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BACKGROUND: Virginiamycin use in poultry selects for Enterococcus faecium with cross-resistance to quinupristin-dalfopristin, a drug for vancomycin-resistant E. faecium in humans. We conducted an epidemiologic study of poultry exposures as risk factors for human carriage of quinupristin-dalfopristin-resistant E. faecium. METHODS: Rectal or fecal samples for E. faecium testing were obtained from 567 newly admitted hospital patients and 100 healthy vegetarians. Participants were interviewed regarding poultry exposure. Retail poultry washes (160 conventional and 26 antibiotic free) were also tested for the presence of E. faecium. Constitutive and inducible quinupristin-dalfopristin resistance were assessed in E. faecium isolates, and resistance genes were identified by polymerase chain reaction. RESULTS: E. faecium was isolated from 105 patients, 65 vegetarians, and 77 conventional and 23 antibiotic-free poultry washes. Constitutive quinupristin-dalfopristin resistance was absent in human E. faecium, but 56% of conventional poultry isolates were quinupristin-dalfopristin resistant. Inducible quinupristin-dalfopristin resistance was more common in samples from patients than in those from vegetarians and in washes of conventional than antibiotic-free poultry. Higher poultry consumption was associated with inducible quinupristin-dalfopristin resistance. vatE was present in 38% of E. faecium isolates from patients and none from vegetarians. Touching raw poultry was associated with the presence of vatE. CONCLUSIONS: Poultry exposure is associated with a quinupristin-dalfopristin resistance gene and inducible quinupristin-dalfopristin resistance in human fecal E. faecium. The continued use of virginiamycin may increase the potential for streptogramin-resistant E. faecium infection in humans. Copyright © 2006 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

Background and Objectives: The Minnesota Department of Health conducts active surveillance for cases of human immunodeficiency virus (HIV) infection and passive surveillance for gonorrhea, Chlamydia trachomatis infection, and syphilis. The authors linked two computerized surveillance databases to assess gonorrhea incidence and risk factors for sexually transmitted disease (STD) acquisition among people with known HIV infection.Study Design: People diagnosed with adolescent/adult HIV infection before 1993 and still alive as of December 31, 1994 were compared to people diagnosed with gonorrhea, chlamydial infection, or primary/secondary syphilis in 1993 or 1994. Records were matched on name, date of birth, and gender. The incidence of reported gonorrhea was calculated and risk factors for STD acquisition were examined.Results: Thirty (1.3%) of 2,315 HIV-infected people were diagnosed with one or more STDs after HIV diagnosis (median interval: 3 years). There were 31 episodes of gonorrhea, seven episodes of chlamydial infection, and one episode of secondary syphilis. The gonorrhea incidence among HIV-infected people was high compared to the general population in Minnesota, even after stratifying by gender, age, and county of residence. STD acquisition was independently associated with female gender (odds ratio [OR] = 3.8; 95% confidence interval [CI] = 1.7, 8.3) and residence in Hennepin County (OR = 2.9; 95% CI = 1.2, 7.1), the most populous county in Minnesota.Conclusions: Linkage of STD and HIV surveillance data is useful as a sentinel for high-risk sexual behavior among HIV-infected people, and it can help identify individuals who require additional interventions to prevent HIV transmission. State and local health departments should consider linking these data sources to assess trends and allocate resources. [ABSTRACT FROM AUTHOR]

The immune response to inactivated influenza vaccines (IIV) is influenced by multiple factors, including hemagglutinin content and egg-based manufacturing. Only two US-licensed vaccines are manufactured without egg passage: cell culture-based inactivated vaccine (ccIIV) and recombinant vaccine (RIV). We conducted a randomized open-label trial in central Wisconsin during the 2018-19 and 2019-20 seasons to compare immunogenicity of sequential vaccination. Participants 18-64 years old were randomized 1:1:1 to receive RIV, ccIIV or IIV in strata defined by number of influenza vaccine doses in the prior 3 years. They were revaccinated with the same product in year two. Paired serum samples were tested by hemagglutination inhibition against egg-adapted and cell-grown vaccine viruses. Serologic endpoints included geometric mean titer (GMT), mean fold rise, and percent seroconversion. There were 373 participants randomized and vaccinated in 2018-19; 332 were revaccinated in 2019-20. In 2018-19, RIV and ccIIV were not more immunogenic than IIV against A/H1N1. The post-vaccination GMT against the cell-grown 3C.2a A/H3N2 vaccine virus was higher for RIV vs IIV ( p  = .001) and RIV vs ccIIV ( p  = .001). The antibody response to influenza B viruses was similar across study arms. In 2019-20, GMT against the cell-grown 3C.3a A/H3N2 vaccine virus was higher for RIV vs IIV ( p  = .03) and for RIV vs ccIIV ( p  = .001). RIV revaccination generated significantly greater backboosting to the antigenically distinct 3C.2a A/H3N2 virus (2018-19 vaccine strain) compared to ccIIV or IIV. This study adds to the evidence that RIV elicits a superior immunologic response against A/H3N2 viruses compared to other licensed influenza vaccine products.

Importance: Influenza vaccine effectiveness (VE) is commonly assessed against prevention of illness that requires medical attention. Few studies have evaluated VE against secondary influenza infections., Objective: To determine the estimated effectiveness of influenza vaccines in preventing secondary infections after influenza was introduced into households., Design, Settings, and Participants: During 3 consecutive influenza seasons (2017-2020), primary cases (the first household members with laboratory-confirmed influenza) and their household contacts in Tennessee and Wisconsin were enrolled into a prospective case-ascertained household transmission cohort study. Participants collected daily symptom diaries and nasal swabs for up to 7 days. Data were analyzed from September 2022 to February 2024., Exposures: Vaccination history, self-reported and verified through review of medical and registry records., Main Outcomes and Measures: Specimens were tested using reverse transcription-polymerase chain reaction to determine influenza infection. Longitudinal chain binomial models were used to estimate secondary infection risk and the effectiveness of influenza vaccines in preventing infection among household contacts overall and by virus type and subtype and/or lineage., Results: The analysis included 699 primary cases and 1581 household contacts. The median (IQR) age of the primary cases was 13 (7-38) years, 381 (54.5%) were female, 60 (8.6%) were Hispanic, 46 (6.6%) were non-Hispanic Black, 553 (79.1%) were Non-Hispanic White, and 343 (49.1%) were vaccinated. Among household contacts, the median age was 31 (10-41) years, 833 (52.7%) were female, 116 (7.3%) were Hispanic, 78 (4.9%) were non-Hispanic Black, 1283 (81.2%) were non-Hispanic White, 792 (50.1%) were vaccinated, and 356 (22.5%) had laboratory-confirmed influenza during follow-up. The overall secondary infection risk of influenza among household contacts was 18.8% (95% CI, 15.9% to 22.0%). The risk was highest among children and was 20.3% (95% CI, 16.4% to 24.9%) for influenza A and 15.9% (95% CI, 11.8% to 21.0%) for influenza B. The overall estimated VE for preventing secondary infections among unvaccinated household contacts was 21.0% (95% CI, 1.4% to 36.7%) and varied by type; estimated VE against influenza A was 5.0% (95% CI, -22.3% to 26.3%) and 56.4% (95% CI, 30.1% to 72.8%) against influenza B., Conclusions and Relevance: After influenza was introduced into households, the risk of secondary influenza among unvaccinated household contacts was approximately 15% to 20%, and highest among children. Estimated VE varied by influenza type, with demonstrated protection against influenza B virus infection.

Elevated body mass index (BMI) has been linked to severe influenza illness and impaired vaccine immunogenicity, but the relationship between BMI and clinical vaccine effectiveness (VE) is less well described. This secondary analysis of data from a test-negative study of outpatients with acute respiratory illness assessed BMI and VE against medically attended, PCR-confirmed influenza over seven seasons (2011-12 through 2017-18). Vaccination status was determined from electronic medical records (EMR) and self-report; BMI was estimated from EMR-documented height and weight categorized for adults as obesity (≥ 30 kg/m 2 ), overweight (25-29 kg/m 2 ), or normal and for children based on standardized z-scales. Current season VE by virus type/subtype was estimated separately for adults and children. Pooled VE for all seasons was calculated as 1-adjusted odds ratios from logistic regression with an interaction term for BMI and vaccination. Among 28,089 adults and 12,380 children, BMI category was not significantly associated with VE against outpatient influenza for any type/subtype. Adjusted VE against A/H3N2, A/H1N1pdm09, and B in adults ranged from 16-31, 46-54, and 44-57%, and in children from 29-34, 57-65, and 50-55%, respectively, across the BMI categories. Elevated BMI was not associated with reduced VE against laboratory confirmed, outpatient influenza illness., (© 2024. The Author(s).)

Isolation of symptomatic infectious persons can reduce influenza transmission. However, virus shedding that occurs without symptoms will be unaffected by such measures. Identifying effective isolation strategies for influenza requires understanding the interplay between individual virus shedding and symptom presentation. From 2017 to 2020, we conducted a case-ascertained household transmission study using influenza real-time RT-qPCR testing of nasal swabs and daily symptom diary reporting for up to 7 days after enrolment (≤14 days after index onset). We assumed real-time RT-qPCR cycle threshold (Ct) values were indicators of quantitative virus shedding and used symptom diaries to create a score that tracked influenza-like illness (ILI) symptoms (fever, cough, or sore throat). We fit phenomenological nonlinear mixed-effects models stratified by age and vaccination status and estimated two quantities influencing isolation effectiveness: shedding before symptom onset and shedding that might occur once isolation ends. We considered different isolation end points (including 24 h after fever resolution or 5 days after symptom onset) and assumptions about the infectiousness of Ct shedding trajectories. Of the 116 household contacts with ≥2 positive tests for longitudinal analyses, 105 (91%) experienced ≥1 ILI symptom. On average, children <5 years experienced greater peak shedding, longer durations of shedding, and elevated ILI symptom scores compared with other age groups. Most individuals (63/105) shed <10% of their total shed virus before symptom onset, and shedding after isolation varied substantially across individuals, isolation end points, and infectiousness assumptions. Our results can inform strategies to reduce transmission from symptomatic individuals infected with influenza., (Published by Oxford University Press on behalf of National Academy of Sciences 2024.)

We describe humoral immune responses in 105 ambulatory patients with laboratory-confirmed SARS-CoV-2 Omicron variant infection. In dried blood spot (DBS) collected within 5 days of illness onset and during convalescence, we measured binding antibody (bAb) against ancestral spike protein receptor binding domain (RBD) and nucleocapsid (N) protein using a commercial multiplex bead assay. Geometric mean bAb concentrations against RBD increased by a factor of 2.5 from 1258 to 3189 units/mL and by a factor of 47 against N protein from 5.5 to 259 units/mL between acute illness and convalescence; lower concentrations were associated with greater geometric mean ratios. Paired DBS specimens may be used to evaluate humoral response to SARS-CoV-2 infection., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Background: World Health Organisation (WHO) and USA Centers for Disease Control and Prevention (U.S. CDC) recommendations now allow simultaneous administration of COVID-19 and other vaccines. We compared antibody responses after coadministration of influenza and bivalent COVID-19 vaccines in the same (ipsilateral) arm vs. different (contralateral) arms., Methods: Pre- and post-vaccination serum samples from individuals in the Prospective Assessment of COVID-19 in a Community (PACC) cohort were used to conduct haemaglutination inhibition (HI) assays with the viruses in the 2022-2023 seasonal influenza vaccine and focus reduction neutralisation tests (FRNT) using a BA.5 SARS-CoV-2 virus. The effect of ipsilateral vs. contralateral vaccination on immune responses was inferred in a model that accounted for higher variance in vaccine responses at lower pre-vaccination titers., Findings: Ipsilateral vaccination did not cause higher influenza vaccine responses compared to contralateral vaccination. The response to SARS-CoV-2 was slightly increased in the ipsilateral group, but equivalence was not excluded., Interpretation: Coadministration of influenza and bivalent COVID-19 vaccines in the same arm or different arms did not strongly influence the antibody response to either vaccine., Funding: This work was supported by the U.S. CDC (grant number: 75D30120C09259)., Competing Interests: Declaration of interests Y.K. has received grant support from Daiichi Sankyo Pharmaceutical, Toyama Chemical, Tauns Laboratories, Shionogi, Otsuka Pharmaceutical, KM Biologics, Kyoritsu Seiyaku, Shinya Corporation, and Fuji Rebio. Y.K. and G.N. are co-founders of FluGen. H.Q.N receives research support unrelated to this work from CSL Seqirus and GSK and honorarium for participating in a consultancy group for Moderna outside the submitted work. J.G.P. and E.A.B. receive research support unrelated to this work from CSL Seqirus. J.P.K. receives research support unrelated to this work from GSK., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Symptoms of COVID-19 including fatigue and dyspnea, may persist for weeks to months after SARS-CoV-2 infection. This study compared self-reported disability among SARS-CoV-2-positive and negative persons with mild to moderate COVID-19-like illness who presented for outpatient care before widespread COVID-19 vaccination., Methods: Unvaccinated adults with COVID-19-like illness enrolled within 10 days of illness onset at three US Flu Vaccine Effectiveness Network sites were tested for SARS-CoV-2 by molecular assay. Enrollees completed an enrollment questionnaire and two follow-up surveys (7-24 days and 2-7 months after illness onset) online or by phone to assess illness characteristics and health status. The second follow-up survey included questions measuring global health, physical function, fatigue, and dyspnea. Scores in the four domains were compared by participants' SARS-CoV-2 test results in univariate analysis and multivariable Gamma regression., Results: During September 22, 2020 - February 13, 2021, 2712 eligible adults were enrolled, 1541 completed the first follow-up survey, and 650 completed the second follow-up survey. SARS-CoV-2-positive participants were more likely to report fever at acute illness but were otherwise comparable to SARS-CoV-2-negative participants. At first follow-up, SARS-CoV-2-positive participants were less likely to have reported fully or mostly recovered from their illness compared to SARS-CoV-2-negative participants. At second follow-up, no differences by SARS-CoV-2 test results were detected in the four domains in the multivariable model., Conclusion: Self-reported disability was similar among outpatient SARS-CoV-2-positive and -negative adults 2-7 months after illness onset., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: We estimated combined protection conferred by prior SARS-CoV-2 infection and COVID-19 vaccination against COVID-19-associated acute respiratory illness (ARI)., Methods: During SARS-CoV-2 Delta (B.1.617.2) and Omicron (B.1.1.529) variant circulation between October 2021 and April 2022, prospectively enrolled adult patients with outpatient ARI had respiratory and filter paper blood specimens collected for SARS-CoV-2 molecular testing and serology. Dried blood spots were tested for immunoglobulin-G antibodies against SARS-CoV-2 nucleocapsid (NP) and spike protein receptor binding domain antigen using a validated multiplex bead assay. Evidence of prior SARS-CoV-2 infection also included documented or self-reported laboratory-confirmed COVID-19. We used documented COVID-19 vaccination status to estimate vaccine effectiveness (VE) by multivariable logistic regression by prior infection status., Results: Four hundred fifty-five (29%) of 1577 participants tested positive for SARS-CoV-2 infection at enrollment; 209 (46%) case-patients and 637 (57%) test-negative patients were NP seropositive, had documented previous laboratory-confirmed COVID-19, or self-reported prior infection. Among previously uninfected patients, three-dose VE was 97% (95% confidence interval [CI], 60%-99%) against Delta, but not statistically significant against Omicron. Among previously infected patients, three-dose VE was 57% (CI, 20%-76%) against Omicron; VE against Delta could not be estimated., Conclusions: Three mRNA COVID-19 vaccine doses provided additional protection against SARS-CoV-2 Omicron variant-associated illness among previously infected participants., (© 2023 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background: US recommendations for COVID-19 vaccine boosters have expanded in terms of age groups covered and numbers of doses recommended, whereas evolution of Omicron sublineages raises questions about ongoing vaccine effectiveness., Methods: We estimated effectiveness of monovalent COVID-19 mRNA booster vaccination versus two-dose primary series during a period of Omicron variant virus circulation in a community cohort with active illness surveillance. Hazard ratios comparing SARS-CoV-2 infection between booster versus primary series vaccinated individuals were estimated using Cox proportional hazards models with time-varying booster status. Models were adjusted for age and prior SARS-CoV-2 infection. The effectiveness of a second booster among adults ≥50 years of age was similarly estimated., Results: The analysis included 883 participants ranging in age, from 5 to >90 years. Relative effectiveness was 51% (95% CI: 34%, 64%) favoring the booster compared with primary series vaccination and did not vary by prior infection status. Relative effectiveness was 74% (95% CI: 57%, 84%) at 15 to 90 days after booster receipt, but declined to 42% (95% CI: 16%, 61%) after 91 to 180 days, and to 36% (95% CI: 3%, 58%) after 180 days. The relative effectiveness of a second booster compared to a single booster was 24% (95% CI: -40% to 61%)., Conclusions: An mRNA vaccine booster dose added significant protection against SARS-CoV-2 infection, but protection decreased over time. A second booster did not add significant protection for adults ≥50 years of age. Uptake of recommended bivalent boosters should be encouraged to increase protection against Omicron BA.4/BA.5 sublineages., Competing Interests: HQM and DLM report research support from Seqirus outside the submitted work. JKM reports research support from Quidel and Seqirus outside the submitted work. All other authors report no potential conflicts., (© 2023 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

In the United States, 2022-23 influenza activity began earlier than usual, increasing in October 2022, and has been associated with high rates of hospitalizations among children* (1). Influenza A(H3N2) represented most influenza viruses detected and subtyped during this period, but A(H1N1)pdm09 viruses cocirculated as well. Most viruses characterized were in the same genetic subclade as and antigenically similar to the viruses included in the 2022-23 Northern Hemisphere influenza vaccine (1,2). Effectiveness of influenza vaccine varies by season, influenza virus subtype, and antigenic match with circulating viruses. This interim report used data from two concurrent studies conducted at Marshfield Clinic Health System (MCHS) in Wisconsin during October 23, 2022-February 10, 2023, to estimate influenza vaccine effectiveness (VE). Overall, VE was 54% against medically attended outpatient acute respiratory illness (ARI) associated with laboratory-confirmed influenza A among patients aged 6 months-64 years. In a community cohort of children and adolescents aged <18 years, VE was 71% against symptomatic laboratory-confirmed influenza A virus infection. These interim analyses indicate that influenza vaccination substantially reduced the risk for medically attended influenza among persons aged <65 years and for symptomatic influenza in children and adolescents. Annual influenza vaccination is the best strategy for preventing influenza and its complications. CDC recommends that health care providers continue to administer annual influenza vaccine to persons aged ≥6 months as long as influenza viruses are circulating (2)., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Huong Q. McLean, Joshua G. Petrie, Jennifer K. Meece, Edward A. Belongia, and Kayla E. Hanson report institutional support from CSL Seqirus. Gregg C. Sylvester is an employee of CSL Seqirus. Yoshihiro Kawaoka reports institutional funding from Fujifilm Toyama Chemical Company, LTD, Shionogi & Company, LTD, Daiichi Sankyo Pharmaceutical, Otsuka Pharmaceutical, KM Biologics, Kyoritsu Seiyaku, Fuji Rebio, Tauns Laboratories, Inc., and FluGen. Yoshihiro Kawaoka and Gabriele Neumann report status as a cofounder and stockholder of FluGen. No other potential conflicts of interest were disclosed.

Background: Measles, mumps, and rubella vaccine (MMR) is routinely administered to children; however, adolescents and adults may receive MMR for various reasons. Safety studies in adolescents and adults are limited. We report on safety of MMR in this age group in the Vaccine Safety Datalink., Methods: We included adolescents (aged 9-17 years) and adults (aged ≥ 18 years) who received ≥ 1 dose of MMR from January 1, 2010-December 31, 2018. Pre-specified outcomes were identified by diagnosis codes. Clinically serious outcomes included anaphylaxis, encephalitis/myelitis, Guillain-Barré syndrome, immune thrombocytopenia, meningitis, and seizure. Non-serious outcomes were allergic reaction, arthropathy, fever, injection site reaction, lymphadenopathy, non-specific reaction, parotitis, rash, and syncope. All serious outcomes underwent medical record review. Outcome-specific incidence was calculated in pre-defined post-vaccination windows. A self-controlled risk interval design was used to determine the relative risk of each outcome in a risk window after vaccination compared to a more distal control window., Results: During the study period, 276,327 MMR doses were administered to adolescents and adults. Mean age of vaccinees was 34.8 years; 65.8 % were female; 53.2 % of doses were administered simultaneously with ≥ 1 other vaccine. Serious outcomes were rare, with incidence ≤ 6 per 100,000 doses for each outcome assessed, and none had a significant elevation in incidence during the risk window compared to the control window. Incidence of non-serious outcomes per 100,000 doses ranged from 3.4 for parotitis to 263.0 for arthropathy. Other common outcomes included injection site reaction and rash (157.0 and 112.9 per 100,000 doses, respectively). Significantly more outcomes were observed during the risk window compared to the control window for all non-serious outcomes except parotitis. Some variability was observed by sex and age group., Conclusion: Serious outcomes after MMR are rare in adolescents and adults, but vaccinees should be counseled regarding anticipated local and systemic non-serious adverse events., (© 2023 The Author(s).)

Recombinant zoster vaccine (RZV) (Shingrix; GlaxoSmithKline, Brentford, United Kingdom) is an adjuvanted glycoprotein vaccine that was licensed in 2017 to prevent herpes zoster (shingles) and its complications in older adults. In this prospective, postlicensure Vaccine Safety Datalink study using electronic health records, we sequentially monitored a real-world population of adults aged ≥50 years who received care in multiple US Vaccine Safety Datalink health systems to identify potentially increased risks of 10 prespecified health outcomes, including stroke, anaphylaxis, and Guillain-Barré syndrome (GBS). Among 647,833 RZV doses administered from January 2018 through December 2019, we did not detect a sustained increased risk of any monitored outcome for RZV recipients relative to either historical (2013-2017) recipients of zoster vaccine live, a live attenuated virus vaccine (Zostavax; Merck & Co., Inc., Kenilworth, New Jersey), or contemporary non-RZV vaccine recipients who had an annual well-person visit during the 2018-2019 study period. We confirmed prelicensure trial findings of increased risks of systemic and local reactions following RZV. Our study provides additional reassurance about the overall safety of RZV. Despite a large sample, uncertainty remains regarding potential associations with GBS due to the limited number of confirmed GBS cases that were observed., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

The safety of 9-valent HPV vaccine (9vHPV) has been established with regard to common and uncommon adverse events. However, investigation of rare and severe adverse events requires extended study periods to capture rare outcomes. This observational cohort study investigated the occurrence of three rare and serious adverse events following 9-valent human papillomavirus (9vHPV) vaccination compared to other vaccinations, in US individuals 9-26 years old, using electronic health record data from the Vaccine Safety Datalink (VSD). We searched for occurrences of Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), and stroke following 9vHPV vaccination from October 4, 2015, through January 2, 2021. We compared the risks of GBS, CIDP, and stroke following 9vHPV vaccination to risks of those outcomes following comparator vaccines commonly given to this age group (Td, Tdap, MenACWY, hepatitis A, and varicella vaccines) from January 1, 2007, through January 2, 2021. We observed 1.2 cases of stroke, 0.3 cases of GBS, and 0.1 cases of CIDP per 100,000 doses of 9vHPV vaccine. After observing more than 1.8 million doses of 9vHPV, we identified no statistically significant increase in risks associated with 9vHPV vaccination for any of these adverse events, either combined or stratified by age (9-17 years of age vs. 18-26 years of age) and sex (males vs. females). Our findings provide additional evidence supporting 9vHPV vaccine safety, over longer time frames and for more serious and rare adverse events.

Background: We estimated SARS-CoV-2 Delta- and Omicron-specific effectiveness of two and three mRNA COVID-19 vaccine doses in adults against symptomatic illness in US outpatient settings., Methods: Between October 1, 2021, and February 12, 2022, research staff consented and enrolled eligible participants who had fever, cough, or loss of taste or smell and sought outpatient medical care or clinical SARS-CoV-2 testing within 10 days of illness onset. Using the test-negative design, we compared the odds of receiving two or three mRNA COVID-19 vaccine doses among SARS-CoV-2 cases versus controls using logistic regression. Regression models were adjusted for study site, age, onset week, and prior SARS-CoV-2 infection. Vaccine effectiveness (VE) was calculated as (1 - adjusted odds ratio) × 100%., Results: Among 3847 participants included for analysis, 574 (32%) of 1775 tested positive for SARS-CoV-2 during the Delta predominant period and 1006 (56%) of 1794 participants tested positive during the Omicron predominant period. When Delta predominated, VE against symptomatic illness in outpatient settings was 63% (95% CI: 51% to 72%) among mRNA two-dose recipients and 96% (95% CI: 93% to 98%) for three-dose recipients. When Omicron predominated, VE was 21% (95% CI: -6% to 41%) among two-dose recipients and 62% (95% CI: 48% to 72%) among three-dose recipients., Conclusions: In this adult population, three mRNA COVID-19 vaccine doses provided substantial protection against symptomatic illness in outpatient settings when the Omicron variant became the predominant cause of COVID-19 in the United States. These findings support the recommendation for a third mRNA COVID-19 vaccine dose., Competing Interests: Ana Florea reports unrelated institutional grant support for research from Gilead, GlaxoSmithKline, Moderna, and Pfizer. Carlos G. Grijalva reports consulting fees from Merck, Pfizer, and Sanofi Pasteur, and institutional grant support from the Agency for Health Care Research and Quality, Campbell Alliance/Syneos Health, the Food and Drug Administration, and the National Institutes of Health. Emily T. Martin reports institutional grant support from Merck. Arnold S. Monto reports personal fees from Sanofi and non‐financial support from Seqirus. Mary Patricia Nowalk reports unrelated institutional grant support and personal fees from Merck Sharp & Dohme and institutional investigator‐initiated grant support from Sanofi Pasteur. Sara Y. Tartof reports unrelated institutional grant support from Pfizer and GlaxoSmithKline. No other potential conflicts of interest were disclosed., (Published 2022. This article is a U.S. Government work and is in the public domain in the USA. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Background: The human papillomavirus (HPV) vaccine is recommended for all adolescents age 11-12 years. HPV vaccine coverage remains suboptimal in the United States though, particularly in rural areas. We surveyed adolescent immunization providers in two Midwestern states to assess rural vs. urban differences in HPV vaccine resources, practices, and attitudes., Methods: A cross-sectional survey was sent to all licensed adolescent care providers in a subset of urban and rural counties in Minnesota and Wisconsin during 2019. Multivariable regression was used to identify attitudes and practices that differentiated rural vs. urban providers., Results: There were 437 survey respondents (31% rural). Significantly fewer rural providers had evening/weekend adolescent vaccination appointments available (adjusted odds ratio (aOR) = 0.21 [95% confidence interval (CI): 0.12, 0.36]), had prior experience with adolescent vaccine quality improvement projects (aOR = 0.52 [95% CI: 0.28, 0.98]), and routinely recommended HPV vaccine during urgent/acute care visits (aOR = 0.37 [95% CI: 0.18, 0.79]). Significantly more rural providers had standing orders to administer all recommended adolescent vaccines (aOR = 2.81 [95% CI: 1.61, 4.91]) and reported giving HPV vaccine information to their patients/families before it is due (aOR = 3.10 [95% CI: 1.68, 5.71])., Conclusions: Rural vs. urban differences in provider practices were mixed in that rural providers do not implement some practices that may promote HPV vaccination, but do implement other practices that promote HPV vaccination. It remains unclear how the observed differences would affect HPV vaccine attitudes or adolescent vaccination decisions for parents in rural areas., (© 2022. The Author(s).)

Reduced COVID-19 vaccine effectiveness (VE) has been observed with increasing predominance of SARS-CoV-2 Delta (B.1.617.2) variant. Two-dose VE against laboratory-confirmed SARS-CoV-2 infection (symptomatic and asymptomatic) was estimated using Cox proportional hazards models with time-varying vaccination status in a prospective rural community cohort of 1266 participants aged ≥12 years. Between November 3, 2020 and December 7, 2021, VE was 56% for mRNA COVID-19 vaccines overall, 65% for Moderna, and 50% for Pfizer-BioNTech. VE when Delta predominated (June to December 2021) was 54% for mRNA COVID-19 vaccines overall, 59% for Moderna, and 52% for Pfizer-BioNTech., (© 2022 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Background: Individuals in contact with persons with COVID-19 are at high risk of developing COVID-19; protection offered by COVID-19 vaccines in the context of known exposure is poorly understood., Methods: Symptomatic outpatients aged ≥12 years reporting acute onset of COVID-19-like illness and tested for SARS-CoV-2 between February 1 and September 30, 2021 were enrolled. Participants were stratified by self-report of having known contact with a COVID-19 case in the 14 days prior to illness onset. Vaccine effectiveness was evaluated using the test-negative study design and multivariable logistic regression., Results: Among 2229 participants, 283/451 (63%) of those reporting contact and 331/1778 (19%) without known contact tested SARS-CoV-2-positive. Adjusted vaccine effectiveness was 71% (95% confidence interval [CI], 49%-83%) among fully vaccinated participants reporting a known contact versus 80% (95% CI, 72%-86%) among those with no known contact (p-value for interaction = 0.2)., Conclusions: This study contributes to growing evidence of the benefits of vaccinations in preventing COVID-19 and support vaccination recommendations and the importance of efforts to increase vaccination coverage., (© Published 2022. This article is a U.S. Government work and is in the public domain in the USA. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Background: Studies have shown that adolescent vaccination rates with human papillomavirus (HPV) and quadrivalent meningococcal conjugate (MenACWY) vaccines are lower in rural areas of the U.S. than in urban areas. We sought to determine factors associated with vaccine acceptance in these two settings., Methods: We conducted a cross-sectional survey of 536 parents or guardians of teens age 13 through 15 years in select rural and urban counties of Minnesota and Wisconsin. We collected information on demographic variables, receipt of adolescent vaccines, and attitudes toward HPV vaccine in particular. Multivariable logistic regression models were used to assess associations between covariates and outcomes of interest (HPV vaccine receipt and MenACWY receipt)., Results: Of the 536 respondents, 267 (50%) resided in a rural county. Most respondents were female (78%) and non-Hispanic White (88%). About half (52%) of teens of the surveyed parents received the three vaccines recommended specifically for adolescents: 90% received tetanus-diphtheria-acellular pertussis (Tdap), 84% received MenACWY, and 60% received one or more doses of HPV vaccine. Rural and urban parents surveyed differed on several covariates relating to teen's health services, parent's demographics, and household characteristics. Parent's perception of the importance that their healthcare providers placed on vaccination with HPV and MenACWY were independently associated with receipt of each of those vaccines (odds ratio [OR] 6.37, 95% confidence interval [CI] 2.90-13.96 and OR 2.15, 95% CI 1.07-4.31, respectively). Parents of vaccinated teens were less likely to report concerns about potential harm from the HPV vaccine or having heard stories about health problems caused by the HPV vaccine., Conclusion: Teen receipt of HPV vaccine and MenACWY appears to be influenced by parents' perception of vaccine importance, provider recommendations, and concerns regarding potential harm from the HPV vaccine. Continued education of providers and parents of the importance of adolescent vaccinations is warranted., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Individuals with type 2 diabetes mellitus experience high rates of influenza virus infection and complications. We compared the magnitude and duration of serologic response to trivalent influenza vaccine in adults aged 50-80 with and without type 2 diabetes mellitus. Serologic response to influenza vaccination was similar in both groups: greater fold-increases in antibody titer occurred among participants with lower pre-vaccination antibody titers. Waning of antibody titers was not influenced by diabetes status., (Published 2021. This article is a U.S. Government work and is in the public domain in the USA. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

In the United States, annual vaccination against seasonal influenza is recommended for all persons aged ≥6 months except when contraindicated (1). Currently available influenza vaccines are designed to protect against four influenza viruses: A(H1N1)pdm09 (the 2009 pandemic virus), A(H3N2), B/Victoria lineage, and B/Yamagata lineage. Most influenza viruses detected this season have been A(H3N2) (2). With the exception of the 2020-21 season, when data were insufficient to generate an estimate, CDC has estimated the effectiveness of seasonal influenza vaccine at preventing laboratory-confirmed, mild/moderate (outpatient) medically attended acute respiratory infection (ARI) each season since 2004-05. This interim report uses data from 3,636 children and adults with ARI enrolled in the U.S. Influenza Vaccine Effectiveness Network during October 4, 2021-February 12, 2022. Overall, vaccine effectiveness (VE) against medically attended outpatient ARI associated with influenza A(H3N2) virus was 16% (95% CI = -16% to 39%), which is considered not statistically significant. This analysis indicates that influenza vaccination did not reduce the risk for outpatient medically attended illness with influenza A(H3N2) viruses that predominated so far this season. Enrollment was insufficient to generate reliable VE estimates by age group or by type of influenza vaccine product (1). CDC recommends influenza antiviral medications as an adjunct to vaccination; the potential public health benefit of antiviral medications is magnified in the context of reduced influenza VE. CDC routinely recommends that health care providers continue to administer influenza vaccine to persons aged ≥6 months as long as influenza viruses are circulating, even when VE against one virus is reduced, because vaccine can prevent serious outcomes (e.g., hospitalization, intensive care unit (ICU) admission, or death) that are associated with influenza A(H3N2) virus infection and might protect against other influenza viruses that could circulate later in the season., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Ana Florea reports unrelated institutional grant support for research from Gilead, GlaxoSmithKline, Moderna, and Pfizer. Carlos G. Grijalva reports consulting fees from Merck, Pfizer, and Sanofi Pasteur, and institutional grant support from the Agency for Health Care Research and Quality, Campbell Alliance/Syneos Health, the Food and Drug Administration, and the National Institutes of Health. Emily T. Martin reports institutional grant support from Merck. Arnold S. Monto reports personal fees from Sanofi and nonfinancial support from Seqirus. Mary Patricia Nowalk reports unrelated institutional grant support and personal fees from Merck Sharp & Dohme and institutional investigator-initiated grant support from Sanofi Pasteur. Sara Y. Tartof reports unrelated institutional grant support from Pfizer and GlaxoSmithKline. David E. Wentworth reports institutional grant support from Seqirus for a cooperative research and development agreement on isolation and propagation of influenza viruses in qualified manufacturing cell lines and patents 10,030,231 (influenza reassortment) and 10,272,149 (modified bat influenza viruses and their uses). No other potential conflicts of interest were disclosed.

Intraseason timing of influenza infection among persons of different ages could reflect relative contributions to propagation of seasonal epidemics and has not been examined among ambulatory patients. Using data from the US Influenza Vaccine Effectiveness Network, we calculated risk ratios derived from comparing weekly numbers of influenza cases prepeak with those postpeak during the 2010-2011 through 2018-2019 influenza seasons. We sought to determine age-specific differences during the ascent versus descent of an influenza season by influenza virus type and subtype. We estimated 95% credible intervals around the risk ratios using Bayesian joint posterior sampling of weekly cases. Our population consisted of ambulatory patients with laboratory-confirmed influenza who enrolled in an influenza vaccine effectiveness study at 5 US sites during 9 influenza seasons after the 2009 influenza A virus subtype H1N1 (H1N1) pandemic. We observed that young children aged <5 years tended to more often be infected with H1N1 during the prepeak period, while adults aged ≥65 years tended to more often be infected with H1N1 during the postpeak period. However, for influenza A virus subtype H3N2, children aged <5 years were more often infected during the postpeak period. These results may reflect a contribution of different age groups to seasonal spread, which may differ by influenza virus type and subtype., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2021. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

The association of influenza vaccine and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was assessed by test-negative design using data collected for a study of outpatient COVID-19-like illness with onset dates from June to September 2020. Multivariable logistic regression models examined the association between receipt of 2019-2020 influenza vaccine and PCR-confirmed SARS-CoV-2 with adjustment for potential confounders. Receipt of influenza vaccine during the 2019-2020 influenza season was not associated with increased odds of SARS-CoV-2 infection in adults (aOR 0.83, 95% CI 0.63 to 1.10) or children (aOR 0.92, 95% CI 0.47 to 1.80)., (© 2021 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Methods for assessing influenza vaccine efficacy and effectiveness have evolved over six decades. Randomized trials remain the gold standard for licensure, but observational studies are needed for annual assessment of vaccine effectiveness (VE). The test-negative design (TND) has become the de facto standard for these field studies. Patients who seek medical care with acute respiratory illness are tested for influenza, and VE is estimated from the odds of vaccination among influenza cases versus test-negative controls. VE varies across seasons, populations, age groups, and products, but VE estimates are consistently higher for A(H1N1)pdm09 and type B compared with A(H3N2). VE studies are increasingly used in combination with molecular epidemiology to understand the viral and immune system factors that drive clinical efficacy and effectiveness. The emerging field of immunoepidemiology offers the potential to understand complex host-virus interactions that affect vaccine protection, and this knowledge will contribute to universal vaccine development., (Copyright © 2021 Cold Spring Harbor Laboratory Press; all rights reserved.)

To prevent further transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), CDC currently recommends that persons who have been in close contact with someone with SARS-CoV-2 infection should quarantine (stay away from other persons) for 14 days after the last known contact.* However, quarantine might be difficult to maintain for a prolonged period. A shorter quarantine might improve compliance, and CDC recommends two options to reduce the duration of quarantine for close contacts without symptoms, based on local circumstances and availability of testing: 1) quarantine can end on day 10 without a test or 2) quarantine can end on day 7 after receiving a negative test result. † However, shorter quarantine might permit ongoing disease transmission from persons who develop symptoms or become infectious near the end of the recommended 14-day period. Interim data from an ongoing study of household transmission of SARS-CoV-2 were analyzed to understand the proportion of household contacts that had detectable virus after a shortened quarantine period. Persons who were household contacts of index patients completed a daily symptom diary and self-collected respiratory specimens for 14 days. Specimens were tested for SARS-CoV-2 using reverse transcription-polymerase chain reaction (RT-PCR). Among 185 household contacts enrolled, 109 (59%) had detectable SARS-CoV-2 at any time; 76% (83/109) of test results were positive within 7 days, and 86% (94 of 109) were positive within 10 days after the index patient's illness onset date. Among household contacts who received negative SARS-CoV-2 test results and were asymptomatic through day 7, there was an 81% chance (95% confidence interval [CI] = 67%-90%) of remaining asymptomatic and receiving negative RT-PCR test results through day 14; this increased to 93% (95% CI = 78%-98%) for household members who were asymptomatic with negative RT-PCR test results through day 10. Although SARS-CoV-2 quarantine periods shorter than 14 days might be easier to adhere to, there is a potential for onward transmission from household contacts released before day 14., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal potential conflicts of interest were disclosed. Carlos G. Grijalva reports personal consulting fees from Sanofi, Merck, and Pfizer; grants from Sanofi, Campbell Alliance, the National Institutes of Health, and the Agency for HealthCare Research and Quality; and a contract from the Food and Drug Administration, outside the submitted work. Natasha B. Halasa reports grants from Sanofi and Quidel, and personal fees from Genetech, outside the submitted work. No other potential conflicts of interest were disclosed.

We compared symptoms and characteristics of 4961 ambulatory patients with and without laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection. Findings indicate that clinical symptoms alone would be insufficient to distinguish between coronavirus disease 2019 and other respiratory infections (eg, influenza) and/or to evaluate the effects of preventive interventions (eg, vaccinations)., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2020.)

Improved understanding of transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), within households could aid control measures. However, few studies have systematically characterized the transmission of SARS-CoV-2 in U.S. households (1). Previously reported transmission rates vary widely, and data on transmission rates from children are limited. To assess household transmission, a case-ascertained study was conducted in Nashville, Tennessee, and Marshfield, Wisconsin, commencing in April 2020. In this study, index patients were defined as the first household members with COVID-19-compatible symptoms who received a positive SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) test result, and who lived with at least one other household member. After enrollment, index patients and household members were trained remotely by study staff members to complete symptom diaries and obtain self-collected specimens, nasal swabs only or nasal swabs and saliva samples, daily for 14 days. For this analysis, specimens from the first 7 days were tested for SARS-CoV-2 using CDC RT-PCR protocols. † A total of 191 enrolled household contacts of 101 index patients reported having no symptoms on the day of the associated index patient's illness onset, and among these 191 contacts, 102 had SARS-CoV-2 detected in either nasal or saliva specimens during follow-up, for a secondary infection rate of 53% (95% confidence interval [CI] = 46%-60%). Among fourteen households in which the index patient was aged <18 years, the secondary infection rate from index patients aged <12 years was 53% (95% CI = 31%-74%) and from index patients aged 12-17 years was 38% (95% CI = 23%-56%). Approximately 75% of secondary infections were identified within 5 days of the index patient's illness onset, and substantial transmission occurred whether the index patient was an adult or a child. Because household transmission of SARS-CoV-2 is common and can occur rapidly after the index patient's illness onset, persons should self-isolate immediately at the onset of COVID-like symptoms, at the time of testing as a result of a high risk exposure, or at the time of a positive test result, whichever comes first. Concurrent to isolation, all members of the household should wear a mask when in shared spaces in the household. § ., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Carlos G. Grijalva reports personal consulting fees from Sanofi, Merck, and Pfizer; grants from Sanofi, Campbell Alliance, the National Institutes of Health, the Agency for HealthCare Research and Quality, and a contract from the Food and Drug Administration, outside the submitted work. Natasha B. Halasa reports grants from Sanofi and Quidel and personal fees from Genetech, outside the submitted work. No other potential conflicts of interest were disclosed.

We developed and evaluated a model to predict serious outcomes among 243 adults ≥60 years old with medically attended respiratory illness and laboratory-confirmed respiratory syncytial virus (RSV); 47 patients had a serious outcome defined as hospital admission, emergency department (ED) visit, or pneumonia diagnosis. The model used logistic regression with penalized maximum likelihood estimation. The reduced penalized model included age ≥ 75 years, ≥1 ED visit in prior year, crackles/rales, tachypnea, wheezing, new/increased sputum, and new/increased dyspnea. The optimal score cutoff yielded sensitivity and specificity of 66.0% and 81.6%. This prediction model provided moderate utility for identifying older adults with elevated risk of complicated RSV illness., (© 2020 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Seasonal variation in the age distribution of influenza A cases suggests that factors other than age shape susceptibility to medically attended infection. We ask whether these differences can be partly explained by protection conferred by childhood influenza infection, which has lasting impacts on immune responses to influenza and protection against new influenza A subtypes (phenomena known as original antigenic sin and immune imprinting). Fitting a statistical model to data from studies of influenza vaccine effectiveness (VE), we find that primary infection appears to reduce the risk of medically attended infection with that subtype throughout life. This effect is stronger for H1N1 compared to H3N2. Additionally, we find evidence that VE varies with both age and birth year, suggesting that VE is sensitive to early exposures. Our findings may improve estimates of age-specific risk and VE in similarly vaccinated populations and thus improve forecasting and vaccination strategies to combat seasonal influenza., Competing Interests: PA, EB, SC No competing interests declared, HM has received funding from Seqirus, unrelated to this work. The author has no other competing interests to declare, (© 2020, Arevalo et al.)

Background: The effects of repeated influenza vaccination in children are not well understood. In this study, we evaluated previous vaccination effects on antibody response after vaccination with trivalent inactivated influenza vaccine (IIV) or quadrivalent live-attenuated influenza vaccine (LAIV) among school-aged children (5-17 years) across 3 seasons., Methods: Children were enrolled in the fall of 2013, 2014, and 2015. The participants received IIV or LAIV according to parent preference (2013-2014) or our randomization scheme (2014-2015). All study children received IIV in 2015-2016. Hemagglutination-inhibition assays measured antibody response to egg-grown vaccine strains from prevaccination and postvaccination serum samples. Geometric mean titers (GMTs) and increases in GMTs from before to after vaccination (geometric mean fold rise [GMFR]) were estimated from repeated-measures linear mixed models., Results: We enrolled 161 children in 2013-2014, 128 in 2014-2015, and 126 in 2015-2016. Among the IIV recipients, responses to the influenza A(H1N1)pdm09 and B vaccine strains were lowest among children who had received a previous-season IIV. The GMFRs for strains A(H1N1)pdm09 and B were 1.5 to 2.3 for previous-season IIV and 4.3 to 12.9 for previous-season LAIV or no previous vaccine. GMFRs were lower for strain A(H3N2), and differences according to previous-season vaccination history were smaller and not significant in most seasons. Most children had a post-IIV vaccination titer of ≥40 for vaccine strains in all seasons, regardless of previous-season vaccination history. Little to no increase in antibody levels was observed after vaccination with LAIV., Conclusions: Serologic response to vaccination was greatest for IIV, but previous-season vaccination modified IIV response to A(H1N1)pdm09 and B. Influenza A(H3N2) responses were low in all groups, and LAIV generated minimal serologic response against all strains., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society.)

Background: Asthma was associated with influenza hospitalizations in children during the 2009 pandemic, but it is unclear if asthma is associated with serious illness during seasonal epidemics. Little is known regarding the effect of vaccination on influenza severity in children with asthma., Methods: Children aged 5-17 years in a community cohort presenting with acute respiratory illness were prospectively enrolled and tested for influenza from 2007-08 through 2017-18 (excluding the 2009-10 pandemic season). Data from the electronic health record were extracted to determine asthma status and serious outcomes associated with influenza infection. A serious outcome was defined as hospitalization, emergency department visit, and/or pneumonia diagnosis within 30 days of symptom onset. Multivariable logistic regression models were used to assess asthma status and effect of vaccination on odds of a serious outcome., Results: One thousand seven hundred and sixty four medically-attended influenza infections among school-aged children were included. Asthma was confirmed in 287 (16%) children. A serious influenza-associated outcome occurred in 104 (6%) children. The odds of a serious outcome did not differ between those with confirmed asthma and those without asthma [adjusted odds ratio (aOR): 1.35, 95% confidence interval (CI): (0.77-2.35), P = .3]. The effect of vaccination on serious outcomes was not modified by asthma status [aOR for children without asthma: 0.55 (95% CI: 0.28-1.07), children with asthma: 1.39 (95% CI: 0.53-3.69); interaction P-value = .12]., Conclusions: Asthma was not a risk factor for serious illness among children with influenza. Additional studies are needed to better understand the role of influenza vaccination in preventing serious outcomes among children with asthma., (© 2019 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

During the 2019-20 influenza season, influenza-like illness (ILI)* activity first exceeded the national baseline during the week ending November 9, 2019, signaling the earliest start to the influenza season since the 2009 influenza A(H1N1) pandemic. Activity remains elevated as of mid-February 2020. In the United States, annual vaccination against seasonal influenza is recommended for all persons aged ≥6 months (1). During each influenza season, CDC estimates seasonal influenza vaccine effectiveness in preventing laboratory-confirmed influenza associated with medically attended acute respiratory illness (ARI). This interim report used data from 4,112 children and adults enrolled in the U.S. Influenza Vaccine Effectiveness Network (U.S. Flu VE Network) during October 23, 2019-January 25, 2020. Overall, vaccine effectiveness (VE) against any influenza virus associated with medically attended ARI was 45% (95% confidence interval [CI] = 36%-53%). VE was estimated to be 50% (95% CI = 39%-59%) against influenza B/Victoria viruses and 37% (95% CI = 19%-52%) against influenza A(H1N1)pdm09, indicating that vaccine has significantly reduced medical visits associated with influenza so far this season. Notably, vaccination provided substantial protection (VE = 55%; 95% CI = 42%-65%) among children and adolescents aged 6 months-17 years. Interim VE estimates are consistent with those from previous seasons, ranging from 40%-60% when influenza vaccines were antigenically matched to circulating viruses. CDC recommends that health care providers continue to administer influenza vaccine to persons aged ≥6 months because influenza activity is ongoing, and the vaccine can still prevent illness, hospitalization, and death associated with currently circulating influenza viruses as well as other influenza viruses that might circulate later in the season., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Richard K. Zimmerman reports grants from Sanofi Pasteur, Pfizer Inc., and Merck & Co., outside the submitted work; Arnold S. Monto reports personal fees from Sanofi Pasteur and Seqirus, outside the submitted work; Emily T. Martin reports consulting fees from Pfizer Inc. and research funding from Merck & Co., outside the submitted work; Michael L. Jackson reports grants from Sanofi Pasteur, outside the submitted work; Mary Patricia Nowalk reports grants from Merck & Co, Inc. and Pfizer, Inc., outside the submitted work; and Huong Q. McLean reports grants from Seqirus, outside the submitted work. No other potential conflicts of interest were disclosed.

Few studies have assessed adolescent human papillomavirus (HPV) vaccine attitudes and whether they are associated with vaccination uptake. This study characterized HPV vaccine attitudes among male and female adolescents, identified factors associated with attitude changes, and examined associations between attitudes and vaccination receipt. Surveys were administered to adolescents aged 15-16 years who had not completed the HPV vaccine series. A modified version of the Carolina HPV Immunization Attitudes and Beliefs Scale (CHIAS) was employed to assess barriers, harms, ineffectiveness, and uncertainties scores. Surveys were available from 108 participants; 63% were male and 33% had initiated the HPV vaccine series at baseline. CHIAS scores significantly decreased (i.e., became more favorable) between baseline and follow-up for barriers (p = 0.01) and uncertainties (p < 0.01). At least one sociodemographic/clinical factor was associated with changes in each score. Attitude changes were not associated with receipt of HPV vaccine, although adolescents with higher baseline harms scores were significantly less likely to receive an HPV vaccine dose (OR = 0.67). Adolescents' HPV vaccine attitudes slightly improved over a one-year period during which an intervention was implemented. More research is needed to learn how parent and adolescent HPV vaccine attitudes form, and how best to address concerns about vaccine harms., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Over five seasons, we determined the proportion of outpatients with laboratory-confirmed, influenza-associated illness who were hospitalized within 30 days following the outpatient visit. Overall, 136 (1.7%) of 7813 influenza-positive patients were hospitalized a median of 4 days after an outpatient visit. Patients aged ≥ 65 years and those with high-risk conditions were at increased risk of hospitalization. After controlling for age and high-risk conditions, vaccination status and infecting influenza virus type were not associated with hospitalization risk among adults., (Published 2018. This article is a U.S. Government work and is in the public domain in the USA. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

In the United States, annual vaccination against seasonal influenza is recommended for all persons aged ≥6 months (https://www.cdc.gov/flu/protect/whoshouldvax.htm). Effectiveness of seasonal influenza vaccine varies by season. During each influenza season since 2004-05, CDC has estimated the effectiveness of seasonal influenza vaccine to prevent laboratory-confirmed influenza associated with medically attended acute respiratory illness (ARI). This interim report uses data from 3,254 children and adults enrolled in the U.S. Influenza Vaccine Effectiveness Network (U.S. Flu VE Network) during November 23, 2018-February 2, 2019. During this period, overall adjusted vaccine effectiveness against all influenza virus infection associated with medically attended ARI was 47% (95% confidence interval [CI] = 34%-57%). For children aged 6 months-17 years, overall vaccine effectiveness was 61% (44%-73%). Seventy-four percent of influenza A infections for which subtype information was available were caused by A(H1N1)pdm09 viruses. Vaccine effectiveness was estimated to be 46% (30%-58%) against illness caused by influenza A(H1N1)pdm09 viruses. CDC recommends that health care providers continue to administer influenza vaccine because influenza activity is ongoing and the vaccine can still prevent illness, hospitalization, and death associated with currently circulating influenza viruses, or other influenza viruses that might circulate later in the season. During the 2017-18 influenza season, in which influenza A(H3N2) predominated, vaccination was estimated to prevent 7.1 million illnesses, 3.7 million medical visits, 109,000 hospitalizations, and 8,000 deaths (1). Vaccination can also reduce the severity of influenza-associated illness (2). Persons aged ≥6 months who have not yet been vaccinated this season should be vaccinated., Competing Interests: All authors have completed and submitted the ICMJE form for disclosure of potential conflicts of interest. Richard Zimmerman reports grants from Sanofi Pasteur, Pfizer, and Merck & Co., outside the submitted work; Arnold S. Monto reports personal fees from Sanofi Pasteur and Seqirus, outside the submitted work; Emily T. Martin reports personal fees from Pfizer, outside the submitted work; Michael L. Jackson reports grants from Sanofi Pasteur, outside the submitted work; Mary Patricia Nowalk reports grants from Merck & Co, Inc. and Pfizer, outside the submitted work; and Huong Q. McLean reports grants from Seqirus, outside the submitted work. No other potential conflicts of interest were disclosed.

Background: The epidemiology and burden of respiratory syncytial virus (RSV) illness are not well defined in older adults., Methods: Adults ≥60 years old seeking outpatient care for acute respiratory illness were recruited from 2004-2005 through 2015-2016 during the winter seasons. RSV was identified from respiratory swabs by multiplex polymerase chain reaction. Clinical characteristics and outcomes were ascertained by interview and medical record abstraction. The incidence of medically attended RSV was estimated for each seasonal cohort., Results: RSV was identified in 243 (11%) of 2257 enrollments (241 of 1832 individuals), including 121 RSV type A and 122 RSV type B. The RSV clinical outcome was serious in 47 (19%), moderate in 155 (64%), and mild in 41 (17%). Serious outcomes included hospital admission (n = 29), emergency department visit (n = 13), and pneumonia (n = 23) and were associated with lower respiratory tract symptoms during the enrollment visit. Moderate outcomes included receipt of a new antibiotic prescription (n = 144; 59%), bronchodilator/nebulizer (n = 45; 19%), or systemic corticosteroids (n = 28; 12%). The relative risk of a serious outcome was significantly increased in persons aged ≥75 years (vs 60-64 years) and in those with chronic obstructive pulmonary disease or congestive heart failure. The average seasonal incidence was 139 cases/10 000, and it was significantly higher in persons with cardiopulmonary disease compared with others (rate ratio, 1.89; 95% confidence interval, 1.44-2.48)., Conclusions: RSV causes substantial outpatient illness with lower respiratory tract involvement. Serious outcomes are common in older patients and those with cardiopulmonary disease.

Self-reported influenza vaccination is generally accurate for the current season, but the accuracy of self-report for vaccination in prior seasons is largely unknown. This study evaluated the accuracy of self-report for current and prior season influenza vaccination among patients with medically attended acute respiratory illness enrolled in a study of influenza vaccine effectiveness during the 2014-15 influenza season. It demonstrates there is a greater potential for exposure misclassification when prior season vaccinations are ascertained by self-report. Percent agreement between self-report and final status was high for both current and prior season vaccination: 97.7% and 93.2%, respectively., (© 2018 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Importance: Some studies have reported negative effects of prior-season influenza vaccination. Prior-season influenza vaccination effects on vaccine effectiveness (VE) in children are not well understood., Objective: To assess the association of prior-season influenza vaccination with subsequent VE in children aged 2 to 17 years., Design, Setting, and Participants: This multiseason, test-negative case-control study was conducted in outpatient clinics at 4 US sites among children aged 2 to 17 years with a medically attended febrile acute respiratory illness. Participants were recruited during the 2013-2014, 2014-2015, and 2015-2016 seasons when influenza circulated locally. Cases were children with influenza confirmed by reverse-transcription polymerase chain reaction. Test-negative control individuals were children with negative test results for influenza., Exposures: Vaccination history, including influenza vaccine type received in the enrollment season (live attenuated influenza vaccine [LAIV], inactivated influenza vaccine [IIV], or no vaccine) and season before enrollment (LAIV, IIV, or no vaccine), determined from medical records and immunization registries., Main Outcomes and Measures: LAIV and IIV effectiveness by influenza type and subtype (influenza A[H1N1]pdm09, influenza A[H3N2], or influenza B), estimated as 100 × (1 - odds ratio) in a logistic regression model with adjustment for potential confounders. Prior season vaccination associations were assessed with an interaction term., Results: Of 3369 children (1749 [52%] male; median age, 6.6 years [range, 2-17 years]) included in the analysis, 772 (23%) had a positive test result for influenza and 1674 (50%) were vaccinated in the enrollment season. Among LAIV recipients, VE against influenza A(H3N2) was higher among children vaccinated in both the enrollment and 1 prior season (50.3% [95% CI, 17.0% to 70.2%]) than among those without 1 prior season vaccination (-82.4% [95% CI, -267.5% to 9.5%], interaction P < .001). The effectiveness of LAIV against influenza A(H1N1)pdm09 was not associated with prior season vaccination among those with prior season vaccination (47.5% [95% CI, 11.4% to 68.9%]) and among those without prior season vaccination (7.8% [95% CI, -101.9% to 57.9%]) (interaction P = .37). Prior season vaccination was not associated with effectiveness of IIV against influenza A(H3N2) (38.7% [95% CI, 6.8% to 59.6%] among those with prior-season vaccination and 23.2% [95% CI, -38.3% to 57.4%] among those without prior-season vaccination, interaction P = .16) or with effectiveness of IIV against influenza A[H1N1]pdm09 (72.4% [95% CI, 56.0% to 82.7%] among those with prior season vaccination and 67.5% [95% CI, 32.1% to 84.4%] among those without prior season vaccination, interaction P = .93). Residual protection from prior season vaccination only (no vaccination in the enrollment season) was observed for influenza B (LAIV: 60.0% [95% CI, 36.8% to 74.7%]; IIV: 60.0% [36.9% to 74.6%]). Similar results were observed in analyses that included repeated vaccination in 2 and 3 prior seasons., Conclusions and Relevance: Influenza VE varied by influenza type and subtype and vaccine type, but prior-season vaccination was not associated with reduced VE. These findings support current recommendations for annual influenza vaccination of children.

Background: Parental attitudes play a key role in their decisions to vaccinate adolescents against the human papillomavirus (HPV). Little is known, however, about the formative experiences that shape parents' attitudes about the HPV vaccine., Methods: We conducted semi-structured interviews with 25 parents of 11-17 year old adolescents in Wisconsin who changed their HPV vaccine attitudes (per prior surveys) over one year. A modified grounded theory approach was then used to generate primary themes of attitudinal determinants., Results: Participants were predominately mothers. We identified three major themes that shaped parents' HPV attitudes: (1) the perceived likelihood of the HPV vaccine preventing cancer, (2) agency in adolescence and gauging their adolescent child's intent for sexual activity, (3) the credibility of HPV vaccine information sources. General messaging around cancer prevention did not always supersede some parents' concerns about the vaccine's perceived link to sexual activity. Parents often viewed their adolescent child's feelings about the HPV vaccine as a gauge of their (child's) intent for sexual activity. Interviewees felt a sense of responsibility to educate themselves about the HPV vaccine using multiple sources and particularly looked to their medical provider to filter conflicting information., Conclusions: More family-specific (vs. disease-prevention) messaging and recommendations may be needed in the clinical environment to sway some parents' negative attitudes about the HPV vaccine. Future research should explore additional strategies to improve HPV vaccine attitudes, such as situating the vaccine in the context of a monogamous lifestyle that many parents wish to impart to their children.

Importance: Acute respiratory infections (ARIs) are the syndrome for which antibiotics are most commonly prescribed; viruses for which antibiotics are ineffective cause most ARIs., Objectives: To characterize antibiotic prescribing among outpatients with ARI during influenza season and to identify targets for reducing inappropriate antibiotic prescribing for common ARI diagnoses, including among outpatients with laboratory-confirmed influenza., Design, Setting, and Participants: Cohort study enrolling outpatients aged 6 months or older with ARI evaluated at outpatient clinics associated with 5 US Influenza Vaccine Effectiveness Network sites during the 2013-2014 and 2014-2015 influenza seasons. All patients received influenza testing by real-time reverse transcriptase-polymerase chain reaction for research purposes only. Antibiotic prescriptions, medical history, and International Classification of Diseases, Ninth Revision diagnosis codes were collected from medical and pharmacy records, as were group A streptococcal (GAS) testing results in a patient subset., Exposure: Visit for ARI, defined by a new cough of 7 days' duration or less., Main Outcomes and Measures: Antibiotic prescription within 7 days of enrollment. Appropriateness of antibiotic prescribing was based on diagnosis codes, clinical information, and influenza and GAS testing results., Results: Of 14 987 patients with ARI (mean [SD] age, 32 [24] years; 8638 [58%] women; 11 892 [80%] white), 6136 (41%) were prescribed an antibiotic. Among these 6136 patients, 2522 (41%) had diagnoses for which antibiotics are not indicated; 2106 (84%) of these patients were diagnosed as having a viral upper respiratory tract infection or bronchitis (acute or not otherwise specified). Among the 3306 patients (22%) not diagnosed as having pneumonia and who had laboratory-confirmed influenza, 945 (29%) were prescribed an antibiotic, accounting for 17% of all antibiotic prescriptions among patients with nonpneumonia ARI. Among 1248 patients with pharyngitis, 1137 (91%) had GAS testing; 440 of the 1248 patients (35%) were prescribed antibiotics, among whom 168 (38%) had negative results on GAS testing. Of 1200 patients with sinusitis and no other indication for antibiotic treatment who received an antibiotic, 454 (38%) had symptoms for 3 days or less prior to the outpatient visit, suggesting acute viral sinusitis not requiring antibiotics., Conclusions and Relevance: Antibiotic overuse remains widespread in the treatment of outpatient ARIs, including among patients with laboratory-confirmed influenza, although study sites may not be representative of other outpatient settings. Identified targets for improved outpatient antibiotic stewardship include eliminating antibiotic treatment of viral upper respiratory tract infections and bronchitis and improving adherence to prescribing guidelines for pharyngitis and sinusitis. Increased access to sensitive and timely virus diagnostic tests, particularly for influenza, may reduce unnecessary antibiotic use for these syndromes.

In the United States, annual vaccination against seasonal influenza is recommended for all persons aged ≥6 months (1). During each influenza season since 2004-05, CDC has estimated the effectiveness of seasonal influenza vaccine to prevent laboratory-confirmed influenza associated with medically attended acute respiratory illness (ARI). This report uses data from 4,562 children and adults enrolled in the U.S. Influenza Vaccine Effectiveness Network (U.S. Flu VE Network) during November 2, 2017-February 3, 2018. During this period, overall adjusted vaccine effectiveness (VE) against influenza A and influenza B virus infection associated with medically attended ARI was 36% (95% confidence interval [CI] = 27%-44%). Most (69%) influenza infections were caused by A(H3N2) viruses. VE was estimated to be 25% (CI = 13% to 36%) against illness caused by influenza A(H3N2) virus, 67% (CI = 54%-76%) against A(H1N1)pdm09 viruses, and 42% (CI = 25%-56%) against influenza B viruses. These early VE estimates underscore the need for ongoing influenza prevention and treatment measures. CDC continues to recommend influenza vaccination because the vaccine can still prevent some infections with currently circulating influenza viruses, which are expected to continue circulating for several weeks. Even with current vaccine effectiveness estimates, vaccination will still prevent influenza illness, including thousands of hospitalizations and deaths. Persons aged ≥6 months who have not yet been vaccinated this season should be vaccinated., Competing Interests: No conflicts of interest were reported.

On October 20, 2017, Zoster Vaccine Recombinant, Adjuvanted (Shingrix, GlaxoSmithKline, [GSK] Research Triangle Park, North Carolina), a 2-dose, subunit vaccine containing recombinant glycoprotein E in combination with a novel adjuvant (AS01 B ), was approved by the Food and Drug Administration for the prevention of herpes zoster in adults aged ≥50 years. The vaccine consists of 2 doses (0.5 mL each), administered intramuscularly, 2-6 months apart (1). On October 25, 2017, the Advisory Committee on Immunization Practices (ACIP) recommended the recombinant zoster vaccine (RZV) for use in immunocompetent adults aged ≥50 years., Competing Interests: No conflicts of interest were reported.

Background: Population-based estimates of influenza-associated outpatient visits including both pandemic and interpandemic seasons are uncommon. Comparisons of such estimates with laboratory-confirmed rates of outpatient influenza are rare., Objective: To estimate influenza-associated outpatient visits in 6 US integrated healthcare delivery organizations enrolling ~7.7 million persons., Methods: Using negative binomial regression methods, we modeled rates of influenza-associated visits with ICD-9-CM-coded pneumonia or acute respiratory outpatient visits during 2001-10. These estimated counts were added to visits coded specifically for influenza to derive estimated rates. We compared these rates with those observed in 2 contemporaneous studies recording RT-PCR-confirmed influenza outpatient visits., Results: Outpatient rates estimated with pneumonia visits were 39 (95% confidence interval [CI], 30-70) and 203 (95% CI, 180-240) per 10 000 person-years, respectively, for interpandemic and pandemic seasons. Corresponding rates estimated with respiratory visits were 185 (95% CI, 161-255) and 542 (95% CI, 441-823) per 10 000 person-years. During the pandemic, children aged 2-17 years had the largest increase in rates (when estimated with pneumonia visits, from 64 [95% CI, 50-121] to 381 [95% CI, 366-481]). Rates estimated with pneumonia visits were consistent with rates of RT-PCR-confirmed influenza visits during 4 of 5 seasons in 1 comparison study. In another, rates estimated with pneumonia visits during the pandemic for children and adults were consistent in timing, peak, and magnitude., Conclusions: Estimated rates of influenza-associated outpatient visits were higher in children than adults during pre-pandemic and pandemic seasons. Rates estimated with pneumonia visits plus influenza-coded visits were similar to rates from studies using RT-PCR-confirmed influenza., (Published 2017. This article is a U.S. Government work and is in the public domain in the USA. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Background: Human papillomavirus (HPV) vaccine coverage rates remain low. This is believed to reflect parental hesitancy, but few studies have examined how changes in parents' attitudes impact HPV vaccine uptake. This study examined the association between changes in parents' vaccine attitudes and HPV vaccine receipt in their adolescent children., Methods: A baseline and 1-year follow-up survey of HPV vaccine attitudes was administered to parents of 11-17 year olds who had not completed the HPV vaccine series. Changes in attitudinal scores (barriers, harms, ineffectiveness, and uncertainties) from the Carolina HPV Immunization Attitudes and Beliefs Scale were assessed. Two outcomes were measured (in parents' adolescent children) over an 18-month period and analyzed using multivariable regression; receipt of next scheduled HPV vaccine dose and 3-dose series completion., Results: There were 221 parents who completed the baseline survey (11% response rate) and 164 with available follow-up data; 60% of their adolescent children received a next HPV vaccine dose and 38% completed the vaccine series at follow-up. Decrease in parents' uncertainties was a significant predictor of vaccine receipt, with each 1-point reduction in uncertainties score associated with 4.9 higher odds of receipt of the next vaccine dose. Higher baseline harms score was the only significant predictor of lower series completion., Conclusions: Reductions in parents' uncertainties appeared to result in greater likelihood of their children receiving the HPV vaccine. Only baseline concerns about vaccine harms were associated with lower series completion rate. Education for parents should emphasize the HPV vaccine's safety profile.

Background: Acute respiratory illnesses (ARIs) are common in school-aged children, but few studies have assessed school absenteeism due to specific respiratory viruses., Objective: To evaluate school absenteeism among children with medically attended ARI due to common viruses., Methods: We analyzed follow-up surveys from children seeking care for acute respiratory illness who were enrolled in the influenza vaccine effectiveness study at Marshfield Clinic during the 2012-2013 through 2014-2015 influenza seasons. Archived influenza-negative respiratory swabs were retested using multiplex RT-PCR to detect 16 respiratory virus targets. Negative binomial and logistic regression models were used to examine the association between school absence and type of respiratory viruses; endpoints included mean days absent from school and prolonged (>2 days) absence. We examined the association between influenza vaccination and school absence among children with RT-PCR-confirmed influenza., Results: Among 1027 children, 2295 days of school were missed due to medically attended ARIs; influenza accounted for 39% of illness episodes and 47% of days missed. Mean days absent were highest for influenza (0.96-1.19) and lowest for coronavirus (0.62). Children with B/Yamagata infection were more likely to report prolonged absence than children with A/H1N1 or A/H3N2 infection [OR (95% CI): 2.1 (1.0, 4.5) and 1.7 (1.0, 2.9), respectively]. Among children with influenza, vaccination status was not associated with prolonged absence., Conclusions: School absenteeism due to medically attended ARIs varies by viral infection. Influenza B infections accounted for the greatest burden of absenteeism., (© 2016 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

In the United States, annual vaccination against seasonal influenza is recommended for all persons aged ≥6 months (1). Each influenza season since 2004-05, CDC has estimated the effectiveness of seasonal influenza vaccine to prevent influenza-associated, medically attended, acute respiratory illness (ARI). This report uses data, as of February 4, 2017, from 3,144 children and adults enrolled in the U.S. Influenza Vaccine Effectiveness Network (U.S. Flu VE Network) during November 28, 2016-February 4, 2017, to estimate an interim adjusted effectiveness of seasonal influenza vaccine for preventing laboratory-confirmed influenza virus infection associated with medically attended ARI. During this period, overall vaccine effectiveness (VE) (adjusted for study site, age group, sex, race/ethnicity, self-rated general health, and days from illness onset to enrollment) against influenza A and influenza B virus infection associated with medically attended ARI was 48% (95% confidence interval [CI] = 37%-57%). Most influenza infections were caused by A (H3N2) viruses. VE was estimated to be 43% (CI = 29%-54%) against illness caused by influenza A (H3N2) virus and 73% (CI = 54%-84%) against influenza B virus. These interim VE estimates indicate that influenza vaccination reduced the risk for outpatient medical visits by almost half. Because influenza activity remains elevated (2), CDC and the Advisory Committee on Immunization Practices recommend that annual influenza vaccination efforts continue as long as influenza viruses are circulating (1). Vaccination with 2016-17 influenza vaccines will reduce the number of infections with most currently circulating influenza viruses. Persons aged ≥6 months who have not yet been vaccinated this season should be vaccinated as soon as possible.

Background: The use of neuraminidase-inhibiting anti-viral medication to treat influenza is relatively infrequent. Rapid, cost-effective methods for diagnosing influenza are needed to enable appropriate prescribing. Multi-viral respiratory panels using reverse transcription polymerase chain reaction (PCR) assays to diagnose influenza are accurate but expensive and more time-consuming than low sensitivity rapid influenza tests. Influenza clinical decision algorithms are both rapid and inexpensive, but most are based on regression analyses that do not account for higher order interactions. This study used classification and regression trees (CART) modeling to estimate probabilities of influenza., Methods: Eligible enrollees ≥ 5 years old (n = 4,173) who presented at ambulatory centers for treatment of acute respiratory illness (≤7 days) with cough or fever in 2011-2012, provided nasal and pharyngeal swabs for PCR testing for influenza, information on demographics, symptoms, personal characteristics and self-reported influenza vaccination status., Results: Antiviral medication was prescribed for just 15 % of those with PCR-confirmed influenza. An algorithm that included fever, cough, and fatigue had sensitivity of 84 %, specificity of 48 %, positive predictive value (PPV) of 23 % and negative predictive value (NPV) of 94 % for the development sample., Conclusions: The CART algorithm has good sensitivity and high NPV, but low PPV for identifying influenza among outpatients ≥5 years. Thus, it is good at identifying a group who do not need testing or antivirals and had fair to good predictive performance for influenza. Further testing of the algorithm in other influenza seasons would help to optimize decisions for lab testing or treatment.