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Acute lower respiratory tract infections (LRTIs) are a major worldwide health problem, particularly in childhood. About 30–50% of acute LRTIs are viral in origin with influenza A infection a key cause of explosive community outbreaks. Many different influenza A viruses occur naturally in animal reservoirs and present a constant threat of zoonotic infections and global pandemics. Since 2009, when pandemic (H1N1) influenza A emerged from a swine origin, there have been a number of different zoonotic influenza A transmissions into the human population, including H1N1 and H3N2 variant viruses in North America and H7N9 viruses in China. The segmented nature of the influenza A virus genome and the circulation of these viruses in wild bird, domestic poultry and mammalian reservoirs presents a continuous opportunity for reassortment of viral genes and the emergence of a novel pandemic virus. Constant vigilance is required. The emergence of severe acute respiratory syndrome in 2003 and Middle East respiratory syndrome coronavirus in 2012, highlights the fact that other serious respiratory viral infections in humans may originate in animals. Enhanced awareness of the potential for serious human respiratory disease in association with travel, or animal exposure, should form part of clinical assessment. Rapid developments in genomic technology improve the ability to diagnose previously undetected pathogens. Preventative measures for influenza include annual vaccination and treatment with antiviral drugs such as neuraminidase inhibitors, oseltamivir and zanamivir. Subtype-dependent resistance to antivirals can develop and should be closely monitored.

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.†.

Objectives The cross-border transmission of infectious diseases is a worldwide public health issue. Current border screening measures are insufficiently sensitive. The study objectives were to describe the epidemiologic pattern of influenza infection among incoming travellers at Xiamen International Airport during nonpandemic periods and to assess the performance of a rapid influenza diagnostic test in border screening. Methods Between May 2015 and May 2016, travellers with influenza-like illnesses entering China at Xiamen International Airport were screened with a rapid test, Flu Dot-ELISA, and the collected specimens were further subjected to virus isolation and phylogenetic analysis. Results Of the 1 540 076 incoming travellers, 1224 cases of influenza-like illness were identified; 261 tested positive in the rapid test, and 176 were confirmed to be influenza through virus culture. The sensitivity and specificity of the rapid test were demonstrated to be 96.6% (170/176) and 91.3% (957/1048), respectively, and the positive predictive and negative predictive values were 65.1% (170/261) and 99.4% (957/963), respectively. The epidemiologic study indicated that H3N2 and (H1N1)pdm09 were dominant in 2015 and 2016, respectively. In 2016, an increased number of influenza B isolates and cocirculation of both Victoria and Yamagata lineage influenza B viruses were observed, and mismatches between circulating influenza A(H1N1)pdm09 and influenza B Victoria lineage strains and vaccine strains also occurred. Conclusions We demonstrated the suitability and value of a high-sensitivity rapid influenza test in border screening and highlighted the importance of incoming travellers as a source of imported infectious diseases.

Epidemiological indicators have shown the substantial impact of influenza B (Flu B) on the development of severe acute respiratory infection (SARI) and on mortality rates. In Brazil, the trivalent vaccine, composed of only one Flu B lineage is available. We investigated Flu B infections in clinical samples collected by the epidemiological surveillance service of Paraná State, Brazil, from 2013 to 2016. The Flu B lineages Yamagata- (B/Yam) and Victoria-like (B/Vic) were identified using the qRT-PCR assay, and notification forms were reviewed. Among 379 Flu B positive samples evaluated, 370 (98%) were characterized as B/Yam or B/Vic lineages. Both co-circulated with a frequency of 47% and 53%, respectively. B/Yam infected equally both genders, while B/Vic was more frequent in females (71%). The median age of patients infected by B/Vic (23y; 11-35) was lower than that of patients infected by B/Yam (32y; 12-50). Mismatch between the vaccine and the circulating strain was observed in the 2013 season, with a high number of SARI cases. B/Vic lineage was associated with a larger number of SARI cases (62%), while B/Yam with influenza-like illness (ILI) (61%). Differences were observed in the strains circulating in separate regions of Paraná State. B/Vic was prevalent in the northwestern (67%) and B/Yam in the southeastern region (60%). The unpredictability of Flu B lineage circulation causes a substantial increase in severe disease during epidemics in a vaccine mismatch season. In addition, the differences in the epidemiological profile of the target population of Flu B infections in relation to other respiratory viruses, as well as among the B/Vic and B/Yam lineages may also be associated to an increase in disease burden. These findings have direct consequences on vaccination strategies. Therefore, further molecular epidemiology studies of Flu B in Brazil are required to corroborate these primary results.

The clinical picture in severe cases of pandemic (H1N1) 2009 influenza is markedly different from the disease pattern seen during epidemics of seasonal influenza, in that many of those affected were previously healthy young people. Current predictions estimate that, during a pandemic wave, 12–30% of the population will develop clinical influenza (compared with 5–15% for seasonal influenza) with 4% of those patients requiring hospital admissions and one in five requiring critical care. This review covers the background, clinical presentation, diagnosis, and treatment. The role of immunization and antiviral drugs is discussed. Experience from the first wave of pandemic (H1N1) 2009 influenza suggests that a number of infected patients become critically ill and require intensive care admission. These patients rapidly develop severe progressive respiratory failure which is often associated with failure of other organs, or marked worsening of underlying airways disease. The critical care management of these patients and the implications for resources is reviewed. Guidance from a range of bodies has been produced in a relatively short period of time in response to pandemic (H1N1) 2009 influenza. Disease severity has the potential to change, especially if there is virus mutation. Clinicians must be prepared for the unexpected and continue to share their experiences to maximize patient outcomes.

Background The 2015/2016 influenza season was characterized in Europe by the circulation of A(H1N1)pdm09 clade 6B.1 and B/Victoria-lineage influenza viruses. The components of the vaccines used in the current and past two seasons in the Valencia region were similar but not well matched to the 2015/2016 dominant influenza-circulating strains. We estimate influenza vaccine effectiveness (IVE) and interference of previous vaccination in preventing admission with A(H1N1)pdm09 or B/Victoria-lineage in this particular season. Methods The Valencia Hospital Network for the Study of Influenza runs an active surveillance hospital-based study to collect clinical and virological data from consecutive admissions possibly related to influenza. Combined nasopharyngeal and pharyngeal swabs are analyzed by reverse transcription polymerase chain reaction, and the hemagglutinin is sequenced in a sample of positive influenza specimens. Vaccination is ascertained consulting a population vaccine information system. We estimate IVE using a test-negative approach. Results During the 2015–2016 season, we recruited 1049 eligible admissions of patients 60 years or older, and 187 tested positive for influenza. The adjusted IVE in preventing admission with A(H1N1)pdm09 was 20.2%; 95% confidence interval (CI) −21.3–47.5% and −33.2%; 95% CI, −140.1–26.1% in preventing admission with B/Victoria-lineage. The majority of A(H1N1)pdm09 sequenced viruses belonged to the emerging 6B.1 subclade, defined by S162N and I216T mutations in the hemagglutinin protein. When we restricted our analysis to those not vaccinated in the previous year, unadjusted IVE was 84.9% (95% CI 9.9–100.0) overall, 77.9% (−32.7–100.0%) in preventing A(H1N1)pdm09 and 48.8% (−219.5–100.0%) in preventing B/Yamagata-lineage admission. Conclusions Our findings indicate that IVE was low in preventing A(H1N1)pdm09 and strongly correlated with vaccination in the previous season. No effect in preventing admission with B/Victoria-lineage was observed. For the 2015/2016 season, IVE was low due to a mismatch and lack of concordance between the circulating and vaccine viruses.

The majority of the Egyptian swine population was culled in the aftermath of the 2009 H1N1 pandemic, but small-scale growing remains. We sampled pigs from piggeries and an abattoir in Cairo. We found virological evidence of infection with avian H9N2 and H5N1 viruses as well as human pandemic H1N1 influenza virus. Serological evidence suggested previous exposure to avian H5N1 and H9N2, human pandemic H1N1, and swine avian-like and human-like viruses. This raises concern about potential reassortment of influenza viruses in pigs and highlights the need for better control and prevention of influenza virus infection in pigs.

SUMMARYPrior studies suggest that the influenza vaccine is protective against some outcomes in hospitalized patients infected with influenza despite vaccination. We utilized surveillance data from Columbus, Ohio to investigate this association over multiple influenza seasons and age groups. Data on laboratory-confirmed influenza-associated hospitalizations were collected as a part of the Influenza Hospitalization Surveillance Project for the 2012–2013, 2013–2014, and 2014–2015 influenza seasons. The association between influenza vaccination status was examined in relation to the outcomes of severe influenza and diagnosis of pneumonia among patients receiving antiviral treatment. Data were analyzed using multivariable logistic regression. We observed no overall association between influenza vaccination status and severe influenza among hospitalized patients. During the 2013–2014 season, those who were vaccinated were 41% less likely to be diagnosed with pneumonia compared with those who were unvaccinated (OR = 0·59 95% CI 0·41–0·86). The influenza vaccine may provide a secondary preventive function against pneumonia among influenza cases requiring hospitalization. However, a protective effect was only observed in 2013–2014, an influenza H1N1 dominant year. Differences in circulating influenza virus strains and vaccine matching to the circulating strains during influenza seasons may impact this association.

The Spanish influenza pandemic in the years 1918–1920 was the largest and most tragic pandemic of infectious disease in human history. Deciphering the structure of the virus (including the determination of complete genome sequence) of this pandemic and the phylogenetic analysis and explanation of its virulence became possible thanks to molecular genetic analysis of the virus isolated from the fixed and frozen lung tissue of influenza victims who died in 1918 and were buried frozen in Alaska and Spitsbergen. Epidemiological data from the course of this pandemic in Poland have not been previously published. For analysis, we used source materials such as clinical studies and case reports of doctors fighting against the pandemic and registries of influenza cases in units of the Polish Army and military hospitals. Clinically, the pandemic of 1918 was characterized by the same symptoms and course as influenza in other years. Pathologically, the disease was similar to the other pandemic, in that the destruction was mostly limited to the respiratory tract. The “Spanish” influenza pandemic of 1918–1920 took place in Poland in 3 epidemic waves. The peaks of morbidity and mortality occurred in the capital, Warsaw, in December 1918 and in December 1919 to January 1920. It is estimated that throughout the pandemic period of 1918–1920 in Poland, 200 000 to 300 000 people died.

Seasonal influenza and RSV were associated with 23.0 and 13.2 allcause deaths/100 000 population annually. The peak mortality rate was in the elderly for influenza and in infants for RSV. And 63% of seasonal influenza and 48% of RSV-associated deaths occurred out-of-hospital., Background Estimates of influenza- and respiratory syncytial virus (RSV)-associated mortality burden are important to guide policy for control. Data are limited on the contribution of out-of-hospital deaths to this mortality. Methods We modeled excess mortality attributable to influenza and RSV infection by applying regression models to weekly deaths from national vital statistics from 2009 through 2013, using influenza and RSV laboratory surveillance data as covariates. We fitted separate models for in- and out-of-hospital deaths. Results There were 509791 average annual deaths in South Africa, of which 44% (95% confidence interval [CI] 43%–45%) occurred out-of-hospital. Seasonal influenza and RSV all-cause mortality rates were 23.0 (95% CI 11.0–30.6) and 13.2 (95% CI 6.4–33.8) per 100000 population annually (2.3% [95%CI 2.3%–2.4%] and 1.3% [95% CI 1.2%–1.4%] of all deaths respectively). The peak mortality rate was in individuals aged ≥75 years (386.0; 95% CI 176.5–466.3) for influenza and in infants (143.4; 95% CI 0–194.8) for RSV. Overall, 63% (95% CI 62%–-65%) of seasonal influenza and 48% (95% CI 47%–49%) of RSV-associated deaths occurred out-of-hospital. Among children aged

European region influenza surveillance Network author lisT - Portugal: Raquel Guiomar, Pedro Pechirra, Paula Cristóvão, Inês Costa, Patricia Conde (National Influenza and Other Respiratory Virus Reference Laboratory, Infectious Diseases Department, National Institute of Health Dr. Ricardo Jorge, Lisbon) and Ana Paula Rodrigues (Department of Epidemiology, National Instituteof Health Dr. Ricardo Jorge, Lisbon) Erratum in: Erratum to "Predominance of influenza A(H3N2) virus genetic subclade 3C.2a1 during an early 2016/17 influenza season in Europe - Contribution of surveillance data from World Health Organization (WHO) European region to the WHO vaccine composition consultation for northern hemisphere 2017/18" [Vaccine 35 (2017) 4828-4835]. [Vaccine. 2018 May 3;36(19):2740-2741. doi: 10.1016/j.vaccine.2017.12.039. Epub 2017 Dec 20]. Disponível em: https://doi.org/10.1016/j.vaccine.2017.12.039 During the European 2016/17 influenza season, A(H3N2) viruses have predominated and the majority clustered in genetic subclade 3C.2a1. Genetic analyses showed that circulating viruses have undergone considerable genetic diversification of the haemagglutinin gene from the current vaccine virus A/Hong Kong/4801/2014 (clade 3C.2a), but the antigenic data that is limited by the challenges with the antigenic characterisation of currently circulating A(H3N2) viruses, showed no clear evidence of antigenic change. The recommended A(H3N2) vaccine component for the northern hemisphere 2017/18 influenza season remained unchanged. However, early and mid-season vaccine effectiveness (VE) estimates were suggestive of reduced VE against A(H3N2) viruses. info:eu-repo/semantics/publishedVersion

The A(H1N1)pdm09 influenza virus reached pandemic level in Spain in 2009, prompting a national vaccination campaign. To avoid transmission to patients, healthcare professionals' vaccination against pandemic influenza is crucial. The main objective of this study was to analyze factors associated with the failure by healthcare professionals to accept the pandemic vaccination in 2009. A cross-sectional survey was conducted of healthcare professionals in seven of Spain's autonomous regions. A questionnaire was used to collect information about personal and professional details, the respondents' flu vaccination status in the 2008-2009 and 2009-2010 seasons (seasonal and pandemic vaccines), and their knowledge and attitudes. A total of 1,661 professionals completed the survey. In the 2009-2010 season, 38.2% had both the seasonal and the pandemic vaccine, 22.1% had had only the seasonal, and 4.7% only the pandemic vaccine. The strongest predictor of not receiving the pandemic vaccine was not having had seasonal vaccinations in that year or the previous year. Those who had not received the pandemic vaccine were more often female; nurses; under 45; denied contact with at-risk groups; and had negative beliefs about the vaccine effectiveness and little concern for getting the disease, being infected at work, or passing it on to patients. It would be prudent to direct preventive campaigns not only at individuals at risk of catching flu but also at health professionals with a negative view of flu vaccine, with a particular focus on nurses, who have a key role in recommending flu vaccine.

Highly pathogenic avian influenza A(H5N8) clade 2.3.4.4 virus emerged in 2016 and spread to Russia, Europe, and Africa. Our analysis of viruses from domestic ducks at Tanguar haor, Bangladesh, showed genetic similarities with other viruses from wild birds in central Asia, suggesting their potential role in the genesis of A(H5N8).

Highlights • A(H3N2) dominated the early stages of the 2016–2017 influenza season. • 36% of hospitalized infected patients received the influenza vaccine. • Circulating A(H3N2) viruses were different from the vaccine strain., Background Influenza vaccine composition is reevaluated each year due to the frequency and accumulation of genetic changes that influenza viruses undergo. The beginning of the 2016–2017 influenza surveillance period in Israel has been marked by the dominance of influenza A(H3N2). Objectives To evaluate the type, subtype, genetic evolution and amino acid substitutions of influenza A(H3N2) viruses detected among community patients with influenza-like illness (ILI) and hospitalized patients with respiratory illness in the first weeks of the 2016–2017 influenza season. Study design Respiratory samples from community patients with influenza-like illness and from hospitalized patients underwent identification, subtyping and molecular characterization. Hemagglutinin sequences were compared to the vaccine strain, phylogenetic tree was created, and amino acid substitutions were determined. Results Influenza A(H3N2) predominated during the early stages of the 2016–2017 influenza season. Noticeably, approximately 20% of community patients and 36% of hospitalized patients, positive for influenza3), received the 2016–2017 influenza vaccine. The influenza A(H3N2) viruses demonstrated genetic divergence from the vaccine strain into three separate subgroups within the 3C.2a clade. One resembled the new 3C.2a1 subclade, one resembled the recently proposed 3C.2a2 subclade and the other was not previously described. Diversity was observed within each subgroup, in terms of additional amino acid substitutions. Conclusions Characterization of the 2016–2017 A(H3N2) influenza viruses is imperative for determining the future influenza vaccine composition.

There is no global monitoring system for influenza vaccination coverage, making it difficult to assess progress towards the 2003 World Health Assembly (WHA) vaccination coverage target. In 2008, the IFPMA Influenza Vaccine Supply International Task Force (IVS) developed a survey method to assess the global distribution of influenza vaccine doses as a proxy for vaccination coverage rates. The latest dose distribution data for 2014 and 2015 was used to update previous analyses. Data were confidentially collected and aggregated by the IFPMA Secretariat, and combined with previous IFPMA IVS survey data (2004-2013). Data were available from 201 countries over the 2004-2015 period. A "hurdle" rate was defined as the number of doses required to reach 15.9% of the population in 2008. Overall, the number of distributed doses progressively increased between 2004 and 2011, driven by a 150% increase in AMRO, then plateaued. One percent fewer doses were distributed in 2015 than in 2011. Twenty-three countries were above the hurdle rate in 2015, compared to 15 in 2004, but distribution was highly uneven in and across all WHO regions. Three WHO regions (AMRO, EURO and WPRO) accounted for about 95% of doses distributed. But in EURO and WPRO, distribution rates in 2015 were only marginally higher than in 2004, and in EURO there was an overall downward trend in dose distribution. The vast majority of countries cannot meet the 2003WHA coverage targets and are inadequately prepared for a global influenza pandemic. With only 5% of influenza vaccine doses being distributed to 50% of the world's population, there is urgency to redress the gross inequities in disease prevention and in pandemic preparedness. The 2003WHA resolution must be reviewed and revised and a call issued for the renewed commitment of Member States to influenza vaccination coverage targets.

Summary Influenza virus is responsible for 18.2%–33.3% of community-dwelling older adult influenza-like illness (ILI) cases in 2 consecutive seasons. Although vaccination protects against influenza virus infection, it had no effect on the overall number of ILI cases in older adults., Background Data on the relative contribution of influenza virus and other respiratory pathogens to respiratory infections in community-dwelling older adults (≥60 years) are needed. Methods A prospective observational cohort study was performed in the Netherlands during 2 winters. Nasopharyngeal and oropharyngeal swabs were collected during influenza-like illness (ILI) episodes and from controls. Viruses and bacteria were identified by multiplex ligation–dependent probe amplification assay and conventional bacterial culture. Results The ILI incidence in the consecutive seasons was 7.2% and 11.6%, and influenza virus caused 18.9% and 34.2% of ILI episodes. Potential pathogen were detected in 80% of the ILI events with influenza virus, coronaviruses, rhinoviruses, human metapneumovirus, respiratory syncytial virus, parainfluenza viruses, and Haemophilus influenzae being the most common. Influenza vaccination reduced influenza virus infection by 73% (95% confidence interval [CI], 26%–90%) and 51% (95% CI, 7%–74%) in ILI patients. However, ILI incidence was similar between vaccinated (7.6% and 10.8%) and nonvaccinated (4.2% and 11.4%) participants in 2011–2012 and 2012–2013, respectively (P > .05). Conclusions Influenza virus is a frequent pathogen in older adults with ILI. Vaccination reduces the number of influenza virus infections but not the overall number of ILI episodes: other pathogens fill the gap. We suggest the existence of a pool of individuals with high susceptibility to respiratory infections. Clinical Trials Registration NTR3386.

Seasonal influenza epidemics and periodic pandemics are important causes of morbidity and mortality. Patients with chronic co-morbid illness, those at the extremes of age and pregnant women are at higher risks of complications requiring hospitalization, whereas young adults and obese individuals were also at increased risk during the A(H1N1) pandemic in 2009. Avian influenza A(H5N1) and A(H7N9) viruses have continued to circulate widely in some poultry populations and infect humans sporadically since 1997 and 2013, respectively. The recent upsurge in human cases of A(H7N9) infections in Mainland China is of great concern. Sporadic human cases of avian A(H5N6), A(H10N8) and A(H6N1) have also emerged in recent years while there are also widespread poultry outbreaks due to A(H5N8) in many countries. Observational studies have shown that treatment with a neuraminidase inhibitor (NAI) for adults hospitalized with severe influenza is associated with lower mortality and better clinical outcomes, especially when administered early in the course of illness. Whether higher than standard doses of NAI would provide greater antiviral effects in such patients will require further investigation. High-dose systemic corticosteroids were associated with worse outcomes in patients with severe influenza. There is an urgent need for developing more effective antiviral therapies for treatment of influenza infections.

The contribution of influenza B to the seasonal influenza burden varies from year-to-year. Although 2 antigenically distinct influenza B virus lineages have co-circulated since 2001, trivalent influenza vaccines (TIVs) contain antigens from only one influenza B virus. B-mismatch or co-circulation of both B lineages results in increased morbidity and mortality attributable to the B lineage absent from the vaccine. Quadrivalent vaccines (QIVs) contain both influenza B lineages. We reviewed currently licensed QIVs and their value by focusing on the preventable disease burden. Modeling studies support that QIVs are expected to prevent more influenza cases, hospitalisations and deaths than TIVs, although estimates of the case numbers prevented vary according to local specificities. The value of QIVs is demonstrated by their capacity to broaden the immune response and reduce the likelihood of a B-mismatched season. Some health authorities have preferentially recommended QIVs over TIVs in their influenza prevention programmes.

Background Since 2014, 17 human cases of infection with the newly emerged highly pathogenic avian influenza A(H5N6) virus have been identified in China to date. The epidemiologic characteristics of laboratory-confirmed A(H5N6) cases were compared to A(H5N1) and A(H7N9) cases in mainland China. Methods Data on laboratory-confirmed H5N6, H5N1, and H7N9 cases identified in mainland China were analyzed to compare epidemiologic characteristics and clinical severity. Severity of confirmed H5N6, H5N1 and H7N9 cases was estimated based on the risk of severe outcomes in hospitalized cases. Results H5N6 cases were older than H5N1 cases with a higher prevalence of underlying medical conditions but younger than H7N9 cases. Epidemiological time-to-event distributions were similar among cases infected with the 3 viruses. In comparison to a fatality risk of 70% (30/43) for hospitalized H5N1 cases and 41% (319/782) for hospitalized H7N9 cases, 12 (75%) out of the 16 hospitalized H5N6 cases were fatal, and 15 (94%) required mechanical ventilation. Conclusion Similar epidemiologic characteristics and high severity were observed in cases of H5N6 and H5N1 virus infection, whereas severity of H7N9 virus infections appeared lower. Continued surveillance of human infections with avian influenza A viruses remains an essential component of pandemic influenza preparedness.

Background Guillain-Barre syndrome (GBS) is a serious acute demyelinating disease that causes weakness and paralysis. The Food and Drug Administration (FDA) began collaborating with the Centers for Medicare and Medicaid Services (CMS) to develop near real-time vaccine safety surveillance capabilities in 2006 and has been monitoring for the risk of GBS after influenza vaccination for every influenza season since 2008. Methods We present results from the 2010/11 to 2013/14 influenza seasons using the Updating Sequential Probability Ratio Test (USPRT), with an overall 1-sided α of 0.05 apportioned equally using a constant alpha-spending plan among 20 consecutive weekly tests, 5 ad hoc tests, and a 26th final end of season test. Observed signals were investigated using the self-controlled risk interval (SCRI) design. Results Over 15 million people were vaccinated in each influenza season. In the 2010/11 influenza season, we observed an elevated GBS risk during the season, with an end of season SCRI analysis finding a nonsignificant increased risk (RR = 1.25, 95% CI: 0.96–1.63). A sensitivity analysis applying the positive predictive value of the ICD-9 code for GBS from the 2009/10 season estimated a RR = 1.98 (95% CI: 1.42–2.76). Although the 2010/11 influenza vaccine suggested an increased GBS risk, surveillance of the identical vaccine in the 2011/12 influenza season did not find an increased GBS risk after vaccination. No signal was observed in the subsequent three influenza seasons. Conclusions Conducting near real-time surveillance using USPRT has proven to be an excellent method for near real-time GBS surveillance after influenza vaccination, as demonstrated by our surveillance efforts during the 2010/11–2013/14 influenza seasons. In the 2010/2011 influenza season, in addition to the 2009 H1N1 influenza pandemic, using near real-time surveillance we were able to observe a signal early in the influenza season and the method has now become routine.

Background There are few longitudinal studies of seasonal influenza-associated neurological disease (IAND) and none from the Southern Hemisphere. Methods We extracted prospectively acquired Australian surveillance data from 2 studies nested within the Paediatric Active Enhanced Disease Surveillance (PAEDS) network: the Influenza Complications Alert Network (FluCAN) study and the Australian Childhood Encephalitis (ACE) study between 2013 and 2015. We described the clinical features and severity of IAND in children, including influenza-associated encephalitis/encephalopathy (IAE). We calculated the proportion of hospitalized influenza that is associated with IAND and IAE, and incidence of IAE. Results Over 3 influenza seasons, we identified 54 cases of IAND at 2 tertiary children's hospitals from Australia that accounted for 7.6% of hospitalized influenza. These included 10 cases of IAE (1.4% hospitalized influenza). The mean annual incidence of IAE among Australian children (aged ≤14 years) was 2.8 per 1000000. The spectrum of IAND was broad and included IAE (n = 10) including distinct acute encephalopathy syndromes, simple febrile seizures (n = 14), other seizures (n = 16), acute ataxia (n = 4), and other subacute syndromes (transverse myelitis [n = 1], opsoclonus myoclonus [n = 1]). Two-thirds of children with IAND were aged ≤4 years; less than half had preexisting neurological disease or other risk factors for severe influenza. IAE caused death or neurological morbidity in half of cases. Conclusions Seasonal influenza is an important cause of acute neurological disease in Australian children. The spectrum of seasonal IAND appears similar to that described during the 2009 H1N1 pandemic. IAE is associated with high morbidity and mortality.

The avian influenza A (H7N9) virus is one subtype of influenza viruses, which has previously been isolated only in birds. Recently, an outbreak of a new avian influenza (H7N9) in China has resulted in numerous infections and high mortality in the humans. The H7N9 virus is low pathogenic in poultry and high pathogenic in human and that is critically different from other avian influenza viruses. An increasing number of the new H7N9 cases and the high mortality have caused a serious global concern. Here, based on the reported data, we propose and analyze an SE-SEIS avian–human influenza model. We prove the global stability results for both the disease-free equilibrium point and the endemic equilibrium point by using a general Bendixson–Dulac theorem. Our reported theoretical results of this paper are expected to help in exploring the development of efficient methods to controlling the spread of avian influenza A(H7N9).

Background/Purpose We conducted a case series study to review the epidemiology of human influenza A(H7N9) infection reported in Hong Kong. Methods We reviewed case records of confirmed human cases of influenza A(H7N9) infection reported in Hong Kong in the 2013–2014 winter season. We compared the median viral shedding duration and interval from illness onset to initiation of oseltamivir treatment between severe and mild cases. We estimated the incubation period of influenza A(H7N9) virus from cases with a single known date of poultry exposure. Results A total of 10 cases were reported and all were imported infection from Mainland China. Four patients died and the cause of death was related to influenza A(H7N9) infection in two patients. The median interval from illness onset to initiation of oseltamivir treatment for the severe cases (4.5 days) was significantly longer than the mild cases (2 days; p = 0.025). Severe cases had a significantly longer viral shedding duration than mild cases ( p = 0.028). The median incubation period for cases with a single known exposure date was 4 days. Nasopharyngeal aspirate taken from the 88 close contacts of the 10 patients all tested negative for influenza A virus using reverse transcription polymerase chain reaction. Conclusion Delayed administration of antiviral treatment may be associated with a more severe illness for influenza A(H7N9) infection. Despite our aggressive contact tracing policy with laboratory testing of all close contacts, no secondary case was identified which implied that the potential of human-to-human transmission of the circulating influenza A(H7N9) virus remains low.

Introduction Epidemiological studies of the 1957 influenza pandemic are scarce, particularly from lower-income settings. Methods We analyzed the spatial-temporal mortality patterns of the 1957 influenza pandemic in Chile, including detailed age-specific mortality data from a large city, and investigated risk factors for severe mortality impact across regions. Results Chile exhibited two waves of excess mortality in winter 1957 and 1959 with a cumulative excess mortality rate of 12 per 10 000, and a ~10-fold mortality difference across provinces. High excess mortality rates were associated with high baseline mortality (R2 =41.8%; P=.02), but not with latitude (P>.7). Excess mortality rates increased sharply with age. Transmissibility declined from R=1.4-2.1 to R=1.2-1.4 between the two pandemic waves. Conclusions The estimated A/H2N2 mortality burden in Chile is the highest on record for this pandemic-about three to five times as severe as that experienced in wealthier nations. The global impact of this pandemic may be substantially underestimated from previous studies based on high-income countries.

Analysis of changes in the population immunity level in adults for more than 20 Russian cities, collaborating with the Federal Center for Influenza, to circulating influenza viruses A(H1N1)pdm09, A(H3N2) and B in the period from 2009 to 2015 performed. By the beginning of the pandemic (October 2009) the population of Russia was almost seronegative to influenza A(H1N1)pdm09 virus. After the pandemia first wave mean geometric titers (GMT)s of antibodies to the pandemic virus increased by 2.6 times, after the second one by 4.9 times in comparison with initial GMT (1:5.5). A consistent increase in GMTs antibody after each of the subsequent seasons of active circulation of pandemic virus was observed reaching the maximum (1:41) by April 2013, after the next epidemic caused by this virus. The proportion of people with protective antibody titers in October 2009 to already started circulating influenza A(H1N1)pdm09 virus was 8.2%, to influenza A(H3N2) virus — 58.3%, and influenza B virus — 59.7%. Level of population immunity in adults to seasonal influenza A(H3N2) and B viruses throughout the observed period was significantly higher than to influenza virus A(H1N1)pdm09. The percentage of persons with protective antibody titers during the observed period varied for virus A(H3N2) in the range from 58.3 to 75.5%, for influenza B virus — from 59.7 to 82.3%. Accordingly, incidence rate for ILI and ARI in adult groups the population during influenza epidemic caused by these pathogens was lower than in the epidemics, associated with active circulation of influenza A(H1N1)pdm09 virus. The data obtained can be used in influenza forecasting for the upcoming season regarding the etiology and the expected epidemic intensity need for the relevant preventing measures development to decrease the burden from influenza.

The intermittent outbreak of pandemic influenza and emergence of novel avian influenza A virus is worldwide threat. Although most patients present with mild symptoms, some deteriorate to severe pneumonia and even death. Great progress in the understanding of the mechanism of disease pathogenesis and a series of vaccines has been promoted worldwide; however, incidence, morbidity, and mortality remains high. To step up vigilance and improve pandemic preparedness, this article elucidates the virology, epidemiology, pathogenesis, clinical characteristics, and treatment of human infections by influenza A viruses, with an emphasis on the influenza A(H1N1)pdm09, H5N1, and H7N9 subtypes.

Background Influenza A and B viruses co-infections are rare events and mainly occurred in immunocompromised patients. Objectives In this study we report an unusually high occurrence of influenza A (H1N1)pdm 2009 and influenza B virus co-infections during the epidemic year 2015–2016. Study design Nasopharyngeal swabs were collected from 1919 patients visiting 26 outpatient clinics distributed throughout Israel and presenting with influenza-like illness. In addition, hospitalized patient tested for influenza viruses were also included in the study. Patients samples collected between October 2015 and April 2016 were tested for the presence of influenza viruses by real-time PCR. Results Of the 1919 patient samples tested, 11 (0.6%) were co-infected with both influenza A(H1N1)pdm 2009 and influenza B/Victoria viruses. Similar observation was noted in four hospitalized patients during the same period. Patients at ages 1–72 years, and their clinical symptoms were similar to that of patients infected with either influenza A or B viruses. Of all patients, only one hospitalized patient was immunocompromised. In conclusion : Co-infection of influenza A(H1N1)pdm 2009 and influenza B viruses is an increasingly recognized phenomenon. This co-infection can occur not only in immunocompromised individuals, but also in immunocompetent patients. Although co-infection appears to be a rare event, it may still play a role in the epidemiology, pathogenicity and evolution of influenza viruses.

// Nehemya Friedman 1, 2, * , Yaron Drori 1, 2, * , Rakefet Pando 3 , Aharona Glatman-Freedman 3, 4 , Hanna Sefty 3 , Ravit Bassal 3 , Yaniv Stein 3 , Tamy Shohat 2, 3 , Ella Mendelson 1, 2 , Musa Hindiyeh 1, 2 , Michal Mandelboim 1, 2 1 Central Virology Laboratory, Ministry of Health, Chaim Sheba Medical Center, Ramat-Gan, Israel 2 Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel 3 The Israel Center for Disease Control, Israel Ministry of Health, Tel-Hashomer, Israel 4 Departments of Pediatrics and Family and Community Medicine, Valhalla, New York, USA * These authors contributed equally to this work Correspondence to: Michal Mandelboim, email: michalman@sheba.health.gov.il Keywords: influenza A, H1N1, vaccine, Clade 6B Received: November 22, 2016 Accepted: March 14, 2017 Published: March 22, 2017 ABSTRACT The last influenza pandemic, caused by the swine A(H1N1)pdm09 influenza virus, began in North America at 2009. Since then, the World Health Organization (WHO) recommended integration of the swine-based virus A/California/07/2009 strain in yearly vaccinations. Yet, infections with A(H1N1)pdm09 have continued in subsequent years. The reasons for this are currently unknown. During the 2015–2016 influenza season, we noted an increased prevalence of A(H1N1)pdm09 influenza virus infection in Israel. Our phylogenetic analysis indicated that the circulating A(H1N1)pdm09 strains belonged to 6B.1 and 6B.2 clades and differed from the vaccinating strain, with approximately 18 amino acid differences found between the circulating strains and the immunizing A/California/07/2009 strain. Hemmaglutination inhibition (HI) assays demonstrated higher antibodies titer against the A/California/07/2009 vaccinating strain as compared to the circulating Israeli strains. We thus suggest that the current vaccination was not sufficiently effective and propose inclusion of the current circulating A(H1N1)pdm09 influenza viruses in the annual vaccine composition.

Humans and swine are both affected by influenza viruses, and swine are considered a potential source of new influenza viruses. Transmission of influenza viruses across species is well documented. The aim of this study was to evaluate the seroprevalence of different influenza virus subtypes in veterinarians working for the Mexican swine industry, using a hemagglutination inhibition test. All sera tested were collected in July 2011. The data were analysed using a generalized linear model and a linear model to study the possible association of seroprevalence with the age of the veterinarian, vaccination status, and biosecurity level of the farm where they work. The observed seroprevalence was 12.3%, 76.5%, 46.9%, and 11.1% for the human subtypes of pandemic influenza virus (pH1N1), seasonal human influenza virus (hH1N1), the swine subtypes of classical swine influenza virus (swH1N1), and triple-reassortant swine influenza virus (swH3N2), respectively. Statistical analysis indicated that age was associated with hH1N1 seroprevalence (P < 0.05). Similarly, age and vaccination were associated with pH1N1 seroprevalence (P < 0.05). On the other hand, none of the studied factors were associated with swH1N1 and swH3N2 seroprevalence. All of the pH1N1-positive sera were from vaccinated veterinarians, whereas all of those not vaccinated tested negative for this subtype. Our findings suggest that, between the onset of the 2009 pandemic and July 2011, the Mexican veterinarians working in the swine industry did not have immunity to the pH1N1 virus; hence, they would have been at risk for infection with this virus if this subtype had been circulating in swine in Mexico prior to 2011.

In the 2015/16 influenza season, the Canadian National Advisory Committee on Immunization (NACI) recommended vaccination with quadrivalent inactivated influenza vaccine (QIV) for infants aged 6–23 months and trivalent inactivated influenza vaccines (TIVs) or QIVs in adults. The objective of this review (GSK study identifier: HO-13-14054) is to examine the epidemiology and disease burden of influenza in Canada and the economic benefits of vaccination. To inform this review, we performed a systematic literature search of relevant Canadian literature and National surveillance data. Influenza B viruses from phylogenetically-distinct lineages (B/Yamagata and B/Victoria) co-circulate in Canada, and are an important cause of influenza complications. Modeling studies, including those postdating the search suggest that switching from TIV to QIV in Canada reduces the burden of influenza and would likely be cost-effective. However, more robust real-world outcomes data is required to inform health policy decision makers on appropriate influenza vaccination strategies for Canada.

In July 2009, the World Health Organization declared the first flu pandemic in nearly 40 years. Although the health effects of the pandemic have been studied, there is little research examining the labor productivity consequences. Using unique sick leave data from the Chilean private health insurance system, we estimate the effect of the pandemic on missed days of work. We estimate that the pandemic increased mean flu days missed by 0.042 days per person-month during the 2009 peak winter months (June and July), representing an 800% increase in missed days relative to the sample mean. Calculations using the estimated effect imply a minimum 0.2% reduction in Chile's labor supply. Copyright © 2017 John Wiley & Sons, Ltd.

Analysis of archival correspondence, the daily logs of troopships transporting soldiers to Europe and the Commonwealth War Graves Commission database for soldier deaths from pneumonia and influenza...

Influenza is one of the most common respiratory diseases in the world, annually causing over one million of deaths. It is triggered by one of the types of influenza viruses (A, B or C). Most usually, it assumes the form of epidemic disease, sometimes it is a pandemic, and is very rare as a sporadic disease. In temperate zones, the influenza occurs seasonally - during the cold months of a year. In tropics, however, it occurs throughout the year, though the highest number of patients is registered during the rainy seasons. Influenza is a mild disease for young and healthy persons; however, if affecting those with a weakened immune system, it can lead to complications and even to death. The only effective preventive measure is vaccination, which precludes the disease. So far, no consensus is reached on whether the vaccination should be compulsory or recommended and who should be vaccinated. In most European countries, vaccination is recommended for certain categories of the population, while the United States recommend it to the entire population above six months of age.

The beginning of 2016 was marked by an epidemic circulation of influenza viruses and a rise in the incidence of influenza and acute respiratory viral infections from the 2nd till the 16th week of the year. The epidemic peaked in week 4-5 (25-31.01.2016 and 01.02-07.02.2016) when the epidemic thresholds were exceeded in 74 and 68 subjects, respectively, in all federal districts of the Russian Federation, and all age groups were involved into the epidemic process. Among the circulating viruses, influenza A(H1N1)pdm09 was predominating (82,0–85,0%), and by the end of the epidemic the number of patients with influenza virus type B increased. Seasonal influenza vaccination has proved to be effective. Based on the characteristics of the isolated influenza viruses, the composition of influenza vaccines for 2016-2017 was changed as recommended by the WHO.

AIM To study the impact of vaccination critical illness due to H1N1pdm09, we compared the incidence and severity of H1N1pdm09 infection in Canada and France. METHODS We studied two national cohorts that included children with documented H1N1pdm09 infection, admitted to a pediatric intensive care unit (PICU) in Canada and in France between October 1, 2009 and January 31, 2010. RESULTS Vaccination coverage prior to admission to PICUs was higher in Canada than in France (21% vs 2% of children respectively, P < 0.001), and in both countries, vaccination coverage prior to admission of these critically ill patients was substantially lower than in the general pediatric population (P < 0.001). In Canada, 160 children (incidence = 2.6/100000 children) were hospitalized in PICU compared to 125 children (incidence = 1.1/100000) in France (P < 0.001). Mortality rates were similar in Canada and France (4.4% vs 6.5%, P = 0.45, respectively), median invasive mechanical ventilation duration and mean PICU length of stay were shorter in Canada (4 d vs 6 d, P = 0.02 and 5.7 d vs 8.2 d, P = 0.03, respectively). H1N1pdm09 vaccination prior to PICU admission was associated with a decreased risk of requiring invasive mechanical ventilation (OR = 0.30, 95%CI: 0.11-0.83, P = 0.02). CONCLUSION The critical illness due to H1N1pdm09 had a higher incidence in Canada than in France. Critically ill children were less likely to have received vaccination prior to hospitalization in comparison to general population and children vaccinated had lower risk of ventilation.

In Poland, around several thousand to several million cases of influenza and suspected influenza are registered. Despite the recommendations, the rate of vaccination against influenza is still very low in all age groups. In the epidemic season 2015/2016, the level of distribution of the seasonal influenza vaccines was 3.4% of the population. The influenza vaccines available in Poland, are inactivated vaccines, which contain fragments of the killed virus – of the split and subunit type – that are unable to multiply in the body and to cause a disease. This paper presents the current recommendations (2016–2017) on immunization and vaccines against seasonal influenza, based on the recommendations of the Advisory Committee on Immunization Practices and the American Academy of Pediatrics. The annual influenza vaccination is the primary means of preventing influenza and its complications.

Vaccine is essentially the only measure by which there is a real opportunity to eliminate an infectious disease. And the flu is no exception. The high variability of influenza virus A/H1N1, which causes a pandemic, and most epidemics, is the problem of creating effective etiotropic treatments and vaccines. The emergence of new vaccine manufacturing technologies, such as genetic engineering, DNA technology, allows for a fresh look at the problem of influenza eradication on the planet. Universal year-round mass vaccination against influenza, not just high-risk groups, should be included in all national vaccination program, but this strategy will help stop influenza infection.

Indonesia has reported highest number of fatal human cases of highly pathogenic avian influenza (HPAI) A (H5N1) virus infection worldwide since 2005. There are limited data available on seasonal and pandemic influenza in Indonesia. During 2012, we conducted a survey of clinicians in two districts in western Java, Indonesia, to assess knowledge, attitudes, and practices (KAP) of clinical diagnosis, testing, and treatment of patients with seasonal influenza, pandemic influenza, or HPAI H5N1 virus infections. Overall, a very low percentage of physician participants reported ever diagnosing hospitalized patients with seasonal, pandemic, or HPAI H5N1 influenza. Use of influenza testing was low in outpatients and hospitalized patients, and use of antiviral treatment was very low for clinically diagnosed influenza patients. Further research is needed to explore health system barriers for influenza diagnostic testing and availability of antivirals for treatment of influenza in Indonesia.

The World Health Organization (WHO) searches influenza virus circulation in community and in natural biocenosis, studies virus strains and their properties, develops diagnostic methods and preventive measures since 1940 th worldwide because of epidemic actuality and high pandemic potential of the influenza virus. The Federal Influenza Center (including Federal Research Institute of Influenza, Saint-Petersburg, and the Center of Virus Ecology, D.I.Ivanovskiy Virology Institute, Honorary Academician N.F.Gamaleya Federal Research Center of Epidemiology and Microbiology, Federal Research Center for Epidemiology and Microbiology, Moscow) performs similar work in Russia in close cooperation with WHO within the framework of the International Programme of Influenza Monitoring. A(H1N1)pdm09 influenza virus dominated in the Northern Hemisphere in the 2015 – 2016 epidemic season. Morbidity growth was noted from the end of January, 2016, to the beginning of March, 2016. The peak morbidity at the 5th week of the year exceeded the epidemic threshold (132 cases per 10,000 of population) and morbidity in the 2014 – 2015 season significantly and approached to the peak morbidity of the 2009 – 2010 epidemic season. The epidemic growth in Russian Federation was provided by three influenza viruses: A(H1N1)pdm09, В and A (H3N2). A(H1N1)pdm09 virus caused 18% of all acute respiratory diseases and accounted for 84% of circulating influenza viruses. Flu was diagnosed in patients of different age with maximal frequency in 3- to 6-year old children. Peak admission number was registered at 5 and 6 weeks (3,538 and 4,109 cases, respectively); this number exceeded the similar parameter of the 2009 – 2010 season. Patients of 15 to 64 years old were admitted more often including those with acute respiratory infection. Two hundred and thirty nine deaths were registered to the 5 th of April, 2016, according to data from the Federal Influenza Center and the Center of Virus Ecology. The diagnosis of A(H1N1)pdm09 flu was confirmed in 97.9% of deaths. Molecular analysis of isolated strains of A(H1N1)pdm09 influenza virus revealed amino acid substitutions in receptor binding site and SA site of hemagglutinin and in genes coding intrinsic proteins PA, NP, M1, and NS1. Influenza virus strains resistive to anti-neuraminidase drugs were encountered in #< 1% in the Northern Hemisphere countries. No strains studied were sensitive to adamantine derivates.

Background Influenza B is characterised by two antigenic lineages; B/Victoria and B/Yamagata. These lineages circulate together with influenza A during influenza seasons, with varying incidence from year to year and by geographic region. Objective To determine the epidemiology of influenza B relative to influenza A in Australia. Methods Laboratory-confirmed influenza notifications between 2001 and 2014 in Australia were obtained from the Australian National Notifiable Diseases Surveillance System. Results A total of 278,485 laboratory-confirmed influenza cases were notified during the study period; comprising influenza A (82.2%), B (17.1%), and ‘other and untyped’ (0.7%). The proportion of notifications that were influenza B was highest in 5-9 year-olds (27.5%) and lowest in persons aged 85 years and over (11.5%). Of all B notifications with lineage determined, 77.1% were B/Victoria and 22.9% were B/Yamagata infections. Mismatches between the dominant B lineage in a season and the trivalent vaccine B lineage occurred in over one-third of seasons during the study years. In general, influenza B notifications peaked later than influenza A notifications. Conclusion The proportion of circulating influenza B in Australia during 2001 to 2014 was slightly lower than the global average and was dominated by B Victoria. Compared with influenza A, influenza B infection was more common among older children and young adults and less common in the very elderly. Influenza B lineage mismatch with the trivalent vaccine occurred about one third of the time. This article is protected by copyright. All rights reserved.

Highlights • LAIV has been used in Russia for decades. • Russian LAIV consistently provides superior effective protection against influenza. • It was incorporated into the WHO global pandemic influenza action plan. • A number of Russian LAIVs against pandemic influenza viruses have been prepared. • Russian LAIV technology was transferred to a number of developing countries., Influenza is a viral infection that affects much of the global population each year. Vaccination remains the most effective tool for preventing the disease. Live attenuated influenza vaccine (LAIV) has been used since the 1950s to protect humans against seasonal influenza. LAIVs developed by the Institute of Experimental Medicine (IEM), Saint Petersburg, Russia, have been successfully used in Russia since 1987. In 2006, the World Health Organization (WHO) announced a Global action plan for influenza vaccines (GAP). WHO, recognizing potential advantages of LAIV over the inactivated influenza vaccine in a pandemic situation, included LAIV in the GAP. BioDiem Ltd., a vaccine development company based in Melbourne, Australia which held the rights for the Russian LAIV, licensed this technology to WHO in 2009. WHO was permitted to grant sub-licenses to vaccine manufacturers in newly industrialized and developing countries to use the Russian LAIV for the development, manufacture, use and sale of pandemic and seasonal LAIVs. To date, WHO has granted sub-licenses to vaccine manufacturers in China (Changchun BCHT Biotechnology Co., Ltd.), India (Serum Institute of India Pvt. Ltd.) and Thailand (Government Pharmaceutical Organization). In parallel, in 2009, IEM signed an agreement with WHO, under which IEM committed to supply pandemic and seasonal candidate vaccine viruses to the sub-licensees. This paper describes the progress made by collaborators from China, India, Russia and Thailand in developing preventive measures, including LAIV against pandemic influenza.

Background: During the pandemic outbreak of the 2009 swine influenza (A(H1N1) pdm09), 32 fatal cases occurred in Norway and 19 of these were included in this study. Objectives: We characterised pulmonary changes in these fatal Norwegian cases. Patients and Methods: Upon hospitalisation, detailed clinical information and specimens from the upper and lower respiratory pathways were collected. At post-mortem, lung tissue was collected, formalin-fixed and paraffin-embedded. Immunohistochemical and light microscopic examination was performed to visualise the local expression of the A(H1N1) pdm09 virus. Reverse transcription-polymerase chain reaction (RT-PCR) and pyrosequencing of the non-fixed specimens allowed the identification of mutations in the influenza virus surface glycoprotein (haemagglutinin gene) particularly at position 222. Results and Conclusions: The overall course of illness lasted from 2 to 40 days (median 9 days). Diffused alveolar damage (DAD) was evident in 11 cases, 4 of which had no apparent underlying illness. Obesity was prominent in 12 cases, where three individuals were classified as otherwise healthy. The HA D222G mutation was detected in six cases, 3 of which had no underlying illness. Immunohistochemistry showed the A(H1N1)pdm09 virus to be prominent at the site of inflammation both in close proximity to and inside alveolar structures in the lung tissue. In addition to a possible role for the HA D222G mutation, our findings indicate that host factors and underlying conditions in the infected individuals are fundamental for disease outcome in many cases. This study increases our understanding of determinants for the clinical outcome of pandemic influenza, which could guide future treatment. publishedVersion

Although efficient human-to-human transmission of avian influenza virus has yet to be seen, in the past two decades avian-to-human transmission of influenza A viruses has been reported. Influenza A/H5N1, in particular, has repeatedly caused human infections associated with high mortality, and since 1998 the virus has evolved into many clades of variants with significant antigenic diversity. In 2013, three (A/H7N9, A/H6N1, and A/H10N8) novel avian influenza viruses (AIVs) breached the animal-human host species barrier in Asia. In humans, roughly 35% of A/H7N9-infected patients succumbed to the zoonotic infection, and two of three A/H10N8 human infections were also lethal; however, neither of these viruses cause influenza-like symptoms in poultry. While most of these cases were associated with direct contact with infected poultry, some involved sustained human-to-human transmission. Thus, these events elicited concern regarding potential AIV pandemics. This article reviews the human incursions associated with AIV variants and the potential role of pigs as an intermediate host that may hasten AIV evolution. In addition, we discuss the known influenza A virus virulence and transmission factors and their evaluation in animal models. With the growing number of human AIV infections, constant vigilance for the emergence of novel viruses is of utmost importance. In addition, careful characterization and pathobiological assessment of these novel variants will help to identify strains of particular concern for future pandemics.

Influenza is a contagious respiratory illness that causes significant human morbidity and mortality, affecting 5-15% of the population in a typical epidemic season. Human influenza epidemics are caused by types A and B, with roughly 25% of human cases due to influenza B. Influenza B is a single-stranded RNA virus with a high mutation rate, and both prior immune history and vaccination put significant pressure on the virus to evolve. Due to the high rate of viral evolution, the influenza B vaccine component of the annual influenza vaccine is updated, roughly every other year in recent years. To predict when an update to the vaccine is needed, an estimate of expected vaccine effectiveness against a range of viral strains is required. We here introduce a method to measure antigenic distance between the influenza B vaccine and circulating viral strains. The measure correlates well with effectiveness of the influenza B component of the annual vaccine in humans between 1979 and 2014. We discuss how this measure of antigenic distance may be used in the context of annual influenza vaccine design and prediction of vaccine effectiveness., 28 pages, 4 figures, 2 tables

Background No comparative review of Vaccine Adverse Event Reporting System (VAERS) submissions following pandemic influenza A (H1N1) 2009 and seasonal influenza vaccinations during the pandemic season among U.S. military personnel has been published. Methods We compared military vs. civilian adverse event reporting rates. Adverse events (AEs) following vaccination were identified from VAERS for adults aged 17–44 years after pandemic (monovalent influenza [MIV], and seasonal (trivalent inactivated influenza [IIV3], live attenuated influenza [LAIV3]) vaccines. Military vaccination coverage was provided by the Department of Defense’s Defense Medical Surveillance System. Civilian vaccination coverage was estimated using data from the National 2009 H1N1 Flu Survey and the Behavioral Risk Factor Surveillance System survey. Results Vaccination coverage was more than four times higher for MIV and more than twenty times higher for LAIV3 in the military than in the civilian population. The reporting rate of serious AE reports following MIV in service personnel (1.19 per 100,000) was about half that reported by the civilian population (2.45 per 100,000). Conversely, the rate of serious AE reports following LAIV3 among service personnel (1.32 per 100,000) was more than twice that of the civilian population. Although fewer military AEs following MIV were reported overall, the rate of Guillain–Barre Syndrome (GBS) (4.01 per million) was four times greater than that in the civilian population. (1.04 per million). Conclusions Despite higher vaccination coverage in service personnel, the rate of serious AEs following MIV was about half that in civilians. The rate of GBS reported following MIV was higher in the military.

Reputation-seeking can explain some decisions of U.S. federal agencies. However, it has remained unclear whether it could be used in the European context where agencies have proliferated in national and regional governance in the past few decades. This article shows that reputation-seeking can occur at autonomous agencies in the European context. A unique participant-observational study of an international public health agency acting in response to the 2009 H1N1 “swine” influenza pandemic provides bases for this conclusion. It adds empirical support for the proposition using real-time observations of and in-depth interviews on the agency’s decision-making processes.

Background Influenza C is usually considered a minor cause of respiratory illness in humans with many infections being asymptomatic or clinically mild. Large outbreaks can occur periodically resulting in significant morbidity. Objectives This study aimed at analyzing the available influenza C clinical samples from two widely separated states of Australia, collected over a 7-year period and to compare them with influenza C viruses detected in other parts of the world in recent years. Patients/Methods Between 2008 and 2014, 86 respiratory samples that were influenza C positive were collected from subjects with influenza-like illness living in the states of Victoria and Western Australia. A battery of other respiratory viruses were also tested for in these influenza C-positive samples. Virus isolation was attempted on all of these clinical samples, and gene sequencing was performed on all influenza C-positive cultures. Results and conclusions Detections of influenza C in respiratory samples were sporadic in most years studied, but higher rates of infection occurred in 2012 and 2014. Many of the patients with influenza C had coinfections with other respiratory pathogens. Phylogenetic analysis of the full-length hemagglutinin–esterase–fusion (HE) gene found that most of the viruses grouped in the C/Sao Paulo/378/82 clade with the remainder grouping in the C/Kanagawa/1/76 clade.