Addressing current limitations of household transmission studies by collecting contact data.

Modeling studies of household transmission data have helped characterize the role of children in influenza and COVID-19 epidemics. However, estimates from these studies may be biased since they do not account for the heterogeneous nature of household contacts. Here, we quantified the impact of contact heterogeneity between household members on the estimation of child relative susceptibility and infectivity. We simulated epidemics of SARS-CoV-2-like and influenza-like infections in a synthetic population of 1,000 households assuming heterogeneous contact levels. Relative contact frequencies were derived from a household contact study according to which contacts are more frequent in the father-mother pair, followed by the child-mother, child-child, and finally child-father pairs. Child susceptibility and infectivity were then estimated while accounting for heterogeneous contacts or not. When ignoring contact heterogeneity, child relative susceptibility was underestimated by approximately 20% in the two disease scenarios. Child relative infectivity was underestimated by 20% when children and adults had different infectivity levels. These results are sensitive to our assumptions of European-style household contact patterns; but they highlight that household studies collecting both disease and contact data are needed to assess the role of complex household contact behavior on disease transmission and improve estimation of key biological parameters.

SARS-CoV-2 outbreaks in secondary school settings in the Netherlands during fall 2020; silent circulation.

BACKGROUND: In fall 2020 when schools in the Netherlands operated under a limited set of COVID-19 measures, we conducted outbreaks studies in four secondary schools to gain insight in the level of school transmission and the role of SARS-CoV-2 transmission via air and surfaces. METHODS: Outbreak studies were performed between 11 November and 15 December 2020 when the wild-type variant of SARS-CoV-2 was dominant. Clusters of SARS-CoV-2 infections within schools were identified through a prospective school surveillance study. All school contacts of cluster cases, irrespective of symptoms, were invited for PCR testing twice within 48 h and 4-7 days later. Combined NTS and saliva samples were collected at each time point along with data on recent exposure and symptoms. Surface and active air samples were collected in the school environment. All samples were PCR-tested and sequenced when possible. RESULTS: Out of 263 sampled school contacts, 24 tested SARS-CoV-2 positive (secondary attack rate 9.1%), of which 62% remained asymptomatic and 42% had a weakly positive test result. Phylogenetic analysis on 12 subjects from 2 schools indicated a cluster of 8 and 2 secondary cases, respectively, but also other distinct strains within outbreaks. Of 51 collected air and 53 surface samples, none were SARS-CoV-2 positive. CONCLUSION: Our study confirmed within school SARS-CoV-2 transmission and substantial silent circulation, but also multiple introductions in some cases. Absence of air or surface contamination suggests environmental contamination is not widespread during school outbreaks.

Transmission of SARS-CoV-2 within households: a remote prospective cohort study in European countries.

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.

Mental Well-being and General Health in Adolescents with Asthma: The Prevention and Incidence of Asthma and Mite Allergy Birth Cohort Study.

OBJECTIVES: To assess whether adolescents with asthma experience a lower mental well-being and lower general health than their peers without asthma. STUDY DESIGN: Data from the Prevention and Incidence of Asthma and Mite Allergy study were used. At the ages of 11, 14, 17, and 20 years, 2651, 2522, 2094, and 2206 participants, respectively, completed questionnaires. Their parents completed questionnaires at the ages of 11 (n = 2660), 14 (n = 2338), and 17 years (n = 1872). Asthma was defined according to the Mechanisms of the Development of Allergy criteria. Mental well-being was measured using the Mental Health Index-5 and was reported by the adolescents. General health, measured on a 4-point Likert scale, was reported by the adolescents and their parents. We estimated associations of asthma with mental well-being and perceived general health using generalized estimating equations. RESULTS: At ages 11, 14, 17, and 20 years, 6.7%, 6.9%, 5.0%, and 6.6%, respectively, of the adolescents had asthma. Adolescents with asthma did not score differently on the Mental Health Index than their peers without asthma. Adolescents with asthma were less likely to experience good or excellent health than their peers without asthma (aOR, 0.37; 95% CI, 0.26-0.51 for intermittent asthma and 0.33; 95% CI, 0.25-0.41 for persistent asthma). These results remain similar across the different ages. CONCLUSIONS: The mental well-being of adolescents with asthma is similar to that of their peers without asthma, although adolescents with asthma are less likely to perceive a good or excellent general health.

Impact of Repeated Influenza Immunization on Respiratory Illness in Children With Preexisting Medical Conditions.

PURPOSE: Annual influenza immunization in medical risk groups is recommended in many countries. Recent evidence suggests that repeated inactivated influenza vaccine (IIV) immunization throughout childhood may impair long-term immunity against influenza. We assessed whether prior immunization altered the effect of IIV in children with preexisting medical conditions on primary care-diagnosed respiratory illness (RI) episodes during the influenza season. METHODS: Electronic records of IIV-immunized children who met the criteria for annual IIV immunization according to Dutch guidelines were extracted from a primary care database from 2004 to 2015. For each year, we collected information on IIV immunization status, primary care-attended RI episodes (including influenza-like illness, acute RI, and asthma exacerbation), and potential confounders. Generalized estimating equations were used to model the association between prior IIV and occurrence of at least one RI episode during the influenza season, with "current year immunized but without IIV history" as reference group. RESULTS: A total of 4,183 children (follow-up duration: 11,493 child-years) were IIV immunized at least once. Adjusted estimates showed lower odds for RI in current year-immunized children with prior IIV compared with those without (odds ratio [OR] = 0.61; 95% CI, 0.47-0.78 for "current year immunized and one IIV in previous 2 years"; OR = 0.85; 95% CI, 0.68-1.07 for "current year immunized and ≥2 IIVs in previous 3 years, including prior year"). CONCLUSION: Repeated IIV immunization in children with preexisting medical conditions has no negative impact on, and may even increase, long-term protection against RI episodes diagnosed during the influenza season in primary care.

Impact of Early-Onset Acute Otitis Media on Multiple Recurrences and Associated Health Care Use.

OBJECTIVE: To quantify the critical age period of first episode of acute otitis media (AOM) and its consequences for AOM recurrences and AOM health care use. STUDY DESIGN: Children enrolled in the Wheezing-Illnesses-STudy-LEidsche-Rijn cohort with at least 1 episode of AOM documented in their primary care health record before 2 years of age were followed until 6 years of age. Data on episodes of AOM and associated primary care consultations, antibiotic prescriptions, and specialist referrals were retrieved. Regression models assessed the presence and shape of the associations between age of first AOM and subsequent episodes of AOM and health care use. RESULTS: A total of 796 of 2026 children (39%) experienced a first AOM before 2 years of age. Each month decrease in age at first AOM in the first 2 years of life increased the risk of developing recurrent AOM (≥3 AOM episodes in 6 months or ≥ 4 in 1 year) linearly by 6% (adjusted risk ratio: 1.06; 95% CI: 1.02-1.10). For first AOM occurring before 9 months, the cumulative 6-year primary care consultation rate increased by 8% (adjusted incidence rate ratio: 1.08; 95% CI: 1.03-1.15) and the associated specialist referral increased by 16% (adjusted risk ratio: 1.16; 95% CI: 1.07-1.27) for each month decrease in age. No associations were found between age at first AOM and total AOM episodes or antibiotic prescriptions. CONCLUSIONS: The association between earlier age of first AOM and recurrent AOM as well as total health care use during childhood is particularly strong before 9 months of age.

Impact of early daycare on healthcare resource use related to upper respiratory tract infections during childhood: prospective WHISTLER cohort study.

BACKGROUND: Daycare attendance is an established risk factor for upper respiratory tract infections (URTI) and acute otitis media (AOM). Whether this results in higher use of healthcare resources during childhood remains unknown. We aim to assess the effect of first year daycare attendance on the timing and use of healthcare resources for URTI and AOM episodes during early childhood. METHODS: In the Wheezing-Illnesses-STudy-LEidsche-Rijn birth cohort, 2,217 children were prospectively followed up to age six years. Children were categorized according to first-year daycare attendance (yes versus no) and age at entry when applicable (age 0 to 2 months, 3 to 5 months and 6 to 12 months). Information on general practitioner (GP) diagnosed URTI and AOM, GP consultations, antibiotic prescriptions and specialist referral was collected from medical records. Daycare attendance was recorded by monthly questionnaires during the first year of life. RESULTS: First-year daycare attendees and non-attendees had similar total six-year rates of GP-diagnosed URTI and AOM episodes (59/100 child-years, 95% confidence interval 57 to 61 versus 56/100 child-years, 53 to 59). Daycare attendees had more GP-diagnosed URTI and AOM episodes before the age of one year and fewer beyond the age of four years than non-attendees (Pinteraction <0.001). Daycare attendees had higher total six-year rates for GP consultation (adjusted rate ratio 1.15, 1.00 to 1.31) and higher risk for specialist referrals (hazard ratio: 1.43, 1.01 to 2.03). The number of antibiotic prescriptions in the first six years of life was only significantly increased among children who entered daycare between six to twelve months of age (rate ratio 1.32, 1.04 to 1.67). This subgroup of child-care attendees also had the highest overall URTI and AOM incidence rates, GP consultation rates and risk for specialist referral. CONCLUSIONS: Children who enter daycare in the first year of life, have URTI and AOM at an earlier age, leading to higher use of healthcare resources compared to non-attendees, especially when entering daycare between six to twelve months. These findings emphasize the need for improved prevention strategies in daycare facilities to lower infection rates at the early ages.

Racial/ethnic and immigrant differences in early childhood diet quality.

OBJECTIVE: 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. DESIGN: 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. SETTING: Project Viva, Boston (MA), USA. SUBJECTS: Children aged 3 years (n 898). RESULTS: 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. CONCLUSIONS: 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.

Influenza Infection and Acute Myocardial Infarction.

BACKGROUND: Acute respiratory infections can trigger acute myocardial infarction. We aimed to quantify the association between laboratory-confirmed influenza infection and acute myocardial infarction, particularly in patients with and without known coronary artery disease. METHODS: This observational, registry-based, self-controlled case series study evaluated the association between laboratory-confirmed influenza infection and occurrence of acute myocardial infarction. Laboratory records on respiratory virus polymerase chain reaction (PCR) testing from 16 laboratories across the Netherlands were linked to national mortality, hospitalization, medication, and administrative registries. Influenza infection was defined as a positive PCR test result. Acute myocardial infarction was defined as a registered diagnostic code for either acute myocardial infarction hospitalization or death. Using a self-controlled case series method, we then compared the incidence of acute myocardial infarction during the risk period (days 1 to 7 after influenza infection) versus the control period (1 year before and 51 weeks after the risk period). RESULTS: Between 2008 and 2019, we identified 158,777 PCR tests for influenza in the study population; 26,221 were positive for influenza, constituting 23,405 unique influenza illness episodes. A total of 406 episodes were identified with acute myocardial infarction occurring within 1 year before and 1 year after confirmed influenza infection and were included in analysis. Twenty-five cases of acute myocardial infarction occurred during the risk period versus 394 during the control period. The adjusted relative incidence of acute myocardial infarction during the risk period compared with the control period was 6.16 (95% confidence interval [CI], 4.11 to 9.24). The relative incidence of acute myocardial infarction in individuals without prior hospitalization for coronary artery disease was 16.60 (95% CI, 10.45 to 26.37) compared with 1.43 (95% CI, 0.53 to 3.84) for those with prior admission for coronary artery disease. CONCLUSIONS: Influenza infection was associated with an increased risk of acute myocardial infarction, especially in individuals without a prior hospitalization for coronary artery disease. (Funded by the Dutch Research Council [NWO].).

Age-specific SARS-CoV-2 transmission differed from human rhinovirus in households during the early COVID-19 pandemic.

OBJECTIVES: Children are generally considered main drivers of transmission for respiratory viruses, but the emergence of SARS-CoV-2 challenged this paradigm. Human rhinovirus (RV) continued to co-circulate throughout the pandemic, allowing for direct comparison of age-specific infectivity and susceptibility within households between these viruses during a time of low SARS-CoV-2 population immunity. METHODS: Households with children were prospectively monitored for ≥23 weeks between August 2020 and July 2021. Upon onset of respiratory symptoms in a household, an outbreak study was initiated, including questionnaires and repeated nasal self-sampling in all household members. Swabs were tested by PCR. Age-stratified within-household secondary attack rates (SARs) were compared between SARS-CoV-2 and RV. RESULTS: A total of 307 households participated, including 582 children and 627 adults. Overall, SAR was lower for SARS-CoV-2 than for RV (aOR 0.55) and age distributions differed between both viruses (p < 0.001). Following household exposure, children were significantly less likely to become infected with SARS-CoV-2 compared to RV (aOR 0.16), whereas this was opposite in adults (aOR 1.71). CONCLUSION: In households, age-specific susceptibility to SARS-CoV-2 and RV differs and drives differences in household transmission between these pathogens. This highlights the importance of characterizing age-specific transmission risks, particularly for emerging infections, to guide appropriate infection control interventions.

Infant nutrition in relation to eating behaviour and fruit and vegetable intake at age 5 years.

Infant nutrition may influence eating behaviour and food preferences in later life. The present study explores whether exclusive breast-feeding duration and age at introduction of solid foods are associated with children's eating behaviour and fruit and vegetable intake at age 5 years. Data were derived from the Amsterdam Born Children and their Development study, a prospective birth cohort in the Netherlands, and included 3624 children. During infancy, data on infant nutrition were collected. Child eating behaviour (satiety responsiveness, enjoyment of food, slowness in eating and food responsiveness) was assessed with the Children's Eating Behaviour Questionnaire; and fruit and vegetable intake was calculated from a validated child FFQ. Both questionnaires were filled in by the mothers after their child turned 5 years. Exclusive breast-feeding duration was not associated with later eating behaviour, although longer exclusive breast-feeding was significantly associated with a higher vegetable intake at age 5 years. Compared with the introduction of solid foods at age 6 months, introduction before the age of 4 months was associated with less satiety responsiveness at age 5 years (ß -0·09; 95 % CI -0·16, -0·02). Introducing solid foods after 6 months was associated with less enjoyment of food (ß -0·07; 95 % CI -0·12, -0·01) and food responsiveness (ß -0·04; 95 % CI -0·07, -0·01). Introducing solid foods before the age of 4 months was associated with a higher fruit intake compared with introduction at 6 months. These findings suggest that prolonged breast-feeding and introduction of solid foods between 4 and 6 months may lead to healthier eating behaviour and food preferences at age 5 years.

Impact of 7-valent versus 10-valent pneumococcal conjugate vaccines on primary care consultations across various age groups in the Netherlands, 5 years after the switch: A time-series analysis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Longitudinal Household Assessment of Respiratory Illness in Children and Parents During the COVID-19 Pandemic.

Importance: In the early COVID-19 pandemic, SARS-CoV-2 testing was only accessible and recommended for symptomatic persons or adults. This restriction hampered assessment of the true incidence of SARS-CoV-2 infection in children as well as detailed characterization of the SARS-CoV-2 disease spectrum and how this spectrum compared with that of other common respiratory illnesses. Objective: To estimate the community incidence of SARS-CoV-2 infection in children and parents and to assess the symptoms and symptom severity of respiratory illness episodes involving SARS-CoV-2-positive test results relative to those with SARS-CoV-2-negative test results. Design, Setting, and Participants: This cohort study randomly selected Dutch households with at least 1 child younger than 18 years. A total of 1209 children and adults from 307 households were prospectively followed up between August 25, 2020, and July 29, 2021, covering the second and third waves of the COVID-19 pandemic. Participation included SARS-CoV-2 screening at 4- to 6-week intervals during the first 23 weeks of participation (core study period; August 25, 2020, to July 29, 2021). Participants in all households finishing the core study before July 1, 2021, were invited to participate in the extended follow-up and to actively report respiratory symptoms using an interactive app until July 1, 2021. At new onset of respiratory symptoms or a SARS-CoV-2 positive test result, a household outbreak study was initiated, which included daily symptom recording, repeated polymerase chain reaction testing (nose-throat swabs and saliva and fecal samples), and SARS-CoV-2 antibody measurement (paired dried blood spots) in all household members. Outbreaks, households, and episodes of respiratory illness were described as positive or negative depending on SARS-CoV-2 test results. Data on participant race and ethnicity were not reported because they were not uniformly collected in the original cohorts and were therefore not representative or informative. Exposures: SARS-CoV-2-positive and SARS-CoV-2-negative respiratory illness episodes. Main Outcomes and Measures: Age-stratified incidence rates, symptoms, and symptom severity for SARS-CoV-2-positive and SARS-CoV-2-negative respiratory illness episodes. Results: Among 307 households including 1209 participants (638 female [52.8%]; 403 [33.3%] aged <12 years, 179 [14.8%] aged 12-17 years, and 627 [51.9%] aged ≥18 years), 183 household outbreaks of respiratory illness were observed during the core study and extended follow-up period, of which 63 (34.4%) were SARS-CoV-2 positive (59 outbreaks [32.2%] during the core study and 4 outbreaks [2.2%] during follow-up). SARS-CoV-2 incidence was similar across all ages (0.24/person-year [PY]; 95% CI, 0.21-0.28/PY). Overall, 33 of 134 confirmed SARS-CoV-2 episodes (24.6%) were asymptomatic. The incidence of SARS-CoV-2-negative respiratory illness episodes was highest in children younger than 12 years (0.94/PY; 95% CI, 0.89-0.97/PY). When comparing SARS-CoV-2-positive vs SARS-CoV-2-negative respiratory illness episodes in children younger than 12 years, no differences were observed in number of symptoms (median [IQR], 2 [2-4] for both groups), symptom severity (median [IQR] maximum symptom severity score, 6 [4-9] vs 7 [6-13]), or symptom duration (median [IQR], 6 [5-12] days vs 8 [4-13] days). However, among adults, SARS-CoV-2-positive episodes had a significantly higher number (median [IQR], 6 [4-8] vs 3 [2-4]), severity (median [IQR] maximum symptom severity score, 15 [9-19] vs 7 [6-11]), and duration (median [IQR] 13 [8-29] days vs 5 [3-11] days; P < .001 for all comparisons) of symptoms vs SARS-CoV-2-negative episodes. Conclusions and Relevance: In this cohort study, during the first pandemic year when mostly partial or full in-person learning occurred, the SARS-CoV-2 incidence rate in children was substantially higher than estimated from routine testing or seroprevalence data and was similar to that of adult household members. Unlike in unvaccinated adults, SARS-CoV-2 symptoms and symptom severity in children were similar to other common respiratory illnesses. These findings may prove useful when developing pediatric COVID-19 vaccine recommendations.

The role of infant feeding practices in the explanation for ethnic differences in infant growth: the Amsterdam Born Children and their Development study.

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 ß 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 (ß 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.

Overweight at age two years in a multi-ethnic cohort (ABCD study): the role of prenatal factors, birth outcomes and postnatal factors.

BACKGROUND: Childhood overweight/obesity is a major public health problem worldwide which disproportionally affects specific ethnic groups. Little is known about whether such differences already exist at an early age and which factors contribute to these ethnic differences. Therefore, the present study assessed possible ethnic differences in overweight at age 2 years, and the potential explanatory role of prenatal factors, birth outcomes and postnatal factors. METHODS: Data were derived from a multi-ethnic cohort in the Netherlands (the ABCD study). Weight and height data of 3,156 singleton infants at age 2 years were used. Five ethnic populations were distinguished: Dutch native (n = 1,718), African descent (n = 238), Turkish (n = 162), Moroccan (n = 245) and other non-Dutch (n = 793). Overweight status was defined by the International Obesity Task Force guidelines. The explanatory role of prenatal factors, birth outcomes and postnatal factors in ethnic disparities in overweight (including obesity) was assessed by logistic regression analysis. RESULTS: Compared to the native Dutch (7.1%), prevalence of overweight was higher in the Turkish (19.8%) and Moroccan (16.7%) group, whereas the prevalence was not increased in the African descent (9.2%) and other non-Dutch (8.8%) group. Although maternal pre-pregnancy body mass index partly explained the ethnic differences, the odds ratio (OR) of being overweight remained higher in the Turkish (OR: 2.66; 95%CI: 1.56-4.53) and Moroccan (OR: 2.11; 95%CI: 1.31-3.38) groups after adjusting for prenatal factors. The remaining differences were largely accounted for by weight gain during the first 6 months of life (postnatal factor). Maternal height, birth weight and gender were independent predictors for overweight at age 2 years, but did not explain the ethnic differences. CONCLUSION: Turkish and Moroccan children in the Netherlands have 2- to 3-fold higher odds for being overweight at age 2 years, which is largely attributed to maternal pre-pregnancy BMI and weight gain during the first 6 months of life. Further study on the underlying factors of this early weight gain is required to tackle ethnic differences in overweight among these children.

Experiences and needs of persons living with a household member infected with SARS-CoV-2: A mixed method study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Community burden and transmission of acute gastroenteritis caused by norovirus and rotavirus in the Netherlands (RotaFam): a prospective household-based cohort study.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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). INTERPRETATION: 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. FUNDING: The Netherlands Organisation for Health Research and Development (grant 91616158).

Defining asthma in children: how well do parents, doctors and spirometry agree?

BACKGROUND: Because diagnosing asthma in school-aged children is challenging, a variety of proxies for asthma are used in clinical practice and research settings as indicators of this disease. We aimed to provide insight into the agreement between various asthma indicators based on parental report, medical diagnosis and spirometry. METHODS: Children from the WHISTLER birth cohort performed spirometry and were followed up with parental ISAAC (International Study of Asthma and Allergies in Childhood) questionnaires about asthma at 5 and 8 years of age. Medical data were extracted from primary care records. We compared 15 asthma indicators based on parental report, medical diagnosis and spirometry using positive agreement, κ statistics and latent class cluster analysis. RESULTS: At 5 years of age, 1007 children completed a study visit, while 803 children visited at 8 years of age. Depending on the indicator, the responder and child's age, the asthma prevalence ranged from 0.2% to 26.6%. Cluster analysis revealed classes related to the presence of recent symptoms and a decreased lung function. Agreement between parents and doctors was generally low with κ coefficients ranging from 0.07 (recent wheeze) to 0.52 (recent asthma medication). Additionally, parental report showed to be sensitive to recall bias over time. CONCLUSIONS: Dependent on the asthma indicator, the responder and the age of the child, substantial differences in agreement were observed between commonly used indicators associated with asthmatic disease in school-aged children. Most agreement between parents and doctors was seen for objective and recent indicators such as the recent use of asthma medication. We advocate caution when literature with different asthma indicators is compared.

Cost-effectiveness of inactivated influenza vaccination in children with medical risk conditions in the Netherlands.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Inactivated influenza vaccine does not reduce all cause respiratory illness in children with pre-existing medical conditions.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: IIV immunization in children with pre-existing medical conditions does not reduce all cause RI episodes encountered in primary care during the influenza season.