Descriptive Epidemiology of Pathogens Associated with Acute Respiratory Infection in a Community-Based Study of K-12 School Children (2015-2023).

School-based outbreaks often precede increased incidence of acute respiratory infections in the greater community. We conducted acute respiratory infection surveillance among children to elucidate commonly detected pathogens in school settings and their unique characteristics and epidemiological patterns. The ORegon CHild Absenteeism due to Respiratory Disease Study (ORCHARDS) is a longitudinal, laboratory-supported, school-based, acute respiratory illness (ARI) surveillance study designed to evaluate the utility of cause-specific student absenteeism monitoring for early detection of increased activity of influenza and other respiratory viruses in schools from kindergarten through 12th grade. Eligible participants with ARIs provided demographic, epidemiologic, and symptom data, along with a nasal swab or oropharyngeal specimen. Multipathogen testing using reverse-transcription polymerase chain reaction (RT-PCR) was performed on all specimens for 18 respiratory viruses and 2 atypical bacterial pathogens (Chlamydia pneumoniae and Mycoplasma pneumoniae). Between 5 January 2015 and 9 June 2023, 3498 children participated. Pathogens were detected in 2455 of 3498 (70%) specimens. Rhinovirus/enteroviruses (36%) and influenza viruses A/B (35%) were most commonly identified in positive specimens. Rhinovirus/enteroviruses and parainfluenza viruses occurred early in the academic year, followed by seasonal coronaviruses, RSV, influenza viruses A/B, and human metapneumovirus. Since its emergence in 2020, SARS-CoV-2 was detected year-round and had a higher median age than the other pathogens. A better understanding of the etiologies, presentations, and patterns of pediatric acute respiratory infections can help inform medical and public health system responses.

Effect of planned school breaks on student absenteeism due to influenza-like illness in school aged children-Oregon School District, Wisconsin September 2014-June 2019.

Background: School-aged children and school reopening dates have important roles in community influenza transmission. Although many studies evaluated the impact of reactive closures during seasonal and pandemic influenza outbreaks on medically attended influenza in surrounding communities, few assess the impact of planned breaks (i.e., school holidays) that coincide with influenza seasons, while accounting for differences in seasonal peak timing. Here, we analyze the effects of winter and spring breaks on influenza risk in school-aged children, measured by student absenteeism due to influenza-like illness (a-ILI). Methods: We compared a-ILI counts in the 2-week periods before and after each winter and spring break over five consecutive years in a single school district. We introduced a "pseudo-break" of 9 days' duration between winter and spring break each year when school was still in session to serve as a control. The same analysis was applied to each pseudo-break to support any findings of true impact. Results: We found strong associations between winter and spring breaks and a reduction in influenza risk, with a nearly 50% reduction in a-ILI counts post-break compared with the period before break, and the greatest impact when break coincided with increased local influenza activity while accounting for possible temporal and community risk confounders. Conclusions: These findings suggest that brief breaks of in-person schooling, such as planned breaks lasting 9-16 calendar days, can effectively reduce influenza in schools and community spread. Additional analyses investigating the impact of well-timed shorter breaks on a-ILI may determine an optimal duration for brief school closures to effectively suppress community transmission of influenza.

Changing pattern of respiratory virus detections among school-aged children in a small community - Dane County, Wisconsin, September to December 2022.

Widespread school closures and other non-pharmaceutical interventions (NPIs), used to limit the spread of SARS-CoV-2, significantly disrupted transmission patterns of seasonal respiratory viruses. As NPIs were relaxed, populations were vulnerable to resurgence. This study within a small community assessed acute respiratory illness among kindergarten through grade 12 students as they returned to public schools from September through December 2022 without masking and distancing requirements. The 277 specimens collected demonstrated a shift from rhinovirus to influenza. With continued circulation of SARS-CoV-2 and return of seasonal respiratory viruses, understanding evolving transmission patterns will play an important role in reducing disease burden.

Adequacy of using a single nasal swab for rapid influenza diagnostic testing, PCR, and whole genome sequencing.

Rapid influenza diagnostic tests (RIDT) demonstrate varying sensitivities, often necessitating reverse transcriptase polymerase chain reaction (RT-PCR) to confirm results. The two methods generally require separate specimens. Using the same anterior nasal swab for both RIDT and molecular confirmation would reduce cost and waste and increase patient comfort. The aim of this study was to determine if RIDT residual nasal swab (rNS) specimens are adequate for RT-PCR and whole genome sequencing (WGS). We performed RT-PCR and WGS on paired rNS and nasopharyngeal or oropharyngeal (NP/OP) swab specimens that were collected from primary care patients across all ages. We randomly selected 199 and 40 paired specimens for RT-PCR and WGS, respectively, from the 962 paired surveillance specimens collected during the 2014-2015 influenza season. Sensitivity and specificity for rNS specimens were 81.3% and 96.7%, respectively, as compared to NP/OP specimens. The mean cycle threshold (Ct) value for the NP/OP specimen was significantly lower when the paired specimens were both positive than when the NP/OP swab was positive and the nasal swab was negative (25.5 vs 29.5; p<0.001). Genomic information was extracted from all 40 rNS specimens and 37 of the 40 NP/OP specimens. Complete WGS reads were available for 67.5% (14 influenza A; 13 influenza B) of the rNS specimens and 59.5% (14 influenza A; 8 influenza B) of the NP/OP specimens. It is feasible to use a single anterior nasal swab for RIDT followed by RT-PCR and/or WGS. This approach may be appropriate in situations where training and supplies are limited. Additional studies are needed to determine if residual nasal swabs from other rapid diagnostic tests produce similar results.

The Influence of Rapid Influenza Diagnostic Testing on Clinician Decision-Making for Patients With Acute Respiratory Infection in Urgent Care.

BACKGROUND: The potential benefits of using rapid influenza diagnostic tests (RIDTs) in urgent care facilities for clinical care and prescribing practices are understudied. We compared antiviral and antibiotic prescribing, imaging, and laboratory ordering in clinical encounters with and without RIDT results. METHODS: We compared patients with acute respiratory infection (ARI) symptoms who received an RIDT and patients who did not at 2 urgent care facilities. Primary analysis using 1-to-1 exact matching resulted in 1145 matched pairs to which McNemar 2 × 2 tests were used to assess the association between the likelihood of prescribing, imaging/laboratory ordering, and RIDT use. Secondary analysis compared the same outcomes using logistic regression among the RIDT-tested population between participants who tested negative (RIDT(-)) and positive (RIDT(+)). RESULTS: Primary analysis revealed that compared to the non-RIDT-tested population, RIDT(+) patients were more likely to be prescribed antivirals (OR, 10.23; 95% CI, 5.78-19.72) and less likely to be prescribed antibiotics (OR, 0.15; 95% CI, .08-.27). Comparing RIDT-tested to non-RIDT-tested participants, RIDT use increased antiviral prescribing odds (OR, 3.07; 95% CI, 2.25-4.26) and reduced antibiotic prescribing odds (OR, 0.52; 95% CI, .43-.63). Secondary analysis identified increased odds of prescribing antivirals (OR, 28.21; 95% CI, 18.15-43.86) and decreased odds of prescribing antibiotics (OR, 0.20; 95% CI, .13-.30) for RIDT(+) participants compared with RIDT(-). CONCLUSIONS: Use of RIDTs in patients presenting with ARI symptoms influences clinician diagnostic and treatment decision-making, which could lead to improved patient outcomes, population-level reductions in influenza burden, and a decreased threat of antibiotic resistance.

Factors influencing sensitivity of a rapid influenza diagnostic test in a community-based population of kindergarten through 12th-grade students: Wisconsin 2015-2020.

Rapid influenza diagnostic tests (RIDTs) have variable sensitivity. In a community-based population of kindergarten through 12th-grade (K-12) students, we assessed factors that may influence RIDT performance using 2368 paired results from Sofia® influenza A + B fluorescent immunoassay and reverse transcription polymerase chain reaction (RT-PCR). RIDT sensitivity and specificity were 76.1% (95% CI: 72.8-79.1) and 97.2% (96.2-97.9), respectively. Factors associated with sensitivity included runny nose (OR = 3.0, p < 0.001), nasal congestion (1.59, p = 0.045), days from symptom onset (per day; 0.75; p < 0.001), myalgia (0.61; p = 0.014), age (per 5 years; 0.55; p = 0.001), and detection of another virus (0.50; p = 0.043). Understanding these factors can aid in interpreting negative results.

Feasibility and Functionality of SARS-CoV-2 Rapid Testing in K-12 School Health Offices.

INTRODUCTION: The COVID-19 pandemic created unprecedented opportunities to introduce rapid SARS-CoV-2 antigen testing (RSAT) into kindergarten through 12th grade (K-12) school settings. We evaluated the feasibility and functionality of Sofia Fluorescent Immunoassay Flu + SARS in 1 school district across the 2021-2022 academic year. METHODS: Seven schools in the Oregon School District (Oregon, Wisconsin) were supplied with RSAT analyzers and test kits, along with minimal training of health office staff. We assessed RSAT utilization among schools, rate of invalid results, and comparability to 952 190 reverse transcription-polymerase chain reaction tests performed countywide during the same time period. A feedback survey was distributed to all 13 health office staff to assess respondents' perceptions regarding the feasibility and acceptability of RSAT in the Oregon School District. RESULTS: Over the school year, 1226 RSATs were performed; SARS-CoV-2 was detected in 103 specimens. Percent positivity was similar to the county level (8.4 vs 9.2%; chi-square = 0.74; P = 0.39). Cross-correlation of weekly positive tests between the Oregon School District and Dane County was maximal with no lag (rs = 0.69; P < 0.001). Health office staff indicated Sofia2 RSAT was easy to perform, and 92.3% reported interest in continuing to utilize RSAT in the upcoming school year. CONCLUSIONS: Implementing a RSAT protocol is feasible and acceptable for monitoring SARS-CoV-2 cases in K-12 school settings. High rates of compliance and confidence in results demonstrate program effectiveness. Continuing to use RSAT in school settings after the urgency of the pandemic subsides could help address future outbreaks of SARS-CoV-2 and other respiratory viruses within schools and in the larger community.

Surveillance of SARS-CoV-2 in Asymptomatic Faculty and Staff at the University of Wisconsin-Madison.

INTRODUCTION: Surveillance of SARS-CoV-2 among university employees is an important part of mitigation strategies to prevent asymptomatic transmission and ensure a safe learning and work environment. Here, we assess the feasibility and performance of a program that relies on monitored self-collected nasal swabs to detect SARS-CoV-2 among asymptomatic faculty and staff. METHODS: We recruited 1,030 faculty and staff via rolling enrollment who completed the required University of Wisconsin-Madison employee COVID-19 training and reported working on campus. Asymptomatic participants visited a designated location during a specified timeframe each week where they self-collected nasal swabs supervised by study staff. Specimens were stored in a cooler between 2 °C and 8 °C, then transported to the Wisconsin Veterinary Diagnostic Laboratory for polymerase chain reaction testing. Symptomatic participants or participants with a known exposure were advised to test elsewhere and follow quarantine guidelines from the Centers for Disease Control and Prevention. RESULTS: Over the course of 31 weeks, 1,030 participants self-collected 17,323 monitored nasal swabs resulting in high participation (90%). SARS-CoV-2 was detected in 16 specimens. Eight specimens were inconclusive but were treated as positive results because of the implied detection of 1 or more SARS-CoV-2 genes. There were no invalid tests. Weekly SARS-CoV-2 incidence among participants ranged from 0 to 1.54% (x̄ = 0.20%). The SARS-CoV-2 incidence among participants was similar to estimated incidence in the greater university employee population. CONCLUSION: Weekly SARS-CoV-2 surveillance of asymptomatic faculty and staff on campus allowed for estimation of weekly SARS-CoV-2 incidence among on-campus employees. This surveillance protocol presents a low-cost, effective, and scalable option to identify asymptomatic cases of SARS-CoV-2 among university employees.

Assessment of potential factors associated with the sensitivity and specificity of Sofia Influenza A+B Fluorescent Immunoassay in an ambulatory care setting.

BACKGROUND: Seasonal influenza leads to an increase in outpatient clinic visits. Timely, accurate, and affordable testing could facilitate improved treatment outcomes. Rapid influenza diagnostic tests (RIDTs) provide results in as little as 15 minutes and are relatively inexpensive, but have reduced sensitivity when compared to RT-PCR. The contributions of multiple factors related to test performance are not well defined for ambulatory care settings. We assessed clinical and laboratory factors that may affect the sensitivity and specificity of Sofia Influenza A+B Fluorescence Immunoassay. STUDY DESIGN: We performed a post-hoc assessment of surveillance data amassed over seven years from five primary care clinics. We analyzed 4,475 paired RIDT and RT-PCR results from specimens collected from patients presenting with respiratory symptoms and examined eleven potential factors with additional sub-categories that could affect RIDT sensitivity. RESULTS: In an unadjusted analysis, greater sensitivity was associated with the presence of an influenza-like illness (ILI), no other virus detected, no seasonal influenza vaccination, younger age, lower cycle threshold value, fewer days since illness onset, nasal discharge, stuffy nose, and fever. After adjustment, presence of an ILI, younger age, fewer days from onset, no co-detection, and presence of a nasal discharge maintained significance. CONCLUSION: Clinical and laboratory factors may affect RIDT sensitivity. Identifying potential factors during point-of-care testing could aid clinicians in appropriately interpreting negative influenza RIDT results.

Cause-specific student absenteeism monitoring in K-12 schools for detection of increased influenza activity in the surrounding community-Dane County, Wisconsin, 2014-2020.

BACKGROUND: Schools are primary venues of influenza amplification with secondary spread to communities. We assessed K-12 student absenteeism monitoring as a means for early detection of influenza activity in the community. MATERIALS AND METHODS: Between September 2014 and March 2020, we conducted a prospective observational study of all-cause (a-TOT), illness-associated (a-I), and influenza-like illness-associated (a-ILI) absenteeism within the Oregon School District (OSD), Dane County, Wisconsin. Absenteeism was reported through the electronic student information system. Students were visited at home where pharyngeal specimens were collected for influenza RT-PCR testing. Surveillance of medically-attended laboratory-confirmed influenza (MAI) occurred in five primary care clinics in and adjoining the OSD. Poisson general additive log linear regression models of daily counts of absenteeism and MAI were compared using correlation analysis. FINDINGS: Influenza was detected in 723 of 2,378 visited students, and in 1,327 of 4,903 MAI patients. Over six influenza seasons, a-ILI was significantly correlated with MAI in the community (r = 0.57; 95% CI: 0.53-0.63) with a one-day lead time and a-I was significantly correlated with MAI in the community (r = 0.49; 0.44-0.54) with a 10-day lead time, while a-TOT performed poorly (r = 0.27; 0.21-0.33), following MAI by six days. DISCUSSION: Surveillance using cause-specific absenteeism was feasible and performed well over a study period marked by diverse presentations of seasonal influenza. Monitoring a-I and a-ILI can provide early warning of seasonal influenza in time for community mitigation efforts.

The Oregon Child Absenteeism Due to Respiratory Disease Study (ORCHARDS): Rationale, objectives, and design.

BACKGROUND: Influenza viruses pose significant disease burdens through seasonal outbreaks and unpredictable pandemics. Existing surveillance programs rely heavily on reporting of medically attended influenza (MAI). Continuously monitoring cause-specific school absenteeism may identify local acceleration of seasonal influenza activity. 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 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 combines automated reporting of daily absenteeism within six schools and home visits to school children with acute respiratory infection (ARI). Demographic, epidemiological, and symptom data are collected along with respiratory specimens. Specimens are tested for influenza and other respiratory viruses. Household members can opt into a supplementary household transmission study. Community comparisons are possible using a pre-existing and highly effective influenza surveillance program, based on MAI at five family medicine clinics in the same geographical area. RESULTS: Over the first 5 years, a-ILI occurred on 6634 (0.20%) of 3,260,461 student school days. Viral pathogens were detected in 64.5% of 1728 children with ARI who received a home visit. Influenza was the most commonly detected virus, noted in 23.3% of ill students. CONCLUSION: ORCHARDS uses a community-based design to detect 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.

Comparison of participant-collected nasal and staff-collected oropharyngeal specimens for human ribonuclease P detection with RT-PCR during a community-based study.

We analyzed 4,352 participant- and staff-collected respiratory specimens from 2,796 subjects in the Oregon Child Absenteeism due to Respiratory Disease Study. Trained staff collected oropharyngeal specimens from school-aged children with acute respiratory illness while household participants of all ages collected their own midturbinate nasal specimens in year one and anterior nasal specimens in year two. Human ribonuclease P levels were measured using RT-PCR for all staff- and participant-collected specimens to determine adequacy, defined as Cycle threshold less than 38. Overall, staff- and participant-collected specimens were 99.9% and 96.4% adequate, respectively. Participant-collected midturbinate specimens were 95.2% adequate in year one, increasing to 97.2% in year two with anterior nasal collection. The mean human ribonuclease P Cycle threshold for participant-collected specimens was 31.18 in year one and 28.48 in year two. The results from this study suggest that community-based participant collection of respiratory specimens is comparable to staff-collected oropharyngeal specimens, is feasible, and may be optimal with anterior nasal collection.

An assessment of parental knowledge, attitudes, and beliefs regarding influenza vaccination.

INTRODUCTION: Seasonal influenza imposes a significant clinical and economic burden. Despite the availability of an annual vaccine to prevent influenza infection and reduce disease severity, influenza vaccination rates remain suboptimal. Research suggests personal experience, perceived effectiveness, and concerns regarding vaccine safety and side effects are the most influential factors in predicting a parent's decision to vaccinate. However, current literature is primarily focused on the vaccine decision-making of healthcare workers and those at high risk for influenza complications. METHODS: To assess parental attitudes and beliefs regarding the influenza vaccine, a brief mixed-methods survey was developed and optimized for an electronic platform. The Health Belief Model informed survey design and data analysis. Questions were classified into five core concepts: knowledge, barriers, benefits, experience, and severity. Participants were solicited from a population of parents whose children had participated in a school-based influenza surveillance study (n = 244, 73% response rate). We tested associations between responses and children's influenza vaccination status the prior season. Categorical questions were tested using Pearson's chi-squared tests and numerical or ordered questions using Mann-Whitney tests. P-values were corrected using the Bonferroni method. RESULTS: Doubting effectiveness, concerns about side effects, inconvenience, and believing the vaccine is unnecessary were barriers negatively associated with parents' decision to vaccinate their children during the 2017-18 flu season (p < 0.001). Knowledge that the vaccine is effective in lowering risk, duration, and severity of influenza; receiving the influenza vaccine as an adult; and recognizing the importance of vaccination to prevent influenza transmission in high-risk populations were positively associated with parents' decision to vaccinate (p < 0.001). CONCLUSION: Understanding barriers and motivators behind parents' decision to vaccinate provides valuable insight that has the potential to shape vaccine messaging, recommendations, and policy. The motivation to vaccinate to prevent influenza transmission in high-risk populations is a novel finding that warrants further investigation.