Background The spatiotemporal patterns of spread of influenza A(H1N1)pdm09 viruses on a countrywide scale are unclear in many tropical/subtropical regions mainly because spatiotemporally representative sequence data is lacking.Methods We isolated, sequenced, and analyzed 383 influenza A(H1N1)pdm09 viral genomes isolated from hospitalized patients between 2009 and 2018 from seven locations across Kenya. Using these genomes and contemporaneously sampled global sequences, we characterized the spread of the virus in Kenya over several seasons using phylodynamic methods.Results The transmission dynamics of influenza A(H1N1)pdm09 virus in Kenya was characterized by: (i) multiple virus introductions into Kenya over the study period, although these were remarkably few, with only a few of those introductions instigating seasonal epidemics that then established local transmission clusters; (ii) persistence of transmission clusters over several epidemic seasons across the country; (iii) seasonal fluctuations in effective reproduction number (Re) associated with lower number of infections and seasonal fluctuations in relative genetic diversity after an initial rapid increase during the early pandemic phase, which broadly corresponded to epidemic peaks in the northern and southern hemispheres; (iv) high virus genetic diversity with greater frequency of seasonal fluctuations in 2009-11 and 2018 and low virus genetic diversity with relatively weaker seasonal fluctuations in 2012-17; and (v) virus migration from multiple geographical regions to multiple geographical destinations in Kenya.Conclusion Considerable influenza virus diversity circulates within Africa, as demonstrated in this report, including virus lineages that are unique to the region, which may be capable of dissemination to other continents through a globally migrating virus population. Further knowledge of the viral lineages that circulate within understudied low-to-middle income tropical and subtropical regions is required to understand the full diversity and global ecology of influenza viruses in humans and to inform vaccination strategies within these regions.Competing Interest StatementThe authors have declared no competing interest.Funding StatementFunding: The authors D.C.O. and C.N.A. were supported by the Initiative to Develop African Research Leaders (IDeAL) through the DELTAS Africa Initiative [DEL-15-003]. The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS)'s Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa's Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust [107769/Z/10/Z] and the UK government. The study was also part funded by a Wellcome Trust grant [1029745] and the USA CDC grant [GH002133]. N.F.M. is supported by the Swiss National Science Foundation (PZEZP3_191891). This paper is published with the permission of the Director of KEMRI.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The Kenya Medical Research Institute (KEMRI) and KEMRI-Wellcome Trust Research Programme Scientific and Ethics Review Unit (SERU), which is mandated to provide ethical approval for research work conducted in Kenya, provided ethical approval for the studies which collected and archived the samples used in these studies. These were approved under the following Scientific Steering Committee (SSC) approvals: 1. SSC No. 1899, SSC No. 2558 and SSC No. 2692; 2. KEMRI-Wellcome Trust Research Programme SSC No. 1055 and SSC No. 1433.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as Clini alTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll generated sequence data were deposited in the Global Initiative on Sharing All Influenza Data (GISAID). https://github.com/DCollinsOwuor/H1N1pdm09_Kenya_Phylodynamics/tree/main/Data/.

The 2017-2018 North American influenza season caused more hospitalizations and deaths than any year since the 2009 H1N1 pandemic. The majority of recorded influenza infections were caused by A(H3N2) viruses, with most of the virus’s North American diversity falling into the A2 clade. Within A2, we observe a subclade which we call A2/re that rose to comprise almost 70% of A(H3N2) viruses circulating in North America by early 2018. Unlike most fast-growing clades, however, A2/re contains no amino acid substitutions in the hemagglutinin (HA) segment. Moreover, HI assays did not suggest substantial antigenic differences between A2/re viruses and viruses sampled during the 2016-2017 season. Rather, we observe that the A2/re clade was the result of a reassortment event that occurred in late 2016 or early 2017 and involved the combination of the HA and PB1 segments of an A2 virus with neuraminidase (NA) and other segments a virus from the clade A1b. The success of this clade shows the need for antigenic analysis that targets NA in addition to HA. Our results illustrate the potential for non-HA drivers of viral success and necessitate the need for more thorough tracking of full viral genomes to better understand the dynamics of influenza epidemics.

The spatiotemporal patterns of spread of influenza A(H1N1)pdm09 viruses on a countrywide scale are unclear in many tropical/subtropical regions mainly because spatiotemporally representative sequence data are lacking. We isolated, sequenced, and analyzed 383 A(H1N1)pdm09 viral genomes from hospitalized patients between 2009 and 2018 from seven locations across Kenya. Using these genomes and contemporaneously sampled global sequences, we characterized the spread of the virus in Kenya over several seasons using phylodynamic methods. The transmission dynamics of A(H1N1)pdm09 virus in Kenya were characterized by (i) multiple virus introductions into Kenya over the study period, although only a few of those introductions instigated local seasonal epidemics that then established local transmission clusters, (ii) persistence of transmission clusters over several epidemic seasons across the country, (iii) seasonal fluctuations in effective reproduction number (R(e)) associated with lower number of infections and seasonal fluctuations in relative genetic diversity after an initial rapid increase during the early pandemic phase, which broadly corresponded to epidemic peaks in the northern and southern hemispheres, (iv) high virus genetic diversity with greater frequency of seasonal fluctuations in 2009-2011 and 2018 and low virus genetic diversity with relatively weaker seasonal fluctuations in 2012-2017, and (v) virus spread across Kenya. Considerable influenza virus diversity circulated within Kenya, including persistent viral lineages that were unique to the country, which may have been capable of dissemination to other continents through a globally migrating virus population. Further knowledge of the viral lineages that circulate within understudied low-to-middle-income tropical and subtropical regions is required to understand the full diversity and global ecology of influenza viruses in humans and to inform vaccination strategies within these regions.

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 five 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 sub-type/lineage and genetic subclades by comparing odds of vaccination in influenza cases versus test-negative controls. RESULTS: Among 8,845 enrollees, 2,722 (31%) tested positive for influenza, including 1,209 (44%) for B/Victoria and 1,405 (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.

BACKGROUND: Influenza causes significant morbidity and mortality and stresses hospital resources during periods of increased circulation. We evaluated the effectiveness of the 2019-2020 influenza vaccine against influenza-associated hospitalizations in the United States. METHODS: We included adults hospitalized with acute respiratory illness at 14 hospitals and tested for influenza viruses by reserve transcription polymerase chain reaction. Vaccine effectiveness (VE) was estimated by comparing the odds of current-season influenza vaccination in test-positive influenza cases versus test-negative controls, adjusting for confounders. VE was stratified by age and major circulating influenza types along with A(H1N1)pdm09 genetic subgroups. RESULTS: 3116 participants were included, including 18% (553) influenza-positive cases. Median age was 63 years. Sixty-seven percent (2079) received vaccination. Overall adjusted VE against influenza viruses was 41% (95% confidence interval [CI]: 27-52). VE against A(H1N1)pdm09 viruses was 40% (95% CI: 24-53) and 33% against B viruses (95% CI: 0-56). Of the two major A(H1N1)pdm09 subgroups (representing 90% of sequenced H1N1 viruses), VE against one group (5A+187A,189E) was 59% (95% CI: 34-75) whereas no significant VE was observed against the other group (5A+156K) [-1%, 95% CI: -61-37]. CONCLUSIONS: In a primarily older population, influenza vaccination was associated with a 41% reduction in risk of hospitalized influenza illness.

Influenza databases now contain over 100,000 worldwide sequence records for strains influenza A(H3N2) and A(H1N1). Although these data facilitate global research efforts and vaccine development practices, they also represent a stumbling block for researchers because of their confusing and heterogeneous annotation. Unclear passaging annotations are particularly concerning given the recent work highlighting the presence and risk of false adaptation signals introduced by cell passaging of viral isolates. With this in mind, we aim to provide a concise outline of why viruses are passaged, a clear overview of passaging annotation nomenclature currently in use, and suggestions for a standardized nomenclature going forward. Our hope is that this summary will empower researchers and clinicians alike to more easily understand a virus sample's passage history when analyzing influenza sequences.

BACKGROUND: The evolution of influenza A viruses results in birth cohorts that have different initial influenza virus exposures. Historically, A/H3 predominant seasons have been associated with more severe influenza-associated disease; however, since the 2009 pandemic there are suggestions that some birth cohorts experience more severe illness in A/H1 predominant seasons. METHODS: U.S. influenza virologic, hospitalization and mortality surveillance data during 2000-2017 were analyzed for cohorts born between 1918 and 1989 that likely had different initial influenza virus exposures based on viruses circulating during early childhood. Relative risk/rate during H3 compared to H1 predominant seasons during pre-pandemic versus pandemic and later periods were calculated for each cohort. RESULTS: During the pre-pandemic period, all cohorts had more influenza-associated disease during H3 predominant seasons than H1 predominant seasons. During the pandemic and later period, four cohorts had higher hospitalization and mortality rates during H1 predominant seasons than H3 predominant seasons. DISCUSSION: Birth cohort differences in risk of influenza-associated disease by influenza A virus subtype can be seen in U.S. influenza surveillance data and differ between pre-pandemic and pandemic and later periods. As the population ages, the amount of influenza-associated disease may be greater in future H1 predominant seasons than H3 predominant seasons.

Influenza A(H3N2) viruses evade human immunity primarily by acquiring antigenic changes in the haemagglutinin (HA). HA receptor-binding features of contemporary A(H3N2) viruses hinder traditional antigenic characterization using haemagglutination inhibition and promote selection of HA mutants. Thus, alternative approaches are needed to reliably assess antigenic relatedness between circulating viruses and vaccines. We developed a high content imaging-based neutralization test (HINT) to reduce antigenic mischaracterization resulting from virus adaptation to cell culture. Ferret reference antisera were raised using clinical specimens containing viruses representing recent vaccine strains. Analysis of viruses circulating during 2011-2018 showed that gain of an N158-linked glycosylation in HA was a molecular determinant of antigenic distancing between A/Hong Kong/4801/2014-like (clade 3C.2a) and A/Texas/50/2012-like viruses (clade 3C.1), while multiple evolutionary HA F193S substitution were linked to antigenic distancing from A/Switzerland/97152963/2013-like (clade 3C.3a) and further antigenic distancing from A/Texas/50/2012-like viruses. Additionally, a few viruses carrying HA T135K and/or I192T showed reduced neutralization by A/Hong Kong/4801/2014-like antiserum. Notably, this technique elucidated the antigenic characteristics of clinical specimens, enabling direct characterization of viruses produced in vivo, and eliminating in vitro culture, which rapidly alters the genotype/phenotype. HINT is a valuable new antigenic analysis tool for vaccine strain selection.

CDC collects, compiles, and analyzes data on influenza activity and viruses in the United States. During September 30, 2018-February 2, 2019,* influenza activity(dagger) in the United States was low during October and November, increased in late December, and remained elevated through early February. As of February 2, 2019, this has been a low-severity influenza season (1), with a lower percentage of outpatient visits for influenza-like illness (ILI), lower rates of hospitalization, and fewer deaths attributed to pneumonia and influenza, compared with recent seasons. Influenza-associated hospitalization rates among children are similar to those observed in influenza A(H1N1)pdm09 predominant seasons; 28 influenza-associated pediatric deaths occurring during the 2018-19 season have been reported to CDC. Whereas influenza A(H1N1)pdm09 viruses predominated in most areas of the country, influenza A(H3N2) viruses have predominated in the southeastern United States, and in recent weeks accounted for a growing proportion of influenza viruses detected in several other regions. Small numbers of influenza B viruses (<3% of all influenza-positive tests performed by public health laboratories) also were reported. The majority of the influenza viruses characterized antigenically are similar to the cell culture-propagated reference viruses representing the 2018-19 Northern Hemisphere influenza vaccine viruses. Health care providers should continue to offer and encourage vaccination to all unvaccinated persons aged >/=6 months as long as influenza viruses are circulating. Finally, regardless of vaccination status, it is important that persons with confirmed or suspected influenza who have severe, complicated, or progressive illness; who require hospitalization; or who are at high risk for influenza complications be treated with antiviral medications.

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.

The anti-influenza therapeutic baloxavir targets cap-dependent endonuclease activity of polymerase acidic (PA) protein. We monitored baloxavir susceptibility in the United States with next generation sequencing analysis supplemented by phenotypic one-cycle infection assay. Analysis of PA sequences of 6,891 influenza A and B viruses collected during 2016/17 and 2017/18 seasons showed amino acid substitutions: I38L (two A(H1N1)pdm09 viruses), E23G (two A(H1N1)pdm09 viruses) and I38M (one A(H3N2) virus); conferring 4-10-fold reduced susceptibility to baloxavir.

During May 20-October 13, 2018,* low levels of influenza activity were reported in the United States, with a mix of influenza A and B viruses circulating. Seasonal influenza activity in the Southern Hemisphere was low overall, with influenza A(H1N1)pdm09 predominating in many regions. Antigenic testing of available influenza A and B viruses indicated that no significant antigenic drift in circulating viruses had emerged. In late September, the components for the 2019 Southern Hemisphere influenza vaccine were selected and included an incremental update to the A(H3N2) vaccine virus used in egg-based vaccine manufacturing; no change was recommended for the A(H3N2) component of cell-manufactured or recombinant influenza vaccines. Annual influenza vaccination is the best method for preventing influenza illness and its complications, and all persons aged >/=6 months who do not have contraindications should receive influenza vaccine, preferably before the onset of influenza circulation in their community, which often begins in October and peaks during December-February. Health care providers should offer vaccination by the end of October and should continue to recommend and administer influenza vaccine to previously unvaccinated patients throughout the 2018-19 influenza season (1). In addition, during May 20-October 13, a small number of nonhuman influenza "variant" virus infections(dagger) were reported in the United States; most were associated with exposure to swine. Although limited human-to-human transmission might have occurred in one instance, no ongoing community transmission was identified. Vulnerable populations, especially young children and other persons at high risk for serious influenza complications, should avoid swine barns at agricultural fairs, or close contact with swine.

The United States 2017-18 influenza season (October 1, 2017-May 19, 2018) was a high severity season with high levels of outpatient clinic and emergency department visits for influenza-like illness (ILI), high influenza-related hospitalization rates, and elevated and geographically widespread influenza activity across the country for an extended period. Nationally, ILI activity began increasing in November, reaching an extended period of high activity during January-February, and remaining elevated through March. Influenza A(H3N2) viruses predominated through February and were predominant overall for the season; influenza B viruses predominated from March onward. This report summarizes U.S. influenza activity* during October 1, 2017-May 19, 2018.(dagger).

Background: During the 2014-2015 influenza season in the United States, 256 cases of influenza-associated parotitis were reported from 27 states. We conducted a case-control study and laboratory investigation to further describe this rare clinical manifestation of influenza. Methods: During February 2015-April 2015, we interviewed 50 cases (with parotitis) and 124 ill controls (without parotitis) with laboratory-confirmed influenza; participants resided in 11 states and were matched by age, state, hospital admission status, and specimen collection date. Influenza viruses were characterized using real-time polymerase chain reaction and next-generation sequencing. We compared cases and controls using conditional logistic regression. Specimens from additional reported cases were also analyzed. Results: Cases, 73% of whom were aged <20 years, experienced painful (86%), unilateral (68%) parotitis a median of 4 (range, 0-16) days after onset of systemic or respiratory symptoms. Cases were more likely than controls to be male (76% vs 51%; P = .005). We detected influenza A(H3N2) viruses, genetic group 3C.2a, in 100% (32/32) of case and 92% (105/108) of control specimens sequenced (P = .22). Influenza B and A(H3N2) 3C.3 and 3C.3b genetic group virus infections were detected in specimens from additional cases. Conclusions: Influenza-associated parotitis, as reported here and in prior sporadic case reports, seems to occur primarily with influenza A(H3N2) virus infection. Because of the different clinical and infection control considerations for mumps and influenza virus infections, we recommend clinicians consider influenza in the differential diagnoses among patients with acute parotitis during the influenza season.

Background: During the 2014-2015 US influenza season, 320 cases of non-mumps parotitis (NMP) among residents of 21 states were reported to the Centers for Disease Control and Prevention (CDC). We conducted an epidemiologic and laboratory investigation to determine viral etiologies and clinical features of NMP during this unusually large occurrence. Methods: NMP was defined as acute parotitis or other salivary gland swelling of >2 days duration in a person with a mumps- negative laboratory result. Using a standardized questionnaire, we collected demographic and clinical information. Buccal samples were tested at the CDC for selected viruses, including mumps, influenza, human parainfluenza viruses (HPIVs) 1-4, adenoviruses, cytomegalovirus, Epstein-Barr virus (EBV), herpes simplex viruses (HSVs) 1 and 2, and human herpes viruses (HHVs) 6A and 6B. Results: Among the 320 patients, 65% were male, median age was 14.5 years (range, 0-90), and 67% reported unilateral parotitis. Commonly reported symptoms included sore throat (55%) and fever (48%). Viruses were detected in 210 (71%) of 294 NMP patients with adequate samples for testing, >/=2 viruses were detected in 37 samples, and 248 total virus detections were made among all samples. These included 156 influenza A(H3N2), 42 HHV6B, 32 EBV, 8 HPIV2, 2 HPIV3, 3 adenovirus, 4 HSV-1, and 1 HSV-2. Influenza A(H3N2), HHV6B, and EBV were the most frequently codetected viruses. Conclusions: Our findings suggest that, in addition to mumps, clinicians should consider respiratory viral (influenza) and herpes viral etiologies for parotitis, particularly among patients without epidemiologic links to mumps cases or outbreaks.

Influenza A(H1) viruses circulating in swine represent an emerging virus threat as zoonotic infections occur sporadically following exposure to swine. A fatal infection caused by an H1N1 variant (H1N1v) virus was detected in a patient with reported exposure to swine and who presented with pneumonia, respiratory failure, and cardiac arrest. To understand the genetic and phenotypic characteristics of the virus, genome sequence analysis, antigenic characterization, and ferret pathogenesis and transmissibility experiments were performed. Antigenic analysis of the virus isolated from the fatal case, A/Ohio/09/2015, demonstrated significant antigenic drift away from classical swine H1N1 variant viruses and H1N1 pandemic 2009 viruses. A substitution in the H1 hemagglutinin (G155E) was identified that likely impacted antigenicity, and reverse genetics was employed to understand the molecular mechanism of antibody escape. Reversion of the substitution to 155G, in a reverse genetics A/Ohio/09/2015 virus, showed that this residue was central to the loss of hemagglutination inhibition by ferret antisera raised against a prototypical H1N1 pandemic 2009 virus (A/California/07/2009), as well as gamma lineage classical swine H1N1 viruses, demonstrating the importance of this residue for antibody recognition of this H1 lineage. When analyzed in the ferret model, A/Ohio/09/2015 and another H1N1v virus (A/Iowa/39/2015), as well as A/California/07/2009, replicated efficiently in the respiratory tract of ferrets. The two H1N1v viruses transmitted efficiently among cohoused ferrets, but respiratory droplet transmission studies showed that A/California/07/2009 transmitted through the air more efficiently. Pre-existing immunity to A/California/07/2009 did not fully protect ferrets from challenge with A/Ohio/09/2015.IMPORTANCE Human infections with classical swine influenza A(H1N1) viruses that circulate in pigs continue to occur in the United States following exposure to swine. To understand the genetic and virologic characteristics of a virus (A/Ohio/09/2015) associated with a fatal infection and a virus associated with a non-fatal infection (A/Iowa/39/2015), we performed genome sequence analysis, antigenic testing, and pathogenicity and transmission studies in a ferret model. Reverse genetics was employed to identify a single antigenic site substitution (HA G155E) responsible for antigenic variation of A/Ohio/09/2015 compared to related classical swine influenza A(H1N1) viruses. Ferrets with pre-existing immunity to the pandemic A(H1N1) virus were challenged with A/Ohio/09/2015 demonstrating decreased protection. This data illustrates the potential for currently circulating swine influenza viruses to infect and cause illness in humans with pre-existing immunity to H1N1 pandemic 2009 viruses and a need for ongoing risk assessment and development of candidate vaccine viruses for improved pandemic preparedness.

Influenza activity in the United States began to increase in early November 2017 and rose sharply from December through February 3, 2018; elevated influenza activity is expected to continue for several more weeks. Influenza A viruses have been most commonly identified, with influenza A(H3N2) viruses predominating, but influenza A(H1N1)pdm09 and influenza B viruses were also reported. This report summarizes U.S. influenza activity* during October 1, 2017-February 3, 2018,(dagger) and updates the previous summary (1).

Background: The effectiveness of influenza vaccine during 2015-2016 was reduced in some age groups as compared to that in previous 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09 virus)-predominant seasons. We hypothesized that the age at first exposure to specific influenza A(H1N1) viruses could influence vaccine effectiveness (VE). Methods: We estimated the effectiveness of influenza vaccine against polymerase chain reaction-confirmed influenza A(H1N1)pdm09-associated medically attended illness from the 2010-2011 season through the 2015-2016 season, according to patient birth cohort using data from the Influenza Vaccine Effectiveness Network. Birth cohorts were defined a priori on the basis of likely immunologic priming with groups of influenza A(H1N1) viruses that circulated during 1918-2015. VE was calculated as 100 x [1 - adjusted odds ratio] from logistic regression models comparing the odds of vaccination among influenza virus-positive versus influenza test-negative patients. Results: A total of 2115 A(H1N1)pdm09 virus-positive and 14 696 influenza virus-negative patients aged >/=6 months were included. VE was 61% (95% confidence interval [CI], 56%-66%) against A(H1N1)pdm09-associated illness during the 2010-2011 through 2013-2014 seasons, compared with 47% (95% CI, 36%-56%) during 2015-2016. During 2015-2016, A(H1N1)pdm09-specific VE was 22% (95% CI, -7%-43%) among adults born during 1958-1979 versus 61% (95% CI, 54%-66%) for all other birth cohorts combined. Conclusion: Findings suggest an association between reduced VE against influenza A(H1N1)pdm09-related illness during 2015-2016 and early exposure to specific influenza A(H1N1) viruses.

Influenza activity in the United States was low during October 2017, but has been increasing since the beginning of November. Influenza A viruses have been most commonly identified, with influenza A(H3N2) viruses predominating. Several influenza activity indicators were higher than is typically seen for this time of year. The majority of influenza viruses characterized during this period were genetically or antigenically similar to the 2017-18 Northern Hemisphere cell-grown vaccine reference viruses. These data indicate that currently circulating viruses have not undergone significant antigenic drift; however, circulating A(H3N2) viruses are antigenically less similar to egg-grown A(H3N2) viruses used for producing the majority of influenza vaccines in the United States. It is difficult to predict which influenza viruses will predominate in the 2017-18 influenza season; however, in recent past seasons in which A(H3N2) viruses predominated, hospitalizations and deaths were more common, and the effectiveness of the vaccine was lower. Annual influenza vaccination is recommended for all persons aged ≥6 months who do not have contraindications. Multiple influenza vaccines are approved and recommended for use during the 2017-18 season, and vaccination should continue to be offered as long as influenza viruses are circulating and unexpired vaccine is available. This report summarizes U.S. influenza activity* during October 1-November 25, 2017 (surveillance weeks 40-47).(dagger).

During May 21-September 23, 2017, the United States experienced low-level seasonal influenza virus activity; however, beginning in early September, CDC received reports of a small number of localized influenza outbreaks caused by influenza A(H3N2) viruses. In addition to influenza A(H3N2) viruses, influenza A(H1N1)pdm09 and influenza B viruses were detected during May-September worldwide and in the United States. Influenza B viruses predominated in the United States from late May through late June, and influenza A viruses predominated beginning in early July. The majority of the influenza viruses collected and received from the United States and other countries during that time have been characterized genetically or antigenically as being similar to the 2017 Southern Hemisphere and 2017-18. Northern Hemisphere cell-grown vaccine reference viruses; however, a smaller proportion of the circulating A(H3N2) viruses showed similarity to the egg-grown A(H3N2) vaccine reference virus which represents the A(H3N2) viruses used for the majority of vaccine production in the United States. Also, during May 21-September 23, 2017, CDC confirmed a total of 33 influenza variant virus infections; two were influenza A(H1N2) variant (H1N2v) viruses (Ohio) and 31 were influenza A(H3N2) variant (H3N2v) viruses (Delaware [1], Maryland [13], North Dakota [1], Pennsylvania [1], and Ohio [15]). An additional 18 specimens from Maryland have tested presumptive positive for H3v and further analysis is being conducted at CDC.

During the 2016-17 influenza season (October 2, 2016-May 20, 2017) in the United States, influenza activity* was moderate. Activity remained low through November, increased during December, and peaked in February nationally, although there were regional differences in the timing of influenza activity. Influenza A(H3N2) viruses predominated through mid-March and were predominant overall for the season, but influenza B viruses were most commonly reported from late March through May. This report summarizes influenza activity in the United States during October 2, 2016-May 20, 2017dagger and updates the previous summary (1).

In February 2016, three influenza B/Victoria/2/87 lineage viruses exhibiting 4- to 158-fold reduced inhibition by neuraminidase inhibitors were detected in Laos. These viruses had an H134N substitution in the neuraminidase and replicated efficiently in vitro and in ferrets. Current antiviral drugs may be ineffective in controlling infections caused by viruses harboring this mutation.

Compared to previous years, seasonal influenza activity commenced early in Sao Paulo State, Brazil, Southern hemisphere during the 2016 year. In order to investigate the genetic pattern of influenza A(H1N1)pdm09 in the State of Sao Paulo a total of 479 respiratory samples, collected in January by Sentinel Surveillance Units, were screened by real-time RT-PCR. A total of 6 Influenza viruses A(H1N1)pdm09 presenting ct values ≤ 30 were sequenced following phylogenetic analysis. The present study identified the circulation of the new 6B.1 subgroup (A/Sao Paulo/10-118/2016 and A/Sao Paulo/3032/2016). In addition, influenza A(H1N1)pdm09 group 6B has also been identified during January in the State of Sao Paulo. Despite amino acid changes and changes in potential glycosylation motifs, 6B.1 viruses were well inhibited by the reference ferret antiserum against A/California/07/2009 virus, the A(H1N1)pdm09 component of the vaccine for the 2016 influenza season.

This report summarizes U.S. influenza activity during October 2, 2016-February 4, 2017, and updates the previous summary. Influenza activity in the United States began to increase in mid-December, remained elevated through February 4, 2017, and is expected to continue for several more weeks. To date, influenza A (H3N2) viruses have predominated overall, but influenza A (H1N1)pdm09 and influenza B viruses have also been identified.

This report summarizes U.S. influenza activity during October 2-December 17, 2016. Influenza activity in the United States remained low in October and has been slowly increasing since November. Influenza A viruses were identified most frequently, with influenza A (H3N2) viruses predominating. Most influenza viruses characterized during this period were genetically or antigenically similar to the reference viruses representing vaccine components recommended for production in the 2016-17 Northern Hemisphere influenza vaccines.

Rapid evolution of influenza A(H3N2) viruses necessitates close monitoring of their antigenic properties so emergence and spread of antigenic drift variants can be rapidly identified. Changes in hemagglutinin (HA) acquired by contemporary A(H3N2) viruses hinder antigenic characterization by traditional methods, thus complicating vaccine strain selection. Sequence-based approaches have been used to infer virus antigenicity; however, they are time-consuming and mid-throughput. To facilitate virological surveillance and epidemiological studies, we have developed and validated a pyrosequencing approach that enables identification of six HA clades of contemporary A(H3N2) viruses. The identification scheme of H3 clade 3C.2, 3C.2a, 3C.2b, 3C.3, 3C.3a and 3C.3b viruses is based on the interrogation of five SNPs within three neighboring HA regions: 412-431; 465-481; and 559-571. Two bioinformatics tools, IdentiFire (Qiagen) and FireComb (developed in-house) were utilized to expedite pyrosequencing data analysis. The assay's analytical sensitivity was 10 focus forming units; and respiratory specimens with CT value < 34 typically produced good quality pyrograms. When applied to 120 A(H3N2) virus isolates and 27 respiratory specimens, the assay displayed 100% agreement with clades determined by HA sequencing coupled with phylogenetics. The multi-SNP analysis described here was readily adopted by another laboratory with pyrosequencing capabilities. Implementation of this approach enhanced virological surveillance and epidemiological studies from 2013-2016 when over 3000 A(H3N2) viruses were examined.

During May 22-September 10, 2016, the United States experienced typical low levels of seasonal influenza activity overall; beginning in late August, clinical laboratories reported a slight increase in influenza positive test results and CDC received reports of a small number of localized influenza outbreaks caused by influenza A (H3N2) viruses. Influenza A (H1N1)pdm09, influenza A (H3N2), and influenza B viruses were detected during May-September in the United States and worldwide. The majority of the influenza viruses collected from the United States and other countries during that time have been characterized antigenically or genetically or both as being similar to the reference viruses representing vaccine components recommended for the 2016-17 Northern Hemisphere vaccine. During May 22-September 10, 2016, 20 influenza variant virusdagger infections were reported; two were influenza A (H1N2) variant (H1N2v) viruses (Minnesota and Wisconsin) and 18 were influenza A (H3N2) variant (H3N2v) viruses (12 from Michigan and six from Ohio).

During the 2015-16 influenza season (October 4, 2015-May 21, 2016) in the United States, influenza activity was lower and peaked later compared with the previous three seasons (2012-13, 2013-14, and 2014-15). Activity remained low from October 2015 until late December 2015 and peaked in mid-March 2016. During the most recent 18 influenza seasons (including this season), only two other seasons have peaked in March (2011-12 and 2005-06). Overall influenza activity was moderate this season, with a lower percentage of outpatient visits for influenza-like illness (ILI), lower hospitalization rates, and a lower percentage of deaths attributed to pneumonia and influenza (P&I) compared with the preceding three seasons. Influenza A(H1N1)pdm09 viruses predominated overall, but influenza A(H3N2) viruses were more commonly identified from October to early December, and influenza B viruses were more commonly identified from mid-April through mid-May. The majority of viruses characterized this season were antigenically similar to the reference viruses representing the recommended components of the 2015-16 Northern Hemisphere influenza vaccine. This report summarizes influenza activity in the United States during the 2015-16 influenza season (October 4, 2015-May 21, 2016) section sign and reports the vaccine virus components recommended for the 2016-17 Northern Hemisphere influenza vaccines.

BACKGROUND: During the 2014-15 US influenza season, expanded genetic characterization of circulating influenza A(H3N2) viruses was used to assess the impact of genetic variability of influenza A(H3N2) viruses on influenza vaccine effectiveness (VE). METHODS: A novel pyrosequencing assay was used to determine genetic group based on hemagglutinin (HA) gene sequences of influenza A(H3N2) viruses from patients enrolled US Flu Vaccine Effectiveness network sites. Vaccine effectiveness was estimated using a test-negative design comparing vaccination among patients infected with influenza A(H3N2) viruses and uninfected patients. RESULTS: Among 9710 enrollees, 1868 (19%) tested positive for influenza A(H3N2); genetic characterization of 1397 viruses showed 1134 (81%) belonged to one HA genetic group (3C.2a) of antigenically drifted H3N2 viruses. Effectiveness of 2014-15 influenza vaccination varied by A(H3N2) genetic group from 1% (95% confidence interval [CI], -14% to 14%) against illness caused by antigenically drifted A(H3N2) group 3C.2a viruses versus 44% (95% CI, 16% to 63%) against illness caused by vaccine-like A(H3N2) group 3C.3b viruses. CONCLUSION: Effectiveness of 2014-15 influenza vaccination varied by genetic group of influenza A(H3N2) virus. Changes in hemagglutinin genes related to antigenic drift were associated with reduced vaccine effectiveness.

From October through mid-December 2015, influenza activity remained low in most regions of the United States. Activity began to increase in late December 2015 and continued to increase slowly through early February 2016. Influenza A viruses have been most frequently identified, with influenza A (H3N2) viruses predominating during October until early December, and influenza A (H1N1)pdm09 viruses predominating from mid-December until early February. Most of the influenza viruses characterized during that time are antigenically similar to vaccine virus strains recommended for inclusion in the 2015-16 Northern Hemisphere vaccines. This report summarizes U.S. influenza activity* during October 4, 2015-February 6, 2016, and updates the previous summary.