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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.

•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 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.

•Inactivated influenza vaccine (IIV) may be effective against severe influenza.•A risk-based programme of IIV in children with medical risk conditions is unlikely to be cost-effective in the Netherlands.•Cost-effectiveness of IIV largely depends on influenza mortality estimates.•More evidence is needed on influenza disease burden and mortality in children with medical conditions. In many countries, annual immunization with inactivated influenza vaccine (IIV) is recommended for children with medical risk conditions. Prior cost-effectiveness analyses found such immunization to be cost saving, but assumed effectiveness against non-severe influenza outcomes and a higher effectiveness against severe influenza outcomes than recent studies would suggest. However, recent vaccine studies do not indicate any reduction in community or outpatient disease episodes in IIV immunized individuals. We therefore evaluated cost-effectiveness of IIV immunization in children with medical risk conditions in the Netherlands, assuming that IIV reduces influenza-related hospitalization and death, but has no meaningful impact on non-severe health outcomes. A health economic decision tree model was developed to evaluate health effects and costs of annual IIV immunization versus no immunization. Model inputs were based on our study on influenza-related primary care visits and other literature. Immunization was considered cost effective if associated costs were less than €20,000 per quality-adjusted life year (QALY) gained. Probabilistic sensitivity analyses were performed to assess robustness of results, and one-way sensitivity analyses and scenario analyses were done to assess the influence of individual parameters. Annual IIV prevents an average of 1.59 influenza-related hospitalizations and 0.02 deaths per 1,000 children with medical risk conditions. This results in an expected QALY gain of 0.43 at incremental costs of €21,564 per 1,000 children, corresponding to an incremental cost-effectiveness ratio (ICER) of €50,297/QALY compared to no immunization. Under base case assumptions, immunization had a 5% probability of being cost effective. Results were most influenced by vaccine efficacy against fatal influenza, QALY loss due to death, and mortality rate. If IIV only reduces severe disease outcomes, as current evidence suggests, annual immunization of medical risk children is unlikely to be cost effective. Results should however be interpreted with caution as cost-effectiveness is largely dependent on incidence and QALY losses for fatal influenza, for which evidence is scarce.

To assess racial/ethnic differences in the diet in young children and the explanatory role of maternal BMI, immigrant status and perception of child's weight. Among white, black and Hispanic 3-year-olds, we used negative binomial and linear regression to examine associations of race/ethnicity with foods and nutrients assessed by a validated FFQ. Project Viva, Boston (MA), USA. Children aged 3 years (n 898). Mean age was 38·3 (sd 2·8) months; 464 (52 %) were boys and 127 mothers (14 %) were immigrants. After adjustment for sociodemographic factors, black and Hispanic children (v. white) had a higher intake of sugar-sweetened beverages (rate ratio (RR) = 2·59 (95 % CI 1·95, 3·48) and RR = 1·59 (95 % CI 1·07, 2·47), respectively) and lower intakes of skimmed/1 % milk (RR = 0·42 (95 % CI 0·33, 0·53) and RR = 0·43 (95 % CI 0·31, 0·61), respectively) and trans-fat (-0·10 (95 % CI -0·18, -0·03) % of energy and -0·15 (95 % CI -0·26, -0·04) % of energy, respectively). Among Hispanics only, a lower intake of snack food (RR = 0·83 (95 % CI 0·72, 0·98)) was found and among blacks only, a higher intake of fast food (RR = 1·28 (95 % CI 1·05, 1·55)) and lower intakes of saturated fat (-0·86 (95 % CI -1·48, -0·23) % of energy), dietary fibre (0·85 (95 % CI 0·08, 1·62) g/d) and Ca (-120 (95 % CI -175, -65) mg/d) were found. Being born outside the USA was associated with more healthful nutrient intakes and less fast food. Three-year-old black and Hispanic (v. white) children ate more sugar-sweetened beverages and less low-fat dairy. Total energy intake was substantially higher in Hispanic children. Snack food (Hispanic children) and fat intakes (black children) tended to be lower. Children of immigrants ate less fast food and bad fats and more fibre.

Rapid early growth in infants may influence overweight and CVD in later life. Both rapid growth and these disease outcomes disproportionately affect some ethnic minorities. We determined ethnic differences in growth rate (Δ standard deviation scores, ΔSDS) during the first 6 months of life and assessed the explanatory role of infant feeding. Data were derived from a multiethnic cohort for the Amsterdam Born Children and their Development study (The Netherlands). Growth data (weight and length) of 2998 term-born singleton infants with no fetal growth restriction were available for five ethnic populations: Dutch (n 1619), African descent (n 174), Turkish (n 167), Moroccan (n 232) and other non-Dutch (n 806). ΔSDS for weight, length and weight-for-length between 4 weeks and 6 months were defined using internal references. Infant feeding pattern (breast-feeding duration, introduction of formula feeding and complementary feeding) in relation to ethnic differences in growth rate was examined by multivariate linear regression. Results showed that the growth rate was higher in almost all ethnic minorities, with β between 0·07 and 0·41 for ΔSDS weight and between 0·12 and 0·42 for ΔSDS length, compared with ethnic Dutch infants. ΔSDS weight-for-length was similar across groups, except for Moroccan infants (β 0·25, P < 0·05) after correction for confounders. In general, exclusive breast-feeding for 4 months was associated with slower growth for all three growth measures. Feeding factors explained, to a small degree, the higher weight and length gain in African descent infants, but not the higher ΔSDS weight-for-length in the Moroccan population. More research is needed to elucidate the underlying mechanisms of the high infant growth rate in Turkish and Moroccan infants.

Norovirus and rotavirus are the dominant pathogens causing acute gastroenteritis in children. To quantify their natural disease burden and transmission, we prospectively monitored households in an endemic setting in the Netherlands, a high-income country that does not have a rotavirus vaccination programme. We did a prospective, household survey-based cohort study in the Netherlands. Randomly selected households from the Dutch Population Register were invited to participate if they had at least three household members, including a child younger than 2 years. A member of each household was asked to record the gastrointestinal symptoms of all household members every day for 10 consecutie weeks using an interactive smartphone application. Real-time detection of acute gastroenteritis onset on the basis of entered symptoms activated requests for the case and one other household member to complete disease questionnaires and provide stool samples. Stool samples were analysed by real-time PCR for norovirus, rotavirus, adenovirus 40/41, and astrovirus. We calculated the per-pathogen proportion of households with at least one secondary acute gastroenteritis episode (epidemiologically but not microbiologically linked), the probability of a secondary episode in household members at risk (secondary attack rate), and the microbiologically confirmed symptomatic and asymptomatic transmission rates. During two seasons (January to March) in 2016 and 2017, 30 660 households were invited to participate, of which 604 households including 2298 individuals were enrolled. 697 acute gastroenteritis episodes were detected in 358 households, with samples obtained from 609 (87%) of 697 episodes. Norovirus (150 [25%] of 609 cases) and rotavirus (91 [15%] cases) were most frequently detected. Astrovirus was detected in 50 (8%) samples and adenovirus 40/41 in 24 (4%) samples. Overall disease severity was higher in patients with rotavirus-positive acute gastroenteritis than those with norovirus-positive acute gastroenteritis. Norovirus led to higher disease burden in adults than did rotavirus. Following an index case, a secondary acute gastroenteritis episode occurred in 34 (35%) of 96 households for norovirus and 26 (46%) of 56 households for rotavirus. Secondary attack rates were 15% (37 of 244 participants) for norovirus and 28% (33 of 120 participants) for rotavirus and asymptomatic transmission rates were 51% (52 of 102 household members) for norovirus and 22% (12 of 55 household members) for rotavirus. The microbiologically confirmed symptomatic transmission rate for norovirus was 10% (25 of 254 household members) and 18% for rotavirus (21 of 119 household members). In households with young family members in a setting without rotavirus vaccination, norovirus is the dominant acute gastroenteritis pathogen, but rotavirus is associated with more severe disease. There was substantial within-household transmission, both symptomatic and asymptomatic. The study provides key quantities on transmission, which can inform vaccine policy decisions and act as a baseline for impact evaluations in high-income settings. The Netherlands Organisation for Health Research and Development (grant 91616158).

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.

Household transmission studies are useful to quantify SARS-CoV-2 transmission dynamics. We conducted a remote prospective household study to quantify transmission, and the effects of subject characteristics, household characteristics, and implemented infection control measures on transmission. Households with a laboratory-confirmed SARS-CoV-2 index case were enrolled < 48 h following test result. Follow-up included digitally daily symptom recording, regular nose-throat self-sampling and paired dried blood spots from all household members. Samples were tested for virus detection and SARS-CoV-2 antibodies. Secondary attack rates (SARs) and associated factors were estimated using logistic regression. In 276 households with 920 participants (276 index cases and 644 household members) daily symptom diaries and questionnaires were completed by 95%, and > 85% completed sample collection. 200 secondary SARS-CoV-2 infections were detected, yielding a household SAR of 45.7% (95% CI 39.7–51.7%) and per-person SAR of 32.6% (95%CI: 28.1-37.4%). 126 (63%) secondary cases were detected at enrollment. Mild (aRR = 0.57) and asymptomatic index cases (aRR = 0.29) were less likely to transmit SARS-CoV-2, compared to index cases with an acute respiratory illness (p = 0.03 for trend), and child index cases (< 12 years aRR = 0.60 and 12-18 years aRR = 0.85) compared to adults (p = 0.03 for trend). Infection control interventions in households had no significant effect on transmission. We found high SARs with the majority of transmissions occuring early after SARS-CoV-2 introduction into the household. This may explain the futile effect of implemented household measures. Age and symptom status of the index case influence secondary transmission. Remote, digitally-supported study designs with self-sampling are feasible for studying transmission under pandemic restrictions.

BackgroundClinical practice guidelines focusing on judicious use of antibiotics for childhood acute otitis media (AOM) have been introduced in many countries around the world.ObjectiveTo systematically review the effects of these guidelines on the prescription of antibiotics and analgesics for children with AOM.MethodsSystematic searches of PubMed, Embase and Cochrane Library from inception to 6 June 2017 using broad search terms. Studies specifically aimed at evaluating the effects of introduction of national AOM practice guidelines on type of antibiotic and/or analgesic prescriptions were included, irrespective of design, setting or language. The Risk Of Bias In Non-randomized Studies of Interventions tool was used to assess risk of bias.ResultsOf 411 unique records retrieved, seven studies conducted in six different countries (France, Italy, Spain, Sweden, UK and USA (twice)) compared data before and after guideline introduction. All studies had an observational design, using longitudinal data of children aged under 15 years (n=200–4.6 million) from either routine care, insurance databases or electronic surveys. Risk of bias of all studies was judged serious to critical.Of the five studies reporting on antibiotic prescription rates, three showed a decline of 5%–12% up to 3 years after guideline introduction and two found no or negligible effect. In one US study, the initial 9% decline decreased to 5% after 4–6 years. The recommended first choice antibiotic was prescribed more frequently (9%–58% increase) after guideline introduction in four out of five studies reporting on this outcome. Analgesic prescription rates for AOM were reported in one US study and increased from 14% to 24% after guideline introduction.ConclusionBased upon what is published, the effects of introduction of national clinical practice guidelines on antibiotic and analgesic prescribing for children with AOM seem modest at the most.RegistrationPROSPERO: CRD42016050976.