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Sample records for 2009-2010 h1n1 influenza

  1. Supply of neuraminidase inhibitors related to reduced influenza A (H1N1) mortality during the 2009-2010 H1N1 pandemic: summary of an ecological study.

    PubMed

    Miller, Paula E; Rambachan, Aksharananda; Hubbard, Roderick J; Li, Jiabai; Meyer, Alison E; Stephens, Peter; Mounts, Anthony W; Rolfes, Melissa A; Penn, Charles R

    2013-09-01

    When the influenza A (H1N1) pandemic spread across the globe from April 2009 to August 2010, many WHO Member States used antiviral drugs, specifically neuraminidase inhibitors (NAIs) oseltamivir and zanamivir, to treat influenza patients in critical condition. Antivirals have been found to be effective in reducing severity and duration of influenza illness, and likely reduce morbidity; however, it is unclear whether NAIs used during the pandemic reduced H1N1 mortality. To assess the association between antivirals and influenza mortality, at an ecologic level, country-level data on supply of oseltamivir and zanamivir were compared to laboratory-confirmed H1N1 deaths (per 100 000 people) from July 2009 to August 2010 in 42 WHO Member States. From this analysis, it was found that each 10% increase in kilograms of oseltamivir, per 100 000 people, was associated with a 1·6% reduction in H1N1 mortality over the pandemic period [relative rate (RR) = 0·84 per log increase in oseltamivir supply]. Each 10% increase in kilogram of active zanamivir, per 100 000, was associated with a 0·3% reduction in H1N1 mortality (RR = 0·97 per log increase). While limitations exist in the inference that can be drawn from an ecologic evaluation, this analysis offers evidence of a protective relationship between antiviral drug supply and influenza mortality and supports a role for influenza antiviral use in future pandemics. This article summarises the original study described previously, which can be accessed through the following citation: Miller PE, Rambachan A, Hubbard RJ, Li J, Meyer AE, et al. (2012) Supply of Neuraminidase Inhibitors Related to Reduced Influenza A (H1N1) Mortality during the 2009-2010 H1N1 Pandemic: An Ecological Study. PLoS ONE 7(9): e43491.

  2. Pandemic influenza A (H1N1) in non-vaccinated, pregnant women in Spain (2009-2010).

    PubMed

    Morales-Suárez-Varela, María; González-Candelas, Fernando; Astray, Jenaro; Alonso, Jordi; Castro, Ady; Cantón, Rafael; Galán, Juan Carlos; Garin, Olatz; Soldevila, Núria; Baricot, Maretva; Castilla, Jesús; Godoy, Pere; Delgado-Rodríguez, Miguel; Martín, Vicente; Mayoral, José María; Pumarola, Tomás; Quintana, José Maria; Tamames, Sonia; Llopis-González, Agustín; Domínguez, Angela

    2014-08-01

    The aim of this study was to investigate the main characteristics of non-vaccinated pregnant women who were hospitalised for influenza A (H1N1) pdm09 pandemic versus pregnant women hospitalised for non-influenza-related reasons in Spain, and to characterise the clinical presentation of the disease in this population to facilitate early diagnosis and future action programmes. Understanding influenza infection during pregnancy is important as pregnant women are a high-risk population for increased morbidity from influenza infection. We investigated the socio-demographic and clinical features of 51 non-vaccinated, pregnant women infected with the pandemic influenza A (H1N1) virus in Spain (cases) and compared them to 114 controls (non-vaccinated and non-infected pregnant women) aged 15-44 years. Substantial and significant odd ratios (ORs) for pandemic influenza A (H1N1) were found for the pregnant women who were obese compared with controls (body mass index > 30) (OR 3.03; 95% confidence intervals 1.13-8.11). The more prevalent symptoms observed in pandemic influenza-infected pregnant women were high temperature, cough (82.4%), malaise (80.5%), myalgia (56.1%), and headaches (54.9%). Our results suggest that the initial symptoms and risk factors for infection of pregnant women with the influenza A (H1N1) pdm09 virus are similar to the symptoms and risk factors for seasonal influenza, which make early diagnosis difficult, and reinforces the need to identify and protect high-risk groups.

  3. Costs of School-Located Influenza Vaccination Clinics in Maine during the 2009-2010 H1N1 Pandemic

    ERIC Educational Resources Information Center

    Cho, Bo-Hyun; Asay, Garrett R. Beeler; Lorick, Suchita A.; Tipton, Meredith L.; Dube, Nancy L.; Messonnier, Mark L.

    2012-01-01

    This study retrospectively estimated costs for a convenience sample of school-located vaccination (SLV) clinics conducted in Maine during the 2009-2010 influenza season. Surveys were developed to capture the cost of labor including unpaid volunteers as well as supplies and materials used in SLV clinics. Six nurses from different school districts…

  4. Pandemic influenza A (H1N1) infection in pregnant and nonpregnant women in Spain (2009-2010).

    PubMed

    Suárez-Varela, María Morales; González-Candelas, Fernando; Astray, Jenaro; Alonso, Jordi; Garin, Olatz; Castro, Ady; Galán, Juan C; Baricot, Maretva; Castilla, Jesús; Godoy, Pere; Delgado-Rodríguez, Miguel; Martin, Vicente; Mayoral, José M; Pumarola, Tomás; Quintana, José M; Tamames, Sonia; Llopis-González, Agustín; Dominguez, Angela

    2014-01-01

    The present study aimed to compare the main features of infection with pandemic influenza A virus in pregnant and nonpregnant women admitted to hospitals in Spain during the first waves of the 2009-2010 influenza pandemic. This was a prospective (November 2009 to June 2010), multicenter observational study. All cases were women of reproductive age who had not been vaccinated against seasonal or pandemic influenza A. Influenza infection was confirmed by reverse transcription-polymerase chain reaction (RT-PCR). The sociodemographic and clinical data of all cases were reviewed. A total of 219 inpatients, including 49 pregnant women and 170 nonpregnant women, were enrolled in the study upon admission to participating hospitals. The most substantially different symptoms between the groups were respiratory distress and unilobar consolidation, both of which were more frequent among nonpregnant women. Antibiotics and systemic corticosteroids were more frequently used in nonpregnant women; however, there were no differences in the rates of treatment with antivirals. Our findings indicated that the compared with nonpregnant women, pregnant women in this study did not have significantly different symptoms and were not at increased risk of complications from pandemic influenza virus infection.

  5. Serological response to influenza A H1N1 vaccine (Pandemrix®) and seasonal influenza vaccine 2009/2010 in renal transplant recipients and in hemodialysis patients.

    PubMed

    Ott, Undine; Sauerbrei, Andreas; Lange, Jeannette; Schäfler, Anna; Walther, Mario; Wolf, Gunter; Wutzler, Peter; Zell, Roland; Krumbholz, Andi

    2012-08-01

    In the present study, antibody response to seasonal influenza vaccination and to the adjuvanted one-shot influenza A H1N1 vaccine (Pandemrix(®)) was investigated in 57 hemodialysis (HD) patients and 48 renal transplant (RT) recipients. Specific antibodies were measured by hemagglutination inhibition (HI) test using a pandemic H1N1 strain and a seasonal H3N2 virus. HI titers of ≥1:40 were considered as protective. Hemodialysis patients showed seroprotection against pandemic H1N1 in 35.1%, against seasonal influenza in 36.8% and against both in 14.0%. In comparison, renal transplant recipients developed protective antibody titers against the pandemic H1N1 virus in 47.9%, against the seasonal H3N2 strain in 31.3% and against both in 18.8%. HD patients and renal transplant recipients younger than 60 years developed protective antibody response to the pandemic influenza H1N1 vaccine in 50.0% of the HD patients and 55.2% of the RT recipients and against seasonal influenza in 45.0/20.7% (HD/RT) of the cases. Patients aged ≥60 years showed seroprotection against pandemic influenza in 27.0/36.8% (HD/RT) and against seasonal influenza in 32.4/47.4% (HD/RT). Side effects were reported in only four patients. In hemodialysis patients and renal transplant recipients, vaccination against pandemic H1N1 and seasonal influenza is well tolerated. However, more than a half of these patients did not develop seroprotective antibody levels. Thus, new vaccines and altered vaccination regimes are likely necessary to achieve relevant antibody levels in these patient groups.

  6. Clinical aspects of influenza A(H1N1)pdm09 cases reported during the pandemic in Brazil, 2009-2010

    PubMed Central

    Rossetto, Érika Valeska; Luna, Expedito José de Albuquerque

    2015-01-01

    ABSTRACT Objective: To describe the clinical aspects of cases of influenza A(H1N1)pdm09 in Brazil. Methods: A descriptive study of cases reported in Sistema de Informação de Agravos de Notificação (SINAN), 2009-2010. Results: As the final classification, we obtained 53,797 (56.79%) reported cases confirmed as a new influenza virus subtype, and 40,926 (43.21%) cases discarded. Fever was the most common sign, recorded in 99.74% of the confirmed and 98.92% of the discarded cases. Among the confirmed cases, the presence of comorbidities was reported in 32.53%, and in 38.29% of the discarded cases. The case fatality rate was 4.04%; 3,267 pregnant women were confirmed positive for influenza A new viral subtype and 2,730 of them were cured. The case fatality rate of pregnant women was 6.88%. Conclusion: The findings suggested concern of the health system with pregnant women, and patients with comorbidities and quality of care may have favored a lower mortality. We recommend that, when caring for patients with severe respiratory symptoms, with comorbidities, or pregnant women, health professionals should consider the need for hospital care, as these factors make up a worse prognosis of infection by the pandemic influenza virus. PMID:26154537

  7. Association between monovalent influenza A (H1N1) pdm09 vaccine and pneumonia among the elderly in the 2009-2010 season in Japan: A case-control study.

    PubMed

    Kondo, Kyoko; Suzuki, Kanzo; Washio, Masakazu; Ohfuji, Satoko; Fukushima, Wakaba; Maeda, Akiko; Hirota, Yoshio

    2015-01-01

    We investigated the association between monovalent influenza A (H1N1) pdm09 (H1N1pdm) vaccine and pneumonia in elderly people. Study design was a hospital-based, matched case-control study. Cases comprised patients ≥ 65 years old who had been newly diagnosed with pneumonia. For each case, 2 controls were defined as individuals with other diseases (not pneumonia) who were matched by sex, age, entry date, and the visited hospital. Study period was the interval from 1 September 2009 until 30 September 2010. Because a pandemic of influenza A (H1N1) occurred during study period, we analyzed selected subjects who had enrolled during the influenza A (H1N1) pandemic. We calculated the odds ratios (ORs) and 95% confidence intervals (CIs) for pneumonia in H1N1pdm-vaccinated subjects compared with unvaccinated subjects using a conditional logistic regression model to assess the association between H1N1pdm vaccine and pneumonia. The subjects during the period of the influenza A (H1N1) pandemic were 20 cases and 40 controls. Subjects who had received H1N1pdm vaccine showed a significantly decreased OR for pneumonia (OR = 0.10, 95% CI = 0.01-0.98) compared with unvaccinated subjects. In conclusion, H1N1pdm vaccination may have prevented pneumonia among the elderly during the 2009-2010 influenza A (H1N1) pandemic in Japan.

  8. Individual Vaccination as Nash Equilibrium in a SIR Model with Application to the 2009-2010 Influenza A (H1N1) Epidemic in France.

    PubMed

    Laguzet, Laetitia; Turinici, Gabriel

    2015-10-01

    The vaccination against ongoing epidemics is seldom compulsory but remains one of the most classical means to fight epidemic propagation. However, recent debates concerning the innocuity of vaccines and their risk with respect to the risk of the epidemic itself lead to severe vaccination campaign failures, and new mass behaviors appeared driven by individual self-interest. Prompted by this context, we analyze, in a Susceptible-Infected-Recovered model, whether egocentric individuals can reach an equilibrium with the rest of the society. Using techniques from the "Mean Field Games" theory, we extend previous results and show that an equilibrium exists and characterizes completely the individual best vaccination strategy (with or without discounting). We also compare with a strategy based only on overall societal optimization and exhibit a situation with nonnegative price of anarchy. Finally, we apply the theory to the 2009-2010 Influenza A (H1N1) vaccination campaign in France and hint that a group of individuals stopped vaccinating at levels that indicated a pessimistic perception of the risk of the vaccine. PMID:26443437

  9. Individual Vaccination as Nash Equilibrium in a SIR Model with Application to the 2009-2010 Influenza A (H1N1) Epidemic in France.

    PubMed

    Laguzet, Laetitia; Turinici, Gabriel

    2015-10-01

    The vaccination against ongoing epidemics is seldom compulsory but remains one of the most classical means to fight epidemic propagation. However, recent debates concerning the innocuity of vaccines and their risk with respect to the risk of the epidemic itself lead to severe vaccination campaign failures, and new mass behaviors appeared driven by individual self-interest. Prompted by this context, we analyze, in a Susceptible-Infected-Recovered model, whether egocentric individuals can reach an equilibrium with the rest of the society. Using techniques from the "Mean Field Games" theory, we extend previous results and show that an equilibrium exists and characterizes completely the individual best vaccination strategy (with or without discounting). We also compare with a strategy based only on overall societal optimization and exhibit a situation with nonnegative price of anarchy. Finally, we apply the theory to the 2009-2010 Influenza A (H1N1) vaccination campaign in France and hint that a group of individuals stopped vaccinating at levels that indicated a pessimistic perception of the risk of the vaccine.

  10. Guillain-Barre syndrome during the 2009-2010 H1N1 influenza vaccination campaign: population-based surveillance among 45 million Americans.

    PubMed

    Wise, Matthew E; Viray, Melissa; Sejvar, James J; Lewis, Paige; Baughman, Andrew L; Connor, Walter; Danila, Richard; Giambrone, Greg P; Hale, Christa; Hogan, Brenna C; Meek, James I; Murphree, Rendi; Oh, John Y; Reingold, Arthur; Tellman, Norisse; Conner, Susan M; Singleton, James A; Lu, Peng-Jun; DeStefano, Frank; Fridkin, Scott K; Vellozzi, Claudia; Morgan, Oliver W

    2012-06-01

    Because of widespread distribution of the influenza A (H1N1) 2009 monovalent vaccine (pH1N1 vaccine) and the prior association between Guillain-Barré syndrome (GBS) and the 1976 H1N1 influenza vaccine, enhanced surveillance was implemented to estimate the magnitude of any increased GBS risk following administration of pH1N1 vaccine. The authors conducted active, population-based surveillance for incident cases of GBS among 45 million persons residing at 10 Emerging Infections Program sites during October 2009-May 2010; GBS was defined according to published criteria. The authors determined medical and vaccine history for GBS cases through medical record review and patient interviews. The authors used vaccine coverage data to estimate person-time exposed and unexposed to pH1N1 vaccine and calculated age- and sex-adjusted rate ratios comparing GBS incidence in these groups, as well as age- and sex-adjusted numbers of excess GBS cases. The authors received 411 reports of confirmed or probable GBS. The rate of GBS immediately following pH1N1 vaccination was 57% higher than in person-time unexposed to vaccine (adjusted rate ratio = 1.57, 95% confidence interval: 1.02, 2.21), corresponding to 0.74 excess GBS cases per million pH1N1 vaccine doses (95% confidence interval: 0.04, 1.56). This excess risk was much smaller than that observed during the 1976 vaccine campaign and was comparable to some previous seasonal influenza vaccine risk assessments.

  11. Preliminary results: surveillance for Guillain-Barré syndrome after receipt of influenza A (H1N1) 2009 monovalent vaccine - United States, 2009-2010.

    PubMed

    2010-06-01

    Guillain-Barré syndrome (GBS) is an uncommon peripheral neuropathy causing paralysis and in severe cases respiratory failure and death. GBS often follows an antecedent gastrointestinal or upper respiratory illness but, in rare cases, can follow vaccination. In 1976, vaccination against a novel swine-origin influenza A (H1N1) virus was associated with a statistically significant increased risk for GBS in the 42 days after vaccination (approximately 10 excess cases per 1 million vaccinations), a consideration in halting the vaccination program in the context of limited influenza virus transmission. To monitor influenza A (H1N1) 2009 monovalent vaccine safety, several federal surveillance systems, including CDC's Emerging Infections Program (EIP), are being used. In October 2009, EIP began active surveillance to assess the risk for GBS after 2009 H1N1 vaccination. Preliminary results from an analysis in EIP comparing GBS patients hospitalized through March 31, 2010, who did and did not receive 2009 H1N1 vaccination showed an estimated age-adjusted rate ratio of 1.77 (GBS incidence of 1.92 per 100,000 person-years among vaccinated persons and 1.21 per 100,000 person-years among unvaccinated persons). If end-of-surveillance analysis confirms this finding, this would correspond to 0.8 excess cases of GBS per 1 million vaccinations, similar to that found in seasonal influenza vaccines. No other federal system to date has detected a statistically significant association between GBS and 2009 H1N1 vaccination. Surveillance and further analyses are ongoing. The 2009 H1N1 vaccine safety profile is similar to that for seasonal influenza vaccines, which have an excellent safety record. Vaccination remains the most effective method to prevent serious illness and death from 2009 H1N1 influenza infection; illness from the 2009 H1N1 influenza virus has been associated with a hospitalization rate of 222 per 1 million and a death rate of 9.7 per 1 million population.

  12. Chart-confirmed guillain-barre syndrome after 2009 H1N1 influenza vaccination among the Medicare population, 2009-2010.

    PubMed

    Polakowski, Laura L; Sandhu, Sukhminder K; Martin, David B; Ball, Robert; Macurdy, Thomas E; Franks, Riley L; Gibbs, Jonathan M; Kropp, Garner F; Avagyan, Armen; Kelman, Jeffrey A; Worrall, Christopher M; Sun, Guoying; Kliman, Rebecca E; Burwen, Dale R

    2013-09-15

    Given the increased risk of Guillain-Barré Syndrome (GBS) found with the 1976 swine influenza vaccine, both active surveillance and end-of-season analyses on chart-confirmed cases were performed across multiple US vaccine safety monitoring systems, including the Medicare system, to evaluate the association of GBS after 2009 monovalent H1N1 influenza vaccination. Medically reviewed cases consisted of H1N1-vaccinated Medicare beneficiaries who were hospitalized for GBS. These cases were then classified by using Brighton Collaboration diagnostic criteria. Thirty-one persons had Brighton level 1, 2, or 3 GBS or Fisher Syndrome, with symptom onset 1-119 days after vaccination. Self-controlled risk interval analyses estimated GBS risk within the 6-week period immediately following H1N1 vaccination compared with a later control period, with additional adjustment for seasonality. Our results showed an elevated risk of GBS with 2009 monovalent H1N1 vaccination (incidence rate ratio = 2.41, 95% confidence interval: 1.14, 5.11; attributable risk = 2.84 per million doses administered, 95% confidence interval: 0.21, 5.48). This observed risk was slightly higher than that seen with previous seasonal influenza vaccines; however, additional results that used a stricter case definition (Brighton level 1 or 2) were not statistically significant, and our ability to account for preceding respiratory/gastrointestinal illness was limited. Furthermore, the observed risk was substantially lower than that seen with the 1976 swine influenza vaccine.

  13. Sociodemographic factors and clinical conditions associated to hospitalization in influenza A (H1N1) 2009 virus infected patients in Spain, 2009-2010.

    PubMed

    González-Candelas, Fernando; Astray, Jenaro; Alonso, Jordi; Castro, Ady; Cantón, Rafael; Galán, Juan Carlos; Garin, Olatz; Sáez, Marc; Soldevila, Nuria; Baricot, Maretva; Castilla, Jesús; Godoy, Pere; Delgado-Rodríguez, Miguel; Martín, Vicente; Mayoral, José María; Pumarola, Tomás; Quintana, José María; Tamames, Sonia; Domínguez, Angela

    2012-01-01

    The emergence and pandemic spread of a new strain of influenza A (H1N1) virus in 2009 resulted in a serious alarm in clinical and public health services all over the world. One distinguishing feature of this new influenza pandemic was the different profile of hospitalized patients compared to those from traditional seasonal influenza infections. Our goal was to analyze sociodemographic and clinical factors associated to hospitalization following infection by influenza A(H1N1) virus. We report the results of a Spanish nationwide study with laboratory confirmed infection by the new pandemic virus in a case-control design based on hospitalized patients. The main risk factors for hospitalization of influenza A (H1N1) 2009 were determined to be obesity (BMI≥40, with an odds-ratio [OR] 14.27), hematological neoplasia (OR 10.71), chronic heart disease, COPD (OR 5.16) and neurological disease, among the clinical conditions, whereas low education level and some ethnic backgrounds (Gypsies and Amerinds) were the sociodemographic variables found associated to hospitalization. The presence of any clinical condition of moderate risk almost triples the risk of hospitalization (OR 2.88) and high risk conditions raise this value markedly (OR 6.43). The risk of hospitalization increased proportionally when for two (OR 2.08) or for three or more (OR 4.86) risk factors were simultaneously present in the same patient. These findings should be considered when a new influenza virus appears in the human population.

  14. Does the weather play a role in the spread of pandemic influenza? A study of H1N1pdm09 infections in France during 2009-2010.

    PubMed

    Vittecoq, M; Roche, B; Cohen, J-M; Renaud, F; Thomas, F; Gauthier-Clerc, M

    2015-12-01

    Understanding patterns of influenza spread and persistence is crucial for pandemic preparedness. The H1N1pdm09 virus caused the first influenza pandemic of the 21st century which resulted in at least 18500 deaths. Based on laboratory-confirmed primary-care case reports we investigated the role of weather conditions and socio-demographic variables in its initial spread and subsequent presence in France. Our findings suggest that low relative humidity and high population density were determinants in shaping the early spread of the virus at the national level. Those conditions also favoured the persistence of viral presence throughout the first 33 weeks of the pandemic. Additionally this persistence was significantly favoured by low insolation. These results confirm the increasingly recognized role of humidity in influenza dynamics and underlie the concomitant effect of insolation. Therefore climatic factors should be taken into account when designing influenza control and prevention measures. PMID:26112598

  15. Sequence analysis of the 2009 pandemic influenza A H1N1 virus haemagglutinin gene from 2009-2010 Brazilian clinical samples.

    PubMed

    Ferreira, João Leandro de Paula; Borborema, Samanta Etel Treiger; Brígido, Luis Fernando de Macedo; Oliveira, Maria Isabel de; Paiva, Terezinha Maria de; Santos, Cecília Luiza Simões dos

    2011-08-01

    In this paper, we analysed the haemagglutinin (HA) gene identified by polymerase chain reaction from 90 influenza A H1N1 virus strains that circulated in Brazil from April 2009-June 2010. A World Health Organization sequencing protocol allowed us to identify amino acid mutations in the HA protein at positions S220T (71%), D239G/N/S (20%), Y247H (4.5%), E252K (3.3%), M274V (2.2%), Q310H (26.7%) and E391K (12%). A fatal outcome was associated with the D239G mutation (p < 0.0001). Brazilian HA genetic diversity, in comparison to a reference strain from California, highlights the role of influenza virus surveillance for study of viral evolution, in addition to monitoring the spread of the virus worldwide.

  16. [Database linkage for surveillance of the influenza A(H1N1)pdm09 pandemic in Brazil, 2009-2010].

    PubMed

    Rossetto, Erika Valeska; Luna, Expedito José de Albuquerque

    2016-07-21

    Based on database linkage, the objective of this study was to describe the epidemiological profile of notified cases and deaths from the new viral subtype of influenza during the influenza pandemic. Secondary data were used from the SINAN (Information System for Notifiable Diseases) and SIM (Mortality Information System) for the years 2009 and 2010. Linkage identified 5,973 deaths of cases notified as pandemic influenza. Of these, 2,170 (36.33%) had been classified in the SINAN as confirmed pandemic influenza, 215 (3.6%) as due to other infectious agents, and 3,340 (55.92%) as ruled out. After linkage, some cases in the SINAN database that were closed as death from influenza (n = 658) or death from other causes (n = 847) could not be located in the SIM database. Database linkage can improve the surveillance system and monitoring of morbidity and mortality. We recommend strengthening influenza surveillance in Brazil using linkage of Ministry of Health databases.

  17. [Database linkage for surveillance of the influenza A(H1N1)pdm09 pandemic in Brazil, 2009-2010].

    PubMed

    Rossetto, Erika Valeska; Luna, Expedito José de Albuquerque

    2016-07-21

    Based on database linkage, the objective of this study was to describe the epidemiological profile of notified cases and deaths from the new viral subtype of influenza during the influenza pandemic. Secondary data were used from the SINAN (Information System for Notifiable Diseases) and SIM (Mortality Information System) for the years 2009 and 2010. Linkage identified 5,973 deaths of cases notified as pandemic influenza. Of these, 2,170 (36.33%) had been classified in the SINAN as confirmed pandemic influenza, 215 (3.6%) as due to other infectious agents, and 3,340 (55.92%) as ruled out. After linkage, some cases in the SINAN database that were closed as death from influenza (n = 658) or death from other causes (n = 847) could not be located in the SIM database. Database linkage can improve the surveillance system and monitoring of morbidity and mortality. We recommend strengthening influenza surveillance in Brazil using linkage of Ministry of Health databases. PMID:27462844

  18. Ethnicity, deprivation and mortality due to 2009 pandemic influenza A(H1N1) in England during the 2009/2010 pandemic and the first post-pandemic season.

    PubMed

    Zhao, H; Harris, R J; Ellis, J; Pebody, R G

    2015-12-01

    The relationship between risk of death following influenza A(H1N1)pdm09 infection and ethnicity and deprivation during the 2009/2010 pandemic period and the first post-pandemic season of 2010/2011 in England was examined. Poisson regression models were used to estimate the mortality risk, adjusted for age, gender, and place of residence. Those of non-White ethnicity experienced an increased mortality risk compared to White populations during the 2009/2010 pandemic [10·5/1000 vs. 6·0/1000 general population; adjusted risk ratio (RR) 1·84, 95% confidence interval (CI) 1·39-2·54] with the highest risk in those of Pakistani ethnicity. However, no significant difference between ethnicities was observed during the following 2010/2011 season. Persons living in areas with the highest level of deprivation had a significantly higher risk of death (RR 2·08, 95% CI 1·49-2·91) compared to the lowest level for both periods. These results highlight the importance of rapid identification of groups at higher risk of severe disease in the early stages of future pandemics to enable the implementation of optimal prevention and control measures for vulnerable populations.

  19. Colds and the Flu: H1N1 Influenza

    MedlinePlus

    MENU Return to Web version Colds and the Flu | H1N1 Influenza What is H1N1 influenza? H1N1 influenza (also known as swine flu) is an infection caused by ... or illness that is more than “just a cold.” When should I see my doctor? If you’ ...

  20. Pandemic H1N1 influenza

    PubMed Central

    Kumar, Anand

    2011-01-01

    The 2009 H1N1 influenza A virus that has targeted not only those with chronic medical illness, the very young and old, but also a large segment of the patient population that has previously been afforded relative protection - those who are young, generally healthy, and immune naive. The illness is mild in most, but results in hospitalization and severe ARDS in an important minority. Among those who become critically ill, 20-40% will die, predominantly of severe hypoxic respiratory failure. However, and potentially in part due to the young age of those affected, intensive care with aggressive oxygenation support will allow most people to recover. The volume of patients infected and with critical illness placed substantial strain on the capacity of the health care system and critical care most specifically. Despite this, the 2009 pandemic has engaged our specialty and highlighted its importance like no other. Thus far, the national and global critical care response has been brisk, collaborative and helpful - not only for this pandemic, but for subsequent challenges in years ahead. PMID:22263101

  1. Sequential Seasonal H1N1 Influenza Virus Infections Protect Ferrets against Novel 2009 H1N1 Influenza Virus

    PubMed Central

    Carter, Donald M.; Bloom, Chalise E.; Nascimento, Eduardo J. M.; Marques, Ernesto T. A.; Craigo, Jodi K.; Cherry, Joshua L.; Lipman, David J.

    2013-01-01

    Individuals <60 years of age had the lowest incidence of infection, with ∼25% of these people having preexisting, cross-reactive antibodies to novel 2009 H1N1 influenza. Many people >60 years old also had preexisting antibodies to novel H1N1. These observations are puzzling because the seasonal H1N1 viruses circulating during the last 60 years were not antigenically similar to novel H1N1. We therefore hypothesized that a sequence of exposures to antigenically different seasonal H1N1 viruses can elicit an antibody response that protects against novel 2009 H1N1. Ferrets were preinfected with seasonal H1N1 viruses and assessed for cross-reactive antibodies to novel H1N1. Serum from infected ferrets was assayed for cross-reactivity to both seasonal and novel 2009 H1N1 strains. These results were compared to those of ferrets that were sequentially infected with H1N1 viruses isolated prior to 1957 or more-recently isolated viruses. Following seroconversion, ferrets were challenged with novel H1N1 influenza virus and assessed for viral titers in the nasal wash, morbidity, and mortality. There was no hemagglutination inhibition (HAI) cross-reactivity in ferrets infected with any single seasonal H1N1 influenza viruses, with limited protection to challenge. However, sequential H1N1 influenza infections reduced the incidence of disease and elicited cross-reactive antibodies to novel H1N1 isolates. The amount and duration of virus shedding and the frequency of transmission following novel H1N1 challenge were reduced. Exposure to multiple seasonal H1N1 influenza viruses, and not to any single H1N1 influenza virus, elicits a breadth of antibodies that neutralize novel H1N1 even though the host was never exposed to the novel H1N1 influenza viruses. PMID:23115287

  2. H1N1 influenza (Swine flu)

    MedlinePlus

    ... regular (seasonal) flu vaccine. You cannot get H1N1 flu virus from eating pork or any other food, drinking ... pools, or using hot tubs or saunas. Any flu virus can spread from person to person when: Someone ...

  3. A surge of flu-associated adult respiratory distress syndrome in an Austrian tertiary care hospital during the 2009/2010 Influenza A H1N1v pandemic.

    PubMed

    Schellongowski, Peter; Ullrich, Roman; Hieber, Cornelia; Hetz, Hubert; Losert, Heidrun; Hermann, Maria; Hermann, Alexander; Gattringer, Klaus-Bernhard; Siersch, Viktoria; Rabitsch, Werner; Fuhrmann, Valentin; Bojic, Andja; Robak, Oliver; Sperr, Wolfgang R; Laczika, Klaus; Locker, Gottfried J; Staudinger, Thomas

    2011-04-01

    We report on 17 patients with influenza A H1N1v-associated Adult Respiratory Distress Syndrome who were admitted to the intensive care unit (ICU) between June 11th 2009 and August 10th 2010 (f/m: 8/9; age: median 39 (IQR 29-54) years; SAPS II: 35 (29-48)). Body mass index was 26 (24-35), 24% were overweight and 29% obese. The Charlson Comorbidity Index was 1 (0-2) and all but one patient had comorbid conditions. The median time between onset of the first symptom and admission to the ICU was 5 days (range 0-14). None of the patients had received vaccination against H1N1v. Nine patients received oseltamivir, only two of them within 48 hours of symptom onset. All patients developed severe ARDS (PaO(2)/FiO(2)-Ratio 60 (55-92); lung injury score 3.8 (3.3-4.0)), were mechanically ventilated and on vasopressor support. Fourteen patients received corticosteroids, 7 patients underwent hemofiltration, and 10 patients needed extracorporeal membrane-oxygenation (ECMO; 8 patients veno-venous, 2 patients veno-arterial), three patients Interventional Lung Assist (ILA) and two patients pump driven extracorporeal low-flow CO(2)-elimination (ECCO(2)-R). Seven of 17 patients (41%) died in the ICU (4 patients due to bleeding, 3 patients due to multi-organ failure), while all other patients survived the hospital (59%). ECMO mortality was 50%. The median ICU length-of-stay was 26 (19-44) vs. 21 (17-25) days (survivors vs. nonsurvivors), days on the ventilator were 18 (14-35) vs. 20 (17-24), and ECMO duration was 10 (8-25) vs. 13 (11-16) days, respectively (all p = n.s.). Compared to a control group of 241 adult intensive care unit patients without H1N1v, length of stay in the ICU, rate of mechanical ventilation, days on the ventilator, and TISS 28 scores were significantly higher in patients with H1N1v. The ICU survival tended to be higher in control patients (79 vs. 59%; p = 0.06). Patients with H1N1v admitted to either of our ICUs were young, overproportionally obese and almost all

  4. Influenza A (H1N1) organising pneumonia.

    PubMed

    Torrego, Alfons; Pajares, Virginia; Mola, Anna; Lerma, Enrique; Franquet, Tomás

    2010-04-27

    In November 2009, countries around the world reported confirmed cases of pandemic influenza H1N1, including over 6000 deaths. No peak in activity has been seen. The most common causes of death are pneumonia and acute respiratory distress syndrome. We report a case of a 55-year-old woman who presented with organising pneumonia associated with influenza A (H1N1) infection confirmed by transbronchial lung biopsy. Organising pneumonia should also be considered as a possible complication of influenza A (H1N1) infection, given that these patients can benefit from early diagnosis and appropriate specific management.

  5. Pandemic (H1N1) 2009 and Seasonal Influenza A (H1N1) Co-infection, New Zealand, 2009

    PubMed Central

    Hall, Richard J.; Sonnberg, Stephanie; Ducatez, Mariette; Paine, Shevaun; Nicol, Mackenzie; Ralston, Jacqui C.; Bandaranayake, Don; Hope, Virginia; Webby, Richard J.; Huang, Sue

    2010-01-01

    Co-infection with seasonal influenza A (H1N1) and pandemic (H1N1) 2009 could result in reassortant viruses that may acquire new characteristics of transmission, virulence, and oseltamivir susceptibility. Results from oseltamivir-sensitivity testing on viral culture suggested the possibility of co-infections with oseltamivir-resistant (seasonal A [H1N1]) and -susceptible (pandemic [H1N1] 2009) viruses. PMID:20875294

  6. The 2009 H1N1 Pandemic Influenza in Korea

    PubMed Central

    2016-01-01

    In late March of 2009, an outbreak of influenza in Mexico, was eventually identified as H1N1 influenza A. In June 2009, the World Health Organization raised a pandemic alert to the highest level. More than 214 countries have reported confirmed cases of pandemic H1N1 influenza A. In Korea, the first case of pandemic influenza A/H1N1 infection was reported on May 2, 2009. Between May 2009 and August 2010, 750,000 cases of pandemic influenza A/H1N1 were confirmed by laboratory test. The H1N1-related death toll was estimated to reach 252 individuals. Almost one billion cases of influenza occurs globally every year, resulting in 300,000 to 500,000 deaths. Influenza vaccination induces virus-neutralizing antibodies, mainly against hemagglutinin, which provide protection from invading virus. New quadrivalent inactivated influenza vaccine generates similar immune responses against the three influenza strains contained in two types of trivalent vaccines and superior responses against the additional B strain. PMID:27066083

  7. 2009 Pandemic Influenza A (H1N1)

    PubMed Central

    Shieh, Wun-Ju; Blau, Dianna M.; Denison, Amy M.; DeLeon-Carnes, Marlene; Adem, Patricia; Bhatnagar, Julu; Sumner, John; Liu, Lindy; Patel, Mitesh; Batten, Brigid; Greer, Patricia; Jones, Tara; Smith, Chalanda; Bartlett, Jeanine; Montague, Jeltley; White, Elizabeth; Rollin, Dominique; Gao, Rongbao; Seales, Cynthia; Jost, Heather; Metcalfe, Maureen; Goldsmith, Cynthia S.; Humphrey, Charles; Schmitz, Ann; Drew, Clifton; Paddock, Christopher; Uyeki, Timothy M.; Zaki, Sherif R.

    2010-01-01

    In the spring of 2009, a novel influenza A (H1N1) virus emerged in North America and spread worldwide to cause the first influenza pandemic since 1968. During the first 4 months, over 500 deaths in the United States had been associated with confirmed 2009 pandemic influenza A (H1N1) [2009 H1N1] virus infection. Pathological evaluation of respiratory specimens from initial influenza-associated deaths suggested marked differences in viral tropism and tissue damage compared with seasonal influenza and prompted further investigation. Available autopsy tissue samples were obtained from 100 US deaths with laboratory-confirmed 2009 H1N1 virus infection. Demographic and clinical data of these case-patients were collected, and the tissues were evaluated by multiple laboratory methods, including histopathological evaluation, special stains, molecular and immunohistochemical assays, viral culture, and electron microscopy. The most prominent histopathological feature observed was diffuse alveolar damage in the lung in all case-patients examined. Alveolar lining cells, including type I and type II pneumocytes, were the primary infected cells. Bacterial co-infections were identified in >25% of the case-patients. Viral pneumonia and immunolocalization of viral antigen in association with diffuse alveolar damage are prominent features of infection with 2009 pandemic influenza A (H1N1) virus. Underlying medical conditions and bacterial co-infections contributed to the fatal outcome of this infection. More studies are needed to understand the multifactorial pathogenesis of this infection. PMID:20508031

  8. H1N1 influenza pneumonia and bacterial coinfection.

    PubMed

    Calbo, Esther; Robles, Alejandro; Sangil, Anna; Benet, Susana; Viladot, Maria Eugenia; Pascual, Vanesa; Barreiro, Bienvenido

    2011-12-01

    The model described by Bewick et al seems to be able to distinguish between H1N1 influenza-related pneumonia and non-H1N1 community acquired pneumonia (CAP) based on five criteria. However, bacterial infection in the influenza group has not been accurately excluded. Therefore, this model could misidentify these patients and lead to an inappropriate treatment. We conducted a prospective observational study to compare mixed pneumonia vs viral pneumonia. In the mixed pneumonia group patients were older, had higher levels of procalcitonine and higher scores of severity. In our cohort the model proposed by Bewick et al would not identify patients with coinfection. PMID:21994246

  9. 'Rhyme or reason?' Saying no to mass vaccination: subjective re-interpretation in the context of the A(H1N1) influenza pandemic in Sweden 2009-2010.

    PubMed

    Lundgren, Britta

    2015-12-01

    During the swine flu pandemic of 2009-2010, all Swedish citizens were recommended to be vaccinated with the influenza vaccine Pandemrix. However, a very serious and unexpected side effect emerged during the summer of 2010: more than 200 children and young adults were diagnosed with narcolepsy after vaccination. Besides the tragic outcome for these children and their families, this adverse side effect suggests future difficulties in obtaining trust in vaccination in cases of emerging pandemics, and thus there is a growing need to find ways to understand the complexities of vaccination decision processes. This article explores written responses to a questionnaire from a Swedish folk life archive as an unconventional source for analysing vaccine decisions. The aim is to investigate how laypersons responded to and re-interpreted the message about the recommended vaccination in their answers. The answers show the confusion and complex circumstances and influences in everyday life that people reflect on when making such important decisions. The issue of confusion is traced back to the initial communications about the vaccination intervention in which both autonomy and solidarity were expected from the population. Common narratives and stories about the media or 'big pharma capitalism' are entangled with private memories, accidental coincidences and serendipitous associations. It is obvious that vaccination interventions that require compliance from large groups of people need to take into account the kind of personal experience narratives that are produced by the complex interplay of the factors described by the informants. PMID:26077985

  10. 'Rhyme or reason?' Saying no to mass vaccination: subjective re-interpretation in the context of the A(H1N1) influenza pandemic in Sweden 2009-2010.

    PubMed

    Lundgren, Britta

    2015-12-01

    During the swine flu pandemic of 2009-2010, all Swedish citizens were recommended to be vaccinated with the influenza vaccine Pandemrix. However, a very serious and unexpected side effect emerged during the summer of 2010: more than 200 children and young adults were diagnosed with narcolepsy after vaccination. Besides the tragic outcome for these children and their families, this adverse side effect suggests future difficulties in obtaining trust in vaccination in cases of emerging pandemics, and thus there is a growing need to find ways to understand the complexities of vaccination decision processes. This article explores written responses to a questionnaire from a Swedish folk life archive as an unconventional source for analysing vaccine decisions. The aim is to investigate how laypersons responded to and re-interpreted the message about the recommended vaccination in their answers. The answers show the confusion and complex circumstances and influences in everyday life that people reflect on when making such important decisions. The issue of confusion is traced back to the initial communications about the vaccination intervention in which both autonomy and solidarity were expected from the population. Common narratives and stories about the media or 'big pharma capitalism' are entangled with private memories, accidental coincidences and serendipitous associations. It is obvious that vaccination interventions that require compliance from large groups of people need to take into account the kind of personal experience narratives that are produced by the complex interplay of the factors described by the informants.

  11. Surveillance of perceptions, knowledge, attitudes and behaviors of the Italian adult population (18-69 years) during the 2009-2010 A/H1N1 influenza pandemic.

    PubMed

    Ferrante, Gianluigi; Baldissera, Sandro; Moghadam, Pirous Fateh; Carrozzi, Giuliano; Trinito, Massimo Oddone; Salmaso, Stefania

    2011-03-01

    Monitoring perceptions, knowledge, attitudes and behaviors of populations during pandemic flu outbreaks is important as it allows communication strategies to be adjusted to meet emerging needs and assessment to be made of the effects of recommendations for prevention. The ongoing Italian Behavioral Risk Factor Surveillance System (PASSI) offered the setting for investigating people's opinions and behaviors regarding the A/H1N1 pandemic. PASSI surveillance is carried out in 126/148 Italian Local Health Units (LHU) through monthly telephone interviews administered by public health staff to a random sample of the resident population 18-69 years. In fall 2009 additional questions exploring issues related to the A/H1N1 flu were added to the standard questionnaire. The pandemic module was administered on a voluntary basis by the 70 participating LHUs from November 2nd, 2009 to February 7th, 2010; 4 047 interviews were collected. Overall 33% of respondents considered it likely that they would catch flu, 26% stated they were worried, 16% reported having limited some daily activities out of home and 22% said they would accept vaccination if offered. All these indicators showed a decreasing trend across the four-month period of observation. The most trusted sources of information were family doctors (81%). Willingness to be vaccinated was associated with worry about pandemic, age, sex, having a chronic disease and timing of the interview. The surveillance allowed us to gather relevant information, crucial for devising appropriate public health interventions. In future disease outbreaks, systems monitoring people's perceptions and behaviors should be included in the preparedness and response plans.

  12. Surveillance for adverse events following receipt of pandemic 2009 H1N1 vaccine in the Post-Licensure Rapid Immunization Safety Monitoring (PRISM) System, 2009-2010.

    PubMed

    Yih, W Katherine; Lee, Grace M; Lieu, Tracy A; Ball, Robert; Kulldorff, Martin; Rett, Melisa; Wahl, Peter M; McMahill-Walraven, Cheryl N; Platt, Richard; Salmon, Daniel A

    2012-06-01

    The Post-Licensure Rapid Immunization Safety Monitoring (PRISM) system is a cohort-based active surveillance network initiated by the US Department of Health and Human Services to supplement preexisting and other vaccine safety monitoring systems in tracking the safety of monovalent pandemic 2009 H1N1 influenza vaccine in the United States during 2009-2010. PRISM investigators conducted retrospective analysis to determine whether 2009 H1N1 vaccination was associated with increased risk of any of 14 prespecified outcomes. Five health insurance and associated companies with 38 million members and 9 state/city immunization registries contributed records on more than 2.6 million doses of 2009 H1N1 vaccine. Data on outcomes came from insurance claims. Complementary designs (self-controlled risk interval, case-centered, and current-vs.-historical comparison) were used to optimize control for confounding and statistical power. The self-controlled risk interval analysis of chart-confirmed Guillain-Barré syndrome found an elevated but not statistically significant incidence rate ratio following receipt of inactivated 2009 H1N1 vaccine (incidence rate ratio = 2.50, 95% confidence interval: 0.42, 15.0) and no cases following live attenuated 2009 H1N1 vaccine. The study did not control for infection prior to Guillain-Barré syndrome, which may have been a confounder. The risks of other health outcomes of interest were generally not significantly elevated after 2009 H1N1 vaccination.

  13. Modeling control strategies for concurrent epidemics of seasonal and pandemic H1N1 influenza.

    PubMed

    Prosper, Olivia; Saucedo, Omar; Thompson, Doria; Torres-Garcia, Griselle; Wang, Xiaohong; Castillo-Chavez, Carlos

    2011-01-01

    The lessons learned from the 2009-2010 H1N1 influenza pandemic, as it moves out of the limelight, should not be under-estimated, particularly since the probability of novel influenza epidemics in the near future is not negligible and the potential consequences might be huge. Hence, as the world, particularly the industrialized world, responded to the potentially devastating effects of this novel A-H1N1 strain with substantial resources, reminders of the recurrent loss of life from a well established foe, seasonal influenza, could not be ignored. The uncertainties associated with the reported and expected levels of morbidity and mortality with this novel A-H1N1 live in a backdrop of deaths, over 200,000 hospitalizations, and millions of infections (20% of the population) attributed to seasonal influenza in the USA alone, each year. So, as the Northern Hemisphere braced for the possibility of a potentially "lethal" second wave of the novel A-H1N1 without a vaccine ready to mitigate its impact, questions of who should be vaccinated first if a vaccine became available, came to the forefront of the discussion. Uncertainty grew as we learned that the vaccine, once available, would be unevenly distributed around the world. Nations capable of acquiring large vaccine supplies soon became aware that those who could pay would have to compete for a limited vaccine stockpile. The challenges faced by nations dealing jointly with seasonal and novel A-H1N1 co-circulating strains under limited resources, that is, those with no access to novel A-H1N1 vaccine supplies, limited access to the seasonal influenza vaccine, and limited access to antivirals (like Tamiflu) are explored in this study. One- and two-strain models are introduced to mimic the influenza dynamics of a single and co-circulating strains, in the context of a single epidemic outbreak. Optimal control theory is used to identify and evaluate the "best" control policies. The controls account for the cost associated with

  14. Experimental infection with H1N1 European swine influenza virus protects pigs from an infection with the 2009 pandemic H1N1 human influenza virus.

    PubMed

    Busquets, Núria; Segalés, Joaquim; Córdoba, Lorena; Mussá, Tufaria; Crisci, Elisa; Martín-Valls, Gerard E; Simon-Grifé, Meritxell; Pérez-Simó, Marta; Pérez-Maíllo, Monica; Núñez, Jose I; Abad, Francesc X; Fraile, Lorenzo; Pina, Sonia; Majó, Natalia; Bensaid, Albert; Domingo, Mariano; Montoya, María

    2010-01-01

    The recent pandemic caused by human influenza virus A(H1N1) 2009 contains ancestral gene segments from North American and Eurasian swine lineages as well as from avian and human influenza lineages. The emergence of this A(H1N1) 2009 poses a potential global threat for human health and the fact that it can infect other species, like pigs, favours a possible encounter with other influenza viruses circulating in swine herds. In Europe, H1N1, H1N2 and H3N2 subtypes of swine influenza virus currently have a high prevalence in commercial farms. To better assess the risk posed by the A(H1N1) 2009 in the actual situation of swine farms, we sought to analyze whether a previous infection with a circulating European avian-like swine A/Swine/Spain/53207/2004 (H1N1) influenza virus (hereafter referred to as SwH1N1) generated or not cross-protective immunity against a subsequent infection with the new human pandemic A/Catalonia/63/2009 (H1N1) influenza virus (hereafter referred to as pH1N1) 21 days apart. Pigs infected only with pH1N1 had mild to moderate pathological findings, consisting on broncho-interstitial pneumonia. However, pigs inoculated with SwH1N1 virus and subsequently infected with pH1N1 had very mild lung lesions, apparently attributed to the remaining lesions caused by SwH1N1 infection. These later pigs also exhibited boosted levels of specific antibodies. Finally, animals firstly infected with SwH1N1 virus and latter infected with pH1N1 exhibited undetectable viral RNA load in nasal swabs and lungs after challenge with pH1N1, indicating a cross-protective effect between both strains.

  15. Scales of governance: the role of surveillance in facilitating new diplomacy during the 2009-2010 H1N1 pandemic.

    PubMed

    Bell, Morag; Warren, Adam; Budd, Lucy

    2012-11-01

    The 2009-2010 H1N1 influenza pandemic has highlighted the importance of global health surveillance. Increasingly, global alerts are based on 'unexpected' 'events' detected by surveillance systems grounded in particular places. An emerging global governance literature investigates the supposedly disruptive impact of public health emergencies on mobilities in an interdependent world. Little consideration has been given to the varied scales of governance--local, national and global--that operate at different stages in the unfolding of an 'event', together with the interactions and tensions between them. By tracking the chronology of the H1N1 pandemic, this paper highlights an emergent dialogue between local and global scales. It also draws attention to moments of national autonomy across the global North and South which undermined the WHO drive for transnational cooperation. PMID:22884291

  16. Scales of governance: the role of surveillance in facilitating new diplomacy during the 2009-2010 H1N1 pandemic.

    PubMed

    Bell, Morag; Warren, Adam; Budd, Lucy

    2012-11-01

    The 2009-2010 H1N1 influenza pandemic has highlighted the importance of global health surveillance. Increasingly, global alerts are based on 'unexpected' 'events' detected by surveillance systems grounded in particular places. An emerging global governance literature investigates the supposedly disruptive impact of public health emergencies on mobilities in an interdependent world. Little consideration has been given to the varied scales of governance--local, national and global--that operate at different stages in the unfolding of an 'event', together with the interactions and tensions between them. By tracking the chronology of the H1N1 pandemic, this paper highlights an emergent dialogue between local and global scales. It also draws attention to moments of national autonomy across the global North and South which undermined the WHO drive for transnational cooperation.

  17. Factors Influencing School Closure and Dismissal Decisions: Influenza A (H1N1), Michigan 2009

    ERIC Educational Resources Information Center

    Dooyema, Carrie A.; Copeland, Daphne; Sinclair, Julie R.; Shi, Jianrong; Wilkins, Melinda; Wells, Eden; Collins, Jim

    2014-01-01

    Background: In fall 2009, many US communities experienced school closures during the influenza A H1N1 pandemic (pH1N1) and the state of Michigan reported 567 closures. We conducted an investigation in Michigan to describe pH1N1-related school policies, practices, and identify factors related to school closures. Methods: We distributed an online…

  18. Protective efficacy of an inactivated Eurasian avian-like H1N1 swine influenza vaccine against homologous H1N1 and heterologous H1N1 and H1N2 viruses in mice.

    PubMed

    Sui, Jinyu; Yang, Dawei; Qiao, Chuanling; Xu, Huiyang; Xu, Bangfeng; Wu, Yunpu; Yang, Huanliang; Chen, Yan; Chen, Hualan

    2016-07-19

    Eurasian avian-like H1N1 (EA H1N1) swine influenza viruses are prevalent in pigs in Europe and Asia, but occasionally cause human infection, which raises concern about their pandemic potential. Here, we produced a whole-virus inactivated vaccine with an EA H1N1 strain (A/swine/Guangxi/18/2011, SW/GX/18/11) and evaluated its efficacy against homologous H1N1 and heterologous H1N1 and H1N2 influenza viruses in mice. A strong humoral immune response, which we measured by hemagglutination inhibition (HI) and virus neutralization (VN), was induced in the vaccine-inoculated mice upon challenge. The inactivated SW/GX/18/11 vaccine provided complete protection against challenge with homologous SW/GX/18/11 virus in mice and provided effective protection against challenge with heterologous H1N1 and H1N2 viruses with distinctive genomic combinations. Our findings suggest that this EA H1N1 vaccine can provide protection against both homologous H1N1 and heterologous H1N1 or H1N2 virus infection. As such, it is an excellent vaccine candidate to prevent H1N1 swine influenza.

  19. Factors Affecting Medical Students' Uptake of the 2009 Pandemic Influenza A (H1N1) Vaccine.

    PubMed

    Lee, Siang I; Aung, Ei M; Chin, Ik S; Hing, Jeremy W; Mummadi, Sanghamitra; Palaniandy, Ghunavadee D; Jordan, Rachel

    2012-01-01

    Background. Pandemic influenza vaccination rate amongst healthcare workers in England 2009/2010 was suboptimal (40.3%). Targeting medical students before they enter the healthcare workforce is an attractive future option. This study assessed the H1N1 vaccine uptake rate amongst medical students and factors that influenced this. Methods. Anonymised, self-administered questionnaire at a medical school. Results. The uptake rate amongst 126 medical students offered the vaccine was 49.2% and intended uptake amongst 77 students was 63.6%. Amongst those offered the vaccine, the strongest barriers to acceptance were fear of side effects (67.9%), lack of vaccine information (50.9%), lack of perceived risk (45.3%), and inconvenience (35.8%). Having a chronic illness (OR 3.4 (95% CI 1.2-10.2)), 4th/5th year of study (OR 3.0 (95% CI 1.3-7.1)), and correct H1N1 knowledge (OR 2.6 (95% CI 1.1-6.0)) were positively associated with uptake. Non-white ethnicity was an independent negative predictor of uptake (OR 0.4 (95% CI 0.2-0.8)). Students who accepted the H1N1 vaccine were three times more likely (OR 3.1 (95% CI 1.2-7.7)) to accept future seasonal influenza vaccination. Conclusion. Efforts to increase uptake should focus on routine introduction of influenza vaccine and creating a culture of uptake during medical school years, evidence-based education on vaccination, and improving vaccine delivery. PMID:23251794

  20. Adoption of Preventive Measures and Attitudes toward the H1N1 Influenza Pandemic in Schools

    ERIC Educational Resources Information Center

    Pérez, Anna; Rodríguez, Tània; López, Maria José; Continente, Xavier; Nebot, Manel

    2016-01-01

    Background: This study describes the perceived impact of H1N1 influenza and the adoption of the recommended measures to address the pandemic in schools. Methods: A cross-sectional self-reported survey was conducted in 433 schools in Barcelona addressed to the school principal or the H1N1 influenza designated person. A descriptive analysis was…

  1. Swine influenza H1N1 virus induces acute inflammatory immune responses in pig lungs: a potential animal model for human H1N1 influenza virus.

    PubMed

    Khatri, Mahesh; Dwivedi, Varun; Krakowka, Steven; Manickam, Cordelia; Ali, Ahmed; Wang, Leyi; Qin, Zhuoming; Renukaradhya, Gourapura J; Lee, Chang-Won

    2010-11-01

    Pigs are capable of generating reassortant influenza viruses of pandemic potential, as both the avian and mammalian influenza viruses can infect pig epithelial cells in the respiratory tract. The source of the current influenza pandemic is H1N1 influenza A virus, possibly of swine origin. This study was conducted to understand better the pathogenesis of H1N1 influenza virus and associated host mucosal immune responses during acute infection in humans. Therefore, we chose a H1N1 swine influenza virus, Sw/OH/24366/07 (SwIV), which has a history of transmission to humans. Clinically, inoculated pigs had nasal discharge and fever and shed virus through nasal secretions. Like pandemic H1N1, SwIV also replicated extensively in both the upper and lower respiratory tracts, and lung lesions were typical of H1N1 infection. We detected innate, proinflammatory, Th1, Th2, and Th3 cytokines, as well as SwIV-specific IgA antibody in lungs of the virus-inoculated pigs. Production of IFN-γ by lymphocytes of the tracheobronchial lymph nodes was also detected. Higher frequencies of cytotoxic T lymphocytes, γδ T cells, dendritic cells, activated T cells, and CD4+ and CD8+ T cells were detected in SwIV-infected pig lungs. Concomitantly, higher frequencies of the immunosuppressive T regulatory cells were also detected in the virus-infected pig lungs. The findings of this study have relevance to pathogenesis of the pandemic H1N1 influenza virus in humans; thus, pigs may serve as a useful animal model to design and test effective mucosal vaccines and therapeutics against influenza virus.

  2. Pediatric Healthcare Response to Pandemic (H1N1) 2009 Influenza Stakeholder Meeting - Summary of Proceedings

    SciTech Connect

    HCTT CHE

    2010-01-01

    The goal of the meeting was to bring together subject matter experts to develop tools and resources for use by the pediatric healthcare community in response to 2009 (H1N1) pandemic influenza activity during the 2009 influenza season.

  3. [Epidemiology of Pandemic Influenza (H1N1) 2009 in Aichi Medical University Hospital].

    PubMed

    Tani, Hiroya; Yamagishi, Yuka; Fuzimaki, Eriko; Kishi, Takahiko; Goto, Minehiro; Mikamo, Hiroshige

    2010-01-01

    We have analyzed epidemiology of pandemic influenza (H1N1) 2009 in Aichi Medical University hospital. As a result, the characteristics of pandemic influenza (H1N1) 2009 was as follows. (1) The number of ordered rapid diagnostic test was 2.8 times compared with the seasonal influenza period. The number of ordered rapid diagnostic test of the seasonal influenza period had the peak in January to March. However, the peak in pandemic influenza (H1N1) 2009 was November. Also, the number of samples on the weekend had been more than that of the weekday. (2) Positive rate of each diagnostic kit did not have the difference between the seasonal influenza (31.3 ± 1.8%) and pandemic influenza (H1N1) 2009 (29.6%). (3) Age on most ordered samples were less than ten years old, and the number of samples in 11 to 20 years old was twice in comparison with the seasonal influenza. (4) Pandemic influenza (H1N1) 2009 in influenza A accounted for 96.9%. (5) Sensitivity and specificity of ESPLINE Influenza A&B-N (FUJIREBIO, Inc., Tokyo, Japan) to the pandemic influenza (H1N1) 2009 were 100% and 100%, respectively. Also, sensitivity and specificity of prorasuto Flu (Mitsubishi Chemical Medience Corporation, Tokyo, Japan) were 77.3%and 98.5%, respectively.

  4. Pathogenesis and transmission of triple-reassortant swine H1N1 influenza viruses isolated before the 2009 H1N1 pandemic.

    PubMed

    Belser, Jessica A; Gustin, Kortney M; Maines, Taronna R; Blau, Dianna M; Zaki, Sherif R; Katz, Jacqueline M; Tumpey, Terrence M

    2011-02-01

    The 2009 H1N1 pandemic influenza virus represents the greatest incidence of human infection with an influenza virus of swine origin to date. Moreover, triple-reassortant swine (TRS) H1N1 viruses, which share similar host and lineage origins with 2009 H1N1 viruses, have been responsible for sporadic human cases since 2005. Similar to 2009 H1N1 viruses, TRS viruses are capable of causing severe disease in previously healthy individuals and frequently manifest with gastrointestinal symptoms; however, their ability to cause severe disease has not been extensively studied. Here, we evaluated the pathogenicity and transmissibility of two TRS viruses associated with disease in humans in the ferret model. TRS and 2009 H1N1 viruses exhibited comparable viral titers and histopathologies following virus infection and were similarly unable to transmit efficiently via respiratory droplets in the ferret model. Utilizing TRS and 2009 H1N1 viruses, we conducted extensive hematologic and blood serum analyses on infected ferrets to identify lymphohematopoietic parameters associated with mild to severe influenza virus infection. Following H1N1 or H5N1 influenza virus infection, ferrets were found to recapitulate several laboratory abnormalities previously documented with human disease, furthering the utility of the ferret model for the assessment of influenza virus pathogenicity.

  5. Interleukin-6 Is a Potential Biomarker for Severe Pandemic H1N1 Influenza A Infection

    PubMed Central

    Paquette, Stéphane G.; Banner, David; Zhao, Zhen; Fang, Yuan; Huang, Stephen S. H.; Leόn, Alberto J.; Ng, Derek C. K.; Almansa, Raquel; Martin-Loeches, Ignacio; Ramirez, Paula; Socias, Lorenzo; Loza, Ana; Blanco, Jesus; Sansonetti, Paola; Rello, Jordi; Andaluz, David; Shum, Bianche; Rubino, Salvatore; de Lejarazu, Raul Ortiz; Tran, Dat; Delogu, Giovanni; Fadda, Giovanni; Krajden, Sigmund; Rubin, Barry B.; Bermejo-Martin, Jesús F.; Kelvin, Alyson A.; Kelvin, David J.

    2012-01-01

    Pandemic H1N1 influenza A (H1N1pdm) is currently a dominant circulating influenza strain worldwide. Severe cases of H1N1pdm infection are characterized by prolonged activation of the immune response, yet the specific role of inflammatory mediators in disease is poorly understood. The inflammatory cytokine IL-6 has been implicated in both seasonal and severe pandemic H1N1 influenza A (H1N1pdm) infection. Here, we investigated the role of IL-6 in severe H1N1pdm infection. We found IL-6 to be an important feature of the host response in both humans and mice infected with H1N1pdm. Elevated levels of IL-6 were associated with severe disease in patients hospitalized with H1N1pdm infection. Notably, serum IL-6 levels associated strongly with the requirement of critical care admission and were predictive of fatal outcome. In C57BL/6J, BALB/cJ, and B6129SF2/J mice, infection with A/Mexico/4108/2009 (H1N1pdm) consistently triggered severe disease and increased IL-6 levels in both lung and serum. Furthermore, in our lethal C57BL/6J mouse model of H1N1pdm infection, global gene expression analysis indicated a pronounced IL-6 associated inflammatory response. Subsequently, we examined disease and outcome in IL-6 deficient mice infected with H1N1pdm. No significant differences in survival, weight loss, viral load, or pathology were observed between IL-6 deficient and wild-type mice following infection. Taken together, our findings suggest IL-6 may be a potential disease severity biomarker, but may not be a suitable therapeutic target in cases of severe H1N1pdm infection due to our mouse data. PMID:22679491

  6. Seizures and retrograde amnesia with cerebrospinal fluid changes following H1N1 influenza vaccination.

    PubMed

    Mitrakrishnan, Shivanthan; Ranjanie, Gamage; Thirunavakarasu, Thivakaran; Manjula, Caldera; Nayananjani, Karunasena

    2011-08-26

    Vaccination against H1N1 influenza of healthcare workers of has been a standard measure to control the epidemic in many countries. Most side effects are minor and transient. Guillain Barre Syndrome and optic neuritis have been major concerns. We report a case of seizures with retrograde amnesia associated with cerebrospinal fluid changes following the H1N1 vaccine.

  7. Alice in Wonderland syndrome in H1N1 influenza: case report.

    PubMed

    Augarten, Arie; Aderka, Dan

    2011-02-01

    The different aspects of the global H1N1 influenza and its complications are currently of great interest. Neurological complications of the disease and its frequency are still unknown. We report a case of an 11-year-old girl who developed Alice in Wonderland syndrome associated with H1N1 influenza. This unique clinical syndrome was previously described in other diseases. The clinician's awareness of the existence of this syndrome in H1N1 influenza might save the child from undergoing extensive diagnostic procedures. PMID:21293218

  8. Comparative analyses of pandemic H1N1 and seasonal H1N1, H3N2, and influenza B infections depict distinct clinical pictures in ferrets.

    PubMed

    Huang, Stephen S H; Banner, David; Fang, Yuan; Ng, Derek C K; Kanagasabai, Thirumagal; Kelvin, David J; Kelvin, Alyson A

    2011-01-01

    Influenza A and B infections are a worldwide health concern to both humans and animals. High genetic evolution rates of the influenza virus allow the constant emergence of new strains and cause illness variation. Since human influenza infections are often complicated by secondary factors such as age and underlying medical conditions, strain or subtype specific clinical features are difficult to assess. Here we infected ferrets with 13 currently circulating influenza strains (including strains of pandemic 2009 H1N1 [H1N1pdm] and seasonal A/H1N1, A/H3N2, and B viruses). The clinical parameters were measured daily for 14 days in stable environmental conditions to compare clinical characteristics. We found that H1N1pdm strains had a more severe physiological impact than all season strains where pandemic A/California/07/2009 was the most clinically pathogenic pandemic strain. The most serious illness among seasonal A/H1N1 and A/H3N2 groups was caused by A/Solomon Islands/03/2006 and A/Perth/16/2009, respectively. Among the 13 studied strains, B/Hubei-Wujiagang/158/2009 presented the mildest clinical symptoms. We have also discovered that disease severity (by clinical illness and histopathology) correlated with influenza specific antibody response but not viral replication in the upper respiratory tract. H1N1pdm induced the highest and most rapid antibody response followed by seasonal A/H3N2, seasonal A/H1N1 and seasonal influenza B (with B/Hubei-Wujiagang/158/2009 inducing the weakest response). Our study is the first to compare the clinical features of multiple circulating influenza strains in ferrets. These findings will help to characterize the clinical pictures of specific influenza strains as well as give insights into the development and administration of appropriate influenza therapeutics.

  9. Pandemic H1N1 influenza surveillance in Haiti, July-December 2009.

    PubMed

    Fitter, David L; Freeman, Nicole M; Buteau, Josiane; Magloire, Roc; Sessions, Wendy M; Guo, Lizheng; Katz, Mark A; Boncy, Jacques

    2013-09-01

    From June 2009 through December 2009, Haiti conducted sentinel surveillance for influenza. 499 samples were collected and tested using real-time RT-PCR. 197 (39.5%) were positive for influenza, including 95 (48%) pandemic (H1N1) 2009, 57 (29%) seasonal influenza A and 45 (23%) influenza B. The median age of pandemic (H1N1) 2009 cases was 21.7; two-thirds of pandemic (H1N1) 2009 cases were in patients aged 6 years - 35 years. Pandemic activity peaked in September and co-circulated with other influenza subtypes. The age distribution and seasonality of pandemic (H1N1) 2009 in Haiti were similar to other countries in the Caribbean region.

  10. Antigenic Patterns and Evolution of the Human Influenza A (H1N1) Virus.

    PubMed

    Liu, Mi; Zhao, Xiang; Hua, Sha; Du, Xiangjun; Peng, Yousong; Li, Xiyan; Lan, Yu; Wang, Dayan; Wu, Aiping; Shu, Yuelong; Jiang, Taijiao

    2015-09-28

    The influenza A (H1N1) virus causes seasonal epidemics that result in severe illnesses and deaths almost every year. A deep understanding of the antigenic patterns and evolution of human influenza A (H1N1) virus is extremely important for its effective surveillance and prevention. Through development of antigenicity inference method for human influenza A (H1N1), named PREDAC-H1, we systematically mapped the antigenic patterns and evolution of the human influenza A (H1N1) virus. Eight dominant antigenic clusters have been inferred for seasonal H1N1 viruses since 1977, which demonstrated sequential replacements over time with a similar pattern in Asia, Europe and North America. Among them, six clusters emerged first in Asia. As for China, three of the eight antigenic clusters were detected in South China earlier than in North China, indicating the leading role of South China in H1N1 transmission. The comprehensive view of the antigenic evolution of human influenza A (H1N1) virus can help formulate better strategy for its prevention and control.

  11. Identification of reassortant pandemic H1N1 influenza virus in Korean pigs.

    PubMed

    Han, Jae Yeon; Park, Sung Jun; Kim, Hye Kwon; Rho, Semi; Nguyen, Giap Van; Song, Daesub; Kang, Bo Kyu; Moon, Hyung Jun; Yeom, Min Joo; Park, Bong Kyun

    2012-05-01

    Since the 2009 pandemic human H1N1 influenza A virus emerged in April 2009, novel reassortant strains have been identified throughout the world. This paper describes the detection and isolation of reassortant strains associated with human pandemic influenza H1N1 and swine influenza H1N2 (SIV) viruses in swine populations in South Korea. Two influenza H1N2 reassortants were detected, and subtyped by PCR. The strains were isolated using Madin- Darby canine kidney (MDCK) cells, and genetically characterized by phylogenetic analysis for genetic diversity. They consisted of human, avian, and swine virus genes that were originated from the 2009 pandemic H1N1 virus and a neuraminidase (NA) gene from H1N2 SIV previously isolated in North America. This identification of reassortment events in swine farms raises concern that reassortant strains may continuously circulate within swine populations, calling for the further study and surveillance of pandemic H1N1 among swine.

  12. Co-circulation of pandemic 2009 H1N1, classical swine H1N1 and avian-like swine H1N1 influenza viruses in pigs in China.

    PubMed

    Chen, Yan; Zhang, Jian; Qiao, Chuanling; Yang, Huanliang; Zhang, Ying; Xin, Xiaoguang; Chen, Hualan

    2013-01-01

    The pandemic A/H1N1 influenza viruses emerged in both Mexico and the United States in March 2009, and were transmitted efficiently in the human population. They were transmitted occasionally from humans to other mammals including pigs, dogs and cats. In this study, we report the isolation and genetic analysis of novel viruses in pigs in China. These viruses were related phylogenetically to the pandemic 2009 H1N1 influenza viruses isolated from humans and pigs, which indicates that the pandemic virus is currently circulating in swine populations, and this hypothesis was further supported by serological surveillance of pig sera collected within the same period. Furthermore, we isolated another two H1N1 viruses belonging to the lineages of classical swine H1N1 virus and avian-like swine H1N1 virus, respectively. Multiple genetic lineages of H1N1 viruses are co-circulating in the swine population, which highlights the importance of intensive surveillance for swine influenza in China.

  13. Effectiveness of seasonal influenza vaccine against pandemic (H1N1) 2009 virus, Australia, 2010.

    PubMed

    Fielding, James E; Grant, Kristina A; Garcia, Katherine; Kelly, Heath A

    2011-07-01

    To estimate effectiveness of seasonal trivalent and monovalent influenza vaccines against pandemic influenza A (H1N1) 2009 virus, we conducted a test-negative case-control study in Victoria, Australia, in 2010. Patients seen for influenza-like illness by general practitioners in a sentinel surveillance network during 2010 were tested for influenza; vaccination status was recorded. Case-patients had positive PCRs for pandemic (H1N1) 2009 virus, and controls had negative influenza test results. Of 319 eligible patients, test results for 139 (44%) were pandemic (H1N1) 2009 virus positive. Adjusted effectiveness of seasonal vaccine against pandemic (H1N1) 2009 virus was 79% (95% confidence interval 33%-93%); effectiveness of monovalent vaccine was 47% and not statistically significant. Vaccine effectiveness was higher among adults. Despite some limitations, this study indicates that the first seasonal trivalent influenza vaccine to include the pandemic (H1N1) 2009 virus strain provided significant protection against laboratory-confirmed pandemic (H1N1) 2009 infection. PMID:21762570

  14. Zoonoses: USDA ARS Lessons Learned During Novel Influenza H1N1 Investigations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Influenza illness was first recognized in pigs during the 1918 human Spanish flu pandemic, and influenza A virus has since remained of importance to the swine industry as a primary respiratory pathogen. Influenza virus H1N1 remained relatively stable in U.S. swine for nearly 80 years following 1918...

  15. Influenza A(H1N1)pdm09 virus infection in giant pandas, China.

    PubMed

    Li, Desheng; Zhu, Ling; Cui, Hengmin; Ling, Shanshan; Fan, Shengtao; Yu, Zhijun; Zhou, Yuancheng; Wang, Tiecheng; Qian, Jun; Xia, Xianzhu; Xu, Zhiwen; Gao, Yuwei; Wang, Chengdong

    2014-03-01

    We confirmed infection with influenza A(H1N1)pdm09 in giant pandas in China during 2009 by using virus isolation and serologic analysis methods. This finding extends the host range of influenza viruses and indicates a need for increased surveillance for and control of influenza viruses among giant pandas. PMID:24565026

  16. Influenza A(H1N1)pdm09 virus infection in giant pandas, China.

    PubMed

    Li, Desheng; Zhu, Ling; Cui, Hengmin; Ling, Shanshan; Fan, Shengtao; Yu, Zhijun; Zhou, Yuancheng; Wang, Tiecheng; Qian, Jun; Xia, Xianzhu; Xu, Zhiwen; Gao, Yuwei; Wang, Chengdong

    2014-03-01

    We confirmed infection with influenza A(H1N1)pdm09 in giant pandas in China during 2009 by using virus isolation and serologic analysis methods. This finding extends the host range of influenza viruses and indicates a need for increased surveillance for and control of influenza viruses among giant pandas.

  17. Influenza virus A(H1N1)2009 antibody-dependent cellular cytotoxicity in young children prior to the H1N1 pandemic.

    PubMed

    Mesman, Annelies W; Westerhuis, Brenda M; Ten Hulscher, Hinke I; Jacobi, Ronald H; de Bruin, Erwin; van Beek, Josine; Buisman, Annemarie M; Koopmans, Marion P; van Binnendijk, Robert S

    2016-09-01

    Pre-existing immunity played a significant role in protection during the latest influenza A virus H1N1 pandemic, especially in older age groups. Structural similarities were found between A(H1N1)2009 and older H1N1 virus strains to which humans had already been exposed. Broadly cross-reactive antibodies capable of neutralizing the A(H1N1)2009 virus have been implicated in this immune protection in adults. We investigated the serological profile of a group of young children aged 9 years (n=55), from whom paired blood samples were available, just prior to the pandemic wave (March 2009) and shortly thereafter (March 2010). On the basis of A(H1N1)2009 seroconversion, 27 of the 55 children (49 %) were confirmed to be infected between these two time points. Within the non-infected group of 28 children (51 %), high levels of seasonal antibodies to H1 and H3 HA1 antigens were detected prior to pandemic exposure, reflecting past infection with H1N1 and H3N2, both of which had circulated in The Netherlands prior to the pandemic. In some children, this reactivity coincided with specific antibody reactivity against A(H1N1)2009. While these antibodies were not able to neutralize the A(H1N1)2009 virus, they were able to mediate antibody-dependent cellular cytotoxicity (ADCC) in vitro upon interaction with the A(H1N1)2009 virus. This finding suggests that cross-reactive antibodies could contribute to immune protection in children via ADCC.

  18. Pandemic and post-pandemic Influenza A (H1N1) infection in critically ill patients

    PubMed Central

    2011-01-01

    Background There is a vast amount of information published regarding the impact of 2009 pandemic Influenza A (pH1N1) virus infection. However, a comparison of risk factors and outcome during the 2010-2011 post-pandemic period has not been described. Methods A prospective, observational, multi-center study was carried out to evaluate the clinical characteristics and demographics of patients with positive RT-PCR for H1N1 admitted to 148 Spanish intensive care units (ICUs). Data were obtained from the 2009 pandemic and compared to the 2010-2011 post-pandemic period. Results Nine hundred and ninety-seven patients with confirmed An/H1N1 infection were included. Six hundred and forty-eight patients affected by 2009 (pH1N1) virus infection and 349 patients affected by the post-pandemic Influenza (H1N1)v infection period were analyzed. Patients during the post-pandemic period were older, had more chronic comorbid conditions and presented with higher severity scores (Acute Physiology And Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA)) on ICU admission. Patients from the post-pandemic Influenza (H1N1)v infection period received empiric antiviral treatment less frequently and with delayed administration. Mortality was significantly higher in the post-pandemic period. Multivariate analysis confirmed that haematological disease, invasive mechanical ventilation and continuous renal replacement therapy were factors independently associated with worse outcome in the two periods. HIV was the only new variable independently associated with higher ICU mortality during the post-pandemic Influenza (H1N1)v infection period. Conclusion Patients from the post-pandemic Influenza (H1N1)v infection period had an unexpectedly higher mortality rate and showed a trend towards affecting a more vulnerable population, in keeping with more typical seasonal viral infection. PMID:22126648

  19. H1N1pdm Influenza Infection in Hospitalized Cancer Patients: Clinical Evolution and Viral Analysis

    PubMed Central

    Bozza, Fernando A.; Mesquita, Milene; Soares, Márcio; Motta, Fernando C.; Pitrowsky, Melissa Tassano; de Lourdes Oliveira, Maria; Mishin, Vasiliy P.; Gubareva, Larissa V.; Whitney, Anne; Rocco, Sandra Amaral; Gonçalves, Vânia Maria C.; Marques, Venceslaine Prado; Velasco, Eduardo; Siqueira, Marilda M.

    2010-01-01

    Background The novel influenza A pandemic virus (H1N1pdm) caused considerable morbidity and mortality worldwide in 2009. The aim of the present study was to evaluate the clinical course, duration of viral shedding, H1N1pdm evolution and emergence of antiviral resistance in hospitalized cancer patients with severe H1N1pdm infections during the winter of 2009 in Brazil. Methods We performed a prospective single-center cohort study in a cancer center in Rio de Janeiro, Brazil. Hospitalized patients with cancer and a confirmed diagnosis of influenza A H1N1pdm were evaluated. The main outcome measures in this study were in-hospital mortality, duration of viral shedding, viral persistence and both functional and molecular analyses of H1N1pdm susceptibility to oseltamivir. Results A total of 44 hospitalized patients with suspected influenza-like illness were screened. A total of 24 had diagnosed H1N1pdm infections. The overall hospital mortality in our cohort was 21%. Thirteen (54%) patients required intensive care. The median age of the studied cohort was 14.5 years (3–69 years). Eighteen (75%) patients had received chemotherapy in the previous month, and 14 were neutropenic at the onset of influenza. A total of 10 patients were evaluated for their duration of viral shedding, and 5 (50%) displayed prolonged viral shedding (median 23, range = 11–63 days); however, this was not associated with the emergence of a resistant H1N1pdm virus. Viral evolution was observed in sequentially collected samples. Conclusions Prolonged influenza A H1N1pdm shedding was observed in cancer patients. However, oseltamivir resistance was not detected. Taken together, our data suggest that severely ill cancer patients may constitute a pandemic virus reservoir with major implications for viral propagation. PMID:21152402

  20. Experience of influenza A H1N1 in a paediatric emergency unit.

    PubMed

    Biçer, Suat; Ercan Sariçoban, Hülya; Özen, Ahmet Oğuzhan; Saf, Coşkun; Ergenekon Ulutaş, Pinar; Gürol, Yeşim; Yilmaz, Gülden; Vitrinel, Ayça; Özelgün, Berna

    2015-06-01

    This study was carried out to evaluate symptoms, clinical findings, treatment options and complications of H1N1 influenza infection in patients who applied to our emergency unit during the influenza season in 2009. The clinical and laboratory findings of children with influenza A (H1N1) during the influenza season in 2009 were evaluated retrospectively. Influenza A was diagnosed by polymerase chain reaction and/or rapid antigen test. Clinical and laboratory findings of the patients with H1N1 (group I) and without H1N1 (group II) were compared. Fever and myalgia were noted to be higher in group I (p <0.05). The mean body temperature in group I was 39.0?, which was statistically different from group II (p <0.001). Myalgia was observed only in group I (15.4%), but not in group II (p <0.05). There were three patients with diarrhoea, two of whom were in group I, and they had no significant respiratory symptoms. Lymphopenia was seen in 18 patients (81.8%) in group I and in four patients (23.5%) in group II (p <0.05). Oseltamivir treatment was applied to 28 patients, where 24 had severe symptoms, nine had comorbid factors and two did not have any of these. The fever was higher in group I and myalgia was present only in group I. In group I, the lymphocyte count was significantly lower than in group II. The fever was higher in patients of H1N1 (average of 39°C) and myalgia was present only in patients with H1N1. The lymphocyte count was significantly lower in patients with H1N1 than those without H1N1. While none of the patients required intensive care, three patients requiring hospitalization were discharged after referral and completion of their treatment.

  1. North American triple reassortant and Eurasian H1N1 swine influenza viruses do not readily reassort to generate a 2009 pandemic H1N1-like virus.

    PubMed

    Ma, Wenjun; Liu, Qinfang; Qiao, Chuanling; del Real, Gustavo; García-Sastre, Adolfo; Webby, Richard J; Richt, Jürgen A

    2014-03-11

    The 2009 pandemic H1N1 virus (pH1N1) was derived through reassortment of North American triple reassortant and Eurasian avian-like swine influenza viruses (SIVs). To date, when, how and where the pH1N1 arose is not understood. To investigate viral reassortment, we coinfected cell cultures and a group of pigs with or without preexisting immunity with a Eurasian H1N1 virus, A/Swine/Spain/53207/2004 (SP04), and a North American triple reassortant H1N1 virus, A/Swine/Kansas/77778/2007 (KS07). The infected pigs were cohoused with one or two groups of contact animals to investigate viral transmission. In coinfected MDCK or PK15 continuous cell lines with KS07 and SP04 viruses, more than 20 different reassortant viruses were found. In pigs without or with preexisting immunity (immunized with commercial inactivated swine influenza vaccines) and coinfected with both viruses, six or seven reassortant viruses, as well as the parental viruses, were identified in bronchoalveolar lavage fluid samples from the lungs. Interestingly, only one or two viruses transmitted to and were detected in contact animals. No reassortant containing a gene constellation similar to that of pH1N1 virus was found in either coinfected cells or pigs, indicating that the reassortment event that resulted in the generation of this virus is a rare event that likely involved specific viral strains and/or a favorable, not-yet-understood environment. IMPORTANCE The 2009 pandemic-like H1N1 virus could not be reproduced either in cell cultures or in pigs coinfected with North American triple reassortant H1N1 and Eurasian H1N1 swine influenza viruses. This finding suggests that the generation of the 2009 pandemic H1N1 virus by reassortment was a rare event that likely involved specific viral strains and unknown factors. Different reassortant viruses were detected in coinfected pigs with and without preexisting immunity, indicating that host immunity plays a relevant role in driving viral reassortment of

  2. Serological Evidence of Pandemic H1N1 Influenza Virus Infections in Greek Swine.

    PubMed

    Kyriakis, C S; Papatsiros, V G; Athanasiou, L V; Valiakos, G; Brown, I H; Simon, G; Van Reeth, K; Tsiodras, S; Spyrou, V; Billinis, C

    2016-08-01

    The introduction of the 2009 pandemic H1N1 (pH1N1) influenza virus in pigs changed the epidemiology of influenza A viruses (IAVs) in swine in Europe and the rest of the world. Previously, three IAV subtypes were found in the European pig population: an avian-like H1N1 and two reassortant H1N2 and H3N2 viruses with human-origin haemagglutinin (HA) and neuraminidase proteins and internal genes of avian decent. These viruses pose antigenically distinct HAs, which allow the retrospective diagnosis of infection in serological investigations. However, cross-reactions between the HA of pH1N1 and the HAs of the other circulating H1 IAVs complicate serological diagnosis. The prevalence of IAVs in Greek swine has been poorly investigated. In this study, we examined and compared haemagglutination inhibition (HI) antibody titres against previously established IAVs and pH1N1 in 908 swine sera from 88 herds, collected before and after the 2009 pandemic. While we confirmed the historic presence of the three IAVs established in European swine, we also found that 4% of the pig sera examined after 2009 had HI antibodies only against the pH1N1 virus. Our results indicate that pH1N1 is circulating in Greek pigs and stress out the importance of a vigorous virological surveillance programme. PMID:26477456

  3. Serological Evidence of Pandemic H1N1 Influenza Virus Infections in Greek Swine.

    PubMed

    Kyriakis, C S; Papatsiros, V G; Athanasiou, L V; Valiakos, G; Brown, I H; Simon, G; Van Reeth, K; Tsiodras, S; Spyrou, V; Billinis, C

    2016-08-01

    The introduction of the 2009 pandemic H1N1 (pH1N1) influenza virus in pigs changed the epidemiology of influenza A viruses (IAVs) in swine in Europe and the rest of the world. Previously, three IAV subtypes were found in the European pig population: an avian-like H1N1 and two reassortant H1N2 and H3N2 viruses with human-origin haemagglutinin (HA) and neuraminidase proteins and internal genes of avian decent. These viruses pose antigenically distinct HAs, which allow the retrospective diagnosis of infection in serological investigations. However, cross-reactions between the HA of pH1N1 and the HAs of the other circulating H1 IAVs complicate serological diagnosis. The prevalence of IAVs in Greek swine has been poorly investigated. In this study, we examined and compared haemagglutination inhibition (HI) antibody titres against previously established IAVs and pH1N1 in 908 swine sera from 88 herds, collected before and after the 2009 pandemic. While we confirmed the historic presence of the three IAVs established in European swine, we also found that 4% of the pig sera examined after 2009 had HI antibodies only against the pH1N1 virus. Our results indicate that pH1N1 is circulating in Greek pigs and stress out the importance of a vigorous virological surveillance programme.

  4. Akt inhibitor MK2206 prevents influenza pH1N1 virus infection in vitro.

    PubMed

    Denisova, Oxana V; Söderholm, Sandra; Virtanen, Salla; Von Schantz, Carina; Bychkov, Dmitrii; Vashchinkina, Elena; Desloovere, Jens; Tynell, Janne; Ikonen, Niina; Theisen, Linda L; Nyman, Tuula A; Matikainen, Sampsa; Kallioniemi, Olli; Julkunen, Ilkka; Muller, Claude P; Saelens, Xavier; Verkhusha, Vladislav V; Kainov, Denis E

    2014-07-01

    The influenza pH1N1 virus caused a global flu pandemic in 2009 and continues manifestation as a seasonal virus. Better understanding of the virus-host cell interaction could result in development of better prevention and treatment options. Here we show that the Akt inhibitor MK2206 blocks influenza pH1N1 virus infection in vitro. In particular, at noncytotoxic concentrations, MK2206 alters Akt signaling and inhibits endocytic uptake of the virus. Interestingly, MK2206 is unable to inhibit H3N2, H7N9, and H5N1 viruses, indicating that pH1N1 evolved specific requirements for efficient infection. Thus, Akt signaling could be exploited further for development of better therapeutics against pH1N1 virus. PMID:24752266

  5. Structural Basis of Preexisting Immunity to the 2009 H1N1 Pandemic Influenza Virus

    SciTech Connect

    Xu, Rui; Ekiert, Damian C.; Krause, Jens C.; Hai, Rong; Crowe, Jr., James E.; Wilson, Ian A.

    2010-05-25

    The 2009 H1N1 swine flu is the first influenza pandemic in decades. The crystal structure of the hemagglutinin from the A/California/04/2009 H1N1 virus shows that its antigenic structure, particularly within the Sa antigenic site, is extremely similar to those of human H1N1 viruses circulating early in the 20th century. The cocrystal structure of the 1918 hemagglutinin with 2D1, an antibody from a survivor of the 1918 Spanish flu that neutralizes both 1918 and 2009 H1N1 viruses, reveals an epitope that is conserved in both pandemic viruses. Thus, antigenic similarity between the 2009 and 1918-like viruses provides an explanation for the age-related immunity to the current influenza pandemic.

  6. Emergence and characterisation of pandemic H1N1 influenza viruses in Hungarian swine herds.

    PubMed

    Bálint, Adám; Kiss, István; Bányai, Krisztián; Biksi, Imre; Szentpáli-Gavallér, Katalin; Magyar, Tibor; Jankovics, István; Rózsa, Mónika; Szalai, Bálint; Takács, Mária; Tóth, Adám György; Dán, Adám

    2013-03-01

    In 2010, two novel porcine H1N1 influenza viruses were isolated from pigs with influenza-like illness in Hungarian swine herds. Sequence and phylogenetic analysis of these strains revealed that they shared molecular features with the pandemic H1N1 influenza virus strains, which emerged globally during 2009. The PB2, HA and NA genes contained unique amino acid changes compared to the available new H1N1 influenza virus sequences of pig origin. Furthermore, the investigated strains could be separated with respect to parallel amino acid substitutions affecting the polymerase genes (PB2, PB1 and PA) and the nucleoprotein (NP) gene, supporting the proposed complementarities between these proteins, all required for the viral fitness. Molecular characterisation of two Hungarian human pandemic H1N1 isolates was also performed, so that we could compare contemporaneous strains of different host species origins. Shared molecular motifs in various genes of animal and human influenza strains suggested that the Hungarian porcine strains could have originated from humans through direct interspecies transmission. This study is among the few that support the natural human-to-pig transmission of the pandemic H1N1 influenza virus.

  7. Pandemic influenza vaccine: characterization of A/California/07/2009 (H1N1) recombinant hemagglutinin protein and insights into H1N1 antigen stability

    PubMed Central

    2012-01-01

    Background The recent H1N1 influenza pandemic illustrated the shortcomings of the vaccine manufacturing process. The A/California/07/2009 H1N1 pandemic influenza vaccine or A(H1N1)pdm09 was available late and in short supply as a result of delays in production caused by low yields and poor antigen stability. Recombinant technology offers the opportunity to shorten manufacturing time. A trivalent recombinant hemagglutinin (rHA) vaccine candidate for seasonal influenza produced using the baculovirus expression vector system (BEVS) was shown to be as effective and safe as egg-derived trivalent inactivated vaccine (TIV) in human clinical studies. In this study, we describe the characterization of the A/California/07/2009 rHA protein and compare the H1N1 pandemic rHA to other seasonal rHA proteins. Results Our data show that, like other rHA proteins, purified A/California/07/2009 rHA forms multimeric rosette-like particles of 20–40 nm that are biologically active and immunogenic in mice as assayed by hemagglutination inhibition (HAI) antibody titers. However, proteolytic digest analysis revealed that A/California/07/2009 rHA is more susceptible to proteolytic degradation than rHA proteins derived from other seasonal influenza viruses. We identified a specific proteolytic site conserved across multiple hemagglutinin (HA) proteins that is likely more accessible in A/California/07/2009 HA, possibly as a result of differences in its protein structure, and may contribute to lower antigen stability. Conclusion We conclude that, similar to the recombinant seasonal influenza vaccine, recombinant A(H1N1)pdm09 vaccine is likely to perform comparably to licensed A(H1N1)pdm09 vaccines and could offer manufacturing advantages. PMID:23110350

  8. Supply of Neuraminidase Inhibitors Related to Reduced Influenza A (H1N1) Mortality during the 2009–2010 H1N1 Pandemic: An Ecological Study

    PubMed Central

    Hubbard, Roderick J.; Li, Jiabai; Meyer, Alison E.; Stephens, Peter; Mounts, Anthony W.; Rolfes, Melissa A.; Penn, Charles R.

    2012-01-01

    Background The influenza A (H1N1) pandemic swept across the globe from April 2009 to August 2010 affecting millions. Many WHO Member States relied on antiviral drugs, specifically neuraminidase inhibitors (NAIs) oseltamivir and zanamivir, to treat influenza patients in critical condition. Such drugs have been found to be effective in reducing severity and duration of influenza illness, and likely reduced morbidity during the pandemic. However, it is less clear whether NAIs used during the pandemic reduced H1N1 mortality. Methods Country-level data on supply of oseltamivir and zanamivir were used to predict H1N1 mortality (per 100,000 people) from July 2009 to August 2010 in forty-two WHO Member States. Poisson regression was used to model the association between NAI supply and H1N1 mortality, with adjustment for economic, demographic, and health-related confounders. Results After adjustment for potential confounders, each 10% increase in kilograms of oseltamivir, per 100,000 people, was associated with a 1.6% reduction in H1N1 mortality over the pandemic period (relative rate (RR) = 0.84 per log increase in oseltamivir supply). While the supply of zanamivir was considerably less than that of oseltamivir in each Member State, each 10% increase in kilogram of active zanamivir, per 100,000, was associated with a 0.3% reduction in H1N1 mortality (RR = 0.97 per log increase). Conclusion While there are limitations to the ecologic nature of these data, this analysis offers evidence of a protective relationship between antiviral drug supply and influenza mortality and supports a role for influenza antiviral use in future pandemics. PMID:22984431

  9. Seroprevalence following the first wave of pandemic influenza A (H1N1) in Turkey, 2009.

    PubMed

    Gözalan, Ayşegül; Altaş, Ayşe Başak; Sevencan, Funda; Akın, Levent; Korukluoğlu, Gülay; Kara, Sükran; Sevindi, Demet Furkan; Ertek, Mustafa

    2012-01-01

    In this study, we sought to describe the community seropositivity of pandemic influenza A (H1N1) in order to estimate immunity shortly after the peak of the first pandemic wave in two provinces in Turkey. This cross-sectional study was conducted in the provinces of Diyarbakir and Ankara, after the first wave of H1N1 incidences in 2009. It was designed to evaluate 276 houses in Diyarbakir and 455 houses in Ankara. Everyone living in these houses was included in the study. An antibody titer of ≥1:40 was considered as a positive result for all age groups. Antibody titers of ≤1:20 were considered as 1 while calculating the log titer and geometric mean. The pandemic H1N1 seropositivity was found to be 24.1% for Ankara and 27.7% for Diyarbakir. In Ankara, seropositivity was statistically associated with the 15-24 age group (odds ratio [OR] = 11.47), pandemic influenza A (H1N1) vaccination (OR = 20.95), and influenza-like illness history (OR = 1.60). In Diyarbakir, H1N1 seropositivity was associated with the 15-24 age group (OR = 8.99) and pandemic influenza A (H1N1) vaccination (OR = 9.94). Because individuals less than 25 years old played an important role in the community transmission of infection and were largely protected against the pandemic influenza A (H1N1) virus, these individuals should be given a high priority for pandemic influenza vaccination in the event of the emergence of another novel pandemic strain.

  10. The resurgence of swine-origin influenza A (H1N1).

    PubMed

    Mossad, Sherif Beniameen

    2009-06-01

    Unexpectedly, swine-origin influenza A (H1N1) virus (S-OIV, informally known as swine flu) appeared in North America at the very end of the 2008-2009 influenza season and began to spread internationally. As the world mobilizes for a potential pandemic, this article summarizes the developments in diagnosis, treatment, and prevention. PMID:19487554

  11. Enhanced Pneumonia With Pandemic 2009 A/H1N1 Swine Influenza Virus in Pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction. Swine influenza A viruses (SIV) in the major swine producing regions of North America consist of multiple subtypes of endemic H1N1, H1N2, and H3N2 derived from swine, avian and human influenza viruses with a triple reassortant internal gene (TRIG) constellation (1). Genetic drift and r...

  12. Influenza virus A (H1N1) in giant anteaters (Myrmecophaga tridactyla).

    PubMed

    Nofs, Sally; Abd-Eldaim, Mohamed; Thomas, Kathy V; Toplon, David; Rouse, Dawn; Kennedy, Melissa

    2009-07-01

    In February 2007, an outbreak of respiratory disease occurred in a group of giant anteaters (Myrmecophaga tridactyla) at the Nashville Zoo. Isolates from 2 affected animals were identified in March 2007 as a type A influenza virus related to human influenza subtype H1N1.

  13. Community transmission of pandemic influenza A (H1N1) in China.

    PubMed

    Liu, Wei; Jiang, Tao; Li, Xiao-Feng; Tang, Fang; Wei, Mao-Ti; Yu, Man; Zhao, Hui; Yu, Xue-Dong; Liu, Li-Juan; Qin, Cheng-Feng; Cao, Wu-Chun

    2010-09-01

    Prophylaxis and treatment with oseltamivir effectively controlled a community outbreak of pandemic influenza A (H1N1) in China. The genetic makeup of strains of different generations seemed to be stable. Travel in confined settings might accelerate the transmission of pandemic influenza in a community outbreak. PMID:20636129

  14. Two seasons' experience with pandemic A H1N1 influenza infection in neonates.

    PubMed

    Martic, Jelena; Savic, Natasa; Jankovic, Borisav; Nedeljkovic, Jasminka; Rakonjac, Zorika; Pejic, Katarina; Markovic-Sovtic, Gordana

    2012-01-01

    There are only a few reports on influenza A H1N1 infection in neonates. In this paper, we present our additional experience on the clinical characteristics, epidemiology and treatment of influenza A H1N1 (2009) infection in 10 newborn infants (aged 9-24 days). Influenza A H1N1 infection was confirmed by real-time reverse transcription-polymerase chain reaction of the nasopharyngeal swab specimens. The majority of neonates presented with fever, respiratory symptoms and lethargy. The respiratory illness ranged from mild symptoms to severe pneumonia requiring mechanical ventilation. Antiviral treatment with oseltamivir was started in five patients (50%). One lethal outcome was observed, while nine patients (90%) had complete recovery. To our knowledge, this is the largest presented series of neonatal cases with different clinical symptoms. We discuss the necessity of initiation of oseltamivir in infants with different clinical features.

  15. Serological survey of 2009 H1N1 influenza in residents of Beijing, China.

    PubMed

    Deng, Y; Pang, X H; Yang, P; Shi, W X; Tian, L L; Liu, B W; Li, S; Cui, S J; Li, Y; Lu, G L; Zhang, L; Zhang, X; Liu, B; Seale, H; Huang, F; Wang, Q Y

    2011-01-01

    In order to determine the prevalence of antibody against 2009 H1N1 influenza in Beijing, we conducted a serological survey in 710 subjects, 1 month after the epidemic peak. We found that 13·8% of our cohort was seropositive. Subjects aged ≥60 years recorded the lowest seroprevalence (4·5%). The age-weighted seroprevalence of 14·0% was far lower than the supposed infection rate at the epidemic peak, derived from the basic reproduction number for 2009 H1N1 virus. For subjects who had received the pandemic vaccine seroprevalence was 51·4%. In subjects aged ≥60 years the seasonal influenza vaccination was not significantly associated with being seropositive. Our study suggests that many factors, and not just the immunological level against 2009 H1N1 influenza in the community, affected the spread of the virus within the population of Beijing. PMID:20854713

  16. Phylogenetic evolution of swine-origin human influenza virus: a pandemic H1N1 2009.

    PubMed

    Kowalczyk, A; Markowska-Daniel, I

    2010-01-01

    The knowledge of the genome constellation in pandemic influenza A virus H1N1 2009 from different countries and different hosts is valuable for monitoring and understanding of the evolution and migration of these strains. The complete genome sequences of selected worldwide distributed influenza A viruses are publicly available and there have been few longitudinal genome studies of human, avian and swine influenza A viruses. All possible to download SIV sequences of influenza A viruses available at GISAID Platform (Global Initiative on Sharing Avian Influenza Data) were analyzed firstly through the web servers of the Influenza Virus Resource in NCBI. Phylogenetic study of circulating human pandemic H1N1 virus indicated that the new variant possesses a distinctive evolutionary trait. There is no one way the pandemic H1N1 have acquired new genes from other distinguishable viruses circulating recently in local human, pig or domestic poultry populations from various geographic regions. The extensive genetic diversity among whole segments present in pandemic H1N1 genome suggests that multiple introduction of virus have taken place during the period 1999-2009. The initial interspecies transmission could have occurred in the long-range past and after it the reassortants steps lead to three lineages: classical SIV prevalent in the North America, avian-like SIV in Europe and avian-like related SIV in Asia. This analysis contributes to the evidence that pigs are not the only hosts playing the role of "mixing vessel", as it was suggested for many years.

  17. Influenza A/H1N1 Severe Pneumonia: Novel Morphocytological Findings in Bronchoalveolar Lavage

    PubMed Central

    Faverio, Paola; Messinesi, Grazia; Brenna, Ambrogio; Pesci, Alberto

    2014-01-01

    We present the results of bronchoalveolar lavage (BAL) performed in three patients with severe influenza A/H1N1 pneumonia complicated by acute respiratory distress syndrome (ARDS). Light microscopy analysis of BAL cytocentrifugates showed the presence of characteristic large, mononuclear, plasmoblastic/plasmocytoid-like cells never described before. Via transmission electron microscopy, these cells were classified as atypical type II pneumocytes and some of them showed cytoplasmic vesicles and inclusions. We concluded that plasmoblastic/plasmocytoid-like type II pneumocytes might represent a morphologic marker of A/H1N1 influenza virus infection as well as reparative cellular activation after diffuse alveolar damage. PMID:25383078

  18. Boosting Heterosubtypic Neutralization Antibodies in Recipients of 2009 Pandemic H1N1 Influenza Vaccine

    PubMed Central

    Qiu, Chao; Huang, Yang; Wang, Qian; Tian, Di; Zhang, Wanju; Hu, Yunwen; Yuan, Zhenghong; Zhang, Xiaoyan

    2012-01-01

    Background. A mass vaccination has been implemented to prevent the spread of 2009 pandemic influenza virus in China. Highly limited information is available on whether this vaccine induces cross-reactive neutralization antibodies against other subtypes of influenza viruses. Methods. We employed pseudovirus-based assays to analyze heterosubtypic neutralization responses in serum samples of 23 recipients of 2009 pandemic influenza vaccine. Results. One dose of pandemic vaccine not only stimulated good neutralization antibodies against cognate influenza virus 2009 influenza A (H1N1), but also raised broad cross-reactive neutralization activities against seasonal H3N2 and highly pathogenic avian influenza virus H5N1 and lesser to H2N2. The cross-reactive neutralization activities were completely abolished after the removal of immunoglobin G (IgG). In contrast, H1N1 vaccination alone in influenza-naive mice elicited only vigorous homologous neutralizing activities but not cross-reactive neutralization activities. Conclusions. Our data suggest that the cross-reactive neutralization epitopes do exist in this vaccine and could elicit significant cross-reactive neutralizing IgG antibodies in the presence of preexisting responses. The exposure to H1N1 vaccine is likely to modify the hierarchical order of preexisting immune responses to influenza viruses. These findings provide insights into the evolution of human immunity to influenza viruses after experiencing multiple influenza virus infections and vaccinations. PMID:22052887

  19. Influenza A(H1N1)pdm09 during air travel

    PubMed Central

    Neatherlin, John; Cramer, Elaine H.; Dubray, Christine; Marienau, Karen J.; Russell, Michelle; Sun, Hong; Whaley, Melissa; Hancock, Kathy; Duong, Krista K.; Kirking, Hannah L.; Schembri, Christopher; Katz, Jacqueline M.; Cohen, Nicole J.; Fishbein, Daniel B.

    2015-01-01

    Summary The global spread of the influenza A(H1N1)pdm09 virus (pH1N1) associated with travelers from North America during the onset of the 2009 pandemic demonstrates the central role of international air travel in virus migration. To characterize risk factors for pH1N1 transmission during air travel, we investigated travelers and airline employees from four North American flights carrying ill travelers with confirmed pH1N1 infection. Of 392 passengers and crew identified, information was available for 290 (74%) passengers were interviewed. Overall attack rates for acute respiratory infection and influenza-like illness 1–7 days after travel were 5.2% and 2.4% respectively. Of 43 individuals that provided sera, 4 (9.3%) tested positive for pH1N1 antibodies, including 3 with serologic evidence of asymptomatic infection. Investigation of novel influenza aboard aircraft may be instructive. However, beyond the initial outbreak phase, it may compete with community-based mitigation activities, and interpretation of findings will be difficult in the context of established community transmission. PMID:23523241

  20. Challenge of N95 Filtering Facepiece Respirators with Viable H1N1 Influenza Aerosols

    PubMed Central

    Harnish, Delbert A.; Heimbuch, Brian K.; Husband, Michael; Lumley, April E.; Kinney, Kimberly; Shaffer, Ronald E.; Wander, Joseph D.

    2015-01-01

    OBJECTIVE Specification of appropriate personal protective equipment for respiratory protection against influenza is somewhat controversial. In a clinical environment, N95 filtering facepiece respirators (FFRs) are often recommended for respiratory protection against infectious aerosols. This study evaluates the ability of N95 FFRs to capture viable H1N1 influenza aerosols. METHODS Five N95 FFR models were challenged with aerosolized viable H1N1 influenza and inert polystyrene latex particles at continuous flow rates of 85 and 170 liters per minute. Virus was assayed using Madin-Darby canine kidney cells to determine the median tissue culture infective dose (TCID50). Aerosols were generated using a Collison nebulizer containing H1N1 influenza virus at 1 × 108 TCID50/mL. To determine filtration efficiency, viable sampling was performed upstream and downstream of the FFR. RESULTS N95 FFRs filtered 0.8-µm particles of both H1N1 influenza and inert origins with more than 95% efficiency. With the exception of 1 model, no statistically significant difference in filtration performance was observed between influenza and inert particles of similar size. Although statistically significant differences were observed for 2 models when comparing the 2 flow rates, the differences have no significance to protection. CONCLUSIONS This study empirically demonstrates that a National Institute for Occupational Safety and Health–approved N95 FFR captures viable H1N1 influenza aerosols as well as or better than its N95 rating, suggesting that a properly fitted FFR reduces inhalation exposure to airborne influenza virus. This study also provides evidence that filtration efficiency is based primarily on particle size rather than the nature of the particle’s origin. PMID:23571366

  1. The novel influenza A (H1N1) virus pandemic: An update

    PubMed Central

    Petrosillo, N.; Di Bella, S.; Drapeau, C. M.; Grilli, E.

    2009-01-01

    In the 4 months since it was first recognized, the pandemic strain of a novel influenza A (H1N1) virus has spread to all continents and, after documentation of human-to-human transmission of the virus in at least three countries in two separate World Health Organization (WHO) regions, the pandemic alert was raised to level 6. The agent responsible for this pandemic, a swine-origin influenza A (H1N1) virus (S-OIV), is characterized by a unique combination of gene segments that has not previously been identified among human or swine influenza A viruses. As of 31th July 2009, 168 countries and overseas territories/communities have each reported at least one laboratory-confirmed case of pandemic H1N1 infection. There have been a total of 162,380 reported cases and 1154 associated deaths. Influenza epidemics usually take off in autumn, and it is important to prepare for an earlier start this season. Estimates from Europe indicate that 230 millions Europe inhabitants will have clinical signs and symptoms of S-OIV this autumn, and 7–35% of the clinical cases will have a fatal outcome, which means that there will be 160,000–750,000 H1N1-related deaths. A vaccine against H1N1 is expected to be the most effective tool for controlling influenza A (H1N1) infection in terms of reducing morbidity and mortality and limiting diffusion. However, there are several issues with regard to vaccine manufacture and approval, as well as production capacity, that remain unsettled. We searched the literature indexed in PubMed as well as the websites of major international health agencies to obtain the material presented in this update on the current S-OIV pandemic. PMID:19881161

  2. [Effect of Yunnan herb Laggera pterodonta against influenza A (H1N1) virus in vitro].

    PubMed

    Xia, Xiao-ling; Sun, Qiang-ming; Wang, Xiao-dan; Zhao, Yu-jiao; Yang, Zi-feng; Huang, Qing-hui; Jiang, Zhi-hong; Wang, Xin-hua; Zhang, Rong-ping

    2015-09-01

    Laggera pterodonta is commonly used for treating influenza in Southwest China, especially in Yunnnan province. The main clinical effects of L. pterodonta include anti-influenza, anti-microbial, anti-inflammatory. To investigate the anti-influenza A (H1N1) virus effect of L. pterodonta, neutralization inhibition and proliferation inhibition tests were performed. MDCK culture method was used to observe the cytopathic effect (CPE) of extracts from L. pterodonta in inhibiting influenza A (H1N1) virus and haemagglutination titre of H1N1 virus in vitro. The culture medium were collected at 24 h, 48 h, 72 h, 96 h, and detected by Real time RT-PCR, in order to compare the effect of different extracts from L. pterodonta on in vitro proliferation of H1N1, virus. The result of neutralization inhibition test showed that hemagglutination titer of ethyl acetate extract were 8 times lower at 72 h; in proliferation inhibition test, hemagglutination titer of ethyl acetate extracts reduced by 2 and 4 times. According to the results of Real time RT-PCR test, the H1N1 inhibition ratio of ethyl acetate extract was 72.5%, while the proliferation inhibition ratio of ethyl acetate extract was 25.3%; as for petroleum ether extracts, the H1N1 inhibition ratio was 60.2%, while the proliferation inhibition ratio was 81.4%. In conclusion, both ethyl acetate extract and petroleum ether extract of L. pterodonta have significant neutralization and direct proliferation inhibition effects on influenza A virus. PMID:26983222

  3. [Effect of Yunnan herb Laggera pterodonta against influenza A (H1N1) virus in vitro].

    PubMed

    Xia, Xiao-ling; Sun, Qiang-ming; Wang, Xiao-dan; Zhao, Yu-jiao; Yang, Zi-feng; Huang, Qing-hui; Jiang, Zhi-hong; Wang, Xin-hua; Zhang, Rong-ping

    2015-09-01

    Laggera pterodonta is commonly used for treating influenza in Southwest China, especially in Yunnnan province. The main clinical effects of L. pterodonta include anti-influenza, anti-microbial, anti-inflammatory. To investigate the anti-influenza A (H1N1) virus effect of L. pterodonta, neutralization inhibition and proliferation inhibition tests were performed. MDCK culture method was used to observe the cytopathic effect (CPE) of extracts from L. pterodonta in inhibiting influenza A (H1N1) virus and haemagglutination titre of H1N1 virus in vitro. The culture medium were collected at 24 h, 48 h, 72 h, 96 h, and detected by Real time RT-PCR, in order to compare the effect of different extracts from L. pterodonta on in vitro proliferation of H1N1, virus. The result of neutralization inhibition test showed that hemagglutination titer of ethyl acetate extract were 8 times lower at 72 h; in proliferation inhibition test, hemagglutination titer of ethyl acetate extracts reduced by 2 and 4 times. According to the results of Real time RT-PCR test, the H1N1 inhibition ratio of ethyl acetate extract was 72.5%, while the proliferation inhibition ratio of ethyl acetate extract was 25.3%; as for petroleum ether extracts, the H1N1 inhibition ratio was 60.2%, while the proliferation inhibition ratio was 81.4%. In conclusion, both ethyl acetate extract and petroleum ether extract of L. pterodonta have significant neutralization and direct proliferation inhibition effects on influenza A virus.

  4. North American Triple Reassortant and Eurasian H1N1 Swine Influenza Viruses Do Not Readily Reassort to Generate a 2009 Pandemic H1N1-Like Virus

    PubMed Central

    Ma, Wenjun; Liu, Qinfang; Qiao, Chuanling; del Real, Gustavo; García-Sastre, Adolfo; Webby, Richard J.; Richt, Jürgen A.

    2014-01-01

    ABSTRACT The 2009 pandemic H1N1 virus (pH1N1) was derived through reassortment of North American triple reassortant and Eurasian avian-like swine influenza viruses (SIVs). To date, when, how and where the pH1N1 arose is not understood. To investigate viral reassortment, we coinfected cell cultures and a group of pigs with or without preexisting immunity with a Eurasian H1N1 virus, A/Swine/Spain/53207/2004 (SP04), and a North American triple reassortant H1N1 virus, A/Swine/Kansas/77778/2007 (KS07). The infected pigs were cohoused with one or two groups of contact animals to investigate viral transmission. In coinfected MDCK or PK15 continuous cell lines with KS07 and SP04 viruses, more than 20 different reassortant viruses were found. In pigs without or with preexisting immunity (immunized with commercial inactivated swine influenza vaccines) and coinfected with both viruses, six or seven reassortant viruses, as well as the parental viruses, were identified in bronchoalveolar lavage fluid samples from the lungs. Interestingly, only one or two viruses transmitted to and were detected in contact animals. No reassortant containing a gene constellation similar to that of pH1N1 virus was found in either coinfected cells or pigs, indicating that the reassortment event that resulted in the generation of this virus is a rare event that likely involved specific viral strains and/or a favorable, not-yet-understood environment. PMID:24618255

  5. H7N9 Influenza Virus Is More Virulent in Ferrets than 2009 Pandemic H1N1 Influenza Virus.

    PubMed

    Yum, Jung; Ku, Keun Bon; Kim, Hyun Soo; Seo, Sang Heui

    2015-12-01

    The novel H7N9 influenza virus has been infecting humans in China since February 2013 and with a mortality rate of about 40%. This study compared the pathogenicity of the H7N9 and 2009 pandemic H1N1 influenza viruses in a ferret model, which shows similar symptoms to those of humans infected with influenza viruses. The H7N9 influenza virus caused a more severe disease than did the 2009 pandemic H1N1 influenza virus. All of the ferrets infected with the H7N9 influenza virus had died by 6 days after infection, while none of those infected with the 2009 pandemic H1N1 influenza virus died. Ferrets infected with the H7N9 influenza virus had higher viral titers in their lungs than did those infected with the 2009 pandemic H1N1 influenza virus. Histological findings indicated that hemorrhagic pneumonia was caused by infection with the H7N9 influenza virus, but not with the 2009 pandemic H1N1 influenza virus. In addition, the lung tissues of ferrets infected with the H7N9 influenza virus contained higher levels of chemokines than did those of ferrets infected with the 2009 pandemic H1N1 influenza virus. This study suggests that close monitoring is needed to prevent human infection by the lethal H7N9 influenza virus.

  6. The early diversification of influenza A/H1N1pdm

    PubMed Central

    Nelson, Martha; Spiro, David; Wentworth, David; Fan, Jiang; Beck, Eric; St. George, Kirsten; Ghedin, Elodie; Halpin, Rebecca; Bera, Jayati; Hine, Erin; Proudfoot, Kathleen; Stockwell, Tim; Lin, Xudong; Griesemer, Sara; Bose, Michael; Jurgens, Lisa; Kumar, Swati; Viboud, Cecile; Holmes, Edward; Henrickson, Kelly

    2009-01-01

    Background Since its initial detection in April 2009, the A/H1N1pdm influenza virus has spread rapidly in humans, with over 5,700 human deaths. However, little is known about the evolutionary dynamics of H1N1pdm and its geographic and temporal diversification. Methods Phylogenetic analysis was conducted upon the concatenated coding regions of whole-genome sequences from 290 H1N1pdm isolates sampled globally between April 1 – July 9, 2009, including relatively large samples from the US states of Wisconsin and New York. Results At least 7 phylogenetically distinct viral clades have disseminated globally and co-circulated in localities that experienced multiple introductions of H1N1pdm. The epidemics in New York and Wisconsin were dominated by two different clades, both phylogenetically distinct from the viruses first identified in California and Mexico, suggesting an important role for founder effects in determining local viral population structures. Conclusions Determining the global diversity of H1N1pdm is central to understanding the evolution and spatial spread of the current pandemic, and to predict its future impact on human populations. Our results indicate that H1N1pdm has already diversified into distinct viral lineages with defined spatial patterns. PMID:20029664

  7. Inside the Outbreak of the 2009 Influenza A (H1N1)v Virus in Mexico

    PubMed Central

    Zepeda-Lopez, Hector M.; Perea-Araujo, Lizbeth; Miliar-García, Angel; Dominguez-López, Aarón; Xoconostle-Cázarez, Beatriz; Lara-Padilla, Eleazar; Ramírez Hernandez, Jorge A.; Sevilla-Reyes, Edgar; Orozco, Maria Esther; Ahued-Ortega, Armando; Villaseñor-Ruiz, Ignacio; Garcia-Cavazos, Ricardo J.; Teran, Luis M.

    2010-01-01

    Background Influenza viruses pose a threat to human health because of their potential to cause global disease. Between mid March and mid April a pandemic influenza A virus emerged in Mexico. This report details 202 cases of infection of humans with the 2009 influenza A virus (H1N1)v which occurred in Mexico City as well as the spread of the virus throughout the entire country. Methodology and Findings From May 1st to May 5th nasopharyngeal swabs, derived from 751 patients, were collected at 220 outpatient clinics and 28 hospitals distributed throughout Mexico City. Analysis of samples using real time RT-PCR revealed that 202 patients out of the 751 subjects (26.9%) were confirmed to be infected with the new virus. All confirmed cases of human infection with the strain influenza (H1N1)v suffered respiratory symptoms. The greatest number of confirmed cases during the outbreak of the 2009 influenza A (H1N1)v were seen in neighbourhoods on the northeast side of Mexico City including Iztapalapa, Gustavo A. Madero, Iztacalco, and Tlahuac which are the most populated areas in Mexico City. Using these data, together with data reported by the Mexican Secretariat of Health (MSH) to date, we plot the course of influenza (H1N1)v activity throughout Mexico. Conclusions Our data, which is backed up by MSH data, show that the greatest numbers of the 2009 influenza A (H1N1) cases were seen in the most populated areas. We speculate on conditions in Mexico which may have sparked this flu pandemic, the first in 41 years. We accept the hypothesis that high population density and a mass gathering which took in Iztapalapa contributed to the rapid spread of the disease which developed in three peaks of activity throughout the Country. PMID:20949040

  8. Correlates of 2009 H1N1 Influenza Vaccine Acceptability among Parents and Their Adolescent Children

    ERIC Educational Resources Information Center

    Painter, Julia E.; Gargano, Lisa M.; Sales, Jessica M.; Morfaw, Christopher; Jones, LaDawna M.; Murray, Dennis; DiClemente, Ralph J.; Hughes, James M.

    2011-01-01

    School-aged children were a priority group for receipt of the pandemic (2009) H1N1 influenza vaccine. Both parental and adolescent attitudes likely influence vaccination behaviors. Data were collected from surveys distributed to middle- and high-school students and their parents in two counties in rural Georgia. Multivariable logistic regression…

  9. In-Flight Transmission of Novel Influenza A (H1N1)

    PubMed Central

    Kim, Joon Hyung; Lee, Dong-Han; Shin, Sang-Sook; Kang, Chun; Kim, Jin Seok; Jun, Byung Yool

    2010-01-01

    The Korea Centers for Disease Control and Prevention confirmed two patients, who had taken the same plane from Los Angeles to Seoul, with novel influenza A (H1N1). Through contact tracing, we concluded that the second patient was infected during the flight. PMID:21191459

  10. Vision Loss Caused by Retinal and Lateral Geniculate Nucleus Infarction in H1N1 Influenza.

    PubMed

    Breker, Dane A; Stacey, Andrew W; Srinivasan, Ashok; Bursztyn, Lulu L C D; Trobe, Jonathan D; Johnson, Mark W

    2015-09-01

    A 13-year-old girl developed encephalopathy and severe bilateral vision loss to the level of light perception within 24 hours of having fever and myalgias heralding H1N1 influenza A. Ophthalmoscopy demonstrated findings of confluent ischemic retinopathy. Brain MRI disclosed lateral geniculate body signal abnormalities indicative of hemorrhagic infarction. Despite aggressive treatment with intravenous corticosteroids, intravenous immunoglobulin, and plasmapheresis, vision did not substantially improve. This case demonstrates that H1N1 can cause simultaneous retinal and lateral geniculate body infarctions, a combination of findings not previously described in any condition. We postulate an immunologic response to the virus marked by occlusive damage to arteriolar endothelium. PMID:25887303

  11. Clinical features of hospitalised children with 2009 H1N1 influenza virus infection.

    PubMed

    Calitri, Carmelina; Gabiano, Clara; Garazzino, Silvia; Pinon, Michele; Zoppo, Marisa; Cuozzo, Margherita; Scolfaro, Carlo; Tovo, Pier-Angelo

    2010-12-01

    Clinical features and outcome of 2009 H1N1 influenza virus in the paediatric setting is ill-defined. The epidemiologic and clinical features of children with confirmed H1N1 influenza virus infection admitted to an Italian tertiary paediatric hospital from August through December 2009 were evaluated. A total of 63 children (mean age 4.3 years) were studied; of these, 29 (46%) had chronic underlying diseases. The most frequent symptoms and signs at admission were fever (97%), cough (60%) and respiratory disturbances (24%). Forty patients (63.5%) had H1N1-related complications: 32 (51%) pulmonary diseases, three (5%) neurological disorders, such as acute encephalitis or acute disseminated encephalomyelitis, and two (3%) haematological alterations. Three patients were admitted to the Intensive Care Unit. Most children (81%) were treated with oseltamivir: one developed rash during treatment; no other adverse events were noticed. All children survived without sequelae. In conclusions, 2009 H1N1 influenza virus infection in children is associated with a wide spectrum of clinical manifestations. Neurological disorders are not exceptional complications. Oseltamivir therapy seems safe also in infants. PMID:20652313

  12. Liver Biochemistry During the Course of Influenza A/H1N1 Infection

    PubMed Central

    Seretis, Charalampos; Lagoudianakis, Emmanuel; Salemis, Nikolaos; Pappas, Apostolos; Gemenetzis, George; Seretis, Fotios; Gourgiotis, Stavros

    2013-01-01

    Despite the multi-systemic effects of influenza A/H1N1 virus, the occurrence of hepatic injury during the natural course of the infection remains a matter of debate. We performed a review of the published clinical studies which assess the above mentioned relationship, reviewing the studies published in PubMed database (English literature), using the key words “H1N1”, “influenza A” and “liver”. We excluded case reports and clinical studies that referred to pediatric and transplanted patients, pregnants and patients with known history of chronic liver diseases. From a total of 96 results, a total of 78 papers met one or more of the exclusion criteria set. Evaluating the remaining 18 published papers, 14 more were excluded as they did not provide any sufficient data, relevant to the subject of our review. Although the analysis of the remaining studies revealed the existence of conflicting results concerning the exact degree and the potential mechanisms of liver injury in H1N1 positive patients, it can be assumed that influenza A/H1N1 virus is -or at least could be- a hepatotropic virus.

  13. The hemagglutinin structure of an avian H1N1 influenza A virus

    SciTech Connect

    Lin, Tianwei; Wang, Gengyan; Li, Anzhang; Zhang, Qian; Wu, Caiming; Zhang, Rongfu; Cai, Qixu; Song, Wenjun; Yuen, Kwok-Yung

    2009-09-15

    The interaction between hemagglutinin (HA) and receptors is a kernel in the study of evolution and host adaptation of H1N1 influenza A viruses. The notion that the avian HA is associated with preferential specificity for receptors with Sia{alpha}2,3Gal glycosidic linkage over those with Sia{alpha}2,6Gal linkage is not all consistent with the available data on H1N1 viruses. By x-ray crystallography, the HA structure of an avian H1N1 influenza A virus, as well as its complexes with the receptor analogs, was determined. The structures revealed no preferential binding of avian receptor analogs over that of the human analog, suggesting that the HA/receptor binding might not be as stringent as is commonly believed in determining the host receptor preference for some subtypes of influenza viruses, such as the H1N1 viruses. The structure also showed difference in glycosylation despite the preservation of related sequences, which may partly contribute to the difference between structures of human and avian origin.

  14. Causal analysis of H1N1pdm09 influenza infection risk in a household cohort

    PubMed Central

    Mansiaux, Yohann; Salez, Nicolas; Lapidus, Nathanael; Setbon, Michel; Andreoletti, Laurent; Leruez-Ville, Marianne; Cauchemez, Simon; Gougeon, Marie-Lise; Vély, Frédéric; Schwarzinger, Michael; Abel, Laurent; Delabre, Rosemary Markovic; Flahault, Antoine; de Lamballerie, Xavier; Carrat, Fabrice

    2015-01-01

    Background Obtaining a comprehensive quantitative figure of the determinants of influenza infection will help identify priority targets for future influenza mitigation interventions. We developed an original causal model integrating highly diverse factors and their dependencies, to identify the most critical determinants of pandemic influenza infection (H1N1pdm09) during the 2010–2011 influenza season. Methods We used data from 601 households (1450 participants) included in a dedicated cohort. Structural equations were used to model direct and indirect relationships between infection and risk perception, compliance with preventive behaviours, social contacts, indoor and outdoor environment, sociodemographic factors and pre-epidemic host susceptibility. Standardised estimates (βstd) were used to assess the strength of associations (ranging from −1 for a completely negative association to 1 for a completely positive association). Results Host susceptibility to H1N1pdm09 and compliance with preventive behaviours were the only two factors directly associated with the infection risk (βstd=0.31 and βstd=−0.21). Compliance with preventive behaviours was influenced by risk perception and preventive measures perception (βstd=0.14 and βstd=0.27). The number and duration of social contacts were not associated with H1N1pdm09 infection. Conclusions Our findings suggest that influenza vaccination in addition to public health communication campaigns focusing on personal preventive measures should be prioritised as potentially efficient interventions to mitigate influenza epidemics. PMID:25416792

  15. Meteorological Influence on the 2009 Influenza A (H1N1) Pandemic in Mainland China.

    NASA Astrophysics Data System (ADS)

    Zhao, X.; Cai, J.; Feng, D.; Bai, Y.; Xu, B.

    2015-12-01

    Since May 2009, a novel influenza A (H1N1) pandemic has spread rapidly in mainland China from Mexico. Although there has been substantial analysis of this influenza, reliable work estimating its spatial dynamics and determinants remain scarce. The survival and transmission of this pandemic virus not only depends on its biological properties, but also a correlation with external environmental factors. In this study, we collected daily influenza A (H1N1) cases and corresponding annual meteorological factors in mainland China from May 2009 to April 2010. By analyzing these data at county-level, a similarity index, which considered the spatio-temporal characteristics of the disease, was proposed to evaluate the role and lag time of meteorological factors in the influenza transmission. The results indicated that the influenza spanned a large geographical area, following an overall trend from east to west across the country. The spatio-temporal transmission of the disease was affected by a series of meteorological variables, especially absolute humidity with a 3-week lag. These findings confirmed that the absolute humidity and other meteorological variables contributed to the local occurrence and dispersal of influenza A (H1N1). The impact of meteorological variables and their lag effects could be involved in the improvement of effective strategies to control and prevent disease outbreaks.

  16. Influenza A(H1N1)pdm09 virus in pigs, Togo, 2013

    PubMed Central

    Ducatez, Mariette F.; Awoume, Félix; Webby, Richard J.

    2015-01-01

    We collected 325 nasal swabs from freshly slaughtered previously healthy pigs from October 2012 through January 2014 in a slaughterhouse near Lomé in Togo. Influenza A virus genome was detected by RT-PCR in 2.5% to 12.3% of the pooled samples, and results of hemagglutinin subtyping RT-PCR assays showed the virus in all the positive pools to be A(H1N1)pdm09. Virus was isolated on MDCK cells from a representative specimen, A/swine/Togo/ONA32/2013(H1N1). The isolate was fully sequenced and harbored 8 genes similar to A(H1N1)pdm09 virus genes circulating in humans in 2012–2013, suggesting human-to-swine transmission of the pathogen. PMID:25778544

  17. Comparative virulence of wild-type H1N1pdm09 influenza A isolates in swine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In 2009, a novel swine-origin H1N1 (H1N1pdm09) influenza A virus (IAV) reached pandemic status and was soon after detected in pigs worldwide. The objective of this study was to evaluate whether differences in the HA protein can affect pathogenicity and antigenicity of H1N1pdm09 in swine. We compared...

  18. Framing of Influenza A (H1N1) pandemic in a Singaporean newspaper.

    PubMed

    Basnyat, Iccha; Lee, Seow Ting

    2015-12-01

    This study seeks to understand how public health messages provided by the government in Singapore during an Influenza A (H1N1) pandemic were framed by the news media for the public. News articles were analyzed to explore how the global pandemic was framed as a local event, providing a unique exploration of the dynamic involving public health communication, news media and the state. Thematic analysis (n = 309) included the government-issued press releases disseminating public health information about H1N1 that were directly linked to news stories (n = 56) and news stories about H1N1 generated by the newspaper (n = 253). Four themes were found: (i) imported disease, (ii) war/battle metaphors, (iii) social responsibility and (iv) lockdown policies. Frame analysis revealed that the news coverage during the H1N1 pandemic reflected how the newspaper framed and mediated the information flow, amplified a positive tone for the government response, emphasized individual responsibility and utilized gain frames to construct local messages about the global H1N1 pandemic that reified Singapore as a nation-state.

  19. Description of a large urban school-located 2009 pandemic H1N1 vaccination campaign, New York City 2009-2010.

    PubMed

    Narciso, Heather E; Pathela, Preeti; Morgenthau, Beth Maldin; Kansagra, Susan M; May, Linda; Scaccia, Allison; Zucker, Jane R

    2012-04-01

    In the spring of 2009, New York City (NYC) experienced the emergence and rapid spread of pandemic influenza A H1N1 virus (pH1N1), which had a high attack rate in children and caused many school closures. During the 2009 fall wave of pH1N1, a school-located vaccination campaign for elementary schoolchildren was conducted in order to reduce infection and transmission in the school setting, thereby reducing the impact of pH1N1 that was observed earlier in the year. In this paper, we describe the planning and outcomes of the NYC school-located vaccination campaign. We compared consent and vaccination data for three vaccination models (school nurse alone, school nurse plus contract nurse, team). Overall, >1,200 of almost 1,600 eligible schools participated, achieving 26.8% consent and 21.5% first-dose vaccination rates, which did not vary significantly by vaccination model. A total of 189,902 doses were administered during two vaccination rounds to 115,668 students at 998 schools included in the analysis; vaccination rates varied by borough, school type, and poverty level. The team model achieved vaccination of more children per day and required fewer vaccination days per school. NYC's campaign is the largest described school-located influenza vaccination campaign to date. Despite substantial challenges, school-located vaccination is feasible in large, urban settings, and during a public health emergency. PMID:22318374

  20. HIV-1 and Its gp120 Inhibits the Influenza A(H1N1)pdm09 Life Cycle in an IFITM3-Dependent Fashion

    PubMed Central

    Mesquita, Milene; Fintelman-Rodrigues, Natalia; Sacramento, Carolina Q.; Abrantes, Juliana L.; Costa, Eduardo; Temerozo, Jairo R.; Siqueira, Marilda M.; Bou-Habib, Dumith Chequer; Souza, Thiago Moreno L.

    2014-01-01

    HIV-1-infected patients co-infected with A(H1N1)pdm09 surprisingly presented benign clinical outcome. The knowledge that HIV-1 changes the host homeostatic equilibrium, which may favor the patient resistance to some co-pathogens, prompted us to investigate whether HIV-1 infection could influence A(H1N1)pdm09 life cycle in vitro. We show here that exposure of A(H1N1)pdm09-infected epithelial cells to HIV-1 viral particles or its gp120 enhanced by 25% the IFITM3 content, resulting in a decrease in influenza replication. This event was dependent on toll-like receptor 2 and 4. Moreover, knockdown of IFITM3 prevented HIV-1 ability to inhibit A(H1N1)pdm09 replication. HIV-1 infection also increased IFITM3 levels in human primary macrophages by almost 100%. Consequently, the arrival of influenza ribonucleoproteins (RNPs) to nucleus of macrophages was inhibited, as evaluated by different approaches. Reduction of influenza RNPs entry into the nucleus tolled A(H1N1)pdm09 life cycle in macrophages earlier than usual, limiting influenza's ability to induce TNF-α. As judged by analysis of the influenza hemagglutin (HA) gene from in vitro experiments and from samples of HIV-1/A(H1N1)pdm09 co-infected individuals, the HIV-1-induced reduction of influenza replication resulted in delayed viral evolution. Our results may provide insights on the mechanisms that may have attenuated the clinical course of Influenza in HIV-1/A(H1N1)pdm09 co-infected patients during the recent influenza form 2009/2010. PMID:24978204

  1. Rhabdomyolysis secondary to influenza A H1N1 vaccine resulting in acute kidney injury.

    PubMed

    Callado, Rodrigo Barbosa; Carneiro, Tassia Gabrielle Ponte; Parahyba, Camille Carneiro da Cunha; Lima, Neiberg de Alcantara; da Silva Junior, Geraldo Bezerra; Daher, Elizabeth de Francesco

    2013-01-01

    Influenza A infection has been described as a major viral cause of infection-induced rhabdomyolysis, but to date, only one reported case was described as having been induced by influenza vaccine. We describe a case of a man who had been using statins and developed rhabdomyolysis the day after influenza A H1N1 vaccination. A 58-year-old man was admitted at the emergency room complaining of impaired gait. The patient reported receiving influenza A H1N1 vaccine 5 days prior to the admission, with symptoms beginning the day after the inoculation. He reported ascending weakness, intense myalgia in the lower back, upper and lower limbs. The admission laboratory tests showed serum creatine phosphokinase: 7600 IU/L, creatinine: 3.0 mg/dL, urea: 185 mg/dL, aspartate aminotransferase: 592 IU/L, alanine aminotransferase: 630 IU/L, potassium: 5.4 mEq/L, lactate dehydrogenase: 2828 IU/L. Despite intravenous fluid therapy, the patient still persisted with oliguria and urinary output of 0.17 ml/kg/h. Hemodialysis was initiated and renal function recovery was observed after two weeks. The patient was hemodynamically stable and asymptomatic at hospital discharge. This is a rare side effect of influenza A H1N1 vaccine. Physicians should advise patients to seek medical care when muscle symptoms are present and consider the possibility of rhabdomyolysis due to vaccination. Trials are required to better define the incidence of this important side effect.

  2. Human swine influenza A [H1N1]: practical advice for clinicians early in the pandemic.

    PubMed

    Fitzgerald, Dominic A

    2009-09-01

    The influenza pandemic the world was waiting for may have arrived, but the early indications are that the first wave of human swine influenza A [H1N1], also referred to as H1N1 Mexico 09 or "swine flu", is highly transmissible but of no greater virulence than seasonal influenza to date. The new swine flu H1N1 virus is a mixture of avian, porcine and human influenza RNA. With twenty thousand confirmed cases worldwide and 117 deaths within 7 weeks of the first acknowledgement of a possible pandemic by Mexican and WHO experts, the mortality rate is less than 0.1% and the majority of deaths centred upon the origin of the epidemic in Mexico [83%]. Swine flu is thus far a relatively mild illness seen predominantly in those who are healthy and under 25 years of age, perhaps reflecting protection from previous human influenza exposure in older people. As the virus spreads internationally, border protection issues have surfaced and public health initiatives are being progressively rolled out to minimise the transmission. Vaccines are being developed which will be trialled in the coming months with a likely availability by August 2009, in time for the northern hemisphere autumn and winter. Vigilance without alarm appears to be the recommendation so far.

  3. Prediction of biological functions on glycosylation site migrations in human influenza H1N1 viruses.

    PubMed

    Sun, Shisheng; Wang, Qinzhe; Zhao, Fei; Chen, Wentian; Li, Zheng

    2012-01-01

    Protein glycosylation alteration is typically employed by various viruses for escaping immune pressures from their hosts. Our previous work had shown that not only the increase of glycosylation sites (glycosites) numbers, but also glycosite migration might be involved in the evolution of human seasonal influenza H1N1 viruses. More importantly, glycosite migration was likely a more effectively alteration way for the host adaption of human influenza H1N1 viruses. In this study, we provided more bioinformatics and statistic evidences for further predicting the significant biological functions of glycosite migration in the host adaptation of human influenza H1N1 viruses, by employing homology modeling and in silico protein glycosylation of representative HA and NA proteins as well as amino acid variability analysis at antigenic sites of HA and NA. The results showed that glycosite migrations in human influenza viruses have at least five possible functions: to more effectively mask the antigenic sites, to more effectively protect the enzymatic cleavage sites of neuraminidase (NA), to stabilize the polymeric structures, to regulate the receptor binding and catalytic activities and to balance the binding activity of hemagglutinin (HA) with the release activity of NA. The information here can provide some constructive suggestions for the function research related to protein glycosylation of influenza viruses, although these predictions still need to be supported by experimental data.

  4. French Experience of 2009 A/H1N1v Influenza in Pregnant Women

    PubMed Central

    Dubar, Grégory; Azria, Elie; Tesnière, Antoine; Dupont, Hervé; Le Ray, Camille; Baugnon, Thomas; Matheron, Sophie; Luton, Dominique; Richard, Jean-Christophe; Launay, Odile; Tsatsaris, Vassilis; Goffinet, François; Mignon, Alexandre

    2010-01-01

    Background The first reports on the pandemic influenza 2009 A/H1N1v from the USA, Mexico, and Australia indicated that this disease was associated with a high mortality in pregnant women. The aim of this study was to describe and compare the characteristics of severe critically ill and non-severe pregnant women with 2009 A/H1N1v-related illness in France. Methodology/Principal Findings A national registry was created to screen pregnant women with laboratory-confirmed 2009 A/H1N1v influenza. Three hundred and fifteen patients from 46 French hospitals were included: 40 patients were admitted to intensive care units (severe outcomes), 111 were hospitalized in obstetric or medical wards (moderate outcomes), and 164 were outpatients (mild outcomes). The 2009 A/H1N1v influenza illness occurred during all pregnancy trimesters, but most women (54%), notably the severe patients (70%), were in the third trimester. Among the severe patients, twenty (50%) underwent mechanical ventilation, and eleven (28%) were treated with extracorporeal membrane oxygenation. Three women died from A/H1N1v influenza. We found a strong association between the development of a severe outcome and both co-existing illnesses (adjusted odds ratio [OR], 5.1; 95% confidence interval [CI], 2.2–11.8) and a delay in oseltamivir treatment after the onset of symptoms (>3 or 5 days) (adjusted OR, 4.8; 95% CI, 1.9–12.1 and 61.2, 95% CI; 14.4–261.3, respectively). Among the 140 deliveries after 22 weeks of gestation known to date, 19 neonates (14%) were admitted to a neonatal intensive care unit, mainly for preterm delivery, and two neonates died. None of these neonates developed 2009 A/H1N1v infection. Conclusions This series confirms the high incidence of complications in pregnant women infected with pandemic A/H1N1v observed in other countries but depicts a lower overall maternal and neonatal mortality and morbidity than indicated in the USA or Australia. Moreover, our data demonstrate the benefit of

  5. Tmprss2 is essential for influenza H1N1 virus pathogenesis in mice.

    PubMed

    Hatesuer, Bastian; Bertram, Stephanie; Mehnert, Nora; Bahgat, Mahmoud M; Nelson, Peter S; Pöhlmann, Stefan; Pöhlman, Stefan; Schughart, Klaus

    2013-01-01

    Annual influenza epidemics and occasional pandemics pose a severe threat to human health. Host cell factors required for viral spread but not for cellular survival are attractive targets for novel approaches to antiviral intervention. The cleavage activation of the influenza virus hemagglutinin (HA) by host cell proteases is essential for viral infectivity. However, it is unknown which proteases activate influenza viruses in mammals. Several candidates have been identified in cell culture studies, leading to the concept that influenza viruses can employ multiple enzymes to ensure their cleavage activation in the host. Here, we show that deletion of a single HA-activating protease gene, Tmprss2, in mice inhibits spread of mono-basic H1N1 influenza viruses, including the pandemic 2009 swine influenza virus. Lung pathology was strongly reduced and mutant mice were protected from weight loss, death and impairment of lung function. Also, after infection with mono-basic H3N2 influenza A virus body weight loss and survival was less severe in Tmprss2 mutant compared to wild type mice. As expected, Tmprss2-deficient mice were not protected from viral spread and pathology after infection with multi-basic H7N7 influenza A virus. In conclusion, these results identify TMPRSS2 as a host cell factor essential for viral spread and pathogenesis of mono-basic H1N1 and H3N2 influenza A viruses. PMID:24348248

  6. Overview of the winter wave of 2009 pandemic influenza A(H1N1)v in Vojvodina, Serbia

    PubMed Central

    Petrović, Vladimir; Šeguljev, Zorica; Ćosić, Gorana; Ristić, Mioljub; Nedeljković, Jasminka; Dragnić, Nataša; Ukropina, Snežana

    2011-01-01

    Aim To analyze the epidemiological data for pandemic influenza A(H1N1)v in the Autonomous Province of Vojvodina, Serbia, during the season of 2009/2010 and to assess whether including severe acute respiratory illness (SARI) hospitalization data to the surveillance system gives a more complete picture of the impact of influenza during the pandemic. Methods From September 2009 to September 2010, the Institute of Public Health of Vojvodina conducted sentinel surveillance of influenza-like illnesses and acute respiratory infections in all hospitalized patients with SARI and virological surveillance of population of Vojvodina according to the European Centers for Disease Control technical document. Results The pandemic influenza outbreak in the province started in October 2009 (week 44) in students who had returned from a school-organized trip to Prague, Bratislava, and Vienna. The highest incidence rate was 1090 per 100 000 inhabitants, found in the week 50. The most affected age group were children 5-14 years old. A total of 1591 patients with severe illness were admitted to regional hospitals, with a case fatality rate of 2%, representing a hospitalization rate of 78.3 per 100 000 inhabitants and a mortality rate of 1.6 per 100 000. Most frequently hospitalized were 15-19 years old patients, male patients, and patients with pneumonia (P < 0.001). The highest case fatality rate was found among patients with acute respiratory distress syndrome (P < 0.001). Nasal/throat swabs were obtained for polymerase chain reaction test from 315 hospitalized patients and 20 non-hospitalized patients, and 145 (46%) and 15 (75%) specimens, respectively, tested positive on A(H1N1)v. Conclusion Sentinel influenza-like illness and SARI surveillance, both followed with virological surveillance, seem to be the optimal method to monitor the full scope of the influenza pandemic (from mild to severe influenza) in Vojvodina. PMID:21495196

  7. Two Years after Pandemic Influenza A/2009/H1N1: What Have We Learned?

    PubMed Central

    Cheng, Vincent C. C.; To, Kelvin K. W.; Tse, Herman; Hung, Ivan F. N.

    2012-01-01

    Summary: The world had been anticipating another influenza pandemic since the last one in 1968. The pandemic influenza A H1N1 2009 virus (A/2009/H1N1) finally arrived, causing the first pandemic influenza of the new millennium, which has affected over 214 countries and caused over 18,449 deaths. Because of the persistent threat from the A/H5N1 virus since 1997 and the outbreak of the severe acute respiratory syndrome (SARS) coronavirus in 2003, medical and scientific communities have been more prepared in mindset and infrastructure. This preparedness has allowed for rapid and effective research on the epidemiological, clinical, pathological, immunological, virological, and other basic scientific aspects of the disease, with impacts on its control. A PubMed search using the keywords “pandemic influenza virus H1N1 2009” yielded over 2,500 publications, which markedly exceeded the number published on previous pandemics. Only representative works with relevance to clinical microbiology and infectious diseases are reviewed in this article. A significant increase in the understanding of this virus and the disease within such a short amount of time has allowed for the timely development of diagnostic tests, treatments, and preventive measures. These findings could prove useful for future randomized controlled clinical trials and the epidemiological control of future pandemics. PMID:22491771

  8. POSTPARTUM AND NEONATAL NURSING CARE DURING THE 2009 H1N1 INFLUENZA PANDEMIC

    PubMed Central

    Zapata, Lauren B.; Ruch-Ross, Holly S.; Williams, Jennifer L.; Ruhl, Catherine

    2016-01-01

    We describe select influenza infection control policies and practices related to postpartum and newborn care during the 2009 H1N1 pandemic. In an online survey of obstetric and neonatal nurses, significantly more nurses indicated a written hospital policy supporting each of the practices during versus before the pandemic. The two practices least oft en implemented were temporary separation of healthy newborns from ill mothers (37.7 percent) and testing newborns for influenza virus infection if signs of influenza were observed (31.4 percent). Presence of written hospital policies increased implementation of practices. Findings may be useful to guide planning for future pandemics or other public health emergencies. PMID:23957794

  9. [A cyclotide against influenza A H1N1 virus from Viola yedoensis].

    PubMed

    Liu, Min-Zhi; Yang, Yan; Zhang, Shu-Xiang; Tang, Liang; Wang, Hui-Min; Chen, Cheng-Juan; Shen, Zhu-Fang; Cheng, Ke-Di; Kong, Jian-Qiang; Wang, Wei

    2014-06-01

    Three cyclotides were isolated from the whole plant of Viola yedoensis in this study. The two, vary peptide E and cycloviolacin Y5, were previously reported, and a novel cycloviolacin VY1 was characterized according to the interpretation of MS/MS fragmentation of peptides which were produced from the reduced and alkylated parent peptide with the digestion of Endo Lys-C, trypsin and chymotrypsin, separately. The stability of remarkable resistance to proteolytic degradation by trypsin and chymotrypsin, and that of thermal denaturation was confirmed again. Besides, the IC50 value of cycloviolacin VY1 against influenza A H1N1 virus was (2.27 +/- 0.20) microg x mL(-1). It is the first cyclotide reported with anti-influenza A H1N1 virus activity in vitro assay.

  10. Influenza A viral loads in respiratory samples collected from patients infected with pandemic H1N1, seasonal H1N1 and H3N2 viruses

    PubMed Central

    2010-01-01

    Background Nasopharyngeal aspirate (NPA), nasal swab (NS), and throat swab (TS) are common specimens used for diagnosis of respiratory virus infections based on the detection of viral genomes, viral antigens and viral isolation. However, there is no documented data regarding the type of specimen that yields the best result of viral detection. In this study, quantitative real time RT-PCR specific for M gene was used to determine influenza A viral loads present in NS, NPA and TS samples collected from patients infected with the 2009 pandemic H1N1, seasonal H1N1 and H3N2 viruses. Various copy numbers of RNA transcripts derived from recombinant plasmids containing complete M gene insert of each virus strain were assayed by RT-PCR. A standard curve for viral RNA quantification was constructed by plotting each Ct value against the log quantity of each standard RNA copy number. Results Copy numbers of M gene were obtained through the extrapolation of Ct values of the test samples against the corresponding standard curve. Among a total of 29 patients with severe influenza enrolled in this study (12 cases of the 2009 pandemic influenza, 5 cases of seasonal H1N1 and 12 cases of seasonal H3N2 virus), NPA was found to contain significantly highest amount of viral loads and followed in order by NS and TS specimen. Viral loads among patients infected with those viruses were comparable regarding type of specimen analyzed. Conclusion Based on M gene copy numbers, we conclude that NPA is the best specimen for detection of influenza A viruses, and followed in order by NS and TS. PMID:20403211

  11. Aminoadamantanes with Persistent in Vitro Efficacy against H1N1 (2009) Influenza A

    PubMed Central

    2015-01-01

    A series of 2-adamantanamines with alkyl adducts of various lengths were examined for efficacy against strains of influenza A including those having an S31N mutation in M2 proton channel that confer resistance to amantadine and rimantadine. The addition of as little as one CH2 group to the methyl adduct of the amantadine/rimantadine analogue, 2-methyl-2-aminoadamantane, led to activity in vitro against two M2 S31N viruses A/Calif/07/2009 (H1N1) and A/PR/8/34 (H1N1) but not to a third A/WS/33 (H1N1). Solid state NMR of the transmembrane domain (TMD) with a site mutation corresponding to S31N shows evidence of drug binding. But electrophysiology using the full length S31N M2 protein in HEK cells showed no blockade. A wild type strain, A/Hong Kong/1/68 (H3N2) developed resistance to representative drugs within one passage with mutations in M2 TMD, but A/Calif/07/2009 S31N was slow (>8 passages) to develop resistance in vitro, and the resistant virus had no mutations in M2 TMD. The results indicate that 2-alkyl-2-aminoadamantane derivatives with sufficient adducts can persistently block p2009 influenza A in vitro through an alternative mechanism. The observations of an HA1 mutation, N160D, near the sialic acid binding site in both 6-resistant A/Calif/07/2009(H1N1) and the broadly resistant A/WS/33(H1N1) and of an HA1 mutation, I325S, in the 6-resistant virus at a cell-culture stable site suggest that the drugs tested here may block infection by direct binding near these critical sites for virus entry to the host cell. PMID:24793875

  12. Transmission of Pandemic Influenza A (H1N1) Virus in a Train in China

    PubMed Central

    Cui, Fuqiang; Luo, Huiming; Zhou, Lei; Yin, Dapeng; Zheng, Canjun; Wang, Dingming; Gong, Jian; Fang, Gang; He, Jianfeng; McFarland, Jeffrey; Yu, Hongjie

    2011-01-01

    Background Pandemic influenza A (H1N1) virus emerged in North America in April 2009 and spread globally. We describe the epidemiology and public health response to the first known outbreak of 2009 H1N1 in a train, which occurred in June 2009 in China. Methods After 2 provinces provided initial reports of 2009 H1N1 infection in 2 persons who had travelled on the same train, we conducted a retrospective epidemiologic investigation to collect information from the passengers, crew members, contacts, and health care providers. We explored the source of infection and possible routes of transmission in the train. All cases were confirmed by real-time reverse transcription polymerase chain reaction testing. Results Train #1223 traveled 40 hours, made 28 stops in 4 Chinese provinces, and boarded 2555 passengers, who logged a total of 59 144 person-hours of travel time. Nineteen confirmed 2009 H1N1 cases were identified. Of these, 13 were infected and developed symptoms on the train and 6 occurred among contacts who developed illness during medical monitoring. In addition, 3 asymptomatic cases were identified based on RT-PCR testing of respiratory swabs from contacts. The attack rate among contacts of confirmed cases in the same car was higher than that among contacts in other cars (3.15% vs. 0%, P < 0.001). Attack rates increased with exposure time. Conclusions Close contact and long exposure may have contributed to the transmission of 2009 H1N1 virus in the train. Trains may have played an important role in the 2009 influenza pandemic. PMID:21646746

  13. Adaptation of influenza A(H1N1)pdm09 virus in experimental mouse models.

    PubMed

    Prokopyeva, E A; Sobolev, I A; Prokopyev, M V; Shestopalov, A M

    2016-04-01

    In the present study, three mouse-adapted variants of influenza A(H1N1)pdm09 virus were obtained by lung-to-lung passages of BALB/c, C57BL/6z and CD1 mice. The significantly increased virulence and pathogenicity of all of the mouse-adapted variants induced 100% mortality in the adapted mice. Genetic analysis indicated that the increased virulence of all of the mouse-adapted variants reflected the incremental acquisition of several mutations in PB2, PB1, HA, NP, NA, and NS2 proteins. Identical amino acid substitutions were also detected in all of the mouse-adapted variants of A(H1N1)pdm09 virus, including PB2 (K251R), PB1 (V652A), NP (I353V), NA (I106V, N248D) and NS1 (G159E). Apparently, influenza A(H1N1)pdm09 virus easily adapted to the host after serial passages in the lungs, inducing 100% lethality in the last experimental group. However, cross-challenge revealed that not all adapted variants are pathogenic for different laboratory mice. Such important results should be considered when using the influenza mice model.

  14. Adaptation of influenza A(H1N1)pdm09 virus in experimental mouse models.

    PubMed

    Prokopyeva, E A; Sobolev, I A; Prokopyev, M V; Shestopalov, A M

    2016-04-01

    In the present study, three mouse-adapted variants of influenza A(H1N1)pdm09 virus were obtained by lung-to-lung passages of BALB/c, C57BL/6z and CD1 mice. The significantly increased virulence and pathogenicity of all of the mouse-adapted variants induced 100% mortality in the adapted mice. Genetic analysis indicated that the increased virulence of all of the mouse-adapted variants reflected the incremental acquisition of several mutations in PB2, PB1, HA, NP, NA, and NS2 proteins. Identical amino acid substitutions were also detected in all of the mouse-adapted variants of A(H1N1)pdm09 virus, including PB2 (K251R), PB1 (V652A), NP (I353V), NA (I106V, N248D) and NS1 (G159E). Apparently, influenza A(H1N1)pdm09 virus easily adapted to the host after serial passages in the lungs, inducing 100% lethality in the last experimental group. However, cross-challenge revealed that not all adapted variants are pathogenic for different laboratory mice. Such important results should be considered when using the influenza mice model. PMID:26829383

  15. Humans and Ferrets with Prior H1N1 Influenza Virus Infections Do Not Exhibit Evidence of Original Antigenic Sin after Infection or Vaccination with the 2009 Pandemic H1N1 Influenza Virus

    PubMed Central

    O'Donnell, Christopher D.; Wright, Amber; Vogel, Leatrice; Boonnak, Kobporn; Treanor, John J.

    2014-01-01

    The hypothesis of original antigenic sin (OAS) states that the imprint established by an individual's first influenza virus infection governs the antibody response thereafter. Subsequent influenza virus infection results in an antibody response against the original infecting virus and an impaired immune response against the newer influenza virus. The purpose of our study was to seek evidence of OAS after infection or vaccination with the 2009 pandemic H1N1 (2009 pH1N1) virus in ferrets and humans previously infected with H1N1 viruses with various antigenic distances from the 2009 pH1N1 virus, including viruses from 1935 through 1999. In ferrets, seasonal H1N1 priming did not diminish the antibody response to infection or vaccination with the 2009 pH1N1 virus, nor did it diminish the T-cell response, indicating the absence of OAS in seasonal H1N1 virus-primed ferrets. Analysis of paired samples of human serum taken before and after vaccination with a monovalent inactivated 2009 pH1N1 vaccine showed a significantly greater-fold rise in the titer of antibody against the 2009 pH1N1 virus than against H1N1 viruses that circulated during the childhood of each subject. Thus, prior experience with H1N1 viruses did not result in an impairment of the antibody response against the 2009 pH1N1 vaccine. Our data from ferrets and humans suggest that prior exposure to H1N1 viruses did not impair the immune response against the 2009 pH1N1 virus. PMID:24648486

  16. A/H1N1 antibodies and TRIB2 autoantibodies in narcolepsy patients diagnosed in conjunction with the Pandemrix vaccination campaign in Sweden 2009-2010.

    PubMed

    Lind, Alexander; Ramelius, Anita; Olsson, Tomas; Arnheim-Dahlström, Lisen; Lamb, Favelle; Khademi, Mohsen; Ambati, Aditya; Maeurer, Markus; Nilsson, Anna-Lena; Bomfim, Izaura Lima; Fink, Katharina; Lernmark, Åke

    2014-05-01

    Narcolepsy is a lifelong sleep disorder related to hypocretin deficiency resulting from a specific loss of hypocretin-producing neurons in the lateral hypothalamic area. The disease is thought to be autoimmune due to a strong association with HLA-DQB1*06:02. In 2009 the World Health Organization (WHO) declared the H1N1 2009 flu pandemic (A/H1N1PDM09). In response to this, the Swedish vaccination campaign began in October of the same year, using the influenza vaccine Pandemrix(®). A few months later an excess of narcolepsy cases was observed. It is still unclear to what extent the vaccination campaign affected humoral autoimmunity associated with narcolepsy. We studied 47 patients with narcolepsy (6-69 years of age) and 80 healthy controls (3-61 years of age) selected after the Pandemrix vaccination campaign. The first aim was to determine antibodies against A/H1N1 and autoantibodies to Tribbles homolog 2 (TRIB2), a narcolepsy autoantigen candidate as well as to GAD65 and IA-2 as disease specificity controls. The second aim was to test if levels and frequencies of these antibodies and autoantibodies were associated with HLA-DQB1*06:02. In vitro transcribed and translated [(35)S]-methionine and -cysteine-labeled influenza A virus (A/California/04/2009/(H1N1)) segment 4 hemagglutinin was used to detect antibodies in a radiobinding assay. Autoantibodies to TRIB2, GAD65 and IA-2 were similarly detected in standard radiobinding assays. The narcolepsy patients had higher median levels of A/H1N1 antibodies than the controls (p = 0.006). A/H1N1 antibody levels were higher among the <13 years old (n = 12) compared to patients who were older than 30 years (n = 12, p = 0.014). Being HLA-DQB1*06:02 positive was associated with higher A/H1N1 antibody levels in both patients and controls (p = 0.026). Serum autoantibody levels to TRIB2 were low overall and high binders did not differ between patients and controls. We observed an association between levels of A/H1N1

  17. A/H1N1 antibodies and TRIB2 autoantibodies in narcolepsy patients diagnosed in conjunction with the Pandemrix vaccination campaign in Sweden 2009-2010.

    PubMed

    Lind, Alexander; Ramelius, Anita; Olsson, Tomas; Arnheim-Dahlström, Lisen; Lamb, Favelle; Khademi, Mohsen; Ambati, Aditya; Maeurer, Markus; Nilsson, Anna-Lena; Bomfim, Izaura Lima; Fink, Katharina; Lernmark, Åke

    2014-05-01

    Narcolepsy is a lifelong sleep disorder related to hypocretin deficiency resulting from a specific loss of hypocretin-producing neurons in the lateral hypothalamic area. The disease is thought to be autoimmune due to a strong association with HLA-DQB1*06:02. In 2009 the World Health Organization (WHO) declared the H1N1 2009 flu pandemic (A/H1N1PDM09). In response to this, the Swedish vaccination campaign began in October of the same year, using the influenza vaccine Pandemrix(®). A few months later an excess of narcolepsy cases was observed. It is still unclear to what extent the vaccination campaign affected humoral autoimmunity associated with narcolepsy. We studied 47 patients with narcolepsy (6-69 years of age) and 80 healthy controls (3-61 years of age) selected after the Pandemrix vaccination campaign. The first aim was to determine antibodies against A/H1N1 and autoantibodies to Tribbles homolog 2 (TRIB2), a narcolepsy autoantigen candidate as well as to GAD65 and IA-2 as disease specificity controls. The second aim was to test if levels and frequencies of these antibodies and autoantibodies were associated with HLA-DQB1*06:02. In vitro transcribed and translated [(35)S]-methionine and -cysteine-labeled influenza A virus (A/California/04/2009/(H1N1)) segment 4 hemagglutinin was used to detect antibodies in a radiobinding assay. Autoantibodies to TRIB2, GAD65 and IA-2 were similarly detected in standard radiobinding assays. The narcolepsy patients had higher median levels of A/H1N1 antibodies than the controls (p = 0.006). A/H1N1 antibody levels were higher among the <13 years old (n = 12) compared to patients who were older than 30 years (n = 12, p = 0.014). Being HLA-DQB1*06:02 positive was associated with higher A/H1N1 antibody levels in both patients and controls (p = 0.026). Serum autoantibody levels to TRIB2 were low overall and high binders did not differ between patients and controls. We observed an association between levels of A/H1N1

  18. An Influenza A/H1N1/2009 Hemagglutinin Vaccine Produced in Escherichia coli

    PubMed Central

    Aguilar-Yáñez, José M.; Portillo-Lara, Roberto; Mendoza-Ochoa, Gonzalo I.; García-Echauri, Sergio A.; López-Pacheco, Felipe; Bulnes-Abundis, David; Salgado-Gallegos, Johari; Lara-Mayorga, Itzel M.; Webb-Vargas, Yenny; León-Angel, Felipe O.; Rivero-Aranda, Ramón E.; Oropeza-Almazán, Yuriana; Ruiz-Palacios, Guillermo M.; Zertuche-Guerra, Manuel I.; DuBois, Rebecca M.; White, Stephen W.; Schultz-Cherry, Stacey; Russell, Charles J.; Alvarez, Mario M.

    2010-01-01

    Background The A/H1N1/2009 influenza pandemic made evident the need for faster and higher-yield methods for the production of influenza vaccines. Platforms based on virus culture in mammalian or insect cells are currently under investigation. Alternatively, expression of fragments of the hemagglutinin (HA) protein in prokaryotic systems can potentially be the most efficacious strategy for the manufacture of large quantities of influenza vaccine in a short period of time. Despite experimental evidence on the immunogenic potential of HA protein constructs expressed in bacteria, it is still generally accepted that glycosylation should be a requirement for vaccine efficacy. Methodology/Principal Findings We expressed the globular HA receptor binding domain, referred to here as HA63–286-RBD, of the influenza A/H1N1/2009 virus in Escherichia coli using a simple, robust and scalable process. The recombinant protein was refolded and purified from the insoluble fraction of the cellular lysate as a single species. Recombinant HA63–286-RBD appears to be properly folded, as shown by analytical ultracentrifugation and bio-recognition assays. It binds specifically to serum antibodies from influenza A/H1N1/2009 patients and was found to be immunogenic, to be capable of triggering the production of neutralizing antibodies, and to have protective activity in the ferret model. Conclusions/Significance Projections based on our production/purification data indicate that this strategy could yield up to half a billion doses of vaccine per month in a medium-scale pharmaceutical production facility equipped for bacterial culture. Also, our findings demonstrate that glycosylation is not a mandatory requirement for influenza vaccine efficacy. PMID:20661476

  19. Neurological events related to influenza A (H1N1) pdm09

    PubMed Central

    Cárdenas, Graciela; Soto-Hernández, José Luis; Díaz-Alba, Alexandra; Ugalde, Yair; Mérida-Puga, Jorge; Rosetti, Marcos; Sciutto, Edda

    2014-01-01

    Objectives To review neurological complications after the influenza A (H1N1) pdm09, highlighting the clinical differences between patients with post-vaccine or viral infection. Design A search on Medline, Ovid, EMBASE, and PubMed databases using the keywords “neurological complications of Influenza AH1N1” or “post-vaccine Influenza AH1N1.” Setting Only papers written in English, Spanish, German, French, Portuguese, and Italian published from March 2009 to December 2012 were included. Sample We included 104 articles presenting a total of 1636 patient cases. In addition, two cases of influenza vaccine-related neurological events from our neurological care center, arising during the period of study, were also included. Main outcome measures Demographic data and clinical diagnosis of neurological complications and outcomes: death, neurological sequelae or recovery after influenza A (H1N1) pdm09 vaccine or infection. Results The retrieved cases were divided into two groups: the post-vaccination group, with 287 patients, and the viral infection group, with 1349 patients. Most patients in the first group were adults. The main neurological complications were Guillain-Barre syndrome (GBS) or polyneuropathy (125), and seizures (23). All patients survived. Pediatric patients were predominant in the viral infection group. In this group, 60 patients (4.7%) died and 52 (30.1%) developed permanent sequelae. A wide spectrum of neurological complications was observed. Conclusions Fatal cases and severe, permanent, neurological sequelae were observed in the infection group only. Clinical outcome was more favorable in the post-vaccination group. In this context, the relevance of an accurate neurological evaluation is demonstrated for all suspicious cases, as well as the need of an appropriate long-term clinical and imaging follow-up of infection and post-vaccination events related to influenza A (H1N1) pdm09, to clearly estimate the magnitude of neurological complications

  20. Modeling influenza epidemics and pandemics: insights into the future of swine flu (H1N1)

    PubMed Central

    Coburn, Brian J; Wagner, Bradley G; Blower, Sally

    2009-01-01

    Here we present a review of the literature of influenza modeling studies, and discuss how these models can provide insights into the future of the currently circulating novel strain of influenza A (H1N1), formerly known as swine flu. We discuss how the feasibility of controlling an epidemic critically depends on the value of the Basic Reproduction Number (R0). The R0 for novel influenza A (H1N1) has recently been estimated to be between 1.4 and 1.6. This value is below values of R0 estimated for the 1918–1919 pandemic strain (mean R0~2: range 1.4 to 2.8) and is comparable to R0 values estimated for seasonal strains of influenza (mean R0 1.3: range 0.9 to 2.1). By reviewing results from previous modeling studies we conclude it is theoretically possible that a pandemic of H1N1 could be contained. However it may not be feasible, even in resource-rich countries, to achieve the necessary levels of vaccination and treatment for control. As a recent modeling study has shown, a global cooperative strategy will be essential in order to control a pandemic. This strategy will require resource-rich countries to share their vaccines and antivirals with resource-constrained and resource-poor countries. We conclude our review by discussing the necessity of developing new biologically complex models. We suggest that these models should simultaneously track the transmission dynamics of multiple strains of influenza in bird, pig and human populations. Such models could be critical for identifying effective new interventions, and informing pandemic preparedness planning. Finally, we show that by modeling cross-species transmission it may be possible to predict the emergence of pandemic strains of influenza. PMID:19545404

  1. Modeling influenza epidemics and pandemics: insights into the future of swine flu (H1N1).

    PubMed

    Coburn, Brian J; Wagner, Bradley G; Blower, Sally

    2009-06-22

    Here we present a review of the literature of influenza modeling studies, and discuss how these models can provide insights into the future of the currently circulating novel strain of influenza A (H1N1), formerly known as swine flu. We discuss how the feasibility of controlling an epidemic critically depends on the value of the Basic Reproduction Number (R0). The R0 for novel influenza A (H1N1) has recently been estimated to be between 1.4 and 1.6. This value is below values of R0 estimated for the 1918-1919 pandemic strain (mean R0 approximately 2: range 1.4 to 2.8) and is comparable to R0 values estimated for seasonal strains of influenza (mean R0 1.3: range 0.9 to 2.1). By reviewing results from previous modeling studies we conclude it is theoretically possible that a pandemic of H1N1 could be contained. However it may not be feasible, even in resource-rich countries, to achieve the necessary levels of vaccination and treatment for control. As a recent modeling study has shown, a global cooperative strategy will be essential in order to control a pandemic. This strategy will require resource-rich countries to share their vaccines and antivirals with resource-constrained and resource-poor countries. We conclude our review by discussing the necessity of developing new biologically complex models. We suggest that these models should simultaneously track the transmission dynamics of multiple strains of influenza in bird, pig and human populations. Such models could be critical for identifying effective new interventions, and informing pandemic preparedness planning. Finally, we show that by modeling cross-species transmission it may be possible to predict the emergence of pandemic strains of influenza.

  2. Continual re-introduction of human pandemic H1N1 influenza A viruses into US swine, 2009-2014

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Human-to-swine transmission of pandemic H1N1 influenza viruses (pH1N1) increased the genetic diversity of influenza A viruses in swine (swIAVs) globally and is linked to the emergence of new pandemic threats, including H3N2v variants. Through phylogenetic analysis of contemporary swIAVs in the Unit...

  3. Academics and competing interests in H1N1 influenza media reporting

    PubMed Central

    Mandeville, Kate L; O'Neill, Sam; Brighouse, Andrew; Walker, Alice; Yarrow, Kielan; Chan, Kenneth

    2014-01-01

    Background Concerns have been raised over competing interests (CoI) among academics during the 2009 to 2010 A/H1N1 pandemic. Media reporting can influence public anxiety and demand for pharmaceutical products. We assessed CoI of academics providing media commentary during the early stages of the pandemic. Methods We performed a retrospective content analysis of UK newspaper articles on A/H1N1 influenza, examining quoted sources. We noted when academics made a risk assessment of the pandemic and compared this with official estimations. We also looked for promotion or rejection of the use of neuraminidase inhibitors or H1N1-specific vaccine. We independently searched for CoI for each academic. Results Academics were the second most frequently quoted source after Ministers of Health. Where both academics and official agencies estimated the risk of H1N1, one in two academics assessed the risk as higher than official predictions. For academics with CoI, the odds of a higher risk assessment were 5.8 times greater than those made by academics without CoI (Wald p value=0.009). One in two academics commenting on the use of neuraminidase inhibitors or vaccine had CoI. The odds of CoI in academics promoting the use of neuraminidase inhibitors were 8.4 times greater than for academics not commenting on their use (Fisher's exact p=0.005). Conclusions There is evidence of CoI among academics providing media commentary during the early H1N1 pandemic. Heightened risk assessments, combined with advocacy for pharmaceutical products to counter this risk, may lead to increased public anxiety and demand. Academics should declare, and journalists report, relevant CoI for media interviews. PMID:24218071

  4. Illness representation on H1N1 influenza and preventive behaviors in the Hong Kong general population.

    PubMed

    Mo, Phoenix K H; Lau, Joseph T F

    2015-12-01

    This study examined illness representations of new influenza Human Swine Influenza A (H1N1) and association with H1N1 preventive behaviors among 300 Chinese adults using a population-based randomized telephone survey. Results showed that relatively few participants thought H1N1 would have serious consequences (12%-15.7%) and few showed negative emotional responses toward H1N1 (9%-24.7%). The majority of the participants thought H1N1 could be controlled by treatment (70.4%-72.7%). Multiple logistic regression analyses showed that treatment control (odds ratio = 1.78) and psychological attribution (odds ratio = .75) were associated with intention to take up influenza vaccination. Emotional representations were associated with lower likelihood of wearing face mask (odds ratio = .77) and hand washing (odds ratio = .67). Results confirm that illness representation variables are associated with H1N1 preventive behaviors.

  5. Origins of the 2009 H1N1 influenza pandemic in swine in Mexico.

    PubMed

    Mena, Ignacio; Nelson, Martha I; Quezada-Monroy, Francisco; Dutta, Jayeeta; Cortes-Fernández, Refugio; Lara-Puente, J Horacio; Castro-Peralta, Felipa; Cunha, Luis F; Trovão, Nídia S; Lozano-Dubernard, Bernardo; Rambaut, Andrew; van Bakel, Harm; García-Sastre, Adolfo

    2016-01-01

    Asia is considered an important source of influenza A virus (IAV) pandemics, owing to large, diverse viral reservoirs in poultry and swine. However, the zoonotic origins of the 2009 A/H1N1 influenza pandemic virus (pdmH1N1) remain unclear, due to conflicting evidence from swine and humans. There is strong evidence that the first human outbreak of pdmH1N1 occurred in Mexico in early 2009. However, no related swine viruses have been detected in Mexico or any part of the Americas, and to date the most closely related ancestor viruses were identified in Asian swine. Here, we use 58 new whole-genome sequences from IAVs collected in Mexican swine to establish that the swine virus responsible for the 2009 pandemic evolved in central Mexico. This finding highlights how the 2009 pandemic arose from a region not considered a pandemic risk, owing to an expansion of IAV diversity in swine resulting from long-distance live swine trade. PMID:27350259

  6. Origins of the 2009 H1N1 influenza pandemic in swine in Mexico.

    PubMed

    Mena, Ignacio; Nelson, Martha I; Quezada-Monroy, Francisco; Dutta, Jayeeta; Cortes-Fernández, Refugio; Lara-Puente, J Horacio; Castro-Peralta, Felipa; Cunha, Luis F; Trovão, Nídia S; Lozano-Dubernard, Bernardo; Rambaut, Andrew; van Bakel, Harm; García-Sastre, Adolfo

    2016-06-28

    Asia is considered an important source of influenza A virus (IAV) pandemics, owing to large, diverse viral reservoirs in poultry and swine. However, the zoonotic origins of the 2009 A/H1N1 influenza pandemic virus (pdmH1N1) remain unclear, due to conflicting evidence from swine and humans. There is strong evidence that the first human outbreak of pdmH1N1 occurred in Mexico in early 2009. However, no related swine viruses have been detected in Mexico or any part of the Americas, and to date the most closely related ancestor viruses were identified in Asian swine. Here, we use 58 new whole-genome sequences from IAVs collected in Mexican swine to establish that the swine virus responsible for the 2009 pandemic evolved in central Mexico. This finding highlights how the 2009 pandemic arose from a region not considered a pandemic risk, owing to an expansion of IAV diversity in swine resulting from long-distance live swine trade.

  7. Origins of the 2009 H1N1 influenza pandemic in swine in Mexico

    PubMed Central

    Mena, Ignacio; Nelson, Martha I; Quezada-Monroy, Francisco; Dutta, Jayeeta; Cortes-Fernández, Refugio; Lara-Puente, J Horacio; Castro-Peralta, Felipa; Cunha, Luis F; Trovão, Nídia S; Lozano-Dubernard, Bernardo; Rambaut, Andrew; van Bakel, Harm; García-Sastre, Adolfo

    2016-01-01

    Asia is considered an important source of influenza A virus (IAV) pandemics, owing to large, diverse viral reservoirs in poultry and swine. However, the zoonotic origins of the 2009 A/H1N1 influenza pandemic virus (pdmH1N1) remain unclear, due to conflicting evidence from swine and humans. There is strong evidence that the first human outbreak of pdmH1N1 occurred in Mexico in early 2009. However, no related swine viruses have been detected in Mexico or any part of the Americas, and to date the most closely related ancestor viruses were identified in Asian swine. Here, we use 58 new whole-genome sequences from IAVs collected in Mexican swine to establish that the swine virus responsible for the 2009 pandemic evolved in central Mexico. This finding highlights how the 2009 pandemic arose from a region not considered a pandemic risk, owing to an expansion of IAV diversity in swine resulting from long-distance live swine trade. DOI: http://dx.doi.org/10.7554/eLife.16777.001 PMID:27350259

  8. [Effect of Yinghua Pinggan granule against influenza A/H1N1 virus in vivo].

    PubMed

    Peng, Xue-qian; He, Yu; Zhou, Hui-fen; Zhang, Yu-yan; Yang, Jie-hong; Chen, Jun-kui; Lu, Yi-yu; Wan, Hai-tong

    2015-10-01

    To study the effect of Yinghua Pinggan granule (YHPG) against influenza A/H1N1 virus in vivo and on the immunologic function of infected mice. The intranasal influenza virus infection was adopted in ICR mouse to establish the influenza virus pneumonia model. At the 3rd and 7th day after the infection, the lung index and pathologic changes in lung tissues of mice were detected. Realtime PCR and flow cytometry were employed to observe the virus load in lung tissues and the levels of CD4+, CD8+, and CD4+/CD8+ in peripheral blood. The result showed that at the 3rd and 7th day after the infection, YHPG (15, 30 g x kg(-1)) can significant decrease in the lung index and virus load in lung tissues of mice infected with influenza virus, alleviate the pathologic changes in lung tissues, significantly increase the levels of CD4+ and CD4+/CD8+ ratio and reduce the levels of CD8+ in whole blood. This indicated that YHPG can inhibit the influenza virus replication, alleviate pulmonary damage and adjust the weak immunologic function of infected mice, with a certain therapeutic effect on mice infected by H1N1 virus in vivo.

  9. Influenza A/H1N1_09: Australia and New Zealand's winter of discontent.

    PubMed

    Kotsimbos, Tom; Waterer, Grant; Jenkins, Christine; Kelly, Paul M; Cheng, Allen; Hancox, Robert J; Holmes, Mark; Wood-Baker, Richard; Bowler, Simon; Irving, Louis; Thompson, Philip

    2010-02-15

    Influenza A/H1N1_09 emerged in Mexico at the end of the Northern Hemisphere winter. Within weeks, the focus shifted to the Southern Hemisphere as the introduction of the novel virus coincided with the beginning of the influenza season. Intensive public health and health services planning had occurred in Australia and New Zealand as preparation for an influenza pandemic before 2009. However, this first pandemic wave was quite different to what had been expected. Key elements of the pandemic and response are outlined from the perspective of clinicians working at the frontline of patient care. In particular, they examine why past influenza pandemics and recent history are poor predictors of the current pandemic, the discordance between potential for transmission and disease severity, the broad clinical spectrum of H1N1_09 infection, clinical and health service management issues, and the relationship between health care and government policy. Finally, they address the need for the respiratory community to show leadership in times of crisis. Lessons learned in Australia and New Zealand during 2009 have important messages for similarly resourced countries in the Northern Hemisphere in the coming months as they face their own influenza season.

  10. A Contributing Role for Anti-Neuraminidase Antibodies on Immunity to Pandemic H1N1 2009 Influenza A Virus

    PubMed Central

    Marcelin, Glendie; DuBois, Rebecca; Rubrum, Adam; Russell, Charles J.; McElhaney, Janet E.; Webby, Richard J.

    2011-01-01

    Background Exposure to contemporary seasonal influenza A viruses affords partial immunity to pandemic H1N1 2009 influenza A virus (pH1N1) infection. The impact of antibodies to the neuraminidase (NA) of seasonal influenza A viruses to cross-immunity against pH1N1 infection is unknown. Methods and Results Antibodies to the NA of different seasonal H1N1 influenza strains were tested for cross-reactivity against A/California/04/09 (pH1N1). A panel of reverse genetic (rg) recombinant viruses was generated containing 7 genes of the H1N1 influenza strain A/Puerto Rico/08/34 (PR8) and the NA gene of either the pandemic H1N1 2009 strain (pH1N1) or one of the following contemporary seasonal H1N1 strains: A/Solomon/03/06 (rg Solomon) or A/Brisbane/59/07 (rg Brisbane). Convalescent sera collected from mice infected with recombinant viruses were measured for cross-reactive antibodies to pH1N1 via Hemagglutinin Inhibition (HI) or Enzyme-Linked Immunosorbent Assay (ELISA). The ectodomain of a recombinant NA protein from the pH1N1 strain (pNA-ecto) was expressed, purified and used in ELISA to measure cross-reactive antibodies. Analysis of sera from elderly humans immunized with trivalent split-inactivated influenza (TIV) seasonal vaccines prior to 2009 revealed considerable cross-reactivity to pNA-ecto. High titers of cross-reactive antibodies were detected in mice inoculated with either rg Solomon or rg Brisbane. Convalescent sera from mice inoculated with recombinant viruses were used to immunize naïve recipient Balb/c mice by passive transfer prior to challenge with pH1N1. Mice receiving rg California sera were better protected than animals receiving rg Solomon or rg Brisbane sera. Conclusions The NA of contemporary seasonal H1N1 influenza strains induces a cross-reactive antibody response to pH1N1 that correlates with reduced lethality from pH1N1 challenge, albeit less efficiently than anti-pH1N1 NA antibodies. These findings demonstrate that seasonal NA antibodies

  11. Novel influenza A (H1N1) in patients with hematologic disease.

    PubMed

    Wei, Ju-ying; Chen, Fei-fei; Jin, Jie; Mai, Wen-yuan; Qian, Wen-bin; Meng, Hai-tao; Mao, Li-ping; Xu, Gai-xiang; Wang, Hua-feng; Lou, Yin-jun; Tong, Hong-yan

    2010-11-01

    Patients with hematologic disease are likely to be at increased risk for infection with influenza. We retrospectively analyzed 11 cases of patients with hematologic disease who were infected with pandemic H1N1 virus in our department, including their clinical manifestations, laboratory and imaging findings, outcomes of antiviral therapy, and factors associated with mortality. Notably, nine patients had lower respiratory tract disease. Five patients progressed to respiratory failure and eventually died, despite treatment with antivirals and/or corticosteroids and/or mechanical ventilation. We concluded that H1N1 2009 infection was associated with a severe course and high rate of mortality in patients with hematologic disease, and early diagnosis and antiviral treatment were important to reduce the rate of severe complications and mortality. PMID:21077745

  12. Persistence of the 2009 pandemic influenza A (H1N1) virus on N95 respirators.

    PubMed

    Coulliette, A D; Perry, K A; Edwards, J R; Noble-Wang, J A

    2013-04-01

    In the United States, the 2009 pandemic influenza A (H1N1) virus (pH1N1) infected almost 20% of the population and caused >200,000 hospitalizations and >10,000 deaths from April 2009 to April 2010. On 24 April 2009, the CDC posted interim guidance on infection control measures in health care settings explicitly for pH1N1 and recommended using filtering face respirators (FFRs) when in close contact with a suspected- or confirmed-to-be-infected individual, particularly when performing aerosol-generating procedures. The persistence and infectivity of pH1N1 were evaluated on FFRs, specifically N95 respirators, under various conditions of absolute humidity (AH) (4.1 × 10(5) mPa, 6.5 × 10(5) mPa, and 14.6 × 10(5) mPa), sample matrices (2% fetal bovine serum [FBS], 5 mg/ml mucin, and viral medium), and times (4, 12, 24, 48, 72, and 144 h). pH1N1 was distributed onto N95 coupons (3.8 to 4.2 cm(2)) and extracted by a vortex-centrifugation-filtration process, and the ability of the remaining virus to replicate was quantified using an enzyme-linked immunosorbent assay (ELISA) to determine the log10 concentration of the infectious virus per coupon. Overall, pH1N1 remained infectious for 6 days, with an approximately 1-log10 loss of virus concentrations over this time period. Time and AH both affected virus survival. We found significantly higher (P ≤ 0.01) reductions in virus concentrations at time points beyond 24 to 72 h (-0.52-log10 reduction) and 144 h (-0.74) at AHs of 6.5 × 10(5) mPa (-0.53) and 14.6 × 10(5) mPa (-0.47). This research supports discarding respirators after close contact with a person with suspected or confirmed influenza infection due to the virus's demonstrated ability to persist and remain infectious. PMID:23335770

  13. Neurologic complications of influenza A(H1N1)pdm09

    PubMed Central

    Khandaker, Gulam; Zurynski, Yvonne; Buttery, Jim; Marshall, Helen; Richmond, Peter C.; Dale, Russell C.; Royle, Jenny; Gold, Michael; Snelling, Tom; Whitehead, Bruce; Jones, Cheryl; Heron, Leon; McCaskill, Mary; Macartney, Kristine; Elliott, Elizabeth J.

    2012-01-01

    Objective: We sought to determine the range and extent of neurologic complications due to pandemic influenza A (H1N1) 2009 infection (pH1N1′09) in children hospitalized with influenza. Methods: Active hospital-based surveillance in 6 Australian tertiary pediatric referral centers between June 1 and September 30, 2009, for children aged <15 years with laboratory-confirmed pH1N1′09. Results: A total of 506 children with pH1N1′09 were hospitalized, of whom 49 (9.7%) had neurologic complications; median age 4.8 years (range 0.5–12.6 years) compared with 3.7 years (0.01–14.9 years) in those without complications. Approximately one-half (55.1%) of the children with neurologic complications had preexisting medical conditions, and 42.8% had preexisting neurologic conditions. On presentation, only 36.7% had the triad of cough, fever, and coryza/runny nose, whereas 38.7% had only 1 or no respiratory symptoms. Seizure was the most common neurologic complication (7.5%). Others included encephalitis/encephalopathy (1.4%), confusion/disorientation (1.0%), loss of consciousness (1.0%), and paralysis/Guillain-Barré syndrome (0.4%). A total of 30.6% needed intensive care unit (ICU) admission, 24.5% required mechanical ventilation, and 2 (4.1%) died. The mean length of stay in hospital was 6.5 days (median 3 days) and mean ICU stay was 4.4 days (median 1.5 days). Conclusions: Neurologic complications are relatively common among children admitted with influenza, and can be life-threatening. The lack of specific treatment for influenza-related neurologic complications underlines the importance of early diagnosis, use of antivirals, and universal influenza vaccination in children. Clinicians should consider influenza in children with neurologic symptoms even with a paucity of respiratory symptoms. PMID:22993280

  14. Emergence of avian H1N1 influenza viruses in pigs in China.

    PubMed

    Guan, Y; Shortridge, K F; Krauss, S; Li, P H; Kawaoka, Y; Webster, R G

    1996-11-01

    Avian influenza A viruses from Asia are recognized as the source of genes that reassorted with human viral genes to generate the Asian/57 (H2N2) and Hong Kong/68 (H3N2) pandemic strains earlier in this century. Here we report the genetic analysis of avian influenza A H1N1 viruses recently isolated from pigs in southern China, a host suspected to generate new pandemic strains through gene reassortment events. Each of the eight gene segments was of avian origin. Phylogenetic analysis indicates that these genes form an Asian sublineage of the Eurasian avian lineage, suggesting that these viruses are an independent introduction into pigs in Asia. The presence of avian influenza viruses in pigs in China places them in an optimal position for transmission to humans and may serve as an early warning of the emergence of the next human influenza virus pandemic.

  15. Cluster analysis of the origins of the new influenza A(H1N1) virus.

    PubMed

    Solovyov, A; Palacios, G; Briese, T; Lipkin, W I; Rabadan, R

    2009-05-28

    In March and April 2009, a new strain of influenza A(H1N1) virus has been isolated in Mexico and the United States. Since the initial reports more than 10,000 cases have been reported to the World Health Organization, all around the world. Several hundred isolates have already been sequenced and deposited in public databases. We have studied the genetics of the new strain and identified its closest relatives through a cluster analysis approach. We show that the new virus combines genetic information related to different swine influenza viruses. Segments PB2, PB1, PA, HA, NP and NS are related to swine H1N2 and H3N2 influenza viruses isolated in North America. Segments NA and M are related to swine influenza viruses isolated in Eurasia. PMID:19480812

  16. T-705 (favipiravir) induces lethal mutagenesis in influenza A H1N1 viruses in vitro.

    PubMed

    Baranovich, Tatiana; Wong, Sook-San; Armstrong, Jianling; Marjuki, Henju; Webby, Richard J; Webster, Robert G; Govorkova, Elena A

    2013-04-01

    Several novel anti-influenza compounds are in various phases of clinical development. One of these, T-705 (favipiravir), has a mechanism of action that is not fully understood but is suggested to target influenza virus RNA-dependent RNA polymerase. We investigated the mechanism of T-705 activity against influenza A (H1N1) viruses by applying selective drug pressure over multiple sequential passages in MDCK cells. We found that T-705 treatment did not select specific mutations in potential target proteins, including PB1, PB2, PA, and NP. Phenotypic assays based on cell viability confirmed that no T-705-resistant variants were selected. In the presence of T-705, titers of infectious virus decreased significantly (P < 0.0001) during serial passage in MDCK cells inoculated with seasonal influenza A (H1N1) viruses at a low multiplicity of infection (MOI; 0.0001 PFU/cell) or with 2009 pandemic H1N1 viruses at a high MOI (10 PFU/cell). There was no corresponding decrease in the number of viral RNA copies; therefore, specific virus infectivity (the ratio of infectious virus yield to viral RNA copy number) was reduced. Sequence analysis showed enrichment of G→A and C→T transversion mutations, increased mutation frequency, and a shift of the nucleotide profiles of individual NP gene clones under drug selection pressure. Our results demonstrate that T-705 induces a high rate of mutation that generates a nonviable viral phenotype and that lethal mutagenesis is a key antiviral mechanism of T-705. Our findings also explain the broad spectrum of activity of T-705 against viruses of multiple families.

  17. T-705 (Favipiravir) Induces Lethal Mutagenesis in Influenza A H1N1 Viruses In Vitro

    PubMed Central

    Baranovich, Tatiana; Wong, Sook-San; Armstrong, Jianling; Marjuki, Henju; Webby, Richard J.; Webster, Robert G.

    2013-01-01

    Several novel anti-influenza compounds are in various phases of clinical development. One of these, T-705 (favipiravir), has a mechanism of action that is not fully understood but is suggested to target influenza virus RNA-dependent RNA polymerase. We investigated the mechanism of T-705 activity against influenza A (H1N1) viruses by applying selective drug pressure over multiple sequential passages in MDCK cells. We found that T-705 treatment did not select specific mutations in potential target proteins, including PB1, PB2, PA, and NP. Phenotypic assays based on cell viability confirmed that no T-705-resistant variants were selected. In the presence of T-705, titers of infectious virus decreased significantly (P < 0.0001) during serial passage in MDCK cells inoculated with seasonal influenza A (H1N1) viruses at a low multiplicity of infection (MOI; 0.0001 PFU/cell) or with 2009 pandemic H1N1 viruses at a high MOI (10 PFU/cell). There was no corresponding decrease in the number of viral RNA copies; therefore, specific virus infectivity (the ratio of infectious virus yield to viral RNA copy number) was reduced. Sequence analysis showed enrichment of G→A and C→T transversion mutations, increased mutation frequency, and a shift of the nucleotide profiles of individual NP gene clones under drug selection pressure. Our results demonstrate that T-705 induces a high rate of mutation that generates a nonviable viral phenotype and that lethal mutagenesis is a key antiviral mechanism of T-705. Our findings also explain the broad spectrum of activity of T-705 against viruses of multiple families. PMID:23325689

  18. Coordination Costs for School-Located Influenza Vaccination Clinics, Maine, 2009 H1N1 Pandemic

    ERIC Educational Resources Information Center

    Asay, Garrett R. Beeler; Cho, Bo-Hyun; Lorick, Suchita A.; Tipton, Meredith L.; Dube, Nancy L.; Messonnier, Mark L.

    2012-01-01

    School nurses played a key role in Maine's school-located influenza vaccination (SLV) clinics during the 2009-2010 pandemic season. The objective of this study was to determine, from the school district perspective, the labor hours and costs associated with outside-clinic coordination activities (OCA). The authors defined OCA as labor hours spent…

  19. Neutralization and Binding Profile of Monoclonal Antibodies Generated Against Influenza A H1N1 Viruses.

    PubMed

    Shembekar, Nachiket; Mallajosyula, Vamsee V Aditya; Malik, Ankita; Saini, Ashok; Varadarajan, Raghavan; Gupta, Satish Kumar

    2016-08-01

    Monoclonal antibodies (MAbs) provide scope for the development of better therapeutics and diagnostic tools. Herein, we describe the binding and neutralization profile(s) for a panel of murine MAbs generated against influenza A H1N1 viruses elicited by immunization with pandemic H1 recombinant hemagglutinin (rHA)/whole virus or seasonal H1 rHA. Neutralizing MAbs, MA-2070 and MA-M, were obtained after pandemic A/California/07/2009 (H1N1) virus/rHA immunization(s). Both MAbs reacted specifically with rHA from A/California/07/2009 and A/England/195/2009 in ELISA. MA-2070 bound rHA of A/California/07/2009 with high affinity (KD = 51.36 ± 9.20 nM) and exhibited potent in vitro neutralization (IC50 = 2.50 μg/mL). MA-2070 bound within the stem domain of HA. MA-M exhibited both hemagglutination inhibition (HI, 1.50 μg/mL) and in vitro neutralization (IC50 = 0.66 μg/mL) activity against the pandemic A/California/07/2009 virus and showed higher binding affinity (KD = 9.80 ± 0.67 nM) than MA-2070. MAb, MA-H generated against the seasonal A/Solomon Islands/03/2006 (H1N1) rHA binds within the head domain and bound the seasonal H1N1 (A/Solomon Islands/03/2006 and A/New Caledonia/20/1990) rHAs with high affinity (KD; 0.72-8.23 nM). MA-H showed high HI (2.50 μg/mL) and in vitro neutralization (IC50 = 2.61 μg/mL) activity against the A/Solomon Islands/03/2006 virus. All 3 MAbs failed to react in ELISA with rHA from various strains of H2N2, H3N2, H5N1, H7N9, and influenza virus B, suggesting their specificity for either pandemic or seasonal H1N1 influenza virus. The MAbs reported here may be useful in developing diagnostic assays.

  20. Early recognition of the 2009 pandemic influenza A (H1N1) pneumonia by chest ultrasound

    PubMed Central

    2012-01-01

    Introduction The clinical picture of the pandemic influenza A (H1N1)v ranges from a self-limiting afebrile infection to a rapidly progressive pneumonia. Prompt diagnosis and well-timed treatment are recommended. Chest radiography (CRx) often fails to detect the early interstitial stage. The aim of this study was to evaluate the role of bedside chest ultrasonography (US) in the early management of the 2009 influenza A (H1N1)v infection. Methods 98 patients who arrived in the Emergency Department complaining of influenza-like symptoms were enrolled in the study. Patients not displaying symptoms of acute respiratory distress were discharged without further investigations. Among patients with clinical suggestion of a community-acquired pneumonia, cases encountering other diagnoses or comorbidities were excluded from the study. Clinical history, laboratory tests, CRx, and computed tomography (CT) scan, if indicated, contributed to define the diagnosis of pneumonia in the remaining patients. Chest US was performed by an emergency physician, looking for presence of interstitial syndrome, alveolar consolidation, pleural line abnormalities, and pleural effusion, in 34 patients with a final diagnosis of pneumonia, in 16 having normal initial CRx, and in 33 without pneumonia, as controls. Results Chest US was carried out without discomfort in all subjects, requiring a relatively short time (9 minutes; range, 7 to 13 minutes). An abnormal US pattern was detected in 32 of 34 patients with pneumonia (94.1%). A prevalent US pattern of interstitial syndrome was depicted in 15 of 16 patients with normal initial CRx, of whom 10 (62.5%) had a final diagnosis of viral (H1N1) pneumonia. Patients with pneumonia and abnormal initial CRx, of whom only four had a final diagnosis of viral (H1N1) pneumonia (22.2%; P < 0.05), mainly displayed an US pattern of alveolar consolidation. Finally, a positive US pattern of interstitial syndrome was found in five of 33 controls (15.1%). False

  1. Neutralization and Binding Profile of Monoclonal Antibodies Generated Against Influenza A H1N1 Viruses.

    PubMed

    Shembekar, Nachiket; Mallajosyula, Vamsee V Aditya; Malik, Ankita; Saini, Ashok; Varadarajan, Raghavan; Gupta, Satish Kumar

    2016-08-01

    Monoclonal antibodies (MAbs) provide scope for the development of better therapeutics and diagnostic tools. Herein, we describe the binding and neutralization profile(s) for a panel of murine MAbs generated against influenza A H1N1 viruses elicited by immunization with pandemic H1 recombinant hemagglutinin (rHA)/whole virus or seasonal H1 rHA. Neutralizing MAbs, MA-2070 and MA-M, were obtained after pandemic A/California/07/2009 (H1N1) virus/rHA immunization(s). Both MAbs reacted specifically with rHA from A/California/07/2009 and A/England/195/2009 in ELISA. MA-2070 bound rHA of A/California/07/2009 with high affinity (KD = 51.36 ± 9.20 nM) and exhibited potent in vitro neutralization (IC50 = 2.50 μg/mL). MA-2070 bound within the stem domain of HA. MA-M exhibited both hemagglutination inhibition (HI, 1.50 μg/mL) and in vitro neutralization (IC50 = 0.66 μg/mL) activity against the pandemic A/California/07/2009 virus and showed higher binding affinity (KD = 9.80 ± 0.67 nM) than MA-2070. MAb, MA-H generated against the seasonal A/Solomon Islands/03/2006 (H1N1) rHA binds within the head domain and bound the seasonal H1N1 (A/Solomon Islands/03/2006 and A/New Caledonia/20/1990) rHAs with high affinity (KD; 0.72-8.23 nM). MA-H showed high HI (2.50 μg/mL) and in vitro neutralization (IC50 = 2.61 μg/mL) activity against the A/Solomon Islands/03/2006 virus. All 3 MAbs failed to react in ELISA with rHA from various strains of H2N2, H3N2, H5N1, H7N9, and influenza virus B, suggesting their specificity for either pandemic or seasonal H1N1 influenza virus. The MAbs reported here may be useful in developing diagnostic assays. PMID:27463230

  2. Caveolin-1 influences human influenza A virus (H1N1) multiplication in cell culture

    PubMed Central

    2010-01-01

    Background The threat of recurring influenza pandemics caused by new viral strains and the occurrence of escape mutants necessitate the search for potent therapeutic targets. The dependence of viruses on cellular factors provides a weak-spot in the viral multiplication strategy and a means to interfere with viral multiplication. Results Using a motif-based search strategy for antiviral targets we identified caveolin-1 (Cav-1) as a putative cellular interaction partner of human influenza A viruses, including the pandemic influenza A virus (H1N1) strains of swine origin circulating from spring 2009 on. The influence of Cav-1 on human influenza A/PR/8/34 (H1N1) virus replication was determined in inhibition and competition experiments. RNAi-mediated Cav-1 knock-down as well as transfection of a dominant-negative Cav-1 mutant results in a decrease in virus titre in infected Madin-Darby canine kidney cells (MDCK), a cell line commonly used in basic influenza research as well as in virus vaccine production. To understand the molecular basis of the phenomenon we focussed on the putative caveolin-1 binding domain (CBD) located in the lumenal, juxtamembranal portion of the M2 matrix protein which has been identified in the motif-based search. Pull-down assays and co-immunoprecipitation experiments showed that caveolin-1 binds to M2. The data suggest, that Cav-1 modulates influenza virus A replication presumably based on M2/Cav-1 interaction. Conclusion As Cav-1 is involved in the human influenza A virus life cycle, the multifunctional protein and its interaction with M2 protein of human influenza A viruses represent a promising starting point for the search for antiviral agents. PMID:20504340

  3. Behavioural response in educated young adults towards influenza A(H1N1)pdm09.

    PubMed

    Chen, S C; Hsieh, N H; You, S H; Wang, C H; Liao, C M

    2015-07-01

    The purpose of this paper was to determine how contact behaviour change influences the indoor transmission of influenza A(H1N1)pdm09 among school children. We incorporated transmission rate matrices constructed from questionnaire responses into an epidemiological model to simulate contact behaviour change during an influenza epidemic. We constructed a dose-response model describing the relationships between contact rate, viral load, and respiratory symptom scores using published experimental human infection data for A(H1N1)pdm09. Findings showed that that mean numbers of contacts were 5.66 ± 6.23 and 1.96 ± 2.76 d-1 in the 13-19 and 40-59 years age groups, respectively. We found that the basic reproduction number (R 0) was <1 during weekends in pandemic periods, implying that school closures or class suspensions are probably an effective social distancing policy to control pandemic influenza transmission. We conclude that human contact behaviour change is a potentially influential factor on influenza infection rates. For substantiation of this effect, we recommend a future study with more comprehensive control measures.

  4. Novel triple-reassortant H1N1 swine influenza viruses in pigs in Tianjin, Northern China.

    PubMed

    Sun, Ying-Feng; Wang, Xiu-Hui; Li, Xiu-Li; Zhang, Li; Li, Hai-Hua; Lu, Chao; Yang, Chun-Lei; Feng, Jing; Han, Wei; Ren, Wei-Ke; Tian, Xiang-Xue; Tong, Guang-Zhi; Wen, Feng; Li, Ze-Jun; Gong, Xiao-Qian; Liu, Xiao-Min; Ruan, Bao-Yang; Yan, Ming-Hua; Yu, Hai

    2016-02-01

    Pigs are susceptible to both human and avian influenza viruses and therefore have been proposed to be mixing vessels for the generation of pandemic influenza viruses through reassortment. In this study, for the first time, we report the isolation and genetic analyses of three novel triple-reassortant H1N1 swine influenza viruses from pigs in Tianjin, Northern China. Phylogenetic analysis showed that these novel viruses contained genes from the 2009 pandemic H1N1 (PB2, PB1, PA and NP), Eurasian swine (HA, NA and M) and triple-reassortant swine (NS) lineages. This indicated that the reassortment among the 2009 pandemic H1N1, Eurasian swine and triple-reassortant swine influenza viruses had taken place in pigs in Tianjin and resulted in the generation of new viruses. Furthermore, three human-like H1N1, two classical swine H1N1 and two Eurasian swine H1N1 viruses were also isolated during the swine influenza virus surveillance from 2009 to 2013, which indicated that multiple genetic lineages of swine H1N1 viruses were co-circulating in the swine population in Tianjin, China. The emergence of novel triple-reassortant H1N1 swine influenza viruses may be a potential threat to human health and emphasizes the importance of further continuous surveillance. PMID:26790939

  5. Novel triple-reassortant H1N1 swine influenza viruses in pigs in Tianjin, Northern China.

    PubMed

    Sun, Ying-Feng; Wang, Xiu-Hui; Li, Xiu-Li; Zhang, Li; Li, Hai-Hua; Lu, Chao; Yang, Chun-Lei; Feng, Jing; Han, Wei; Ren, Wei-Ke; Tian, Xiang-Xue; Tong, Guang-Zhi; Wen, Feng; Li, Ze-Jun; Gong, Xiao-Qian; Liu, Xiao-Min; Ruan, Bao-Yang; Yan, Ming-Hua; Yu, Hai

    2016-02-01

    Pigs are susceptible to both human and avian influenza viruses and therefore have been proposed to be mixing vessels for the generation of pandemic influenza viruses through reassortment. In this study, for the first time, we report the isolation and genetic analyses of three novel triple-reassortant H1N1 swine influenza viruses from pigs in Tianjin, Northern China. Phylogenetic analysis showed that these novel viruses contained genes from the 2009 pandemic H1N1 (PB2, PB1, PA and NP), Eurasian swine (HA, NA and M) and triple-reassortant swine (NS) lineages. This indicated that the reassortment among the 2009 pandemic H1N1, Eurasian swine and triple-reassortant swine influenza viruses had taken place in pigs in Tianjin and resulted in the generation of new viruses. Furthermore, three human-like H1N1, two classical swine H1N1 and two Eurasian swine H1N1 viruses were also isolated during the swine influenza virus surveillance from 2009 to 2013, which indicated that multiple genetic lineages of swine H1N1 viruses were co-circulating in the swine population in Tianjin, China. The emergence of novel triple-reassortant H1N1 swine influenza viruses may be a potential threat to human health and emphasizes the importance of further continuous surveillance.

  6. The Genomic Contributions of Avian H1N1 Influenza A Viruses to the Evolution of Mammalian Strains.

    PubMed

    Koçer, Zeynep A; Carter, Robert; Wu, Gang; Zhang, Jinghui; Webster, Robert G

    2015-01-01

    Among the influenza A viruses (IAVs) in wild aquatic birds, only H1, H2, and H3 subtypes have caused epidemics in humans. H1N1 viruses of avian origin have also caused 3 of 5 pandemics. To understand the reappearance of H1N1 in the context of pandemic emergence, we investigated whether avian H1N1 IAVs have contributed to the evolution of human, swine, and 2009 pandemic H1N1 IAVs. On the basis of phylogenetic analysis, we concluded that the polymerase gene segments (especially PB2 and PA) circulating in North American avian H1N1 IAVs have been reintroduced to swine multiple times, resulting in different lineages that led to the emergence of the 2009 pandemic H1N1 IAVs. Moreover, the similar topologies of hemagglutinin and nucleoprotein and neuraminidase and matrix gene segments suggest that each surface glycoprotein coevolved with an internal gene segment within the H1N1 subtype. The genotype of avian H1N1 IAVs of Charadriiformes origin isolated in 2009 differs from that of avian H1N1 IAVs of Anseriformes origin. When the antigenic sites in the hemagglutinin of all 31 North American avian H1N1 IAVs were considered, 60%-80% of the amino acids at the antigenic sites were identical to those in 1918 and/or 2009 pandemic H1N1 viruses. Thus, although the pathogenicity of avian H1N1 IAVs could not be inferred from the phylogeny due to the small dataset, the evolutionary process within the H1N1 IAV subtype suggests that the circulation of H1N1 IAVs in wild birds poses a continuous threat for future influenza pandemics in humans. PMID:26208281

  7. The Genomic Contributions of Avian H1N1 Influenza A Viruses to the Evolution of Mammalian Strains.

    PubMed

    Koçer, Zeynep A; Carter, Robert; Wu, Gang; Zhang, Jinghui; Webster, Robert G

    2015-01-01

    Among the influenza A viruses (IAVs) in wild aquatic birds, only H1, H2, and H3 subtypes have caused epidemics in humans. H1N1 viruses of avian origin have also caused 3 of 5 pandemics. To understand the reappearance of H1N1 in the context of pandemic emergence, we investigated whether avian H1N1 IAVs have contributed to the evolution of human, swine, and 2009 pandemic H1N1 IAVs. On the basis of phylogenetic analysis, we concluded that the polymerase gene segments (especially PB2 and PA) circulating in North American avian H1N1 IAVs have been reintroduced to swine multiple times, resulting in different lineages that led to the emergence of the 2009 pandemic H1N1 IAVs. Moreover, the similar topologies of hemagglutinin and nucleoprotein and neuraminidase and matrix gene segments suggest that each surface glycoprotein coevolved with an internal gene segment within the H1N1 subtype. The genotype of avian H1N1 IAVs of Charadriiformes origin isolated in 2009 differs from that of avian H1N1 IAVs of Anseriformes origin. When the antigenic sites in the hemagglutinin of all 31 North American avian H1N1 IAVs were considered, 60%-80% of the amino acids at the antigenic sites were identical to those in 1918 and/or 2009 pandemic H1N1 viruses. Thus, although the pathogenicity of avian H1N1 IAVs could not be inferred from the phylogeny due to the small dataset, the evolutionary process within the H1N1 IAV subtype suggests that the circulation of H1N1 IAVs in wild birds poses a continuous threat for future influenza pandemics in humans.

  8. Transcription analysis on response of swine lung to H1N1 swine influenza virus

    PubMed Central

    2011-01-01

    Background As a mild, highly contagious, respiratory disease, swine influenza always damages the innate immune systems, and increases susceptibility to secondary infections which results in considerable morbidity and mortality in pigs. Nevertheless, the systematical host response of pigs to swine influenza virus infection remains largely unknown. To explore it, a time-course gene expression profiling was performed for comprehensive analysis of the global host response induced by H1N1 swine influenza virus in pigs. Results At the early stage of H1N1 swine virus infection, pigs were suffering mild respiratory symptoms and pathological changes. A total of 268 porcine genes showing differential expression (DE) after inoculation were identified to compare with the controls on day 3 post infection (PID) (Fold change ≥ 2, p < 0.05). The DE genes were involved in many vital functional classes, mainly including signal transduction, immune response, inflammatory response, cell adhesion and cell-cell signalling. Noticeably, the genes associated with immune and inflammatory response showed highly overexpressed. Through the pathway analysis, the significant pathways mainly concerned with Cell adhesion molecules, Cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway and MAPK signaling pathway, suggesting that the host took different strategies to activate these pathways so as to prevent virus infections at the early stage. However, on PID 7, the predominant function classes of DE genes included signal transduction, metabolism, transcription, development and transport. Furthermore, the most significant pathways switched to PPAR signaling pathway and complement and coagulation cascades, showing that the host might start to repair excessive tissue damage by anti-inflammatory functions. These results on PID 7 demonstrated beneficial turnover for host to prevent excessive inflammatory damage and recover the normal state by activating these clusters of genes

  9. Immunogenicity of Virus Like Particle Forming Baculoviral DNA Vaccine against Pandemic Influenza H1N1.

    PubMed

    Gwon, Yong-Dae; Kim, Sehyun; Cho, Yeondong; Heo, Yoonki; Cho, Hansam; Park, Kihoon; Lee, Hee-Jung; Choi, Jiwon; Poo, Haryoung; Kim, Young Bong

    2016-01-01

    An outbreak of influenza H1N1 in 2009, representing the first influenza pandemic of the 21st century, was transmitted to over a million individuals and claimed 18,449 lives. The current status in many countries is to prepare influenza vaccine using cell-based or egg-based killed vaccine. However, traditional influenza vaccine platforms have several limitations. To overcome these limitations, many researchers have tried various approaches to develop alternative production platforms. One of the alternative approach, we reported the efficacy of influenza HA vaccination using a baculoviral DNA vaccine (AcHERV-HA). However, the immune response elicited by the AcHERV-HA vaccine, which only targets the HA antigen, was lower than that of the commercial killed vaccine. To overcome the limitations of this previous vaccine, we constructed a human endogenous retrovirus (HERV) envelope-coated, baculovirus-based, virus-like-particle (VLP)-forming DNA vaccine (termed AcHERV-VLP) against pandemic influenza A/California/04/2009 (pH1N1). BALB/c mice immunized with AcHERV-VLP (1×107 FFU AcHERV-VLP, i.m.) and compared with mice immunized with the killed vaccine or mice immunized with AcHERV-HA. As a result, AcHERV-VLP immunization produced a greater humoral immune response and exhibited neutralizing activity with an intrasubgroup H1 strain (PR8), elicited neutralizing antibody production, a high level of interferon-γ secretion in splenocytes, and diminished virus shedding in the lung after challenge with a lethal dose of influenza virus. In conclusion, VLP-forming baculovirus DNA vaccine could be a potential vaccine candidate capable of efficiently delivering DNA to the vaccinee and VLP forming DNA eliciting stronger immunogenicity than egg-based killed vaccines. PMID:27149064

  10. Immunogenicity of Virus Like Particle Forming Baculoviral DNA Vaccine against Pandemic Influenza H1N1

    PubMed Central

    Gwon, Yong-Dae; Kim, Sehyun; Cho, Yeondong; Heo, Yoonki; Cho, Hansam; Park, Kihoon; Lee, Hee-Jung; Choi, Jiwon; Poo, Haryoung; Kim, Young Bong

    2016-01-01

    An outbreak of influenza H1N1 in 2009, representing the first influenza pandemic of the 21st century, was transmitted to over a million individuals and claimed 18,449 lives. The current status in many countries is to prepare influenza vaccine using cell-based or egg-based killed vaccine. However, traditional influenza vaccine platforms have several limitations. To overcome these limitations, many researchers have tried various approaches to develop alternative production platforms. One of the alternative approach, we reported the efficacy of influenza HA vaccination using a baculoviral DNA vaccine (AcHERV-HA). However, the immune response elicited by the AcHERV-HA vaccine, which only targets the HA antigen, was lower than that of the commercial killed vaccine. To overcome the limitations of this previous vaccine, we constructed a human endogenous retrovirus (HERV) envelope-coated, baculovirus-based, virus-like-particle (VLP)–forming DNA vaccine (termed AcHERV-VLP) against pandemic influenza A/California/04/2009 (pH1N1). BALB/c mice immunized with AcHERV-VLP (1×107 FFU AcHERV-VLP, i.m.) and compared with mice immunized with the killed vaccine or mice immunized with AcHERV-HA. As a result, AcHERV-VLP immunization produced a greater humoral immune response and exhibited neutralizing activity with an intrasubgroup H1 strain (PR8), elicited neutralizing antibody production, a high level of interferon-γ secretion in splenocytes, and diminished virus shedding in the lung after challenge with a lethal dose of influenza virus. In conclusion, VLP-forming baculovirus DNA vaccine could be a potential vaccine candidate capable of efficiently delivering DNA to the vaccinee and VLP forming DNA eliciting stronger immunogenicity than egg-based killed vaccines. PMID:27149064

  11. An update on swine-origin influenza virus A/H1N1: a review.

    PubMed

    Schnitzler, Sebastian U; Schnitzler, Paul

    2009-12-01

    Influenza viruses cause annual epidemics and occasional pandemics that have claimed the lives of millions. The emergence of new strains will continue to pose challenges to public health and the scientific communities. The recent flu pandemic caused by a swine-origin influenza virus A/H1N1 (S-OIV) presents an opportunity to examine virulence factors, the spread of the infection and to prepare for major influenza outbreaks in the future. The virus contains a novel constellation of gene segments, the nearest known precursors being viruses found in swine and it probably arose through reassortment of two viruses of swine origin. Specific markers for virulence can be evaluated in the viral genome, PB1-F2 is a molecular marker of pathogenicity but is not present in the new S-OIV. While attention was focused on a threat of an avian influenza H5N1 pandemic emerging from Asia, a novel influenza virus of swine origin emerged in North America, and is now spreading worldwide. However, S-OIV demonstrates that even serotypes already encountered in past human pandemics may constitute new pandemic threats. There are concerns that this virus may mutate or reassort with existing influenza viruses giving rise to more transmissible or more pathogenic viruses. The 1918 Spanish flu pandemic virus was relatively mild in its first wave and acquired more virulence when it returned in the winter. Thus preparedness on a global scale against a potential more virulent strain is highly recommended. Most isolates of the new S-OIVs are susceptible to neuraminidase inhibitors, and currently a vaccine against the pandemic strain is being manufactured and will be available this fall. This review summarizes the current information on the new pandemic swine-origin influenza virus A/H1N1.

  12. Genesis and pathogenesis of the 1918 pandemic H1N1 influenza A virus.

    PubMed

    Worobey, Michael; Han, Guan-Zhu; Rambaut, Andrew

    2014-06-01

    The source, timing, and geographical origin of the 1918-1920 pandemic influenza A virus have remained tenaciously obscure for nearly a century, as have the reasons for its unusual severity among young adults. Here, we reconstruct the origins of the pandemic virus and the classic swine influenza and (postpandemic) seasonal H1N1 lineages using a host-specific molecular clock approach that is demonstrably more accurate than previous methods. Our results suggest that the 1918 pandemic virus originated shortly before 1918 when a human H1 virus, which we infer emerged before ∼1907, acquired avian N1 neuraminidase and internal protein genes. We find that the resulting pandemic virus jumped directly to swine but was likely displaced in humans by ∼1922 by a reassortant with an antigenically distinct H1 HA. Hence, although the swine lineage was a direct descendent of the pandemic virus, the post-1918 seasonal H1N1 lineage evidently was not, at least for HA. These findings help resolve several seemingly disparate observations from 20th century influenza epidemiology, seroarcheology, and immunology. The phylogenetic results, combined with these other lines of evidence, suggest that the high mortality in 1918 among adults aged ∼20 to ∼40 y may have been due primarily to their childhood exposure to a doubly heterosubtypic putative H3N8 virus, which we estimate circulated from ∼1889-1900. All other age groups (except immunologically naive infants) were likely partially protected by childhood exposure to N1 and/or H1-related antigens. Similar processes may underlie age-specific mortality differences between seasonal H1N1 vs. H3N2 and human H5N1 vs. H7N9 infections.

  13. Measured dynamic social contact patterns explain the spread of H1N1v influenza.

    PubMed

    Eames, Ken T D; Tilston, Natasha L; Brooks-Pollock, Ellen; Edmunds, W John

    2012-01-01

    Patterns of social mixing are key determinants of epidemic spread. Here we present the results of an internet-based social contact survey completed by a cohort of participants over 9,000 times between July 2009 and March 2010, during the 2009 H1N1v influenza epidemic. We quantify the changes in social contact patterns over time, finding that school children make 40% fewer contacts during holiday periods than during term time. We use these dynamically varying contact patterns to parameterise an age-structured model of influenza spread, capturing well the observed patterns of incidence; the changing contact patterns resulted in a fall of approximately 35% in the reproduction number of influenza during the holidays. This work illustrates the importance of including changing mixing patterns in epidemic models. We conclude that changes in contact patterns explain changes in disease incidence, and that the timing of school terms drove the 2009 H1N1v epidemic in the UK. Changes in social mixing patterns can be usefully measured through simple internet-based surveys. PMID:22412366

  14. Emergence and pandemic potential of swine-origin H1N1 influenza virus.

    PubMed

    Neumann, Gabriele; Noda, Takeshi; Kawaoka, Yoshihiro

    2009-06-18

    Influenza viruses cause annual epidemics and occasional pandemics that have claimed the lives of millions. The emergence of new strains will continue to pose challenges to public health and the scientific communities. A prime example is the recent emergence of swine-origin H1N1 viruses that have transmitted to and spread among humans, resulting in outbreaks internationally. Efforts to control these outbreaks and real-time monitoring of the evolution of this virus should provide us with invaluable information to direct infectious disease control programmes and to improve understanding of the factors that determine viral pathogenicity and/or transmissibility.

  15. Uptake of pandemic influenza (H1N1)-2009 vaccines in Brazil, 2010.

    PubMed

    Domingues, Carla Magda Allan S; de Oliveira, Wanderson Kleber

    2012-07-01

    In 2010, the Brazilian Ministry of Health organized a mass vaccination campaign of selected priority groups in response to the 2009 H1N1 influenza pandemic. The campaign was conducted in six phases from March to July, 2010. Priority groups included healthcare professionals, indigenous persons, pregnant women, young children, persons with chronic illnesses and otherwise healthy adults 20-39 years of age. Over 89 million doses of pandemic influenza vaccines were administered, surpassing immunization targets among several priority groups, including healthcare professionals. We reviewed strategies used in Brazil to promote vaccination against pandemic influenza as well as factors external to the campaign that may have contributed to vaccine uptake among priority groups. PMID:22609010

  16. Acute disseminated encephalomyelitis following 2009 H1N1 influenza vaccination.

    PubMed

    Maeda, Kengo; Idehara, Ryo

    2012-01-01

    Since the worldwide spread of the novel influenza type A virus in 2009, trivalent vaccines against H1N1 (pandemic) 09 and seasonal influenza have been used. We describe a 33-year-old woman who presented with hypoesthesia below the Th7 level fifteen days after vaccination without any preceding infection. Cerebrospinal fluid showed an increased level of myelin basic protein and positive oligoclonal IgG bands. Magnetic resonance imaging revealed disseminated lesions in the brain and thoracic cord. Steroid therapy improved her symptoms. She was diagnosed as having acute disseminated encephalomyelitis (ADEM) possibly related to the vaccination. As a potential adverse effect of the influenza vaccine, in addition to Guillain-Barré syndrome, ADEM should also be recognized. PMID:22821116

  17. Successful treatment of naturally occurring influenza A/USSR/77 H1N1.

    PubMed

    Van Voris, L P; Betts, R F; Hayden, F G; Christmas, W A; Douglas, R G

    1981-03-20

    Forty-five university students with proved influenza A/USSR/77 H1N1 infection were randomly treated with either amantadine hydrochloride (14 students), rimantadine hydrochloride (19 students), or placebo (12 students). By 48 hours after initiation of therapy, amantadine and rimantadine recipients had significantly less fever and greater improvement compared with subjects given the placebo. Minor reversible CNS side effects at the end of the five-day course of therapy were observed in one third of the amantadine-treated subjects. However, both amantadine and rimantadine recipients returned to classes earlier and shed smaller amounts of virus than placebo recipients. Thus, both drugs exerted a notable therapeutic effect. Hence, during an influenza outbreak, five days of empirical therapy with amantadine or rimantadine for persons with an influenza-like syndrome should ameliorate clinical symptoms and might decrease spread of virus.

  18. Prior Infections With Seasonal Influenza A/H1N1 Virus Reduced the Illness Severity and Epidemic Intensity of Pandemic H1N1 Influenza in Healthy Adults

    PubMed Central

    Atmar, Robert L.; Franco, Luis M.; Quarles, John M.; Niño, Diane; Wells, Janet M.; Arden, Nancy; Cheung, Sheree; Belmont, John W.

    2012-01-01

    Background. A new influenza A/H1N1 (pH1N1) virus emerged in April 2009, proceeded to spread worldwide, and was designated as an influenza pandemic. A/H1N1 viruses had circulated in 1918–1957 and 1977–2009 and were in the annual vaccine during 1977–2009. Methods. Serum antibody to the pH1N1 and seasonal A/H1N1 viruses was measured in 579 healthy adults at enrollment (fall 2009) and after surveillance for illness (spring 2010). Subjects reporting with moderate to severe acute respiratory illness had illness and virus quantitation for 1 week; evaluations for missed illnesses were conducted over holiday periods and at the spring 2010 visit. Results. After excluding 66 subjects who received pH1N1 vaccine, 513 remained. Seventy-seven had reported with moderate to severe illnesses; 31 were infected with pH1N1 virus, and 30 with a rhinovirus. Determining etiology from clinical findings was not possible, but fever and prominent myalgias favored influenza and prominent rhinorrhea favored rhinovirus. Tests of fall and spring antibody indicated pH1N1 infection of 23% had occurred, with the rate decreasing with increasing anti-pH1N1 antibody; a similar pattern was seen for influenza-associated illness. A reducing frequency of pH1N1 infections was also seen with increasing antibody to the recent seasonal A/H1N1 virus (A/Brisbane/59/07). Preexisting antibody to pH1N1 virus, responses to a single vaccine dose, a low infection-to-illness ratio, and a short duration of illness and virus shedding among those with influenza indicated presence of considerable preexisting immunity to pH1N1 in the population. Conclusions. The 2009 A/H1N1 epidemic among healthy adults was relatively mild, most likely because of immunity from prior infections with A/H1N1 viruses. PMID:22075792

  19. Human Dendritic Cell Response Signatures Distinguish 1918, Pandemic, and Seasonal H1N1 Influenza Viruses

    PubMed Central

    Hartmann, Boris M.; Thakar, Juilee; Albrecht, Randy A.; Avey, Stefan; Zaslavsky, Elena; Marjanovic, Nada; Chikina, Maria; Fribourg, Miguel; Hayot, Fernand; Schmolke, Mirco; Meng, Hailong; Wetmur, James; García-Sastre, Adolfo

    2015-01-01

    ABSTRACT Influenza viruses continue to present global threats to human health. Antigenic drift and shift, genetic reassortment, and cross-species transmission generate new strains with differences in epidemiology and clinical severity. We compared the temporal transcriptional responses of human dendritic cells (DC) to infection with two pandemic (A/Brevig Mission/1/1918, A/California/4/2009) and two seasonal (A/New Caledonia/20/1999, A/Texas/36/1991) H1N1 influenza viruses. Strain-specific response differences included stronger activation of NF-κB following infection with A/New Caledonia/20/1999 and a unique cluster of genes expressed following infection with A/Brevig Mission/1/1918. A common antiviral program showing strain-specific timing was identified in the early DC response and found to correspond with reported transcript changes in blood during symptomatic human influenza virus infection. Comparison of the global responses to the seasonal and pandemic strains showed that a dramatic divergence occurred after 4 h, with only the seasonal strains inducing widespread mRNA loss. IMPORTANCE Continuously evolving influenza viruses present a global threat to human health; however, these host responses display strain-dependent differences that are incompletely understood. Thus, we conducted a detailed comparative study assessing the immune responses of human DC to infection with two pandemic and two seasonal H1N1 influenza strains. We identified in the immune response to viral infection both common and strain-specific features. Among the stain-specific elements were a time shift of the interferon-stimulated gene response, selective induction of NF-κB signaling by one of the seasonal strains, and massive RNA degradation as early as 4 h postinfection by the seasonal, but not the pandemic, viruses. These findings illuminate new aspects of the distinct differences in the immune responses to pandemic and seasonal influenza viruses. PMID:26223639

  20. Limited novel influenza A (H1N1) 09 infection in travelling high‐school tour group

    PubMed Central

    Mardani, Janine; Calder, Lester; Laurie, Karen; Barr, Ian; Kelso, Anne; Jones, Nicholas

    2010-01-01

    Please cite this paper as: Mardani et al. (2011) Limited novel influenza A (H1N1) 09 infection in travelling high‐school tour group. Influenza and Other Respiratory Viruses 5(1), 47–51. Background  A single case of novel influenza A (H1N1) 09 infection was identified by PCR among a New Zealand high‐school group that toured California in April 2009. Close monitoring of the tour group and their New Zealand contacts identified 11 other tour members with respiratory symptoms who were investigated. In all nine instances where nasopharyngeal swabs were indicated, tests were negative for novel influenza A (H1N1) 09 by PCR. Objective  To determine whether serology could identify any cases of novel influenza A (H1N1) 09 that had not been detected by PCR. Methods  Acute and convalescent serological testing for antibodies against pandemic (H1N1) 2009 and seasonal A (H1N1) influenza viruses using haemagglutination inhibition assays and microneutralisation assays. Results  Serological analysis of symptomatic tour members identified a further possible case of novel influenza A (H1N1) 09 infection. The possible case had not been tested by PCR because he or she had already received prophylaxis with oseltamivir. Conclusions  These findings suggest infection among tour group members was limited despite prolonged periods of close contact during travel. Furthermore, multiple public health interventions are likely to have effectively prevented an outbreak following the tour group’s return. PMID:21138540

  1. Oseltamivir-Resistant Influenza A(H1N1)pdm09 Viruses, United States, 2013–14

    PubMed Central

    Okomo-Adhiambo, Margaret; Fry, Alicia M.; Su, Su; Nguyen, Ha T.; Elal, Anwar Abd; Negron, Elizabeth; Hand, Julie; Garten, Rebecca J.; Barnes, John; Xiyan, Xu; Villanueva, Julie M.

    2015-01-01

    We report characteristics of oseltamivir-resistant influenza A(H1N1)pdm09 viruses and patients infected with these viruses in the United States. During 2013–14, fifty-nine (1.2%) of 4,968 analyzed US influenza A(H1N1)pdm09 viruses had the H275Y oseltamivir resistance–conferring neuraminidase substitution. Our results emphasize the need for local surveillance for neuraminidase inhibitor susceptibility among circulating influenza viruses. PMID:25532050

  2. Development and characterization of a panel of cross-reactive monoclonal antibodies generated using H1N1 influenza virus.

    PubMed

    Guo, Chun-yan; Tang, Yi-gui; Qi, Zong-li; Liu, Yang; Zhao, Xiang-rong; Huo, Xue-ping; Li, Yan; Feng, Qing; Zhao, Peng-hua; Wang, Xin; Li, Yuan; Wang, Hai-fang; Hu, Jun; Zhang, Xin-jian

    2015-08-01

    To characterize the antigenic epitopes of the hemagglutinin (HA) protein of H1N1 influenza virus, a panel consisting of 84 clones of murine monoclonal antibodies (mAbs) were generated using the HA proteins from the 2009 pandemic H1N1 vaccine lysate and the seasonal influenza H1N1(A1) vaccines. Thirty-three (39%) of the 84 mAbs were found to be strain-specific, and 6 (7%) of the 84 mAbs were subtype-specific. Twenty (24%) of the 84 mAbs recognized the common HA epitopes shared by 2009 pandemic H1N1, seasonal A1 (H1N1), and A3 (H3N2) influenza viruses. Twenty-five of the 84 clones recognized the common HA epitopes shared by the 2009 pandemic H1N1, seasonal A1 (H1N1) and A3 (H3N2) human influenza viruses, and H5N1 and H9N2 avian influenza viruses. We found that of the 16 (19%) clones of the 84 mAbs panel that were cross-reactive with human respiratory pathogens, 15 were made using the HA of the seasonal A1 (H1N1) virus and 1 was made using the HA of the 2009 pandemic H1N1 influenza virus. Immunohistochemical analysis of the tissue microarray (TMA) showed that 4 of the 84 mAb clones cross-reacted with human tissue (brain and pancreas). Our results indicated that the influenza virus HA antigenic epitopes not only induce type-, subtype-, and strain-specific monoclonal antibodies against influenza A virus but also cross-reactive monoclonal antibodies against human tissues. Further investigations of these cross-reactive (heterophilic) epitopes may significantly improve our understanding of viral antigenic variation, epidemics, pathophysiologic mechanisms, and adverse effects of influenza vaccines.

  3. Molecular epidemiology study of swine influenza virus revealing a reassorted virus H1N1 in swine farms in Cuba.

    PubMed

    Pérez, Lester J; Perera, Carmen Laura; Coronado, Liani; Rios, Liliam; Vega, Armando; Frías, Maria T; Ganges, Llilianne; Núñez, José Ignacio; Díaz de Arce, Heidy

    2015-05-01

    In this report, we describe the emergence of reassorted H1N1 swine influenza virus, originated from a reassortment event between the H1N1 pandemic influenza virus (H1N1p/2009) and endemic swine influenza virus in Cuban swine population. In November 2010, a clinical respiratory outbreak was reported on a pig fattening farm in Cuba. Phylogenetic analysis showed that all the genes of one of the isolate obtained, with the exception of neuraminidase, belonged to the H1N1p/2009 cluster. This finding suggests that H1N1pdm has been established in swine and has become a reservoir of reassortment that may produce new viruses with both animal and public health risks. PMID:25745869

  4. Molecular epidemiology study of swine influenza virus revealing a reassorted virus H1N1 in swine farms in Cuba.

    PubMed

    Pérez, Lester J; Perera, Carmen Laura; Coronado, Liani; Rios, Liliam; Vega, Armando; Frías, Maria T; Ganges, Llilianne; Núñez, José Ignacio; Díaz de Arce, Heidy

    2015-05-01

    In this report, we describe the emergence of reassorted H1N1 swine influenza virus, originated from a reassortment event between the H1N1 pandemic influenza virus (H1N1p/2009) and endemic swine influenza virus in Cuban swine population. In November 2010, a clinical respiratory outbreak was reported on a pig fattening farm in Cuba. Phylogenetic analysis showed that all the genes of one of the isolate obtained, with the exception of neuraminidase, belonged to the H1N1p/2009 cluster. This finding suggests that H1N1pdm has been established in swine and has become a reservoir of reassortment that may produce new viruses with both animal and public health risks.

  5. Early Outbreak of 2009 Influenza A (H1N1) in Mexico Prior to Identification of pH1N1 Virus

    PubMed Central

    Hsieh, Ying-Hen; Ma, Stefan; Velasco Hernandez, Jorge X.; Lee, Vernon J.; Lim, Wei Yen

    2011-01-01

    Background In the aftermath of the global spread of 2009 influenza A (pH1N1) virus, still very little is known of the early stages of the outbreak in Mexico during the early months of the year, before the virus was identified. Methodology/Main Findings We fit a simple mathematical model, the Richards model, to the number of excess laboratory-confirmed influenza cases in Mexico and Mexico City during the first 15 weeks in 2009 over the average influenza case number of the previous five baseline years of 2004-2008 during the same period to ascertain the turning point (or the peak incidence) of a wave of early influenza infections, and to estimate the transmissibility of the virus during these early months in terms of its basic reproduction number. The results indicate that there may have been an early epidemic in Mexico City as well as in all of Mexico during February/March. Based on excess influenza cases, the estimated basic reproduction number R0 for the early outbreak was 1.59 (0.55 to 2.62) for Mexico City during weeks 5–9, and 1.25 (0.76, 1.74) for all of Mexico during weeks 5–14. Conclusions We established the existence of an early epidemic in Mexico City and in all of Mexico during February/March utilizing the routine influenza surveillance data, although the location of seeding is unknown. Moreover, estimates of R0 as well as the time of peak incidence (the turning point) for Mexico City and all of Mexico indicate that the early epidemic in Mexico City in February/March had been more transmissible (larger R0) and peaked earlier than the rest of the country. Our conclusion lends support to the possibility that the virus could have already spread to other continents prior to the identification of the virus and the reporting of lab-confirmed pH1N1 cases in North America in April. PMID:21909366

  6. Novel (pandemic) influenza A H1N1 in healthcare facilities: implications for prevention and control.

    PubMed

    Maltezou, Helena C

    2010-07-01

    In April 2009 a novel (pandemic) influenza A H1N1 virus was identified in Mexico and the USA and spread throughout the world over a short period of time. Although the virulence of novel influenza was no greater than that of seasonal influenza, a major patient load and wave of admissions were faced. There are few evidence-based data available to guide infection control measures for novel influenza, however what is clear is that the novel virus is a very efficient agent for rapid spread and onset of outbreaks in healthcare settings. There are few reports on the nosocomial transmission of novel influenza, however outbreaks with severe morbidity and mortality may occur among high-risk groups. Last y efforts were made in several countries to build infection control capacity in healthcare facilities and to improve employee and patient safety. Adherence of healthcare workers to recommendations for vaccination against novel influenza and the use of personal protective equipment are emerging as major obstacles in achieving this goal. The use of N95 respirators instead of surgical masks for all close contacts, as recommended by the Centers for Disease Control and Prevention and in contrast with recommendations for seasonal influenza, is a major shift in everyday practice.

  7. Correlates of 2009 Pandemic H1N1 Influenza Vaccine Acceptance among Middle and High School Teachers in Rural Georgia

    ERIC Educational Resources Information Center

    Gargano, Lisa M.; Painter, Julia E.; Sales, Jessica M.; Morfaw, Christopher; Jones, LaDawna M.; Weiss, Paul; Murray, Dennis; DiClemente, Ralph J.; Hughes, James M.

    2011-01-01

    Background: Teachers play an essential role in the school community, and H1N1 vaccination of teachers is critical to protect not only themselves but also adolescents they come in contact within the classroom through herd immunity. School-aged children have a greater risk of developing H1N1 disease than seasonal influenza. The goal of this study…

  8. Genetic characterization of Thai swine influenza viruses after the introduction of pandemic H1N1 2009.

    PubMed

    Charoenvisal, Nataya; Keawcharoen, Juthatip; Sreta, Donruethai; Chaiyawong, Supassama; Nonthabenjawan, Nutthawan; Tantawet, Siriporn; Jittimanee, Suphattra; Arunorat, Jirapat; Amonsin, Alongkorn; Thanawongnuwech, Roongroje

    2013-08-01

    Pandemic H1N1 2009 (pH1N1), influenza virus containing triple reassortant internal genes (TRIG) from avian, human, and swine influenza viruses emerged in 2009 as a highly infectious virus that was able to be transmitted from humans to pigs. During June 2010-May 2012, influenza virus surveillance was conducted in Thai pig population. Twenty-three samples (1.75%) were successfully isolated from total of 1,335 samples. Interestingly, pH1N1 (7 isolates, 30.34%), reassortant pH1N1 (rH1N1) (1 isolate, 4.35%), Thai endemic H1N1 (enH1N1) (3 isolates, 13.04%), reassortant H3N2 with pH1N1 internal genes (rH3N2) (9 isolates, 39.13%), and reassortant H1N2 with pH1N1 internal genes (rH1N2) (3 isolates, 13.04%) were found. It should be noted that rH1N1, rH1N2, and rH3N2 viruses contained the internal genes of pH1N1 virus having a TRIG cassette descendant from the North American swine lineage. Although all isolates in this study were obtained from mild clinically sick pigs, the viruses were still highly infective and possibly may play an important role in human-animal interfacing transmission. In addition, the TRIG cassette may have an influence on antigenic shift resulting in emergence of novel viruses, as seen in this study. Continuing surveillance of influenza A natural hosts, particularly in pigs is necessary.

  9. Community responses to communication campaigns for influenza A (H1N1): a focus group study

    PubMed Central

    2012-01-01

    Background This research was a part of a contestable rapid response initiative launched by the Health Research Council of New Zealand and the Ministry of Health in response to the 2009 influenza A pandemic. The aim was to provide health authorities in New Zealand with evidence-based practical information to guide the development and delivery of effective health messages for H1N1 and other health campaigns. This study contributed to the initiative by providing qualitative data about community responses to key health messages in the 2009 and 2010 H1N1 campaigns, the impact of messages on behavioural change and the differential impact on vulnerable groups in New Zealand. Methods Qualitative data were collected on community responses to key health messages in the 2009 and 2010 Ministry of Health H1N1 campaigns, the impact of messages on behaviour and the differential impact on vulnerable groups. Eight focus groups were held in the winter of 2010 with 80 participants from groups identified by the Ministry of Health as vulnerable to the H1N1 virus, such as people with chronic health conditions, pregnant women, children, Pacific Peoples and Māori. Because this study was part of a rapid response initiative, focus groups were selected as the most efficient means of data collection in the time available. For Māori, focus group discussion (hui) is a culturally appropriate methodology. Results Thematic analysis of data identified four major themes: personal and community risk, building community strategies, responsibility and information sources. People wanted messages about specific actions that they could take to protect themselves and their families and to mitigate any consequences. They wanted transparent and factual communication where both good and bad news is conveyed by people who they could trust. Conclusions The responses from all groups endorsed the need for community based risk management including information dissemination. Engaging with communities will be

  10. Antiviral activity of silver nanoparticle/chitosan composites against H1N1 influenza A virus

    NASA Astrophysics Data System (ADS)

    Mori, Yasutaka; Ono, Takeshi; Miyahira, Yasushi; Nguyen, Vinh Quang; Matsui, Takemi; Ishihara, Masayuki

    2013-02-01

    Silver nanoparticle (Ag NP)/chitosan (Ch) composites with antiviral activity against H1N1 influenza A virus were prepared. The Ag NP/Ch composites were obtained as yellow or brown floc-like powders following reaction at room temperature in aqueous medium. Ag NPs (3.5, 6.5, and 12.9 nm average diameters) were embedded into the chitosan matrix without aggregation or size alternation. The antiviral activity of the Ag NP/Ch composites was evaluated by comparing the TCID50 ratio of viral suspensions treated with the composites to untreated suspensions. For all sizes of Ag NPs tested, antiviral activity against H1N1 influenza A virus increased as the concentration of Ag NPs increased; chitosan alone exhibited no antiviral activity. Size dependence of the Ag NPs on antiviral activity was also observed: antiviral activity was generally stronger with smaller Ag NPs in the composites. These results indicate that Ag NP/Ch composites interacting with viruses exhibit antiviral activity.

  11. [Direct immunofluorescence assay performance in diagnosis of the Influenza A(H1N1) virus].

    PubMed

    Pianciola, Luis; González, Gladys; Mazzeo, Melina; Navello, Mariano; Quidel, Natalia; Bulgheroni, María Fernanda

    2010-06-01

    By 25 April 2009, less than one month after the first human with Influenza A(H1N1) virus was detected in Mexico, the disease had already spread to more than 40 countries, with over 10,000 cases reported. Due to its unpredictability, this type of virus requires appropriate, reliable, and safe diagnostic methods that are also accessible to clinical laboratories. Through the analysis of 291 samples taken from patients with suspected Influenza A(H1N1) virus infection in Neuquén, Argentina, this study compares the two diagnostic methods used simultaneously: direct immunofluorescence assay (DFA) and real-time polymerase chain reaction (RT-PCR). DFA had a sensitivity of 44.4%, a specificity of 99.6%, a positive predictive value of 95.2%, and a negative predictive value of 90.7%. Positive results obtained with this method can be considered true positives. A negative result does not rule out the presence of the virus. In this case, the sample should be examined by RT-PCR. Out of a total of 291 samples, there were 45 positive results with RT-PCR and 21 positive results with DFA.

  12. The 2009 pandemic H1N1 and triple-reassortant swine H1N1 influenza viruses replicate efficiently but elicit an attenuated inflammatory response in polarized human bronchial epithelial cells.

    PubMed

    Zeng, Hui; Pappas, Claudia; Katz, Jacqueline M; Tumpey, Terrence M

    2011-01-01

    The pandemic H1N1 virus of 2009 (2009 H1N1) produced a spectrum of disease ranging from mild illness to severe illness and death. Respiratory symptoms were frequently associated with virus infection, with relatively high rate of gastrointestinal symptoms reported. To better understand 2009 H1N1 virus pathogenesis in humans, we studied virus and host responses following infection of two cell types: polarized bronchial and pharyngeal epithelial cells, which exhibit many features of the human airway epithelium, and colon epithelial cells to serve as a human intestinal cell model. Selected 2009 H1N1 viruses were compared to both seasonal H1N1 and triple-reassortant swine H1N1 influenza viruses that have circulated among North American pigs since before the 2009 pandemic. All H1N1 viruses replicated productively in airway cells; however, in contrast to seasonal H1N1 virus infection, infection with the 2009 H1N1 and triple-reassortant swine H1N1 viruses resulted in an attenuated inflammatory response, a weaker interferon response, and reduced cell death. Additionally, the H1N1 viruses of swine origin replicated less efficiently at the temperature of the human proximal airways (33°C). We also observed that the 2009 H1N1 viruses replicated to significantly higher titers than seasonal H1N1 virus in polarized colon epithelial cells. These studies reveal that in comparison to seasonal influenza virus, H1N1 viruses of swine origin poorly activate multiple aspects of the human innate response, which may contribute to the virulence of these viruses. In addition, their less efficient replication at human upper airway temperatures has implications for the understanding of pandemic H1N1 virus adaptation to humans.

  13. Phylodynamics of H1N1/2009 influenza reveals the transition from host adaptation to immune-driven selection

    PubMed Central

    Su, Yvonne C. F.; Bahl, Justin; Joseph, Udayan; Butt, Ka Man; Peck, Heidi A.; Koay, Evelyn S. C.; Oon, Lynette L. E.; Barr, Ian G.; Vijaykrishna, Dhanasekaran; Smith, Gavin J. D.

    2015-01-01

    Influenza A H1N1/2009 virus that emerged from swine rapidly replaced the previous seasonal H1N1 virus. Although the early emergence and diversification of H1N1/2009 is well characterized, the ongoing evolutionary and global transmission dynamics of the virus remain poorly investigated. To address this we analyse >3,000 H1N1/2009 genomes, including 214 full genomes generated from our surveillance in Singapore, in conjunction with antigenic data. Here we show that natural selection acting on H1N1/2009 directly after introduction into humans was driven by adaptation to the new host. Since then, selection has been driven by immunological escape, with these changes corresponding to restricted antigenic diversity in the virus population. We also show that H1N1/2009 viruses have been subject to regular seasonal bottlenecks and a global reduction in antigenic and genetic diversity in 2014. PMID:26245473

  14. Phylodynamics of H1N1/2009 influenza reveals the transition from host adaptation to immune-driven selection.

    PubMed

    Su, Yvonne C F; Bahl, Justin; Joseph, Udayan; Butt, Ka Man; Peck, Heidi A; Koay, Evelyn S C; Oon, Lynette L E; Barr, Ian G; Vijaykrishna, Dhanasekaran; Smith, Gavin J D

    2015-08-06

    Influenza A H1N1/2009 virus that emerged from swine rapidly replaced the previous seasonal H1N1 virus. Although the early emergence and diversification of H1N1/2009 is well characterized, the ongoing evolutionary and global transmission dynamics of the virus remain poorly investigated. To address this we analyse >3,000 H1N1/2009 genomes, including 214 full genomes generated from our surveillance in Singapore, in conjunction with antigenic data. Here we show that natural selection acting on H1N1/2009 directly after introduction into humans was driven by adaptation to the new host. Since then, selection has been driven by immunological escape, with these changes corresponding to restricted antigenic diversity in the virus population. We also show that H1N1/2009 viruses have been subject to regular seasonal bottlenecks and a global reduction in antigenic and genetic diversity in 2014.

  15. Neuraminidase Activity and Resistance of 2009 Pandemic H1N1 Influenza Virus to Antiviral Activity in Bronchoalveolar Fluid

    PubMed Central

    Ruangrung, Kanyarat; Suptawiwat, Ornpreya; Maneechotesuwan, Kittipong; Boonarkart, Chompunuch; Chakritbudsabong, Warunya; Assawabhumi, Jirawatna; Bhattarakosol, Parvapan; Uiprasertkul, Mongkol; Puthavathana, Pilaipan; Wiriyarat, Witthawat; Jongkaewwattana, Anan

    2016-01-01

    ABSTRACT Human bronchoalveolar fluid is known to have anti-influenza activity. It is believed to be a frontline innate defense against the virus. Several antiviral factors, including surfactant protein D, are believed to contribute to the activity. The 2009 pandemic H1N1 influenza virus was previously shown to be less sensitive to surfactant protein D. Nevertheless, whether different influenza virus strains have different sensitivities to the overall anti-influenza activity of human bronchoalveolar fluid was not known. We compared the sensitivities of 2009 pandemic H1N1, seasonal H1N1, and seasonal H3N2 influenza virus strains to inhibition by human bronchoalveolar lavage (BAL) fluid. The pandemic and seasonal H1N1 strains showed lower sensitivity to human BAL fluid than the H3N2 strains. The BAL fluid anti-influenza activity could be enhanced by oseltamivir, indicating that the viral neuraminidase (NA) activity could provide resistance to the antiviral defense. In accordance with this finding, the BAL fluid anti-influenza activity was found to be sensitive to sialidase. The oseltamivir resistance mutation H275Y rendered the pandemic H1N1 virus but not the seasonal H1N1 virus more sensitive to BAL fluid. Since only the seasonal H1N1 but not the pandemic H1N1 had compensatory mutations that allowed oseltamivir-resistant strains to maintain NA enzymatic activity and transmission fitness, the resistance to BAL fluid of the drug-resistant seasonal H1N1 virus might play a role in viral fitness. IMPORTANCE Human airway secretion contains anti-influenza activity. Different influenza strains may vary in their susceptibilities to this antiviral activity. Here we show that the 2009 pandemic and seasonal H1N1 influenza viruses were less sensitive to human bronchoalveolar lavage (BAL) fluid than H3N2 seasonal influenza virus. The resistance to the pulmonary innate antiviral activity of the pandemic virus was determined by its neuraminidase (NA) gene, and it was shown that the

  16. Response to the 2009 influenza A(H1N1) pandemic in Italy.

    PubMed

    Rizzo, C; Rota, M C; Bella, A; Giannitelli, S; De Santis, S; Nacca, G; Pompa, M G; Vellucci, L; Salmaso, S; Declich, S

    2010-12-01

    In Italy, the arrival of the 2009 pandemic influenza A(H1N1) virus triggered an integrated response that was mainly based on the 2006 National Pandemic Preparedness and Response Plan. In this article we analyse the main activities implemented for epidemiological surveillance, containment and mitigation of the pandemic influenza and the lesson learned from this experience. Overall, from week 31 (27 July – 2 August) of 2009 to week 17 (26 April – 2 May) of 2010, we estimate that there were approximately 5,600,000 cases of influenza-like illness (ILI) who received medical attention (with almost 2,000 laboratory-confirmed cases of pandemic influenza from May to October 2009). A total of 1,106 confirmed cases were admitted to hospital for serious conditions, of whom 532 were admitted to intensive care units. There were 260 reported deaths due to pandemic influenza. Approximately 870,000 first doses of the pandemic vaccine were administered, representing a vaccine coverage of 4% of the target population. One of the possible reasons for the low uptake of the pandemic vaccine in the target population could be the communication strategy adopted, for both the general population and healthcare workers, which turned out to be a major challenge. Active involvement of all health professionals (at local, regional and national level) in influenza pandemic preparedness and response should be encouraged in the future.

  17. The 2009 A/H1N1 pandemic influenza and the nursing home.

    PubMed

    Gravenstein, Stefan; Pop-Vicas, Aurora; Ambrozaitis, Arvydas

    2010-12-01

    Seasonal and pandemic influenza clinically remain remarkably similar in long-term care populations. Clinicians cannot distinguish clinical influenza, whether seasonal or pandemic H1N1, from other respiratory viral infections in individual patients. Part of the difficulty in the clinical diagnosis relates to fewer clinical features that might help with diagnostic differentiation, such as fever. However, the nursing home provides an epidemiologic context that can prove helpful to clinicians who inquire--by considering illness patterns among others in the facility, both staff and residents. This can lead to more timely diagnosis and treatment in the resident, and prophylaxis--an opportunity to protect the remaining residents and staff. Check out the treatment guidelines posted on the CDC website to be sure to select the best agents, because antiviral resistance patterns have been rapidly changing. PMID:21214077

  18. Transmission and control in an institutional pandemic influenza A(H1N1) 2009 outbreak.

    PubMed

    Arinaminpathy, N; Raphaely, N; Saldana, L; Hodgekiss, C; Dandridge, J; Knox, K; McCarthy, N D

    2012-06-01

    A pandemic influenza A(H1N1) 2009 outbreak in a summer school affected 117/276 (42%) students. Residential social contact was associated with risk of infection, and there was no evidence for transmission associated with the classroom setting. Although the summer school had new admissions each week, which provided susceptible students the outbreak was controlled using routine infection control measures (isolation of cases, basic hygiene measures and avoidance of particularly high-risk social events) and prompt treatment of cases. This was in the absence of chemoprophylaxis or vaccination and without altering the basic educational activities of the school. Modelling of the outbreak allowed estimation of the impact of interventions on transmission. These models and follow-up surveillance supported the effectiveness of routine infection control measures to stop the spread of influenza even in this high-risk setting for transmission. PMID:21859502

  19. Reduced replication capacity of influenza A(H1N1)pdm09 virus during the 2010-2011 winter season in Tottori, Japan.

    PubMed

    Tsuneki, Akeno; Itagaki, Asao; Tsuchie, Hideaki; Tokuhara, Misato; Okada, Takayoshi; Narai, Sakae; Kasagi, Masaaki; Tanaka, Kiyoshi; Kageyama, Seiji

    2013-11-01

    A novel swine-origin influenza A(H1N1)pdm09 virus has been circulating in humans since March-April, 2009. The 2009-2010 epidemic involved predominantly a single subtype of A(H1N1)pdm09 (at 96%, 46/48) in the sentinel sites of this study. However, A(H1N1)pdm09 started to circulate together with other type/subtype (49%, 33/68) at the first peak in the next epidemic season in 2010-2011: A(H1N1)pdm09/A(H3N2) (9%, 6/68), A(H1N1)pdm09/B (35%, 24/68), and A(H1N1)pdm09/A(H3N2)/B (4%, 3/68). Single infection of A(H1N1)pdm09 became a rare event (8%, 5/65) at the second peak of the same season in 2010-2011 compared with that at the first peak (50%, 34/68). Concurrently with this decline, single infections of others, A(H3N2) or B, became evident (6%, 4/65; 14%, 9/65, respectively). Triple infections were more common (29%, 19/65) at the second peak than at the first peak (4%). The A(H1N1)pdm09 detected in 2010-2011 produced less virus upon 72 hr of incubation in vitro after the inoculations at 10(4) and 3,300 copies/ml (2.3 × 10(9) and 2.3 × 10(9) copies/ml on average) than that in 2009-2010 (3.7 × 10(9) and 1.3 × 10(10) copies/ml on average; P<0.05 by ANOVA test), respectively. As described above, the replication capacity of A(H1N1)pdm09 seems to have deteriorated in the 2010-2011 season presumably due to substantial herd immunity and allowed the existence of other type/subtype. These results suggest that assessment of replication capacity is indispensable for analysis of influenza epidemics.

  20. Streptococcus pneumoniae Coinfection Is Correlated with the Severity of H1N1 Pandemic Influenza

    PubMed Central

    Cisterna, Daniel; Savji, Nazir; Bussetti, Ana Valeria; Kapoor, Vishal; Hui, Jeffrey; Tokarz, Rafal; Briese, Thomas; Baumeister, Elsa; Lipkin, W. Ian

    2009-01-01

    Background Initial reports in May 2009 of the novel influenza strain H1N1pdm estimated a case fatality rate (CFR) of 0.6%, similar to that of seasonal influenza. In July 2009, however, Argentina reported 3056 cases with 137 deaths, representing a CFR of 4.5%. Potential explanations for increased CFR included virus reassortment or genetic drift, or infection of a more vulnerable population. Virus genomic sequencing of 26 Argentinian samples representing both severe and mild disease indicated no evidence of reassortment, mutations associated with resistance to antiviral drugs, or genetic drift that might contribute to virulence. Furthermore, no evidence was found for increased frequency of risk factors for H1N1pdm disease. Methods/Principal Findings We examined nasopharyngeal swab samples (NPS) from 199 cases of H1N1pdm infection from Argentina with MassTag PCR, testing for 33 additional microbial agents. The study population consisted of 199 H1N1pdm-infected subjects sampled between 23 June and 4 July 2009. Thirty-nine had severe disease defined as death (n = 20) or hospitalization (n = 19); 160 had mild disease. At least one additional agent of potential pathogenic importance was identified in 152 samples (76%), including Streptococcus pneumoniae (n = 62); Haemophilus influenzae (n = 104); human respiratory syncytial virus A (n = 11) and B (n = 1); human rhinovirus A (n = 1) and B (n = 4); human coronaviruses 229E (n = 1) and OC43 (n = 2); Klebsiella pneumoniae (n = 2); Acinetobacter baumannii (n = 2); Serratia marcescens (n = 1); and Staphylococcus aureus (n = 35) and methicillin-resistant S. aureus (MRSA, n = 6). The presence of S. pneumoniae was strongly correlated with severe disease. S. pneumoniae was present in 56.4% of severe cases versus 25% of mild cases; more than one-third of H1N1pdm NPS with S. pneumoniae were from subjects with severe disease (22 of 62 S. pneumoniae-positive NPS, p = 0

  1. Impact on Pregnancies in South Brazil from the Influenza A (H1N1) Pandemic: Cohort Study

    PubMed Central

    da Silva, André Anjos; Ranieri, Tani Maria Schilling; Torres, Fernanda Duarte; Vianna, Fernanda Sales Luiz; Paniz, Graziella Rangel; Sanseverino, Paula Baptista; Picon, Paulo Dornelles; de Azevedo, Pietro Baptista; Costa, Marta Haas; Schuler-Faccini, Lavinia; Sanseverino, Maria Teresa Vieira

    2014-01-01

    Introduction The emergence of a new subtype of the influenza virus in 2009 generated interest in the international medical community, the media, and the general population. Pregnant women are considered to be a group at risk of serious complications related to the H1N1 influenza virus. The aim of this study was to evaluate the outcomes and teratogenic effects of pregnancies exposed to the H1N1 virus during the Influenza A epidemic that occurred in the state of Rio Grande do Sul in 2009. Methods This is an uncontrolled prospective cohort study of pregnant women with suspected symptoms of Influenza A who were reported in the Information System for Notifiable Diseases – Influenza (SINAN-Influenza) during the epidemic of 2009 (database from the state of Rio Grande do Sul, Brazil). There were 589 cases of pregnant women with suspected infection. Among these, 243 were tested by PCR and included in the analysis. The main outcome measures were: maternal deaths, pregnancy outcome, stillbirths, premature births, low birth weight, congenital malformations, and odds ratios for H1N1+ and non-H1N1 pregnant women. Results There were one hundred and sixty-three (67%) confirmed cases of H1N1, 34 cases (14%) of seasonal Influenza A and 46 (19%) who were negative for Influenza A. There was no difference between the three groups in clinical parameters of the disease. There were 24 maternal deaths — 18 of them had H1N1. There were 8 stillbirths — 5 were children of H1N1 infected mothers. There were no differences in perinatal outcomes. Conclusions The present data do not indicate an increase in teratogenic risk from exposure to the influenza A (H1N1) virus. These results will help to strengthen the data and clarify the health issues that arose after the pandemic. PMID:24558404

  2. Antibody Recognition of the Pandemic H1N1 Influenza Virus Hemagglutinin Receptor Binding Site

    PubMed Central

    Hong, Minsun; Lee, Peter S.; Hoffman, Ryan M. B.; Zhu, Xueyong; Krause, Jens C.; Laursen, Nick S.; Yoon, Sung-il; Song, Langzhou; Tussey, Lynda; Crowe, James E.; Ward, Andrew B.

    2013-01-01

    Influenza virus is a global health concern due to its unpredictable pandemic potential. This potential threat was realized in 2009 when an H1N1 virus emerged that resembled the 1918 virus in antigenicity but fortunately was not nearly as deadly. 5J8 is a human antibody that potently neutralizes a broad spectrum of H1N1 viruses, including the 1918 and 2009 pandemic viruses. Here, we present the crystal structure of 5J8 Fab in complex with a bacterially expressed and refolded globular head domain from the hemagglutinin (HA) of the A/California/07/2009 (H1N1) pandemic virus. 5J8 recognizes a conserved epitope in and around the receptor binding site (RBS), and its HCDR3 closely mimics interactions of the sialic acid receptor. Electron microscopy (EM) reconstructions of 5J8 Fab in complex with an HA trimer from a 1986 H1 strain and with an engineered stabilized HA trimer from the 2009 H1 pandemic virus showed a similar mode of binding. As for other characterized RBS-targeted antibodies, 5J8 uses avidity to extend its breadth and affinity against divergent H1 strains. 5J8 selectively interacts with HA insertion residue 133a, which is conserved in pandemic H1 strains and has precluded binding of other RBS-targeted antibodies. Thus, the RBS of divergent HAs is targeted by 5J8 and adds to the growing arsenal of common recognition motifs for design of therapeutics and vaccines. Moreover, consistent with previous studies, the bacterially expressed H1 HA properly refolds, retaining its antigenic structure, and presents a low-cost and rapid alternative for engineering and manufacturing candidate flu vaccines. PMID:24027321

  3. Antibody recognition of the pandemic H1N1 Influenza virus hemagglutinin receptor binding site.

    PubMed

    Hong, Minsun; Lee, Peter S; Hoffman, Ryan M B; Zhu, Xueyong; Krause, Jens C; Laursen, Nick S; Yoon, Sung-Il; Song, Langzhou; Tussey, Lynda; Crowe, James E; Ward, Andrew B; Wilson, Ian A

    2013-11-01

    Influenza virus is a global health concern due to its unpredictable pandemic potential. This potential threat was realized in 2009 when an H1N1 virus emerged that resembled the 1918 virus in antigenicity but fortunately was not nearly as deadly. 5J8 is a human antibody that potently neutralizes a broad spectrum of H1N1 viruses, including the 1918 and 2009 pandemic viruses. Here, we present the crystal structure of 5J8 Fab in complex with a bacterially expressed and refolded globular head domain from the hemagglutinin (HA) of the A/California/07/2009 (H1N1) pandemic virus. 5J8 recognizes a conserved epitope in and around the receptor binding site (RBS), and its HCDR3 closely mimics interactions of the sialic acid receptor. Electron microscopy (EM) reconstructions of 5J8 Fab in complex with an HA trimer from a 1986 H1 strain and with an engineered stabilized HA trimer from the 2009 H1 pandemic virus showed a similar mode of binding. As for other characterized RBS-targeted antibodies, 5J8 uses avidity to extend its breadth and affinity against divergent H1 strains. 5J8 selectively interacts with HA insertion residue 133a, which is conserved in pandemic H1 strains and has precluded binding of other RBS-targeted antibodies. Thus, the RBS of divergent HAs is targeted by 5J8 and adds to the growing arsenal of common recognition motifs for design of therapeutics and vaccines. Moreover, consistent with previous studies, the bacterially expressed H1 HA properly refolds, retaining its antigenic structure, and presents a low-cost and rapid alternative for engineering and manufacturing candidate flu vaccines.

  4. [Pathogenic effect of pandemic influenza virus H1N1 under replication in cultures of human cells].

    PubMed

    Zhirnov, O P; Vorob'eva, I V; Safonova, O A; Malyshev, N A; Schwalm, F; Klenk, H -D

    2013-01-01

    The propagation of the pandemic influenza virus H1N1 in cultures of bronchial (Calu-3) and intestinal (Caco-2) differentiated epithelial cells of human origin was studied. The canine epithelial cell lines, MDCK-H and MDCK-2, were comparatively tested. The two human cell lines were found to be highly sensitive to the influenza pandemic strains A/Hamburg/05/09 and A/Moscow/501/2011 and maintained their replication without addition of trypsin to culture medium. Virus strains of seasonal influenza H1N1, such as A/Moscow/450/2003, A/Memphis/14/96, and laboratory strain A/PR/8/34, multiplied in these human cells in similar manner. The intracellular cleavage HA0-->HA1+HA2 by the host virus-activating protease (IAP) occurred in both human cell lines under infection with each influenza virus H1N1 including pandemic ones. Comparatively, this cleavage of all influenza H1N1 virus strains appeared to be either undetectable or low-detectible in MDCK-H and MDCK-2, respectively, thereby implying low levels of active IAP in these cells. Multiplication of pandemic and seasonal influenza H1N1 viruses in Calu-3 and Caco-2 cells caused cytopathic effect, which was accompanied with low autophagy and apoptosis events. These data allow recommending human cell lines, Calu-3 and Caco-2, for optimized isolation and passaging of clinical strains of Influenza pandemic viruses H1N1.

  5. Influenza H1N1 Infection Leading To Cardiac Tamponade in a Previously Healthy Patient: A Case Report

    PubMed Central

    Sidhu, Robinder S.; Sharma, Abhinav; Paterson, Ian D.; Bainey, Kevin R.

    2016-01-01

    Introduction The cardiac manifestations of influenza A are broad, ranging from self-limited pericarditis to fatal cardiomyopathy. The 2009 H1N1 influenza A (H1N1) strain is a rare cause of pericarditis, and its role in developing a pericardial effusion leading to tamponade has infrequently been reported. Case Presentation We describe a case of a young female with no prior cardiovascular history who presents with a pericardial effusion and shock secondary to cardiac tamponade from pericarditis due to H1N1 influenza A. Conclusions This case highlights the potential severity of H1N1 infections and the utility of considering cardiac tamponade in patients presenting with influenza symptoms and circulatory collapse. PMID:27800452

  6. Characterization of the upper respiratory tract microbiomes of patients with pandemic H1N1 influenza.

    PubMed

    Chaban, Bonnie; Albert, Arianne; Links, Matthew G; Gardy, Jennifer; Tang, Patrick; Hill, Janet E

    2013-01-01

    The upper respiratory tract microbiome has an important role in respiratory health. Influenza A is a common viral infection that challenges that health, and a well-recognized sequela is bacterial pneumonia. Given this connection, we sought to characterize the upper respiratory tract microbiota of individuals suffering from the pandemic H1N1 influenza A outbreak of 2009 and determine if microbiome profiles could be correlated with patient characteristics. We determined the microbial profiles of 65 samples from H1N1 patients by cpn60 universal target amplification and sequencing. Profiles were examined at the phylum and nearest neighbor "species" levels using the characteristics of patient gender, age, originating health authority, sample type and designation (STAT/non-STAT). At the phylum level, Actinobacteria-, Firmicutes- and Proteobacteria-dominated microbiomes were observed, with none of the patient characteristics showing significant profile composition differences. At the nearest neighbor "species" level, the upper respiratory tract microbiomes were composed of 13-20 "species" and showed a trend towards increasing diversity with patient age. Interestingly, at an individual level, most patients had one to three organisms dominant in their microbiota. A limited number of discrete microbiome profiles were observed, shared among influenza patients regardless of patient status variables. To assess the validity of analyses derived from sequence read abundance, several bacterial species were quantified by quantitative PCR and compared to the abundance of cpn60 sequence read counts obtained in the study. A strong positive correlation between read abundance and absolute bacterial quantification was observed. This study represents the first examination of the upper respiratory tract microbiome using a target other than the 16S rRNA gene and to our knowledge, the first thorough examination of this microbiome during a viral infection. PMID:23844261

  7. Characterization of the Upper Respiratory Tract Microbiomes of Patients with Pandemic H1N1 Influenza

    PubMed Central

    Chaban, Bonnie; Albert, Arianne; Links, Matthew G.; Gardy, Jennifer; Tang, Patrick; Hill, Janet E.

    2013-01-01

    The upper respiratory tract microbiome has an important role in respiratory health. Influenza A is a common viral infection that challenges that health, and a well-recognized sequela is bacterial pneumonia. Given this connection, we sought to characterize the upper respiratory tract microbiota of individuals suffering from the pandemic H1N1 influenza A outbreak of 2009 and determine if microbiome profiles could be correlated with patient characteristics. We determined the microbial profiles of 65 samples from H1N1 patients by cpn60 universal target amplification and sequencing. Profiles were examined at the phylum and nearest neighbor “species” levels using the characteristics of patient gender, age, originating health authority, sample type and designation (STAT/non-STAT). At the phylum level, Actinobacteria-, Firmicutes- and Proteobacteria-dominated microbiomes were observed, with none of the patient characteristics showing significant profile composition differences. At the nearest neighbor “species” level, the upper respiratory tract microbiomes were composed of 13-20 “species” and showed a trend towards increasing diversity with patient age. Interestingly, at an individual level, most patients had one to three organisms dominant in their microbiota. A limited number of discrete microbiome profiles were observed, shared among influenza patients regardless of patient status variables. To assess the validity of analyses derived from sequence read abundance, several bacterial species were quantified by quantitative PCR and compared to the abundance of cpn60 sequence read counts obtained in the study. A strong positive correlation between read abundance and absolute bacterial quantification was observed. This study represents the first examination of the upper respiratory tract microbiome using a target other than the 16S rRNA gene and to our knowledge, the first thorough examination of this microbiome during a viral infection. PMID:23844261

  8. Influenza virus H1N1 activates platelets through FcγRIIA signaling and thrombin generation.

    PubMed

    Boilard, Eric; Paré, Guillaume; Rousseau, Matthieu; Cloutier, Nathalie; Dubuc, Isabelle; Lévesque, Tania; Borgeat, Pierre; Flamand, Louis

    2014-05-01

    Platelets play crucial functions in hemostasis and the prevention of bleeding. During H1N1 influenza A virus infection, platelets display activation markers. The platelet activation triggers during H1N1 infection remain elusive. We observed that H1N1 induces surface receptor activation, lipid mediator synthesis, and release of microparticles from platelets. These activation processes require the presence of serum/plasma, pointing to the contribution of soluble factor(s). Considering that immune complexes in the H1N1 pandemic were reported to play a pathogenic role, we assessed their contribution in H1N1-induced platelet activation. In influenza-immunized subjects, we observed that the virus scaffolds with immunoglobulin G (IgG) to form immune complexes that promote platelet activation. Mechanistically, this activation occurs through stimulation of low-affinity type 2 receptor for Fc portion of IgG (FcγRIIA), a receptor for immune complexes, independently of thrombin. Using a combination of in vitro and in vivo approaches, we found that the antibodies from H3N2-immunized mice activate transgenic mouse platelets that express FcγRIIA when put in the presence of H1N1, suggesting that cross-reacting influenza antibodies suffice. Alternatively, H1N1 can activate platelets via thrombin formation, independently of complement and FcγRIIA. These observations identify both the adaptive immune response and the innate response against pathogens as 2 intertwined processes that activate platelets during influenza infections.

  9. Reassortment Networks and the evolution of pandemic H1N1 swine-origin influenza.

    PubMed

    Bokhari, Shahid H; Pomeroy, Laura W; Janies, Daniel A

    2012-01-01

    Prior research developed Reassortment Networks to reconstruct the evolution of segmented viruses under both reassortment and mutation. We report their application to the swine-origin pandemic H1N1 virus (S-OIV). A database of all influenza A viruses, for which complete genome sequences were available in Genbank by October 2009, was created and dynamic programming was used to compute distances between all corresponding segments. A reassortment network was created to obtain the minimum cost evolutionary paths from all viruses to the exemplar S-OIV A/California/04/2009. This analysis took 35 hours on the Cray Extreme Multithreading (XMT) supercomputer, which has special hardware to permit efficient parallelization. Six specific H1N1/H1N2 bottleneck viruses were identified that almost always lie on minimum cost paths to S-OIV. We conjecture that these viruses are crucial to S-OIV evolution and worthy of careful study from a molecular biology viewpoint. In phylogenetics, ancestors are typically medians that have no functional constraints. In our method, ancestors are not inferred, but rather chosen from previously observed viruses along a path of mutation and reassortment leading to the target virus. This specificity and functional constraint render our results actionable for further experiments in vitro and in vivo. PMID:22076498

  10. Public sources of information and information needs for pandemic influenza A(H1N1).

    PubMed

    Wong, Li Ping; Sam, I-Ching

    2010-12-01

    Providing health information during disease outbreaks is a fundamental component of outbreak control strategies. This study aimed to explore sources of influenza A(H1N1)-related information, specific information needs and preferences of the lay public during the peak of the outbreak. A cross-sectional, population-based, computer-assisted telephone interview of 1,050 respondents was conducted in Malaysia between July 11 and September 12, 2009. Newspaper, television and family were three main sources of information about A(H1N1). There were substantial ethnic differences; the Malays were significantly more likely to identify television as main source, while newspapers and family were identified as the main sources by the Chinese and Indians, respectively. Overall, the two main information needs identified were prevention and treatment. The Malays expressed lesser need for overall information than other ethnic groups. The three most preferred sources of information were television, newspapers and healthcare providers. There were significant positive correlations between amount of information received with knowledge (r = 0.149), perceived susceptibility to infection (r = 0.177), and other behavioral responses. Health information dissemination should be dedicated to meeting the information needs of diverse sociodemographic and ethnic groups. The findings highlight the importance of providing information that increases awareness and behavioral changes in disease prevention yet reduce fear.

  11. Reassortment Networks and the evolution of pandemic H1N1 swine-origin influenza.

    PubMed

    Bokhari, Shahid H; Pomeroy, Laura W; Janies, Daniel A

    2012-01-01

    Prior research developed Reassortment Networks to reconstruct the evolution of segmented viruses under both reassortment and mutation. We report their application to the swine-origin pandemic H1N1 virus (S-OIV). A database of all influenza A viruses, for which complete genome sequences were available in Genbank by October 2009, was created and dynamic programming was used to compute distances between all corresponding segments. A reassortment network was created to obtain the minimum cost evolutionary paths from all viruses to the exemplar S-OIV A/California/04/2009. This analysis took 35 hours on the Cray Extreme Multithreading (XMT) supercomputer, which has special hardware to permit efficient parallelization. Six specific H1N1/H1N2 bottleneck viruses were identified that almost always lie on minimum cost paths to S-OIV. We conjecture that these viruses are crucial to S-OIV evolution and worthy of careful study from a molecular biology viewpoint. In phylogenetics, ancestors are typically medians that have no functional constraints. In our method, ancestors are not inferred, but rather chosen from previously observed viruses along a path of mutation and reassortment leading to the target virus. This specificity and functional constraint render our results actionable for further experiments in vitro and in vivo.

  12. Characterizing the Epidemiology of the 2009 Influenza A/H1N1 Pandemic in Mexico

    PubMed Central

    Chowell, Gerardo; Echevarría-Zuno, Santiago; Viboud, Cécile; Simonsen, Lone; Tamerius, James; Miller, Mark A.; Borja-Aburto, Víctor H.

    2011-01-01

    Background Mexico's local and national authorities initiated an intense public health response during the early stages of the 2009 A/H1N1 pandemic. In this study we analyzed the epidemiological patterns of the pandemic during April–December 2009 in Mexico and evaluated the impact of nonmedical interventions, school cycles, and demographic factors on influenza transmission. Methods and Findings We used influenza surveillance data compiled by the Mexican Institute for Social Security, representing 40% of the population, to study patterns in influenza-like illness (ILIs) hospitalizations, deaths, and case-fatality rate by pandemic wave and geographical region. We also estimated the reproduction number (R) on the basis of the growth rate of daily cases, and used a transmission model to evaluate the effectiveness of mitigation strategies initiated during the spring pandemic wave. A total of 117,626 ILI cases were identified during April–December 2009, of which 30.6% were tested for influenza, and 23.3% were positive for the influenza A/H1N1 pandemic virus. A three-wave pandemic profile was identified, with an initial wave in April–May (Mexico City area), a second wave in June–July (southeastern states), and a geographically widespread third wave in August–December. The median age of laboratory confirmed ILI cases was ∼18 years overall and increased to ∼31 years during autumn (p<0.0001). The case-fatality ratio among ILI cases was 1.2% overall, and highest (5.5%) among people over 60 years. The regional R estimates were 1.8–2.1, 1.6–1.9, and 1.2–1.3 for the spring, summer, and fall waves, respectively. We estimate that the 18-day period of mandatory school closures and other social distancing measures implemented in the greater Mexico City area was associated with a 29%–37% reduction in influenza transmission in spring 2009. In addition, an increase in R was observed in late May and early June in the southeast states, after mandatory school

  13. Guillain-Barre syndrome, influenzalike illnesses, and influenza vaccination during seasons with and without circulating A/H1N1 viruses.

    PubMed

    Grimaldi-Bensouda, Lamiae; Alpérovitch, Annick; Besson, Gérard; Vial, Christophe; Cuisset, Jean-Marie; Papeix, Caroline; Lyon-Caen, Olivier; Benichou, Jacques; Rossignol, Michel

    2011-08-01

    The role of influenzalike illnesses and influenza vaccination in the development of Guillain-Barré syndrome (GBS), particularly the role of A/H1N1 epidemics and A/H1N1 vaccination, is debated. Data on all incident GBS cases meeting the Brighton Collaboration criteria that were diagnosed at 25 neurology centers in France were prospectively collected between March 2007 and June 2010, covering 3 influenzavirus seasons, including the 2009-2010 A/H1N1 outbreak. A total of 457 general practitioners provided a registry of patients from which 1,080 controls were matched by age, gender, index date (calendar month), and region to 145 cases. Causal relations were assessed by multivariate case-control analysis with adjustment for risk factors (personal and family history of autoimmune disorders, among others), while matching on age, gender, and calendar time. Influenza (seasonal or A/H1N1) or influenzalike symptoms in the 2 months preceding the index date was associated with GBS, with a matched odds ratio of 2.3 (95% confidence interval (CI): 0.7, 8.2). The difference in the rates of GBS occurring between influenza virus circulation periods and noncirculation periods was highly statistically significant (P = 0.004). Adjusted odds ratios for GBS occurrence within 6 weeks after seasonal and A/H1N1 vaccination were 1.3 (95% CI: 0.4, 4.1) and 0.9 (95% CI: 0.1, 7.6), respectively. Study results confirm that influenza virus is a likely risk factor for GBS. Conversely, no new concerns have arisen regarding influenza vaccination.

  14. Efficacy of Inactivated Swine Influenza Virus Vaccines Against the 2009 A/H1N1 Influenza Virus in Pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The gene constellation of the 2009 pandemic A/H1N1 virus is a unique combination from swine influenza A viruses (SIV) of North American and Eurasian lineages, but prior to April 2009 had never before been identified in swine or other species. Although its hemagglutinin gene is related to North Ameri...

  15. Efficacy of Inactivated Swine Influenza Virus Vaccines Against 2009 H1N1 Influenza Virus in Pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction. The gene constellation of the 2009 pandemic H1N1 virus is a unique combination from swine influenza A viruses (SIV) of North American and Eurasian lineages, but prior to April 2009 had never before been identified in swine or other species (1). Although its hemagglutinin gene is relat...

  16. [Colorimetric detection of human influenza A H1N1 virus by reverse transcription loop mediated isothermal amplification].

    PubMed

    Nie, Kai; Wang, Da-Yan; Qin, Meng; Gao, Rong-Bao; Wang, Miao; Zou, Shu-Mei; Han, Feng; Zhao, Xiang; Li, Xi-Yan; Shu, Yue-Long; Ma, Xue-Jun

    2010-03-01

    A simple, rapid and sensitive colorimetric Reverse Transcription Loop Mediated Isothermal Amplification (RT-LAMP) method was established to detect human influenza A H1N1 virus. The method employed a set of six specially designed primers that recognized eight distinct sequences of the HA gene for amplification of nucleic acid under isothermal conditions at 65 degrees C for one and half hour. The amplification process of RT-LAMP was monitored by the addition of HNB (Hydroxy naphthol blue) dye prior to amplification. A positive reaction was indicated by a color change from violet to sky blue and confirmed by agarose electrophoresis. The specificity of the RT-LAMP assay was validated by cross-reaction with different swine and human influenza virus including human seasonal influenza A /H1N1 A /H3N2, influenza B and swine A /H1N1. The sensitivity of this assay was evaluated by serial dilutions of RNA molecules from in vitro transcription of human influenza A H1N1 HA gene. The assay was further evaluated with 30 clinical specimens with suspected pandemic influenza A H1N1 virus infection in parallel with RT-PCR detection and 26 clinical specimens with seasonal influenza virus infection. Our results showed that the RT-LAMP was able to achieve a sensitivity of 60 RNA copies with high specificity, and detection rate was comparable to that of the RT-PCR with the clinical samples of pandemic influenza A H1N1 infection. The RT-LAMP reaction with HNB could also be measured at 650nm in a microplate reader for quantitative analysis. Thus, we concluded that this colorimetric RT-LAMP assay had potential for the rapid screening of the human influenza A H1N1 virus infection in National influenza monitoring network laboratories and sentinel hospitals of provincial and municipal region in China.

  17. The influenza A(H1N1) epidemic in Mexico. Lessons learned

    PubMed Central

    Córdova-Villalobos, José A; Sarti, Elsa; Arzoz-Padrés, Jacqueline; Manuell-Lee, Gabriel; Méndez, Josefina Romero; Kuri-Morales, Pablo

    2009-01-01

    Several influenza pandemics have taken place throughout history and it was assumed that the pandemic would emerge from a new human virus resulting from the adaptation of an avian virus strain. Mexico, since 2003 had developed a National Preparedness and Response Plan for an Influenza Pandemic focused in risk communication, health promotion, healthcare, epidemiological surveillance, strategic stockpile, research and development. This plan was challenged on April 2009, when a new influenza A(H1N1) strain of swine origen was detected in Mexico. The situation faced, the decisions and actions taken, allowed to control the first epidemic wave in the country. This document describes the critical moments faced and explicitly point out the lessons learned focused on the decided support by the government, the National Pandemic Influenza Plan, the coordination among all the government levels, the presence and solidarity of international organizations with timely and daily information, diagnosis and the positive effect on the population following the preventive hygienic measures recommended by the health authorities. The international community will be able to use the Mexican experience in the interest of global health. PMID:19785747

  18. Pandemic swine influenza virus (H1N1): A threatening evolution.

    PubMed

    Khanna, Madhu; Kumar, Binod; Gupta, Neha; Kumar, Prashant; Gupta, Ankit; Vijayan, V K; Kaur, Harpreet

    2009-12-01

    "Survival of the fittest" is an old axiom laid down by the great evolutionist Charles Darwin and microorganisms seem to have exploited this statement to a great extent. The ability of viruses to adapt themselves to the changing environment has made it possible to inhabit itself in this vast world for the past millions of years. Experts are well versed with the fact that influenza viruses have the capability to trade genetic components from one to the other within animal and human population. In mid April 2009, the Centers for Disease Control and Prevention and the World Health Organization had recognized a dramatic increase in number of influenza cases. These current 2009 infections were found to be caused by a new strain of influenza type A H1N1 virus which is a re-assortment of several strains of influenza viruses commonly infecting human, avian, and swine population. This evolution is quite dependent on swine population which acts as a main reservoir for the reassortment event in virus. With the current rate of progress and the efforts of heath authorities worldwide, we have still not lost the race against fighting this virus. This article gives an insight to the probable source of origin and the evolutionary progress it has gone through that makes it a potential threat in the future, the current scenario and the possible measures that may be explored to further strengthen the war against pandemic.

  19. From where did the 2009 'swine-origin' influenza A virus (H1N1) emerge?

    PubMed

    Gibbs, Adrian J; Armstrong, John S; Downie, Jean C

    2009-11-24

    The swine-origin influenza A (H1N1) virus that appeared in 2009 and was first found in human beings in Mexico, is a reassortant with at least three parents. Six of the genes are closest in sequence to those of H1N2 'triple-reassortant' influenza viruses isolated from pigs in North America around 1999-2000. Its other two genes are from different Eurasian 'avian-like' viruses of pigs; the NA gene is closest to H1N1 viruses isolated in Europe in 1991-1993, and the MP gene is closest to H3N2 viruses isolated in Asia in 1999-2000. The sequences of these genes do not directly reveal the immediate source of the virus as the closest were from isolates collected more than a decade before the human pandemic started. The three parents of the virus may have been assembled in one place by natural means, such as by migrating birds, however the consistent link with pig viruses suggests that human activity was involved. We discuss a published suggestion that unsampled pig herds, the intercontinental live pig trade, together with porous quarantine barriers, generated the reassortant. We contrast that suggestion with the possibility that laboratory errors involving the sharing of virus isolates and cultured cells, or perhaps vaccine production, may have been involved. Gene sequences from isolates that bridge the time and phylogenetic gap between the new virus and its parents will distinguish between these possibilities, and we suggest where they should be sought. It is important that the source of the new virus be found if we wish to avoid future pandemics rather than just trying to minimize the consequences after they have emerged. Influenza virus is a very significant zoonotic pathogen. Public confidence in influenza research, and the agribusinesses that are based on influenza's many hosts, has been eroded by several recent events involving the virus. Measures that might restore confidence include establishing a unified international administrative framework coordinating

  20. Thoracic computerized tomographic (CT) findings in 2009 influenza A (H1N1) virus infection in Isfahan, Iran

    PubMed Central

    Rostami, Mojtaba; Javadi, Abbas-Ali; Khorvash, Farzin; Mostafavizadeh, Kamyar; Adibi, Atoosa; Babak, Anahita; Ataei, Behrooz; Meidani, Mohsen; Naeini, Alireza Emami; Salehi, Hasan; Avijgan, Majid; Yazdani, Mohammad Reza; Rezaei, Farshid

    2011-01-01

    BACKGROUND: Pandemic 2009 H1N1 influenza A virus arrived at Isfahan in August 2009. The virus is still circulating in the world. The abnormal thoracic computerized tomographic (CT) scan findings vary widely among the studies of 2009 H1N1 influenza. We evaluated the thoracic CT findings in patients with 2009 H1N1 virus infection to describe findings compared to previously reported findings, and to suggest patterns that may be suggestive for 2009 influenza A (H1N1) in an appropriate clinical setting. METHODS: Retrospectively, the archive of all patients with a diagnosis of 2009 H1N1 influenza A were reviewed, in Al-Zahra Hospital in Isfahan, central Iran, between September 23rd 2009 to February 20th 2010. Out of 216 patients with confirmed 2009 influenza A (H1N1) virus, 26 cases with abnormal CT were enrolled in the study. Radiologic findings were characterized by the type and pattern of opacities and zonal distribution. RESULTS: Patchy infiltration (34.6%), lobar consolidation (30.8%), and interstitial infiltration (26.9%) with airbronchogram (38.5%) were the predominant findings in our patients. Bilateral distribution was seen in 80.8% of the patients. Only one patient (3.8%) showed ground-glass opacity, predominant radiographic finding in the previous reports and severe acute respiratory syndrome (SARS). CONCLUSIONS: The most common thoracic CT findings in pandemic H1N1 were patchy infiltration, lobar consolidation, and interstitial infiltration with airbronchogram and bilateral distribution. While these findings can be associated with other infections; they may be suggestive to 2009 influenza A (H1N1) in the appropriate clinical setting. Various radiographic patterns can be seen in thoracic CT scans of the influenza patients. Imaging findings are nonspecific. PMID:22091280

  1. Isolation and phylogenetic analysis of avian-origin European H1N1 swine influenza viruses in Jiangsu, China.

    PubMed

    Zhao, Guo; Pan, Jinjin; Gu, Xiaobing; Lu, Xinlun; Li, Qunhui; Zhu, Jie; Chen, Chaoyang; Duan, Zhiqiang; Xu, Quangang; Wang, Xiaobo; Hu, Shunlin; Liu, Wenbo; Peng, Daxin; Liu, Xiaowen; Wang, Xiaoquan; Liu, Xiufan

    2012-04-01

    Isolates of the A(H1N1)pdm2009 virus were first identified in asymptomatic swine in Jiangsu province, China in January 2010, indicating that the virus has retro-infected swine after circulating through humans in mainland China. The purpose of this study was to determine whether the avian-origin European H1N1 swine influenza virus (SIV) and the A(H1N1)pdm2009 virus are cocirculating in swine in Jiangsu province of China. From May 2010 to May 2011, 1,030 nasal swab samples were collected from healthy swine in Jiangsu province of China and were tested for influenza A H1N1 using reverse transcription-PCR. Fragments of the complete genomes of viruses from the samples that were positive for influenza A H1N1 were sequenced and analysed. A total of 32 avian-origin European H1N1 SIVs were isolated, and no A(H1N1)pdm2009 viruses were identified; full-length genomes of 18 strains were sequenced. The eight gene segments of some of the isolated H1N1 viruses have 99.1-99.8% sequence identity with the human A/Jiangsu/ALS1/2011(H1N1) isolates in the same region. Our study indicates that the avian-origin European H1N1 SIVs remain endemic in swine and have retro-infected humans after circulating through swine, which may present a risk factor for public health.

  2. Macrophage activation syndrome induced by A/H1N1 influenza in cystic fibrosis.

    PubMed

    Casciaro, Rosaria; Cresta, Federico; Favilli, Federica; Naselli, Aldo; De Alessandri, Alessandra; Minicucci, Laura

    2014-02-01

    Bacterial respiratory infections have an important impact on the development and progression of pulmonary disease in cystic fibrosis (CF). Viral infections are possible triggers of acute deterioration in the clinical status of CF patients. Macrophage activation syndrome (MAS) is a life-threatening complication of rheumatic disease characterized by pancytopenia, hepatitis, hyperferritinemia, coagulopathy, and neurologic symptoms. This syndrome is thought to be caused by the activation and uncontrolled proliferation of T lymphocytes and well-differentiated macrophages, leading to widespread hemophagocytosis and cytokine overproduction. Here, we report the case of a boy affected by CF who developed MAS triggered by pandemic H1N1 influenza; good clinical response was obtained through high dose prednisone treatment. PMID:23401277

  3. Exhaled aerosol transmission of pandemic and seasonal H1N1 influenza viruses in the ferret.

    PubMed

    Koster, Frederick; Gouveia, Kristine; Zhou, Yue; Lowery, Kristin; Russell, Robert; MacInnes, Heather; Pollock, Zemmie; Layton, R Colby; Cromwell, Jennifer; Toleno, Denise; Pyle, John; Zubelewicz, Michael; Harrod, Kevin; Sampath, Rangarajan; Hofstadler, Steven; Gao, Peng; Liu, Yushi; Cheng, Yung-Sung

    2012-01-01

    Person-to-person transmission of influenza viruses occurs by contact (direct and fomites) and non-contact (droplet and small particle aerosol) routes, but the quantitative dynamics and relative contributions of these routes are incompletely understood. The transmissibility of influenza strains estimated from secondary attack rates in closed human populations is confounded by large variations in population susceptibilities. An experimental method to phenotype strains for transmissibility in an animal model could provide relative efficiencies of transmission. We developed an experimental method to detect exhaled viral aerosol transmission between unanesthetized infected and susceptible ferrets, measured aerosol particle size and number, and quantified the viral genomic RNA in the exhaled aerosol. During brief 3-hour exposures to exhaled viral aerosols in airflow-controlled chambers, three strains of pandemic 2009 H1N1 strains were frequently transmitted to susceptible ferrets. In contrast one seasonal H1N1 strain was not transmitted in spite of higher levels of viral RNA in the exhaled aerosol. Among three pandemic strains, the two strains causing weight loss and illness in the intranasally infected 'donor' ferrets were transmitted less efficiently from the donor than the strain causing no detectable illness, suggesting that the mucosal inflammatory response may attenuate viable exhaled virus. Although exhaled viral RNA remained constant, transmission efficiency diminished from day 1 to day 5 after donor infection. Thus, aerosol transmission between ferrets may be dependent on at least four characteristics of virus-host relationships including the level of exhaled virus, infectious particle size, mucosal inflammation, and viral replication efficiency in susceptible mucosa.

  4. Predicting peptide vaccine candidates against H1N1 influenza virus through theoretical approaches.

    PubMed

    Bello, Martiniano; Campos-Rodriguez, Rafael; Rojas-Hernandez, Saul; Contis-Montes de Oca, Arturo; Correa-Basurto, José

    2015-05-01

    Identification of potential epitopes that might activate the immune system has been facilitated by the employment of algorithms that use experimental data as templates. However, in order to prove the affinity and the map of interactions between the receptor (major histocompatibility complex, MHC, or T-cell receptor) and the potential epitope, further computational studies are required. Docking and molecular dynamics (MDs) simulations have been an effective source of generating structural information at molecular level in immunology. Herein, in order to provide a detailed understanding of the origins of epitope recognition and to select the best peptide candidate to develop an epitope-based vaccine, docking and MDs simulations in combination with MMGBSA free energy calculations and per-residue free energy decomposition were performed, taking as starting complexes those formed between four designed epitopes (P1-P4) from hemagglutinin (HA) of the H1N1 influenza virus and MHC-II anchored in POPC membrane. Our results revealed that the energetic contributions of individual amino acids within the pMHC-II complexes are mainly dictated by van der Waals interactions and the nonpolar part of solvation energy, whereas the electrostatic interactions corresponding to hydrogen bonds and salt bridges determine the binding specificity, being the most favorable interactions formed between p4 and MHC-II. Then, P1-P4 epitopes were synthesized and tested experimentally to compare theoretical and experimental results. Experimental results show that P4 elicited the highest strong humoral immune response to HA of the H1N1 and may induce antibodies that are cross-reactive to other influenza subtypes, suggesting that it could be a good candidate for the development of a peptide-based vaccine.

  5. Influenza a (H1N1) outbreak and challenges for pharmacotherapy.

    PubMed

    Chawla, Raman; Sharma, Rakesh Kumar; Bhardwaj, Janak Raj

    2009-01-01

    Influenza A (H1N1) virus, a genetic reassortment of endemic strain of human, avian flu and swine flu, with an inherent ability to mutate continuously has developed a subtype which is causing present flu in humans. As on 10th May, 2009, twenty nine countries are affected with officially reported 4379 cases with Mexico--1626 affected (45 deaths), US 2254 affected (02 deaths); Canada 280 (01 deaths) and Costa Ricia -8 cases (01 death) respectively. Rest of 15 countries have reported less than 100 officially confirmed cases of H1N1 infection. WHO has already declared Pandemic Alert V on 29th April, 2009. If the present flu achieves equivalent virulence to that of 1918-19 pandemic flu, expected deaths will be 62 million people. Travel advisory, stockpiling of antiviral drugs--Tamiflu & Relenza; vaccine development, activation of business continuity planning for maintenance of essential serives etc., are some of the important mitigation approaches, being followed all over the world. WHO has a regional reserve of 10,000 million doses of anti-viral drugs. National Disaster Management Authority (NDMA), Government of India, an apex body for disaster management, in active coordination with Ministry of Health & other stakeholders/service providers is maintaining a constant state of vigil on the present Influenza A (H1N1) outbreak. In collaboration with UNDMT, NDMA has outlined a strategy for Pandemic Preparedness beyond Health in April, 2008. Various non-pharmaceutical interventions like detection, isolation and quarantine are required to contain the situation. Accordingly, stockpiling of 10 million doses of anti viral drugs, surveillance at airports, isolation with strict enforcement of quarantine procedures, sustained supply of respiratory masks & other personal protective equipment; deployment of rapid response teams are some of the activities being undertaken by Indian Government proactively. As situation goes to Phase VI, there will be a shift in strategy from active

  6. Mortality attributable to pandemic influenza A (H1N1) 2009 in San Luis Potosí, Mexico

    PubMed Central

    Comas‐García, Andreu; García‐Sepúlveda, Christian A.; Méndez‐de Lira, José J.; Aranda‐Romo, Saray; Hernández‐Salinas, Alba E.; Noyola, Daniel E.

    2010-01-01

    Please cite this paper as: Comas‐García et al. (2011) Mortality attributable to pandemic influenza A (H1N1) 2009 in San Luis Potosí, Mexico. Influenza and Other Respiratory Viruses 5(2), 76–82. Background  Acute respiratory infections are a leading cause of morbidity and mortality worldwide. Starting in 2009, pandemic influenza A(H1N1) 2009 virus has become one of the leading respiratory pathogens worldwide. However, the overall impact of this virus as a cause of mortality has not been clearly defined. Objectives  To determine the impact of pandemic influenza A(H1N1) 2009 on mortality in a Mexican population. Methods  We assessed the impact of pandemic influenza virus on mortality during the first and second outbreaks in San Luis Potosí, Mexico, and compared it to mortality associated with seasonal influenza and respiratory syncytial virus (RSV) during the previous winter seasons. Results  We estimated that, on average, 8·1% of all deaths that occurred during the 2003–2009 seasons were attributable to influenza and RSV. During the first pandemic influenza A(H1N1) 2009 outbreak, there was an increase in mortality in persons 5–59 years of age, but not during the second outbreak (Fall of 2009). Overall, pandemic influenza A (H1N1) 2009 outbreaks had similar effects on mortality to those associated with seasonal influenza virus epidemics. Conclusions  The impact of influenza A(H1N1) 2009 virus on mortality during the first year of the pandemic was similar to that observed for seasonal influenza. The establishment of real‐time surveillance systems capable of integrating virological, morbidity, and mortality data may result in the timely identification of outbreaks so as to allow for the institution of appropriate control measures to reduce the impact of emerging pathogens on the population. PMID:21306570

  7. Transcriptomic Profiling in Childhood H1N1/09 Influenza Reveals Reduced Expression of Protein Synthesis Genes

    PubMed Central

    Herberg, Jethro A.; Kaforou, Myrsini; Gormley, Stuart; Sumner, Edward R.; Patel, Sanjay; Jones, Kelsey D. J.; Paulus, Stéphane; Fink, Colin; Martinon-Torres, Federico; Montana, Giovanni; Wright, Victoria J.; Levin, Michael

    2013-01-01

    We compared the blood RNA transcriptome of children hospitalized with influenza A H1N1/09, respiratory syncytial virus (RSV) or bacterial infection, and healthy controls. Compared to controls, H1N1/09 patients showed increased expression of inflammatory pathway genes and reduced expression of adaptive immune pathway genes. This was validated on an independent cohort. The most significant function distinguishing H1N1/09 patients from controls was protein synthesis, with reduced gene expression. Reduced expression of protein synthesis genes also characterized the H1N1/09 expression profile compared to children with RSV and bacterial infection, suggesting that this is a key component of the pathophysiological response in children hospitalized with H1N1/09 infection. PMID:23901082

  8. The Effect of Risk Perception on the 2009 H1N1 Pandemic Influenza Dynamics

    PubMed Central

    Poletti, Piero; Ajelli, Marco; Merler, Stefano

    2011-01-01

    Background The 2009 H1N1 pandemic influenza dynamics in Italy was characterized by a notable pattern: as it emerged from the analysis of influenza-like illness data, after an initial period (September–mid-October 2009) characterized by a slow exponential increase in the weekly incidence, a sudden and sharp increase of the growth rate was observed by mid-October. The aim here is to understand whether spontaneous behavioral changes in the population could be responsible for such a pattern of epidemic spread. Methodology/Principal Findings In order to face this issue, a mathematical model of influenza transmission, accounting for spontaneous behavioral changes driven by cost/benefit considerations on the perceived risk of infection, is proposed and validated against empirical epidemiological data. The performed investigation revealed that an initial overestimation of the risk of infection in the general population, possibly induced by the high concern for the emergence of a new influenza pandemic, results in a pattern of spread compliant with the observed one. This finding is also supported by the analysis of antiviral drugs purchase over the epidemic period. Moreover, by assuming a generation time of 2.5 days, the initially diffuse misperception of the risk of infection led to a relatively low value of the reproductive number , which increased to in the subsequent phase of the pandemic. Conclusions/Significance This study highlights that spontaneous behavioral changes in the population, not accounted by the large majority of influenza transmission models, can not be neglected to correctly inform public health decisions. In fact, individual choices can drastically affect the epidemic spread, by altering timing, dynamics and overall number of cases. PMID:21326878

  9. H1N1 influenza virus induces narcolepsy-like sleep disruption and targets sleep-wake regulatory neurons in mice.

    PubMed

    Tesoriero, Chiara; Codita, Alina; Zhang, Ming-Dong; Cherninsky, Andrij; Karlsson, Håkan; Grassi-Zucconi, Gigliola; Bertini, Giuseppe; Harkany, Tibor; Ljungberg, Karl; Liljeström, Peter; Hökfelt, Tomas G M; Bentivoglio, Marina; Kristensson, Krister

    2016-01-19

    An increased incidence in the sleep-disorder narcolepsy has been associated with the 2009-2010 pandemic of H1N1 influenza virus in China and with mass vaccination campaigns against influenza during the pandemic in Finland and Sweden. Pathogenetic mechanisms of narcolepsy have so far mainly focused on autoimmunity. We here tested an alternative working hypothesis involving a direct role of influenza virus infection in the pathogenesis of narcolepsy in susceptible subjects. We show that infection with H1N1 influenza virus in mice that lack B and T cells (Recombinant activating gene 1-deficient mice) can lead to narcoleptic-like sleep-wake fragmentation and sleep structure alterations. Interestingly, the infection targeted brainstem and hypothalamic neurons, including orexin/hypocretin-producing neurons that regulate sleep-wake stability and are affected in narcolepsy. Because changes occurred in the absence of adaptive autoimmune responses, the findings show that brain infections with H1N1 virus have the potential to cause per se narcoleptic-like sleep disruption.

  10. Influenza A(H1N1) Oseltamivir Resistant Viruses in the Netherlands During the Winter 2007/2008

    PubMed Central

    Dijkstra, Frederika; Jonges, Marcel; van Beek, Ruud; Donker, Gé A; Schellevis, François G; Koopmans, Marion; van der Sande, Marianne A.B; Osterhaus, Albert D.M.E; Boucher, Charles A.B; Rimmelzwaan, Guus F; Meijer, Adam

    2011-01-01

    Background: Antiviral susceptibility surveillance in the Netherlands was intensified after the first reports about the emergence of influenza A(H1N1) oseltamivir resistant viruses in Norway in January, 2008. Methods: Within the existing influenza surveillance an additional questionnaire study was performed to retrospectively assess possible risk factors and establish clinical outcome of all patients with influenza virus A(H1N1) positive specimens. To discriminate resistant and sensitive viruses, fifty percent inhibitory concentrations for the neuramidase inhibitors oseltamivir and zanamivir were determined in a neuraminidase inhibition assay. Mutations previously associated with resistance to neuramidase inhibitors and M2 blockers (amantadine and rimantadine) were searched for by nucleotide sequencing of neuraminidase and M2 genes respectively. Results: Among 171 patients infected with A(H1N1) viruses an overall prevalence of oseltamivir resistance of 27% (95% CI: 20-34%) was found. None of influenza A(H1N1) oseltamivir resistant viruses tested was resistant against amantadine or zanamivir. Patient characteristics, underlying conditions, influenza vaccination, symptoms, complications, and exposure to oseltamivir and other antivirals did not differ significantly between patients infected with resistant and sensitive A(H1N1) viruses. Conclusion: In 2007/2008 a large proportion of influenza A(H1N1) viruses resistant to oseltamivir was detected. There were no clinical differences between patients infected with resistant and sensitive A(H1N1) viruses. Continuous monitoring of the antiviral drug sensitivity profile of influenza viruses is justified, preferably using the existing sentinel surveillance, however, complemented with data from the more severe end of the clinical spectrum. In order to act timely on emergencies of public health importance we suggest setting up a surveillance system that can guarantee rapid access to the latter. PMID:22253652

  11. Immune history shapes specificity of pandemic H1N1 influenza antibody responses

    PubMed Central

    Li, Yang; Myers, Jaclyn L.; Bostick, David L.; Sullivan, Colleen B.; Madara, Jonathan; Linderman, Susanne L.; Liu, Qin; Carter, Donald M.; Wrammert, Jens; Esposito, Susanna; Principi, Nicola; Plotkin, Joshua B.; Ross, Ted M.; Ahmed, Rafi; Wilson, Patrick C.

    2013-01-01

    Human antibody responses against the 2009 pandemic H1N1 (pH1N1) virus are predominantly directed against conserved epitopes in the stalk and receptor-binding domain of the hemagglutinin (HA) protein. This is in stark contrast to pH1N1 antibody responses generated in ferrets, which are focused on the variable Sa antigenic site of HA. Here, we show that most humans born between 1983 and 1996 elicited pH1N1 antibody responses that are directed against an epitope near the HA receptor–binding domain. Importantly, most individuals born before 1983 or after 1996 did not elicit pH1N1 antibodies to this HA epitope. The HAs of most seasonal H1N1 (sH1N1) viruses that circulated between 1983 and 1996 possess a critical K133 amino acid in this HA epitope, whereas this amino acid is either mutated or deleted in most sH1N1 viruses circulating before 1983 or after 1996. We sequentially infected ferrets with a 1991 sH1N1 virus and then a pH1N1 virus. Sera isolated from these animals were directed against the HA epitope involving amino acid K133. These data suggest that the specificity of pH1N1 antibody responses can be shifted to epitopes near the HA receptor–binding domain after sequential infections with sH1N1 and pH1N1 viruses that share homology in this region. PMID:23857983

  12. Enhanced influenza surveillance on Réunion Island (southern hemisphere) in the context of the emergence of influenza A(H1N1)v.

    PubMed

    D'Ortenzio, E; Do, C; Renault, P; Weber, F; Filleul, L

    2009-06-11

    With the winter season on the southern hemisphere that starts in Reunion Island in June seasonal influenza activity usually increases shortly afterwards. The new influenza A(H1N1)v virus is rapidly spreading worldwide and may reach the island during the coming winter season. We have therefore enhanced influenza surveillance to detect the introduction of influenza A(H1N1)v, monitor its spread and impact on public health and characterise potential viral changes, particularly if seasonal influenza A(H1N1), resistant to oseltamivir, co-circulates with A(H1N1)v. PMID:19531342

  13. Computer-aided assessment of pulmonary disease in novel swine-origin H1N1 influenza on CT

    NASA Astrophysics Data System (ADS)

    Yao, Jianhua; Dwyer, Andrew J.; Summers, Ronald M.; Mollura, Daniel J.

    2011-03-01

    The 2009 pandemic is a global outbreak of novel H1N1 influenza. Radiologic images can be used to assess the presence and severity of pulmonary infection. We develop a computer-aided assessment system to analyze the CT images from Swine-Origin Influenza A virus (S-OIV) novel H1N1 cases. The technique is based on the analysis of lung texture patterns and classification using a support vector machine (SVM). Pixel-wise tissue classification is computed from the SVM value. The method was validated on four H1N1 cases and ten normal cases. We demonstrated that the technique can detect regions of pulmonary abnormality in novel H1N1 patients and differentiate these regions from visually normal lung (area under the ROC curve is 0.993). This technique can also be applied to differentiate regions infected by different pulmonary diseases.

  14. Human vs. animal outbreaks of the 2009 swine-origin H1N1 influenza A epidemic.

    PubMed

    Scotch, Matthew; Brownstein, John S; Vegso, Sally; Galusha, Deron; Rabinowitz, Peter

    2011-09-01

    The majority of emerging infectious diseases are zoonotic in origin, including recently emerging influenza viruses such as the 2009 swine-origin H1N1 influenza A epidemic. The epidemic that year affected both human and animal populations as it spread globally. In fact, before the end of 2009, 14 different countries reported H1N1 infected swine. In order to better understand the zoonotic nature of the epidemic and the relationship between human and animal disease surveillance data streams, we compared 2009 reports of H1N1 infection to define the temporal relationship between reported cases in animals and humans. Generally, human cases preceded animal cases at a country-level, supporting the potential of H1N1 infection to be a "reverse zoonosis", and the value of integrating human and animal disease report data.

  15. Differentiation of human influenza A viruses including the pandemic subtype H1N1/2009 by conventional multiplex PCR.

    PubMed

    Furuse, Yuki; Odagiri, Takashi; Okada, Takashi; Khandaker, Irona; Shimabukuro, Kozue; Sawayama, Rumi; Suzuki, Akira; Oshitani, Hitoshi

    2010-09-01

    April 2009 witnessed the emergence of a novel H1N1 influenza A virus infecting the human population. Currently, pandemic and seasonal influenza viruses are co-circulating in human populations. Understanding the course of the emerging pandemic virus is important. It is still unknown how the novel virus co-circulates with or outcompetes seasonal viruses. Sustainable and detailed influenza surveillance is required throughout the world including developing countries. In the present study, a multiplex PCR using four primers was developed, which was designed to differentiate the pandemic H1N1 virus from the seasonal H1N1 and H3N2 viruses, to obtain amplicons of different sizes. Multiplex PCR analysis could clearly differentiate the three subtypes of human influenza A virus. This assay was performed using 206 clinical samples collected in 2009 in Japan. Between February and April, four samples were subtyped as seasonal H1N1 and four as seasonal H3N2. All samples collected after July were subtyped as pandemic H1N1. Currently, pandemic viruses seem to have replaced seasonal viruses almost completely in Japan. This is a highly sensitive method and its cost is low. Influenza surveillance using this assay would provide significant information on the epidemiology of both pandemic and seasonal influenza.

  16. Initial psychological responses to Influenza A, H1N1 ("Swine flu")

    PubMed Central

    2009-01-01

    Background The outbreak of the pandemic flu, Influenza A H1N1 (Swine Flu) in early 2009, provided a major challenge to health services around the world. Previous pandemics have led to stockpiling of goods, the victimisation of particular population groups, and the cancellation of travel and the boycotting of particular foods (e.g. pork). We examined initial behavioural and attitudinal responses towards Influenza A, H1N1 ("Swine flu") in the six days following the WHO pandemic alert level 5, and regional differences in these responses. Methods 328 respondents completed a cross-sectional Internet or paper-based questionnaire study in Malaysia (N = 180) or Europe (N = 148). Measures assessed changes in transport usage, purchase of preparatory goods for a pandemic, perceived risk groups, indicators of anxiety, assessed estimated mortality rates for seasonal flu, effectiveness of seasonal flu vaccination, and changes in pork consumption Results 26% of the respondents were 'very concerned' about being a flu victim (42% Malaysians, 5% Europeans, p < .001). 36% reported reduced public transport use (48% Malaysia, 22% Europe, p < .001), 39% flight cancellations (56% Malaysia, 17% Europe, p < .001). 8% had purchased preparatory materials (e.g. face masks: 8% Malaysia, 7% Europe), 41% Malaysia (15% Europe) intended to do so (p < .001). 63% of Europeans, 19% of Malaysians had discussed the pandemic with friends (p < .001). Groups seen as at 'high risk' of infection included the immune compromised (mentioned by 87% respondents), pig farmers (70%), elderly (57%), prostitutes/highly sexually active (53%), and the homeless (53%). In data collected only in Europe, 64% greatly underestimated the mortality rates of seasonal flu, 26% believed seasonal flu vaccination gave protection against swine flu. 7% had reduced/stopped eating pork. 3% had purchased anti-viral drugs for use at home, while 32% intended to do so if the pandemic worsened. Conclusion Initial responses to Influenza A

  17. Timeliness of contact tracing among flight passengers for influenza A/H1N1 2009

    PubMed Central

    2011-01-01

    Background During the initial containment phase of influenza A/H1N1 2009, close contacts of cases were traced to provide antiviral prophylaxis within 48 h after exposure and to alert them on signs of disease for early diagnosis and treatment. Passengers seated on the same row, two rows in front or behind a patient infectious for influenza, during a flight of ≥ 4 h were considered close contacts. This study evaluates the timeliness of flight-contact tracing (CT) as performed following national and international CT requests addressed to the Center of Infectious Disease Control (CIb/RIVM), and implemented by the Municipal Health Services of Schiphol Airport. Methods Elapsed days between date of flight arrival and the date passenger lists became available (contact details identified - CI) was used as proxy for timeliness of CT. In a retrospective study, dates of flight arrival, onset of illness, laboratory diagnosis, CT request and identification of contacts details through passenger lists, following CT requests to the RIVM for flights landed at Schiphol Airport were collected and analyzed. Results 24 requests for CT were identified. Three of these were declined as over 4 days had elapsed since flight arrival. In 17 out of 21 requests, contact details were obtained within 7 days after arrival (81%). The average delay between arrival and CI was 3,9 days (range 2-7), mainly caused by delay in diagnosis of the index patient after arrival (2,6 days). In four flights (19%), contacts were not identified or only after > 7 days. CI involving Dutch airlines was faster than non-Dutch airlines (P < 0,05). Passenger locator cards did not improve timeliness of CI. In only three flights contact details were identified within 2 days after arrival. Conclusion CT for influenza A/H1N1 2009 among flight passengers was not successful for timely provision of prophylaxis. CT had little additional value for alerting passengers for disease symptoms, as this information already was provided

  18. Asthma and severity of 2009 novel H1N1 influenza: A population-based case-control study

    PubMed Central

    Santillan Salas, Carlos F.; Mehra, Sonia; Pardo Crespo, Maria R.; Juhn, Young J.

    2015-01-01

    Background Asthma has been shown to be associated with an increased risk of the 2009 novel H1N1 influenza (H1N1) infection among children. However, little is known about the role of asthma in severity of H1N1 infection. Objective To determine the association between asthma and other atopic conditions and severity of H1N1 infection. Patients and Methods We conducted a population-based case-control study. Cases were all Olmsted County, MN residents admitted to the hospital within a week of a positive test for H1N1. Controls who had a positive H1N1 but were not admitted to hospital were individually matched to cases with regard to birthday, gender, clinic registration date, diagnostic method, and calendar month of influenza testing. Asthma was ascertained using predetermined criteria. Data were fit to conditional logistic regression models. Results There were 46 eligible individuals admitted to hospitals with H1N1 infection during the study period. Ninety-seven controls were individually matched to their corresponding cases. Among cases, 23 (50%) were male and 29 (63.0%) were Caucasians. The median age at hospitalization was 20.7 years. Twenty-five (54.4%) cases had asthma before the date of hospitalization, compared to 33 (34.0%) controls (matched OR: 2.31; 95% CI, 1.13–4.73; p=0.02). This association approached statistical significance after adjusting for all pertinent covariates (adjusted matched OR: 2.55; 95% CI, 0.98–6.64; p=0.055). Conclusion Asthma may be associated with severe H1N1 infection. In addition to timely influenza vaccination for asthmatics, consideration for prophylactic treatment for unimmunized asthmatics with significant exposure to influenza and immunized asthmatics with early flu-like symptoms should be given. PMID:23947393

  19. Investigating 2009 pandemic influenza A (H1N1) in US schools: what have we learned?

    PubMed

    Iuliano, A Danielle; Dawood, Fatimah S; Silk, Benjamin J; Bhattarai, Achuyt; Copeland, Daphne; Doshi, Saumil; France, Anne Marie; Jackson, Michael L; Kennedy, Erin; Loustalot, Fleetwood; Marchbanks, Tiffany; Mitchell, Tarissa; Averhoff, Francisco; Olsen, Sonja J; Swerdlow, David L; Finelli, Lyn

    2011-01-01

    US investigations of school-based outbreaks of 2009 pandemic influenza A (H1N1) virus infection characterized influenza-like illness (ILI) attack rates, transmission risk factors, and adherence to nonpharmaceutical interventions. We summarize seven school-based investigations conducted during April-June 2009 to determine what questions might be answered by future investigations. Surveys were administered 5-28 days after identification of the outbreaks, and participation rates varied among households (39-86%) and individuals (24-49%). Compared with adults (4%-10%) and children aged <4 years (2%-7%), elementary through university students had higher ILI attack rates (4%-32%). Large gatherings or close contact with sick persons were identified as transmission risk factors. More participants reported adherence to hygiene measures, but fewer reported adherence to isolation measures. Challenges included low participation and delays in survey initiation that potentially introduced bias. Although school-based investigations can increase our understanding of epidemiology and prevention strategy effectiveness, investigators should decide which objectives are most feasible, given timing and design constraints. PMID:21342889

  20. Pandemic influenza A(H1N1) 2009 vaccines in the European Union.

    PubMed

    Johansen, K; Nicoll, A; Ciancio, B C; Kramarz, P

    2009-01-01

    Pandemic vaccines from four manufacturers are now available for use within the European Union (EU). Use of these vaccines will protect individuals and reduce the impact on health services to more manageable levels. The majority of the severely ill will be from known risk groups and the best strategy will be to start vaccinating in line with the recommendation from the European Union Health Security Committee prioritizing adults and children with chronic conditions, pregnant women and healthcare workers. The composition of authorized vaccines is reviewed in this article. The vaccine strain in all authorized pandemic vaccines worldwide is based on the same initial isolate of influenza A/California/7/2009 (H1N1)v but the vaccines differ in conditions for virus propagation, antigen preparation, antigen content and whether they are adjuvanted or not. The vaccines are likely to be effective since no significant genetic or antigenic drift has occurred and there are already mechanisms for estimating clinical effectiveness. Influenza vaccines have good safety records and no safety concerns have so far been encountered with any of the vaccines developed. However, special mechanisms have been devised for the early detection and rigorous investigation of possible significant side effects in Europe through post-marketing surveillance and analysis. Delivery of the vaccines to the risk groups will pose difficulties where those with chronic illnesses are not readily identifiable to the healthcare services. There is considerable scope for European added value through Member States with excess vaccines making them available to other states. PMID:19883538

  1. Transmission of pandemic (H1N1) 2009 influenza to healthcare personnel in the United States.

    PubMed

    Wise, Matthew E; De Perio, Marie; Halpin, John; Jhung, Michael; Magill, Shelley; Black, Stephanie R; Gerber, Susan I; Harriman, Kathleen; Rosenberg, Jon; Borlaug, Gwen; Finelli, Lyn; Olsen, Sonja J; Swerdlow, David L; Kallen, Alexander J

    2011-01-01

    After identification of pandemic 2009 influenza (pH1N1) in the United States, the Centers for Disease Control and Prevention (CDC) worked with state and local health officials to characterize infections among healthcare personnel (HCP). Detailed information, including likely routes of exposure, was reported for 70 HCP from 22 states. Thirty-five cases (50%) were classified as being infected in healthcare settings, 18 cases (26%) were considered to have been infected in community settings, and no definitive source was identified for 17 cases (24%). Of the 23 HCP infected by ill patients, only 20% reported using an N95 respirator or surgical mask during all encounters and more than half worked in outpatient clinics. In addition to community transmission, likely patient-to-HCP and HCP-to-HCP transmission were identified in healthcare settings, highlighting the need for comprehensive infection control strategies including administration of influenza vaccine, appropriate management of ill HCP, and adherence to infection control precautions. PMID:21342895

  2. Structural Characterization of the 1918 Influenza H1N1 Neuraminidase

    SciTech Connect

    Xu, X.; Zhu, X.; Dwek, R.A.; Stevens, J.; Wilson, I.A.

    2009-05-28

    Influenza virus neuraminidase (NA) plays a crucial role in facilitating the spread of newly synthesized virus in the host and is an important target for controlling disease progression. The NA crystal structure from the 1918 'Spanish flu' (A/Brevig Mission/1/18 H1N1) and that of its complex with zanamivir (Relenza) at 1.65-{angstrom} and 1.45-{angstrom} resolutions, respectively, corroborated the successful expression of correctly folded NA tetramers in a baculovirus expression system. An additional cavity adjacent to the substrate-binding site is observed in N1, compared to N2 and N9 NAs, including H5N1. This cavity arises from an open conformation of the 150 loop (Gly147 to Asp151) and appears to be conserved among group 1 NAs (N1, N4, N5, and N8). It closes upon zanamivir binding. Three calcium sites were identified, including a novel site that may be conserved in N1 and N4. Thus, these high-resolution structures, combined with our recombinant expression system, provide new opportunities to augment the limited arsenal of therapeutics against influenza.

  3. Outbreak of 2009 pandemic influenza A (H1N1) on a Peruvian Navy ship - June-July 2009.

    PubMed

    2010-02-19

    On June 25, 2009, a naval cadet reported to the infirmary of a 355-crewman Peruvian Navy ship with a febrile acute respiratory infection (FARI) 5 days after the ship docked in San Francisco, California. Pandemic 2009 influenza A (H1N1) virus was suspected as the cause because it was circulating in the city at that time. A test for pandemic H1N1 by real-time reverse transcription--polymerase chain reaction (rRT-PCR) was positive. During the subsequent 3 weeks, as the ship continued its cruise, 77 additional crew members developed confirmed pandemic H1N1 influenza. The U.S. Naval Medical Research Center Detachment (NMRCD), in collaboration with the Peruvian Navy, conducted an investigation to describe the outbreak and determine the attack rate for pandemic H1N1 influenza on the ship. This report summarizes the results of that investigation, which indicated that, of the 85 patients with FARI, 78 (92%) tested positive for pandemic H1N1 by rRT-PCR. The attack rate for confirmed pandemic H1N1 influenza was 22.0%. The most frequent symptoms, other than fever, were cough, headache, nasal congestion, and malaise. No complications or deaths occurred. Patients were treated according to World Health Organization (WHO) influenza treatment guidelines; six patients received antiviral medication because of preexisting comorbidities. A shipboard respiratory surveillance program, which had been implemented aboard the ship before its departure from Peru, permitted the early detection of the outbreak. Subsequent implementation of control measures might have slowed the outbreak. Laboratory disease surveillance and adequate outbreak control procedures might reduce transmission of pandemic H1N1 influenza aboard ships.

  4. Design and Characterization of a Computationally Optimized Broadly Reactive Hemagglutinin Vaccine for H1N1 Influenza Viruses

    PubMed Central

    Carter, Donald M.; Darby, Christopher A.; Lefoley, Bradford C.; Crevar, Corey J.; Alefantis, Timothy; Oomen, Raymond; Anderson, Stephen F.; Strugnell, Tod; Cortés-Garcia, Guadalupe; Vogel, Thorsten U.; Parrington, Mark; Kleanthous, Harold

    2016-01-01

    ABSTRACT One of the challenges of developing influenza A vaccines is the diversity of antigenically distinct isolates. Previously, a novel hemagglutinin (HA) for H5N1 influenza was derived from a methodology termed computationally optimized broadly reactive antigen (COBRA). This COBRA HA elicited a broad antibody response against H5N1 isolates from different clades. We now report the development and characterization of a COBRA-based vaccine for both seasonal and pandemic H1N1 influenza virus isolates. Nine prototype H1N1 COBRA HA proteins were developed and tested in mice using a virus-like particle (VLP) format for the elicitation of broadly reactive, functional antibody responses and protection against viral challenge. These candidates were designed to recognize H1N1 viruses isolated within the last 30 years. In addition, several COBRA candidates were designed based on sequences of H1N1 viruses spanning the past 100 years, including modern pandemic H1N1 isolates. Four of the 9 H1N1 COBRA HA proteins (X1, X3, X6, and P1) had the broadest hemagglutination inhibition (HAI) activity against a panel of 17 H1N1 viruses. These vaccines were used in cocktails or prime-boost combinations. The most effective regimens that both elicited the broadest HAI response and protected mice against a pandemic H1N1 challenge were vaccines that contained the P1 COBRA VLP and either the X3 or X6 COBRA VLP vaccine. These mice had little or no detectable viral replication, comparable to that observed with a matched licensed vaccine. This is the first report describing a COBRA-based HA vaccine strategy that elicits a universal, broadly reactive, protective response against seasonal and pandemic H1N1 isolates. IMPORTANCE Universal influenza vaccine approaches have the potential to be paradigm shifting for the influenza vaccine field, with the goal of replacing the current standard of care with broadly cross-protective vaccines. We have used COBRA technology to develop an HA head

  5. The survival of influenza A(H1N1)pdm09 virus on 4 household surfaces.

    PubMed

    Oxford, John; Berezin, Eitan N; Courvalin, Patrice; Dwyer, Dominic E; Exner, Martin; Jana, Laura A; Kaku, Mitsuo; Lee, Christopher; Letlape, Kgosi; Low, Donald E; Madani, Tariq Ahmed; Rubino, Joseph R; Saini, Narendra; Schoub, Barry D; Signorelli, Carlo; Tierno, Philip M; Zhong, Xuhui

    2014-04-01

    We investigated the survival of a pandemic strain of influenza A H1N1 on a variety of common household surfaces where multiple samples were taken from 4 types of common household fomite at 7 time points. Results showed that influenza A H1N1sw virus particles remained infectious for 48 hours on a wooden surface, for 24 hours on stainless steel and plastic surfaces, and for 8 hours on a cloth surface, although virus recovery from the cloth may have been suboptimal. Our results suggest that pandemic influenza A H1N1 can survive on common household fomites for extended periods of time, and that good hand hygiene and regular disinfection of commonly touched surfaces should be practiced during the influenza season to help reduce transmission.

  6. The survival of influenza A(H1N1)pdm09 virus on 4 household surfaces.

    PubMed

    Oxford, John; Berezin, Eitan N; Courvalin, Patrice; Dwyer, Dominic E; Exner, Martin; Jana, Laura A; Kaku, Mitsuo; Lee, Christopher; Letlape, Kgosi; Low, Donald E; Madani, Tariq Ahmed; Rubino, Joseph R; Saini, Narendra; Schoub, Barry D; Signorelli, Carlo; Tierno, Philip M; Zhong, Xuhui

    2014-04-01

    We investigated the survival of a pandemic strain of influenza A H1N1 on a variety of common household surfaces where multiple samples were taken from 4 types of common household fomite at 7 time points. Results showed that influenza A H1N1sw virus particles remained infectious for 48 hours on a wooden surface, for 24 hours on stainless steel and plastic surfaces, and for 8 hours on a cloth surface, although virus recovery from the cloth may have been suboptimal. Our results suggest that pandemic influenza A H1N1 can survive on common household fomites for extended periods of time, and that good hand hygiene and regular disinfection of commonly touched surfaces should be practiced during the influenza season to help reduce transmission. PMID:24679569

  7. Multiple Reassortment Events in the Evolutionary History of H1N1 Influenza A Virus Since 1918

    PubMed Central

    Nelson, Martha I.; Viboud, Cécile; Simonsen, Lone; Bennett, Ryan T.; Griesemer, Sara B.; St. George, Kirsten; Taylor, Jill; Spiro, David J.; Sengamalay, Naomi A.; Ghedin, Elodie; Taubenberger, Jeffery K.; Holmes, Edward C.

    2008-01-01

    The H1N1 subtype of influenza A virus has caused substantial morbidity and mortality in humans, first documented in the global pandemic of 1918 and continuing to the present day. Despite this disease burden, the evolutionary history of the A/H1N1 virus is not well understood, particularly whether there is a virological basis for several notable epidemics of unusual severity in the 1940s and 1950s. Using a data set of 71 representative complete genome sequences sampled between 1918 and 2006, we show that segmental reassortment has played an important role in the genomic evolution of A/H1N1 since 1918. Specifically, we demonstrate that an A/H1N1 isolate from the 1947 epidemic acquired novel PB2 and HA genes through intra-subtype reassortment, which may explain the abrupt antigenic evolution of this virus. Similarly, the 1951 influenza epidemic may also have been associated with reassortant A/H1N1 viruses. Intra-subtype reassortment therefore appears to be a more important process in the evolution and epidemiology of H1N1 influenza A virus than previously realized. PMID:18463694

  8. Cytophagic histiocytic panniculitis after H1N1 vaccination: a case report and review of the cutaneous side effects of influenza vaccines.

    PubMed

    Pauwels, C; Livideanu, C Bulai; Maza, A; Lamant, L; Paul, C

    2011-01-01

    Cytophagic histiocytic panniculitis (CHP) is a rare disease mostly caused by viral infections and/or lymphoproliferative diseases. We describe a case of CHP associated with H1N1 vaccine during the winter 2009-2010 vaccination campaign and discuss the cutaneous side effects of influenza vaccines. A 6-year-old child presented with inflammatory subcutaneous nodules, which had appeared 1 month after the first injection of H1N1 vaccine and 1 week after the second injection. There was no history of recent infection. The skin lesions spontaneously disappeared without scarring. In CHP the abnormal cytokine secretion from neoplastic or reactive T cells promotes monocyte-macrophage activation and haemophagocytosis. Vaccination is not a common cause of CHP, but it seems possible that, as in infectious diseases, reactive T cells to the vaccine antigen could trigger CHP.

  9. Reassortment ability of the 2009 pandemic H1N1 influenza virus with circulating human and avian influenza viruses: public health risk implications.

    PubMed

    Stincarelli, Maria; Arvia, Rosaria; De Marco, Maria Alessandra; Clausi, Valeria; Corcioli, Fabiana; Cotti, Claudia; Delogu, Mauro; Donatelli, Isabella; Azzi, Alberta; Giannecchini, Simone

    2013-08-01

    Exploring the reassortment ability of the 2009 pandemic H1N1 (A/H1N1pdm09) influenza virus with other circulating human or avian influenza viruses is the main concern related to the generation of more virulent or new variants having implications for public health. After different coinfection experiments in human A549 cells, by using the A/H1N1pdm09 virus plus one of human seasonal influenza viruses of H1N1 and H3N2 subtype or one of H11, H10, H9, H7 and H1 avian influenza viruses, several reassortant viruses were obtained. Among these, the HA of H1N1 was the main segment of human seasonal influenza virus reassorted in the A/H1N1pdm09 virus backbone. Conversely, HA and each of the three polymerase segments, alone or in combination, of the avian influenza viruses mainly reassorted in the A/H1N1pdm09 virus backbone. Of note, A/H1N1pdm09 viruses that reassorted with HA of H1N1 seasonal human or H11N6 avian viruses or carried different combination of avian origin polymerase segments, exerted a higher replication effectiveness than that of the parental viruses. These results confirm that reassortment of the A/H1N1pdm09 with circulating low pathogenic avian influenza viruses should not be misjudged in the prediction of the next pandemic.

  10. Agglutination of human O erythrocytes by influenza A(H1N1) viruses freshly isolated from patients.

    PubMed

    Murakami, T; Haruki, K; Seto, Y; Kimura, T; Minoshiro, S; Shibe, K

    1991-04-01

    The hemagglutinin titers of 10 influenza A (H1N1) viruses were examined using the erythrocytes of several species. Human O erythrocytes showed the highest agglutination titer to the viruses, whereas chicken erythrocytes showed a low titer. These findings were noted for at least 10 passages by serial dilutions of the viruses in Madin-Darby canine kidney (MDCK) cells. All influenza A(H1N1) viruses, plaque-cloned directly from throat-washing specimens of patients, also agglutinated human O but not chicken erythrocytes. The results of a hemadsorption test indicated that chicken erythrocytes possess less affinity to MDCK cells infected with the A/Osaka City/2/88(H1N1) stain than to those infected with the A/Yamagata/120/86(H1N1) strain which is used as an inactivated influenza vaccine in Japan. However, there were no significant differences between the A/Osaka City/2/88 and the A/Yamagata/120/86 strains in the hemagglutination inhibition test. Since human O erythrocytes have high agglutination activity to influenza A(H1N1) and also to A(H3N2) and B viruses in MDCK cells, these erythrocytes may be useful for the serological diagnosis of influenza. PMID:2066386

  11. Agglutination of human O erythrocytes by influenza A(H1N1) viruses freshly isolated from patients.

    PubMed

    Murakami, T; Haruki, K; Seto, Y; Kimura, T; Minoshiro, S; Shibe, K

    1991-04-01

    The hemagglutinin titers of 10 influenza A (H1N1) viruses were examined using the erythrocytes of several species. Human O erythrocytes showed the highest agglutination titer to the viruses, whereas chicken erythrocytes showed a low titer. These findings were noted for at least 10 passages by serial dilutions of the viruses in Madin-Darby canine kidney (MDCK) cells. All influenza A(H1N1) viruses, plaque-cloned directly from throat-washing specimens of patients, also agglutinated human O but not chicken erythrocytes. The results of a hemadsorption test indicated that chicken erythrocytes possess less affinity to MDCK cells infected with the A/Osaka City/2/88(H1N1) stain than to those infected with the A/Yamagata/120/86(H1N1) strain which is used as an inactivated influenza vaccine in Japan. However, there were no significant differences between the A/Osaka City/2/88 and the A/Yamagata/120/86 strains in the hemagglutination inhibition test. Since human O erythrocytes have high agglutination activity to influenza A(H1N1) and also to A(H3N2) and B viruses in MDCK cells, these erythrocytes may be useful for the serological diagnosis of influenza.

  12. Outbreak of Influenza A(H1N1) in a Kidney Transplant Unit-Protective Effect of Vaccination.

    PubMed

    Helanterä, I; Anttila, V-J; Lappalainen, M; Lempinen, M; Isoniemi, H

    2015-09-01

    Seasonal influenza vaccination is recommended for patients with end-stage renal disease (ESRD), despite suggested inferior efficacy among these patients. We characterize an outbreak of influenza A(H1N1) in a kidney transplant unit. Altogether 23 patients were treated on the ward for postoperative care after kidney transplantation during the outbreak. After the first positive case, all patients were tested with nasopharyngeal swab tests and 7 patients were diagnosed with influenza A(H1N1). Altogether 17/23 patients had received adequate seasonal influenza vaccination, of whom 2/17 tested positive for influenza (one asymptomatic, one with mild cough). Five of six unvaccinated patients were diagnosed with influenza A(H1N1); 3/5 suffered from severe respiratory failure and were treated with ventilator support in the ICU, but all died due to acute respiratory distress syndrome, whereas 2/5 suffered from mild viral pneumonitis and recovered fully. The risk of influenza infection and mortality was significantly increased in unvaccinated patients (odds ratio 37.5 [95% CI 2.7-507.5, p = 0.01] and 6.7 [95% CI 2.3-18.9, p = 0.003], respectively). Influenza A(H1N1) had a high mortality in our cohort of nonvaccinated immunosuppressed patients early after kidney transplantation. None of the vaccinated patients developed serious disease, supporting the role of vaccination also for ESRD patients.

  13. Determination of current reference viruses for serological study of swine influenza viruses after the introduction of pandemic 2009 H1N1 (pdmH1N1) in Thailand.

    PubMed

    Arunorat, Jirapat; Charoenvisal, Nataya; Woonwong, Yonlayong; Kedkovid, Roongtham; Thanawongnuwech, Roongroje

    2016-10-01

    Since the introduction of pandemic H1N1 2009 virus (pdmH1N1) in pigs, the status of Thai swine influenza virus (SIV) has changed. The pdmH1N1 and its reassortant viruses have become the predominant strain circulating in the Thai swine population based on the surveillance data from 2012 to 2014. For this reason, the reference viruses for serological assays using the hemagglutination inhibition (HI) test needed to be updated. Six anti-sera against reference viruses from 2006 to 2009 (enH1N1-06, enH1N1-09, enH1N2-09, pdmH1N1-09, enH3N2-07 and enH3N2-09) were used for the HI test with four contemporary viruses (enH1N1-10, pdmH1N1-10, rH1N2 and rH3N2) and the selected reference viruses were tested with sera collected from the field to determine the current SIV status. The results showed that anti-sera of swH1N1-06 had the highest titers against enH1N1-10. Anti-sera of pdmH1N1-09 had the highest titers against pdmH1N1-10 and rH1N2, whereas, anti-sera of enH3N2-09 had the highest titers against rH3N2. The results demonstrated that enH1N1-06, pdmH1N1-09 and enH3N2-09 should be selected as reference viruses for contemporary serological studies and HI tests. The seroprevalence results from 410 samples revealed enH1N1 (37.79%), pdmH1N1 (37.32%) and H3N2 (35.86%), respectively. The present study indicated that pdmH1N1 was widespread and commonly found in the Thai pig population increasing the risk of novel reassortant viruses and should be added as a reference virus for HI test. SIV surveillance program and serological studies should be conducted for the benefits of SIV control and prevention as well as monitoring for zoonotic potential. PMID:27355862

  14. Identification of Amino Acid Substitutions Supporting Antigenic Change of Influenza A(H1N1)pdm09 Viruses

    PubMed Central

    Koel, Björn F.; Mögling, Ramona; Chutinimitkul, Salin; Fraaij, Pieter L.; Burke, David F.; van der Vliet, Stefan; de Wit, Emmie; Bestebroer, Theo M.; Rimmelzwaan, Guus F.; Osterhaus, Albert D. M. E.; Smith, Derek J.; Fouchier, Ron A. M.

    2015-01-01

    ABSTRACT The majority of currently circulating influenza A(H1N1) viruses are antigenically similar to the virus that caused the 2009 influenza pandemic. However, antigenic variants are expected to emerge as population immunity increases. Amino acid substitutions in the hemagglutinin protein can result in escape from neutralizing antibodies, affect viral fitness, and change receptor preference. In this study, we constructed mutants with substitutions in the hemagglutinin of A/Netherlands/602/09 in an attenuated backbone to explore amino acid changes that may contribute to emergence of antigenic variants in the human population. Our analysis revealed that single substitutions affecting the loop that consists of amino acid positions 151 to 159 located adjacent to the receptor binding site caused escape from ferret and human antibodies elicited after primary A(H1N1)pdm09 virus infection. The majority of these substitutions resulted in similar or increased replication efficiency in vitro compared to that of the virus carrying the wild-type hemagglutinin and did not result in a change of receptor preference. However, none of the substitutions was sufficient for escape from the antibodies in sera from individuals that experienced both seasonal and pandemic A(H1N1) virus infections. These results suggest that antibodies directed against epitopes on seasonal A(H1N1) viruses contribute to neutralization of A(H1N1)pdm09 antigenic variants, thereby limiting the number of possible substitutions that could lead to escape from population immunity. IMPORTANCE Influenza A viruses can cause significant morbidity and mortality in humans. Amino acid substitutions in the hemagglutinin protein can result in escape from antibody-mediated neutralization. This allows the virus to reinfect individuals that have acquired immunity to previously circulating strains through infection or vaccination. To date, the vast majority of A(H1N1)pdm09 strains remain antigenically similar to the virus

  15. Infant Respiratory Outcomes Associated with Prenatal Exposure to Maternal 2009 A/H1N1 Influenza Vaccination

    PubMed Central

    Fell, Deshayne B.; Wilson, Kumanan; Ducharme, Robin; Hawken, Steven; Sprague, Ann E.; Kwong, Jeffrey C.; Smith, Graeme; Wen, Shi Wu; Walker, Mark C.

    2016-01-01

    Background Infants are at high risk for influenza illness, but are ineligible for vaccination before 6 months. Transfer of maternal antibodies to the fetus has been demonstrated for 2009 A/H1N1 pandemic vaccines; however, clinical effectiveness is unknown. Our objective was to evaluate the association between 2009 A/H1N1 pandemic vaccination during pregnancy and rates of infant influenza and pneumonia. Methods We linked a population-based birth cohort to administrative databases to measure rates of influenza and pneumonia diagnosed during ambulatory physician visits, hospitalizations and emergency department visits during one year of follow-up. We estimated incidence rate ratios and 95% confidence intervals (95% CI) using Poisson regression, comparing infants born to A/H1N1-vaccinated women (vaccine-exposed infants) with unexposed infants, adjusted for confounding using high-dimensional propensity scores. Results Among 117,335 infants in the study, 36,033 (31%) were born to A/H1N1-vaccinated women. Crude rates of influenza during the pandemic (per 100,000 infant-days) for vaccine-exposed and unexposed infants were similar (2.19, 95% CI: 1.27–3.76 and 3.60, 95% CI: 2.51–5.14, respectively), as were crude rates of influenza and pneumonia combined. We did not observe any significant differences in rates of study outcomes between study groups during the second wave of the 2009 A/H1N1 pandemic, nor during any post-pandemic time period. Conclusion We observed no difference in rates of study outcomes among infants born to A/H1N1-vaccinated mothers relative to unexposed infants born during the second A/H1N1 pandemic wave; however, due to late availability of the pandemic vaccine, the available follow-up time during the pandemic time period was very limited. PMID:27486858

  16. Sequential Infection in Ferrets with Antigenically Distinct Seasonal H1N1 Influenza Viruses Boosts Hemagglutinin Stalk-Specific Antibodies

    PubMed Central

    Kirchenbaum, Greg A.; Carter, Donald M.

    2015-01-01

    ABSTRACT Broadly reactive antibodies targeting the conserved hemagglutinin (HA) stalk region are elicited following sequential infection or vaccination with influenza viruses belonging to divergent subtypes and/or expressing antigenically distinct HA globular head domains. Here, we demonstrate, through the use of novel chimeric HA proteins and competitive binding assays, that sequential infection of ferrets with antigenically distinct seasonal H1N1 (sH1N1) influenza virus isolates induced an HA stalk-specific antibody response. Additionally, stalk-specific antibody titers were boosted following sequential infection with antigenically distinct sH1N1 isolates in spite of preexisting, cross-reactive, HA-specific antibody titers. Despite a decline in stalk-specific serum antibody titers, sequential sH1N1 influenza virus-infected ferrets were protected from challenge with a novel H1N1 influenza virus (A/California/07/2009), and these ferrets poorly transmitted the virus to naive contacts. Collectively, these findings indicate that HA stalk-specific antibodies are commonly elicited in ferrets following sequential infection with antigenically distinct sH1N1 influenza virus isolates lacking HA receptor-binding site cross-reactivity and can protect ferrets against a pathogenic novel H1N1 virus. IMPORTANCE The influenza virus hemagglutinin (HA) is a major target of the humoral immune response following infection and/or seasonal vaccination. While antibodies targeting the receptor-binding pocket of HA possess strong neutralization capacities, these antibodies are largely strain specific and do not confer protection against antigenic drift variant or novel HA subtype-expressing viruses. In contrast, antibodies targeting the conserved stalk region of HA exhibit broader reactivity among viruses within and among influenza virus subtypes. Here, we show that sequential infection of ferrets with antigenically distinct seasonal H1N1 influenza viruses boosts the antibody responses

  17. Pandemic Potential of a Strain of Influenza A (H1N1): Early Findings

    PubMed Central

    Fraser, Christophe; Donnelly, Christl A.; Cauchemez, Simon; Hanage, William P.; Van Kerkhove, Maria D.; Hollingsworth, T. Déirdre; Griffin, Jamie; Baggaley, Rebecca F.; Jenkins, Helen E.; Lyons, Emily J.; Jombart, Thibaut; Hinsley, Wes R.; Grassly, Nicholas C.; Balloux, Francois; Ghani, Azra C.; Ferguson, Neil M.; Rambaut, Andrew; Pybus, Oliver G.; Lopez-Gatell, Hugo; Alpuche-Aranda, Celia M.; Chapela, Ietza Bojorquez; Zavala, Ethel Palacios; Guevara, Dulce Ma. Espejo; Checchi, Francesco; Garcia, Erika; Hugonnet, Stephane; Roth, Cathy

    2013-01-01

    A novel influenza A (H1N1) virus has spread rapidly across the globe. Judging its pandemic potential is difficult with limited data, but nevertheless essential to inform appropriate health responses. By analyzing the outbreak in Mexico, early data on international spread, and viral genetic diversity, we make an early assessment of transmissibility and severity. Our estimates suggest that 23,000 (range 6000 to 32,000) individuals had been infected in Mexico by late April, giving an estimated case fatality ratio (CFR) of 0.4% (range: 0.3 to 1.8%) based on confirmed and suspected deaths reported to that time. In a community outbreak in the small community of La Gloria, Veracruz, no deaths were attributed to infection, giving an upper 95% bound on CFR of 0.6%. Thus, although substantial uncertainty remains, clinical severity appears less than that seen in the 1918 influenza pandemic but comparable with that seen in the 1957 pandemic. Clinical attack rates in children in La Gloria were twice that in adults (<15 years of age: 61%; ≥15 years: 29%). Three different epidemiological analyses gave basic reproduction number (R0) estimates in the range of 1.4 to 1.6, whereas a genetic analysis gave a central estimate of 1.2. This range of values is consistent with 14 to 73 generations of human-to-human transmission having occurred in Mexico to late April. Transmissibility is therefore substantially higher than that of seasonal flu, and comparable with lower estimates of R0 obtained from previous influenza pandemics. PMID:19433588

  18. Inactivated Seasonal Influenza Vaccines Increase Serum Antibodies to the Neuraminidase of Pandemic Influenza A(H1N1) 2009 Virus in an Age-Dependent Manner

    PubMed Central

    Marcelin, Glendie; Bland, Hilliary M.; Negovetich, Nicholas J.; Sandbulte, Matthew R.; Ellebedy, Ali H.; Webb, Ashley D.; Griffin, Yolanda S.; DeBeauchamp, Jennifer L.; McElhaney, Janet E.; Webby, Richard J.

    2010-01-01

    Levels of preexisting antibodies to the hemagglutinin of pandemic influenza A(H1N1) 2009 (hereafter pandemic H1N1) virus positively correlate with age. The impact of contemporary seasonal influenza vaccines on establishing immunity to other pandemic H1N1 proteins is unknown. We measured serum antibodies to the neuraminidase (NA) of pandemic H1N1 in adults prior to and after vaccination with seasonal trivalent inactivated influenza vaccines. Serum antibodies to pandemic H1N1 NA were observed in all age groups; however, vaccination elevated levels of pandemic H1N1 NA antibodies predominately in elderly individuals (age,⩾60 years). Therefore, contemporary seasonal vaccines likely contribute to reduction of pandemic H1N1-associated disease in older individuals. PMID:20979454

  19. Racial Disparities in Exposure, Susceptibility, and Access to Health Care in the US H1N1 Influenza Pandemic

    PubMed Central

    Kumar, Supriya; Freimuth, Vicki S.; Musa, Donald; Casteneda-Angarita, Nestor; Kidwell, Kelley

    2011-01-01

    Objectives. We conducted the first empirical examination of disparities in H1N1 exposure, susceptibility to H1N1 complications, and access to health care during the H1N1 influenza pandemic. Methods. We conducted a nationally representative survey among a sample drawn from more than 60 000 US households. We analyzed responses from 1479 adults, including significant numbers of Blacks and Hispanics. The survey asked respondents about their ability to impose social distance in response to public health recommendations, their chronic health conditions, and their access to health care. Results. Risk of exposure to H1N1 was significantly related to race and ethnicity. Spanish-speaking Hispanics were at greatest risk of exposure but were less susceptible to complications from H1N1. Disparities in access to health care remained significant for Spanish-speaking Hispanics after controlling for other demographic factors. We used measures based on prevalence of chronic conditions to determine that Blacks were the most susceptible to complications from H1N1. Conclusions. We found significant race/ethnicity-related disparities in potential risk from H1N1 flu. Disparities in the risks of exposure, susceptibility (particularly to severe disease), and access to health care may interact to exacerbate existing health inequalities and contribute to increased morbidity and mortality in these populations. PMID:21164098

  20. Coinfection with influenza A(H1N1)pdm09 and dengue virus in fatal cases

    PubMed Central

    Perdigão, Anne Carolinne Bezerra; Ramalho, Izabel Letícia Cavalcante; Guedes, Maria Izabel Florindo; Braga, Deborah Nunes Melo; Cavalcanti, Luciano Pamplona Góes; de Melo, Maria Elisabeth Lisboa; Araújo, Rafael Montenegro de Carvalho; Lima, Elza Gadelha; da Silva, Luciene Alexandre Bié; Araújo, Lia de Carvalho; Araújo, Fernanda Montenegro de Carvalho

    2016-01-01

    Abstract We report on four patients with fatal influenza A(H1N1)pdm09 and dengue virus coinfections. Clinical, necropsy and histopathologic findings presented in all cases were characteristic of influenza-dengue coinfections, and all were laboratory-confirmed for both infections. The possibility of influenza and dengue coinfection should be considered in locations where these two viruses’ epidemic periods coincide to avoid fatal outcomes. Dengue is a mosquito-borne viral infection caused by one of the four dengue viruses (DENV-1 to 4). Each of these viruses is capable of causing nonspecific febrile illnesses, classic dengue fever and dengue haemorrhagic fever (Gubler 1998). As a result, dengue is often difficult to diagnose clinically, especially because peak dengue season often coincides with that of other common febrile illnesses in tropical regions (Chacon et al. 2015). In April 2009, a new virus, influenza A/H1N1/pandemic (FluA/H1N1/09pdm), caused a severe outbreak in Mexico. The virus quickly spread throughout the world, and in June 2009, the World Health Organization declared a pandemic (WHO 2010). In Brazil, the first laboratory confirmed case of FluA/H1N1/09pdm was in July 2009 (Pires Neto et al. 2013). The state of Ceará, in Northeast Brazil, is a dengue endemic area. In this state, the virus influenza A(H1N1)pdm09 has circulated since 2009, and through the first half of 2012, 11 deaths caused by the virus were confirmed (Pires Neto et al. 2013). The influenza and dengue seasons in Ceará overlap, which led to diagnostic difficulties. We report four cases of laboratory-confirmed coinfection of deadly influenza A(H1N1)pdm09 with DENV, which occurred during the dengue and influenza season in 2012 and 2013 in Ceará. PMID:27598244

  1. Coinfection with influenza A(H1N1)pdm09 and dengue virus in fatal cases.

    PubMed

    Perdigão, Anne Carolinne Bezerra; Ramalho, Izabel Letícia Cavalcante; Guedes, Maria Izabel Florindo; Braga, Deborah Nunes Melo; Cavalcanti, Luciano Pamplona Góes; Melo, Maria Elisabeth Lisboa de; Araújo, Rafael Montenegro de Carvalho; Lima, Elza Gadelha; Silva, Luciene Alexandre Bié da; Araújo, Lia de Carvalho; Araújo, Fernanda Montenegro de Carvalho

    2016-09-01

    We report on four patients with fatal influenza A(H1N1)pdm09 and dengue virus coinfections. Clinical, necropsy and histopathologic findings presented in all cases were characteristic of influenza-dengue coinfections, and all were laboratory-confirmed for both infections. The possibility of influenza and dengue coinfection should be considered in locations where these two viruses' epidemic periods coincide to avoid fatal outcomes. Dengue is a mosquito-borne viral infection caused by one of the four dengue viruses (DENV-1 to 4). Each of these viruses is capable of causing nonspecific febrile illnesses, classic dengue fever and dengue haemorrhagic fever (Gubler 1998). As a result, dengue is often difficult to diagnose clinically, especially because peak dengue season often coincides with that of other common febrile illnesses in tropical regions (Chacon et al. 2015). In April 2009, a new virus, influenza A/H1N1/pandemic (FluA/H1N1/09pdm), caused a severe outbreak in Mexico. The virus quickly spread throughout the world, and in June 2009, the World Health Organization declared a pandemic (WHO 2010). In Brazil, the first laboratory confirmed case of FluA/H1N1/09pdm was in July 2009 (Pires Neto et al. 2013). The state of Ceará, in Northeast Brazil, is a dengue endemic area. In this state, the virus influenza A(H1N1)pdm09 has circulated since 2009, and through the first half of 2012, 11 deaths caused by the virus were confirmed (Pires Neto et al. 2013). The influenza and dengue seasons in Ceará overlap, which led to diagnostic difficulties. We report four cases of laboratory-confirmed coinfection of deadly influenza A(H1N1)pdm09 with DENV, which occurred during the dengue and influenza season in 2012 and 2013 in Ceará.

  2. Coinfection with influenza A(H1N1)pdm09 and dengue virus in fatal cases.

    PubMed

    Perdigão, Anne Carolinne Bezerra; Ramalho, Izabel Letícia Cavalcante; Guedes, Maria Izabel Florindo; Braga, Deborah Nunes Melo; Cavalcanti, Luciano Pamplona Góes; Melo, Maria Elisabeth Lisboa de; Araújo, Rafael Montenegro de Carvalho; Lima, Elza Gadelha; Silva, Luciene Alexandre Bié da; Araújo, Lia de Carvalho; Araújo, Fernanda Montenegro de Carvalho

    2016-09-01

    We report on four patients with fatal influenza A(H1N1)pdm09 and dengue virus coinfections. Clinical, necropsy and histopathologic findings presented in all cases were characteristic of influenza-dengue coinfections, and all were laboratory-confirmed for both infections. The possibility of influenza and dengue coinfection should be considered in locations where these two viruses' epidemic periods coincide to avoid fatal outcomes. Dengue is a mosquito-borne viral infection caused by one of the four dengue viruses (DENV-1 to 4). Each of these viruses is capable of causing nonspecific febrile illnesses, classic dengue fever and dengue haemorrhagic fever (Gubler 1998). As a result, dengue is often difficult to diagnose clinically, especially because peak dengue season often coincides with that of other common febrile illnesses in tropical regions (Chacon et al. 2015). In April 2009, a new virus, influenza A/H1N1/pandemic (FluA/H1N1/09pdm), caused a severe outbreak in Mexico. The virus quickly spread throughout the world, and in June 2009, the World Health Organization declared a pandemic (WHO 2010). In Brazil, the first laboratory confirmed case of FluA/H1N1/09pdm was in July 2009 (Pires Neto et al. 2013). The state of Ceará, in Northeast Brazil, is a dengue endemic area. In this state, the virus influenza A(H1N1)pdm09 has circulated since 2009, and through the first half of 2012, 11 deaths caused by the virus were confirmed (Pires Neto et al. 2013). The influenza and dengue seasons in Ceará overlap, which led to diagnostic difficulties. We report four cases of laboratory-confirmed coinfection of deadly influenza A(H1N1)pdm09 with DENV, which occurred during the dengue and influenza season in 2012 and 2013 in Ceará. PMID:27598244

  3. Antiviral therapy in seasonal influenza and 2009 H1N1 pandemic influenza: Korean experiences and perspectives.

    PubMed

    Song, Joon Young; Noh, Ji Yun; Choi, Won Suk; Cheong, Hee Jin; Kim, Woo Joo

    2015-01-01

    Influenza is a major cause of substantial morbidity and mortality in humans every year. Vaccination is the main strategy to prevent influenza infection, but antiviral agents also play an important role in the control of both seasonal and pandemic influenza. During the influenza A/H1N1 pandemic in 2009, early prompt antiviral therapy may have reduced the severity of the influenza outcomes including pneumonia, hospitalization and mortality in the Republic of Korea. Since the 2009 H1N1 pandemic, there have been increasing usages of antiviral agents for the treatment of patients with seasonal influenza. Although currently rare, antiviral resistance among influenza viruses may emerge and increase with increased use of neuraminidase inhibitors. New agents with different modes of action are under investigation, including favipiravir, DAS181, nitazoxanide and broad-spectrum neutralizing monoclonal antibodies. Data are limited with respect to high-dose and combination antiviral therapies. So, clinical trials are warranted to evaluate diverse antiviral combinations that may be synergistic and less likely to induce breakthrough resistance.

  4. Contemporary Seasonal Influenza A (H1N1) Virus Infection Primes for a More Robust Response To Split Inactivated Pandemic Influenza A (H1N1) Virus Vaccination in Ferrets ▿

    PubMed Central

    Ellebedy, Ali H.; Fabrizio, Thomas P.; Kayali, Ghazi; Oguin, Thomas H.; Brown, Scott A.; Rehg, Jerold; Thomas, Paul G.; Webby, Richard J.

    2010-01-01

    Human influenza pandemics occur when influenza viruses to which the population has little or no immunity emerge and acquire the ability to achieve human-to-human transmission. In April 2009, cases of a novel H1N1 influenza virus in children in the southwestern United States were reported. It was retrospectively shown that these cases represented the spread of this virus from an ongoing outbreak in Mexico. The emergence of the pandemic led to a number of national vaccination programs. Surprisingly, early human clinical trial data have shown that a single dose of nonadjuvanted pandemic influenza A (H1N1) 2009 monovalent inactivated vaccine (pMIV) has led to a seroprotective response in a majority of individuals, despite earlier studies showing a lack of cross-reactivity between seasonal and pandemic H1N1 viruses. Here we show that previous exposure to a contemporary seasonal H1N1 influenza virus and to a lesser degree a seasonal influenza virus trivalent inactivated vaccine is able to prime for a higher antibody response after a subsequent dose of pMIV in ferrets. The more protective response was partially dependent on the presence of CD8+ cells. Two doses of pMIV were also able to induce a detectable antibody response that provided protection from subsequent challenge. These data show that previous infection with seasonal H1N1 influenza viruses likely explains the requirement for only a single dose of pMIV in adults and that vaccination campaigns with the current pandemic influenza vaccines should reduce viral burden and disease severity in humans. PMID:20962210

  5. Identification of Suitable Natural Inhibitor against Influenza A (H1N1) Neuraminidase Protein by Molecular Docking

    PubMed Central

    Sahoo, Maheswata; Jena, Lingaraja; Rath, Surya Narayan

    2016-01-01

    The influenza A (H1N1) virus, also known as swine flu is a leading cause of morbidity and mortality since 2009. There is a need to explore novel anti-viral drugs for overcoming the epidemics. Traditionally, different plant extracts of garlic, ginger, kalmegh, ajwain, green tea, turmeric, menthe, tulsi, etc. have been used as hopeful source of prevention and treatment of human influenza. The H1N1 virus contains an important glycoprotein, known as neuraminidase (NA) that is mainly responsible for initiation of viral infection and is essential for the life cycle of H1N1. It is responsible for sialic acid cleavage from glycans of the infected cell. We employed amino acid sequence of H1N1 NA to predict the tertiary structure using Phyre2 server and validated using ProCheck, ProSA, ProQ, and ERRAT server. Further, the modelled structure was docked with thirteen natural compounds of plant origin using AutoDock4.2. Most of the natural compounds showed effective inhibitory activity against H1N1 NA in binding condition. This study also highlights interaction of these natural inhibitors with amino residues of NA protein. Furthermore, among 13 natural compounds, theaflavin, found in green tea, was observed to inhibit H1N1 NA proteins strongly supported by lowest docking energy. Hence, it may be of interest to consider theaflavin for further in vitro and in vivo evaluation. PMID:27729839

  6. "Trivalent influenza vaccination of healthy adults 3 years after the onset of swine-origin H1N1 pandemic: restricted immunogenicity of the new A/H1N1v constituent?".

    PubMed

    Allwinn, R; Bickel, M; Lassmann, C; Wicker, S; Friedrichs, I

    2013-04-01

    Influenza vaccination is advised annually to reduce the burden of influenza disease. For sufficient vaccine campaigns also a continuous adoption of influenza vaccines are necessary, due to particularly high genetic variability of influenza A virus. Therefore, we evaluate the effectiveness of the trivalent influenza vaccine 2010/2011, against influenza A (H1N1, H3N2) and influenza B. Immune response was investigated in paired sera from 92 healthcare workers with the hemagglutination inhibition assay (HI). Protective antibody levels (HI titer ≥40) were found after vaccination for influenza A/California/07/2009(H1N1): 84.71 % [GMT: 115.34]; for influenza A/Perth/16/2009(H3N2): 94.94 % [GMT: 268.47] and for influenza B/Brisbane/60/2008: 96.20 % [GMT: 176.83]; matching with the currently circulating virus strains. However, the highest seroprevalence rate was found against influenza B; pre- and post-vaccination titers as well, which may be due to comparatively high virus preservation. Remarkable, lowest seropositivity was seen against H1N1. Despite the significant titer rise, sufficient H1N1 herd immunity was still not achieved. It can be assumed that a high influenza A herd immunity may be a requirement for a successful booster vaccination.

  7. Infectious Progeny of 2009 A (H1N1) Influenza Virus Replicated in and Released from Human Neutrophils.

    PubMed

    Zhang, Zhang; Huang, Tao; Yu, Feiyuan; Liu, Xingmu; Zhao, Conghui; Chen, Xueling; Kelvin, David J; Gu, Jiang

    2015-01-01

    Various reports have indicated that a number of viruses could infect neutrophils, but the multiplication of viruses in neutrophils was abortive. Based on our previous finding that avian influenza viral RNA and proteins were present in the nucleus of infected human neutrophils in vivo, we investigated the possibility of 2009 A (H1N1) influenza viral synthesis in infected neutrophils and possible release of infectious progeny from host cells. In this study we found that human neutrophils in vitro without detectable level of sialic acid expression could be infected by this virus strain. We also show that the infected neutrophils can not only synthesize 2009 A (H1N1) viral mRNA and proteins, but also produce infectious progeny. These findings suggest that infectious progeny of 2009 A (H1N1) influenza virus could be replicated in and released from human neutrophils with possible clinical implications. PMID:26639836

  8. Infectious Progeny of 2009 A (H1N1) Influenza Virus Replicated in and Released from Human Neutrophils.

    PubMed

    Zhang, Zhang; Huang, Tao; Yu, Feiyuan; Liu, Xingmu; Zhao, Conghui; Chen, Xueling; Kelvin, David J; Gu, Jiang

    2015-12-07

    Various reports have indicated that a number of viruses could infect neutrophils, but the multiplication of viruses in neutrophils was abortive. Based on our previous finding that avian influenza viral RNA and proteins were present in the nucleus of infected human neutrophils in vivo, we investigated the possibility of 2009 A (H1N1) influenza viral synthesis in infected neutrophils and possible release of infectious progeny from host cells. In this study we found that human neutrophils in vitro without detectable level of sialic acid expression could be infected by this virus strain. We also show that the infected neutrophils can not only synthesize 2009 A (H1N1) viral mRNA and proteins, but also produce infectious progeny. These findings suggest that infectious progeny of 2009 A (H1N1) influenza virus could be replicated in and released from human neutrophils with possible clinical implications.

  9. Infectious Progeny of 2009 A (H1N1) Influenza Virus Replicated in and Released from Human Neutrophils

    PubMed Central

    Zhang, Zhang; Huang, Tao; Yu, Feiyuan; Liu, Xingmu; Zhao, Conghui; Chen, Xueling; Kelvin, David J.; Gu, Jiang

    2015-01-01

    Various reports have indicated that a number of viruses could infect neutrophils, but the multiplication of viruses in neutrophils was abortive. Based on our previous finding that avian influenza viral RNA and proteins were present in the nucleus of infected human neutrophils in vivo, we investigated the possibility of 2009 A (H1N1) influenza viral synthesis in infected neutrophils and possible release of infectious progeny from host cells. In this study we found that human neutrophils in vitro without detectable level of sialic acid expression could be infected by this virus strain. We also show that the infected neutrophils can not only synthesize 2009 A (H1N1) viral mRNA and proteins, but also produce infectious progeny. These findings suggest that infectious progeny of 2009 A (H1N1) influenza virus could be replicated in and released from human neutrophils with possible clinical implications. PMID:26639836

  10. Computational 3D structures of drug-targeting proteins in the 2009-H1N1 influenza A virus

    NASA Astrophysics Data System (ADS)

    Du, Qi-Shi; Wang, Shu-Qing; Huang, Ri-Bo; Chou, Kuo-Chen

    2010-01-01

    The neuraminidase (NA) and M2 proton channel of influenza virus are the drug-targeting proteins, based on which several drugs were developed. However these once powerful drugs encountered drug-resistant problem to the H5N1 and H1N1 flu. To address this problem, the computational 3D structures of NA and M2 proteins of 2009-H1N1 influenza virus were built using the molecular modeling technique and computational chemistry method. Based on the models the structure features of NA and M2 proteins were analyzed, the docking structures of drug-protein complexes were computed, and the residue mutations were annotated. The results may help to solve the drug-resistant problem and stimulate designing more effective drugs against 2009-H1N1 influenza pandemic.

  11. Pandemic H1N1 influenza A directly induces a robust and acute inflammatory gene signature in primary human bronchial epithelial cells downstream of membrane fusion

    SciTech Connect

    Paquette, Stéphane G.; Banner, David; Chi, Le Thi Bao; Leon, Alberto J.; Xu, Luoling; Ran, Longsi; Huang, Stephen S.H.; Farooqui, Amber; and others

    2014-01-05

    Pandemic H1N1 influenza A (H1N1pdm) elicits stronger pulmonary inflammation than previously circulating seasonal H1N1 influenza A (sH1N1), yet mechanisms of inflammatory activation in respiratory epithelial cells during H1N1pdm infection are unclear. We investigated host responses to H1N1pdm/sH1N1 infection and virus entry mechanisms in primary human bronchial epithelial cells in vitro. H1N1pdm infection rapidly initiated a robust inflammatory gene signature (3 h post-infection) not elicited by sH1N1 infection. Protein secretion inhibition had no effect on gene induction. Infection with membrane fusion deficient H1N1pdm failed to induce robust inflammatory gene expression which was rescued with restoration of fusion ability, suggesting H1N1pdm directly triggered the inflammatory signature downstream of membrane fusion. Investigation of intra-virion components revealed H1N1pdm viral RNA (vRNA) triggered a stronger inflammatory phenotype than sH1N1 vRNA. Thus, our study is first to report H1N1pdm induces greater inflammatory gene expression than sH1N1 in vitro due to direct virus–epithelial cell interaction. - Highlights: • We investigated H1N1pdm/sH1N1 infection in primary epithelial cells. • H1N1pdm directly initiated a robust inflammatory gene signature, sH1N1 did not. • H1N1pdm viral RNA triggered a stronger response than sH1N1. • H1N1pdm induces greater response due to direct virus–cell interaction. • These results have potential to impact vaccine and therapeutic development.

  12. Pediatric hospital admissions from influenza A (H1N1) in Brazil: effects of the 2010 vaccination campaign

    PubMed Central

    Marcos, Ana Carolina Cavalcanti; Pelissoni, Fernanda D'Angelo Monteiro; Cunegundes, Kelly Simone Almeida; Abramczyk, Marcelo Luiz; Bellei, Nancy Cristina Junqueira; Sanches, Nivea Aparecida Pissaia; de Moraes-Pinto, Maria Isabel

    2012-01-01

    In 2009, the influenza A (H1N1) virus spread rapidly around the world, causing the first pandemic of the 21st Century. In 2010, there was a vaccination campaign against this new virus subtype to reduce the morbidity and mortality of the disease in some countries, including Brazil. Herein, we describe the clinical and epidemiological characteristics of patients under 19 years of age who were hospitalized with confirmed influenza A (H1N1) infection in 2009 and 2010. We retrospectively reviewed files from the pediatric patients who were admitted to a university hospital with real-time polymerase chain reaction (RT-PCR) confirmed influenza A (H1N1) infection in 2009 and 2010. There were 37 hospitalized patients with influenza A (H1N1) in 2009 and 2 in 2010. In 2009, many of the hospitalized children had an underlying chronic disease and a lower median age than those not hospitalized. Of the hospitalized patients, 78% had a chronic disease, primarily pneumopathy (48%). The main signs and symptoms of influenza were fever (97%), cough (76%), and dyspnea (59%). Complications occurred in 81% of the patients. The median length of hospitalization was five days; 27% of the patients required intensive care, and two died. In 2010, two patients were hospitalized with influenza A (H1N1): one infant with adenovirus co-infection who had received one previous H1N1 vaccine dose and presented with respiratory sequelae and a 2-month-old infant who had a hospital-acquired infection. An impressive reduction in hospital admissions was observed in 2010 when the vaccination campaign took place in Brazil. PMID:23070350

  13. Antibodies against avian-like A (H1N1) swine influenza virus among swine farm residents in eastern China.

    PubMed

    Yin, Xiuchen; Yin, Xin; Rao, Baizhong; Xie, Chunfang; Zhang, Pengchao; Qi, Xian; Wei, Ping; Liu, Huili

    2014-04-01

    In 2007, the avian-like H1N1 virus (A/swine/Zhejiang/1/07) was first isolated in pigs in China. Recently, it was reported that a 3-year-old boy was infected with avian-like A (H1N1) swine influenza virus (SIV) in Jiangsu Province, China. To investigate the prevalence of avian-like A (H1N1) SIV infection among swine farm residents in eastern China, an active influenza surveillance program was conducted on swine farms in this region from May 21, 2010 through April 22, 2012. A total of 1,162 participants were enrolled, including 1,136 persons from 48 pig farms, as well as 26 pig farm veterinarians. A total of 10.7% and 7.8% swine farm residents were positive for antibodies against avian-like A (H1N1) SIV by HI and NT assay, respectively, using 40 as the cut-off antibody titer. Meanwhile, all the serum samples collected from a control of healthy city residents were negative against avian-like A (H1N1) SIV. As the difference in numbers of antibody positive samples between the swine farm residents and health city residents controls was statistically significant (P = 0.002), these data suggest that occupational exposure to pigs may increase swine farm residents' and veterinarians' risk of avian-like A (H1N1) SIV infection in eastern China. This study provides the first data on avian-like A (H1N1) SIV infections in humans in China; the potential for avian-like A (H1N1) SIV entering the human population should also be taken into consideration.

  14. Dependence of the results of ecological-epidemic investigation of influenza A(H1N1) on immunity

    NASA Astrophysics Data System (ADS)

    Fathudinova, Mohinav; Alimova, Barno; Rahimova, Halima

    2016-07-01

    This report presents the results of ecology-epidemical and immunological researches influ-enza virus A (H1 N1) and acute respiratory infection in Dushanbe from 2011 till 2015. The received results epidemiological and immunological analysis showed us, that last years has been changed not only characteristics of influenza epidemic, but it can not be notice the low-er of intensively of the collective immunity to actual versions influenza viruses A and B

  15. A/H1N1 pandemic influenza vaccination: A retrospective evaluation of adverse maternal, fetal and neonatal outcomes in a cohort of pregnant women in Italy.

    PubMed

    Fabiani, Massimo; Bella, Antonino; Rota, Maria C; Clagnan, Elena; Gallo, Tolinda; D'Amato, Maurizio; Pezzotti, Patrizio; Ferrara, Lorenza; Demicheli, Vittorio; Martinelli, Domenico; Prato, Rosa; Rizzo, Caterina

    2015-05-01

    Although concerns about safety of influenza vaccination during pregnancy have been raised in the past, vaccination of pregnant women was recommended in many countries during the 2009 A/H1N1 pandemic influenza. A retrospective cohort study was conducted to evaluate the risk of adverse maternal, fetal and neonatal outcomes among pregnant women vaccinated with a MF59-adjuvanted A/H1N1 pandemic influenza vaccine. The study was carried out in four Italian regions (Piemonte, Friuli-Venezia-Giulia, Lazio, and Puglia) among 102,077 pregnant women potentially exposed during the second or third trimester of gestation to the vaccination campaign implemented in 2009/2010. Based on data retrieved from the regional administrative databases, the statistical analysis was performed using the Cox proportional-hazards model, adjusting for the propensity score to account for the potential confounding effect due to the socio-demographic characteristics and the clinical and reproductive history of women. A total of 100,332 pregnant women were eligible for the analysis. Of these, 2003 (2.0%) received the A/H1N1 pandemic influenza vaccination during the second or third trimester of gestation. We did not observe any statistically significant association between the A/H1N1 pandemic influenza vaccination and different maternal outcomes (hospital admissions for influenza, pneumonia, hypertension, eclampsia, diabetes, thyroid disease, and anaemia), fetal outcomes (fetal death after the 22nd gestational week) and neonatal outcomes (pre-term birth, low birth weight, low 5-min Apgar score, and congenital malformations). Pre-existing health-risk conditions (hospital admissions and drug prescriptions for specific diseases before the onset of pregnancy) were observed more frequently among vaccinated women, thus suggesting that concomitant chronic conditions increased vaccination uptake. The results of this study add some evidence on the safety of A/H1N1 pandemic influenza vaccination during

  16. Multiple Reassortment between Pandemic (H1N1) 2009 and Endemic Influenza Viruses in Pigs, United States

    PubMed Central

    Ducatez, Mariette F.; Hause, Ben; Stigger-Rosser, Evelyn; Darnell, Daniel; Corzo, Cesar; Juleen, Kevin; Simonson, Randy; Brockwell-Staats, Christy; Rubrum, Adam; Wang, David; Webb, Ashley; Crumpton, Jeri-Carol; Lowe, James; Gramer, Marie

    2011-01-01

    As a result of human-to-pig transmission, pandemic influenza A (H1N1) 2009 virus was detected in pigs soon after it emerged in humans. In the United States, this transmission was quickly followed by multiple reassortment between the pandemic virus and endemic swine viruses. Nine reassortant viruses representing 7 genotypes were detected in commercial pig farms in the United States. Field observations suggested that the newly described reassortant viruses did not differ substantially from pandemic (H1N1) 2009 or endemic strains in their ability to cause disease. Comparable growth properties of reassortant and endemic viruses in vitro supported these observations; similarly, a representative reassortant virus replicated in ferrets to the same extent as did pandemic (H1N1) 2009 and endemic swine virus. These novel reassortant viruses highlight the increasing complexity of influenza viruses within pig populations and the frequency at which viral diversification occurs in this ecologically important viral reservoir. PMID:21892996

  17. Toward a method for tracking virus evolutionary trajectory applied to the pandemic H1N1 2009 influenza virus.

    PubMed

    Squires, R Burke; Pickett, Brett E; Das, Sajal; Scheuermann, Richard H

    2014-12-01

    In 2009 a novel pandemic H1N1 influenza virus (H1N1pdm09) emerged as the first official influenza pandemic of the 21st century. Early genomic sequence analysis pointed to the swine origin of the virus. Here we report a novel computational approach to determine the evolutionary trajectory of viral sequences that uses data-driven estimations of nucleotide substitution rates to track the gradual accumulation of observed sequence alterations over time. Phylogenetic analysis and multiple sequence alignments show that sequences belonging to the resulting evolutionary trajectory of the H1N1pdm09 lineage exhibit a gradual accumulation of sequence variations and tight temporal correlations in the topological structure of the phylogenetic trees. These results suggest that our evolutionary trajectory analysis (ETA) can more effectively pinpoint the evolutionary history of viruses, including the host and geographical location traversed by each segment, when compared against either BLAST or traditional phylogenetic analysis alone.

  18. Increased Pathogenicity of a Reassortant 2009 Pandemic H1N1 Influenza Virus Containing an H5N1 Hemagglutinin▿

    PubMed Central

    Cline, Troy D.; Karlsson, Erik A.; Freiden, Pamela; Seufzer, Bradley J.; Rehg, Jerold E.; Webby, Richard J.; Schultz-Cherry, Stacey

    2011-01-01

    A novel H1N1 influenza virus emerged in 2009 (pH1N1) to become the first influenza pandemic of the 21st century. This virus is now cocirculating with highly pathogenic H5N1 avian influenza viruses in many parts of the world, raising concerns that a reassortment event may lead to highly pathogenic influenza strains with the capacity to infect humans more readily and cause severe disease. To investigate the virulence of pH1N1-H5N1 reassortant viruses, we created pH1N1 (A/California/04/2009) viruses expressing individual genes from an avian H5N1 influenza strain (A/Hong Kong/483/1997). Using several in vitro models of virus replication, we observed increased replication for a reassortant CA/09 virus expressing the hemagglutinin (HA) gene of HK/483 (CA/09-483HA) relative to that of either parental CA/09 virus or reassortant CA/09 expressing other HK/483 genes. This increased replication correlated with enhanced pathogenicity in infected mice similar to that of the parental HK/483 strain. The serial passage of the CA/09 parental virus and the CA/09-483HA virus through primary human lung epithelial cells resulted in increased pathogenicity, suggesting that these viruses easily adapt to humans and become more virulent. In contrast, serial passage attenuated the parental HK/483 virus in vitro and resulted in slightly reduced morbidity in vivo, suggesting that sustained replication in humans attenuates H5N1 avian influenza viruses. Taken together, these data suggest that reassortment between cocirculating human pH1N1 and avian H5N1 influenza strains will result in a virus with the potential for increased pathogenicity in mammals. PMID:21917948

  19. Clinical and Virological Factors Associated with Viremia in Pandemic Influenza A/H1N1/2009 Virus Infection

    PubMed Central

    Tse, Herman; To, Kelvin K. W.; Wen, Xi; Chen, Honglin; Chan, Kwok-Hung; Tsoi, Hoi-Wah; Li, Iris W. S.; Yuen, Kwok-Yung

    2011-01-01

    Background Positive detection of viral RNA in blood and other non-respiratory specimens occurs in severe human influenza A/H5N1 viral infection but is not known to occur commonly in seasonal human influenza infection. Recently, viral RNA was detected in the blood of patients suffering from severe pandemic influenza A/H1N1/2009 viral infection, although the significance of viremia had not been previously studied. Our study aims to explore the clinical and virological factors associated with pandemic influenza A/H1N1/2009 viremia and to determine its clinical significance. Methodology/Principal Findings Clinical data of patients admitted to hospitals in Hong Kong between May 2009 and April 2010 and tested positive for pandemic influenza A/H1N1/2009 was collected. Viral RNA was detected by reverse-transcription polymerase chain reactions (RT-PCR) targeting the matrix (M) and HA genes of pandemic influenza A/H1N1/2009 virus from the following specimens: nasopharyngeal aspirate (NPA), endotracheal aspirate (ETA), blood, stool and rectal swab. Stool and/ or rectal swab was obtained only if the patient complained of any gastrointestinal symptoms. A total of 139 patients were included in the study, with viral RNA being detected in the blood of 14 patients by RT-PCR. The occurrence of viremia was strongly associated with a severe clinical presentation and a higher mortality rate, although the latter association was not statistically significant. D222G/N quasispecies were observed in 90% of the blood samples. Conclusion Presence of pandemic influenza A/H1N1/2009 viremia is an indicator of disease severity and strongly associated with D222G/N mutation in the viral hemagglutinin protein. PMID:21980333

  20. Pandemic H1N1 influenza A directly induces a robust and acute inflammatory gene signature in primary human bronchial epithelial cells downstream of membrane fusion.

    PubMed

    Paquette, Stéphane G; Banner, David; Chi, Le Thi Bao; Leόn, Alberto J; Xu, Luoling; Ran, Longsi; Huang, Stephen S H; Farooqui, Amber; Kelvin, David J; Kelvin, Alyson A

    2014-01-01

    Pandemic H1N1 influenza A (H1N1pdm) elicits stronger pulmonary inflammation than previously circulating seasonal H1N1 influenza A (sH1N1), yet mechanisms of inflammatory activation in respiratory epithelial cells during H1N1pdm infection are unclear. We investigated host responses to H1N1pdm/sH1N1 infection and virus entry mechanisms in primary human bronchial epithelial cells in vitro. H1N1pdm infection rapidly initiated a robust inflammatory gene signature (3 h post-infection) not elicited by sH1N1 infection. Protein secretion inhibition had no effect on gene induction. Infection with membrane fusion deficient H1N1pdm failed to induce robust inflammatory gene expression which was rescued with restoration of fusion ability, suggesting H1N1pdm directly triggered the inflammatory signature downstream of membrane fusion. Investigation of intra-virion components revealed H1N1pdm viral RNA (vRNA) triggered a stronger inflammatory phenotype than sH1N1 vRNA. Thus, our study is first to report H1N1pdm induces greater inflammatory gene expression than sH1N1 in vitro due to direct virus-epithelial cell interaction.

  1. Co-infection of classic swine H1N1 influenza virus in pigs persistently infected with porcine rubulavirus.

    PubMed

    Rivera-Benitez, José Francisco; De la Luz-Armendáriz, Jazmín; Saavedra-Montañez, Manuel; Jasso-Escutia, Miguel Ángel; Sánchez-Betancourt, Ivan; Pérez-Torres, Armando; Reyes-Leyva, Julio; Hernández, Jesús; Martínez-Lara, Atalo; Ramírez-Mendoza, Humberto

    2016-02-29

    Porcine rubulavirus (PorPV) and swine influenza virus infection causes respiratory disease in pigs. PorPV persistent infection could facilitate the establishment of secondary infections. The aim of this study was to analyse the pathogenicity of classic swine H1N1 influenza virus (swH1N1) in growing pigs persistently infected with porcine rubulavirus. Conventional six-week-old pigs were intranasally inoculated with PorPV, swH1N1, or PorPV/swH1N1. A mock-infected group was included. The co-infection with swH1N1 was at 44 days post-infection (DPI), right after clinical signs of PorPV infection had stopped. The pigs of the co-infection group presented an increase of clinical signs compared to the simple infection groups. In all infected groups, the most recurrent lung lesion was hyperplasia of the bronchiolar-associated lymphoid tissue and interstitial pneumonia. By means of immunohistochemical evaluation it was possible to demonstrate the presence of the two viral agents infecting simultaneously the bronchiolar epithelium. Viral excretion of PorPV in nasal and oral fluid was recorded at 28 and 52 DPI, respectively. PorPV persisted in several samples from respiratory tissues (RT), secondary lymphoid organs (SLO), and bronchoalveolar lavage fluid (BALF). For swH1N1, the viral excretion in nasal fluids was significantly higher in single-infected swH1N1 pigs than in the co-infected group. However, the co-infection group exhibited an increase in the presence of swH1N1 in RT, SLO, and BALF at two days after co-infection. In conclusion, the results obtained confirm an increase in the clinical signs of infection, and PorPV was observed to impact the spread of swH1N1 in analysed tissues in the early stage of co-infection, although viral shedding was not enhanced. In the present study, the interaction of swH1N1 infection is demonstrated in pigs persistently infected with PorPV.

  2. Immune and inflammatory response in pigs during acute influenza caused by H1N1 swine influenza virus.

    PubMed

    Pomorska-Mól, Małgorzata; Markowska-Daniel, Iwona; Kwit, Krzysztof; Czyżewska, Ewelina; Dors, Arkadiusz; Rachubik, Jarosław; Pejsak, Zygmunt

    2014-10-01

    Swine influenza (SI) is an acute respiratory disease of pigs, caused by swine influenza virus (SIV). Little is known about the inflammatory response in the lung during acute SI and its correlation with clinical signs or lung pathology. Moreover, until now there has been a limited amount of data available on the relationship between the concentrations of pro- and anti-inflammatory cytokines in the lungs and the serum concentration of acute-phase proteins (APPs) in SIV-infected pigs. In the present study, the porcine inflammatory and immune responses during acute influenza caused by H1N1 SIV (SwH1N1) were studied. Nine pigs were infected intratracheally, and five served as controls. Antibodies against SIV were measured by haemagglutination inhibition assay, and the influenza-virus-specific T-cell response was measured using a proliferation assay. C-reactive protein (CRP), haptoglobin (Hp), serum amyloid A (SAA), and pig major acute-phase protein (Pig-MAP) the concentrations in serum and concentration of IL-1β, IL-6, IL-8, IL-10, TNF-α and IFN-γ in lung tissues were measured using commercial ELISAs.

  3. Multiyear Persistence of 2 Pandemic A/H1N1 Influenza Virus Lineages in West Africa

    PubMed Central

    Nelson, Martha I.; Njouom, Richard; Viboud, Cecile; Niang, Mbayame N. D.; Kadjo, Hervé; Ampofo, William; Adebayo, Adedeji; Tarnagda, Zekiba; Miller, Mark A.; Holmes, Edward C.; Diop, Ousmane M.

    2014-01-01

    Our understanding of the global ecology of influenza viruses is impeded by historically low levels of viral surveillance in Africa. Increased genetic sequencing of African A/H1N1 pandemic influenza viruses during 2009–2013 revealed multiyear persistence of 2 viral lineages within West Africa, raising questions about the roles of reduced air traffic and the asynchrony of seasonal influenza epidemics among West African countries in the evolution of independent lineages. The potential for novel influenza virus lineages to evolve within Africa warrants intensified influenza surveillance in Africa and other understudied areas. PMID:24446525

  4. Evaluation of 2009 pandemic influenza A (H1N1) exposures and illness among physicians in training

    PubMed Central

    de Perio, Marie A.; Brueck, Scott E.; Mueller, Charles A.; Milne, Caroline K.; Rubin, Michael A.; Gundlapalli, Adi V.; Mayer, Jeanmarie

    2015-01-01

    Background A cluster of influenza-like illness (ILI) among physicians in training during the 2009 influenza A (H1N1) pandemic (pH1N1) led to a health hazard evaluation. Methods We conducted a cross-sectional study to examine exposures, infection control practices, ILI prevalence, and transmission among physicians in training at 4 affiliated hospitals during the pandemic. We administered an electronic survey and met with physicians in training and hospital personnel. Results Of the 88 responding physicians, 85% reported exposure to pH1N1. Exposures occurred at work from patients or coworkers and outside of work from coworkers, household members, or the community. Thirteen cases of ILI were reported in May-June 2009; 10 respondents reported working while ill (duration, 1-4 days). Between 13% and 88% of respondents knew which personal protective equipment (PPE) was recommended when caring for influenza patients at the 4 hospitals. The most common reasons for not using PPE were not knowing that a patient had pH1N1 or ILI and not having PPE readily available. Conclusions Physicians in training have gaps in their knowledge of and adherence to recommended PPE and compliance with work restrictions. Our findings underscore the importance of installing isolation precaution signage, making PPE readily available near patients with influenza, and facilitating work restrictions for ill health care personnel. PMID:22622511

  5. Metabolic syndrome as an independent risk factor of hypoxaemia in influenza A (H1N1) 2009 pandemic.

    PubMed

    Bijani, Behzad; Pahlevan, Ali Asghar; Qasemi-Barqi, Reza; Jahanihashemi, Hassan

    2016-06-01

    A swine-origin influenza A (H1N1) emerged as a pandemic in 2009. We investigated the association between the overweight, metabolic syndrome and the severity of disease in the confirmed cases in Qazvin province, Iran. The study sample included all patients over 12 years old with confirmed influenza A (H1N1) in the province of Qazvin, Iran, in the 2009 pandemic, excluding pregnant women. To define overweight, sex and age-specific body mass index (BMI) cutoffs recommended by the International Obesity Task Force were used. Metabolic syndrome was defined by ATP III criteria. Multiple logistic regression analysis was performed to identify statistically independent predictors of hypoxaemia. Out of 55 confirmed cases, 28 (50.9%) were overweight and 24 (45.3%) were identified as having metabolic syndrome by ATP III criteria. Twenty four patients had hypoxaemia (arterial oxygen saturation below 90%) during the course of the disease. In multivariate logistic regression analysis, pulmonary co-morbidity (OR=9.54; 95% CI, 1.36 to 66.88; p= 0.023) and the metabolic syndrome (OR=18.66; 95% CI, 1.60 to 217.47; p= 0.019) were revealed to be independent risk factors for hypoxaemia in influenza A (H1N1) pdm09. The results of the present study reveal the role of the metabolic syndrome on the severity of influenza A (H1N1) pdm09 infection. PMID:27367322

  6. Molecular dynamics analysis of antibody recognition and escape by human H1N1 influenza hemagglutinin.

    PubMed

    Ieong, Pek; Amaro, Rommie E; Li, Wilfred W

    2015-06-01

    The antibody immunoglobulin (Ig) 2D1 is effective against the 1918 hemagglutinin (HA) and also known to cross-neutralize the 2009 pandemic H1N1 influenza HA through a similar epitope. However, the detailed mechanism of neutralization remains unclear. We conducted molecular dynamics (MD) simulations to study the interactions between Ig-2D1 and the HAs from the 1918 pandemic flu (A/South Carolina/1/1918, 18HA), the 2009 pandemic flu (A/California/04/2009, 09HA), a 2009 pandemic flu mutant (A/California/04/2009, 09HA_mut), and the 2006 seasonal flu (A/Solomon Islands/3/2006, 06HA). MM-PBSA analyses suggest the approximate free energy of binding (ΔG) between Ig-2D1 and 18HA is -74.4 kcal/mol. In comparison with 18HA, 09HA and 06HA bind Ig-2D1 ∼6 kcal/mol (ΔΔG) weaker, and the 09HA_mut bind Ig-2D1 only half as strong. We also analyzed the contributions of individual epitope residues using the free-energy decomposition method. Two important salt bridges are found between the HAs and Ig-2D1. In 09HA, a serine-to-asparagine mutation coincided with a salt bridge destabilization, hydrogen bond losses, and a water pocket formation between 09HA and Ig-2D1. In 09HA_mut, a lysine-to-glutamic-acid mutation leads to the loss of both salt bridges and destabilizes interactions with Ig-2D1. Even though 06HA has a similar ΔG to 09HA, it is not recognized by Ig-2D1 in vivo. Because 06HA contains two potential glycosylation sites that could mask the epitope, our results suggest that Ig-2D1 may be active against 06HA only in the absence of glycosylation. Overall, our simulation results are in good agreement with observations from biological experiments and offer novel mechanistic insights, to our knowledge, into the immune escape of the influenza virus. PMID:26039171

  7. Impact of influenza A(H1N1)pdm09 virus on circulation dynamics of seasonal influenza strains in Kenya.

    PubMed

    Majanja, Janet; Njoroge, Rose N; Achilla, Rachel; Wurapa, Eyako K; Wadegu, Meshack; Mukunzi, Silvanos; Mwangi, Josephat; Njiri, James; Gachara, George; Bulimo, Wallace

    2013-05-01

    We describe virus variations from patients with influenza-like illness before and after the appearance of influenza A(H1N1)pdm09 in Kenya during January 2008-July 2011. A total of 11,592 nasopharyngeal swabs were collected from consenting patients. Seasonal influenza B, A/H1N1, A/H3N2, A/H5N1, and influenza A(H1N1)pdm09 viruses were detected by real-time reverse transcription-polymerase chain reaction. Of patients enrolled, 2073 (17.9%) had influenza. A total of 1,524 (73.4%) of 2,073 samples were positive for influenza A virus and 549 (26.6%) were positive for influenza B virus. Influenza B virus predominated in 2008 and seasonal A(H1N1) virus predominated in the first half of 2009. Influenza A(H1N1)pdm09 virus predominated in the second half of 2009. Influenza A/H3N2 virus predominated in 2010, and co-circulation of influenza A(H1N1)pdm09 virus and influenza B virus predominated the first half of 2011. The reduction and displacement of seasonal A(H1N1) virus was the most obvious effect of the arrival of influenza A(H1N1)pdm09 virus. The decision of the World Health Organization to replace seasonal A(H1N1) virus with the pandemic virus strain for the southern hemisphere vaccine was appropriate for Kenya.

  8. [Impact of school closings on the influenza A (H1N1) outbreak in Tierra del Fuego, Argentina].

    PubMed

    Orellano, Pablo Wenceslao; Grassi, Aurora; Reynoso, Julieta Itatí; Palmieri, Abel; Uez, Osvaldo; Carlino, Orestes

    2010-03-01

    The impact of school closings on reducing the number of cases of influenza-like illness during an outbreak of influenza A (H1N1), which reached pandemic proportions, was assessed, along with other control measures, in the two main cities of Tierra del Fuego Province in southern Argentina. The incidence before and after the school closings in 2009 was compared by means of the t-test for related samples. By week 40, 6 901 cases of influenza-like illness had been detected, 281 of which were confirmed as influenza A (H1N1) through laboratory tests; 38 patients were hospitalized. After the intervention, there were nearly 10 times fewer cases than the average recorded in the health centers. The results indicate that closing schools during the influenza A (H1N1) outbreak resulted in a significantly lower incidence of influenza-like illness. However, the impact of other measures, such as case management and protection against exposure, should not be ignored. Timely implementation of this intervention, together with other measures, can help minimize the spread of influenza outbreaks.

  9. Genetic Characteristics and Immunogenicity of Pandemic H1N1 Influenza Virus Isolate from Pig in Korea

    PubMed Central

    Moon, Hyoung Joon; Oh, Jin Sik; Na, Woonsung; Yeom, Minjoo; Han, Sang Yoon; Kim, Sung Jae; Park, Bong Kyun

    2016-01-01

    A pandemic influenza A (H1N1) virus strain was isolated from a pig farm in Korea in December 2009. The strain was propagated in and isolated from both the Madin-Darby canine kidney cell line and embryonated eggs. The partial and complete sequences of the strain were identical to those of A/California/04/2009, with >99% sequence similarity in the HA, NA, M, NS, NP, PA, PB1, and PB2 genes. The isolated strain was inactivated and used to prepare a swine influenza vaccine. This trial vaccine, containing the new isolate that has high sequence similarity with the pandemic influenza A (H1N1) virus, resulted in seroconversion in Guinea pigs and piglets. This strain could therefore be a potential vaccine candidate for swine influenza control in commercial farms. PMID:27799877

  10. Genetic divergence of influenza A NS1 gene in pandemic 2009 H1N1 isolates with respect to H1N1 and H3N2 isolates from previous seasonal epidemics

    PubMed Central

    2010-01-01

    Background The Influenza A pandemic sustained by a new H1N1 variant (H1N1v) started in Mexico and the USA at the end of April 2009 spreading worldwide in a few weeks. In this study we investigate the variability of the NS1 gene of the pandemic H1N1v strain with respect to previous seasonal strains circulating in humans and the potential selection of virus variants through isolation in cell culture. Methods During the period April 27th 2009-Jan 15th 2010, 1633 potential 2009 H1N1v cases have been screened at our center using the CDC detection and typing realtime RT-PCR assays. Virus isolation on MDCK cells was systematically performed in 1/10 positive cases. A subset of 51 H1N1v strains isolated in the period May-September 2009 was selected for NS1 gene sequencing. In addition, 15 H1N1 and 47 H3N2 virus isolates from three previous seasonal epidemics (2006-2009) were analyzed in parallel. Results A low variability in the NS1 amino acid (aa) sequence among H1N1v isolates was shown (aa identity 99.5%). A slightly higher NS1 variability was observed among H1N1 and H3N2 strains from previous epidemics (aa identity 98.6% and 98.9%, respectively). The H1N1v strains were closely related (aa identity 92.1%) to swine reference strain (A/swine/Oklahoma/042169/2008). In contrast, substantial divergence (aa identity 83.4%) with respect to human reference strain A/Brevig Mission/1/1918 and previous epidemic strains H1N1 and H3N2 (aa identity 78.9% and 77.6%, respectively) was shown. Specific sequence signatures of uncertain significance in the new virus variant were a C-terminus deletion and a T215P substitution. Conclusions The H1N1v NS1 gene was more conserved than that of previous epidemic strains. In addition, a closer genetic identity of H1N1v with the swine than the human reference strains was shown. Hot-spots were shown in the H1N1v NS1 aa sequence whose biologic relevance remains to be investigated. PMID:20809948

  11. Update on Influenza Diagnostics: Lessons from the Novel H1N1 Influenza A Pandemic

    PubMed Central

    Henrickson, Kelly J.

    2012-01-01

    Summary: The menu of diagnostic tools that can be utilized to establish a diagnosis of influenza is extensive and includes classic virology techniques as well as new and emerging methods. This review of how the various existing diagnostic methods have been utilized, first in the context of a rapidly evolving outbreak of novel influenza virus and then during the different subsequent phases and waves of the pandemic, demonstrates the unique roles, advantages, and limitations of each of these methods. Rapid antigen tests were used extensively throughout the pandemic. Recognition of the low negative predictive values of these tests is important. Private laboratories with preexisting expertise, infrastructure, and resources for rapid development, validation, and implementation of laboratory-developed assays played an unprecedented role in helping to meet the diagnostic demands during the pandemic. FDA-cleared assays remain an important element of the diagnostic armamentarium during a pandemic, and a process must be developed with the FDA to allow manufacturers to modify these assays for detection of novel strains in a timely fashion. The need and role for subtyping of influenza viruses and antiviral susceptibility testing will likely depend on qualitative (circulating subtypes and their resistance patterns) and quantitative (relative prevalence) characterization of influenza viruses circulating during future epidemics and pandemics. PMID:22491775

  12. Characterization In Vitro and In Vivo of a Pandemic H1N1 Influenza Virus from a Fatal Case

    PubMed Central

    Cuevas, Maria Teresa; Pozo, Francisco; Guerra, Susana; García-Barreno, Blanca; Martinez-Orellana, Pamela; Pérez-Breña, Pilar; Montoya, Maria; Melero, Jose Antonio; Pizarro, Manuel; Ortin, Juan; Casas, Inmaculada; Nieto, Amelia

    2013-01-01

    Pandemic 2009 H1N1 (pH1N1) influenza viruses caused mild symptoms in most infected patients. However, a greater rate of severe disease was observed in healthy young adults and children without co-morbid conditions. Here we tested whether influenza strains displaying differential virulence could be present among circulating pH1N1 viruses. The biological properties and the genotype of viruses isolated from a patient showing mild disease (M) or from a fatal case (F), both without known co-morbid conditions were compared in vitro and in vivo. The F virus presented faster growth kinetics and stronger induction of cytokines than M virus in human alveolar lung epithelial cells. In the murine model in vivo, the F virus showed a stronger morbidity and mortality than M virus. Remarkably, a higher proportion of mice presenting infectious virus in the hearts, was found in F virus-infected animals. Altogether, the data indicate that strains of pH1N1 virus with enhanced pathogenicity circulated during the 2009 pandemic. In addition, examination of chemokine receptor 5 (CCR5) genotype, recently reported as involved in severe influenza virus disease, revealed that the F virus-infected patient was homozygous for the deleted form of CCR5 receptor (CCR5Δ32). PMID:23326447

  13. Integrated microfluidic system for rapid detection of influenza H1N1 virus using a sandwich-based aptamer assay.

    PubMed

    Tseng, Yi-Ting; Wang, Chih-Hung; Chang, Chih-Peng; Lee, Gwo-Bin

    2016-08-15

    The rapid spread of influenza-associated H1N1 viruses has caused serious concern in recent years. Therefore, there is an urgent need for the development of automatic, point-of-care devices for rapid diagnosis of the influenza virus. Conventional approaches suffer from several critical issues; notably, they are time-consuming, labor-intensive, and are characterized by relatively low sensitivity. In this work, we present a new approach for fluorescence-based detection of the influenza A H1N1 virus using a sandwich-based aptamer assay that is automatically performed on an integrated microfluidic system. The entire detection process was shortened to 30min using this chip-based system which is much faster than the conventional viral culture method. The limit of detection was significantly improved to 0.032 hemagglutination unit due to the high affinity and high specificity of the H1N1-specific aptamers. The results showed that the two-aptamer microfluidic system had about 10(3) times higher sensitivity than the conventional serological diagnosis. It was demonstrated that the developed microfluidic system may play as a powerful tool in the detection of the H1N1 virus.

  14. Structural characterization of a protective epitope spanning A(H1N1)pdm09 influenza virus neuraminidase monomers

    PubMed Central

    Wan, Hongquan; Yang, Hua; Shore, David A.; Garten, Rebecca J.; Couzens, Laura; Gao, Jin; Jiang, Lianlian; Carney, Paul J.; Villanueva, Julie; Stevens, James; Eichelberger, Maryna C.

    2015-01-01

    A(H1N1)pdm09 influenza A viruses predominated in the 2013–2014 USA influenza season, and although most of these viruses remain sensitive to Food and Drug Administration-approved neuraminidase (NA) inhibitors, alternative therapies are needed. Here we show that monoclonal antibody CD6, selected for binding to the NA of the prototypic A(H1N1)pdm09 virus, A/California/07/2009, protects mice against lethal virus challenge. The crystal structure of NA in complex with CD6 Fab reveals a unique epitope, where the heavy-chain complementarity determining regions (HCDRs) 1 and 2 bind one NA monomer, the light-chain CDR2 binds the neighbouring monomer, whereas HCDR3 interacts with both monomers. This 30-amino-acid epitope spans the lateral face of an NA dimer and is conserved among circulating A(H1N1)pdm09 viruses. These results suggest that the large, lateral CD6 epitope may be an effective target of antibodies selected for development as therapeutic agents against circulating H1N1 influenza viruses. PMID:25668439

  15. Identification and analysis of the first 2009 pandemic H1N1 influenza virus from U.S. feral swine.

    PubMed

    Clavijo, A; Nikooienejad, A; Esfahani, M S; Metz, R P; Schwartz, S; Atashpaz-Gargari, E; Deliberto, T J; Lutman, M W; Pedersen, K; Bazan, L R; Koster, L G; Jenkins-Moore, M; Swenson, S L; Zhang, M; Beckham, T; Johnson, C D; Bounpheng, M

    2013-08-01

    The first case of pandemic H1N1 influenza (pH1N1) virus in feral swine in the United States was identified in Texas through the United States Department of Agriculture (USDA) Wildlife Services' surveillance program. Two samples were identified as pandemic influenza by reverse transcriptase quantitative PCR (RT-qPCR). Full-genome Sanger sequencing of all eight influenza segments was performed. In addition, Illumina deep sequencing of the original diagnostic samples and their respective virus isolation cultures were performed to assess the feasibility of using an unbiased whole-genome linear target amplification method and multiple sample sequencing in a single Illumina GAIIx lane. Identical sequences were obtained using both techniques. Phylogenetic analysis indicated that all gene segments belonged to the pH1N1 (2009) lineage. In conclusion, we have identified the first pH1N1 isolate in feral swine in the United States and have demonstrated the use of an easy unbiased linear amplification method for deep sequencing of multiple samples.

  16. Integrated microfluidic system for rapid detection of influenza H1N1 virus using a sandwich-based aptamer assay.

    PubMed

    Tseng, Yi-Ting; Wang, Chih-Hung; Chang, Chih-Peng; Lee, Gwo-Bin

    2016-08-15

    The rapid spread of influenza-associated H1N1 viruses has caused serious concern in recent years. Therefore, there is an urgent need for the development of automatic, point-of-care devices for rapid diagnosis of the influenza virus. Conventional approaches suffer from several critical issues; notably, they are time-consuming, labor-intensive, and are characterized by relatively low sensitivity. In this work, we present a new approach for fluorescence-based detection of the influenza A H1N1 virus using a sandwich-based aptamer assay that is automatically performed on an integrated microfluidic system. The entire detection process was shortened to 30min using this chip-based system which is much faster than the conventional viral culture method. The limit of detection was significantly improved to 0.032 hemagglutination unit due to the high affinity and high specificity of the H1N1-specific aptamers. The results showed that the two-aptamer microfluidic system had about 10(3) times higher sensitivity than the conventional serological diagnosis. It was demonstrated that the developed microfluidic system may play as a powerful tool in the detection of the H1N1 virus. PMID:27054814

  17. Oseltamivir–Resistant Pandemic H1N1/2009 Influenza Virus Possesses Lower Transmissibility and Fitness in Ferrets

    PubMed Central

    Duan, Susu; Boltz, David A.; Seiler, Patrick; Li, Jiang; Bragstad, Karoline; Nielsen, Lars P.; Webby, Richard J.; Webster, Robert G.; Govorkova, Elena A.

    2010-01-01

    The neuraminidase (NA) inhibitor oseltamivir offers an important immediate option for the control of influenza, and its clinical use has increased substantially during the recent H1N1 pandemic. In view of the high prevalence of oseltamivir-resistant seasonal H1N1 influenza viruses in 2007–2008, there is an urgent need to characterize the transmissibility and fitness of oseltamivir-resistant H1N1/2009 viruses, although resistant variants have been isolated at a low rate. Here we studied the transmissibility of a closely matched pair of pandemic H1N1/2009 clinical isolates, one oseltamivir-sensitive and one resistant, in the ferret model. The resistant H275Y mutant was derived from a patient on oseltamivir prophylaxis and was the first oseltamivir-resistant isolate of the pandemic virus. Full genome sequencing revealed that the pair of viruses differed only at NA amino acid position 275. We found that the oseltamivir-resistant H1N1/2009 virus was not transmitted efficiently in ferrets via respiratory droplets (0/2), while it retained efficient transmission via direct contact (2/2). The sensitive H1N1/2009 virus was efficiently transmitted via both routes (2/2 and 1/2, respectively). The wild-type H1N1/2009 and the resistant mutant appeared to cause a similar disease course in ferrets without apparent attenuation of clinical signs. We compared viral fitness within the host by co-infecting a ferret with oseltamivir-sensitive and -resistant H1N1/2009 viruses and found that the resistant virus showed less growth capability (fitness). The NA of the resistant virus showed reduced substrate-binding affinity and catalytic activity in vitro and delayed initial growth in MDCK and MDCK-SIAT1 cells. These findings may in part explain its less efficient transmission. The fact that the oseltamivir-resistant H1N1/2009 virus retained efficient transmission through direct contact underlines the necessity of continuous monitoring of drug resistance and characterization of possible

  18. Efficacy of a high-growth reassortant H1N1 influenza virus vaccine against the classical swine H1N1 subtype influenza virus in mice and pigs.

    PubMed

    Wen, Feng; Yu, Hai; Yang, Fu-Ru; Huang, Meng; Yang, Sheng; Zhou, Yan-Jun; Li, Ze-Jun; Tong, Guang-Zhi

    2014-11-01

    Swine influenza (SI) is an acute, highly contagious respiratory disease caused by swine influenza A viruses (SwIVs), and it poses a potential global threat to human health. Classical H1N1 (cH1N1) SwIVs are still circulating and remain the predominant subtype in the swine population in China. In this study, a high-growth reassortant virus (GD/PR8) harboring the hemagglutinin (HA) and neuraminidase (NA) genes from a novel cH1N1 isolate in China, A/Swine/Guangdong/1/2011 (GD/11) and six internal genes from the high-growth A/Puerto Rico/8/34(PR8) virus was generated by plasmid-based reverse genetics and tested as a candidate seed virus for the preparation of an inactivated vaccine. The protective efficacy of this vaccine was evaluated in mice and pigs challenged with GD/11 virus. Prime and boost inoculation of GD/PR8 vaccine yielded high-titer serum hemagglutination inhibiting (HI) antibodies and IgG antibodies for GD/11 in both mice and pigs. Complete protection of mice and pigs against cH1N1 SIV challenge was observed, with significantly fewer lung lesions and reduced viral shedding in vaccine-inoculated animals compared with unvaccinated control animals. Our data demonstrated that the GD/PR8 may serve as the seed virus for a promising SwIVs vaccine to protect the swine population.

  19. Influenza vaccination in the Americas: Progress and challenges after the 2009 A(H1N1) influenza pandemic

    PubMed Central

    Ropero-Álvarez, Alba María; El Omeiri, Nathalie; Kurtis, Hannah Jane; Danovaro-Holliday, M. Carolina; Ruiz-Matus, Cuauhtémoc

    2016-01-01

    ABSTRACT Background: There has been considerable uptake of seasonal influenza vaccines in the Americas compared to other regions. We describe the current influenza vaccination target groups, recent progress in vaccine uptake and in generating evidence on influenza seasonality and vaccine effectiveness for immunization programs. We also discuss persistent challenges, 5 years after the A(H1N1) 2009 influenza pandemic. Methods: We compiled and summarized data annually reported by countries to the Pan American Health Organization/World Health Organization (PAHO/WHO) through the WHO/UNICEF joint report form on immunization, information obtained through PAHO's Revolving Fund for Vaccine Procurement and communications with managers of national Expanded Programs on Immunization (EPI). Results: Since 2008, 25 countries/territories in the Americas have introduced new target groups for vaccination or expanded the age ranges of existing target groups. As of 2014, 40 (89%) out of 45 countries/territories have policies established for seasonal influenza vaccination. Currently, 29 (64%) countries/territories target pregnant women for vaccination, the highest priority group according to WHO´s Stategic Advisory Group of Experts and PAHO/WHO's Technical Advisory Group on Vaccine-preventable Diseases, compared to only 7 (16%) in 2008. Among 23 countries reporting coverage data, on average, 75% of adults ≥60 years, 45% of children aged 6–23 months, 32% of children aged 5–2 years, 59% of pregnant women, 78% of healthcare workers, and 90% of individuals with chronic conditions were vaccinated during the 2013–14 Northern Hemisphere or 2014 Southern Hemisphere influenza vaccination activities. Difficulties however persist in the estimation of vaccination coverage, especially for pregnant women and persons with chronic conditions. Since 2007, 6 tropical countries have changed their vaccine formulation from the Northern to the Southern Hemisphere formulation and the timing of

  20. Genetic makeup of amantadine-resistant and oseltamivir-resistant human influenza A/H1N1 viruses.

    PubMed

    Zaraket, Hassan; Saito, Reiko; Suzuki, Yasushi; Baranovich, Tatiana; Dapat, Clyde; Caperig-Dapat, Isolde; Suzuki, Hiroshi

    2010-04-01

    The emergence and widespread occurrence of antiviral drug-resistant seasonal human influenza A viruses, especially oseltamivir-resistant A/H1N1 virus, are major concerns. To understand the genetic background of antiviral drug-resistant A/H1N1 viruses, we performed full genome sequencing of prepandemic A/H1N1 strains. Seasonal influenza A/H1N1 viruses, including antiviral-susceptible viruses, amantadine-resistant viruses, and oseltamivir-resistant viruses, obtained from several areas in Japan during the 2007-2008 and 2008-2009 influenza seasons were analyzed. Sequencing of the full genomes of these viruses was performed, and the phylogenetic relationships among the sequences of each individual genome segment were inferred. Reference genome sequences from the Influenza Virus Resource database were included to determine the closest ancestor for each segment. Phylogenetic analysis revealed that the oseltamivir-resistant strain evolved from a reassortant oseltamivir-susceptible strain (clade 2B) which circulated in the 2007-2008 season by acquiring the H275Y resistance-conferring mutation in the NA gene. The oseltamivir-resistant lineage (corresponding to the Northern European resistant lineage) represented 100% of the H1N1 isolates from the 2008-2009 season and further acquired at least one mutation in each of the polymerase basic protein 2 (PB2), polymerase basic protein 1 (PB1), hemagglutinin (HA), and neuraminidase (NA) genes. Therefore, a reassortment event involving two distinct oseltamivir-susceptible lineages, followed by the H275Y substitution in the NA gene and other mutations elsewhere in the genome, contributed to the emergence of the oseltamivir-resistant lineage. In contrast, amantadine-resistant viruses from the 2007-2008 season distinctly clustered in clade 2C and were characterized by extensive amino acid substitutions across their genomes, suggesting that a fitness gap among its genetic components might have driven these mutations to maintain it in the

  1. Molecular and phylogenetic analysis of influenza A H1N1 pandemic viruses in Cuba, May 2009 to August 2010.

    PubMed

    Ramos, Alexander Piñón; Herrera, Belsy Acosta; Ramírez, Odalys Valdés; García, Amely Arencibia; Jiménez, Mayra Muné; Valdés, Clara Savón; Fernández, Angel Goyenechea; González, Grehete; Fernández, Suset I Oropesa; Báez, Guelsys González; Espinosa, Bárbara Hernández

    2013-07-01

    The influenza A(H1N1)pdm09 virus was detected in Cuba in May 2009. The introduction of a new virus with increased transmissibility into a population makes surveillance of the pandemic strain to the molecular level necessary. The aim of the present study was the molecular and phylogenetic analysis of pandemic influenza A(H1N1)pdm09 strains that circulated in Cuba between May 2009 and August 2010. Seventy clinical samples were included in the study. Nucleotide sequences from the hemagglutinin HA1 region segment were obtained directly from clinical samples. Genetic distances were calculated using MEGA v.5.05. A phylogenetic tree was constructed using MrBayes v.3.1.2 software. Potential N-glycosylation sites were predicted using NetNGlyc server 1.0. The 48 Cuban sequences of influenza A(H1N1)pdm09 obtained were similar to the A/California/07/2009 (H1N1) vaccine strain. Most of the Cuban strains belonged to clade 7. Cuban viruses showed amino acid changes, some of them located at three antigenic sites: Ca, Sa, and Sb. Two dominant mutations were detected: P83S (100%) and S203T (85.7%). Glycosylation site analysis revealed the gain of one site at position 162 in 13 sequences. The findings in this study contribute to our understanding of the progress of the influenza A(H1N1)pdm09 virus, since this virus is at the starting point of its evolution in humans.

  2. Genetic makeup of amantadine-resistant and oseltamivir-resistant human influenza A/H1N1 viruses.

    PubMed

    Zaraket, Hassan; Saito, Reiko; Suzuki, Yasushi; Baranovich, Tatiana; Dapat, Clyde; Caperig-Dapat, Isolde; Suzuki, Hiroshi

    2010-04-01

    The emergence and widespread occurrence of antiviral drug-resistant seasonal human influenza A viruses, especially oseltamivir-resistant A/H1N1 virus, are major concerns. To understand the genetic background of antiviral drug-resistant A/H1N1 viruses, we performed full genome sequencing of prepandemic A/H1N1 strains. Seasonal influenza A/H1N1 viruses, including antiviral-susceptible viruses, amantadine-resistant viruses, and oseltamivir-resistant viruses, obtained from several areas in Japan during the 2007-2008 and 2008-2009 influenza seasons were analyzed. Sequencing of the full genomes of these viruses was performed, and the phylogenetic relationships among the sequences of each individual genome segment were inferred. Reference genome sequences from the Influenza Virus Resource database were included to determine the closest ancestor for each segment. Phylogenetic analysis revealed that the oseltamivir-resistant strain evolved from a reassortant oseltamivir-susceptible strain (clade 2B) which circulated in the 2007-2008 season by acquiring the H275Y resistance-conferring mutation in the NA gene. The oseltamivir-resistant lineage (corresponding to the Northern European resistant lineage) represented 100% of the H1N1 isolates from the 2008-2009 season and further acquired at least one mutation in each of the polymerase basic protein 2 (PB2), polymerase basic protein 1 (PB1), hemagglutinin (HA), and neuraminidase (NA) genes. Therefore, a reassortment event involving two distinct oseltamivir-susceptible lineages, followed by the H275Y substitution in the NA gene and other mutations elsewhere in the genome, contributed to the emergence of the oseltamivir-resistant lineage. In contrast, amantadine-resistant viruses from the 2007-2008 season distinctly clustered in clade 2C and were characterized by extensive amino acid substitutions across their genomes, suggesting that a fitness gap among its genetic components might have driven these mutations to maintain it in the

  3. PLC-γ1 is involved in the inflammatory response induced by influenza A virus H1N1 infection.

    PubMed

    Zhu, Liqian; Yuan, Chen; Ding, Xiuyan; Xu, Shuai; Yang, Jiayun; Liang, Yuying; Zhu, Qiyun

    2016-09-01

    We have previously reported that phosphoinositide-specific phospholipase γ1 (PLC-γ1) signaling is activated by influenza virus H1N1 infection and mediates efficient viral entry in human epithelial cells. In this study, we show that H1N1 also activates PLCγ-1 signaling in human promonocytic cell line -derived macrophages. Surprisingly, the activated PLCγ-1 signaling is not important for viral replication in macrophages, but is involved in the virus-induced inflammatory responses. PLC-γ1-specific inhibitor U73122 strongly inhibits the H1N1 virus-induced NF-κB signaling, blocking the up-regulation of TNF-α, IL-6, MIP-1α, and reactive oxidative species. In a positive feedback loop, IL-1β and TNF-α activate the PLCγ-1 signaling in both epithelial and macrophage cell lines. In summary, we have shown for the first time that the PLCγ-1 signaling plays an important role in the H1N1-induced inflammatory responses. Our study suggests that targeting the PLCγ-1 signaling is a potential antiviral therapy against H1N1 by inhibiting both viral replication and excessive inflammation.

  4. Cold-adapted pandemic 2009 H1N1 influenza virus live vaccine elicits cross-reactive immune responses against seasonal and H5 influenza A viruses.

    PubMed

    Jang, Yo Han; Byun, Young Ho; Lee, Yoon Jae; Lee, Yun Ha; Lee, Kwang-Hee; Seong, Baik Lin

    2012-05-01

    The rapid transmission of the pandemic 2009 H1N1 influenza virus (pH1N1) among humans has raised the concern of a potential emergence of reassortment between pH1N1 and highly pathogenic influenza strains, especially the avian H5N1 influenza virus. Here, we report that the cold-adapted pH1N1 live attenuated vaccine (CApH1N1) elicits cross-reactive immunity to seasonal and H5 influenza A viruses in the mouse model. Immunization with CApH1N1 induced both systemic and mucosal antibodies with broad reactivity to seasonal and H5 strains, including HAPI H5N1 and the avian H5N2 virus, providing complete protection against heterologous and heterosubtypic lethal challenges. Our results not only accentuate the merit of using live attenuated influenza virus vaccines in view of cross-reactivity but also represent the potential of CApH1N1 live vaccine for mitigating the clinical severity of infections that arise from reassortments between pH1N1 and highly pathogenic H5 subtype viruses.

  5. Socioeconomic Factors Influencing Hospitalized Patients with Pneumonia Due to Influenza A(H1N1)pdm09 in Mexico

    PubMed Central

    Manabe, Toshie; Higuera Iglesias, Anjarath Lorena; Vazquez Manriquez, Maria Eugenia; Martinez Valadez, Eduarda Leticia; Ramos, Leticia Alfaro; Izumi, Shinyu; Takasaki, Jin; Kudo, Koichiro

    2012-01-01

    Background In addition to clinical aspects and pathogen characteristics, people's health-related behavior and socioeconomic conditions can affect the occurrence and severity of diseases including influenza A(H1N1)pdm09. Methodology and Principal Findings A face-to-face interview survey was conducted in a hospital in Mexico City at the time of follow-up consultation for hospitalized patients with pneumonia due to influenza virus infection. In all, 302 subjects were enrolled and divided into two groups based on the period of hospitalization. Among them, 211 tested positive for influenza A(H1N1)pdm09 virus by real-time reverse-transcriptase-polymerase-chain-reaction during the pandemic period (Group-pdm) and 91 tested positive for influenza A virus in the post-pandemic period (Group-post). All subjects were treated with oseltamivir. Data on the demographic characteristics, socioeconomic status, living environment, and information relating to A(H1N1)pdm09, and related clinical data were compared between subjects in Group-pdm and those in Group-post. The ability of household income to pay for utilities, food, and health care services as well as housing quality in terms of construction materials and number of rooms revealed a significant difference: Group-post had lower socioeconomic status than Group-pdm. Group-post had lower availability of information regarding H1N1 influenza than Group-pdm. These results indicate that subjects in Group-post had difficulty receiving necessary information relating to influenza and were more likely to be impoverished than those in Group-pdm. Possible factors influencing time to seeking health care were number of household rooms, having received information on the necessity of quick access to health care, and house construction materials. Conclusions Health-care-seeking behavior, poverty level, and the distribution of information affect the occurrence and severity of pneumonia due to H1N1 virus from a socioeconomic point of view. These

  6. A model survey for assessing 2009 pandemic influenza A (H1N1) virus disease burden in the workplace.

    PubMed

    Gindler, Jacqueline; Grohskopf, Lisa A; Biggerstaff, Matthew; Finelli, Lyn

    2011-01-01

    Emergence of 2009 pandemic influenza A (H1N1) (pH1N1) virus in 2009 raised concern about the potential impact of widespread or severe disease on the nation's workforce. The Centers for Disease Control and Prevention recommended that employers develop flexible pandemic response plans. We used the Behavioral Risk Factor Surveillance System's influenza module as a model for a brief workplace survey to ascertain the influenza-like illness (ILI) burden on epidemiology staff in Centers for Disease Control and Prevention Emergency Operations Center. Fifty-seven (78%) of 73 recipients completed the survey. Ten (18%) met the ILI case definition. The 10 respondent ILI cases missed 24 total work days, although none sought medical care. Eleven (14%) of 77 household contacts also had ILI, but no ILI case was hospitalized. This survey enabled us to rapidly obtain information about our workforce ILI burden and evaluate the potential need for additional resources because of employee absence.

  7. Unseasonal transmission of H3N2 influenza A virus during the swine-origin H1N1 pandemic.

    PubMed

    Ghedin, Elodie; Wentworth, David E; Halpin, Rebecca A; Lin, Xudong; Bera, Jayati; DePasse, Jay; Fitch, Adam; Griesemer, Sara; Hine, Erin; Katzel, Daniel A; Overton, Larry; Proudfoot, Kathleen; Sitz, Jeffrey; Szczypinski, Bridget; StGeorge, Kirsten; Spiro, David J; Holmes, Edward C

    2010-06-01

    The initial wave of swine-origin influenza A virus (pandemic H1N1/09) in the United States during the spring and summer of 2009 also resulted in an increased vigilance and sampling of seasonal influenza viruses (H1N1 and H3N2), even though they are normally characterized by very low incidence outside of the winter months. To explore the nature of virus evolution during this influenza "off-season," we conducted a phylogenetic analysis of H1N1 and H3N2 sequences sampled during April to June 2009 in New York State. Our analysis revealed that multiple lineages of both viruses were introduced and cocirculated during this time, as is typical of influenza virus during the winter. Strikingly, however, we also found strong evidence for the presence of a large transmission chain of H3N2 viruses centered on the south-east of New York State and which continued until at least 1 June 2009. These results suggest that the unseasonal transmission of influenza A viruses may be more widespread than is usually supposed.

  8. Rapid detection and differentiation of swine-origin influenza A virus (H1N1/2009) from other seasonal influenza A viruses.

    PubMed

    Zhao, Jiangqin; Wang, Xue; Ragupathy, Viswanath; Zhang, Panhe; Tang, Wei; Ye, Zhiping; Eichelberger, Maryna; Hewlett, Indira

    2012-11-09

    We previously developed a rapid and simple gold nanoparticle(NP)-based genomic microarray assay for identification of the avian H5N1 virus and its discrimination from other influenza A virus strains (H1N1, H3N2). In this study, we expanded the platform to detect the 2009 swine-origin influenza A virus (H1N1/2009). Multiple specific capture and intermediate oligonucleotides were designed for the matrix (M), hemagglutinin (HA), and neuraminidase (NA) genes of the H1N1/2009 virus. The H1N1/2009 microarrays were printed in the same format as those of the seasonal influenza H1N1 and H3N2 for the HA, NA, and M genes. Viral RNA was tested using capture-target-intermediate oligonucleotide hybridization and gold NP-mediated silver staining. The signal from the 4 capture-target-intermediates of the HA and NA genes was specific for H1N1/2009 virus and showed no cross hybridization with viral RNA from other influenza strains H1N1, H3N2, and H5N1. All of the 3 M gene captures showed strong affinity with H1N1/2009 viral RNA, with 2 out of the 3 M gene captures showing cross hybridization with the H1N1, H3N2, and H5N1 samples tested. The current assay was able to detect H1N1/2009 and distinguish it from other influenza A viruses. This new method may be useful for simultaneous detection and subtyping of influenza A viruses and can be rapidly modified to detect other emerging influenza strains in public health settings.

  9. The new pandemic influenza A/(H1N1)pdm09 virus: is it really "new"?

    PubMed

    Baldo, V; Bertoncello, C; Cocchio, S; Fonzo, M; Pillon, P; Buja, A; Baldovin, T

    2016-01-01

    In June 2009, the World Health Organization (WHO) issued a pandemic alert concerning the spread of an influenza A (H1N1) virus that showed distinctive genetic characteristics vis-à-vis both seasonal influenza strains and vaccine strains. The main mutation occurred in the gene coding for hemagglutinin (HA). Mathematical models were developed to calculate the transmissibility of the virus; the results indicated a significant overlap with the transmissibility of previous pandemic strains and seasonal strains. The remarkable feature of A/(H1N1)pdm09, compared with seasonal strains, is its high fatality rate and its higher incidence among younger people. Data provided by the WHO on the number of deaths caused by A/(H1N1)pdm09 only include laboratory-confirmed cases. Some authors suggest that these data could underestimate the magnitude of the event, as laboratory confirmation is not obtained in all cases. It is important to bear in mind that the A/(H1N1)pdm09 virus is still circulating in the population. It is therefore essential to maintain its epidemiological and virological surveillance. PMID:27346935

  10. Comparing Deaths from Influenza H1N1 and Seasonal Influenza A: Main Sociodemographic and Clinical Differences between the Most Prevalent 2009 Viruses

    PubMed Central

    Gutierrez, Juan Pablo

    2012-01-01

    Background. During the 2009 spring epidemic outbreak in Mexico, an important research and policy question faced was related to the differences in clinical profile and population characteristics of those affected by the new H1N1 virus compared with the seasonal virus. Methods and Findings. Data from clinical files from all influenza A deaths in Mexico between April 10 and July 13, 2009 were analyzed to describe differences in clinical and socioeconomic profile between H1N1 and non-H1N1 cases. A total of 324 influenza A mortality cases were studied of which 239 presented rt-PCR confirmation for H1N1 virus and 85 for seasonal influenza A. From the differences of means and multivariate logistic regression, it was found that H1N1 deaths occurred in younger and less educated people, and among those who engage in activities where there is increased contact with other unknown persons (OR 4.52, 95% CI 1.56–13.14). Clinical symptoms were similar except for dyspnea, headache, and chest pain that were less frequently found among H1N1 cases. Conclusions. Findings suggest that age, education, and occupation are factors that may be useful to identify risk for H1N1 among influenza cases, and also that patients with early dyspnea, headache, and chest pain are more likely to be non-H1N1 cases. PMID:23346393

  11. Risk of Guillain–Barré syndrome following pandemic influenza A(H1N1) 2009 vaccination in Germany†

    PubMed Central

    Prestel, Jürgen; Volkers, Peter; Mentzer, Dirk; Lehmann, Helmar C; Hartung, Hans-Peter; Keller-Stanislawski, Brigitte

    2014-01-01

    Purpose A prospective, epidemiologic study was conducted to assess whether the 2009 pandemic influenza A(H1N1) vaccination in Germany almost exclusively using an AS03-adjuvanted vaccine (Pandemrix) impacts the risk of Guillain–Barré syndrome (GBS) and its variant Fisher syndrome (FS). Methods Potential cases of GBS/FS were reported by 351 participating hospitals throughout Germany. The self-controlled case series methodology was applied to all GBS/FS cases fulfilling the Brighton Collaboration (BC) case definition (levels 1–3 of diagnostic certainty) with symptom onset between 1 November 2009 and 30 September 2010 reported until end of December 2010. Results Out of 676 GBS/FS reports, in 30 cases, GBS/FS (BC levels 1–3) occurred within 150 days following influenza A(H1N1) vaccination. The relative incidence of GBS/FS within the primary risk period (days 5–42 post-vaccination) compared with the control period (days 43–150 post-vaccination) was 4.65 (95%CI [2.17, 9.98]). Similar results were found when stratifying for infections within 3 weeks prior to onset of GBS/FS and when excluding cases with additional seasonal influenza vaccination. The overall result of temporally adjusted analyses supported the primary finding of an increased relative incidence of GBS/FS following influenza A(H1N1) vaccination. Conclusions The results indicate an increased risk of GBS/FS in temporal association with pandemic influenza A(H1N1) vaccination in Germany. © 2014 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd. PMID:24817531

  12. Comparative virulence of wild-type H1N1pdm09 influenza A isolates in swine.

    PubMed

    Henningson, Jamie N; Rajao, Daniela S; Kitikoon, Pravina; Lorusso, Alessio; Culhane, Marie R; Lewis, Nicola S; Anderson, Tavis K; Vincent, Amy L

    2015-03-23

    In 2009, a novel swine-origin H1N1 (H1N1pdm09) influenza A virus (IAV) reached pandemic status and was soon after detected in pigs worldwide. The objective of this study was to evaluate whether differences in the HA protein can affect pathogenicity and antigenicity of H1N1pdm09 in swine. We compared lung pathology, viral replication and shedding and the antigenic relationships of four wild-type H1N1pdm09 viruses in pigs: one human (CA/09) and three isolated in swine after the pandemic (IL/09, IL/10, and MN/10). The swine strains were selected based upon unique amino acid substitutions in the HA protein. All selected viruses resulted in mild disease and viral shedding through nasal and oral fluids, however, viral replication and the degree of pathology varied between the isolates. A/Swine/IL/5265/2010 (IL/10), with substitutions I120M, S146G, S186P, V252M, had lower viral titers in the lungs and nasal secretions and fewer lung lesions. The other two swine viruses caused respiratory pathology and replicated to titers similar to the human CA/09, although MN/10 (with mutations D45Y, K304E, A425S) had lower nasal shedding. Swine-adapted H1N1pdm09 have zoonotic potential, and have reassorted with other co-circulating swine viruses, influencing the evolution of IAV in swine globally. Further, our results suggest that amino acid changes in the HA gene have the potential to alter the virulence of H1N1pdm09 in swine. Importantly, the limited clinical signs in pigs could result in continued circulation of these viruses with other endemic swine IAVs providing opportunities for reassortment.

  13. Novel swine-origin influenza virus A (H1N1): the first pandemic of the 21st century.

    PubMed

    Chang, Luan-Yin; Shih, Shin-Ru; Shao, Pei-Lan; Huang, Daniel Tsung-Ning; Huang, Li-Min

    2009-07-01

    An influenza epidemic was detected in April 2009 at the border between the United States and Mexico. The virus was identified soon after to be a swine-origin influenza virus A (S-OIV A) (H1N1). This virus has an HA gene that is derived from the 1918 swine influenza virus and other genes from human, avian, and Eurasian swine influenza viruses. Clinically, it behaves similarly to seasonal influenza. The only differentiating characteristics are vomiting and diarrhea in a quarter of infected patients, which are rare in seasonal influenza. On June 11, 2009, the World Health Organization declared the first pandemic of the 21st century, caused by S-OIV A (H1N1). Vaccination is the only way to dampen this pandemic. Many questions await answers, including the clinical impact of the pandemic, optimal doses of vaccine, and the future destiny of the virus. A breakthrough in vaccinology against influenza is needed to address the recurring influenza pandemic.

  14. Characterization of an artificial swine-origin influenza virus with the same gene combination as H1N1/2009 virus: a genesis clue of pandemic strain.

    PubMed

    Zhao, Xueli; Sun, Yipeng; Pu, Juan; Fan, Lihong; Shi, Weimin; Hu, Yanxin; Yang, Jun; Xu, Qi; Wang, Jingjing; Hou, Dongjun; Ma, Guangpeng; Liu, Jinhua

    2011-01-01

    Pandemic H1N1/2009 influenza virus, derived from a reassortment of avian, human, and swine influenza viruses, possesses a unique gene segment combination that had not been detected previously in animal and human populations. Whether such a gene combination could result in the pathogenicity and transmission as H1N1/2009 virus remains unclear. In the present study, we used reverse genetics to construct a reassortant virus (rH1N1) with the same gene combination as H1N1/2009 virus (NA and M genes from a Eurasian avian-like H1N1 swine virus and another six genes from a North American triple-reassortant H1N2 swine virus). Characterization of rH1N1 in mice showed that this virus had higher replicability and pathogenicity than those of the seasonal human H1N1 and Eurasian avian-like swine H1N1 viruses, but was similar to the H1N1/2009 and triple-reassortant H1N2 viruses. Experiments performed on guinea pigs showed that rH1N1 was not transmissible, whereas pandemic H1N1/2009 displayed efficient transmissibility. To further determine which gene segment played a key role in transmissibility, we constructed a series of reassortants derived from rH1N1 and H1N1/2009 viruses. Direct contact transmission studies demonstrated that the HA and NS genes contributed to the transmission of H1N1/2009 virus. Second, the HA gene of H1N1/2009 virus, when combined with the H1N1/2009 NA gene, conferred efficient contact transmission among guinea pigs. The present results reveal that not only gene segment reassortment but also amino acid mutation were needed for the generation of the pandemic influenza virus.

  15. Diversity of the murine antibody response targeting influenza A(H1N1pdm09) hemagglutinin

    PubMed Central

    Wilson, Jason R.; Tzeng, Wen-Pin; Spesock, April; Music, Nedzad; Guo, Zhu; Barrington, Robert; Stevens, James; Donis, Ruben O.; Katz, Jacqueline M.; York, Ian A.

    2016-01-01

    We infected mice with the 2009 influenza A pandemic virus (H1N1pdm09), boosted with an inactivated vaccine, and cloned immunoglobulins (Igs) from HA-specific B cells. Based on the redundancy in germline gene utilization, we inferred that between 72–130 unique IgH VDJ and 35 different IgL VJ combinations comprised the anti-HA recall response. The IgH VH1 and IgL VK14 variable gene families were employed most frequently. A representative panel of antibodies were cloned and expressed to confirm reactivity with H1N1pdm09 HA. The majority of the recombinant antibodies were of high avidity and capable of inhibiting H1N1pdm09 hemagglutination. Three of these antibodies were subtype-specific cross-reactive, binding to the HA of A/South Carolina/1/1918(H1N1), and one further reacted with A/swine/Iowa/15/1930(H1N1). These results help define the genetic diversity of the influenza anti-HA antibody repertoire profile induced following infection and vaccination, which may facilitate the development of influenza vaccines that are more protective and broadly neutralizing. Importance Protection against influenza viruses is mediated mainly by antibodies, and in most cases this antibody response is narrow, only providing protection against closely-related viruses. In spite of this limited range of protection, recent findings indicate individuals immune to one influenza virus may contain antibodies (generally a minority of the overall response) that are more broadly reactive. These findings have raised the possibility that influenza vaccines could induce a more broadly protective response, reducing the need for frequent vaccine strain changes. However, interpretation of these observations is hampered by the lack of quantitative characterization of the antibody repertoire. In this study, we used single-cell cloning of influenza HA-specific B cells to assess the diversity and nature of the antibody response to influenza hemagglutinin in mice. Our findings help put bounds on the

  16. H1N1 influenza: the trigger of diabetic ketoacidosis in a young woman with ketosis-prone diabetes.

    PubMed

    Tan, Huiwen; Wang, Chun; Yu, Yerong

    2012-02-01

    In this study, the authors report a case of new-onset ketosis-prone diabetes in a 21-year-old Chinese woman with H1N1 influenza, who presented with fever, polyuria and loss of appetite for 3 days before admission. She was hospitalized and diagnosed with acute-onset diabetic ketoacidosis for the first time. Her diabetes-associated antibodies were negative. Interestingly, she had an unexplained fever and her white blood cell count was low at admission and remained low for several days. She was believed to have a viral infection, which was found to be H1N1 influenza infection. The literature regarding virus infection and diabetic ketoacidosis is reviewed. The precipitating factors, symptomatology, pathophysiology and management of ketosis-prone diabetes are discussed in the current case report.

  17. Quantitative detection of Staphylococcus aureus, Streptococcus pneumoniae and Haemophilus influenzae in patients with new influenza A (H1N1)/2009 and influenza A/2010 virus infection

    PubMed Central

    Safaeyan, Firouzeh; Nahaei, Mohammad Reza; Seifi, Sirus Jedary; Kafil, Hossein Samadi; Sadeghi, Javid

    2015-01-01

    Introduction: Viral influenza is a seasonal infection associated with significant morbidity and mortality. In the United States more than 35,000 deaths and 200,000 hospitalizations are recorded annually due to influenza. Secondary bacterial infections or co-infections associated with cases of influenza are a leading cause of severe morbidity and mortality, especially among high-risk groups such as the elderly and young children. Aim: The aim of the present study was the quantitative detection of S. aureus, S. pneumoniae and H. influenzae in a group of patients with seasonal influenza A, influenza A (H1N1) pandemic 2009, and patients with symptoms of respiratory infection, but the negative for H1N1 serving as control group. Method: In total, 625 patients suspected respiratory infection from April 2009 to April 2010 were studied. There were 58 patients with influenza A H1N1 and 567 patients negative for influenza A H1N1. From November 2010 to February 2011, 158 patients with respiratory symptoms were analyzed for seasonal influenza A. There were 25 patients with seasonal influenza A. To check the colonization status among the healthy individuals 62 healthy persons were further investigated. Individual were screened in parallel. The choices of special genes were amplified from clinical specimens using real-time PCR with a cutoff of 104 CFU/mL to differentiate colonization from infection in respiratory tract. Results: S. aureus, S. pneumoniae and H. influenzae were detected in 12%, 26% and 33% of patients with H1N1, while the corresponding figures were 9%, 19%, and 31% for H1N1 negative patients. Among patients with seasonal influenza A 12% S. aureus, 24% S. pneumoniae, and 32% H. influenzae co-infections were detected, while influenza negative control group yielded 5% S. aureus, 11% S. pneumoniae, and 10% H. influenzae, respectively. Conclusion: The results of this study indicated that the serotype of pandemic H1N1 2009 did not increase incidence of secondary

  18. Rapid research response to the 2009 A(H1N1)pdm09 influenza pandemic (Revised)

    PubMed Central

    2013-01-01

    Background When novel influenza viruses cause human infections, it is critical to characterize the illnesses, viruses, and immune responses to infection in order to develop diagnostics, treatments, and vaccines. The objective of the study was to collect samples from patients with suspected or confirmed A(H1N1)pdm09 infections that could be made available to the scientific community. Respiratory secretions, sera and peripheral blood mononuclear cells (PBMCs) were collected sequentially (when possible) from patients presenting with suspected or previously confirmed A(H1N1)pdm09 infections. Clinical manifestations and illness outcomes were assessed. Respiratory secretions were tested for the presence of A(H1N1)pdm09 virus by means of isolation in tissue culture and real time RT-PCR. Sera were tested for the presence and level of HAI and neutralizing antibodies against the A(H1N1)pdm09 virus. Findings and conclusions Thirty patients with confirmed A(H1N1)pdm09 infection were enrolled at Baylor College of Medicine (BCM). Clinical manifestations of illness were consistent with typical influenza. Twenty-eight of 30 had virological confirmation of illness; all recovered fully. Most patients had serum antibody responses or high levels of antibody in convalescent samples. Virus-positive samples were sent to J. Craig Venter Institute for sequencing and sequences were deposited in GenBank. Large volumes of sera collected from 2 convalescent adults were used to standardize antibody assays; aliquots of these sera are available from the repository. Aliquots of serum, PBMCs and stool collected from BCM subjects and subjects enrolled at other study sites are available for use by the scientific community, upon request. PMID:23641940

  19. Prospective cohort study of the safety of an influenza A(H1N1) vaccine in pregnant Chinese women.

    PubMed

    Ma, Fubao; Zhang, Longhua; Jiang, Renjie; Zhang, Jinlin; Wang, Huaqing; Gao, Xiaozhi; Li, Xiuhong; Liu, Yuanbao

    2014-09-01

    To monitor and evaluate the safety of the influenza A(H1N1) vaccine in pregnant women and its influence on the fetus and neonate, we performed a prospective study in which 122 pregnant Chinese women who received the influenza A(H1N1) vaccine and 104 pregnant women who did not receive any vaccine (serving as controls) were observed. The results indicated that the seroconversion rate in the vaccinated group was 90.4% (95% confidence interval [CI], 82.6% to 95.5%). The rate of adverse events following immunization in the pregnant women who received the influenza A(H1N1) vaccine was 3.3%. The spontaneous abortion rates in the vaccinated group and the unvaccinated group were 0.8% and 1.9%, respectively (exact probability test, P = 0.470), the prolonged-pregnancy rates were 8.2% and 4.8%, respectively (χ(2) = 1.041, P = 0.308), the low-birth-weight rates were 1.6% and 0.95%, respectively (exact probability test, P = 1.000), and the spontaneous-labor rates were 70.5% and 75%, respectively (χ(2) = 0.573, P = 0.449). All newborns who have an Apgar score of ≥7 are considered healthy; Apgar scores of ≥9 were observed in 38.5% and 57.7% of newborns in the vaccinated group and the unvaccinated group, respectively (χ(2) = 8.274, P = 0.004). From these results, we conclude that the influenza A(H1N1) vaccine is safe for pregnant women and has no observed adverse effects on fetal growth. (This study has been registered at ClinicalTrials.gov under registration no. NCT01842997.).

  20. Inefficient control of host gene expression by the 2009 pandemic H1N1 influenza A virus NS1 protein.

    PubMed

    Hale, Benjamin G; Steel, John; Medina, Rafael A; Manicassamy, Balaji; Ye, Jianqiang; Hickman, Danielle; Hai, Rong; Schmolke, Mirco; Lowen, Anice C; Perez, Daniel R; García-Sastre, Adolfo

    2010-07-01

    In 2009, a novel swine-origin H1N1 influenza A virus emerged. Here, we characterize the multifunctional NS1 protein of this human pandemic virus in order to understand factors that may contribute to replication efficiency or pathogenicity. Although the 2009 H1N1 virus NS1 protein (2009/NS1) is an effective interferon antagonist, we found that this NS1 (unlike those of previous human-adapted influenza A viruses) is unable to block general host gene expression in human or swine cells. This property could be restored in 2009/NS1 by replacing R108, E125, and G189 with residues corresponding to human virus consensus. Mechanistically, these previously undescribed mutations acted by increasing binding of 2009/NS1 to the cellular pre-mRNA processing protein CPSF30. A recombinant 2009 H1N1 influenza A virus (A/California/04/09) expressing NS1 with these gain-of-function substitutions was more efficient than the wild type at antagonizing host innate immune responses in primary human epithelial cells. However, such mutations had no significant effect on virus replication in either human or swine tissue culture substrates. Surprisingly, in a mouse model of pathogenicity, the mutant virus appeared to cause less morbidity, and was cleared faster, than the wild type. The mutant virus also demonstrated reduced titers in the upper respiratory tracts of ferrets; however, contact and aerosol transmissibility of the virus was unaffected. Our data highlight a potential human adaptation of NS1 that seems absent in "classically derived" swine-origin influenza A viruses, including the 2009 H1N1 virus. We discuss the impact that a natural future gain of this NS1 function may have on the new pandemic virus in humans.

  1. Novel reassortant influenza viruses between pandemic (H1N1) 2009 and other influenza viruses pose a risk to public health.

    PubMed

    Kong, Weili; Wang, Feibing; Dong, Bin; Ou, Changbo; Meng, Demei; Liu, Jinhua; Fan, Zhen-Chuan

    2015-12-01

    Influenza A virus (IAV) is characterized by eight single-stranded, negative sense RNA segments, which allows for gene reassortment among different IAV subtypes when they co-infect a single host cell simultaneously. Genetic reassortment is an important way to favor the evolution of influenza virus. Novel reassortant virus may pose a pandemic among humans. In history, three human pandemic influenza viruses were caused by genetic reassortment between avian, human and swine influenza viruses. Since 2009, pandemic (H1N1) 2009 (pdm/09 H1N1) influenza virus composed of two swine influenza virus genes highlighted the genetic reassortment again. Due to wide host species and high transmission of the pdm/09 H1N1 influenza virus, many different avian, human or swine influenza virus subtypes may reassert with it to generate novel reassortant viruses, which may result in a next pandemic among humans. So, it is necessary to understand the potential threat of current reassortant viruses between the pdm/09 H1N1 and other influenza viruses to public health. This study summarized the status of the reassortant viruses between the pdm/09 H1N1 and other influenza viruses of different species origins in natural and experimental conditions. The aim of this summarization is to facilitate us to further understand the potential threats of novel reassortant influenza viruses to public health and to make effective prevention and control strategies for these pathogens. PMID:26344393

  2. Novel reassortant influenza viruses between pandemic (H1N1) 2009 and other influenza viruses pose a risk to public health.

    PubMed

    Kong, Weili; Wang, Feibing; Dong, Bin; Ou, Changbo; Meng, Demei; Liu, Jinhua; Fan, Zhen-Chuan

    2015-12-01

    Influenza A virus (IAV) is characterized by eight single-stranded, negative sense RNA segments, which allows for gene reassortment among different IAV subtypes when they co-infect a single host cell simultaneously. Genetic reassortment is an important way to favor the evolution of influenza virus. Novel reassortant virus may pose a pandemic among humans. In history, three human pandemic influenza viruses were caused by genetic reassortment between avian, human and swine influenza viruses. Since 2009, pandemic (H1N1) 2009 (pdm/09 H1N1) influenza virus composed of two swine influenza virus genes highlighted the genetic reassortment again. Due to wide host species and high transmission of the pdm/09 H1N1 influenza virus, many different avian, human or swine influenza virus subtypes may reassert with it to generate novel reassortant viruses, which may result in a next pandemic among humans. So, it is necessary to understand the potential threat of current reassortant viruses between the pdm/09 H1N1 and other influenza viruses to public health. This study summarized the status of the reassortant viruses between the pdm/09 H1N1 and other influenza viruses of different species origins in natural and experimental conditions. The aim of this summarization is to facilitate us to further understand the potential threats of novel reassortant influenza viruses to public health and to make effective prevention and control strategies for these pathogens.

  3. TGF-β Blood Levels Distinguish Between Influenza A (H1N1)pdm09 Virus Sepsis and Sepsis due to Other Forms of Community-Acquired Pneumonia.

    PubMed

    Rendón-Ramirez, Erick J; Ortiz-Stern, Alejandro; Martinez-Mejia, Corazon; Salinas-Carmona, Mario C; Rendon, Adrian; Mata-Tijerina, Viviana L; Rosas-Taraco, Adrian G

    2015-06-01

    There is a strong interest in finding adequate biomarkers to aid in the diagnosis and prognosis of influenza A (H1N1)pdm09 virus infection. In this study, serum levels of inflammatory cytokines and laboratory markers were evaluated to assess their usefulness as biomarkers of influenza A (H1N1)pdm09 and their association with fatal cases. Serum samples of consecutive patients with a clinical presentation suggestive of influenza A (H1N1)pdm09 and progression to sepsis were evaluated. Serum inflammatory cytokines and routine laboratory tests were performed and correlated with positivity for influenza A (H1N1)pdm09 influenza by real time reverse transcription polymerase chain reaction and the results of three clinical severity scores (Sequential Organ Failure Assessment [SOFA], CURB-65, and Acute Physiology and Chronic Health Evaluation II [APACHE II]). High SOFA scores and some of its individual components, but not CURB-65 or APACHE II scores, correlate with fatal cases regardless of etiology. Total and unconjugated bilirubin, Ca(++), Cl(-), prothrombin times, and partial thromboplastin times discriminate influenza A (H1N1)pdm09 from other causes of community-acquired pneumonia. High levels of IL-8, IL-10, and IL-17 were increased in influenza A (H1N1)pdm09 patients when compared with controls (p<0.05). IL-6 levels were significantly elevated in influenza A (H1N1)pdm09 patients and non-(H1N1)pdm09 patients when compared with controls (p<0.05). TGF-β serum levels discern between healthy controls, influenza A (H1N1)pdm09 patients, and patients with other causes of community-acquired pneumonia. TGF-β levels were negatively correlated with SOFA on admission in influenza A (H1N1)pdm09 patients. TGF-β levels are a useful tool for differentiating influenza A (H1N1)pdm09 from other causes of pneumonia progressing to sepsis.

  4. Specific Inhibitory Effect of κ-Carrageenan Polysaccharide on Swine Pandemic 2009 H1N1 Influenza Virus.

    PubMed

    Shao, Qiang; Guo, Qiang; Xu, Wen ping; Li, Zandong; Zhao, Tong tong

    2015-01-01

    The 2009 influenza A H1N1 pandemic placed unprecedented demands on antiviral drug resources and the vaccine industry. Carrageenan, an extractive of red algae, has been proven to inhibit infection and multiplication of various enveloped viruses. The aim of this study was to examine the ability of κ-carrageenan to inhibit swine pandemic 2009 H1N1 influenza virus to gain an understanding of antiviral ability of κ-carrageenan. It was here demonstrated that κ-carrageenan had no cytotoxicity at concentrations below 1000 μg/ml. Hemagglutination, 50% tissue culture infectious dose (TCID50) and cytopathic effect (CPE) inhibition assays showed that κ-carrageenan inhibited A/Swine/Shandong/731/2009 H1N1 (SW731) and A/California/04/2009 H1N1 (CA04) replication in a dose-dependent fashion. Mechanism studies show that the inhibition of SW731 multiplication and mRNA expression was maximized when κ-carrageenan was added before or during adsorption. The result of Hemagglutination inhibition assay indicate that κ-carrageenan specifically targeted HA of SW731 and CA04, both of which are pandemic H1N/2009 viruses, without effect on A/Pureto Rico/8/34 H1N1 (PR8), A/WSN/1933 H1N1 (WSN), A/Swine/Beijing/26/2008 H1N1 (SW26), A/Chicken/Shandong/LY/2008 H9N2 (LY08), and A/Chicken/Shandong/ZB/2007 H9N2 (ZB07) viruses. Immunofluorescence assay and Western blot showed that κ-carrageenan also inhibited SW731 protein expression after its internalization into cells. These results suggest that κ-carrageenan can significantly inhibit SW731 replication by interfering with a few replication steps in the SW731 life cycles, including adsorption, transcription, and viral protein expression, especially interactions between HA and cells. In this way, κ-carrageenan might be a suitable alternative approach to therapy meant to address anti-IAV, which contains an HA homologous to that of SW731.

  5. Evolutionary Dynamics of Local Pandemic H1N1/2009 Influenza Virus Lineages Revealed by Whole-Genome Analysis

    PubMed Central

    Baillie, Gregory J.; Galiano, Monica; Agapow, Paul-Michael; Myers, Richard; Chiam, Rachael; Gall, Astrid; Palser, Anne L.; Watson, Simon J.; Hedge, Jessica; Underwood, Anthony; Platt, Steven; McLean, Estelle; Pebody, Richard G.; Rambaut, Andrew; Green, Jonathan; Daniels, Rod; Pybus, Oliver G.; Zambon, Maria

    2012-01-01

    Virus gene sequencing and phylogenetics can be used to study the epidemiological dynamics of rapidly evolving viruses. With complete genome data, it becomes possible to identify and trace individual transmission chains of viruses such as influenza virus during the course of an epidemic. Here we sequenced 153 pandemic influenza H1N1/09 virus genomes from United Kingdom isolates from the first (127 isolates) and second (26 isolates) waves of the 2009 pandemic and used their sequences, dates of isolation, and geographical locations to infer the genetic epidemiology of the epidemic in the United Kingdom. We demonstrate that the epidemic in the United Kingdom was composed of many cocirculating lineages, among which at least 13 were exclusively or predominantly United Kingdom clusters. The estimated divergence times of two of the clusters predate the detection of pandemic H1N1/09 virus in the United Kingdom, suggesting that the pandemic H1N1/09 virus was already circulating in the United Kingdom before the first clinical case. Crucially, three clusters contain isolates from the second wave of infections in the United Kingdom, two of which represent chains of transmission that appear to have persisted within the United Kingdom between the first and second waves. This demonstrates that whole-genome analysis can track in fine detail the behavior of individual influenza virus lineages during the course of a single epidemic or pandemic. PMID:22013031

  6. New genetic variants of influenza A(H1N1)pdm09 detected in Cuba during 2011-2013.

    PubMed

    Arencibia, Amely; Acosta, Belsy; Muné, Mayra; Valdés, Odalys; Fernandez, Leandro; Medina, Isel; Savón, Clara; Oropesa, Suset; Gonzalez, Grehete; Roque, Rosmery; Gonzalez, Guelsys; Hernández, Bárbara; Goyenechea, Angel; Piñón, Alexander

    2015-06-01

    Influenza A(H1N1)pdm09 virus has evolved continually since its emergence in 2009. For influenza virus strains, genetic changes occurring in HA1 domain of the hemagglutinin cause the emergence of new variants. The aim of our study is to establish genetic associations between 35 A(H1N1)pdm09 viruses circulating in Cuba in 2011-2012 and 2012-2013 seasons, and A/California/07/2009 strain recommended by WHO as the H1N1 component of the influenza vaccine. The phylogenetic analysis revealed the circulation of clades 3, 6A, 6B, 6C and 7. Mutations were detected in the antigenic site or in the receptor-binding domains of HA1 segment, including S174P, S179N, K180Q, S202T, S220T and R222K. Substitutions S174P, S179N, K180Q and R222K were detected in Cuban strains for the first time.

  7. Acute phase protein response during subclinical infection of pigs with H1N1 swine influenza virus.

    PubMed

    Pomorska-Mól, Małgorzata; Markowska-Daniel, Iwona; Pejsak, Zygmunt

    2012-10-12

    In the present study acute phase proteins (APPs) responses in pigs after subclinical infection with H1N1 swine influenza virus (SwH1N1) were evaluated. Fourteen 5 weeks old, seronegative piglets, both sexes were used. Ten of them were infected intranasally with SwH1N1. C-reactive protein (CRP), haptoglobin (Hp), serum amyloid A (SAA) and pig major acute phase protein (Pig-MAP) concentrations in serum were measured using commercial ELISAs. No significant clinical signs were observed in any of the infected pigs, however, all infected animals developed specific antibodies against SwH1N1 and viral shedding was observed from 2 to 5 dpi. Only concentrations of Hp and SAA were significantly induced after infection, with mean maximum levels from days 1 to 2 post infection (dpi). The concentrations of CRP and Pig-MAP remained generally unchanged, however in half of infected pigs the concentration of CRP tended to increase at 1 dpi (but without statistical significance). The results of our study confirmed that monitoring of APPs may be useful for detection of subclinically infected pigs. The use of SAA or Hp and Pig-MAP may be a valuable in combination [i.e. Hp (increased concentration) and Pig-MAP (unchanged concentration)] to detect subclinically SIV infected pigs, or to identify pigs actually producing a large amount of virus. Additional studies need to be done in order to confirm these findings.

  8. Fever screening during the influenza (H1N1-2009) pandemic at Narita International Airport, Japan

    PubMed Central

    2011-01-01

    Background Entry screening tends to start with a search for febrile international passengers, and infrared thermoscanners have been employed for fever screening in Japan. We aimed to retrospectively assess the feasibility of detecting influenza cases based on fever screening as a sole measure. Methods Two datasets were collected at Narita International Airport during the 2009 pandemic. The first contained confirmed influenza cases (n = 16) whose diagnosis took place at the airport during the early stages of the pandemic, and the second contained a selected and suspected fraction of passengers (self-reported or detected by an infrared thermoscanner; n = 1,049) screened from September 2009 to January 2010. The sensitivity of fever (38.0°C) for detecting H1N1-2009 was estimated, and the diagnostic performances of the infrared thermoscanners in detecting hyperthermia at cut-off levels of 37.5°C, 38.0°C and 38.5°C were also estimated. Results The sensitivity of fever for detecting H1N1-2009 cases upon arrival was estimated to be 22.2% (95% confidence interval: 0, 55.6) among nine confirmed H1N1-2009 cases, and 55.6% of the H1N1-2009 cases were under antipyretic medications upon arrival. The sensitivity and specificity of the infrared thermoscanners in detecting hyperthermia ranged from 50.8-70.4% and 63.6-81.7%, respectively. The positive predictive value appeared to be as low as 37.3-68.0%. Conclusions The sensitivity of entry screening is a product of the sensitivity of fever for detecting influenza cases and the sensitivity of the infrared thermoscanners in detecting fever. Given the additional presence of confounding factors and unrestricted medications among passengers, reliance on fever alone is unlikely to be feasible as an entry screening measure. PMID:21539735

  9. Efficacy of Influenza A H1N1/2009 Vaccine in Hemodialysis and Kidney Transplant Patients

    PubMed Central

    Collado, Silvia; Mir, Marisa; Cao, Higini; Barbosa, Francesc; Serra, Consol; Hidalgo, Carlota; Faura, Anna; Montero, Milagros; García de Lomas, Juan; Horcajada, Juan P.; Puig, Josep M.; Pascual, Julio

    2011-01-01

    Summary Background and objectives Data are needed to assess safety and efficacy of the 2009 pandemic influenza A H1N1 vaccine in renal patients. Design, setting, participants, & measurements We prospectively evaluated seroconversion, predictors of response, and vaccine safety in renal patients. Hemagglutination inhibition tests to detect serum antibodies against a new influenza A-H1N1 virus were performed in 79 transplant patients, 48 hemodialysis patients, and 15 healthy workers before and 1 month after vaccination. Healthy controls and 88 of 127 renal patients were vaccinated. Seroconversion was defined as at least 2 dilutions increase in titer. Results We excluded 19 individuals seroprotected (≥1/40) against the novel H1N1 in the initial sample. Efficacy rate in the 96 vaccinated individuals was 43.7% (42 of 96 seroconverted versus four of 27 nonvaccinated patients, P = 0.007). For vaccinated subgroups, efficacy was 41.8% in transplant patients (P = 0.039 versus nonvaccinated), 33.3% in hemodialysis patients (P = 0.450), and 81.8% in controls. Healthy controls showed better response to vaccine than transplant (P = 0.021) and dialysis (P = 0.012) patients. For the transplant subgroup, longer time after transplantation (P = 0.028) was associated with seroconversion, but no influence was found for age, gender, renal function, or immunosuppression. In the hemodialysis subgroup, younger age was associated with response (55.7 ± 20.8 versus 71.6 ± 10.1 years, P = 0.042), but other specific variables, including Kt/V or time on dialysis, were not. No serious adverse events were reported, and kidney function was stable. Conclusion The novel influenza A 2009 H1N1 vaccine was safe in renal patients, although administration of a single dose of adjuvanted vaccine induced a poor response in these patients. PMID:21852661

  10. Transmission Characteristics of the 2009 H1N1 Influenza Pandemic: Comparison of 8 Southern Hemisphere Countries

    PubMed Central

    Opatowski, Lulla; Fraser, Christophe; Griffin, Jamie; de Silva, Eric; Van Kerkhove, Maria D.; Lyons, Emily J.; Cauchemez, Simon; Ferguson, Neil M.

    2011-01-01

    While in Northern hemisphere countries, the pandemic H1N1 virus (H1N1pdm) was introduced outside of the typical influenza season, Southern hemisphere countries experienced a single wave of transmission during their 2009 winter season. This provides a unique opportunity to compare the spread of a single virus in different countries and study the factors influencing its transmission. Here, we estimate and compare transmission characteristics of H1N1pdm for eight Southern hemisphere countries/states: Argentina, Australia, Bolivia, Brazil, Chile, New Zealand, South Africa and Victoria (Australia). Weekly incidence of cases and age-distribution of cumulative cases were extracted from public reports of countries' surveillance systems. Estimates of the reproduction numbers, R0, empirically derived from the country-epidemics' early exponential phase, were positively associated with the proportion of children in the populations (p = 0.004). To explore the role of demography in explaining differences in transmission intensity, we then fitted a dynamic age-structured model of influenza transmission to available incidence data for each country independently, and for all the countries simultaneously. Posterior median estimates of R0 ranged 1.2–1.8 for the country-specific fits, and 1.29–1.47 for the global fits. Corresponding estimates for overall attack-rate were in the range 20–50%. All model fits indicated a significant decrease in susceptibility to infection with age. These results confirm the transmissibility of the 2009 H1N1 pandemic virus was relatively low compared with past pandemics. The pattern of age-dependent susceptibility found confirms that older populations had substantial – though partial - pre-existing immunity, presumably due to exposure to heterologous influenza strains. Our analysis indicates that between-country-differences in transmission were at least partly due to differences in population demography. PMID:21909272

  11. Pre-existing immunity against swine-origin H1N1 influenza viruses in the general human population

    PubMed Central

    Greenbaum, Jason A.; Kotturi, Maya F.; Kim, Yohan; Oseroff, Carla; Vaughan, Kerrie; Salimi, Nima; Vita, Randi; Ponomarenko, Julia; Scheuermann, Richard H.; Sette, Alessandro; Peters, Bjoern

    2009-01-01

    A major concern about the ongoing swine-origin H1N1 influenza virus (S-OIV) outbreak is that the virus may be so different from seasonal H1N1 that little immune protection exists in the human population. In this study, we examined the molecular basis for pre-existing immunity against S-OIV, namely the recognition of viral immune epitopes by T cells or B cells/antibodies that have been previously primed by circulating influenza strains. Using data from the Immune Epitope Database, we found that only 31% (8/26) of B-cell epitopes present in recently circulating H1N1 strains are conserved in the S-OIV, with only 17% (1/6) conserved in the hemagglutinin (HA) and neuraminidase (NA) surface proteins. In contrast, 69% (54/78) of the epitopes recognized by CD8+ T cells are completely invariant. We further demonstrate experimentally that some memory T-cell immunity against S-OIV is present in the adult population and that such memory is of similar magnitude as the pre-existing memory against seasonal H1N1 influenza. Because protection from infection is antibody mediated, a new vaccine based on the specific S-OIV HA and NA proteins is likely to be required to prevent infection. However, T cells are known to blunt disease severity. Therefore, the conservation of a large fraction of T-cell epitopes suggests that the severity of an S-OIV infection, as far as it is determined by susceptibility of the virus to immune attack, would not differ much from that of seasonal flu. These results are consistent with reports about disease incidence, severity, and mortality rates associated with human S-OIV. PMID:19918065

  12. Productive Infection of Human Skeletal Muscle Cells by Pandemic and Seasonal Influenza A(H1N1) Viruses

    PubMed Central

    Desdouits, Marion; Munier, Sandie; Prevost, Marie-Christine; Jeannin, Patricia; Butler-Browne, Gillian; Ozden, Simona; Gessain, Antoine; Van Der Werf, Sylvie; Naffakh, Nadia; Ceccaldi, Pierre-Emmanuel

    2013-01-01

    Besides the classical respiratory and systemic symptoms, unusual complications of influenza A infection in humans involve the skeletal muscles. Numerous cases of acute myopathy and/or rhabdomyolysis have been reported, particularly following the outbreak of pandemic influenza A(H1N1) in 2009. The pathogenesis of these influenza-associated myopathies (IAM) remains unkown, although the direct infection of muscle cells is suspected. Here, we studied the susceptibility of cultured human primary muscle cells to a 2009 pandemic and a 2008 seasonal influenza A(H1N1) isolate. Using cells from different donors, we found that differentiated muscle cells (i. e. myotubes) were highly susceptible to infection by both influenza A(H1N1) isolates, whereas undifferentiated cells (i. e. myoblasts) were partially resistant. The receptors for influenza viruses, α2-6 and α2-3 linked sialic acids, were detected on the surface of myotubes and myoblasts. Time line of viral nucleoprotein (NP) expression and nuclear export showed that the first steps of the viral replication cycle could take place in muscle cells. Infected myotubes and myoblasts exhibited budding virions and nuclear inclusions as observed by transmission electron microscopy and correlative light and electron microscopy. Myotubes, but not myoblasts, yielded infectious virus progeny that could further infect naive muscle cells after proteolytic treatment. Infection led to a cytopathic effect with the lysis of muscle cells, as characterized by the release of lactate dehydrogenase. The secretion of proinflammatory cytokines by muscle cells was not affected following infection. Our results are compatible with the hypothesis of a direct muscle infection causing rhabdomyolysis in IAM patients. PMID:24223983

  13. In vivo and in vitro studies on the antiviral activities of viperin against influenza H1N1 virus infection.

    PubMed

    Tan, Kai Sen; Olfat, Farzad; Phoon, Meng Chee; Hsu, Jung Pu; Howe, Josephine L C; Seet, Ju Ee; Chin, Keh Chuang; Chow, Vincent T K

    2012-06-01

    Influenza A virus has caused a number of pandemics in past decades, including the recent H1N1-2009 pandemic. Viperin is an interferon (IFN)-inducible protein of innate immunity, and acts as a broad-spectrum antiviral protein. We explored the antiviral activities and mechanisms of viperin during influenza virus (IFV) infection in vitro and in vivo. Wild-type (WT) HeLa and viperin-expressing HeLa cells were infected with influenza A/WSN/33/H1N1 (WSN33) virus, and subjected to virological, light and electron microscopic analyses. Viperin expression reduced virus replication and titres, and restricted viral budding. Young and old viperin-knockout (KO) mice and WT control animals were challenged with influenza WSN33 at lethal doses of 10(3) and 10(4) p.f.u. via the intratracheal route. Lungs were subjected to histopathological, virological and molecular studies. Upon lethal IFV challenge, both WT and KO mice revealed similar trends of infection and recovery with similar mortality rates. Viral quantification assay and histopathological evaluation of lungs from different time points showed no significant difference in viral loads and lung damage scores between the two groups of mice. Although the in vitro studies demonstrated the ability of viperin to restrict influenza H1N1 virus replication, the viperin-deficient mouse model indicated that absence of viperin enhanced neither the viral load nor pulmonary damage in the lungs of infected mice. This may be due to the compensation of IFN-stimulated genes in the lungs and/or the influenza non-structural protein 1-mediated IFN antagonism dampening the IFN response, thereby rendering the loss of viperin insignificant. Nevertheless, further investigations that exploit the antiviral mechanisms of viperin as prophylaxis are still warranted.

  14. [Measures taken by a university hospital for the prevention and control of the 2009 H1N1 influenza].

    PubMed

    Hayashi, Jun; Murata, Masayuki; Furusyo, Norihiro; Hoshina, Takayuki; Shimono, Nobuyuki

    2010-09-01

    After extensive discussion with the Fukuoka City government of measures for the prevention and control of the 2009 H1N1 influenza pandemic, Kyushu University Hospital organized the infection control teams of 39 hospitals in the Fukuoka City area in preparation for a possible outbreak. A facility was set up at Kyushu University Hospital for the screening of outpatients with fever, and those with influenza and an underlying disease or severe symptoms were admitted to the hospital. 37 (22%) of the 171 outpatients with fever were infected with the new strain of influenza, confirmed by rapid influenza antigen test and PCR: Of these 37 patients, 17 (45.9%) were negative by influenza antigen test. Other 37 patients (5 adults, 32 children) were admitted, all of whom were successfully treated with neuraminidase inhibitors and discharged with no aftereffects.

  15. Detection of swine-origin influenza A (H1N1) viruses using a paired surface plasma waves biosensor

    NASA Astrophysics Data System (ADS)

    Su, Li-Chen; Chang, Ying-Feng; Li, Ying-Chang; Hsieh, Jo-Ping; Lee, Cheng-Chung; Chou, Chien

    2010-08-01

    In order to enhance the sensitivity of conventional rapid test technique for the detection of swine-origin influenza A (H1N1) viruses (S-OIVs), we used a paired surface plasma waves biosensor (PSPWB) based on SPR in conjunction with an optical heterodyne technique. Experimentally, PSPWB showed a 125-fold improvement at least in the S-OIV detection as compared to conventional enzyme linked immunosorbent assay. Moreover, the detection limit of the PSPWB for the S-OIV detection was enhanced 250-fold in buffer at least in comparison with that of conventional rapid influenza diagnostic test.

  16. Structure and anti-influenza A (H1N1) virus activity of three polysaccharides from Eucheuma denticulatum

    NASA Astrophysics Data System (ADS)

    Yu, Guangli; Li, Miaomiao; Wang, Wei; Liu, Xin; Zhao, Xiaoliang; Lv, Youjing; Li, Guangsheng; Jiao, Guangling; Zhao, Xia

    2012-12-01

    Three polysaccharides (EW, EH and EA) were prepared from a red alga Eucheuma denticulatum by sequential extraction with cold water, hot water and sodium hydroxide water solution. Their monosaccharide compositions, relative molecular mass and structural characterization were determined by gas chromatography, high performance 1iquid chromatography, fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy methods. EW was hybrid ı/κ/ν-carrageenan (70 ı/17κ/13ν-carrabiose), EH was mainly ı-carrageenan, and EA was mainly α-1,4-Glucan (88%) but mixed with small amount of ı-carrageenan (12%). The relative molecular mass of EW, EH and EA was 480, 580 and 510 kDa, respectively. The anti-influenza A (H1N1) virus activity of these three polysaccharides was evaluated using the Madin-Darby canine kidney cells model. EW showed good anti-H1N1 virus activity, its IC50 was 276.5 μg mL-1, and the inhibition rate to H1N1 virus was 52% when its concentration was 250 μg mL-1. The IC50 of ı-carrageenan EH was 366.4 μg mL-1, whereas EA showed lower anti-H1N1 virus activity (IC50>430 μg mL-1). Available data obtained give positive evidence that the hybrid carrageenan EW from Eucheuma denticulatum can be used as potential anti-H1N1 virus inhibitor in future.

  17. Adverse events following influenza A (H1N1) 2009 monovalent vaccines reported to the Vaccine Adverse Event Reporting System, United States, October 1, 2009-January 31, 2010.

    PubMed

    Vellozzi, Claudia; Broder, Karen R; Haber, Penina; Guh, Alice; Nguyen, Michael; Cano, Maria; Lewis, Paige; McNeil, Michael M; Bryant, Marthe; Singleton, James; Martin, David; DeStefano, Frank

    2010-10-21

    The United States (US) influenza A (H1N1) 2009 monovalent (2009-H1N1) vaccination program began in October 2009. Reports to the vaccine adverse event reporting system (VAERS), a US spontaneous reporting system, were reviewed to identify potential rare events or unusual adverse event (AE) patterns after 2009-H1N1 vaccination. The adverse event profile after 2009-H1N1 vaccine in VAERS (∼10,000 reports) was consistent with that of seasonal influenza vaccines, although the reporting rate was higher after 2009-H1N1 than seasonal influenza vaccines, this may be, at least in part, a reflection of stimulated reporting. Death, Guillain-Barré syndrome and anaphylaxis reports after 2009-H1N1 vaccination were rare (each <2 per million doses administered).

  18. Pathogenicity and transmissibility of reassortant H9 influenza viruses with genes from pandemic H1N1 virus.

    PubMed

    Qiao, Chuanling; Liu, Qinfang; Bawa, Bhupinder; Shen, Huigang; Qi, Wenbao; Chen, Ying; Mok, Chris Ka Pun; García-Sastre, Adolfo; Richt, Jürgen A; Ma, Wenjun

    2012-11-01

    Both H9N2 avian influenza and 2009 pandemic H1N1 viruses (pH1N1) are able to infect humans and swine, which has raised concerns that novel reassortant H9 viruses with pH1N1 genes might be generated in these hosts by reassortment. Although previous studies have demonstrated that reassortant H9 viruses with pH1N1 genes show increased virulence in mice and transmissibility in ferrets, the virulence and transmissibility of reassortant H9 viruses in natural hosts such as chickens and swine remain unknown. This study generated two reassortant H9 viruses (H9N2/CA09 and H9N1/CA09) in the background of the pH1N1 A/California/04/2009 (CA09) virus by replacing either both the haemagglutinin (HA) and neuraminidase (NA) genes or only the HA gene with the respective genes from the A/quail/Hong Kong/G1/1997 (H9N2) virus and evaluated their replication, pathogenicity and transmission in chickens and pigs compared with the parental viruses. Chickens that were infected with the parental H9N2 and reassortant H9 viruses seroconverted. The parental H9N2 and reassortant H9N2/CA09 viruses were transmitted to sentinel chickens, but H9N1/CA09 virus was not. The parental H9N2 replicated poorly and was not transmitted in pigs, whereas both H9N2/CA09 and H9N1/CA09 viruses replicated and were transmitted efficiently in pigs, similar to the pH1N1 virus. These results demonstrated that reassortant H9 viruses with pH1N1 genes show enhanced replication and transmissibility in pigs compared with the parental H9N2 virus, indicating that they may pose a threat for humans if such reassortants arise in swine.

  19. An outbreak of 2009 pandemic influenza A (H1N1) virus infection in an elementary school in Pennsylvania.

    PubMed

    Marchbanks, Tiffany L; Bhattarai, Achuyt; Fagan, Ryan P; Ostroff, Stephen; Sodha, Samir V; Moll, Mària E; Lee, Bruce Y; Chang, Chung-Chou H; Ennis, Brent; Britz, Phyllis; Fiore, Anthony; Nguyen, Michael; Palekar, Rakhee; Archer, W Roodly; Gift, Thomas L; Leap, Rebecca; Nygren, Benjamin L; Cauchemez, Simon; Angulo, Frederick J; Swerdlow, David

    2011-01-01

    In May 2009, one of the earliest outbreaks of 2009 pandemic influenza A virus (pH1N1) infection resulted in the closure of a semi-rural Pennsylvania elementary school. Two sequential telephone surveys were administered to 1345 students (85% of the students enrolled in the school) and household members in 313 households to collect data on influenza-like illness (ILI). A total of 167 persons (12.4%) among those in the surveyed households, including 93 (24.0%) of the School A students, reported ILI. Students were 3.1 times more likely than were other household members to develop ILI (95% confidence interval [CI], 2.3-4.1). Fourth-grade students were more likely to be affected than were students in other grades (relative risk, 2.2; 95% CI, 1.2-3.9). pH1N1 was confirmed in 26 (72.2%) of the individuals tested by real-time reverse-transcriptase polymerase chain reaction. The outbreak did not resume upon the reopening of the school after the 7-day closure. This investigation found that pH1N1 outbreaks at schools can have substantial attack rates; however, grades and classrooms are affected variably. Additional study is warranted to determine the effectiveness of school closure during outbreaks. PMID:21342888

  20. A pandemic H1N1 influenza virus-like particle vaccine induces cross-protection in mice.

    PubMed

    Inn, Kyung-Soo; Lee, Gi-Ja; Quan, Fu-Shi

    2014-01-01

    Influenza virus-like particles (VLPs) represent promising alternative vaccines. However, it is necessary to demonstrate that influenza VLPs confer cross-protection against antigenically distinct viruses. In this study, a VLP vaccine comprising hemagglutinin (HA) and M1 from the A/California/04/2009 (H1N1) were used and its ability to induce cross-protective efficacy against heterologous viruses A/PR/8/34 (H1N1) and A/New Caledonia/20/99 (H1N1) in mice was assessed. Vaccination with 2009 H1 VLPs induced significantly higher levels of IgG cross-reactive with these heterologous viruses after the second boost compared to after the prime or first boost. Lung virus titers also decreased significantly and the lung cross-reactive IgG response after lethal virus challenge was significantly greater in immunized mice compared to naïve mice. Vaccinated mice showed 100% protection against A/PR/8/34 and A/Caledonia/20/99 viruses with only moderate body weight loss and induction of cross-reactive recall, IgG antibody-secreting cell responses. The variations in HA amino acid sequences and antigenic sites were determined and correlated with induction of cross-protective immunity. These results indicate that VLPs can be used as an effective vaccine that confers cross-protection against antigenically distinct viruses.

  1. Modelling the epidemic spread of an H1N1 influenza outbreak in a rural university town.

    PubMed

    Vaidya, N K; Morgan, M; Jones, T; Miller, L; Lapin, S; Schwartz, E J

    2015-06-01

    Knowledge of mechanisms of infection in vulnerable populations is needed in order to prepare for future outbreaks. Here, using a unique dataset collected during a 2009 outbreak of influenza A(H1N1)pdm09 in a university town, we evaluated mechanisms of infection and identified that an epidemiological model containing partial protection of susceptibles best describes H1N1 dynamics in a rural university environment. We found that the protected group was over 14 times less susceptible to H1N1 infection than unprotected susceptibles. Our estimates show that the basic reproductive rate, R 0, was 5·96 (95% confidence interval 5·83-6·61), and, importantly, R 0 could be decreased to below 1 and similar epidemics could be avoided by increasing the proportion of the initial protected group. Moreover, several weeks into the epidemic, this protected group generated more new infections than the unprotected susceptible group, and thus, such protected groups should be taken into account while studying influenza epidemics in similar settings. PMID:25323631

  2. An outbreak of 2009 pandemic influenza A (H1N1) virus infection in an elementary school in Pennsylvania.

    PubMed

    Marchbanks, Tiffany L; Bhattarai, Achuyt; Fagan, Ryan P; Ostroff, Stephen; Sodha, Samir V; Moll, Mària E; Lee, Bruce Y; Chang, Chung-Chou H; Ennis, Brent; Britz, Phyllis; Fiore, Anthony; Nguyen, Michael; Palekar, Rakhee; Archer, W Roodly; Gift, Thomas L; Leap, Rebecca; Nygren, Benjamin L; Cauchemez, Simon; Angulo, Frederick J; Swerdlow, David

    2011-01-01

    In May 2009, one of the earliest outbreaks of 2009 pandemic influenza A virus (pH1N1) infection resulted in the closure of a semi-rural Pennsylvania elementary school. Two sequential telephone surveys were administered to 1345 students (85% of the students enrolled in the school) and household members in 313 households to collect data on influenza-like illness (ILI). A total of 167 persons (12.4%) among those in the surveyed households, including 93 (24.0%) of the School A students, reported ILI. Students were 3.1 times more likely than were other household members to develop ILI (95% confidence interval [CI], 2.3-4.1). Fourth-grade students were more likely to be affected than were students in other grades (relative risk, 2.2; 95% CI, 1.2-3.9). pH1N1 was confirmed in 26 (72.2%) of the individuals tested by real-time reverse-transcriptase polymerase chain reaction. The outbreak did not resume upon the reopening of the school after the 7-day closure. This investigation found that pH1N1 outbreaks at schools can have substantial attack rates; however, grades and classrooms are affected variably. Additional study is warranted to determine the effectiveness of school closure during outbreaks.

  3. Gene signatures related to HAI response following influenza A/H1N1 vaccine in older individuals.

    PubMed

    Ovsyannikova, Inna G; Oberg, Ann L; Kennedy, Richard B; Zimmermann, Michael T; Haralambieva, Iana H; Goergen, Krista M; Grill, Diane E; Poland, Gregory A

    2016-05-01

    To assess gene signatures related to humoral response among healthy older subjects following seasonal influenza vaccination, we studied 94 healthy adults (50-74 years old) who received one documented dose of licensed trivalent influenza vaccine containing the A/California/7/2009 (H1N1)-like virus strain. Influenza-specific antibody (HAI) titer in serum samples and next-generation sequencing on PBMCs were performed using blood samples collected prior to (Day 0) and at two timepoints after (Days 3 and 28) vaccination. We identified a number of uncharacterized genes (ZNF300, NUP1333, KLK1 and others) and confirmed previous studies demonstrating specific genes/genesets that are important mediators of host immune responses and that displayed associations with antibody response to influenza A/H1N1 vaccine. These included interferon-regulatory transcription factors (IRF1/IRF2/IRF6/IRF7/IRF9), chemokine/chemokine receptors (CCR5/CCR9/CCL5), cytokine/cytokine receptors (IFNG/IL10RA/TNFRSF1A), protein kinases (MAP2K4/MAPK3), growth factor receptor (TGFBR1). The identification of gene signatures associated with antibody response represents an early stage in the science for which further research is needed. Such research may assist in the design of better vaccines to facilitate improved defenses against new influenza virus strains, as well as better understanding the genetic drivers of immune responses. PMID:27441275

  4. A case of central diabetes insipidus following probable type A/H1N1 influenza infection.

    PubMed

    Kobayashi, Takaaki; Miwa, Takashi; Odawara, Masato

    2011-01-01

    The major causes of central diabetes insipidus (CDI) are neoplastic or infiltrative lesions of the hypothalamus or pituitary gland, severe head injuries, or pituitary or hypothalamic surgery. Lymphocytic infundibuloneurophysitis (LINH) is associated with autoimmune inflammatory disease of the pituitary gland, but the exact etiology is unknown. CDI caused by viral infections has been rarely reported. Here, we describe the case of a 22-year-old man who was in good health until 2 months prior to admission, presented with acute development of polyuria and polydipsia, and showed increased urinary volume up to 9000 mL/day. The patient showed elevated serum osmolality and low urine osmolality, with a low level of antidiuretic hormone. Endocrinological findings revealed CDI, but his arterial pituitary function appeared normal. Magnetic resonance imaging revealed significant enlargement of the pituitary stalk. We suspected CDI due to LINH based on non-transsphenoidal biopsy findings. He was diagnosed as type A influenza,and given oral therapeutic agents. However, acute onset of polyuria and polydipsia occurred 10 days after the influenza diagnosis. The available epidemiological information regarding the outbreak of influenza around that time strongly suggested that the patient was infected with the A/H1N1 influenza virus, although this virus had not been detected on polymerase chain reaction testing. In the present case, the autoimmune mechanism of LINH may have been associated with novel influenza A/H1N1 virus infection.

  5. [Is obesity an adverse prognostic factor for pulmonary manifestations of influenza? Lesson from complicated disease course H1N1].

    PubMed

    Zoubková, Renata; Máca, Jan; Handlos, Petr; Rudinská, Lenka; Nytra, Ivana; Chýlek, Václav; Vavrošová, Jana

    2014-01-01

    Influenza viruses cause annual epidemics that occur at different times in both the northern and southern hemisphere. In cases of seasonal influenza these are usually mild forms of the disease, which rarely lead to death of the patient. Vulnerable groups include the elderly, the young or those with comorbidities, where the virus affects tens of thousands of victims around the world. Occasionally, however, large epidemics appear caused by a dangerous variant of a new virus, which is usually characterized by high contagiousness and pathogenicity (virulence). Consequently, it is often accompanied by a complicated disease course and associated with high mortality. In 2009, a viral pandemic disease marked pH1N1 2009 Influenza A appeared. Even though the initial predictions were far worse, the course of influenza caused by this virus was often complicated by acute respiratory failure in the form of acute respiratory distress syndrome (ARDS). This formed part of the wider multiple organ failure syndrome (MODS). This type of virus often infects younger age groups and is more contagious compared to the seasonal flu. In order to illustrate the complicated forms of viral infections pH1N1 2009 Influenza A we present three case studies which demonstrate complicated pulmonary manifestation, which take the primary form of ARDS. PMID:25561242

  6. Survival of Influenza A(H1N1) on Materials Found in Households: Implications for Infection Control

    PubMed Central

    Greatorex, Jane S.; Digard, Paul; Curran, Martin D.; Moynihan, Robert; Wensley, Harrison; Wreghitt, Tim; Varsani, Harsha; Garcia, Fayna; Enstone, Joanne; Nguyen-Van-Tam, Jonathan S.

    2011-01-01

    Background The majority of influenza transmission occurs in homes, schools and workplaces, where many frequently touched communal items are situated. However the importance of transmission via fomites is unclear since few data exist on the survival of virus on commonly touched surfaces. We therefore measured the viability over time of two H1N1 influenza strains applied to a variety of materials commonly found in households and workplaces. Methodology and Principal Findings Influenza A/PuertoRico/8/34 (PR8) or A/Cambridge/AHO4/2009 (pandemic H1N1) viruses were inoculated onto a wide range of surfaces used in home and work environments, then sampled at set times following incubation at stabilised temperature and humidity. Virus genome was measured by RT-PCR; plaque assay (for PR8) or fluorescent focus formation (for pandemic H1N1) was used to assess the survival of viable virus. Conclusions/Significance The genome of either virus could be detected on most surfaces 24 h after application with relatively little drop in copy number, with the exception of unsealed wood surfaces. In contrast, virus viability dropped much more rapidly. Live virus was recovered from most surfaces tested four hours after application and from some non-porous materials after nine hours, but had fallen below the level of detection from all surfaces at 24 h. We conclude that influenza A transmission via fomites is possible but unlikely to occur for long periods after surface contamination (unless re-inoculation occurs). In situations involving a high probability of influenza transmission, our data suggest a hierarchy of priorities for surface decontamination in the multi-surface environments of home and hospitals. PMID:22132172

  7. Adoption of preventive behaviors in response to the 2009 H1N1 influenza pandemic: a multiethnic perspective

    PubMed Central

    SteelFisher, Gillian K; Blendon, Robert J; Kang, Minah; Ward, Johanna R M; Kahn, Emily B; Maddox, Kathryn EW; Lubell, Keri M; Tucker, Myra; Ben-Porath, Eran N

    2015-01-01

    Background As public health leaders prepare for possible future influenza pandemics, the rapid spread of 2009 H1N1 influenza highlights the need to focus on measures the public can adopt to help slow disease transmission. Such measures may relate to hygiene (e.g., hand washing), social distancing (e.g., avoiding places where many people gather), and pharmaceutical interventions (e.g., vaccination). Given the disproportionate impact of public health emergencies on minority communities in the United States, it is important to understand whether there are differences in acceptance across racial/ethnic groups that could lead to targeted and more effective policies and communications. Objectives This study explores racial/ethnic differences in the adoption of preventive behaviors during the 2009 H1N1 influenza pandemic. Patients/Methods Data are from a national telephone poll conducted March 17 to April 11, 2010, among a representative sample of 1123 white, 330 African American, 317 Hispanic, 268 Asian, and 262 American Indian/Alaska Native adults in the USA. Results People in at least one racial/ethnic minority group were more likely than whites to adopt several behaviors related to hygiene, social distancing, and healthcare access, including increased hand washing and talking with a healthcare provider (P-values <0·05). Exceptions included avoiding others with influenza-like illnesses and receiving 2009 H1N1 and seasonal influenza vaccinations. After we controlled the data for socioeconomic status, demographic factors, healthcare access, and illness- and vaccine-related attitudes, nearly all racial/ethnic differences in behaviors persisted. Conclusions Minority groups appear to be receptive to several preventive behaviors, but barriers to vaccination are more pervasive. PMID:25688806

  8. Factors associated with death in hospitalized pneumonia patients with 2009 H1N1 influenza in Shenyang, China

    PubMed Central

    2010-01-01

    Background During the spring of 2009, a pandemic influenza A (H1N1) virus emerged and spread globally. We describe the clinical characteristics and factors associated with the death of patients who were hospitalized with 2009 H1N1 influenza pneumonia in Shenyang, China, from November to December 2009. Methods We carried out a retrospective chart review of 68 patients who were hospitalized with pneumonia and confirmed to have 2009 H1N1 virus infection by a real time RT-PCR assay of respiratory specimens. Results Of the 68 patients we studied, 30 (44%) were admitted to an intensive care unit and 10 (14.7%) died. The median age of patients was 41 years (range, 18-66), and only one patient was over 65 years of age. The male to female ratio was 2.78:1 (50:18). Of the 68 patients, 23 (34%) had at least one underlying medical condition, 9 (13%) had a cigarette index ≥400 and 22 (32%) were obese. All patients underwent chest radiography on admission and the findings were consistent with pneumonia in all cases. All patients were treated with oseltamivir and treatment was initiated at a median time of seven days after the onset of illness. The laboratory test results indicated lymphopenia, hypoproteinemia and elevated lactic dehydrogenase and C reactive protein levels. Of the 68 patients, 33 (52%) showed a reduction in CD4 T cell counts. Of the 58 patients who survived, 31 (53%) had lymphopenia and 27 recovered from this condition after five days. Of the 10 patients who died, nine (90%) had lymphopenia and only two patients recovered from this condition after five days. Obesity and recovery from lymphopenia after five days were factors associated with death, as determined by multivariate logistic-regression analysis (obesity, odds ratio = 23.06; lymphocytopenia reversion, odds ration = 28.69). Conclusions During the evaluation period in Shenyang, China, 2009 H1N1 influenza caused severe illness requiring hospitalization in 68 patients, 10 (14.7%) of which died. Many of

  9. Changes to the dynamic nature of hemagglutinin and the emergence of the 2009 pandemic H1N1 influenza virus

    PubMed Central

    Yoon, Sun-Woo; Chen, Noam; Ducatez, Mariette F.; McBride, Ryan; Barman, Subrata; Fabrizio, Thomas P.; Webster, Robert G.; Haliloglu, Turkan; Paulson, James C.; Russell, Charles J.; Hertz, Tomer; Ben-Tal, Nir; Webby, Richard J.

    2015-01-01

    The virologic factors that limit the transmission of swine influenza viruses between humans are unresolved. While it has been shown that acquisition of the neuraminidase (NA) and matrix (M) gene segments from a Eurasian-lineage swine virus was required for airborne transmission of the 2009 pandemic H1N1 virus (H1N1pdm09), we show here that an arginine to lysine change in the hemagglutinin (HA) was also necessary. This change at position 149 was distal to the receptor binding site but affected virus-receptor affinity and HA dynamics, allowing the virus to replicate more efficiently in nasal turbinate epithelium and subsequently transmit between ferrets. Receptor affinity should be considered as a factor limiting swine virus spread in humans. PMID:26269288

  10. Changes to the dynamic nature of hemagglutinin and the emergence of the 2009 pandemic H1N1 influenza virus.

    PubMed

    Yoon, Sun-Woo; Chen, Noam; Ducatez, Mariette F; McBride, Ryan; Barman, Subrata; Fabrizio, Thomas P; Webster, Robert G; Haliloglu, Turkan; Paulson, James C; Russell, Charles J; Hertz, Tomer; Ben-Tal, Nir; Webby, Richard J

    2015-01-01

    The virologic factors that limit the transmission of swine influenza viruses between humans are unresolved. While it has been shown that acquisition of the neuraminidase (NA) and matrix (M) gene segments from a Eurasian-lineage swine virus was required for airborne transmission of the 2009 pandemic H1N1 virus (H1N1pdm09), we show here that an arginine to lysine change in the hemagglutinin (HA) was also necessary. This change at position 149 was distal to the receptor binding site but affected virus-receptor affinity and HA dynamics, allowing the virus to replicate more efficiently in nasal turbinate epithelium and subsequently transmit between ferrets. Receptor affinity should be considered as a factor limiting swine virus spread in humans. PMID:26269288

  11. [Political dimensions of an epidemic: the case of influenza A (H1N1) in the Argentine press].

    PubMed

    Sy, Anahi; Spinelli, Hugo

    2016-03-01

    The current study addresses social representations of the influenza A (H1N1) epidemic in Argentina in 2009, in the country's mainstream newspapers. The methodology was twofold, qualitative and quantitative, with an analysis of two dimensions: the construction of the epidemic as an "object" (designation and characterization) and the sources of information in the news stories, seeking to identify the social actors involved in each case. The results show that designating the epidemic as "H1N1" rather than "swine flu" was a conscious political decision to exempt a hazardous form of livestock production from its role in the disease, while focusing responsibility on individual patients. The study addresses the relations between recommendations by policy spokespersons (especially at the international level), the pharmaceuticalization of the epidemic, shifting of the population's demands to validate biomedical hegemony, and local press coverage of the epidemic. PMID:27049316

  12. Changes to the dynamic nature of hemagglutinin and the emergence of the 2009 pandemic H1N1 influenza virus.

    PubMed

    Yoon, Sun-Woo; Chen, Noam; Ducatez, Mariette F; McBride, Ryan; Barman, Subrata; Fabrizio, Thomas P; Webster, Robert G; Haliloglu, Turkan; Paulson, James C; Russell, Charles J; Hertz, Tomer; Ben-Tal, Nir; Webby, Richard J

    2015-01-01

    The virologic factors that limit the transmission of swine influenza viruses between humans are unresolved. While it has been shown that acquisition of the neuraminidase (NA) and matrix (M) gene segments from a Eurasian-lineage swine virus was required for airborne transmission of the 2009 pandemic H1N1 virus (H1N1pdm09), we show here that an arginine to lysine change in the hemagglutinin (HA) was also necessary. This change at position 149 was distal to the receptor binding site but affected virus-receptor affinity and HA dynamics, allowing the virus to replicate more efficiently in nasal turbinate epithelium and subsequently transmit between ferrets. Receptor affinity should be considered as a factor limiting swine virus spread in humans.

  13. Immunogenicity and safety of pandemic influenza A (H1N1) 2009 vaccine: systematic review and meta-analysis.

    PubMed

    Yin, J Kevin; Khandaker, Gulam; Rashid, Harunor; Heron, Leon; Ridda, Iman; Booy, Robert

    2011-09-01

    The emergence of the 2009 H1N1 pandemic has highlighted the need to have immunogenicity and safety data on the new pandemic vaccines. There is already considerable heterogeneity in the types of vaccine available and of study performed around the world. A systematic review and meta-analysis is needed to assess the immunogenicity and safety of pandemic influenza A (H1N1) 2009 vaccines. We searched Medline, EMBASE, the Cochrane Library and other online databases up to 1st October 2010 for studies in any language comparing different pandemic H1N1 vaccines, with or without placebo, in healthy populations aged at least 6 months. The primary outcome was seroprotection according to haemagglutination inhibition (HI). Safety outcomes were adverse events. Meta-analysis was performed for the primary outcome. We identified 18 articles, 1 only on safety and 17 on immunogenicity, although 1 was a duplicate. We included 16 articles in the meta-analysis, covering 17,921 subjects. Adequate seroprotection (≥70%) was almost invariably achieved in all age groups, and even after one dose and at low antigen content (except in children under 3 years receiving one dose of non-adjuvanted vaccine). Non-adjuvanted vaccine from international companies and adjuvanted vaccines containing oil in water emulsion (e.g. AS03, MF59), rather than aluminium, performed better. Two serious vaccination-associated adverse events were reported, both of which resolved fully. No death or case of Guillain-Barré syndrome was reported. The pandemic influenza (H1N1) 2009 vaccine, with or without adjuvant, appears generally to be seroprotective after just one dose and safe among healthy populations aged ≥36 months; very young children (6-35 months) may need to receive two doses of non-adjuvanted vaccine or one dose of AS03(A/B)-adjuvanted product to achieve seroprotection.

  14. Clinical and laboratory features distinguishing pandemic H1N1 influenza-related pneumonia from interpandemic community-acquired pneumonia in adults

    PubMed Central

    Bewick, Thomas; Myles, Puja; Greenwood, Sonia; Nguyen-Van-Tam, Jonathan S; Brett, Stephen J; Semple, Malcolm G; Openshaw, Peter J; Bannister, Barbara; Read, Robert C; Taylor, Bruce L; McMenamin, Jim; Enstone, Joanne E; Nicholson, Karl G

    2011-01-01

    Background Early identification of patients with H1N1 influenza-related pneumonia is desirable for the early instigation of antiviral agents. A study was undertaken to investigate whether adults admitted to hospital with H1N1 influenza-related pneumonia could be distinguished clinically from patients with non-H1N1 community-acquired pneumonia (CAP). Methods Between May 2009 and January 2010, clinical and epidemiological data of patients with confirmed H1N1 influenza infection admitted to 75 hospitals in the UK were collected by the Influenza Clinical Information Network (FLU-CIN). Adults with H1N1 influenza-related pneumonia were identified and compared with a prospective study cohort of adults with CAP hospitalised between September 2008 and June 2010, excluding those admitted during the period of the pandemic. Results Of 1046 adults with confirmed H1N1 influenza infection in the FLU-CIN cohort, 254 (25%) had H1N1 influenza-related pneumonia on admission to hospital. In-hospital mortality of these patients was 11.4% compared with 14.0% in patients with inter-pandemic CAP (n=648). A multivariate logistic regression model was generated by assigning one point for each of five clinical criteria: age ≤65 years, mental orientation, temperature ≥38°C, leucocyte count ≤12×109/l and bilateral radiographic consolidation. A score of 4 or 5 predicted H1N1 influenza-related pneumonia with a positive likelihood ratio of 9.0. A score of 0 or 1 had a positive likelihood ratio of 75.7 for excluding it. Conclusion There are substantial clinical differences between H1N1 influenza-related pneumonia and inter-pandemic CAP. A model based on five simple clinical criteria enables the early identification of adults admitted with H1N1 influenza-related pneumonia. PMID:21252388

  15. Incidence and Epidemiology of Hospitalized Influenza Cases in Rural Thailand during the Influenza A (H1N1)pdm09 Pandemic, 2009–2010

    PubMed Central

    Baggett, Henry C.; Chittaganpitch, Malinee; Thamthitiwat, Somsak; Prapasiri, Prabda; Naorat, Sathapana; Sawatwong, Pongpun; Ditsungnoen, Darunee; Olsen, Sonja J.; Simmerman, James M.; Srisaengchai, Prasong; Chantra, Somrak; Peruski, Leonard F.; Sawanpanyalert, Pathom; Maloney, Susan A.; Akarasewi, Pasakorn

    2012-01-01

    Background Data on the burden of the 2009 influenza pandemic in Asia are limited. Influenza A(H1N1)pdm09 was first reported in Thailand in May 2009. We assessed incidence and epidemiology of influenza-associated hospitalizations during 2009–2010. Methods We conducted active, population-based surveillance for hospitalized cases of acute lower respiratory infection (ALRI) in all 20 hospitals in two rural provinces. ALRI patients were sampled 1∶2 for participation in an etiology study in which nasopharyngeal swabs were collected for influenza virus testing by PCR. Results Of 7,207 patients tested, 902 (12.5%) were influenza-positive, including 190 (7.8%) of 2,436 children aged <5 years; 86% were influenza A virus (46% A(H1N1)pdm09, 30% H3N2, 6.5% H1N1, 3.5% not subtyped) and 13% were influenza B virus. Cases of influenza A(H1N1)pdm09 first peaked in August 2009 when 17% of tested patients were positive. Subsequent peaks during 2009 and 2010 represented a mix of influenza A(H1N1)pdm09, H3N2, and influenza B viruses. The estimated annual incidence of hospitalized influenza cases was 136 per 100,000, highest in ages <5 years (477 per 100,000) and >75 years (407 per 100,000). The incidence of influenza A(H1N1)pdm09 was 62 per 100,000 (214 per 100,000 in children <5 years). Eleven influenza-infected patients required mechanical ventilation, and four patients died, all adults with influenza A(H1N1)pdm09 (1) or H3N2 (3). Conclusions Influenza-associated hospitalization rates in Thailand during 2009–10 were substantial and exceeded rates described in western countries. Influenza A(H1N1)pdm09 predominated, but H3N2 also caused notable morbidity. Expanded influenza vaccination coverage could have considerable public health impact, especially in young children. PMID:23139802

  16. Spatial and Temporal Characteristics of the 2009 A/H1N1 Influenza Pandemic in Peru

    PubMed Central

    Chowell, Gerardo; Viboud, Cécile; Munayco, Cesar V.; Gómez, Jorge; Simonsen, Lone; Miller, Mark A.; Tamerius, James; Fiestas, Victor; Halsey, Eric S.; Laguna-Torres, Victor A.

    2011-01-01

    Background Highly refined surveillance data on the 2009 A/H1N1 influenza pandemic are crucial to quantify the spatial and temporal characteristics of the pandemic. There is little information about the spatial-temporal dynamics of pandemic influenza in South America. Here we provide a quantitative description of the age-specific morbidity pandemic patterns across administrative areas of Peru. Methods We used daily cases of influenza-like-illness, tests for A/H1N1 influenza virus infections, and laboratory-confirmed A/H1N1 influenza cases reported to the epidemiological surveillance system of Peru's Ministry of Health from May 1 to December 31, 2009. We analyzed the geographic spread of the pandemic waves and their association with the winter school vacation period, demographic factors, and absolute humidity. We also estimated the reproduction number and quantified the association between the winter school vacation period and the age distribution of cases. Results The national pandemic curve revealed a bimodal winter pandemic wave, with the first peak limited to school age children in the Lima metropolitan area, and the second peak more geographically widespread. The reproduction number was estimated at 1.6–2.2 for the Lima metropolitan area and 1.3–1.5 in the rest of Peru. We found a significant association between the timing of the school vacation period and changes in the age distribution of cases, while earlier pandemic onset was correlated with large population size. By contrast there was no association between pandemic dynamics and absolute humidity. Conclusions Our results indicate substantial spatial variation in pandemic patterns across Peru, with two pandemic waves of varying timing and impact by age and region. Moreover, the Peru data suggest a hierarchical transmission pattern of pandemic influenza A/H1N1 driven by large population centers. The higher reproduction number of the first pandemic wave could be explained by high contact rates among school

  17. Hemagglutinin-neuraminidase balance confers respiratory-droplet transmissibility of the pandemic H1N1 influenza virus in ferrets.

    PubMed

    Yen, Hui-Ling; Liang, Chi-Hui; Wu, Chung-Yi; Forrest, Heather L; Ferguson, Angela; Choy, Ka-Tim; Jones, Jeremy; Wong, Diana Dik-Yan; Cheung, Peter Pak-Hang; Hsu, Che-Hsiung; Li, Olive T; Yuen, Kit M; Chan, Renee W Y; Poon, Leo L M; Chan, Michael C W; Nicholls, John M; Krauss, Scott; Wong, Chi-Huey; Guan, Yi; Webster, Robert G; Webby, Richard J; Peiris, Malik

    2011-08-23

    A novel reassortant derived from North American triple-reassortant (TRsw) and Eurasian swine (EAsw) influenza viruses acquired sustained human-to-human transmissibility and caused the 2009 influenza pandemic. To identify molecular determinants that allowed efficient transmission of the pandemic H1N1 virus among humans, we evaluated the direct-contact and respiratory-droplet transmissibility in ferrets of representative swine influenza viruses of different lineages obtained through a 13-y surveillance program in southern China. Whereas all viruses studied were transmitted by direct contact with varying efficiency, respiratory-droplet transmissibility (albeit inefficient) was observed only in the TRsw-like A/swine/Hong Kong/915/04 (sw915) (H1N2) virus. The sw915 virus had acquired the M gene derived from EAsw and differed from the gene constellation of the pandemic H1N1 virus by the neuraminidase (NA) gene alone. Glycan array analysis showed that pandemic H1N1 virus A/HK/415742/09 (HK415742) and sw915 possess similar receptor-binding specificity and affinity for α2,6-linked sialosides. Sw915 titers in differentiated normal human bronchial epithelial cells and in ferret nasal washes were lower than those of HK415742. Introducing the NA from pandemic HK415742 into sw915 did not increase viral replication efficiency but increased respiratory-droplet transmissibility, despite a substantial amino acid difference between the two viruses. The NA of the pandemic HK415742 virus possessed significantly higher enzyme activity than that of sw915 or other swine influenza viruses. Our results suggest that a unique gene constellation and hemagglutinin-neuraminidase balance play a critical role in acquisition of efficient and sustained human-to-human transmissibility.

  18. Hemagglutinin–neuraminidase balance confers respiratory-droplet transmissibility of the pandemic H1N1 influenza virus in ferrets

    PubMed Central

    Yen, Hui-Ling; Liang, Chi-Hui; Wu, Chung-Yi; Forrest, Heather L.; Ferguson, Angela; Choy, Ka-Tim; Jones, Jeremy; Wong, Diana Dik-Yan; Cheung, Peter Pak-Hang; Hsu, Che-Hsiung; Li, Olive T.; Yuen, Kit M.; Chan, Renee W. Y.; Poon, Leo L. M.; Chan, Michael C. W.; Nicholls, John M.; Krauss, Scott; Wong, Chi-Huey; Guan, Yi; Webster, Robert G.; Webby, Richard J.; Peiris, Malik

    2011-01-01

    A novel reassortant derived from North American triple-reassortant (TRsw) and Eurasian swine (EAsw) influenza viruses acquired sustained human-to-human transmissibility and caused the 2009 influenza pandemic. To identify molecular determinants that allowed efficient transmission of the pandemic H1N1 virus among humans, we evaluated the direct-contact and respiratory-droplet transmissibility in ferrets of representative swine influenza viruses of different lineages obtained through a 13-y surveillance program in southern China. Whereas all viruses studied were transmitted by direct contact with varying efficiency, respiratory-droplet transmissibility (albeit inefficient) was observed only in the TRsw-like A/swine/Hong Kong/915/04 (sw915) (H1N2) virus. The sw915 virus had acquired the M gene derived from EAsw and differed from the gene constellation of the pandemic H1N1 virus by the neuraminidase (NA) gene alone. Glycan array analysis showed that pandemic H1N1 virus A/HK/415742/09 (HK415742) and sw915 possess similar receptor-binding specificity and affinity for α2,6-linked sialosides. Sw915 titers in differentiated normal human bronchial epithelial cells and in ferret nasal washes were lower than those of HK415742. Introducing the NA from pandemic HK415742 into sw915 did not increase viral replication efficiency but increased respiratory-droplet transmissibility, despite a substantial amino acid difference between the two viruses. The NA of the pandemic HK415742 virus possessed significantly higher enzyme activity than that of sw915 or other swine influenza viruses. Our results suggest that a unique gene constellation and hemagglutinin–neuraminidase balance play a critical role in acquisition of efficient and sustained human-to-human transmissibility. PMID:21825167

  19. Electrical immunosensor based on dielectrophoretically-deposited carbon nanotubes for detection of influenza virus H1N1.

    PubMed

    Singh, Renu; Sharma, Abhinav; Hong, Seongkyeol; Jang, Jaesung

    2014-11-01

    The influenza virus has received extensive attention due to the recent H1N1 pandemics originating from swine. This study reports a label-free, highly sensitive, and selective electrical immunosensor for the detection of influenza virus H1N1 based on dielectrophoretically deposited single-walled carbon nanotubes (SWCNTs). COOH-functionalized SWCNTs were deposited on a self-assembled monolayer of polyelectrolyte polydiallyldimethyl-ammonium chloride (PDDA) between two gold electrodes by dielectrophoretic and electrostatic forces, which resulted in reproducible, uniform, aligned, and aggregation-free SWCNT channels (2-10 μm in length). Avidin was immobilized onto the PDDA-SWCNT channels, and viral antibodies were immobilized using biotin-avidin coupling. The resistance of the channels increased with the binding of the influenza viruses to the antibodies. These immunosensors showed linear behavior as the virus concentration was varied from 1 to 10(4) PFU ml(-1) along with a detection time of 30 min. The immunosensors with a 2 μm channel length detected 1 PFU ml(-1) of the influenza virus accurately (R(2) = 0.99) and selectively from MS2 bacteriophages. These immunosensors have the potential to become an important component of a point-of-care test kit that will enable a rapid clinical diagnosis.

  20. The role of radiology in influenza: novel H1N1 and lessons learned from the 1918 pandemic.

    PubMed

    Mollura, Daniel J; Morens, David M; Taubenberger, Jeffery K; Bray, Mike

    2010-09-01

    The pandemic of swine-origin H1N1 influenza that began in early 2009 has provided evidence that radiology can assist in the early diagnosis of severe cases, raising new opportunities for the further development of infectious disease imaging. To help define radiology's role in present and future influenza outbreaks, it is important to understand how radiologists have responded to past epidemics and how these outbreaks influenced the development of imaging science. The authors review the role of radiology in the most severe influenza outbreak in history, the "great pandemic" of 1918, which arrived only 23 years after the discovery of x-rays. In large part because of the coincidental increase in the radiologic capacity of military hospitals for World War I, the 1918 pandemic firmly reinforced the role of radiologists as collaborators with clinicians and pathologists at an early stage in radiology's development, in addition to producing a radical expansion of radiologic research on pulmonary infections. Radiology's solid foundation from the 1918 experience in medical practice and research now affords significant opportunities to respond to the current H1N1 pandemic and future epidemics through similar interdisciplinary strategies that integrate imaging science with pathology, virology, and clinical studies. The broad range of current imaging capabilities will make it possible to study influenza at the cellular level, in animal models, and in human clinical trials to elucidate the pathogenesis of severe illness and improve clinical outcomes.

  1. Efficacy of a pandemic (H1N1) 2009 virus vaccine in pigs against the pandemic influenza virus is superior to commercially available swine influenza vaccines.

    PubMed

    Loeffen, W L A; Stockhofe, N; Weesendorp, E; van Zoelen-Bos, D; Heutink, R; Quak, S; Goovaerts, D; Heldens, J G M; Maas, R; Moormann, R J; Koch, G

    2011-09-28

    In April 2009 a new influenza A/H1N1 strain, currently named "pandemic (H1N1) influenza 2009" (H1N1v), started the first official pandemic in humans since 1968. Several incursions of this virus in pig herds have also been reported from all over the world. Vaccination of pigs may be an option to reduce exposure of human contacts with infected pigs, thereby preventing cross-species transfer, but also to protect pigs themselves, should this virus cause damage in the pig population. Three swine influenza vaccines, two of them commercially available and one experimental, were therefore tested and compared for their efficacy against an H1N1v challenge. One of the commercial vaccines is based on an American classical H1N1 influenza strain, the other is based on a European avian H1N1 influenza strain. The experimental vaccine is based on reassortant virus NYMC X179A (containing the hemagglutinin (HA) and neuraminidase (NA) genes of A/California/7/2009 (H1N1v) and the internal genes of A/Puerto Rico/8/34 (H1N1)). Excretion of infectious virus was reduced by 0.5-3 log(10) by the commercial vaccines, depending on vaccine and sample type. Both vaccines were able to reduce virus replication especially in the lower respiratory tract, with less pathological lesions in vaccinated and subsequently challenged pigs than in unvaccinated controls. In pigs vaccinated with the experimental vaccine, excretion levels of infectious virus in nasal and oropharyngeal swabs, were at or below 1 log(10)TCID(50) per swab and lasted for only 1 or 2 days. An inactivated vaccine containing the HA and NA of an H1N1v is able to protect pigs from an infection with H1N1v, whereas swine influenza vaccines that are currently available are of limited efficaciousness. Whether vaccination of pigs against H1N1v will become opportune remains to be seen and will depend on future evolution of this strain in the pig population. Close monitoring of the pig population, focussing on presence and evolution of

  2. Household Transmission of Influenza A(H1N1)pdm09 in the Pandemic and Post-Pandemic Seasons

    PubMed Central

    Casado, Itziar; Martínez-Baz, Iván; Burgui, Rosana; Irisarri, Fátima; Arriazu, Maite; Elía, Fernando; Navascués, Ana; Ezpeleta, Carmen; Aldaz, Pablo; Castilla, Jesús

    2014-01-01

    Background The transmission of influenza viruses occurs person to person and is facilitated by contacts within enclosed environments such as households. The aim of this study was to evaluate secondary attack rates and factors associated with household transmission of laboratory-confirmed influenza A(H1N1)pdm09 in the pandemic and post-pandemic seasons. Methods During the 2009–2010 and 2010–2011 influenza seasons, 76 sentinel physicians in Navarra, Spain, took nasopharyngeal and pharyngeal swabs from patients diagnosed with influenza-like illness. A trained nurse telephoned households of those patients who were laboratory-confirmed for influenza A(H1N1)pdm09 to ask about the symptoms, risk factors and vaccination status of each household member. Results In the 405 households with a patient laboratory-confirmed for influenza A(H1N1)pdm09, 977 susceptible contacts were identified; 16% of them (95% CI 14–19%) presented influenza-like illness and were considered as secondary cases. The secondary attack rate was 14% in 2009–2010 and 19% in the 2010–2011 season (p = 0.049), an increase that mainly affected persons with major chronic conditions. In the multivariate logistic regression analysis, the risk of being a secondary case was higher in the 2010–2011 season than in the 2009–2010 season (adjusted odds ratio: 1.72; 95% CI 1.17–2.54), and in children under 5 years, with a decreasing risk in older contacts. Influenza vaccination was associated with lesser incidence of influenza-like illness near to statistical significance (adjusted odds ratio: 0.29; 95% CI 0.08–1.03). Conclusion The secondary attack rate in households was higher in the second season than in the first pandemic season. Children had a greater risk of infection. Preventive measures should be maintained in the second pandemic season, especially in high-risk persons. PMID:25254376

  3. Nosocomial outbreak of the pandemic Influenza A (H1N1) 2009 in critical hematologic patients during seasonal influenza 2010-2011: detection of oseltamivir resistant variant viruses

    PubMed Central

    2013-01-01

    Background The pandemic influenza A (H1N1) 2009 (H1N1pdm09) virus infection caused illness and death among people worldwide, particularly in hematologic/oncologic patients because influenza infected individuals can shed virus for prolonged periods, thus increasing the chances for the development of drug-resistant strains such as oseltamivir-resistant (OST-r) variant. Methods The aim of our study was to retrospectively evaluate the clinical importance of OST-r variant in circulating strains of the pandemic H1N1pdm09 virus. By means of RT-PCR and Sanger sequencing we analysed the presence of OST-r variant in 76 H1N1pdm09 laboratory-confirmed cases, hospitalized at the hematologic/oncologic ward at Spedali Civili of Brescia –Italy. Results Out of 76 hospitalized hematologic/oncologic patients, 23 patients (30.2%) were infected by H1N1pdm09 virus. Further investigation revealed that 3 patients were positive for the OST-r variant carrying the H275Y mutation. All the 23 infected patients were immuno-compromised, and were under treatment or had been treated previously with oseltamivir. Three patients died (13%) after admission to intensive care unit and only one of them developed H275Y mutation. Conclusions Our retrospective observational study shows that pandemic influenza A (H1N1) 2009 virus can cause significant morbidity and even mortality in hematologic/oncologic patients and confirms the high rate of nosocomial transmission of pandemic H1N1pdm09 virus in these critical subjects. Indeed, the reduction in host defences in these hospitalized patients favoured the prolonged use of antiviral therapy and permitted the development of OST-r strain. Strategies as diagnostic vigilance, early isolation of patients and seasonal influenza A(H1N1) vaccination may prevent transmission of influenza in high risk individuals. PMID:23496867

  4. [Comparative study of the differential susceptibility of different cell lines to pandemic H1N1v influenza viruses and avian influenza, swine influenza, and human influenza viruses].

    PubMed

    Danilenko, D M; Smirnova, T D; Gudkova, T M; Eropkin, M Iu; Kiselev, O I

    2011-01-01

    The proliferation characteristics of influenza viruses of different origin were tested in various human and animal cell cultures. Pandemic H1N1v influenza and swine influenza viruses were shown to have a low infectious activity in virtually all the test lines. In spite of this, the replication of this group of viruses may be detected by de novo NP synthesis. These viruses are able to activate programmed cell death. Moreover, a low inoculative virus dose exerts a stimulating effect on cell proliferation in both suspension and monolayer cell lines.

  5. Experimental infection of European starlings (Sturnus vulgaris) and house sparrows (Passer domesticus) with pandemic 2009 H1N1 and swine H1N1 and H3N2 triple reassortant influenza viruses.

    PubMed

    Nemeth, Nicole M; Oesterle, Paul T; Poulson, Rebecca L; Jones, Cheryl A; Tompkins, S Mark; Brown, Justin D; Stallknecht, David E

    2013-04-01

    European Starlings (Sturnus vulgaris) and House Sparrows (Passer domesticus) are common peridomestic passerine birds that are often associated with domestic animal production facilities. This association provides a potential means for pathogen transmission between facilities. We inoculated European Starlings and House Sparrows with three non-avian influenza virus strains: two swine isolates (H1N1 and H3N2) and one human isolate representing the H1N1 pandemic strain that originated from swine. No viral shedding was observed in House Sparrows, and shedding was minimal and transient in two of 12 (17%) European Starlings. One of these two infected Starlings seroconverted 14 days after inoculation. These results suggest that these two passerine species are minimally susceptible to current influenza viruses in domestic pigs and therefore pose a negligible risk for transmission between or within swine production facilities. PMID:23568924

  6. Diversifying Selection Analysis Predicts Antigenic Evolution of 2009 Pandemic H1N1 Influenza A Virus in Humans

    PubMed Central

    Lee, Alexandra J.; Das, Suman R.; Wang, Wei; Fitzgerald, Theresa; Pickett, Brett E.; Aevermann, Brian D.; Topham, David J.; Falsey, Ann R.

    2015-01-01

    ABSTRACT Although a large number of immune epitopes have been identified in the influenza A virus (IAV) hemagglutinin (HA) protein using various experimental systems, it is unclear which are involved in protective immunity to natural infection in humans. We developed a data mining approach analyzing natural H1N1 human isolates to identify HA protein regions that may be targeted by the human immune system and can predict the evolution of IAV. We identified 16 amino acid sites experiencing diversifying selection during the evolution of prepandemic seasonal H1N1 strains and found that 11 sites were located in experimentally determined B-cell/antibody (Ab) epitopes, including three distinct neutralizing Caton epitopes: Sa, Sb, and Ca2 [A. J. Caton, G. G. Brownlee, J. W. Yewdell, and W. Gerhard, Cell 31:417–427, 1982, http://dx.doi.org/10.1016/0092-8674(82)90135-0]. We predicted that these diversified epitope regions would be the targets of mutation as the 2009 H1N1 pandemic (pH1N1) lineage evolves in response to the development of population-level protective immunity in humans. Using a chi-squared goodness-of-fit test, we identified 10 amino acid sites that significantly differed between the pH1N1 isolates and isolates from the recent 2012-2013 and 2013-2014 influenza seasons. Three of these sites were located in the same diversified B-cell/Ab epitope regions as identified in the analysis of prepandemic sequences, including Sa and Sb. As predicted, hemagglutination inhibition (HI) assays using human sera from subjects vaccinated with the initial pH1N1 isolate demonstrated reduced reactivity against 2013-2014 isolates. Taken together, these results suggest that diversifying selection analysis can identify key immune epitopes responsible for protective immunity to influenza virus in humans and thereby predict virus evolution. IMPORTANCE The WHO estimates that approximately 5 to 10% of adults and 20 to 30% of children in the world are infected by influenza virus each

  7. Risk Factors for Severe Outcomes following 2009 Influenza A (H1N1) Infection: A Global Pooled Analysis

    PubMed Central

    Van Kerkhove, Maria D.; Vandemaele, Katelijn A. H.; Shinde, Vivek; Jaramillo-Gutierrez, Giovanna; Koukounari, Artemis; Donnelly, Christl A.; Carlino, Luis O.; Owen, Rhonda; Paterson, Beverly; Pelletier, Louise; Vachon, Julie; Gonzalez, Claudia; Hongjie, Yu; Zijian, Feng; Chuang, Shuk Kwan; Au, Albert; Buda, Silke; Krause, Gerard; Haas, Walter; Bonmarin, Isabelle; Taniguichi, Kiyosu; Nakajima, Kensuke; Shobayashi, Tokuaki; Takayama, Yoshihiro; Sunagawa, Tomi; Heraud, Jean Michel; Orelle, Arnaud; Palacios, Ethel; van der Sande, Marianne A. B.; Wielders, C. C. H. Lieke; Hunt, Darren; Cutter, Jeffrey; Lee, Vernon J.; Thomas, Juno; Santa-Olalla, Patricia; Sierra-Moros, Maria J.; Hanshaoworakul, Wanna; Ungchusak, Kumnuan; Pebody, Richard; Jain, Seema; Mounts, Anthony W.

    2011-01-01

    Background Since the start of the 2009 influenza A pandemic (H1N1pdm), the World Health Organization and its member states have gathered information to characterize the clinical severity of H1N1pdm infection and to assist policy makers to determine risk groups for targeted control measures. Methods and Findings Data were collected on approximately 70,000 laboratory-confirmed hospitalized H1N1pdm patients, 9,700 patients admitted to intensive care units (ICUs), and 2,500 deaths reported between 1 April 2009 and 1 January 2010 from 19 countries or administrative regions—Argentina, Australia, Canada, Chile, China, France, Germany, Hong Kong SAR, Japan, Madagascar, Mexico, the Netherlands, New Zealand, Singapore, South Africa, Spain, Thailand, the United States, and the United Kingdom—to characterize and compare the distribution of risk factors among H1N1pdm patients at three levels of severity: hospitalizations, ICU admissions, and deaths. The median age of patients increased with severity of disease. The highest per capita risk of hospitalization was among patients <5 y and 5–14 y (relative risk [RR] = 3.3 and 3.2, respectively, compared to the general population), whereas the highest risk of death per capita was in the age groups 50–64 y and ≥65 y (RR = 1.5 and 1.6, respectively, compared to the general population). Similarly, the ratio of H1N1pdm deaths to hospitalizations increased with age and was the highest in the ≥65-y-old age group, indicating that while infection rates have been observed to be very low in the oldest age group, risk of death in those over the age of 64 y who became infected was higher than in younger groups. The proportion of H1N1pdm patients with one or more reported chronic conditions increased with severity (median = 31.1%, 52.3%, and 61.8% of hospitalized, ICU-admitted, and fatal H1N1pdm cases, respectively). With the exception of the risk factors asthma, pregnancy, and obesity, the proportion of patients with each

  8. Novel influenza A (H1N1) virus infections among health-care personnel - United States, April-May 2009.

    PubMed

    2009-06-19

    Soon after identification of novel influenza A (H1N1) virus infections in the United States in mid-April 2009, CDC provided interim recommendations to reduce the risk for transmission in health-care settings. These included recommendations on use of personal protective equipment (PPE), management of health-care personnel (HCP) after unprotected exposures, and instruction of ill HCP not to report to work. To better understand the risk for acquiring infection with the virus among HCP and the impact of infection-control recommendations, CDC solicited reports of infected HCP from state health departments. As of May 13, CDC had received 48 reports of confirmed or probable infections with novel influenza A (H1N1) virus; of these, 26 reports included detailed case reports with information regarding risk factors that might have led to infection. Of the 26 cases, 13 (50%) HCP were deemed to have acquired infection in a health-care setting, including one instance of probable HCP to HCP transmission and 12 instances of probable or possible patient to HCP transmission. Eleven HCP had probable or possible acquisition in the community, and two had no reported exposures in either health-care or community settings. Among 11 HCP with probable or possible patient to HCP acquisition and available information on PPE use, only three reported always using either a surgical mask or an N95 respirator. These findings suggest that transmission of novel influenza A (H1N1) virus to HCP is occurring in both health-care and community settings and that additional messages aimed at reinforcing current infection-control recommendations are needed. PMID:19543199

  9. Effectiveness of common healthcare disinfectants against H1N1 influenza virus on reusable elastomeric respirators.

    PubMed

    Subhash, Shobha S; Cavaiuolo, Maria; Radonovich, Lewis J; Eagan, Aaron; Lee, Martin L; Campbell, Sheldon; Martinello, Richard A

    2014-07-01

    This study evaluated the efficacy of 3 common hospital disinfectants to inactivate influenza virus on elastomeric respirators. Quaternary ammonium/isopropyl alcohol and bleach detergent wipes eliminated live virus, whereas 70% isopropyl alcohol alone was ineffective.

  10. Hospitalization Fatality Risk of Influenza A(H1N1)pdm09: A Systematic Review and Meta-Analysis

    PubMed Central

    Wong, Jessica Y.; Kelly, Heath; Cheung, Chung-Mei M.; Shiu, Eunice Y.; Wu, Peng; Ni, Michael Y.; Ip, Dennis K. M.; Cowling, Benjamin J.

    2015-01-01

    During the 2009 influenza pandemic, uncertainty surrounding the severity of human infections with the influenza A(H1N1)pdm09 virus hindered the calibration of the early public health response. The case fatality risk was widely used to assess severity, but another underexplored and potentially more immediate measure is the hospitalization fatality risk (HFR), defined as the probability of death among H1N1pdm09 cases who required hospitalization for medical reasons. In this review, we searched for relevant studies published in MEDLINE (PubMed) and EMBASE between April 1, 2009, and January 9, 2014. Crude estimates of the HFR ranged from 0% to 52%, with higher estimates from tertiary-care referral hospitals in countries with a lower gross domestic product, but in wealthy countries the estimate was 1%–3% in all settings. Point estimates increased substantially with age and with lower gross domestic product. Early in the next pandemic, estimation of a standardized HFR may provide a picture of the severity of infection, particularly if it is presented in comparison with a similarly standardized HFR for seasonal influenza in the same setting. PMID:26188191

  11. Immunologic Characterization of a Rhesus Macaque H1N1 Challenge Model for Candidate Influenza Virus Vaccine Assessment

    PubMed Central

    Skinner, Jason A.; Zurawski, Sandra M.; Sugimoto, Chie; Vinet-Oliphant, Heather; Vinod, Parvathi; Xue, Yaming; Russell-Lodrigue, Kasi; Albrecht, Randy A.; García-Sastre, Adolfo; Salazar, Andres M.; Roy, Chad J.; Kuroda, Marcelo J.; Oh, SangKon

    2014-01-01

    Despite the availability of annually formulated vaccines, influenza virus infection remains a worldwide public health burden. Therefore, it is important to develop preclinical challenge models that enable the evaluation of vaccine candidates while elucidating mechanisms of protection. Here, we report that naive rhesus macaques challenged with 2009 pandemic H1N1 (pH1N1) influenza virus do not develop observable clinical symptoms of disease but develop a subclinical biphasic fever on days 1 and 5 to 6 postchallenge. Whole blood microarray analysis further revealed that interferon activity was associated with fever. We then tested whether type I interferon activity in the blood is a correlate of vaccine efficacy. The animals immunized with candidate vaccines carrying hemagglutinin (HA) or nucleoprotein (NP) exhibited significantly reduced interferon activity on days 5 to 6 postchallenge. Supported by cellular and serological data, we conclude that blood interferon activity is a prominent marker that provides a convenient metric of influenza virus vaccine efficacy in the subclinical rhesus macaque model. PMID:25298110

  12. Lack of Group X Secreted Phospholipase A2 Increases Survival Following Pandemic H1N1 Influenza Infection

    PubMed Central

    Kelvin, Alyson A.; Degousee, Norbert; Banner, David; Stefanski, Eva; Leon, Alberto J.; Angoulvant, Denis; Paquette, Stéphane G.; Huang, Stephen S. H.; Danesh, Ali; Robbins, Clinton S.; Noyan, Hossein; Husain, Mansoor; Lambeau, Gerard; Gelb, Michael H.; Kelvin, David J.; Rubin, Barry B.

    2014-01-01

    The role of Group X secreted phospholipase A2 (GX-sPLA2) during influenza infection has not been previously investigated. We examined the role of (Reviewer 2 Minor Comment 2) GX-sPLA2 during H1N1 pandemic influenza infection in a GX-sPLA2 gene targeted mouse (GX−/−) model and found that survival after infection was significantly greater in GX−/− mice than in GX+/+ mice. Downstream products of GX-sPLA2 activity, PGD2, PGE2, LTB4, cysteinyl leukotrienes and Lipoxin A4 were significantly lower in GX−/− mice BAL fluid. Lung microarray analysis identified an earlier and more robust induction of T and B cell associated genes in GX−/− mice. Based on the central role of sPLA2 enzymes as key initiators of inflammatory processes, we propose that activation of GX-sPLA2 during H1N1pdm infection is an early step of pulmonary inflammation and its (Reviewer 2 Minor Comment 2) inhibition increases adaptive immunity and improves survival. Our findings suggest that GX-sPLA2 may be a potential therapeutic target during influenza. PMID:24725934

  13. Genetic and pathobiologic characterization of pandemic H1N1 2009 influenza viruses from a naturally infected swine herd.

    PubMed

    Weingartl, Hana M; Berhane, Yohannes; Hisanaga, Tamiko; Neufeld, James; Kehler, Helen; Emburry-Hyatt, Carissa; Hooper-McGreevy, Kathleen; Kasloff, Samantha; Dalman, Brett; Bystrom, Jan; Alexandersen, Soren; Li, Yan; Pasick, John

    2010-03-01

    Since its initial identification in Mexico and the United States, concerns have been raised that the novel H1N1 influenza virus might cause a pandemic of severity comparable to that of the 1918 pandemic. In late April 2009, viruses phylogenetically related to pandemic H1N1 influenza virus were isolated from an outbreak on a Canadian pig farm. This outbreak also had epidemiological links to a suspected human case. Experimental infections carried out in pigs using one of the swine isolates from this outbreak and the human isolate A/Mexico/InDRE4487/2009 showed differences in virus recovery from the lower respiratory tract. Virus was consistently isolated from the lungs of pigs infected with A/Mexico/InDRE4487/2009, while only one pig infected with A/swine/Alberta/OTH-33-8/2008 yielded live virus from the lung, despite comparable amounts of viral RNA and antigen in both groups of pigs. Clinical disease resembled other influenza virus infections in swine, albeit with somewhat prolonged virus antigen detection and delayed viral-RNA clearance from the lungs. There was also a noteworthy amount of genotypic variability among the viruses isolated from the pigs on the farm. This, along with the somewhat irregular pathobiological characteristics observed in experimentally infected animals, suggests that although the virus may be of swine origin, significant viral evolution may still be ongoing.

  14. Functional balance of the hemagglutinin and neuraminidase activities accompanies the emergence of the 2009 H1N1 influenza pandemic.

    PubMed

    Xu, Rui; Zhu, Xueyong; McBride, Ryan; Nycholat, Corwin M; Yu, Wenli; Paulson, James C; Wilson, Ian A

    2012-09-01

    The 2009 H1N1 influenza pandemic is the first human pandemic in decades and was of swine origin. Although swine are believed to be an intermediate host in the emergence of new human influenza viruses, there is still little known about the host barriers that keep swine influenza viruses from entering the human population. We surveyed swine progenitors and human viruses from the 2009 pandemic and measured the activities of the hemagglutinin (HA) and neuraminidase (NA), which are the two viral surface proteins that interact with host glycan receptors. A functional balance of these two activities (HA binding and NA cleavage) is found in human viruses but not in the swine progenitors. The human 2009 H1N1 pandemic virus exhibited both low HA avidity for glycan receptors as a result of mutations near the receptor binding site and weak NA enzymatic activity. Thus, a functional match between the hemagglutinin and neuraminidase appears to be necessary for efficient transmission between humans and may be an indicator of the pandemic potential of zoonotic viruses.

  15. MS2 Coliphage as a Surrogate for 2009 Pandemic Influenza A (H1N1) Virus (pH1N1) in Surface Survival Studies on N95 Filtering Facepiece Respirators

    PubMed Central

    Coulliette, A.D.; Perry, K.A.; Fisher, E.M.; Edwards, J.R.; Shaffer, R.E.; Noble-Wang, J.

    2015-01-01

    Research on influenza viruses regarding transmission and survival has surged in the recent years due to infectious emerging strains and outbreaks such as the 2009 Influenza A (H1N1) pandemic. MS2 coliphage has been applied as a surrogate for pathogenic respiratory viruses, such as influenza, as it’s safe for personnel to handle and requires less time and labor to measure virus infectivity. However, direct comparisons to determine the effectiveness of coliphage as a surrogate for influenza virus regarding droplet persistence on personal protective equipment such as N95 filtering facepiece respirators (FFRs) are lacking. Persistence of viral droplets deposited on FFRs in healthcare settings is important to discern due to the potential risk of infection via indirect fomite transmission. The objective of this study was to determine if MS2 coliphage could be applied as a surrogate for influenza A viruses for studying persistence when applied to the FFRs as a droplet. The persistence of MS2 coliphage and 2009 Pandemic Influenza A (H1N1) Virus on FFR coupons in different matrices (viral media, 2% fetal bovine serum, and 5 mg ml−1 mucin) were compared over time (4, 12, 24, 48, 72, and 144 hours) in typical absolute humidity conditions (4.1 × 105 mPa [18°C/20% relative humidity (RH)]). Data revealed significant differences in viral infectivity over the 6-day period (H1N1- P <0.0001; MS2 - P <0.005), although a significant correlation of viral log10 reduction in 2% FBS (P <0.01) was illustrated. Overall, MS2 coliphage was not determined to be a sufficient surrogate for influenza A virus with respect to droplet persistence when applied to the N95 FFR as a droplet. PMID:26500392

  16. Point of Care Strategy for Rapid Diagnosis of Novel A/H1N1 Influenza Virus

    PubMed Central

    Nougairede, Antoine; Ninove, Laetitia; Zandotti, Christine; de Lamballerie, Xavier; Gazin, Celine; Drancourt, Michel; La Scola, Bernard; Raoult, Didier; Charrel, Remi N.

    2010-01-01

    Background Within months of the emergence of the novel A/H1N1 pandemic influenza virus (nA/H1N1v), systematic screening for the surveillance of the pandemic was abandoned in France and in some other countries. At the end of June 2009, we implemented, for the public hospitals of Marseille, a Point Of Care (POC) strategy for rapid diagnosis of the novel A/H1N1 influenza virus, in order to maintain local surveillance and to evaluate locally the kinetics of the pandemic. Methodology/Principal Findings Two POC laboratories, located in strategic places, were organized to receive and test samples 24 h/24. POC strategy consisted of receiving and processing naso-pharyngeal specimens in preparation for the rapid influenza diagnostic test (RIDT) and real-time RT-PCR assay (rtRT-PCR). This strategy had the theoretical capacity of processing up to 36 samples per 24 h. When the flow of samples was too high, the rtRT-PCR test was abandoned in the POC laboratories and transferred to the core virology laboratory. Confirmatory diagnosis was performed in the core virology laboratory twice a day using two distinct rtRT-PCR techniques that detect either influenza A virus or nA/N1N1v. Over a period of three months, 1974 samples were received in the POC laboratories, of which 111 were positive for nA/H1N1v. Specificity and sensitivity of RIDT were 100%, and 57.7% respectively. Positive results obtained using RIDT were transmitted to clinical practitioners in less than 2 hours. POC processed rtRT-PCR results were available within 7 hours, and rtRT-PCR confirmation within 24 hours. Conclusions/Significance The POC strategy is of benefit, in all cases (with or without rtRT-PCR assay), because it provides continuous reception/processing of samples and reduction of the time to provide consolidated results to the clinical practitioners. We believe that implementation of the POC strategy for the largest number of suspect cases may improve the quality of patient care and our knowledge of the

  17. The influenza A (H1N1) pandemic in Reunion Island: knowledge, perceived risk and precautionary behaviour

    PubMed Central

    2013-01-01

    Background The effectiveness of preventive measures depends on prevailing attitudes and mindsets within a population. Perceived risk is central to a shift in mindset and behaviour. The present study aims to investigate the perceived severity, vulnerability and precautionary behaviour adopted in response to the influenza A (H1N1) epidemic that broke out in 2009 on Reunion Island (Indian Ocean). As no H1N1 vaccination was available at the time, non-medical interventions appeared of crucial importance to the control of the epidemic. Methods A cross sectional survey was conducted in Reunion Island between November 2009 and April 2010 within 2 months of the passage of the influenza A (H1N1) epidemic wave. Individual contacts representing 725 households (one contact per household) were interviewed by telephone using validated questionnaires on perceived risks. Mean scores were calculated for perceived severity, vulnerability, efficacy of preventive measures and precautionary behaviour. Univariate analysis was applied to identify preventive measures and attitudes and multivariate analysis was used to study the determinants of precautionary behaviour. Results More than 95% of contacted persons accepted to participate to the survey. Eighty seven percent of respondents believed that prevention was possible. On average, three out of six preventive measures were deemed effective. Spontaneously, 57% of the respondents reported that they took one or more preventive measures. This percentage increased to 87% after the interviewer detailed possible precautions one by one. The main precautions taken were frequent hand washing (59%) and avoidance of crowded places (34%). In multivariate logistic regression analysis the following factors were significantly associated with taking one or more preventive measures: young age, previous vaccination against seasonal influenza, having had seasonal influenza in the last five years, effectiveness of the preventive measures taken and low

  18. Influenza A/H1N1 septic shock in a patient with systemic lupus erythematosus. A case report

    PubMed Central

    2011-01-01

    Background Immunocompromised patients, such as systemic lupus erythematosus (SLE) sufferers have an increased risk of mortality, following influenza infection. In the recent pandemic, influenza A H1NI virus caused 18449 deaths, mainly because of adult respiratory distress syndrome or bacterial co-infections. Case Presentation In this case report, an SLE patient with viral-induced septic shock, without overt pulmonary involvement, is discussed. The patient was administered oseltamivir and supportive treatment, including wide-spectrum antibiotics, vasopressors and steroids, according to the guidelines proposed for bacterial sepsis and septic shock. She finally survived and experienced a lupus flare soon after intensive care unit (ICU) discharge. Conclusions To our knowledge, this is the first case to report severe septic shock from influenza A/H1N1 virus, without overt pulmonary involvement. PMID:22206235

  19. Neuraminidase Inhibitors and Hospital Mortality in British Patients with H1N1 Influenza A: A Re-Analysis of Observational Data

    PubMed Central

    Wolkewitz, Martin; Schumacher, Martin

    2016-01-01

    Background Observational studies claimed reducing effects of neuraminidase inhibitors (NI) on hospital mortality in patients with H1N1 influenza A. It has been criticized that such findings are prone to common and serious survival biases. Methods With observational data from the FLU-CIN study group, multi-state and dynamic prediction models have been used to avoid such biases. The data included 1391 patients with confirmed pandemic influenza A/H1N1 infection collected during 2009-2010 in the UK. Due to their close relationship, the main outcome measures were hospital death and length of hospital stay. Findings There is no direct effect of NI on the hospital death rate; the hazard ratio (HR) of NI was 1.03 (95%-CI: 0.64–1.66). The discharge rate is increased for NI patients (HR = 1.89 (95%-CI: 1.65–2.16)) indicating that NI-treated patients stay shorter in hospital than NI-untreated patients, on average 3.10 days (95%-CI: 2.07–4.14). We also showed that the initiation timing of NI treatment (≤ 2 days versus > 2 days after onset) made no difference on the effects on the hospital death and discharge hazards. The hazard ratios remain stable after adjusting for potential confounders measured at admission (such as comorbidities and influenza-related clinical symptoms). Conclusions The potential beneficial effect of NI on hospitalized patients in the UK is rather a reduction of the length of hospital stay than a reduction of the mortality rate. There seems to be no confounding by indication and no differences if NI is given early or late. Different effects could be present in other populations (such as non-hospitalized individuals) or countries. Careful interpretation of the effect on length of hospital stay is needed due to potentially different discharge policies of NI-treated and NI-untreated patients. PMID:27583403

  20. Simultaneous discrimination and detection of influenza A(H1N1)pdm09 and seasonal influenza A viruses using a rapid immunogold biosensor.

    PubMed

    Apiwat, Chayachon; Wiriyachaiporn, Natpapas; Maneeprakorn, Weerakanya; Dharakul, Tararaj; Thepthai, Charin; Puthavathana, Pilaipan; Siritantikorn, Sontana; Horthongkham, Navin

    2014-07-01

    A rapid immunogold biosensor for the simultaneous discrimination of influenza A(H1N1)pdm09 and seasonal influenza A viruses was developed successfully. Monoclonal antibodies (mAbs) that were specific for the hemagglutinin protein of the A(H1N1)pdm09 virus were produced, and the best mAb pairs were selected. Using an mAb that was specific for the influenza A nucleoprotein, a rapid immunogold biosensor for the discrimination and detection of A(H1N1)pdm09/seasonal influenza viruses was developed. When tested with 72 virus isolates, the system achieved 100 % detection of the A(H1N1)pdm09 virus without cross-reactivity against seasonal influenza A (H1, H3 subtypes) and B viruses, parainfluenza viruses, respiratory syncytial viruses, and adenoviruses. The detection limits for A(H1N1)pdm09 and seasonal strains were 5 × 10(2)-7.5 × 10(3) and 1 × 10(3)-7.5 × 10(5) TCID50/mL, respectively. When tested with 49 clinical specimens, the specificity was high (100 %). The sensitivity for the detection of A(H1N1)pdm09 and seasonal strains was 90 % and 100 %, respectively, which correlated with the results of real-time reverse transcription polymerase chain reaction as a reference method. The ability of the system to detect and discriminate the A(H1N1)pdm09 strain from the seasonal strains suggests that this method may be beneficial for investigation of outbreaks and diagnostic applications. Furthermore, this method might be a useful platform for developing a rapid diagnostic system for the simultaneous discrimination of other influenza virus subtypes during future outbreaks. PMID:24402634

  1. Gene expression analysis in children with complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis.

    PubMed

    Tsuge, Mitsuru; Oka, Takashi; Yamashita, Nobuko; Saito, Yukie; Fujii, Yosuke; Nagaoka, Yoshiharu; Yashiro, Masato; Tsukahara, Hirokazu; Morishima, Tsuneo

    2014-02-01

    Viral infections have been implicated as a cause of complex seizures in children. The pathogenic differences in complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis remain unclear. This study analyzed the gene expression profiles in the peripheral whole blood from pediatric patients with complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis. The gene expression profiles of ten patients (five with seizures and five without) with influenza A(H1N1)pdm09 and six patients (three with seizures and three without) with rotavirus gastroenteritis were examined. Gene expression profiles in the whole blood were different in complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis. Transcripts related to the immune response were significantly differentially expressed in complex seizures with influenza A(H1N1)pdm09, and transcripts related to the stress response were significantly differentially expressed in complex seizures with rotavirus gastroenteritis. Pathway analysis showed that the mitogen-activated protein kinases in the T cell receptor signaling pathway were activated in complex seizures due to influenza A(H1N1)pdm09. Dysregulation of the genes related to immune response or stress response could contribute to the pathogenic differences of the complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis.

  2. MicroRNA expression profiles and networks in mouse lung infected with H1N1 influenza virus.

    PubMed

    Bao, Yanyan; Gao, Yingjie; Jin, Yahong; Cong, Weihong; Pan, Xin; Cui, Xiaolan

    2015-10-01

    Influenza A viruses can cause localized outbreaks and worldwide pandemics, owing to their high transmissibility and wide host range. As such, they are among the major diseases that cause human death. However, the molecular changes induced by influenza A virus infection in lung tissue are not entirely clear. Changes in microRNA (miRNA) expression occur in many pathological and physiological processes, and influenza A virus infection has been shown to alter miRNA expression in cultured cells and animal models. In this study, we mined key miRNAs closely related to influenza A virus infection and explored cellular regulatory mechanisms against influenza A virus infection, by building networks among miRNAs and genes, gene ontologies (GOs), and pathways. In this study, miRNAs and mRNAs induced by H1N1 influenza virus infection were measured by gene chips, and we found that 82 miRNAs and 3371 mRNAs were differentially expressed. The 82 miRNAs were further analyzed with the series test of cluster (STC) analysis. Three of the 16 cluster profiles identified by STC, which include 46 miRNAs in the three profiles, changed significantly. Using potential target genes of the 46 miRNAs, we looked for intersections of these genes with 3371 differentially expressed mRNAs; 719 intersection genes were identified. Based on the GO or KEGG databases, we attained GOs or pathways for all of the above intersection genes. Fisher's and χ (2) test were used to calculate p value and false discovery rate (FDR), and according to the standard of p < 0.001, 241 GOs and 76 pathways were filtered. Based on these data, miRNA-gene, miRNA-GO, and miRNA-pathway networks were built. We then extracted three classes of GOs (related to inflammatory and immune response, cell cycle, proliferation and apoptosis, and signal transduction) to build three subgraphs, and pathways strictly related with H1N1 influenza virus infection were filtered to extract a subgraph of the miRNA-pathway network. Last, according

  3. Dietary lactosucrose suppresses influenza A (H1N1) virus infection in mice

    PubMed Central

    KISHINO, Eriko; TAKEMURA, Naho; MASAKI, Hisaharu; ITO, Tetsuya; NAKAZAWA, Masatoshi

    2015-01-01

    This study examined the effects of lactosucrose (4G-β-D-galactosylsucrose) on influenza A virus infections in mice. First, the effects of lactosucrose on fermentation in the cecum and on immune function were investigated. In female BALB/c mice, lactosucrose supplementation for 6 weeks promoted cecal fermentation and increased both secretory IgA (SIgA) levels in feces and total IgA and IgG2a concentrations in serum. Both the percentage of CD4+ T cells in Peyer’s patches and the cytotoxic activity of splenic natural killer (NK) cells increased significantly in response to lactosucrose. Next, we examined the effects of lactosucrose on low-dose influenza A virus infection in mice. After 2 weeks of dietary supplementation with lactosucrose, the mice were infected with low-dose influenza A virus. At 7 days post infection, a comparison with control mice showed that weight loss was suppressed, as were viral titers in the lungs. In the spleens of lactosucrose-fed mice, there was an increase in the percentage of NK cells. Lastly, mice fed lactosucrose were challenged with a lethal dose of influenza A virus. The survival rate of these mice was significantly higher than that of mice fed a control diet. These results suggested that lactosucrose supplementation suppresses influenza A virus infection by augmenting innate immune responses and enhancing cellular and mucosal immunity. PMID:26594606

  4. Evidence of Cross-Reactive Immunity to 2009 Pandemic Influenza A Virus in Workers Seropositive to Swine H1N1 Influenza Viruses Circulating in Italy

    PubMed Central

    De Marco, Maria A.; Porru, Stefano; Cordioli, Paolo; Cesana, Bruno M.; Moreno, Ana; Calzoletti, Laura; Bonfanti, Lebana; Boni, Arianna; Di Carlo, Antonio Scotto; Arici, Cecilia; Carta, Angela; Castrucci, Maria R.; Donatelli, Isabella; Tomao, Paola; Peri, Vittoria M.; Di Trani, Livia; Vonesch, Nicoletta

    2013-01-01

    Background Pigs play a key epidemiologic role in the ecology of influenza A viruses (IAVs) emerging from animal hosts and transmitted to humans. Between 2008 and 2010, we investigated the health risk of occupational exposure to swine influenza viruses (SIVs) in Italy, during the emergence and spread of the 2009 H1N1 pandemic (H1N1pdm) virus. Methodology/Principal Findings Serum samples from 123 swine workers (SWs) and 379 control subjects (Cs), not exposed to pig herds, were tested by haemagglutination inhibition (HI) assay against selected SIVs belonging to H1N1 (swH1N1), H1N2 (swH1N2) and H3N2 (swH3N2) subtypes circulating in the study area. Potential cross-reactivity between swine and human IAVs was evaluated by testing sera against recent, pandemic and seasonal, human influenza viruses (H1N1 and H3N2 antigenic subtypes). Samples tested against swH1N1 and H1N1pdm viruses were categorized into sera collected before (n. 84 SWs; n. 234 Cs) and after (n. 39 SWs; n. 145 Cs) the pandemic peak. HI-antibody titers ≥10 were considered positive. In both pre-pandemic and post-pandemic peak subperiods, SWs showed significantly higher swH1N1 seroprevalences when compared with Cs (52.4% vs. 4.7% and 59% vs. 9.7%, respectively). Comparable HI results were obtained against H1N1pdm antigen (58.3% vs. 7.7% and 59% vs. 31.7%, respectively). No differences were found between HI seroreactivity detected in SWs and Cs against swH1N2 (33.3% vs. 40.4%) and swH3N2 (51.2 vs. 55.4%) viruses. These findings indicate the occurrence of swH1N1 transmission from pigs to Italian SWs. Conclusion/Significance A significant increase of H1N1pdm seroprevalences occurred in the post-pandemic peak subperiod in the Cs (p<0.001) whereas SWs showed no differences between the two subperiods, suggesting a possible occurrence of cross-protective immunity related to previous swH1N1 infections. These data underline the importance of risk assessment and occupational health surveillance activities aimed at

  5. Outcomes of Influenza A(H1N1)pdm09 Virus Infection: Results from Two International Cohort Studies

    PubMed Central

    Lynfield, Ruth; Davey, Richard; Dwyer, Dominic E.; Losso, Marcelo H.; Wentworth, Deborah; Cozzi-Lepri, Alessandro; Herman-Lamin, Kathy; Cholewinska, Grazyna; David, Daniel; Kuetter, Stefan; Ternesgen, Zelalem; Uyeki, Timothy M.; Lane, H. Clifford; Lundgren, Jens; Neaton, James D.

    2014-01-01

    Background Data from prospectively planned cohort studies on risk of major clinical outcomes and prognostic factors for patients with influenza A(H1N1)pdm09 virus are limited. In 2009, in order to assess outcomes and evaluate risk factors for progression of illness, two cohort studies were initiated: FLU 002 in outpatients and FLU 003 in hospitalized patients. Methods and Findings Between October 2009 and December 2012, adults with influenza-like illness (ILI) were enrolled; outpatients were followed for 14 days and inpatients for 60 days. Disease progression was defined as hospitalization and/or death for outpatients, and hospitalization for >28 days, transfer to intensive care unit (ICU) if enrolled from general ward, and/or death for inpatients. Infection was confirmed by RT-PCR. 590 FLU 002 and 392 FLU 003 patients with influenza A (H1N1)pdm09 were enrolled from 81 sites in 17 countries at 2 days (IQR 1–3) and 6 days (IQR 4–10) following ILI onset, respectively. Disease progression was experienced by 29 (1 death) outpatients (5.1%; 95% CI: 3.4–7.2%) and 80 inpatients [death (32), hospitalization >28 days (43) or ICU transfer (20)] (21.6%; 95% CI: 17.5–26.2%). Disease progression (death) for hospitalized patients was 53.1% (26.6%) and 12.8% (3.8%), respectively, for those enrolled in the ICU and general ward. In pooled analyses for both studies, predictors of disease progression were age, longer duration of symptoms at enrollment and immunosuppression. Patients hospitalized during the pandemic period had a poorer prognosis than in subsequent seasons. Conclusions Patients with influenza A(H1N1)pdm09, particularly when requiring hospital admission, are at high risk for disease progression, especially if they are older, immunodeficient, or admitted late in infection. These data reinforce the need for international trials of novel treatment strategies for influenza infection and serve as a reminder of the need to monitor the severity of seasonal and pandemic

  6. Effectiveness of neuraminidase inhibitors in preventing hospitalization during the H1N1 influenza pandemic in British Columbia, Canada

    PubMed Central

    Marra, Fawziah; Chong, Mei; Henry, Bonnie; Patrick, David M.; Kendall, Perry

    2014-01-01

    Objectives In British Columbia (BC), Canada, neuraminidase inhibitors (NIs) were publicly funded during the 2009 A(H1N1)pdm09 pandemic for treatment of high-risk patients and/or anyone with moderate-to-severe illness. We assessed antiviral effectiveness (AVE) against hospitalization in that context. Methods A population-based cohort study was conducted using linked administrative data. The cohort included all individuals living in BC during the study period (1 September to 31 December 2009) with a diagnostic code consistent with influenza or pandemic H1N1. The main study period pertained to the second-wave A(H1N1)pdm09 circulation (1 October to 31 December 2009), with sensitivity analyses around the more specific pandemic peak (18 October to 7 November). Exposure was defined by same-day NI prescription. The main outcome was all-cause hospitalization within 14 days of the outpatient influenza diagnosis. Cox proportional hazards models assessed AVE with 1 : 1 propensity-score matching and covariate adjustment. Results After matching, there were 304/58 061 NI-exposed and 345/58 061 unexposed patients hospitalized during the main study period. The very young [<6 months (35.0; 95% CI 16.7–73.4)], the old [65–79 years (13.7; 95% CI 10.1–18.6)] and the very old [≥80 years (38.7; 95% CI 26.6–56.5)] had the highest hospitalization rate per 1000 patients overall. Fully adjusted AVE against all-cause hospitalization during the main study period was 16% (95% CI 2%–28%), similar to the pandemic peak (15%; 95% CI −4%–30%). Conclusions The use of NIs was associated with modest protection against hospitalization during the 2009 pandemic, but appeared underutilized in affected age groups with the highest hospitalization risk. PMID:24346762

  7. Genetic and Phylogenetic Analyses of Influenza A H1N1pdm Virus in Buenos Aires, Argentina ▿ †

    PubMed Central

    Barrero, P. R.; Viegas, M.; Valinotto, L. E.; Mistchenko, A. S.

    2011-01-01

    An influenza pandemic caused by swine-origin influenza virus A/H1N1 (H1N1pdm) spread worldwide in 2009, with 12,080 confirmed cases and 626 deaths occurring in Argentina. A total of 330 H1N1pdm viruses were detected from May to August 2009, and phylogenetic and genetic analyses of 21 complete genome sequences from both mild and fatal cases were achieved with reference to concatenated whole genomes. In addition, the analysis of another 16 hemagglutinin (HA), neuraminidase (NA), and matrix (M) gene sequences of Argentinean isolates was performed. The microevolution timeline was assessed and resistance monitoring of an NA fragment from 228 samples throughout the 2009 pandemic peak was performed by sequencing and pyrosequencing. We also assessed the viral growth kinetics for samples with replacements at the genomic level or special clinical features. In this study, we found by Bayesian inference that the Argentinean complete genome sequences clustered with globally distributed clade 7 sequences. The HA sequences were related to samples from the northern hemisphere autumn-winter from September to December 2009. The NA of Argentinean sequences belonged to the New York group. The N-4 fragment as well as the hierarchical clustering of samples showed that a consensus sequence prevailed in time but also that different variants, including five H275Y oseltamivir-resistant strains, arose from May to August 2009. Fatal and oseltamivir-resistant isolates had impaired growth and a small plaque phenotype compared to oseltamivir-sensitive and consensus strains. Although these strains might not be fit enough to spread in the entire population, molecular surveillance proved to be essential to monitor resistance and viral dynamics in our country. PMID:21047959

  8. THE EFFECT OF FEVER ON HOSPITAL PRESENTATION, DIAGNOSIS AND TREATMENT IN PATIENTS WITH H1N1/09 INFLUENZA

    PubMed Central

    Sopirala, Madhuri M.; Haas, Douglas M; Ali, Naeem A.; Mangino, Julie E.; Pan, Xueliang; Turner, Abigail Norris

    2014-01-01

    Objective Fever is typically considered part of the influenza-like illness in H1N1/09 influenza. We assessed the proportion of patients that did not have fever as part of their illness prior to hospital presentation. We assessed the role of fever on the delay in hospital presentation, diagnosis and treatment of these patients. Methods We performed a retrospective analysis of all hospitalized adult patients with laboratory-confirmed pandemic H1N1/09 at a tertiary care center in the United States from June 1 to December 31, 2009. Results Fifty-six of 135 study patients (42%) had no fever; 31 (23%) required ICU admission and nine (7%) died. Those without fever had higher Charlson index (p=0.01), significantly longer time to hospital presentation (median four vs. two days, p<0.001), longer time to treatment since the onset of illness (median five vs. two days, p =0.001), and were more frequently in an ICU (p=0.01). After adjustment for age (<40 vs ≥40) and Charlson index (0, 1-2, ≥3), patients without fever had significantly increased likelihood of late hospital presentation (greater than two days from the onset of illness) (p=0.001) and also had increased likelihood of ICU stay (p=0.05). Conclusions Forty-two percent of patients with laboratory-confirmed H1N1/09 did not have fever as part of their illness prior to hospital presentation. Patients without fever had delayed presentation to the hospital and thus experienced delayed treatment. PMID:23024066

  9. Identification of swine H1N2/pandemic H1N1 reassortant influenza virus in pigs, United States.

    PubMed

    Ali, Ahmed; Khatri, Mahesh; Wang, Leyi; Saif, Yehia M; Lee, Chang-Won

    2012-07-01

    In October and November 2010, novel H1N2 reassortant influenza viruses were identified from pigs showing mild respiratory signs that included cough and depression. Sequence and phylogenetic analysis showed that the novel H1N2 reassortants possesses HA and NA genes derived from recent H1N2 swine isolates similar to those isolated from Midwest. Compared to the majority of reported reassortants, both viruses preserved human-like host restrictive and putative antigenic sites in their HA and NA genes. The four internal genes, PB2, PB1, PA, and NS were similar to the contemporary swine triple reassortant viruses' internal genes (TRIG). Interestingly, NP and M genes of the novel reassortants were derived from the 2009 pandemic H1N1. The NP and M proteins of the two isolates demonstrated one (E16G) and four (G34A, D53E, I109T, and V313I) amino acid changes in the M2 and NP proteins, respectively. Similar amino acid changes were also noticed upon incorporation of the 2009 pandemic H1N1 NP in other reassortant viruses reported in the U.S. Thus the role of those amino acids in relation to host adaptation need to be further investigated. The reassortments of pandemic H1N1 with swine influenza viruses and the potential of interspecies transmission of these reassortants from swine to other species including human indicate the importance of systematic surveillance of swine population to determine the origin, the prevalence of similar reassortants in the U.S. and their impact on both swine production and public health.

  10. What have we learned from the novel influenza A (H1N1) pandemic in 2009 for strengthening pandemic influenza preparedness?

    PubMed

    Santos-Preciado, José; Franco-Paredes, Carlos; Hernandez-Flores, Isabel; Tellez, Ildefonso; Del Rio, Carlos; Tapia-Conyer, Roberto

    2009-11-01

    We need to apply lessons learned from previous influenza pandemics to continuously update preparedness and response plans. It has become evident that strengthening networks of international referral laboratories coupled with scaling-up efforts to expand epidemiological surveillance networks is critical for responding and mitigating the impact of influenza pandemics. The current swine-related influenza A (H1N1) pandemic has also shown that international collaboration remains a critical component to effectively respond to influenza pandemics in the current globalized world.

  11. Performance of the Directigen EZ Flu A+B rapid influenza diagnostic test to detect pandemic influenza A/H1N1 2009.

    PubMed

    Boyanton, Bobby L; Almradi, Amro; Mehta, Tejal; Robinson-Dunn, Barbara

    2014-04-01

    The Directigen EZ Flu A+B rapid influenza diagnostic test, as compared to real-time reverse transcriptase polymerase chain reaction, demonstrated suboptimal performance to detect pandemic influenza A/H1N1 2009. Age- and viral load-stratified test sensitivity ranged from 33.3 to 84.6% and 0 to 100%, respectively.

  12. Pandemic Swine-Origin H1N1 Influenza A Virus Isolates Show Heterogeneous Virulence in Macaques ▿ ‡

    PubMed Central

    Safronetz, David; Rockx, Barry; Feldmann, Friederike; Belisle, Sarah E.; Palermo, Robert E.; Brining, Douglas; Gardner, Don; Proll, Sean C.; Marzi, Andrea; Tsuda, Yoshimi; LaCasse, Rachel A.; Kercher, Lisa; York, Anthony; Korth, Marcus J.; Long, Dan; Rosenke, Rebecca; Shupert, W. Lesley; Aranda, Celia Alpuche; Mattoon, John S.; Kobasa, Darwyn; Kobinger, Gary; Li, Yan; Taubenberger, Jeffery K.; Richt, Jürgen A.; Parnell, Michael; Ebihara, Hideki; Kawaoka, Yoshihiro; Katze, Michael G.; Feldmann, Heinz

    2011-01-01

    The first influenza pandemic of the new millennium was caused by a newly emerged swine-origin influenza virus (SOIV) (H1N1). This new virus is characterized by a previously unknown constellation of gene segments derived from North American and Eurasian swine lineages and the absence of common markers predictive of human adaptation. Overall, human infections appeared to be mild, but an alarming number of young individuals presented with symptoms atypical for seasonal influenza. The new SOIV also showed a sustained human-to-human transmissibility and higher reproduction ratio than common seasonal viruses, altogether indicating a higher pathogenic potential for this newly emerged virus. To study the virulence of the SOIV, we used a recently established cynomolgus macaque model and compared parameters of clinical disease, virology, host responses, and pathology/histopathology with a current seasonal H1N1 virus. We here show that infection of macaques with two genetically similar but clinically distinct SOIV isolates from the early stage of the pandemic (A/Mexico/4108/2009 and A/Mexico/InDRE4487/2009) resulted in upper and lower respiratory tract infections and clinical disease ranging from mild to severe pneumonia that was clearly advanced over the mild infection caused by A/Kawasaki/UTK-4/2009, a current seasonal strain. Unexpectedly, we observed heterogeneity among the two SOIV isolates in virus replication, host transcriptional and cytokine responses, and disease progression, demonstrating a higher pathogenic potential for A/Mexico/InDRE4487/2009. Differences in virulence may explain more severe disease, as was seen with certain individuals infected with the emerged pandemic influenza virus. Thus, the nonhuman primate model closely mimics influenza in humans. PMID:21084481

  13. Serum activin A and B, and follistatin in critically ill patients with influenza A(H1N1) infection

    PubMed Central

    2014-01-01

    Background Activin A and its binding protein follistatin (FS) are increased in inflammatory disorders and sepsis. Overexpression of activin A in the lung causes similar histopathological changes as acute respiratory distress syndrome (ARDS). ARDS and severe respiratory failure are complications of influenza A(H1N1) infection. Interleukin 6 (IL-6), which in experimental studies increases after activin A release, is known to be related to the severity of H1N1 infection. Our aim was to evaluate the levels of activin A, activin B, FS, IL-6 and IL-10 and their association with the severity of respiratory failure in critically ill H1N1 patients. Methods A substudy of a prospective, observational cohort of H1N1 patients in Finnish intensive care units (ICU). Clinical information was recorded during ICU treatment, and serum activin A, activin B, FS, IL-6 and IL-10 were measured at admission to ICU and on days 2 and 7. Results Blood samples from 29 patients were analysed. At the time of admission to intensive care unit, elevated serum levels above the normal range for respective age group and sex were observed in 44% for activin A, 57% for activin B, and 39% for FS. In 13 of the 29 patients, serial samples at all time points were available and in these the highest activin A, activin B and FS were above the normal range in 85%, 100% and 46% of the patients, respectively. No difference in baseline or highest activin A or activin B was found in patients with or without acute lung injury (ALI) or ARDS (P > 0.05 for all). Peak levels of IL-6 were significantly elevated in ALI/ARDS patients. Peak activin A and activin A/FS were associated with ventilatory support free-days, severity of acute illness and length of ICU stay (P < 0.05 for all). Conclusions Higher than normal values of these proteins were common in patients with H1N1 infection but we found no association with the severity of their respiratory failure. PMID:24885241

  14. The value of radiographic findings for the progression of pandemic 2009 influenza A/H1N1 virus infection

    PubMed Central

    2013-01-01

    Background Most illnesses caused by pandemic influenza A (H1N1) pdm09 virus (A/H1N1) infection are acute and self-limiting among children. However, in some children, disease progression is rapid and may require hospitalization and transfer to a pediatric intensive care unit (PICU). We investigated factors associated with rapid disease progression among children admitted to hospital for A/H1N1 infection, particularly findings on initial chest radiographs. Methods In this retrospective study, we investigated the records of children who had received a laboratory or clinical diagnosis of A/H1N1 infection and were admitted to the largest children’s hospital in Japan between May 2009 and March 2010. The medical records were reviewed for age, underlying diseases, vital signs on admission, initial chest radiographic findings, and clinical outcomes. According to chest radiographic findings, patients were classified into 4 groups, as follows: [1] normal (n = 46), [2] hilar and/or peribronchial markings alone (n = 64), [3] consolidation (n = 64), and [4] other findings (n = 29). Factors associated with clinical outcomes were analyzed using logistic regression. Results Two hundreds and three patients (median 6.8 years) were enrolled in this study. Fifteen percent (31/203) of patients were admitted to PICU. Among 31 patients, 39% (12/31) of patients required mechanical ventilation (MV). When the initial chest radiographic findings were compared between patients with consolidation (n = 64) and those without consolidation (n = 139), a higher percentage of patients with consolidation were admitted to PICU (29.7% vs.8.6%, P < 0.001) and required MV (17.2% vs. 0.7%, P < 0.001). These findings remain significant when the data were analyzed with the logistic regression (P < 0.001, P < 0.001, respectively). Conclusions Consolidation on initial chest radiographs was the most significant factor to predict clinical course of hospitalized children with the 2009 A/H1N1 infection. PMID

  15. In situ molecular identification of the Influenza A (H1N1) 2009 Neuraminidase in patients with severe and fatal infections during a pandemic in Mexico City

    PubMed Central

    2013-01-01

    Background In April 2009, public health surveillance detected an increased number of influenza-like illnesses in Mexico City’s hospitals. The etiological agent was subsequently determined to be a spread of a worldwide novel influenza A (H1N1) triple reassortant. The purpose of the present study was to demonstrate that molecular detection of pandemic influenza A (H1N1) 2009 strains is possible in archival material such as paraffin-embedded lung samples. Methods In order to detect A (H1N1) virus sequences in archived biological samples, eight paraffin-embedded lung samples from patients who died of pneumonia and respiratory failure were tested for influenza A (H1N1) Neuraminidase (NA) RNA using in situ RT-PCR. Results We detected NA transcripts in 100% of the previously diagnosed A (H1N1)-positive samples as a cytoplasmic signal. No expression was detected by in situ RT-PCR in two Influenza-like Illness A (H1N1)-negative patients using standard protocols nor in a non-related cervical cell line. In situ relative transcription levels correlated with those obtained when in vitro RT-PCR assays were performed. Partial sequences of the NA gene from A (H1N1)-positive patients were obtained by the in situ RT-PCR-sequencing method. Sequence analysis showed 98% similarity with influenza viruses reported previously in other places. Conclusions We have successfully amplified specific influenza A (H1N1) NA sequences using stored clinical material; results suggest that this strategy could be useful when clinical RNA samples are quantity limited, or when poor quality is obtained. Here, we provide a very sensitive method that specifically detects the neuraminidase viral RNA in lung samples from patients who died from pneumonia caused by Influenza A (H1N1) outbreak in Mexico City. PMID:23327529

  16. Short communication: antiviral activity of subcritical water extract of Brassica juncea against influenza virus A/H1N1 in nonfat milk.

    PubMed

    Lee, N-K; Lee, J-H; Lim, S-M; Lee, K A; Kim, Y B; Chang, P-S; Paik, H-D

    2014-09-01

    Subcritical water extract (SWE) of Brassica juncea was studied for antiviral effects against influenza virus A/H1N1 and for the possibility of application as a nonfat milk supplement for use as an "antiviral food." At maximum nontoxic concentrations, SWE had higher antiviral activity against influenza virus A/H1N1 than n-hexane, ethanol, or hot water (80°C) extracts. Addition of 0.5mg/mL of B. juncea SWE to culture medium led to 50.35% cell viability (% antiviral activity) for Madin-Darby canine kidney cells infected with influenza virus A/H1N1. Nonfat milk supplemented with 0.28mg/mL of B. juncea SWE showed 39.62% antiviral activity against influenza virus A/H1N1. Thus, the use of B. juncea SWE as a food supplement might aid in protection from influenza viral infection.

  17. Short communication: antiviral activity of subcritical water extract of Brassica juncea against influenza virus A/H1N1 in nonfat milk.

    PubMed

    Lee, N-K; Lee, J-H; Lim, S-M; Lee, K A; Kim, Y B; Chang, P-S; Paik, H-D

    2014-09-01

    Subcritical water extract (SWE) of Brassica juncea was studied for antiviral effects against influenza virus A/H1N1 and for the possibility of application as a nonfat milk supplement for use as an "antiviral food." At maximum nontoxic concentrations, SWE had higher antiviral activity against influenza virus A/H1N1 than n-hexane, ethanol, or hot water (80°C) extracts. Addition of 0.5mg/mL of B. juncea SWE to culture medium led to 50.35% cell viability (% antiviral activity) for Madin-Darby canine kidney cells infected with influenza virus A/H1N1. Nonfat milk supplemented with 0.28mg/mL of B. juncea SWE showed 39.62% antiviral activity against influenza virus A/H1N1. Thus, the use of B. juncea SWE as a food supplement might aid in protection from influenza viral infection. PMID:25022686

  18. [Spatial and temporal spread predictability of influenza A H1N1 epidemic in Argentina by the percolation method].

    PubMed

    Cuestas, Eduardo; Vilaró, Mario; Serra, Pablo

    2011-01-01

    The influenza A H1N1 epidemic has spread rapidly worldwide on account of the current conditions of high interconnectivity and transport speed both among people and countries. The spatial spread of the epidemics can be explained by the percolation theory which allows to estimate a threshold beyond which the transmission of the infection among different geographic regions occurs. The aim of this study was to test the predictive ability of the percolation model of influenza A H1N1 epidemic in Argentina according to data gathered by the National Department of Public Health. In the model, the country was considered as a set of irregular, contiguous and continuous geometric figures, which can be represented in two dimensions on a plane. We analyzed the proportion of infected provinces at the moment of percolation in relation to time in days and compared observed and expected values by curvilinear equations in a logistic model. Percolation occurred on day 45. The expected value generated by the model was 42.4 days, 95 % CI 28.5 to 56.3. The difference between observed and expected values was p = 0.997. We conclude that the model has good fit and predictive capacity.

  19. Epistatic interactions between neuraminidase mutations facilitated the emergence of the oseltamivir-resistant H1N1 influenza viruses

    PubMed Central

    Duan, Susu; Govorkova, Elena A.; Bahl, Justin; Zaraket, Hassan; Baranovich, Tatiana; Seiler, Patrick; Prevost, Kristi; Webster, Robert G.; Webby, Richard J.

    2014-01-01

    Oseltamivir-resistant H1N1 influenza viruses carrying the H275Y neuraminidase mutation predominated worldwide during the 2007–2009 seasons. While several neuraminidase substitutions were found to be necessary to counteract the adverse effects of H275Y, the order and impact of evolutionary events involved remain elusive. Here, we reconstruct H1N1 ne