Predictors of Severity of Influenza-Related Hospitalizations: Results From the Global Influenza Hospital Surveillance Network (GIHSN).

BACKGROUND: The Global Influenza Hospital Surveillance Network (GIHSN) has since 2012 provided patient-level data on severe influenza-like-illnesses from >100 participating clinical sites worldwide based on a core protocol and consistent case definitions. METHODS: We used multivariable logistic regression to assess the risk of intensive care unit admission, mechanical ventilation, and in-hospital death among hospitalized patients with influenza and explored the role of patient-level covariates and country income level. RESULTS: The data set included 73 121 patients hospitalized with respiratory illness in 22 countries, including 15 660 with laboratory-confirmed influenza. After adjusting for patient-level covariates we found a 7-fold increase in the risk of influenza-related intensive care unit admission in lower middle-income countries (LMICs), compared with high-income countries (P = .01). The risk of mechanical ventilation and in-hospital death also increased by 4-fold in LMICs, though these differences were not statistically significant. We also find that influenza mortality increased significantly with older age and number of comorbid conditions. Across all severity outcomes studied and after controlling for patient characteristics, infection with influenza A/H1N1pdm09 was more severe than with A/H3N2. CONCLUSIONS: Our study provides new information on influenza severity in underresourced populations, particularly those in LMICs.

Do pregnant persons want influenza vaccines? Knowledge, attitudes, perceptions, and practices toward influenza vaccines in 8 low- and middle-income countries.

BACKGROUND: While vaccination is the most effective way to prevent influenza infection and adverse outcomes, and despite WHO recommendations to vaccinate pregnant persons, access to seasonal influenza vaccines remains low. We explored knowledge, attitudes, and practices of pregnant persons about seasonal influenza vaccines to inform actions to improve vaccine uptake among this priority population. METHODS: We pooled individual-level data from cross-sectional surveys assessing pregnant persons' attitudes toward seasonal influenza vaccines in eight low- and middle-income countries during 2018-2019. The eight countries used a standard protocol and questionnaire to measure attitudes and intents toward influenza vaccination. We stratified by country-level (presence/absence of a national influenza vaccination program, country income group, geographic region) and individual-level factors. FINDINGS: Our analysis included 8,556 pregnant persons from eight low- and middle-income countries with and without seasonal influenza vaccination programs. Most pregnant persons (6,323, 74%) were willing to receive influenza vaccine if it was offered for free. Willingness differed by presence of an existing influenza vaccination program; acceptance was higher in countries without influenza vaccination programs (2,383, 89%) than in those with such programs (3,940, 67%, p < 0.001). INTERPRETATION: Most pregnant persons in middle-income countries, regardless of influenza vaccination program status, were willing to be vaccinated against influenza if the vaccine was provided free of charge. National investments in influenza vaccination programs may be well-received by pregnant persons, leading to averted illness both in pregnant persons themselves and in their newborn babies. FUNDING: US Centers for Disease Control and Prevention.

Costs and cost-effectiveness of influenza illness and vaccination in low- and middle-income countries: A systematic review from 2012 to 2022.

BACKGROUND: Historically, lack of data on cost-effectiveness of influenza vaccination has been identified as a barrier to vaccine use in low- and middle-income countries. We conducted a systematic review of economic evaluations describing (1) costs of influenza illness; (2) costs of influenza vaccination programs; and (3) vaccination cost-effectiveness from low- and middle-income countries to assess if gaps persist that could hinder global implementation of influenza vaccination programs. METHODS AND FINDINGS: We performed a systematic search in Medline, Embase, Cochrane Library, CINAHL, and Scopus in January 2022 and October 2023 using a combination of the following key words: "influenza" AND "cost" OR "economic." The search included studies with publication years 2012 through 2022. Studies were eligible if they (1) presented original, peer-reviewed findings on cost of illness, cost of vaccination program, or cost-effectiveness of vaccination for seasonal influenza; and (2) included data for at least 1 low- or middle-income country. We abstracted general study characteristics and data specific to each of the 3 study types. Of 54 included studies, 26 presented data on cost-effectiveness, 24 on cost-of-illness, and 5 on program costs. Represented countries were classified as upper-middle income (UMIC; n = 12), lower-middle income (LMIC; n = 7), and low-income (LIC; n = 3). The most evaluated target groups were children (n = 26 studies), older adults (n = 17), and persons with chronic medical conditions (n = 12); fewer studies evaluated pregnant persons (n = 9), healthcare workers (n = 5), and persons in congregate living settings (n = 1). Costs-of-illness were generally higher in UMICs than in LMICs/LICs; however, the highest national economic burden, as a percent of gross domestic product and national health expenditure, was reported from an LIC. Among studies that evaluated the cost-effectiveness of influenza vaccine introduction, most (88%) interpreted at least 1 scenario per target group as either cost-effective or cost-saving, based on thresholds designated in the study. Key limitations of this work included (1) heterogeneity across included studies; (2) restrictiveness of the inclusion criteria used; and (3) potential for missed influenza burden from use of sentinel surveillance systems. CONCLUSIONS: The 54 studies identified in this review suggest an increased momentum to generate economic evidence about influenza illness and vaccination from low- and middle-income countries during 2012 to 2022. However, given that we observed substantial heterogeneity, continued evaluation of the economic burden of influenza illness and costs/cost-effectiveness of influenza vaccination, particularly in LICs and among underrepresented target groups (e.g., healthcare workers and pregnant persons), is needed. Use of standardized methodology could facilitate pooling across settings and knowledge sharing to strengthen global influenza vaccination programs.

Potential health and economic impact of paediatric vaccination using next-generation influenza vaccines in Kenya: a modelling study.

BACKGROUND: Influenza is a major year-round cause of respiratory illness in Kenya, particularly in children under 5. Current influenza vaccines result in short-term, strain-specific immunity and were found in a previous study not to be cost-effective in Kenya. However, next-generation vaccines are in development that may have a greater impact and cost-effectiveness profile. METHODS: We expanded a model previously used to evaluate the cost-effectiveness of seasonal influenza vaccines in Kenya to include next-generation vaccines by allowing for enhanced vaccine characteristics and multi-annual immunity. We specifically examined vaccinating children under 5 years of age with improved vaccines, evaluating vaccines with combinations of increased vaccine effectiveness, cross-protection between strains (breadth) and duration of immunity. We evaluated cost-effectiveness using incremental cost-effectiveness ratios (ICERs) and incremental net monetary benefits (INMBs) for a range of values for the willingness-to-pay (WTP) per DALY averted. Finally, we estimated threshold per-dose vaccine prices at which vaccination becomes cost-effective. RESULTS: Next-generation vaccines can be cost-effective, dependent on the vaccine characteristics and assumed WTP thresholds. Universal vaccines (assumed to provide long-term and broad immunity) are most cost-effective in Kenya across three of four WTP thresholds evaluated, with the lowest median value of ICER per DALY averted ($263, 95% Credible Interval (CrI): $ - 1698, $1061) and the highest median INMBs. At a WTP of $623, universal vaccines are cost-effective at or below a median price of $5.16 per dose (95% CrI: $0.94, $18.57). We also show that the assumed mechanism underlying infection-derived immunity strongly impacts vaccine outcomes. CONCLUSIONS: This evaluation provides evidence for country-level decision makers about future next-generation vaccine introduction, as well as global research funders about the potential market for these vaccines. Next-generation vaccines may offer a cost-effective intervention to reduce influenza burden in low-income countries with year-round seasonality like Kenya.

Comparisons in the Health and Economic Assessments of Using Quadrivalent Versus Trivalent Influenza Vaccines: A Systematic Literature Review.

OBJECTIVES: Seasonal influenza vaccines protect against 3 (trivalent influenza vaccine [IIV3]) or 4 (quadrivalent influenza vaccine [IIV4]) viruses. IIV4 costs more than IIV3, and there is a trade-off between incremental cost and protection. This is especially the case in low- and middle-income countries (LMICs) with limited budgets; previous reviews have not identified studies of IIV4-IIV3 comparisons in LMICs. We summarized the literature that compared health and economic outcomes of IIV4 and IIV3, focused on LMICs. METHODS: We systematically searched 5 databases for articles published before October 6, 2021, that modeled health or economic effects of IIV4 versus IIV3. We abstracted data and compared findings among countries and models. RESULTS: Thirty-eight studies fit our selection criteria; 10 included LMICs. Most studies (N = 31) reported that IIV4 was cost-saving or cost-effective compared with IIV3; we observed no difference in health or economic outcomes between LMICs and other countries. Based on cost differences of influenza vaccines, only one study compared coverage of IIV3 with IIV4 and reported that the maximum IIV4 price that would still yield greater public health impact than IIV3 was 13% to 22% higher than IIV3. CONCLUSIONS: When vaccination coverage with IIV4 and IIV3 is the same, IIV4 tends to be not only more effective but more cost-effective than IIV3, even with relatively high price differences between vaccine types. Alternatively, where funding is limited as in most LMICs, higher vaccine coverage can be achieved with IIV3 than IIV4, which could result in more favorable health and economic outcomes.

Leveraging International Influenza Surveillance Systems and Programs during the COVID-19 Pandemic.

A network of global respiratory disease surveillance systems and partnerships has been built over decades as a direct response to the persistent threat of seasonal, zoonotic, and pandemic influenza. These efforts have been spearheaded by the World Health Organization, country ministries of health, the US Centers for Disease Control and Prevention, nongovernmental organizations, academic groups, and others. During the COVID-19 pandemic, the US Centers for Disease Control and Prevention worked closely with ministries of health in partner countries and the World Health Organization to leverage influenza surveillance systems and programs to respond to SARS-CoV-2 transmission. Countries used existing surveillance systems for severe acute respiratory infection and influenza-like illness, respiratory virus laboratory resources, pandemic influenza preparedness plans, and ongoing population-based influenza studies to track, study, and respond to SARS-CoV-2 infections. The incorporation of COVID-19 surveillance into existing influenza sentinel surveillance systems can support continued global surveillance for respiratory viruses with pandemic potential.

United States Centers for Disease Control and Prevention support for influenza surveillance, 2013-2021.

Objective: To assess the stability of improvements in global respiratory virus surveillance in countries supported by the United States Centers for Disease Control and Prevention (CDC) after reductions in CDC funding and with the stress of the coronavirus disease 2019 (COVID-19) pandemic. Methods: We assessed whether national influenza surveillance systems of CDC-funded countries: (i) continued to analyse as many specimens between 2013 and 2021; (ii) participated in activities of the World Health Organization's (WHO) Global Influenza Surveillance and Response System; (iii) tested enough specimens to detect rare events or signals of unusual activity; and (iv) demonstrated stability before and during the COVID-19 pandemic. We used CDC budget records and data from the WHO Global Influenza Surveillance and Response System. Findings: While CDC reduced per-country influenza funding by about 75% over 10 years, the number of specimens tested annually remained stable (mean 2261). Reporting varied substantially by country and transmission zone. Countries funded by CDC accounted for 71% (range 61-75%) of specimens included in WHO consultations on the composition of influenza virus vaccines. In 2019, only eight of the 17 transmission zones sent enough specimens to WHO collaborating centres before the vaccine composition meeting to reliably identify antigenic variants. Conclusion: Great progress has been made in the global understanding of influenza trends and seasonality. To optimize surveillance to identify atypical influenza viruses, and to integrate molecular testing, sequencing and reporting of severe acute respiratory syndrome coronavirus 2 into existing systems, funding must continue to support these efforts.

Global burden of influenza-associated lower respiratory tract infections and hospitalizations among adults: A systematic review and meta-analysis.

BACKGROUND: Influenza illness burden is substantial, particularly among young children, older adults, and those with underlying conditions. Initiatives are underway to develop better global estimates for influenza-associated hospitalizations and deaths. Knowledge gaps remain regarding the role of influenza viruses in severe respiratory disease and hospitalizations among adults, particularly in lower-income settings. METHODS AND FINDINGS: We aggregated published data from a systematic review and unpublished data from surveillance platforms to generate global meta-analytic estimates for the proportion of acute respiratory hospitalizations associated with influenza viruses among adults. We searched 9 online databases (Medline, Embase, CINAHL, Cochrane Library, Scopus, Global Health, LILACS, WHOLIS, and CNKI; 1 January 1996-31 December 2016) to identify observational studies of influenza-associated hospitalizations in adults, and assessed eligible papers for bias using a simplified Newcastle-Ottawa scale for observational data. We applied meta-analytic proportions to global estimates of lower respiratory infections (LRIs) and hospitalizations from the Global Burden of Disease study in adults ≥20 years and by age groups (20-64 years and ≥65 years) to obtain the number of influenza-associated LRI episodes and hospitalizations for 2016. Data from 63 sources showed that influenza was associated with 14.1% (95% CI 12.1%-16.5%) of acute respiratory hospitalizations among all adults, with no significant differences by age group. The 63 data sources represent published observational studies (n = 28) and unpublished surveillance data (n = 35), from all World Health Organization regions (Africa, n = 8; Americas, n = 11; Eastern Mediterranean, n = 7; Europe, n = 8; Southeast Asia, n = 11; Western Pacific, n = 18). Data quality for published data sources was predominantly moderate or high (75%, n = 56/75). We estimate 32,126,000 (95% CI 20,484,000-46,129,000) influenza-associated LRI episodes and 5,678,000 (95% CI 3,205,000-9,432,000) LRI hospitalizations occur each year among adults. While adults <65 years contribute most influenza-associated LRI hospitalizations and episodes (3,464,000 [95% CI 1,885,000-5,978,000] LRI hospitalizations and 31,087,000 [95% CI 19,987,000-44,444,000] LRI episodes), hospitalization rates were highest in those ≥65 years (437/100,000 person-years [95% CI 265-612/100,000 person-years]). For this analysis, published articles were limited in their inclusion of stratified testing data by year and age group. Lack of information regarding influenza vaccination of the study population was also a limitation across both types of data sources. CONCLUSIONS: In this meta-analysis, we estimated that influenza viruses are associated with over 5 million hospitalizations worldwide per year. Inclusion of both published and unpublished findings allowed for increased power to generate stratified estimates, and improved representation from lower-income countries. Together, the available data demonstrate the importance of influenza viruses as a cause of severe disease and hospitalizations in younger and older adults worldwide.

Global Seasonal Influenza Mortality Estimates: A Comparison of 3 Different Approaches.

Prior to updating global influenza-associated mortality estimates, the World Health Organization convened a consultation in July 2017 to understand differences in methodology and implications for results of 3 influenza mortality projects from the US Centers for Disease Control and Prevention (CDC), the Netherlands Institute for Health Service Research's Global Pandemic Mortality Project II (GLaMOR), and the Institute for Health Metrics and Evaluation (IHME). The expert panel reviewed estimates and discussed differences in data sources, analysis, and modeling assumptions. We performed a comparison analysis of the estimates. Influenza-associated respiratory death counts were comparable between CDC and GLaMOR; the IHME estimate was considerably lower. The greatest country-specific influenza-associated fold differences in mortality rate between CDC and IHME estimates and between GLaMOR and IHME estimates were among countries in Southeast Asia and the Eastern Mediterranean region. The data envelope used for the calculation was one of the major differences (CDC and GLaMOR: all respiratory deaths; IHME: lower-respiratory infection deaths). With the assumption that there is only one cause of death for each death, IHME estimates a fraction of the full influenza-associated respiratory mortality that is measured by the other 2 groups. Wide variability of parameters was observed. Continued coordination between groups could assist with better understanding of methodological differences and new approaches to estimating influenza deaths globally.

Immunogenicity and Viral Shedding of Russian-Backbone, Seasonal, Trivalent, Live, Attenuated Influenza Vaccine in a Phase II, Randomized, Placebo-Controlled Trial Among Preschool-Aged Children in Urban Bangladesh.

BACKGROUND: We evaluated a Russian-backbone, live, attenuated influenza vaccine (LAIV) for immunogenicity and viral shedding in a randomized, placebo-controlled trial among Bangladeshi children. METHODS: Healthy children received a single, intranasal dose of LAIV containing the 2011-2012 recommended formulation or placebo. Nasopharyngeal wash (NPW) specimens were collected on days 0, 2, 4, and 7. Reverse transcription polymerase chain reactions and sequencing identified the influenza virus (vaccine or wild-type). On days 0 and 21, blood specimens were collected to assess immunogenicity using hemagglutination inhibition, microneutralization, and immunoglobulin A (IgA) and G enzyme-linked immunosorbent assays (ELISAs); NPW specimens were also collected to assess mucosal immunogenicity using kinetic IgA ELISA. RESULTS: We enrolled 300 children aged 24 through 59 months in the immunogenicity and viral shedding analyses. Among children receiving LAIV, 45% and 67% shed A/H3N2 and B vaccine strains, respectively. No child shed A/H1N1 vaccine strain. There were significantly higher day 21 geometric mean titers (GMTs) for the LAIV, as compared to the placebo groups, in all immunoassays for A/H3N2 and B (log10 titer P < .0001; GMT Ratio >2.0). Among immunoassays for A/H1N1, only the mucosal IgA GMT was significantly higher than placebo at day 21 (log10 titer P = .0465). CONCLUSIONS: Children vaccinated with LAIV had serum and mucosal antibody responses to A/H3N2 and B, but only a mucosal IgA response to A/H1N1. Many children shed A/H3N2 and B vaccine strains, but none shed A/H1N1. More research is needed to determine the reason for decreased LAIV A/H1N1 immunogenicity and virus shedding. CLINICAL TRIALS REGISTRATION: NCT01625689.

Estimates of global seasonal influenza-associated respiratory mortality: a modelling study.

BACKGROUND: Estimates of influenza-associated mortality are important for national and international decision making on public health priorities. Previous estimates of 250 000-500 000 annual influenza deaths are outdated. We updated the estimated number of global annual influenza-associated respiratory deaths using country-specific influenza-associated excess respiratory mortality estimates from 1999-2015. METHODS: We estimated country-specific influenza-associated respiratory excess mortality rates (EMR) for 33 countries using time series log-linear regression models with vital death records and influenza surveillance data. To extrapolate estimates to countries without data, we divided countries into three analytic divisions for three age groups (<65 years, 65-74 years, and ≥75 years) using WHO Global Health Estimate (GHE) respiratory infection mortality rates. We calculated mortality rate ratios (MRR) to account for differences in risk of influenza death across countries by comparing GHE respiratory infection mortality rates from countries without EMR estimates with those with estimates. To calculate death estimates for individual countries within each age-specific analytic division, we multiplied randomly selected mean annual EMRs by the country's MRR and population. Global 95% credible interval (CrI) estimates were obtained from the posterior distribution of the sum of country-specific estimates to represent the range of possible influenza-associated deaths in a season or year. We calculated influenza-associated deaths for children younger than 5 years for 92 countries with high rates of mortality due to respiratory infection using the same methods. FINDINGS: EMR-contributing countries represented 57% of the global population. The estimated mean annual influenza-associated respiratory EMR ranged from 0·1 to 6·4 per 100 000 individuals for people younger than 65 years, 2·9 to 44·0 per 100 000 individuals for people aged between 65 and 74 years, and 17·9 to 223·5 per 100 000 for people older than 75 years. We estimated that 291 243-645 832 seasonal influenza-associated respiratory deaths (4·0-8·8 per 100 000 individuals) occur annually. The highest mortality rates were estimated in sub-Saharan Africa (2·8-16·5 per 100 000 individuals), southeast Asia (3·5-9·2 per 100 000 individuals), and among people aged 75 years or older (51·3-99·4 per 100 000 individuals). For 92 countries, we estimated that among children younger than 5 years, 9243-105 690 influenza-associated respiratory deaths occur annually. INTERPRETATION: These global influenza-associated respiratory mortality estimates are higher than previously reported, suggesting that previous estimates might have underestimated disease burden. The contribution of non-respiratory causes of death to global influenza-associated mortality should be investigated. FUNDING: None.

A ten-year China-US laboratory collaboration: improving response to influenza threats in China and the world, 2004-2014.

The emergence of severe acute respiratory syndrome (SARS) underscored the importance of influenza detection and response in China. From 2004, the Chinese National Influenza Center (CNIC) and the United States Centers for Disease Control and Prevention (USCDC) initiated Cooperative Agreements to build capacity in influenza surveillance in China.From 2004 to 2014, CNIC and USCDC collaborated on the following activities: 1) developing human technical expertise in virology and epidemiology in China; 2) developing a comprehensive influenza surveillance system by enhancing influenza-like illness (ILI) reporting and virological characterization; 3) strengthening analysis, utilization and dissemination of surveillance data; and 4) improving early response to influenza viruses with pandemic potential.Since 2004, CNIC expanded its national influenza surveillance and response system which, as of 2014, included 408 laboratories and 554 sentinel hospitals. With support from USCDC, more than 2500 public health staff from China received virology and epidemiology training, enabling > 98% network laboratories to establish virus isolation and/or nucleic acid detection techniques. CNIC established viral drug resistance surveillance and platforms for gene sequencing, reverse genetics, serologic detection, and vaccine strains development. CNIC also built a bioinformatics platform to strengthen data analysis and utilization, publishing weekly on-line influenza surveillance reports in English and Chinese. The surveillance system collects 200,000-400,000 specimens and tests more than 20,000 influenza viruses annually, which provides valuable information for World Health Organization (WHO) influenza vaccine strain recommendations. In 2010, CNIC became the sixth WHO Collaborating Centre for Influenza. CNIC has strengthened virus and data sharing, and has provided training and reagents for other countries to improve global capacity for influenza control and prevention.The collaboration's successes were built upon shared mission and values, emphasis on long-term capacity development and sustainability, and leadership commitment.

Implementing a Multisite Clinical Trial in the Midst of an Ebola Outbreak: Lessons Learned From the Sierra Leone Trial to Introduce a Vaccine Against Ebola.

The Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE), a phase 2/3 trial of investigational rVSV∆G-ZEBOV-GP vaccine, was conducted during an unprecedented Ebola epidemic. More than 8600 eligible healthcare and frontline response workers were individually randomized to immediate (within 7 days) or deferred (within 18-24 weeks) vaccination and followed for 6 months after vaccination for serious adverse events and Ebola virus infection. Key challenges included limited infrastructure to support trial activities, unreliable electricity, and staff with limited clinical trial experience. Study staff made substantial infrastructure investments, including renovation of enrollment sites, laboratories, and government cold chain facilities, and imported equipment to store and transport vaccine at ≤-60oC. STRIVE built capacity by providing didactic and practical research training to >350 staff, which was reinforced with daily review and feedback meetings. The operational challenges of safety follow-up were addressed by issuing mobile telephones to participants, making home visits, and establishing a nurse triage hotline. Before the Ebola outbreak, Sierra Leone had limited infrastructure and staff to conduct clinical trials. Without interfering with the outbreak response, STRIVE responded to an urgent need and helped build this capacity. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220].

Progress and Remaining Gaps in Estimating the Global Disease Burden of Influenza.

Influenza has long been a global public health priority because of the threat of another global pandemic. Although data are available for the annual burden of seasonal influenza in many developed countries, fewer disease burden data are available for low-income and tropical countries. In recent years, however, the surveillance systems created as part of national pandemic preparedness efforts have produced substantial data on the epidemiology and impact of influenza in countries where data were sparse. These data are leading to greater interest in seasonal influenza, including implementation of vaccination programs. However, a lack of quality data on severe influenza, nonrespiratory outcomes, and high-risk groups, as well as a need for better mathematical models and economic evaluations, are some of the major gaps that remain. These gaps are the focus of multilateral research and surveillance efforts that will strengthen global efforts in influenza control in the future.

Systematic Assessment of Multiple Routine and Near Real-Time Indicators to Classify the Severity of Influenza Seasons and Pandemics in the United States, 2003-2004 Through 2015-2016.

Assessments of influenza season severity can guide public health action. We used the moving epidemic method to develop intensity thresholds (ITs) for 3 US surveillance indicators from the 2003-2004 through 2014-2015 influenza seasons (excluding the 2009 pandemic). The indicators were: 1) outpatient visits for influenza-like illness; 2) influenza-related hospitalizations; and 3) influenza- and pneumonia-related deaths. ITs were developed for the population overall and separately for children, adults, and older adults, and they were set at the upper limit of the 50% (IT50), 90% (IT90), and 98% (IT98) 1-sided confidence intervals of the geometric mean of each season's 3 highest values. Severity was classified as low if ≥2 systems peaked below IT50, moderate if ≥2 peaked between IT50 and IT90, high if ≥2 peaked between IT90 and IT98, and very high if ≥2 peaked above IT98. We pilot-tested this method with the 2015-2016 season and the 2009 pandemic. Overall, 4 seasons were classified as low severity, 7 as moderate, 2 as high, and none as very high. Among the age groups, older adults had the most seasons (n = 3) classified as high, and children were the only group to have seasons (n = 2) classified as very high. We will apply this method to classify the severity of future seasons and inform pandemic response.

Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices - United States, 2017-18 Influenza Season.

This report updates the 2016-17 recommendations of the Advisory Committee on Immunization Practices (ACIP) regarding the use of seasonal influenza vaccines (MMWR Recomm Rep 2016;65[No. RR-5]). Routine annual influenza vaccination is recommended for all persons aged ≥6 months who do not have contraindications. A licensed, recommended, and age-appropriate vaccine should be used.For the 2017-18 season, quadrivalent and trivalent influenza vaccines will be available. Inactivated influenza vaccines (IIVs) will be available in trivalent (IIV3) and quadrivalent (IIV4) formulations. Recombinant influenza vaccine (RIV) will be available in trivalent (RIV3) and quadrivalent (RIV4) formulations. Live attenuated influenza vaccine (LAIV4) is not recommended for use during the 2017-18 season due to concerns about its effectiveness against (H1N1)pdm09 viruses during the 2013-14 and 2015-16 seasons. Recommendations for different vaccine types and specific populations are discussed. No preferential recommendation is made for one influenza vaccine product over another for persons for whom more than one licensed, recommended product is available.Updates to the recommendations described in this report reflect discussions during public meetings of ACIP held on October 20, 2016; February 22, 2017; and June 21, 2017. New and updated information in this report includes the following:•Vaccine viruses included in the 2017-18 U.S. trivalent influenza vaccines will be an A/Michigan/45/2015 (H1N1)pdm09-like virus, an A/Hong Kong/4801/2014 (H3N2)-like virus, and a B/Brisbane/60/2008-like virus (Victoria lineage). Quadrivalent influenza vaccines will contain these three viruses and an additional influenza B vaccine virus, a B/Phuket/3073/2013-like virus (Yamagata lineage).• Information on recent licensures and labelling changes is discussed, including licensure of Afluria Quadrivalent (IIV4; Seqirus, Parkville, Victoria, Australia); Flublok Quadrivalent (RIV4; Protein Sciences, Meriden, Connecticut); and expansion of the age indication for FluLaval Quadrivalent (IIV4; ID Biomedical Corporation of Quebec, Quebec City, Quebec, Canada), previously licensed for ≥3 years, to ≥6 months.• Pregnant women may receive any licensed, recommended, age-appropriate influenza vaccine.• Afluria (IIV3; Seqirus, Parkville, Victoria, Australia) may be used for persons aged ≥5 years, consistent with Food and Drug Administration-approved labeling.• FluMist Quadrivalent (LAIV4; MedImmune, Gaithersburg, Maryland) should not be used during the 2017-18 season due to concerns about its effectiveness against influenza A(H1N1)pdm09 viruses in the United States during the 2013-14 and 2015-16 influenza seasons.This report focuses on the recommendations for use of vaccines for the prevention and control of influenza during the 2017-18 season in the United States. A Background Document containing further information and a summary of these recommendations are available at https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/flu.html. These recommendations apply to licensed influenza vaccines used within Food and Drug Administration-licensed indications, including those licensed after the publication date of this report. Updates and other information are available at CDC's influenza website (https://www.cdc.gov/flu). Vaccination and health care providers should check CDC's influenza website periodically for additional information.

The Global Threat of Animal Influenza Viruses of Zoonotic Concern: Then and Now.

Animal influenza viruses can reassort or mutate to infect and spread sustainably among people and cause a devastating worldwide pandemic. Since the first evidence of human infection with an animal influenza virus, in 1958, 16 different novel, zoonotic influenza A virus subtype groups in 29 countries, Taiwan, and Hong Kong have caused human infections, with differing severity and frequency. The frequency of novel influenza virus detection is increasing, and human infections with influenza A(H5N1) and A(H7N9) viruses are now annual seasonal occurrences in Asia. The study of the epidemiology and virology of animal influenza viruses is key to understanding pandemic risk and informing preparedness. This supplement brings together select recent articles that look at the risk of emergence and transmission of and approaches to prevent novel influenza virus infections.

Avian Influenza A(H7N2) Virus in Human Exposed to Sick Cats, New York, USA, 2016.

An outbreak of influenza A(H7N2) virus in cats in a shelter in New York, NY, USA, resulted in zoonotic transmission. Virus isolated from the infected human was closely related to virus isolated from a cat; both were related to low pathogenicity avian influenza A(H7N2) viruses detected in the United States during the early 2000s.

Estimating Direct and Indirect Protective Effect of Influenza Vaccination in the United States.

With influenza vaccination rates in the United States recently exceeding 45% of the population, it is important to understand the impact that vaccination is having on influenza transmission. In this study, we used a Bayesian modeling approach, combined with a simple dynamical model of influenza transmission, to estimate this impact. The combined framework synthesized evidence from a range of data sources relating to influenza transmission and vaccination in the United States. We found that, for seasonal epidemics, the number of infections averted ranged from 9.6 million in the 2006-2007 season (95% credible interval (CI): 8.7, 10.9) to 37.2 million (95% CI: 34.1, 39.6) in the 2012-2013 season. Expressed in relative terms, the proportion averted ranged from 20.8% (95% CI: 16.8, 24.3) of potential infections in the 2011-2012 season to 47.5% (95% CI: 43.7, 50.8) in the 2008-2009 season. The percentage averted was only 1.04% (95% CI: 0.15, 3.2) for the 2009 H1N1 pandemic, owing to the late timing of the vaccination program in relation to the pandemic in the Northern hemisphere. In the future, further vaccination coverage, as well as improved influenza vaccines (especially those offering better protection in the elderly), could have an even stronger effect on annual influenza epidemics.

Prevention and Control of Seasonal Influenza with Vaccines.

This report updates the 2015-16 recommendations of the Advisory Committee on Immunization Practices (ACIP) regarding the use of seasonal influenza vaccines (Grohskopf LA, Sokolow LZ, Olsen SJ, Bresee JS, Broder KR, Karron RA. Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices, United States, 2015-16 influenza season. MMWR Morb Mortal Wkly Rep 2015;64:818-25). Routine annual influenza vaccination is recommended for all persons aged ≥6 months who do not have contraindications. For the 2016-17 influenza season, inactivated influenza vaccines (IIVs) will be available in both trivalent (IIV3) and quadrivalent (IIV4) formulations. Recombinant influenza vaccine (RIV) will be available in a trivalent formulation (RIV3). In light of concerns regarding low effectiveness against influenza A(H1N1)pdm09 in the United States during the 2013-14 and 2015-16 seasons, for the 2016-17 season, ACIP makes the interim recommendation that live attenuated influenza vaccine (LAIV4) should not be used. Vaccine virus strains included in the 2016-17 U.S. trivalent influenza vaccines will be an A/California/7/2009 (H1N1)-like virus, an A/Hong Kong/4801/2014 (H3N2)-like virus, and a B/Brisbane/60/2008-like virus (Victoria lineage). Quadrivalent vaccines will include an additional influenza B virus strain, a B/Phuket/3073/2013-like virus (Yamagata lineage).Recommendations for use of different vaccine types and specific populations are discussed. A licensed, age-appropriate vaccine should be used. No preferential recommendation is made for one influenza vaccine product over another for persons for whom more than one licensed, recommended product is otherwise appropriate. This information is intended for vaccination providers, immunization program personnel, and public health personnel. Information in this report reflects discussions during public meetings of ACIP held on October 21, 2015; February 24, 2016; and June 22, 2016. These recommendations apply to all licensed influenza vaccines used within Food and Drug Administration-licensed indications, including those licensed after the publication date of this report. Updates and other information are available at CDC's influenza website (http://www.cdc.gov/flu). Vaccination and health care providers should check CDC's influenza website periodically for additional information.