, respectively. Having ≥6 parent-reported infections up to age 3 years was associated with a 0.23 (95% CI 0.01–0.44) higher BMI z-score compared to <2 parent-reported infections.ConclusionsFor all infectious disease measures an increase in BMI z-score for the highest childhood exposure to infectious disease was observed, although only statistically significant for parent-reported infections. These results do not show an evident link with infection severity, but suggest a possible cumulative effect of repeated symptomatic infections on overweight development.

The effectiveness of inactivated influenza vaccine (IIV) immunization in preventing all cause respiratory illness (RI) in children with pre-existing medical conditions has not been fully established and varies from season to season. This study aims to quantify the overall impact of IIV immunization on primary care attended RI episodes in children with pre-existing medical conditions, using robust observational data spanning twelve influenza seasons. Electronic records of IIV eligible children aged 6 months to 18 years were extracted from primary care databases over the years 2004–2015. IIV eligibility criteria according to Dutch guidelines included (chronic) respiratory and cardiovascular disease and diabetes mellitus. For each year, information on IIV immunization status, primary care attended RI episodes (including influenza, acute respiratory tract infections and asthma exacerbations) and potential confounders were collected. Generalized estimating equations were used to model the association between IIV status and occurrence of at least one RI episode during the influenza epidemic period with “current year immunized” as reference group. Robustness of findings were assessed by performing various sensitivity analyzes in which (i) seasons with a mismatch between the dominant circulating influenza virus and vaccine strain were excluded, (ii) influenza periods were further restricted to weeks with at least 30% influenza virus positive specimens in sentinel surveillance (instead of 5%), (iii) propensity scores were used to adjust for confounding. In total, 11,797 children (follow-up duration: 38,701 child-years) were eligible for IIV for ≥ one season with 29% immunized at least once. The adjusted odds for primary care attended RI episodes during the influenza epidemic period did not differ between current season immunized versus not immunized children (adjusted OR:1.01; 95%CI:0.90–1.13). The various sensitivity analysis showed comparable results. IIV immunization in children with pre-existing medical conditions does not reduce all cause RI episodes encountered in primary care during the influenza season.

This study aims to estimate the incidence of arbovirus infections among Dutch travellers and subsequent potential risk of importation. For this prospective, fully remote study, Dutch travellers visiting arbovirus endemic countries between August 2018 to March 2020 were recruited through (social) media and travel-clinics. Interested travellers could register online. Participants completed questionnaires and kept a daily symptom log during travel using a custom-made study app. Travellers reporting symptoms suggestive of arbovirus infection were invited to self-collect a dry-blood spot sample (DBS) upon return. In a sub-cohort of participants, post-travel DBS were also collected if asymptomatic. Participants mailed the DBS to the laboratory to be tested by PCR for ZIKV, DENV and CHIKV, along with IgG and IgM antibody testing. Of 1222 subjects registering online, 737 (60.3 %) completed the baseline questionnaire and ≥60 % of symptom diaries and were included in the analysis. Arbovirus-like symptoms were reported by 73 participants (9.9 %). A post-travel DBS was obtained from 67 symptomatic and 154 asymptomatic travellers. None were RT-PCR positive for ZIKV, DENV or CHIKV. Two symptomatic travellers were IgM positive indicating probable recent arbovirus infection. An additional ten cases were IgG positive/IgM negative suggesting possible previous arbovirus exposure. The estimated incidence proportion and rate of travel-related arbovirus infection were 2.7–16.3/1000 trips and 3.9–23.4/1000 person-months, respectively. While a small proportion of travellers to arbovirus endemic areas have evidence of recent infection, the risk of arbovirus importation by returning travellers appears low as viraemia was not detected in any participant upon return.