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.

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.

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.

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.

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.

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.

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.

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).

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.

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 acute otitis media clinical practice guidelines on antibiotic and analgesic prescriptions: a systematic review.

BACKGROUND: Clinical practice guidelines focusing on judicious use of antibiotics for childhood acute otitis media (AOM) have been introduced in many countries around the world. OBJECTIVE: To systematically review the effects of these guidelines on the prescription of antibiotics and analgesics for children with AOM. METHODS: Systematic 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. RESULTS: Of 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. CONCLUSION: Based 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. REGISTRATION: PROSPERO: CRD42016050976.

Report of the 5th European expert meeting on rotavirus vaccination (EEROVAC).

The Fifth European Expert Meeting on Rotavirus Vaccination was convened in Utrecht, The Netherlands, in March 2017. The 2-day meeting included invited lectures as well as original oral and poster presentations and brought together experts from 21 countries. Summary findings of the meeting include: Rotavirus vaccination programmes in Europe have resulted in reductions of 60-90% in rotavirus outpatient visits and hospitalizations. Long term trends indicate this impact is sustained over the years. Herd effects, protecting unvaccinated children and neonates too young to be vaccinated have been observed in many European countries. Early evidence now also suggests that rotavirus vaccination may be instrumental in the prevention of celiac disease. Special attention should be given to preterm infants, who may age out of the vaccination window before hospital discharge and to HIV infected children who are at increased risk of severe rotavirus AGE. There is a small but increased risk of IS following rotavirus vaccination and parents should therefore be informed about possible signs and symptoms of IS. New insights in rotavirus genetic susceptibility and interactions with microbiome may open opportunities for interventions to improve protection by vaccination, in particular in LMIC. The development of several novel rotavirus vaccines discussed at the meeting is also promising in this respect.

Acute Otitis Media During Infancy: Parent-reported Incidence and Modifiable Risk Factors.

BACKGROUND: Age at exposure to acute otitis media (AOM) risk factors such as day care attendance, lack of breastfeeding and tobacco smoke is little studied but important for targeting AOM prevention strategies. Moreover, studies are typically restricted to clinically diagnosed AOM, while a significant subset can occur outside the health care system, depending on the country setting. This study aims to determine risk factor exposure and effect of its timing within the first year of life on parent-reported AOM symptom episodes. METHODS: In the WHeezing and Illnesses STudy LEidsche Rijn birth-cohort study, 1056 children were prospectively followed during their first year of life. Group day care attendance, breastfeeding and tobacco smoke exposure were recorded monthly and parent-reported AOM symptoms daily. Generalized estimating equations were used to estimate the association between the time-varying risk factors and AOM symptom episodes, while correcting for confounding by indication. RESULTS: The first-year incidence rate of parent-reported AOM was 569/1000 child-years [95% confidence interval (CI): 523-618]. Children who attended day care had higher odds of developing AOM symptom episodes compared with those not attending (odds ratio: 5.0; 95% CI: 2.6-9.6). Tobacco smoke exposure and (a history of) breastfeeding were not associated with AOM. Test for interaction revealed that the effect of day care increased with each month younger in age. CONCLUSIONS: First-year day care attendance is a major risk factor for AOM symptom episodes among infants in the community. This adjusted effect estimate is higher than previously reported and is age-dependent. AOM prevention strategies in day care facilities should therefore focus in particular on the youngest age groups.

Antibiotic Treatment for First Episode of Acute Otitis Media Is Not Associated with Future Recurrences.

OBJECTIVE: Antibiotic treatment of acute otitis media (AOM) has been suggested to increase the risk of future AOM episodes by causing unfavorable shifts in microbial flora. Because current evidence on this topic is inconclusive and long-term follow-up data are scarce, we wanted to estimate the effect of antibiotic treatment for a first AOM episode occurring during infancy on AOM recurrences and AOM-related health care utilization later in life. METHODS: We obtained demographic information and risk factors from data of the Wheezing Illnesses Study Leidsche Rijn, a prospective birth cohort study in which all healthy newborns born in Leidsche Rijn (between 2001 and 2012), The Netherlands, were enrolled. These data were linked to children's primary care electronic health records up to the age of four. Children with at least one family physician-diagnosed AOM episode before the age of two were included in analyses. The exposure of interest was the prescription of oral antibiotics (yes vs no) for a child's first AOM episode before the age of two years. RESULTS: 848 children were included in analyses and 512 (60%) children were prescribed antibiotics for their first AOM episode. Antibiotic treatment was not associated with an increased risk of total AOM recurrences (adjusted rate ratio: 0.94, 95% CI: 0.78-1.13), recurrent AOM (≥3 episodes in 6 months or ≥4 in one year; adjusted risk ratio: 0.79, 95% CI: 0.57-1.11), or with increased AOM-related health care utilization during children's first four years of life. CONCLUSIONS: Oral antibiotic treatment of a first AOM episode occurring during infancy does not affect the number of AOM recurrences and AOM-related health care utilization later in life. This information can be used when weighing the pros and cons of various AOM treatment options.

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.

First-year Daycare and Incidence of Acute Gastroenteritis.

BACKGROUND: Daycare attendance has been associated with increased acute gastroenteritis (AGE) incidence in the first years of life. We investigated the effects of first-year daycare attendance on AGE incidence and primary care contact rate up to age 6 years. METHODS: Children enrolled in the Wheezing Illnesses Study Leidsche Rijn cohort were managed until age 6 years. Data on primary care diagnosed AGE episodes and number of associated contacts per episode were collected from health records. Children were categorized according to first year daycare attendance and age-month at entry when applicable. Generalized estimating equations were used to assess associations between first-year daycare and AGE incidence or primary care contact rate. RESULTS: A total of 1344 out of 2220 children (83%) attended daycare before age 1 year. Overall, the 6-year primary care AGE incidence rate (IR) among first-year daycare attendees and nonattendees was comparable (IR: 12.2/100 vs 13.3/100 child-years). First-year daycare attendees had a higher AGE incidence during the first year (IRR: 1.13; 95% confidence interval: 1.06-1.21) and lower during the third to sixth year of age compared with nonattendees (P < .001). The daycare-associated increase in AGE incidence was most pronounced during the first 12 months after enrollment into daycare and demonstrated clear seasonality. A similar pattern was observed for primary care contact rate per AGE episode. CONCLUSIONS: First-year daycare attendance advances the timing of AGE infections, resulting in increased AGE disease burden in the first year and relative protection thereafter. Protection against AGE infection persists at least up to age 6 years. Future studies should address whether this protective effect persists during later childhood.

Lack of Impact of Body Mass Index at Young Age on Otitis Media Occurrence During Preschool Years: Wheezing Illnesses Study Leidsche Rijn Cohort Study.

Using data on weight and height at 6 and 11 months of age and primary care electronic health records data from 1960 children participating in the Wheezing Illnesses Study Leidsche Rijn birth cohort study, we found that body mass index at 6 and 11 months of age was not associated with otitis media occurrence during the first 4 years of life.

Parent-reported symptoms of acute otitis media during the first year of life: what is beneath the surface?

BACKGROUND: Most estimates of the incidence of acute otitis media (AOM) are based on general practitioner (GP) or pediatrician diagnoses. It is likely that these figures underestimate the community incidence of AOM since parents do not visit their doctor every time their child suffers from acute ear symptoms. The impact of these symptom episodes may be substantial since they affect the child's quality of life and parents' productivity. METHODS: To determine AOM symptoms in the community, we measured parent-reported AOM symptoms daily for 12 consecutive months in 1,260 children participating in a prospective birth cohort in the Netherlands. The mean age of these children was at study enrollment 0.9 months (standard deviation 0.6). A parent-reported AOM symptom episode was defined as fever (temperature 38˚C or above) plus at least one of the following symptoms: ear pain and ear discharge. These febrile AOM symptom episodes were linked to GP-consultations and diagnoses in the GP electronic health records. RESULTS: With an estimated 624 parent-reported symptom episodes per 1,000 child-years (95% CI: 577 to 674) incidence of febrile AOM symptoms during the child's first year is high. The GP was consulted in half of these symptom episodes and AOM was diagnosed in 49% of these consultations. CONCLUSIONS AND RELEVANCE: The incidence of febrile AOM symptoms in the first year of life is high in Dutch children and leads to a GP-consultation in only half of the cases. This suggests that AOM symptomatology in the community is underestimated when focusing on GP-diagnosed AOM episodes alone, since a considerable proportion of febrile AOM symptom episodes are treated symptomatically by parents at home and do not come to the attention of the GP. Having data on community AOM symptomatology available for each country is important when the potential impact of preventive and therapeutic interventions for AOM are studied.