The Effect of Preexisting Immunity on Virus Detection and Immune Responses in a Phase II, Randomized Trial of a Russian-Backbone, Live, Attenuated Influenza Vaccine in Bangladeshi Children.

BACKGROUND: In a 2012 Phase II clinical trial, 300 Bangladeshi children aged 24 to 59 months with no prior influenza vaccine exposure were randomized to receive a single intranasally-administered dose of either trivalent, Russian-backbone, live, attenuated influenza vaccine (LAIV) or placebo. Protocol-defined analyses, presented in the companion manuscript, demonstrate decreased viral detection and immunogenicity for A/H1N1pdm09, relative to the A/H3N2 and B strains. This post hoc analysis of the trial data aims to investigate the LAIV strain differences by testing the hypothesis that preexisting humoral and mucosal immunity may influence viral recovery and immune responses after LAIV receipt. METHODS: We used logistic regressions to evaluate the relations between markers of preexisting immunity (ie, hemagglutination inhibition [HAI], microneutralization, and immunoglobulin G and immunoglobulin A (both serum and mucosal antibodies) and LAIV viral recovery in the week post-vaccination. We then tested for potential effect modification by baseline HAI titers (ie, <10 versus ≥10) and week 1 viral recovery on the LAIV-induced serum and mucosal immune responses, measured between days 0 and 21 post-vaccination. RESULTS: Higher levels of preexisting immunity to influenza A/H3N2 and B were strongly associated with strain-specific prevention of viral shedding upon LAIV receipt. While evidence of LAIV immunogenicity was observed for all 3 strains, the magnitudes of immune responses were most pronounced in children with no evidence of preexisting HAI and in those with detectable virus. CONCLUSIONS: The results provide evidence for a bidirectional association between viral replication and immunity, and underscore the importance of accounting for preexisting immunity when evaluating virologic and immunologic responses to LAIVs. CLINICAL TRIALS REGISTRATION: NCT01625689.

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.

Update: Influenza Activity - United States, September 30, 2018-February 2, 2019.

CDC collects, compiles, and analyzes data on influenza activity and viruses in the United States. During September 30, 2018-February 2, 2019,* influenza activity† 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.

Pathogenesis and transmission of avian influenza A (H7N9) virus in ferrets and mice.

On 29 March 2013, the Chinese Center for Disease Control and Prevention confirmed the first reported case of human infection with an avian influenza A(H7N9) virus. The recent human infections with H7N9 virus, totalling over 130 cases with 39 fatalities to date, have been characterized by severe pulmonary disease and acute respiratory distress syndrome (ARDS). This is concerning because H7 viruses have typically been associated with ocular disease in humans, rather than severe respiratory disease. This recent outbreak underscores the need to better understand the pathogenesis and transmission of these viruses in mammals. Here we assess the ability of A/Anhui/1/2013 and A/Shanghai/1/2013 (H7N9) viruses, isolated from fatal human cases, to cause disease in mice and ferrets and to transmit to naive animals. Both H7N9 viruses replicated to higher titre in human airway epithelial cells and in the respiratory tract of ferrets compared to a seasonal H3N2 virus. Moreover, the H7N9 viruses showed greater infectivity and lethality in mice compared to genetically related H7N9 and H9N2 viruses. The H7N9 viruses were readily transmitted to naive ferrets through direct contact but, unlike the seasonal H3N2 virus, did not transmit readily by respiratory droplets. The lack of efficient respiratory droplet transmission was corroborated by low receptor-binding specificity for human-like α2,6-linked sialosides. Our results indicate that H7N9 viruses have the capacity for efficient replication in mammals and human airway cells and highlight the need for continued public health surveillance of this emerging virus.

Kinetics of Serological Responses in Critically Ill Patients Hospitalized With 2009 Pandemic Influenza A(H1N1) Virus Infection in Canada, 2009-2011.

Background: The kinetics of the antibody response during severe influenza are not well documented. Methods: Critically ill patients infected with 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09), confirmed by reverse-transcription polymerase chain reaction analysis or seroconversion (defined as a ≥4-fold rise in titers), during 2009-2011 in Canada were prospectively studied. Antibody titers in serially collected sera were determined using hemagglutinin inhibition (HAI) and microneutralization assays. Average antibody curves were estimated using linear mixed-effects models and compared by patient outcome, age, and corticosteroid treatment. Results: Of 47 patients with A(H1N1)pdm09 virus infection (median age, 47 years), 59% had baseline HAI titers of <40, and 68% had baseline neutralizing titers of <40. Antibody titers rose quickly after symptom onset, and, by day 14, 83% of patients had HAI titers of ≥40, and 80% had neutralizing titers ≥40. Baseline HAI titers were significantly higher in patients who died compared with patients who survived; however, the antibody kinetics were similar by patient outcome and corticosteroid treatment. Geometric mean titers over time in older patients were lower than those in younger patients. Conclusions: Critically ill patients with influenza A(H1N1)pdm09 virus infection had strong HAI and neutralizing antibody responses during their illness. Antibody kinetics differed by age but were not associated with patient outcome.

Influence of Immune Priming and Egg Adaptation in the Vaccine on Antibody Responses to Circulating A(H1N1)pdm09 Viruses After Influenza Vaccination in Adults.

Background: Although ferret antisera used in influenza surveillance did not detect antigenic drift of A(H1N1)pdm09 viruses during the 2015-2016 season, low vaccine effectiveness was reported in adults. We investigated the immune basis of low responses to circulating A(H1N1)pdm09 viruses after vaccination. Methods: Prevaccination and postvaccination serum samples collected from >300 adults (aged 18-49 years) in 6 seasons (2010-2011 to 2015-2016) were analyzed using hemagglutination inhibition assays to evaluate the antibody responses to 13 A(H1N1) viruses circulated from 1977 to 2016. Microneutralization and serum adsorption assays were used to verify the 163K and 223R specificity of antibodies. Results: Individual antibody profiles to A(H1N1) viruses revealed 3 priming patterns: USSR/77, TW/86, or NC/99 priming. More than 20% of adults had reduced titers to cell-propagated circulating 6B.1 and 6B.2 A(H1N1)pdm09 viruses compared with the A/California/07/2009 vaccine virus X-179A. Significantly reduced antibody reactivity to circulating viruses bearing K163Q was observed only in the USSR/77-primed cohort, whereas significantly lower reactivity caused by egg-adapted Q223R change was detected across all 3 cohorts. Conclusion: Both 163K specificity driven by immune priming and 223R specificity from egg-adapted changes in the vaccine contributed to low responses to circulating A(H1N1)pdm09 viruses after vaccination. Our study highlights the need to incorporate human serology in influenza surveillance and vaccine strain selection.

Community-Acquired Pneumonia Requiring Hospitalization among U.S. Adults.

BACKGROUND: Community-acquired pneumonia is a leading infectious cause of hospitalization and death among U.S. adults. Incidence estimates of pneumonia confirmed radiographically and with the use of current laboratory diagnostic tests are needed. METHODS: We conducted active population-based surveillance for community-acquired pneumonia requiring hospitalization among adults 18 years of age or older in five hospitals in Chicago and Nashville. Patients with recent hospitalization or severe immunosuppression were excluded. Blood, urine, and respiratory specimens were systematically collected for culture, serologic testing, antigen detection, and molecular diagnostic testing. Study radiologists independently reviewed chest radiographs. We calculated population-based incidence rates of community-acquired pneumonia requiring hospitalization according to age and pathogen. RESULTS: From January 2010 through June 2012, we enrolled 2488 of 3634 eligible adults (68%). Among 2320 adults with radiographic evidence of pneumonia (93%), the median age of the patients was 57 years (interquartile range, 46 to 71); 498 patients (21%) required intensive care, and 52 (2%) died. Among 2259 patients who had radiographic evidence of pneumonia and specimens available for both bacterial and viral testing, a pathogen was detected in 853 (38%): one or more viruses in 530 (23%), bacteria in 247 (11%), bacterial and viral pathogens in 59 (3%), and a fungal or mycobacterial pathogen in 17 (1%). The most common pathogens were human rhinovirus (in 9% of patients), influenza virus (in 6%), and Streptococcus pneumoniae (in 5%). The annual incidence of pneumonia was 24.8 cases (95% confidence interval, 23.5 to 26.1) per 10,000 adults, with the highest rates among adults 65 to 79 years of age (63.0 cases per 10,000 adults) and those 80 years of age or older (164.3 cases per 10,000 adults). For each pathogen, the incidence increased with age. CONCLUSIONS: The incidence of community-acquired pneumonia requiring hospitalization was highest among the oldest adults. Despite current diagnostic tests, no pathogen was detected in the majority of patients. Respiratory viruses were detected more frequently than bacteria. (Funded by the Influenza Division of the National Center for Immunizations and Respiratory Diseases.).

Community-acquired pneumonia requiring hospitalization among U.S. children.

BACKGROUND: Incidence estimates of hospitalizations for community-acquired pneumonia among children in the United States that are based on prospective data collection are limited. Updated estimates of pneumonia that has been confirmed radiographically and with the use of current laboratory diagnostic tests are needed. METHODS: We conducted active population-based surveillance for community-acquired pneumonia requiring hospitalization among children younger than 18 years of age in three hospitals in Memphis, Nashville, and Salt Lake City. We excluded children with recent hospitalization or severe immunosuppression. Blood and respiratory specimens were systematically collected for pathogen detection with the use of multiple methods. Chest radiographs were reviewed independently by study radiologists. RESULTS: From January 2010 through June 2012, we enrolled 2638 of 3803 eligible children (69%), 2358 of whom (89%) had radiographic evidence of pneumonia. The median age of the children was 2 years (interquartile range, 1 to 6); 497 of 2358 children (21%) required intensive care, and 3 (<1%) died. Among 2222 children with radiographic evidence of pneumonia and with specimens available for bacterial and viral testing, a viral or bacterial pathogen was detected in 1802 (81%), one or more viruses in 1472 (66%), bacteria in 175 (8%), and both bacterial and viral pathogens in 155 (7%). The annual incidence of pneumonia was 15.7 cases per 10,000 children (95% confidence interval [CI], 14.9 to 16.5), with the highest rate among children younger than 2 years of age (62.2 cases per 10,000 children; 95% CI, 57.6 to 67.1). Respiratory syncytial virus was more common among children younger than 5 years of age than among older children (37% vs. 8%), as were adenovirus (15% vs. 3%) and human metapneumovirus (15% vs. 8%). Mycoplasma pneumoniae was more common among children 5 years of age or older than among younger children (19% vs. 3%). CONCLUSIONS: The burden of hospitalization for children with community-acquired pneumonia was highest among the very young, with respiratory viruses the most commonly detected causes of pneumonia. (Funded by the Influenza Division of the National Center for Immunization and Respiratory Diseases.).

Influenza Activity - United States, September 30-December 1, 2018.

Influenza activity in the United States was low during October 2018, and, although it increased slowly during November, activity remains low across most of the country.* During the week ending December 1, 2018, the percentage of outpatient visits for influenza-like illness† (ILI) was equal to the national baseline§ (Figure) and was at or slightly above the region-specific baseline in four of the 10 U.S. Department of Health and Human Services regions¶ (Regions 4 and 7-9). The majority of jurisdictions experienced minimal or low ILI activity since September 30; however, two experienced moderate ILI activity, and two experienced high ILI activity** during the week ending December 1. The percentage of deaths attributed to pneumonia and influenza remains below the epidemic threshold,†† and the rate of influenza-associated hospitalizations remains low. Five laboratory-confirmed, influenza-associated pediatric deaths occurring since September 30 have been reported to CDC. During the week ending December 1, the majority of jurisdictions (40 states, the District of Columbia, Puerto Rico, and U.S. Virgin Islands) reported sporadic or local geographic spread of influenza activity, nine states reported regional activity, and one state reported widespread activity.§§.

Update: Influenza Activity - United States and Worldwide, May 20-October 13, 2018.

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† 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.§.

Update: Influenza Activity - United States, October 1, 2017-February 3, 2018.

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,† and updates the previous summary (1).

Update: Influenza Activity in the United States During the 2017-18 Season and Composition of the 2018-19 Influenza Vaccine.

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.†.

Cross-Reactive Antibody Responses to Novel H5Nx Influenza Viruses Following Homologous and Heterologous Prime-Boost Vaccination with a Prepandemic Stockpiled A(H5N1) Vaccine in Humans.

Recently, novel highly pathogenic avian influenza H5Nx viruses (clade 2.3.4.4) caused outbreaks in US poultry. We evaluated the potential of a stockpiled A(H5N1) A/Anhui/1/2005 (clade 2.3.4) vaccine to elicit cross-reactive antibody responses to these emerging viruses. Sera from subjects who received 2 doses of MF59-adjuvanted A/Anhui/1/2005, or 1 dose of MF59-adjuvanted A/Anhui/1/2005 following priming with a clade 1 vaccine were characterized by microneutralization assays and modified hemagglutination inhibition (HI) assays. Only heterologous prime-boost vaccination induced modest cross-reactive HI antibody responses to H5Nx viruses. Heterologous prime-boost may provide a more effective vaccination strategy to broaden the antibody responses to emerging viruses.

Effect of Priming With Seasonal Influenza A(H3N2) Virus on the Prevalence of Cross-Reactive Hemagglutination-Inhibition Antibodies to Swine-Origin A(H3N2) Variants.

Background: Recent outbreaks of swine-origin influenza A(H3N2) variant (H3N2v) viruses have raised public health concerns. Previous studies indicated that older children and young adults had the highest levels of hemagglutination-inhibition (HI) antibodies to 2010-2011 H3N2v viruses. However, newly emerging 2013 H3N2v have acquired antigenic mutations in the hemagglutinin at amino acid position 145 (N145K/R). We estimated the levels of serologic cross-reactivity among humans primed with seasonal influenza A(H3N2) (sH3N2), using postinfection ferret antisera. We also explored age-related HI antibody responses to 2012-2013 H3N2v viruses. Methods: Human and ferret antisera were tested in HI assays against 1 representative 2012 H3N2v (145N) and 2 2013 H3N2v (145K/R) viruses, together with 9 sH3N2 viruses circulating since 1968. Results: Low levels of cross-reactivity between the H3N2v and sH3N2 viruses from the 1970s-1990s were observed using postinfection ferret antisera. The overall seroprevalence among the sH3N2-primed population against 2012-2013 H3N2v viruses was >50%, and age-related seroprevalence was observed. Seroprevalence was significantly higher to 2013 H3N2v than to 2012 H3N2v viruses among some children likely to have been primed with A/Sydney/5/97-like (145K) or A/Wuhan/359/95-like viruses (145K). Conclusions: A single substitution (N145K/R) was sufficient to affect seropositivity to H3N2v viruses in some individuals. Insight into age-related antibody responses to newly emerging H3N2v viruses is critical for risk assessment and pandemic preparedness.

A Pyrosequencing-Based Approach to High-Throughput Identification of Influenza A(H3N2) Virus Clades Harboring Antigenic Drift Variants.

The rapid evolution of influenza A(H3N2) viruses necessitates close monitoring of their antigenic properties so the 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 developed and validated a pyrosequencing approach that enables identification of six HA clades of contemporary A(H3N2) viruses. The identification scheme of viruses of the H3 clades 3C.2, 3C.2a, 3C.2b, 3C.3, 3C.3a, and 3C.3b is based on the interrogation of five single nucleotide polymorphisms (SNPs) within three neighboring HA regions, namely 412 to 431, 465 to 481, and 559 to 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 threshold cycle (CT) values of <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. The implementation of this approach enhanced the findings from virological surveillance and epidemiological studies between 2013 and 2016, which examined more than 3,000 A(H3N2) viruses.

Increase in Human Infections with Avian Influenza A(H7N9) Virus During the Fifth Epidemic - China, October 2016-February 2017.

During March 2013-February 24, 2017, annual epidemics of avian influenza A(H7N9) in China resulted in 1,258 avian influenza A(H7N9) virus infections in humans being reported to the World Health Organization (WHO) by the National Health and Family Planning Commission of China and other regional sources (1). During the first four epidemics, 88% of patients developed pneumonia, 68% were admitted to an intensive care unit, and 41% died (2). Candidate vaccine viruses (CVVs) were developed, and vaccine was manufactured based on representative viruses detected after the emergence of A(H7N9) virus in humans in 2013. During the ongoing fifth epidemic (beginning October 1, 2016),* 460 human infections with A(H7N9) virus have been reported, including 453 in mainland China, six associated with travel to mainland China from Hong Kong (four cases), Macao (one) and Taiwan (one), and one in an asymptomatic poultry worker in Macao (1). Although the clinical characteristics and risk factors for human infections do not appear to have changed (2,3), the reported human infections during the fifth epidemic represent a significant increase compared with the first four epidemics, which resulted in 135 (first epidemic), 320 (second), 226 (third), and 119 (fourth epidemic) human infections (2). Most human infections continue to result in severe respiratory illness and have been associated with poultry exposure. Although some limited human-to-human spread continues to be identified, no sustained human-to-human A(H7N9) transmission has been observed (2,3).

Update: Influenza Activity - United States and Worldwide, May 21-September 23, 2017.

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.

Update: Increase in Human Infections with Novel Asian Lineage Avian Influenza A(H7N9) Viruses During the Fifth Epidemic - China, October 1, 2016-August 7, 2017.

Among all influenza viruses assessed using CDC's Influenza Risk Assessment Tool (IRAT), the Asian lineage avian influenza A(H7N9) virus (Asian H7N9), first reported in China in March 2013,* is ranked as the influenza virus with the highest potential pandemic risk (1). During October 1, 2016-August 7, 2017, the National Health and Family Planning Commission of China; CDC, Taiwan; the Hong Kong Centre for Health Protection; and the Macao CDC reported 759 human infections with Asian H7N9 viruses, including 281 deaths, to the World Health Organization (WHO), making this the largest of the five epidemics of Asian H7N9 infections that have occurred since 2013 (Figure 1). This report summarizes new viral and epidemiologic features identified during the fifth epidemic of Asian H7N9 in China and summarizes ongoing measures to enhance pandemic preparedness. Infections in humans and poultry were reported from most areas of China, including provinces bordering other countries, indicating extensive, ongoing geographic spread. The risk to the general public is very low and most human infections were, and continue to be, associated with poultry exposure, especially at live bird markets in mainland China. Throughout the first four epidemics of Asian H7N9 infections, only low pathogenic avian influenza (LPAI) viruses were detected among human, poultry, and environmental specimens and samples. During the fifth epidemic, mutations were detected among some Asian H7N9 viruses, identifying the emergence of high pathogenic avian influenza (HPAI) viruses as well as viruses with reduced susceptibility to influenza antiviral medications recommended for treatment. Furthermore, the fifth-epidemic viruses diverged genetically into two separate lineages (Pearl River Delta lineage and Yangtze River Delta lineage), with Yangtze River Delta lineage viruses emerging as antigenically different compared with those from earlier epidemics. Because of its pandemic potential, candidate vaccine viruses (CVV) were produced in 2013 that have been used to make vaccines against Asian H7N9 viruses circulating at that time. CDC is working with partners to enhance surveillance for Asian H7N9 viruses in humans and poultry, to improve laboratory capability to detect and characterize H7N9 viruses, and to develop, test and distribute new CVV that could be used for vaccine production if a vaccine is needed.

Update: Influenza Activity in the United States During the 2016-17 Season and Composition of the 2017-18 Influenza Vaccine.

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, 2017† and updates the previous summary (1).

Update: Influenza Activity - United States, October 2, 2016-February 4, 2017.

This report summarizes U.S. influenza activity* during October 2, 2016-February 4, 2017,† and updates the previous summary (1). 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.