Influenza Vaccine Effectiveness Against Influenza A(H3N2)-Related Illness in the United States During the 2021-2022 Influenza Season.

BACKGROUND: In the United States, influenza activity during the 2021-2022 season was modest and sufficient enough to estimate influenza vaccine effectiveness (VE) for the first time since the beginning of the coronavirus disease 2019 pandemic. We estimated influenza VE against laboratory-confirmed outpatient acute illness caused by predominant A(H3N2) viruses. METHODS: Between October 2021 and April 2022, research staff across 7 sites enrolled patients aged ≥6 months seeking outpatient care for acute respiratory illness with cough. Using a test-negative design, we assessed VE against influenza A(H3N2). Due to strong correlation between influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, participants who tested positive for SARS-CoV-2 were excluded from VE estimations. Estimates were adjusted for site, age, month of illness, race/ethnicity, and general health status. RESULTS: Among 6260 participants, 468 (7%) tested positive for influenza only, including 440 (94%) for A(H3N2). All 206 sequenced A(H3N2) viruses were characterized as belonging to genetic group 3C.2a1b subclade 2a.2, which has antigenic differences from the 2021-2022 season A(H3N2) vaccine component that belongs to clade 3C.2a1b subclade 2a.1. After excluding 1948 SARS-CoV-2-positive patients, 4312 patients were included in analyses of influenza VE; 2463 (57%) were vaccinated against influenza. Effectiveness against A(H3N2) for all ages was 36% (95% confidence interval, 20%-49%) overall. CONCLUSIONS: Influenza vaccination in 2021-2022 provided protection against influenza A(H3N2)-related outpatient visits among young persons.

Symptoms, viral loads, and rebound among COVID-19 outpatients treated with nirmatrelvir/ritonavir compared to propensity score matched untreated individuals.

BACKGROUND: Nirmatrelvir/ritonavir (N/R) reduces severe outcomes among patients with COVID-19; however, rebound after treatment has been reported. We compared symptom and viral dynamics in community-based individuals with COVID-19 who completed N/R and similar untreated individuals. METHODS: We identified symptomatic participants who tested SARS-CoV-2 positive and were N/R eligible from a COVID-19 household transmission study: index cases from ambulatory settings and their households were enrolled, collecting daily symptoms, medication use, and respiratory specimens for quantitative PCR for 10 days, March 2022-May 2023. Participants who completed N/R (treated) were propensity score matched to untreated participants. We compared symptom rebound, viral load (VL) rebound, average daily symptoms, and average daily VL by treatment status measured after N/R completion or, if untreated, seven days after symptom onset. RESULTS: Treated (n=130) and untreated participants (n=241) had similar baseline characteristics. After treatment completion, treated participants had greater occurrence of symptom rebound (32% vs 20%; p=0.009) and VL rebound (27% vs 7%; p<0.001). Average daily symptoms were lower among treated participants compared to untreated participants without symptom rebound (1.0 vs 1.6; p<0.01), but not statistically lower with symptom rebound (3.0 vs 3.4; p=0.5). Treated participants had lower average daily VLs without VL rebound (0.9 vs 2.6; p<0.01), but not statistically lower with VL rebound (4.8 vs 5.1; p=0.7). CONCLUSIONS: Individuals who completed N/R experienced fewer symptoms and lower VL but were more likely to have rebound compared to untreated individuals. Providers should still prescribe N/R, when indicated, and communicate possible increased rebound risk to patients.

Work Attendance with Acute Respiratory Illness Before and During COVID-19 Pandemic, United States, 2018-2022.

Both SARS-CoV-2 and influenza virus can be transmitted by asymptomatic, presymptomatic, or symptomatic infected persons. We assessed effects on work attendance while ill before and during the COVID-19 pandemic in the United States by analyzing data collected prospectively from persons with acute respiratory illnesses enrolled in a multistate study during 2018-2022. Persons with previous hybrid work experience were significantly less likely to work onsite on the day before through the first 3 days of illness than those without that experience, an effect more pronounced during the COVID-19 pandemic than during prepandemic influenza seasons. Persons with influenza or COVID-19 were significantly less likely to work onsite than persons with other acute respiratory illnesses. Among persons with positive COVID-19 test results available by the second or third day of illness, few worked onsite. Hybrid and remote work policies might reduce workplace exposures and help reduce spread of respiratory viruses.

Interim Estimates of 2022-23 Seasonal Influenza Vaccine Effectiveness - Wisconsin, October 2022-February 2023.

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).

Racial and ethnic disparities in influenza vaccination coverage among pregnant women in the United States: The contribution of vaccine-related attitudes.

OBJECTIVE: Racial and ethnic disparities in influenza vaccination coverage among pregnant women in the United States have been documented. This study assessed the contribution of vaccine-related attitudes to coverage disparities. METHODS: Surveys were conducted following the 2019-2020 and 2020-2021 influenza seasons in a US research network. Using electronic health record data to identify pregnant women, random samples were selected for surveying; non-Hispanic Black women and influenza-unvaccinated women were oversampled. Regression-based decomposition analyses were used to assess the contribution of vaccine-related attitudes to racial and ethnic differences in influenza vaccination. Data were combined across survey years, and analyses were weighted and accounted for survey design. RESULTS: Survey response rate was 41.2% (721 of 1748) for 2019-2020 and 39.3% (706 of 1798) for 2020-2021. Self-reported influenza vaccination was higher among non-Hispanic White respondents (79.4% coverage, 95% CI 73.1%-85.7%) than Hispanic (66.2% coverage, 95% CI 52.5%-79.9%) and non-Hispanic Black (55.8% coverage, 95% CI 50.2%-61.4%) respondents. For all racial and ethnic groups, a high proportion (generally >80%) reported being seen for care, recommended for influenza vaccination, and offered vaccination. In decomposition analyses, vaccine-related attitudes (e.g., worry about vaccination causing influenza; concern about vaccine safety and effectiveness) explained a statistically significant portion of the observed racial and ethnic disparities in vaccination. Maternal age, education, and health status were not significant contributors after controlling for vaccine-related attitudes. CONCLUSIONS: In a setting with relatively high influenza vaccination coverage among pregnant women, racial and ethnic disparities in coverage were identified. Vaccine-related attitudes were associated with the disparities observed.

Household Transmission of Influenza A Viruses in 2021-2022.

Importance: Influenza virus infections declined globally during the COVID-19 pandemic. Loss of natural immunity from lower rates of influenza infection and documented antigenic changes in circulating viruses may have resulted in increased susceptibility to influenza virus infection during the 2021-2022 influenza season. Objective: To compare the risk of influenza virus infection among household contacts of patients with influenza during the 2021-2022 influenza season with risk of influenza virus infection among household contacts during influenza seasons before the COVID-19 pandemic in the US. Design, Setting, and Participants: This prospective study of influenza transmission enrolled households in 2 states before the COVID-19 pandemic (2017-2020) and in 4 US states during the 2021-2022 influenza season. Primary cases were individuals with the earliest laboratory-confirmed influenza A(H3N2) virus infection in a household. Household contacts were people living with the primary cases who self-collected nasal swabs daily for influenza molecular testing and completed symptom diaries daily for 5 to 10 days after enrollment. Exposures: Household contacts living with a primary case. Main Outcomes and Measures: Relative risk of laboratory-confirmed influenza A(H3N2) virus infection in household contacts during the 2021-2022 season compared with prepandemic seasons. Risk estimates were adjusted for age, vaccination status, frequency of interaction with the primary case, and household density. Subgroup analyses by age, vaccination status, and frequency of interaction with the primary case were also conducted. Results: During the prepandemic seasons, 152 primary cases (median age, 13 years; 3.9% Black; 52.0% female) and 353 household contacts (median age, 33 years; 2.8% Black; 54.1% female) were included and during the 2021-2022 influenza season, 84 primary cases (median age, 10 years; 13.1% Black; 52.4% female) and 186 household contacts (median age, 28.5 years; 14.0% Black; 63.4% female) were included in the analysis. During the prepandemic influenza seasons, 20.1% (71/353) of household contacts were infected with influenza A(H3N2) viruses compared with 50.0% (93/186) of household contacts in 2021-2022. The adjusted relative risk of A(H3N2) virus infection in 2021-2022 was 2.31 (95% CI, 1.86-2.86) compared with prepandemic seasons. Conclusions and Relevance: Among cohorts in 5 US states, there was a significantly increased risk of household transmission of influenza A(H3N2) in 2021-2022 compared with prepandemic seasons. Additional research is needed to understand reasons for this association.

SARS-CoV-2 Virus Dynamics in Recently Infected People-Data From a Household Transmission Study.

We used daily real-time reverse-transcription polymerase chain reaction (RT-PCR) results from 67 cases of SARS-CoV-2 infection in a household transmission study, conducted April 2020-May 2021, to examine the trajectory of cycle threshold (Ct) values, an inverse correlate of viral RNA concentration. Ct values varied across RT-PCR platforms and by participant age. Specimens collected from children and adolescents had higher Ct values and adults aged ≥50 years showed lower Ct values than adults aged 18-49 years. Ct values were lower on days when participants reported experiencing symptoms, with the lowest Ct value occurring 2-6 days after symptom onset.

Role of Age in the Spread of Influenza, 2011-2019: Data From the US Influenza Vaccine Effectiveness Network.

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.

Interim Estimates of 2021-22 Seasonal Influenza Vaccine Effectiveness - United States, February 2022.

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.

Human papillomavirus vaccine beliefs and practice characteristics in rural and urban adolescent care providers.

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.

Impact of Immune Priming, Vaccination, and Infection on Influenza A(H3N2) Antibody Landscapes in Children.

BACKGROUND: Preexisting antibodies to influenza, shaped by early infection and subsequent exposures, may impact responses to influenza vaccination. METHODS: We enrolled 72 children (aged 7-17 years) in 2015-2016; all received inactivated influenza vaccines. Forty-one were also vaccinated in 2014-2015, with 12 becoming infected with A(H3N2) in 2014-2015. Thirty-one children did not have documented influenza exposures in the prior 5 seasons. Sera were collected pre- and postvaccination in both seasons. We constructed antibody landscapes using hemagglutination inhibition antibody titers against 16 A(H3N2) viruses representative of major antigenic clusters that circulated between 1968 and 2015. RESULTS: The breadth of the antibody landscapes increased with age. Vaccine-induced antibody responses correlated with boosting of titers to previously encountered antigens. Postvaccination titers were the highest against vaccine antigens rather than the historic A(H3N2) viruses previously encountered. Prevaccination titers to the vaccine were the strongest predictors of postvaccination titers. Responses to vaccine antigens did not differ by likely priming virus. Influenza A(H3N2)-infected children in 2014-2015 had narrower antibody landscapes than those uninfected, but prior season infection status had little effect on antibody landscapes following 2015-2016 vaccination. CONCLUSIONS: A(H3N2) antibody landscapes in children were largely determined by age-related immune priming, rather than recent vaccination or infection.

Messenger RNA Vaccine Effectiveness Against Coronavirus Disease 2019 Among Symptomatic Outpatients Aged ≥16 Years in the United States, February-May 2021.

Evaluations of vaccine effectiveness (VE) are important to monitor as coronavirus disease 2019 (COVID-19) vaccines are introduced in the general population. Research staff enrolled symptomatic participants seeking outpatient medical care for COVID-19-like illness or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing from a multisite network. VE was evaluated using the test-negative design. Among 236 SARS-CoV-2 nucleic acid amplification test-positive and 576 test-negative participants aged ≥16 years, the VE of messenger RNA vaccines against COVID-19 was 91% (95% confidence interval, 83%-95%) for full vaccination and 75% (55%-87%) for partial vaccination. Vaccination was associated with prevention of most COVID-19 cases among people seeking outpatient medical care.

Adverse Events Among Young Adults Following a Third Dose of Measles-Mumps-Rubella Vaccine.

BACKGROUND: A third measles-mumps-rubella vaccine (MMR) dose (MMR3) is recommended in the United States for persons at increased risk for mumps during outbreaks. MMR3 is also likely given to persons who might have received 2 doses of MMR but lack documentation. Since MMR3 safety data are limited, we describe adverse events in persons receiving MMR3 in a nonoutbreak setting. METHODS: Young adults with 2 documented MMR doses were administered MMR3. From 2 weeks before until 4 weeks after MMR3 receipt, participants reported daily on 11 solicited, common symptoms potentially associated with MMR. Weekly rate differences in post- vs prevaccination (baseline) were evaluated by Poisson regression. Baseline rates were subtracted from postvaccination rates of significantly different symptoms to estimate the number and percentage of participants with excess risk for symptoms post-MMR3. Descriptive analyses were performed for 3 postvaccination injection-site symptoms. RESULTS: The 662 participants were aged 18-28 years (median = 20 years); 56% were women. Headache, joint problems, diarrhea, and lymphadenopathy rates were significantly higher postvaccination vs baseline. We estimate that 119 participants (18%) reported more symptoms after MMR3 than prevaccination. By symptom, 13%, 10%, 8%, and 6% experienced increased symptoms of headache, joint problems, diarrhea, and lymphadenopathy, respectively, after MMR3. The median onset was Days 3-6 postvaccination; the median duration was 1-2 days. One healthcare visit for a potential vaccination-related symptom (urticaria) was reported. Injection-site symptoms were reported by 163 participants (25%); the median duration was 1-2 days. CONCLUSIONS: Reported systemic and local events were mild and transient. MMR3 is safe and tolerable among young adults.

Effects of Prior Season Vaccination on Current Season Vaccine Effectiveness in the United States Flu Vaccine Effectiveness Network, 2012-2013 Through 2017-2018.

BACKGROUND: We compared effects of prior vaccination and added or lost protection from current season vaccination among those previously vaccinated. METHODS: Our analysis included data from the US Flu Vaccine Effectiveness Network among participants ≥9 years old with acute respiratory illness from 2012-2013 through 2017-2018. Vaccine protection was estimated using multivariate logistic regression with an interaction term for effect of prior season vaccination on current season vaccine effectiveness. Models were adjusted for age, calendar time, high-risk status, site, and season for combined estimates. We estimated protection by combinations of current and prior vaccination compared to unvaccinated in both seasons or current vaccination among prior vaccinated. RESULTS: A total of 31 819 participants were included. Vaccine protection against any influenza averaged 42% (95% confidence interval [CI], 38%-47%) among those vaccinated only the current season, 37% (95% CI, 33-40) among those vaccinated both seasons, and 26% (95% CI, 18%-32%) among those vaccinated only the prior season, compared with participants vaccinated neither season. Current season vaccination reduced the odds of any influenza among patients unvaccinated the prior season by 42% (95% CI, 37%-46%), including 57%, 27%, and 55% against A(H1N1), A(H3N2), and influenza B, respectively. Among participants vaccinated the prior season, current season vaccination further reduced the odds of any influenza by 15% (95% CI, 7%-23%), including 29% against A(H1N1) and 26% against B viruses, but not against A(H3N2). CONCLUSIONS: Our findings support Advisory Committee on Immunization Practices recommendations for annual influenza vaccination. Benefits of current season vaccination varied among participants with and without prior season vaccination, by virus type/subtype and season.

Effectiveness of Trivalent and Quadrivalent Inactivated Vaccines Against Influenza B in the United States, 2011-2012 to 2016-2017.

BACKGROUND: Since 2013, quadrivalent influenza vaccines containing 2 B viruses gradually replaced trivalent vaccines in the United States. We compared the vaccine effectiveness of quadrivalent to trivalent inactivated vaccines (IIV4 to IIV3, respectively) against illness due to influenza B during the transition, when IIV4 use increased rapidly. METHODS: The US Influenza Vaccine Effectiveness (Flu VE) Network analyzed 25 019 of 42 600 outpatients aged ≥6 months who enrolled within 7 days of illness onset during 6 seasons from 2011-2012. Upper respiratory specimens were tested for the influenza virus type and B lineage. Using logistic regression, we estimated IIV4 or IIV3 effectiveness by comparing the odds of an influenza B infection overall and the odds of B lineage among vaccinated versus unvaccinated participants. Over 4 seasons from 2013-2014, we compared the relative odds of an influenza B infection among IIV4 versus IIV3 recipients. RESULTS: Trivalent vaccines included the predominantly circulating B lineage in 4 of 6 seasons. During 4 influenza seasons when both IIV4 and IIV3 were widely used, the overall effectiveness against any influenza B was 53% (95% confidence interval [CI], 45-59) for IIV4 versus 45% (95% CI, 34-54) for IIV3. IIV4 was more effective than IIV3 against the B lineage not included in IIV3, but comparative effectiveness against illnesses related to any influenza B favored neither vaccine valency. CONCLUSIONS: The uptake of quadrivalent inactivated influenza vaccines was not associated with increased protection against any influenza B illness, despite the higher effectiveness of quadrivalent vaccines against the added B virus lineage. Public health impact and cost-benefit analyses are needed globally.

Influenza Vaccine Effectiveness in Inpatient and Outpatient Settings in the United States, 2015-2018.

BACKGROUND: Demonstration of influenza vaccine effectiveness (VE) against hospitalized illness in addition to milder outpatient illness may strengthen vaccination messaging. Our objective was to compare patient characteristics and VE between United States (US) inpatient and outpatient VE networks. METHODS: We tested adults with acute respiratory illness (ARI) for influenza within 1 outpatient-based and 1 hospital-based VE network from 2015 through 2018. We compared age, sex, and high-risk conditions. The test-negative design was used to compare vaccination odds in influenza-positive cases vs influenza-negative controls. We estimated VE using logistic regression adjusting for site, age, sex, race/ethnicity, peak influenza activity, time to testing from, season (overall VE), and underlying conditions. VE differences (ΔVE) were assessed with 95% confidence intervals (CIs) determined through bootstrapping with significance defined as excluding the null. RESULTS: The networks enrolled 14 573 (4144 influenza-positive) outpatients and 6769 (1452 influenza-positive) inpatients. Inpatients were older (median, 62 years vs 49 years) and had more high-risk conditions (median, 4 vs 1). Overall VE across seasons was 31% (95% CI, 26%-37%) among outpatients and 36% (95% CI, 27%-44%) among inpatients. Strain-specific VE (95% CI) among outpatients vs inpatients was 37% (25%-47%) vs 53% (37%-64%) against H1N1pdm09; 19% (9%-27%) vs 23% (8%-35%) against H3N2; and 46% (38%-53%) vs 46% (31%-58%) against B viruses. ΔVE was not significant for any comparison across all sites. CONCLUSIONS: Inpatients and outpatients with ARI represent distinct populations. Despite comparatively poor health among inpatients, influenza vaccination was effective in preventing influenza-associated hospitalizations.

Effect of Antigenic Drift on Influenza Vaccine Effectiveness in the United States-2019-2020.

BACKGROUND: At the start of the 2019-2020 influenza season, concern arose that circulating B/Victoria viruses of the globally emerging clade V1A.3 were antigenically drifted from the strain included in the vaccine. Intense B/Victoria activity was followed by circulation of genetically diverse A(H1N1)pdm09 viruses that were also antigenically drifted. We measured vaccine effectiveness (VE) in the United States against illness from these emerging viruses. METHODS: We enrolled outpatients aged ≥6 months with acute respiratory illness at 5 sites. Respiratory specimens were tested for influenza by reverse-transcriptase polymerase chain reaction (RT-PCR). Using the test-negative design, we determined influenza VE by virus subtype/lineage and genetic subclades by comparing odds of vaccination in influenza cases versus test-negative controls. RESULTS: Among 8845 enrollees, 2722 (31%) tested positive for influenza, including 1209 (44%) for B/Victoria and 1405 (51%) for A(H1N1)pdm09. Effectiveness against any influenza illness was 39% (95% confidence interval [CI]: 32-44), 45% (95% CI: 37-52) against B/Victoria and 30% (95% CI: 21-39) against A(H1N1)pdm09-associated illness. Vaccination offered no protection against A(H1N1)pdm09 viruses with antigenically drifted clade 6B.1A 183P-5A+156K HA genes (VE 7%; 95% CI: -14 to 23%) which predominated after January. CONCLUSIONS: Vaccination provided protection against influenza illness, mainly due to infections from B/Victoria viruses. Vaccine protection against illness from A(H1N1)pdm09 was lower than historically observed effectiveness of 40%-60%, due to late-season vaccine mismatch following emergence of antigenically drifted viruses. The effect of drift on vaccine protection is not easy to predict and, even in drifted years, significant protection can be observed.

Implications of Shortened Quarantine Among Household Contacts of Index Patients with Confirmed SARS-CoV-2 Infection - Tennessee and Wisconsin, April-September 2020.

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.

Spread of Antigenically Drifted Influenza A(H3N2) Viruses and Vaccine Effectiveness in the United States During the 2018-2019 Season.

BACKGROUND: Increased illness due to antigenically drifted A(H3N2) clade 3C.3a influenza viruses prompted concerns about vaccine effectiveness (VE) and vaccine strain selection. We used US virologic surveillance and US Influenza Vaccine Effectiveness (Flu VE) Network data to evaluate consequences of this clade. METHODS: Distribution of influenza viruses was described using virologic surveillance data. The Flu VE Network enrolled ambulatory care patients aged ≥6 months with acute respiratory illness at 5 sites. Respiratory specimens were tested for influenza by means of reverse-transcriptase polymerase chain reaction and were sequenced. Using a test-negative design, we estimated VE, comparing the odds of influenza among vaccinated versus unvaccinated participants. RESULTS: During the 2018-2019 influenza season, A(H3N2) clade 3C.3a viruses caused an increasing proportion of influenza cases. Among 2763 Flu VE Network case patients, 1325 (48%) were infected with A(H1N1)pdm09 and 1350 (49%) with A(H3N2); clade 3C.3a accounted for 977 (93%) of 1054 sequenced A(H3N2) viruses. VE was 44% (95% confidence interval, 37%-51%) against A(H1N1)pdm09 and 9% (-4% to 20%) against A(H3N2); VE was 5% (-10% to 19%) against A(H3N2) clade 3C.3a viruses. CONCLUSIONS: The predominance of A(H3N2) clade 3C.3a viruses during the latter part of the 2018-2019 season was associated with decreased VE, supporting the A(H3N2) vaccine component update for 2019-2020 northern hemisphere influenza vaccines.

Reducing Antibiotic Use in Ambulatory Care Through Influenza Vaccination.

BACKGROUND: Improving appropriate antibiotic use is crucial for combating antibiotic resistance and unnecessary adverse drug reactions. Acute respiratory illness (ARI) commonly causes outpatient visits and accounts for ~41% of antibiotics used in the United States. We examined the influence of influenza vaccination on reducing antibiotic prescriptions among outpatients with ARI. METHODS: We enrolled outpatients aged ≥6 months with ARI from 50-60 US clinics during 5 winters (2013-2018) and tested for influenza with RT-PCR; results were unavailable for clinical decision making and clinical influenza testing was infrequent. We collected antibiotic prescriptions and diagnosis codes for ARI syndromes. We calculated vaccine effectiveness (VE) by comparing vaccination odds among influenza-positive cases with test-negative controls. We estimated ARI visits and antibiotic prescriptions averted by influenza vaccination using estimates of VE, coverage, and prevalence of antibiotic prescriptions and influenza. RESULTS: Among 37 487 ARI outpatients, 9659 (26%) were influenza positive. Overall, 36% of ARI and 26% of influenza-positive patients were prescribed antibiotics. The top 3 prevalent ARI syndromes included: viral upper respiratory tract infection (47%), pharyngitis (18%), and allergy or asthma (11%). Among patients testing positive for influenza, 77% did not receive an ICD-CM diagnostic code for influenza. Overall, VE against influenza-associated ARI was 35% (95% CI, 32-39%). Vaccination prevented 5.6% of all ARI syndromes, ranging from 2.8% (sinusitis) to 11% (clinical influenza). Influenza vaccination averted 1 in 25 (3.8%; 95% CI, 3.6-4.1%) antibiotic prescriptions among ARI outpatients during influenza seasons. CONCLUSIONS: Vaccination and accurate influenza diagnosis may curb unnecessary antibiotic use and reduce the global threat of antibiotic resistance.