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Concept: Avian influenza

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Highly pathogenic avian H5N1 influenza A viruses occasionally infect humans, but currently do not transmit efficiently among humans. The viral haemagglutinin (HA) protein is a known host-range determinant as it mediates virus binding to host-specific cellular receptors. Here we assess the molecular changes in HA that would allow a virus possessing subtype H5 HA to be transmissible among mammals. We identified a reassortant H5 HA/H1N1 virus-comprising H5 HA (from an H5N1 virus) with four mutations and the remaining seven gene segments from a 2009 pandemic H1N1 virus-that was capable of droplet transmission in a ferret model. The transmissible H5 reassortant virus preferentially recognized human-type receptors, replicated efficiently in ferrets, caused lung lesions and weight loss, but was not highly pathogenic and did not cause mortality. These results indicate that H5 HA can convert to an HA that supports efficient viral transmission in mammals; however, we do not know whether the four mutations in the H5 HA identified here would render a wholly avian H5N1 virus transmissible. The genetic origin of the remaining seven viral gene segments may also critically contribute to transmissibility in mammals. Nevertheless, as H5N1 viruses continue to evolve and infect humans, receptor-binding variants of H5N1 viruses with pandemic potential, including avian-human reassortant viruses as tested here, may emerge. Our findings emphasize the need to prepare for potential pandemics caused by influenza viruses possessing H5 HA, and will help individuals conducting surveillance in regions with circulating H5N1 viruses to recognize key residues that predict the pandemic potential of isolates, which will inform the development, production and distribution of effective countermeasures.

Concepts: Virus, Influenza, Avian influenza, Influenza pandemic, Transmission and infection of H5N1, Pandemic, 2009 flu pandemic, Influenza A virus subtype H5N1

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Influenza A H5N1 has killed millions of birds and raises serious public health concern because of its potential to spread to humans and cause a global pandemic. While the early focus was in Asia, recent evidence suggests that Egypt is a new epicenter for the disease. This includes characterization of a variant clade 2.2.1.1, which has been found almost exclusively in Egypt.We analyzed 226 HA and 92 NA sequences with an emphasis on the H5N1 2.2.1.1 strains in Egypt using a Bayesian discrete phylogeography approach. This allowed modeling of virus dispersion between Egyptian governorates including the most likely origin.

Concepts: Public health, Epidemiology, Influenza, Avian influenza, Influenza pandemic, Pandemic, 2009 flu pandemic, Egypt

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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).

Concepts: Virus, Influenza, Avian influenza, People's Republic of China, Pandemic, Influenza vaccine, World Health Organization, Hong Kong

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Severe disease in humans caused by a novel influenza A virus that is distinct from circulating human influenza A viruses is a seminal event. It might herald sporadic human infections from an animal source - e.g., highly pathogenic avian influenza (HPAI) A (H5N1) virus; or it might signal the start of an influenza pandemic - e.g., influenza A(H1N1)pdm09 virus. Therefore, the discovery of novel influenza A (H7N9) virus infections in three critically ill patients reported in the Journal by Gao and colleagues is of major public health significance. Chinese scientists are to be congratulated for the apparent speed with which . . .

Concepts: Microbiology, Virus, Influenza, Avian influenza, Influenza pandemic, Pandemic, Influenza vaccine, Influenza A virus subtype H5N1

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Background Infection of poultry with influenza A subtype H7 viruses occurs worldwide, but the introduction of this subtype to humans in Asia has not been observed previously. In March 2013, three urban residents of Shanghai or Anhui, China, presented with rapidly progressing lower respiratory tract infections and were found to be infected with a novel reassortant avian-origin influenza A (H7N9) virus. Methods We obtained and analyzed clinical, epidemiologic, and virologic data from these patients. Respiratory specimens were tested for influenza and other respiratory viruses by means of real-time reverse-transcriptase-polymerase-chain-reaction assays, viral culturing, and sequence analyses. Results A novel reassortant avian-origin influenza A (H7N9) virus was isolated from respiratory specimens obtained from all three patients and was identified as H7N9. Sequencing analyses revealed that all the genes from these three viruses were of avian origin, with six internal genes from avian influenza A (H9N2) viruses. Substitution Q226L (H3 numbering) at the 210-loop in the hemagglutinin (HA) gene was found in the A/Anhui/1/2013 and A/Shanghai/2/2013 virus but not in the A/Shanghai/1/2013 virus. A T160A mutation was identified at the 150-loop in the HA gene of all three viruses. A deletion of five amino acids in the neuraminidase (NA) stalk region was found in all three viruses. All three patients presented with fever, cough, and dyspnea. Two of the patients had a history of recent exposure to poultry. Chest radiography revealed diffuse opacities and consolidation. Complications included acute respiratory distress syndrome and multiorgan failure. All three patients died. Conclusions Novel reassortant H7N9 viruses were associated with severe and fatal respiratory disease in three patients. (Funded by the National Basic Research Program of China and others.).

Concepts: DNA, Pulmonology, Virus, Infection, Acute respiratory distress syndrome, Influenza, Avian influenza, Transmission and infection of H5N1

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 The 2014-15 influenza season was distinguished by an A(H3N2) epidemic of antigenically-drifted virus and vaccine containing identical components to 2013-14. We report 2014-15 vaccine effectiveness (VE) estimates from Canada and explore contributing agent-host factors.

Concepts: Immune system, Infectious disease, Virus, Vaccine, Vaccination, Influenza, Avian influenza, Influenza vaccine

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Background The first identified cases of avian influenza A (H7N9) virus infection in humans occurred in China during February and March 2013. We analyzed data obtained from field investigations to characterize the epidemiologic characteristics of H7N9 cases in China as of April 17, 2013. Methods Field investigations were conducted for each confirmed case of H7N9 virus infection. A patient was considered to have a confirmed case if the presence of the H7N9 virus was verified by means of real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR), viral isolation, or serologic testing. Information on demographic characteristics, exposure history, and illness timelines was obtained from patients with confirmed cases. Close contacts were monitored for 7 days for symptoms of illness. Throat swabs were obtained from contacts in whom symptoms developed and were tested for the presence of the H7N9 virus testing by means of real-time RT-PCR. Results Among 82 persons with confirmed H7N9 virus infection, the median age was 63 years (range, 2 to 89), 73% were male, and 84% were urban residents. Confirmed cases occurred in six areas of China. Of 77 persons with available data, 4 were poultry workers, and 77% had a history of exposure to live animals, including chickens (76%). A total of 17 persons (21%) died after a median duration of illness of 11 days, 60 remain critically ill, and 4 with clinically mild cases were discharged from the hospital; 1 pediatric patient was not admitted to the hospital. In two family clusters, human-to-human transmission of H7N9 virus could not be ruled out. A total of 1251 of the 1689 close contacts of case patients completed the monitoring period; respiratory symptoms developed in 19 of them (1.5%), all of whom tested negative for the H7N9 virus. Conclusions Most persons with confirmed H7N9 virus infection were critically ill and epidemiologically unrelated. Laboratory-confirmed human-to-human H7N9 virus transmission was not documented among close contacts, but such transmission could not be ruled out in two families.

Concepts: Epidemiology, Patient, Virus, Illness, Influenza, Avian influenza, Influenza pandemic, Influenza vaccine

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In the United States, annual vaccination against seasonal influenza is recommended for all persons aged ≥6 months (1). Each influenza season since 2004-05, CDC has estimated the effectiveness of seasonal influenza vaccine to prevent influenza-associated, medically attended, acute respiratory illness (ARI). This report uses data, as of February 4, 2017, from 3,144 children and adults enrolled in the U.S. Influenza Vaccine Effectiveness Network (U.S. Flu VE Network) during November 28, 2016-February 4, 2017, to estimate an interim adjusted effectiveness of seasonal influenza vaccine for preventing laboratory-confirmed influenza virus infection associated with medically attended ARI. During this period, overall vaccine effectiveness (VE) (adjusted for study site, age group, sex, race/ethnicity, self-rated general health, and days from illness onset to enrollment) against influenza A and influenza B virus infection associated with medically attended ARI was 48% (95% confidence interval [CI] = 37%-57%). Most influenza infections were caused by A (H3N2) viruses. VE was estimated to be 43% (CI = 29%-54%) against illness caused by influenza A (H3N2) virus and 73% (CI = 54%-84%) against influenza B virus. These interim VE estimates indicate that influenza vaccination reduced the risk for outpatient medical visits by almost half. Because influenza activity remains elevated (2), CDC and the Advisory Committee on Immunization Practices recommend that annual influenza vaccination efforts continue as long as influenza viruses are circulating (1). Vaccination with 2016-17 influenza vaccines will reduce the number of infections with most currently circulating influenza viruses. Persons aged ≥6 months who have not yet been vaccinated this season should be vaccinated as soon as possible.

Concepts: Immune system, Virus, Vaccine, Vaccination, Influenza, Avian influenza, Influenza pandemic, Influenza vaccine

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Assessment of the effect of influenza on populations, including risk of infection, illness if infected, illness severity, and consultation rates, is essential to inform future control and prevention. We aimed to compare the community burden and severity of seasonal and pandemic influenza across different age groups and study years and gain insight into the extent to which traditional surveillance underestimates this burden.

Concepts: Infectious disease, Influenza, Avian influenza, Influenza pandemic, Transmission and infection of H5N1, Pandemic, Influenza vaccine, World Health Organization