key: cord-0258122-l6myqyv3 authors: Temte, J. L.; Barlow, S.; Goss, M.; Temte, E.; Schemmel, A.; Maerz, B.; Bell, C.; Comp, L.; Arnold, M.; Breunig, K.; Clifford, S.; Reisdorf, E.; Shult, P.; Wedig, M.; Haupt, T.; Conway, J.; Gangnon, R.; Fowlkes, A.; Uzicanin, A. title: The Oregon Child Absenteeism Due to Respiratory Disease Study (ORCHARDS):Rationale, Objectives, and Design date: 2021-02-04 journal: nan DOI: 10.1101/2021.02.01.21250878 sha: 7a1fc1c610320ad9ae71e8bee6cc06ddb1a9ace6 doc_id: 258122 cord_uid: l6myqyv3 Background: Influenza viruses pose significant disease burdens through annual seasonal outbreaks and unpredictable pandemics. Existing influenza surveillance programs have relied heavily on reporting of medically attended influenza (MAI). Continuously monitoring cause-specific school absenteeism may identify local activity acceleration of seasonal influenza. The Oregon Child Absenteeism Due to Respiratory Disease Study (ORCHARDS; Oregon, WI) implements daily school-based monitoring of influenza-like illness-specific student absenteeism (a-ILI) in pre-kindergarten through grade 12 schools and assesses this approach for early detection of accelerated influenza and other respiratory pathogen transmission in schools and surrounding communities. Methods: Starting in September 2014, ORCHARDS has combined reporting of daily absenteeism though automated processes within 6 schools and home visits to school children with acute respiratory infections (ARI). Demographic, epidemiological, and symptom data are collected along with respiratory specimens. Specimens are tested for influenza and other respiratory viruses. Household members may participate in a supplementary household transmission study. Community comparisons are made possible using a pre-existing, long-standing, and highly effective influenza surveillance program, based on MAI at 5 primary care clinics in the same geographical area. Results: Over the first 5 years, a-ILI occurred on 6,634 (0.20%) of 3,260,461 student school days. Viral pathogens were detected in 64.5% of 1,728 children visited at home with ARI. Influenza was the most commonly detected virus, noted in 23.3% of ill students. Influenza (p<0.001) and adenovirus (P=0.004) were significantly associated with a-ILI. Discussion: ORCHARDS uses a community-based design to detect and evaluate influenza trends over multiple seasons and to evaluate the utility of absenteeism for early detection of accelerated influenza and other respiratory pathogen transmission in schools and surrounding communities. Initial findings suggest the study design is succeeding in collecting appropriate data to achieve study objectives. continuously monitoring cause-specific absenteeism, such as ILI, over the entire school year to identify local activity acceleration of seasonal influenza is not well researched or understood. II. ORCHARDS overview statement. The goal of Oregon Child Absenteeism Due to Respiratory Disease Study (ORCHARDS) is to develop and implement a system for daily school-based monitoring of ILIspecific student absenteeism in pre-kindergarten (4K) through grade 12 schools and assess the system's usability for early detection of accelerated influenza and other respiratory pathogen transmission in schools and surrounding communities. The theoretical relationships between influenza infection in school-aged children, K-12 absenteeism, and influenza infection in the surrounding community are demonstrated in Figure 1 . • Develop an automated cause-specific school absentee monitoring system to identify school absences related to ILI in 4K-12 students across the selected school district on a daily basis (Figure 1 ; component 1). • Determine the etiology of ILI in absent students ( Figure 1 ; component 2). • Detect within-household transmission of influenza in households from which a student has been absent from school due to ILI (Figure 1; component 3 ). • Compare the data from ILI-and influenza-specific student absenteeism in the participating schools to data routinely collected in complementary influenza surveillance in the health care facilities serving the same general population of the school district (Figure 1; component 4) . . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Reporting unscheduled absences: We introduced minimal modifications to an existing absenteeism reporting system. Parents report unscheduled absences to attendance staff using an automated telephone system. Callers are prompted to provide the student's name and the reason for absence, including symptoms if the child has a cold or flu-like illness. We worked with OSD to provide uniform messaging on each school's absentee line with additional information pertaining to influenza-like illness (ILI) symptoms: "Please inform us if your child has any flu-like symptoms such as fever with cough, sneezing, chills, sore throat, body aches, fatigue, runny nose, and/or stuffy nose." In the event that a student is absent without a report, OSD attendance staff-in the interest of child safety-make repeated efforts to contact the home or parents/guardians before the end of the day. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted February 4, 2021. ; https://doi.org/10.1101/2021.02.01.21250878 doi: medRxiv preprint Absenteeism definition: Because of variability among the OSD schools in terms of the number of class periods, from 2 to 10 per day, for which a child can be absent and for simplicity/generalizability of electronic data retrieval, if a student is absent part of a school day, we consider them absent for the entire day. Types of absenteeism: All-cause or total absenteeism (a-TOT) is defined as an absence for any reason. Absence due to illness (a-I) is an absence due to any reported illness. Absence due to ILI (a-ILI) is a subset of a-I for which ILI symptoms are reported. These operational definitions likely underestimated a-I and a-ILI due to under-reporting by parents. a-ILI definition: We considered established definitions for ILI. (22) (23) For simplicity of recognition by nonmedical attendance staff members, we used a simplified version of the CDC standard definition. ILI for ORCHARDS is defined as the presence of fever and at least one respiratory tract symptom (cough, sore throat, nasal congestion, or runny nose). We selected these symptoms based on data from the Wisconsin component of the Influenza Incidence Surveillance Project (W-IISP).(8) Reported fever plus one or more of these symptoms, as compared to respiratory symptoms in the absence of fever, is associated with a 9-fold increase in underlying influenza infection in school-aged children presenting for primary medical care (Temte, unpublished). Data system: OSD utilizes Infinite Campus® (24), a commercially available electronic student information system (SIS), to track student scheduling, enrollment, performance, and attendance. This system allows attendance staff to identify a student, select a period, and select a reason for absence from a modifiable, drop-down pick list. The OSD Information Technology (IT) staff added an option for "Absent due to influenza-like illness" (a-ILI); this required less than 5 minutes to enable. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) Data extraction and secure file transfer: OSD IT staff created an automated process within Infinite Campus® to extract daily counts of absent individuals by school, grade, and absence type (a-TOT, a-I We track daily totals of absentee counts in each category. In addition, we calculate the average daily count for each week of the school year in each category. The data flow is illustrated in Figure 3 . School incentive: Each school receives $4,000 per year to defray costs associated with IT support and effort by the attendance staff. Contact and screening: To comply with FERPA, interested parents/guardians voluntarily call the study line to determine if their child qualifies for a home visit. Students are not required to be absent to participate and it is not necessary for school to be in session for home visits to occur. If a student meets the inclusion criteria, a 20-minute home visit occurs within 2 days of initial phone contact and within 7 days of symptom onset. (1) student attends, or is eligible to attend (e.g., home schooled), a school within the OSD (2) student has an illness characterized by at least 2 of 6 acute respiratory infection (ARI)/ILI symptoms (nasal discharge; nasal congestion; sneezing; sore throat; cough; fever) (3) student scores at least 2 points on the Jackson scale (26) (27) (28) Exclusion criteria include: . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) (2) illness onset more than 7 days before anticipated time of specimen collection (3) anatomical defect for which nasal specimen collection is contraindicated (4) student participated too recently (<7 days during peak influenza period and <30 days during other times, as determined by medically-attended surveillance program) At the end of the screening process for a student meeting study criteria, family members are invited to participate in an optional household influenza transmission sub-study. Participation is allowed even if individual members opt out or are unable to complete the entire study. Inclusion criteria include: 1. individuals of any age/gender residing in the same household as ORCHARDS participant 2. fluent in English 3. able to provide appropriate consent/assent Exclusion criteria include: 1. anatomical defect for which nasal sampling is contraindicated 2. household participated too recently (<7 days during peak influenza period and <30 days during other times, as determined by medically-attended surveillance program) Acquiring informed consent/assent: Research coordinators obtain written informed consent from parents/guardians and/or adult students, and assent from younger students using forms tailored to reading levels based on age. Consent allows assessment of immunization records through the Wisconsin Immunization Registry and advanced laboratory analyses of respiratory specimens. Participants can opt . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Research coordinators call parents/guardians with RIDT results within 24 hours (usually less than 4 hours) of the home visit. Laboratory confirmed results are mailed to families within 2 weeks of a home visit, and are accepted as documentation for an excused absence by the OSD. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted February 4, 2021. Contact and screening: At the ORCHARDS home visit, families expressing interest in the sub-study receive a packet containing sub-study information, instructions, consents/assents, and a small collection kit for each household member. The collection kit contains a data form, 2 nasal swabs, and 2 small (Table 3) . . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted February 4, 2021. ; https://doi.org/10.1101/2021.02.01.21250878 doi: medRxiv preprint 3. Household member illness assessment on Day 7, one week after the initial visit ("Follow-up" section): information about any cold or flu-like illnesses occurring over the past 7 days (Table 3) Household incentive for participation: As an incentive for completing the household sub-study, participating families receive a $50 gift card to local businesses when specimens are retrieved. Rapid influenza diagnostic test: We use the Quidel® Sofia® Influenza A+B fluorescent immunoassay for initial assessment of nasal specimens for ORCHARDS participants.(32) RIDT is performed at a nearby clinical facility within 6 hours of specimen collection following instructions outlined in the package insert. RIDT is not performed on specimens from household members. Influenza rRT-PCR: All specimens from students and household members (Day 0 and Day 7) are tested at WSLH for influenza A and B virus and Human RNase P (RP) using the in-vitro diagnostic (IVD) FDA-. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted February 4, 2021. All other project data are kept in password-protected security-ensured REDCap databases. Data analysts are restricted to viewing outcome data, and are unable to access personal identifiers. IVh. Community engagement and study promotion. The primary mode of ORCHARDS recruitment is the reminder within the absenteeism reporting system. Information is also provided at the OSD's unified registration each August and through e-mails to OSD families. We employ flyers, posters, and brochures at community sites, presentations at community events, mailings, postcards, the study website (www.fammed.wisc.edu/orchards/), and Facebook page (www.facebook.com/orchardstudy/). Moreover, the study team has extensive personal connections with the community through long-term residency within the OSD, children attending school in the district, and participation in school-based activities. IVi. IRB and project oversight. All components of this proposed study were reviewed and approved by the Human Subjects Committees of the Education and Social/Behavioral Sciences IRB (initial approval on September 4, 2013) and the University of Wisconsin Health Sciences-IRB (initial approval on December . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Va. Absenteeism data. Over the first 5 years of ORCHARDS, we have evaluated 3,260,461 student days (enrollment multiplied by school days). Total absenteeism accounted for 301,427 (9.2%) of potential student days, a-I accounted for 58,126 (1.8%) student days, and a-ILI accounted for 6,634 (0.2%) student . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted February 4, 2021. ; https://doi.org/10.1101/2021.02.01.21250878 doi: medRxiv preprint days. The daily counts for each type of absenteeism, showing the variability, are depicted in Figure 4 . The annual levels of absenteeism were similar across all 5 years (Table 4) . Vb. Home visits and basic virology. We completed 1,728 home visits for children with ARI. Children ranged in age from 4 to 18 years (mean ± std.dev. = 9.9±2.5 years). There were more male (57%) than female (43%) participants. Home visits occurred, on average, 56.3±46.5 hours after onset of symptoms. The number of home visits per day were positively correlated with a-Tot (rs=0.20; p<0.001), a-I (rs=0.41; p<0.001) and a-ILI (rs=0.40; p<0.001). Most children (79%) reported school absenteeism due to the current illness episode. Pathogens were detected in 1,115 (65%) specimens; the majority (99%) of these were viral. Codetections of viruses were noted in 66 students (6% of individuals with virus detections). Influenza was the most commonly detected virus, noted in 402 (23%) students, followed by rhinovirus/enterovirus. The numbers of viruses detected are provided in Table 5 . A simple, validated definition of influenza-like illness-related absence (a-ILI) is a prerequisite for monitoring. We used multivariate binary logistic regression to assess the relationships between pathogens and a-ILI within individual students while adjusting for age and sex. Cases for which no viruses were identified served as the reference set. Of the participating students (Table 6 ). Other viruses were not associated with a-ILI. Accordingly, absence from school due to ILI using a simple definition . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted February 4, 2021. ; https://doi.org/10.1101/2021.02.01.21250878 doi: medRxiv preprint (absent with fever and a respiratory symptom) is strongly associated with laboratory-confirmed influenza. In contrast to routine national surveillance systems that rely on sentinel outpatient or inpatient data on medically attended cases of ILI, ORCHARDS uses a community-based design. It is well recognized that most cases of influenza do not present for medical attendance (40). Even less common are hospitalized cases of influenza and influenza-related mortality (41-42). It is also recognized that the attack rates of influenza are much higher in school-aged children than for any other demographic group (40), and that influenza has a significant contribution to school absenteeism.(43) Accordingly, ORCHARDS was designed to detect and evaluate-over multiple seasons-the temporal trends of influenza detection among the age group which is central to community-wide influenza transmission (school-aged children), and which may be less represented among MAI cases. A number of studies evaluating absenteeism and influenza predate ORCHARDS (15) (16) (17) (18) 44) , but many have been limited by evaluating a single outbreak. Influenza does not follow a regular pattern in an area but rather encompasses outbreaks of variable magnitudes and temporal patterns due to differing influenza types, subtypes and clades (45, 46) ; this necessitates multiyear assessment of monitoring systems to assess generalizability. Moreover, influenza outbreaks can occur at any time over a fairly wide seasonal range (47), thus making assessments over several seasons necessary to evaluate for effects of timing. Finally, an observational approach allows accumulation of multiple periods of planned and unplanned (weather-related) school breaks that may allow evaluation of school closure for outbreak response. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted February 4, 2021. ; https://doi.org/10.1101/2021.02.01.21250878 doi: medRxiv preprint ORCHARDS takes advantage of a pre-existing, long-standing, and highly effective influenza surveillance system that has provided consistent evaluation of seasonal and pandemic influenza since October 2009 as a "gold standard" for daily comparability. This parallel system is based on MAI surveillance at 5 primary care clinics which overlap with the study catchment area and uses very similar data instruments and identical laboratory methods. The community involvement, longitudinal nature, and external comparability make ORCHARDS a unique study platform to evaluate the role of school-aged children on influenza transmission and the utility of cause-specific absenteeism monitoring for identifying influenza outbreaks. Initial findings suggest the study design is succeeding in collecting appropriate data to achieve study objectives. Early detection of influenza within a community is critical for public health mitigation and the reduction of overall disease burden. Additional studies are needed to determine the effect of school closure on influenza transmission. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted February 4, 2021. The datasets generated and/or analyzed during the current study are not publicly available because the study is ongoing, but may be available from the corresponding author on reasonable request. Dr. Jonathan Temte has received financial and material support from Quidel Corporation. Dr. John This study has been supported by CDC through the cooperative agreement # 5U01CK000542-02-00. The findings and conclusions in this study are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 14. Best K-12 Student Information Systems. Accessed 10/20/2019 at: https://www.g2.com/categories/k-12-student-information-systems. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted February 4, 2021. ; https://doi.org/10.1101/2021.02.01.21250878 doi: medRxiv preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted February 4, 2021. ; . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted February 4, 2021. ; CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted February 4, 2021. ; . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted February 4, 2021. ; https://doi.org/10.1101/2021.02.01.21250878 doi: medRxiv preprint . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted February 4, 2021. ; https://doi.org/10.1101/2021.02.01.21250878 doi: medRxiv preprint Figure 1 . Theoretical framework of ORCHARDS demonstrating the relationships between influenza in school-aged children, K-12 school absenteeism, and medically attended influenza in the community. The relatedness of the four components (C1-C4) of ORCHARDS and the three primary hypotheses (H1-H3) are provided. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted February 4, 2021. ; https://doi.org/10.1101/2021.02.01.21250878 doi: medRxiv preprint . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted February 4, 2021. ; https://doi.org/10.1101/2021.02.01.21250878 doi: medRxiv preprint Figure 3 . Flow diagram of absenteeism data from telephone reporting by parents/guardians, to entry into the student information system at the Oregon School District, to data transfer to the ORCHARDS research team. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted February 4, 2021. ; https://doi.org/10.1101/2021.02.01.21250878 doi: medRxiv preprint Economic burden of seasonal influenza in the United States. Vaccine Lessons from influenza pandemics of the last 100 years Comparison of 3 school-based influenza surveillance indicators: Lessons learned from 2009 pandemic influenza A (H1N1)-Denver Metropolitan Region, Colorado Evaluation of school absenteeism data for early outbreak detection School absence data for influenza surveillance: a pilot study in the United Kingdom Decipher my Data project and schools. Are school absences correlated with influenza surveillance data in England? Results from Decipher My Data-A Research Project conducted through Scientific Engagement with Schools United States Census. Quick Facts Wisconsin Department of Public Instruction. 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The Wisconsin State Lab of Hygiene provided excellent laboratory support and advice on best practices.