Science.gov

Sample records for 2009-2010 h1n1 influenza

  1. A DESCRIPTIVE STUDY OF PANDEMIC INFLUENZA A(H1N1)PDM09 IN BRAZIL, 2009 - 2010.

    PubMed

    Rossetto, Erika Valeska; Luna, Expedito José de Albuquerque

    2016-11-03

    Influenza A viruses undergo frequent antigenic mutations and may thus cause seasonal epidemics and pandemics. The aim of this study was to recover the epidemiological history of the pandemic influenza A(H1N1)pdm09 in Brazil. A descriptive study was conducted in 2009-2010. The Brazilian Information System for reportable diseases (SINAN) was the data source. A total of 105,054 suspected cases of influenza A(H1N1)pdm09 were reported to SINAN. Of these, 53,797 (51.2%) were classified as the new influenza virus subtype. Among the confirmed cases, 56.7% were female, the mean age was 26.31 (SD ± 18.1) years. Fever was the most common sign among the confirmed cases (99.7%) and the presence of comorbidities was reported in 32.5% of cases. In 2009 there were confirmed cases in all 26 Brazilian States and the Federal District. The incidence (per 100,000 inhabitants) of severe influenza in the population was 28.0 in 2009 and 0.5 in 2010. The states of Paraná (301.3), Santa Catarina (36.0) and Rio Grande do Sul (27.4) presented the highest incidence; 46.4% of the confirmed cases were hospitalized and 47,643 were cured (93.8%). The case-fatality rate was 3.9% in 2009. The pandemic virus A(H1N1)pdm09 hit Brazil between April/2009 and December/2010 with an important difference in the geographic pattern distribution of the cases from the northeast to the south of the country. Children and young adults were the most affected. The limitations of the study were data quality and inconsistencies in the final classification of cases in SINAN. This study highlights the urgent need for improvements in the surveillance of emerging diseases in Brazil.

  2. A DESCRIPTIVE STUDY OF PANDEMIC INFLUENZA A(H1N1)PDM09 IN BRAZIL, 2009 - 2010

    PubMed Central

    ROSSETTO, Erika Valeska; LUNA, Expedito José de Albuquerque

    2016-01-01

    SUMMARY Influenza A viruses undergo frequent antigenic mutations and may thus cause seasonal epidemics and pandemics. The aim of this study was to recover the epidemiological history of the pandemic influenza A(H1N1)pdm09 in Brazil. A descriptive study was conducted in 2009-2010. The Brazilian Information System for reportable diseases (SINAN) was the data source. A total of 105,054 suspected cases of influenza A(H1N1)pdm09 were reported to SINAN. Of these, 53,797 (51.2%) were classified as the new influenza virus subtype. Among the confirmed cases, 56.7% were female, the mean age was 26.31 (SD ± 18.1) years. Fever was the most common sign among the confirmed cases (99.7%) and the presence of comorbidities was reported in 32.5% of cases. In 2009 there were confirmed cases in all 26 Brazilian States and the Federal District. The incidence (per 100,000 inhabitants) of severe influenza in the population was 28.0 in 2009 and 0.5 in 2010. The states of Paraná (301.3), Santa Catarina (36.0) and Rio Grande do Sul (27.4) presented the highest incidence; 46.4% of the confirmed cases were hospitalized and 47,643 were cured (93.8%). The case-fatality rate was 3.9% in 2009. The pandemic virus A(H1N1)pdm09 hit Brazil between April/2009 and December/2010 with an important difference in the geographic pattern distribution of the cases from the northeast to the south of the country. Children and young adults were the most affected. The limitations of the study were data quality and inconsistencies in the final classification of cases in SINAN. This study highlights the urgent need for improvements in the surveillance of emerging diseases in Brazil. PMID:27828619

  3. School illness absenteeism during 2009 influenza A (H1N1) pandemic--South Dakota, 2009-2010.

    PubMed

    Kightlinger, Lon; Horan, Vickie

    2013-05-01

    Schools are important amplification settings of influenza virus transmission. We demonstrated correlation of school absenteeism (due to any illness) with other influenza A (H1N1) activity surveillance data during the 2009 pandemic. We collected nonspecific illness student absenteeism data from August 17, 2009 through April 3, 2010 from 187 voluntarily participating South Dakota schools using weekly online surveys. Relative risks (RR) were calculated as the ratio of the probability of absenteeism during elevated weeks versus the probability of absenteeism during the baseline weeks (RR = 1.89). We used Pearson correlation to associate absenteeism with laboratory-confirmed influenza cases, influenza cases diagnosed by rapid tests, influenza-associated hospitalizations and deaths reported in South Dakota during the 2009 H1N1 pandemic period. School-absenteeism data correlated strongly with data from these other influenza surveillance sources.

  4. 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.

  5. 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.

  6. Effectiveness of the monovalent influenza A(H1N1)2009 vaccine in Navarre, Spain, 2009-2010: cohort and case-control study.

    PubMed

    Castilla, Jesús; Morán, Julio; Martínez-Artola, Víctor; Fernández-Alonso, Mirian; Guevara, Marcela; Cenoz, Manuel García; Reina, Gabriel; Alvarez, Nerea; Arriazu, Maite; Elía, Fernando; Salcedo, Esther; Barricarte, Aurelio

    2011-08-11

    We defined a population-based cohort (596,755 subjects) in Navarre, Spain, using electronic records from physicians, to evaluate the effectiveness of the monovalent A(H1N1)2009 vaccine in preventing influenza in the 2009-2010 pandemic season. During the 9-week period of vaccine availability and circulation of the A(H1N1)2009 virus, 4608 cases of medically attended influenza-like illness (MA-ILI) were registered (46 per 1000 person-years). After adjustment for sociodemographic covariables, outpatient visits and major chronic conditions, vaccination was associated with a 32% (95% CI: 8-50%) reduction in the overall incidence of MA-ILI. In a test negative case-control analysis nested in the cohort, swabs from 633 patients were included, and 123 were confirmed for A(H1N1)2009 influenza. No confirmed case had received A(H1N1)2009 vaccine versus 9.6% of controls (p<0.001). The vaccine effectiveness in preventing laboratory-confirmed influenza was 89% (95% CI: 36-100%) after adjusting for age, health care setting, major chronic conditions and period. Pandemic vaccine was effective in preventing MA-ILI and confirmed cases of influenza A(H1N1)2009 in the 2009-2010 season.

  7. 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…

  8. Costs of school-located influenza vaccination clinics in Maine during the 2009-2010 H1N1 pandemic.

    PubMed

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

    2012-10-01

    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 completed a clinic day survey on staff time; four of the six also provided data for materials and supplies. For all clinics, average per-dose labor cost was estimated at $5.95. Average per-dose material cost, excluding vaccine, was $5.76. From the four complete clinic survey responses, total per-dose cost was estimated to be an average of $13.51 (range = $4.91-$32.39). Use of donated materials and uncompensated volunteer staff could substantially reduce per-dose cost. Average per-dose cost could also be lowered by increasing the number of doses administered in a clinic.

  9. 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

  10. 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.

  11. Impact of the 2009/2010 influenza A (H1N1) pandemic on trends in influenza hospitalization, diagnostic testing, and treatment.

    PubMed

    Hernandez, Jaime E; Grainger, Joanne; Simonsen, Lone; Collis, Phil; Edelman, Laurel; Sheridan, William P

    2012-09-01

    Analysis of a US hospitalization database demonstrated that more influenza patients were hospitalized and the age distribution of hospitalizations was younger during the 2009 (H1N1) influenza A pandemic compared with the three previous influenza seasons. The duration of hospital stay remained stable in all four seasons. A higher proportion of patients was treated with antivirals (P < 0·0001), comprised almost entirely of neuraminidase inhibitors, and the proportion was highest in those with influenza confirmed by diagnostic testing (P < 0·0001). Approximately one-third remained untreated. Young children had the lowest rate of neuraminidase-inhibitor treatment during the 2009 pandemic (P < 0·05).

  12. Phase II Trial in Adults of Concurrent or Sequential 2009 Pandemic H1N1 and 2009-2010 Seasonal Trivalent Influenza Vaccinations

    PubMed Central

    Frey, Sharon E.; Bernstein, David I.; Brady, Rebecca C.; Keitel, Wendy A.; Sahly, Hana El; Rouphael, Nadine Georges; Mulligan, Mark J.; Atmar, Robert L.; Edupuganti, Srilatha; Patel, Shital M.; Dickey, Michelle; Graham, Irene; Anderson, Edwin L.; Noah, Diana L.; Hill, Heather; Wolff, Mark; Belshe, Robert B.

    2014-01-01

    Background During the 2009 influenza pandemic both seasonal and 2009 pandemic vaccines were recommended. We conducted a randomized trial of monovalent 2009-H1N1 vaccine and seasonal trivalent inactivated influenza vaccine (IIV3) given sequentially or concurrently to adults. Methods Adults randomized to 4 study groups and stratified by age (18-64 and ≥65 years) received 1 dose of seasonal IIV3 or placebo and 2 doses of 2009-H1N1 vaccine or placebo in one of 4 combinations, i.e., H1N1+Placebo/H1N1+Placebo/IIV3 (HP/HP/V3), H1N1+ IIV3/H1N1+Placebo/Placebo (HV3/HP/P), H1N1+Placebo/H1N1+ IIV3/Placebo (HP/HV3/P), and IIV3+Placebo/H1N1+Placebo/H1N1 (V3P/HP/H). Intramuscular injections were given three times at 21 day intervals. Sera for antibody assays were obtained prior to and 21 days after each vaccination. Reactogenicity and adverse events were monitored. Results Eight hundred-five (805) adults were enrolled. All combinations of vaccines were safe and well tolerated. In general, one dose of 2009-H1N1 and one dose of IIV3, regardless of sequence or concurrency of administration, were immunogenic in adults. There were no significant differences in geometric mean titers (GMT) or the proportions of subjects with ≥4-fold rise in antibody responses and titers ≥40 for any vaccine group or between age strata for 2009-H1N1 after the first or second dose, although the vaccine sequence affected the titers to the IIV3 antigens. Hemagglutination inhibition antibody (HAI) GMTs against 2009-H1N1 for the combined age strata 21 days after the first 2009-H1N1 dose were 190.4, 182.1, 232.9 and 157.5 for HP/HP/V3, HV3/HP/P, HP/HV3/P and V3P/HP/H, respectively. While IIV3 GMTs were adequate they were generally lower than the 2009-H1N1 GMTs. In a subset of subjects, there was good correlation between HAI and microneutralization (MN) titers (Spearman's correlation coefficient 0.92). Conclusions All vaccine combinations were generally well tolerated. Immune responses to one dose of 2009

  13. [Clinical course of influenza A(H1N1)v in children treated in Warsaw in season 2009/2010].

    PubMed

    Talarek, Ewa; Dembiński, Łukasz; Radzikowski, Andrzej; Smalisz-Skrzypczyk, Katarzyna; Jackowska, Teresa; Marczyńska, Magdalena

    2010-01-01

    In the autumn 2009 in Poland there was an outbreak of influenza A(H1N1)v, approximately 1/3 of confirmed cases in children younger than 14 years. The aim of the study was an epidemiologic and clinical characteristics of pediatric patients with influenza A(H1N1)v and evaluation of antiviral treatment safety. The medical records of 100 children with confirmed influenza A(H1N1)v were reviewed. 48% of children had risk factors for severe clinical course, including 23 younger than 2 years. The most common symptoms were fever (89%) and cough (68%). In 20% children pneumonia was diagnosed, other complications were uncommon. 4 patients required mechanical ventilation and 3 died, all with severe underlying conditions. In 62% of patients oseltamivir was used and it was well tolerated.

  14. 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.

  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. Perspectives of Pulmonologists on the 2009-2010 H1N1 Vaccination Effort.

    PubMed

    Clark, Sarah J; Cowan, Anne E; Wortley, Pascale M

    2012-01-01

    Persons with high-risk conditions such as asthma were a target group for H1N1 vaccine recommendations. We conducted a mailed survey of a national sample of pulmonologists to understand their participation in the 2009-2010 H1N1 vaccine campaign. The response rate was 59%. The majority of pulmonologists strongly recommended H1N1 vaccine for children (73%) and adults aged 25-64 years (51%). Only 60% of respondents administered H1N1 vaccine in their practice compared to 87% who offered seasonal influenza vaccine. Other than vaccine supply, respondents who provided H1N1 vaccine reported few logistical problems. Two-thirds of respondents would be very likely to vaccinate during a future influenza pandemic; this rate was higher among those who provided H1N1 vaccine and/or seasonal flu vaccine. In total, the H1N1 vaccine-related experiences of pulmonologists seemed to be positive. However, additional efforts are needed to increase participation in future pandemic vaccination campaigns.

  17. [Influenza pandemic (H1N1) 2009].

    PubMed

    Oshitani, Hitoshi

    2009-12-01

    In the past, influenza pandemics have been occurring every 20 to 30 years. Highly pathogenic avian influenza A(H5N1) has been causing unprecedented global outbreaks since 2003 and many human cases with a high case fatality rate have also been reported. But the virus that caused a pandemic in 2009 was A(H1N1) that was originated from swine influenza. The same subtype, A(H1N1) has been circulating in human population since 1977. This pandemic (H1N1) 2009 is also not as virulent as A(H5N1) in humans. Many aspects of pandemic (H1N1) 2009 are different from what we had been expecting. We should reconsider the concepts and the strategies for influenza pandemic by reviewing current pandemic (H1N1).

  18. Using surveillance data to estimate pandemic vaccine effectiveness against laboratory confirmed influenza A(H1N1)2009 infection: two case-control studies, Spain, season 2009-2010

    PubMed Central

    2011-01-01

    Background Physicians of the Spanish Influenza Sentinel Surveillance System report and systematically swab patients attended to their practices for influenza-like illness (ILI). Within the surveillance system, some Spanish regions also participated in an observational study aiming at estimating influenza vaccine effectiveness (cycEVA study). During the season 2009-2010, we estimated pandemic influenza vaccine effectiveness using both the influenza surveillance data and the cycEVA study. Methods We conducted two case-control studies using the test-negative design, between weeks 48/2009 and 8/2010 of the pandemic season. The surveillance-based study included all swabbed patients in the sentinel surveillance system. The cycEVA study included swabbed patients from seven Spanish regions. Cases were laboratory-confirmed pandemic influenza A(H1N1)2009. Controls were ILI patients testing negative for any type of influenza. Variables collected in both studies included demographic data, vaccination status, laboratory results, chronic conditions, and pregnancy. Additionally, cycEVA questionnaire collected data on previous influenza vaccination, smoking, functional status, hospitalisations, visits to the general practitioners, and obesity. We used logistic regression to calculate adjusted odds ratios (OR), computing pandemic influenza vaccine effectiveness as (1-OR)*100. Results We included 331 cases and 995 controls in the surveillance-based study and 85 cases and 351 controls in the cycEVA study. We detected nine (2.7%) and two (2.4%) vaccine failures in the surveillance-based and cycEVA studies, respectively. Adjusting for variables collected in surveillance database and swabbing month, pandemic influenza vaccine effectiveness was 62% (95% confidence interval (CI): -5; 87). The cycEVA vaccine effectiveness was 64% (95%CI: -225; 96) when adjusting for common variables with the surveillance system and 75% (95%CI: -293; 98) adjusting for all variables collected. Conclusion

  19. Risk of confirmed Guillain-Barre syndrome following receipt of monovalent inactivated influenza A (H1N1) and seasonal influenza vaccines in the Vaccine Safety Datalink Project, 2009-2010.

    PubMed

    Greene, Sharon K; Rett, Melisa; Weintraub, Eric S; Li, Lingling; Yin, Ruihua; Amato, Anthony A; Ho, Doreen T; Sheikh, Sarah I; Fireman, Bruce H; Daley, Matthew F; Belongia, Edward A; Jacobsen, Steven J; Baxter, Roger; Lieu, Tracy A; Kulldorff, Martin; Vellozzi, Claudia; Lee, Grace M

    2012-06-01

    An increased risk of Guillain-Barré syndrome (GBS) following administration of the 1976 swine influenza vaccine led to a heightened focus on GBS when monovalent vaccines against a novel influenza A (H1N1) virus of swine origin were introduced in 2009. GBS cases following receipt of monovalent inactivated (MIV) and seasonal trivalent inactivated (TIV) influenza vaccines in the Vaccine Safety Datalink Project in 2009-2010 were identified in electronic data and confirmed by medical record review. Within 1-42 days following vaccination, 9 cases were confirmed in MIV recipients (1.48 million doses), and 8 cases were confirmed in TIV-only recipients who did not also receive MIV during 2009-2010 (1.72 million doses). Five cases following MIV and 1 case following TIV-only had an antecedent respiratory infection, a known GBS risk factor; furthermore, unlike TIV, MIV administration was concurrent with heightened influenza activity. In a self-controlled risk interval analysis comparing GBS onset within 1-42 days following MIV with GBS onset 43-127 days following MIV, the risk difference was 5.0 cases per million doses (95% confidence interval: 0.5, 9.5). No statistically significant increased GBS risk was found within 1-42 days following TIV-only vaccination versus 43-84 days following vaccination (risk difference = 1.1 cases per million doses, 95% confidence interval: -3.1, 5.4). Further evaluation to assess GBS risk following both vaccination and respiratory infection is warranted.

  20. Department of Defense Biological Threat Responses to the 2009-2010 H1N1 Influenza Outbreak: A Real World Exercise (Counterproliferation Paper Number 51, April 2011)

    DTIC Science & Technology

    2011-04-01

    influenza - epidemic/>. 11Influenza of 1918 ( Spanish Flu) and the US Navy. Navy Dept. Library. 8 Jun. 2010 <http://www.history.navy.mil/library/online...influenza_main.htm>. 12 Oxford, JS, et al. “World War I May Have Allowed the Emergence of “ Spanish ” Influenza .” Lancet Infectious Diseases 2:2... Influenza of 1918 ( Spanish Flu) and the US Navy. 17 Feb. 2006. Navy Department Library. 8 Jun. 2010. <http

  1. 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.

  2. Isolation and characterization of pandemic H1N1 influenza viruses in pigs in Brazil

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Influenza A virus (IAV) infections are endemic diseases in pork producing countries around the world. The emergence of the pandemic 2009 human H1N1 influenza A virus (pH1N1) raised questions about the occurrence of this virus in Brazilian swine populations. During a 2009-2010 swine influenza virus r...

  3. A subregional analysis of epidemiologic and genetic characteristics of influenza A(H1N1)pdm09 in Africa: Senegal, Cape Verde, Mauritania, and Guinea, 2009-2010.

    PubMed

    Dia, Ndongo; Ndiaye, Mbayame Niang; Monteiro, Maria de Lourdes; Koivogui, Lamine; Bara, Mohamed Ould; Diop, Ousmane M

    2013-05-01

    During the pandemic 2009 episode, we conducted laboratory-based surveillance in four countries from West Africa: Senegal, Mauritania, Cape Verde, and Guinea. Specimens were obtained from 3,155 patients: 2,264 patients from Senegal, 498 patients from Cape Verde, 227 patients from Mauritania, and 166 patients from Guinea; 911 (28.9%) patients were positive for influenza, 826 (90.7%) patients were positive for influenza A, and 85 (9.3%) patients were positive for influenza B. Among the influenza A positives, 503 (60.9%) positives were H1N1pdm09, 314 (38.0%) positives were H3N2, and 9 (1.1%) positives were seasonal H1N1. The highest detection rate for seasonal influenza viruses (17.1%) occurred in the 5-14 years age group. However, for A(H1N1)pdm09, the detection rate was highest in the 15-24 years age group (35.8%). Based on the present study data, the timeline of detection of A(H1N1)pdm09 viruses in these four countries should be Cape Verde, Guinea, Mauritania, and finally, Senegal. Genetic and antigenic analyses were performed in some isolates.

  4. 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

  5. '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.

  6. 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.

  7. Pandemic H1N1 influenza virus in Chilean commercial turkeys with genetic and serologic comparisons to U.S. H1N1 avian influenza vaccine isolates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Beginning in April 2009, a novel H1N1 influenza virus has caused acute respiratory disease in humans, first in Mexico and then spreading around the world. The resulting pandemic influenza A H1N1 2009 (pH1N1) virus was isolated in swine in Canada in June, 2009, and later in turkey breeders in Chile, ...

  8. 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

  9. 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.

  10. 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.

  11. Influenza A/H1N1 2009 Pandemic and Respiratory Virus Infections, Beijing, 2009–2010

    PubMed Central

    Wang, Wei; Vernet, Guy; Paranhos-Baccalà, Gláucia; Jin, Qi; Wang, Jianwei

    2012-01-01

    To determine the role of the pandemic influenza A/H1N1 2009 (A/H1N1 2009pdm) in acute respiratory tract infections (ARTIs) and its impact on the epidemic of seasonal influenza viruses and other common respiratory viruses, nasal and throat swabs taken from 7,776 patients with suspected viral ARTIs from 2006 through 2010 in Beijing, China were screened by real-time PCR for influenza virus typing and subtyping and by multiplex or single PCR tests for other common respiratory viruses. We observed a distinctive dual peak pattern of influenza epidemic during the A/H1N1 2009pdm in Beijing, China, which was formed by the A/H1N1 2009pdm, and a subsequent influenza B epidemic in year 2009/2010. Our analysis also shows a small peak formed by a seasonal H3N2 epidemic prior to the A/H1N1 2009pdm peak. Parallel detection of multiple respiratory viruses shows that the epidemic of common respiratory viruses, except human rhinovirus, was delayed during the pandemic of the A/H1N1 2009pdm. The H1N1 2009pdm mainly caused upper respiratory tract infections in the sampled patients; patients infected with H1N1 2009pdm had a higher percentage of cough than those infected with seasonal influenza or other respiratory viruses. Our findings indicate that A/H1N1 2009pdm and other respiratory viruses except human rhinovirus could interfere with each other during their transmission between human beings. Understanding the mechanisms and effects of such interference is needed for effective control of future influenza epidemics. PMID:23029253

  12. Influenza A H1N1 2009 (Swine Flu) and Pregnancy.

    PubMed

    Lim, Boon H; Mahmood, Tahir A

    2011-08-01

    The Influenza A H1N1 pandemic (A H1N1) occurred between June 2009 and August 2010. Although the pandemic is now over, the virus has emerged as the predominant strain in the current seasonal influenza phase in the northern hemisphere. The A H1N1 influenza is a novel strain of the influenza A virus and is widely known as swine flu. The virus contains a mixture of genetic material from human, pig and bird flu virus. It is a new variety of flu which people have not had much immunity to. Much has been learnt from the Pandemic of 2009/2010 but the messages about vaccination and treatment seem to be taken slowly by the clinical profession. Most people affected by the virus, including pregnant women, suffer a mild viral illness, and make a full recovery. The median duration of illness is around seven days. This influenza typically affects the younger age group i.e. from the ages of 5-65 years. Current experience shows that the age group experiencing increased morbidity and mortality rates are in those under 65 years of age. Pregnant women, because of their altered immunity and physiological adaptations, are at higher risk of developing pulmonary complications, especially in the second and third trimesters. In the United Kingdom, twelve maternal deaths were reported to be associated with the H1N1 virus during the pandemic and clear avoidable factors were identified (Modder, Review of Maternal Deaths in the UK related to A H1N1 2009 influenza (CMACE). www.cmace.org.uk, 2010). The pregnancy outcomes were also poor for women who were affected by the virus with a fivefold increase in the perinatal mortality rate and threefold increase in the preterm delivery rate (Yates et al. Health Technol Assess 14(34):109-182, 2010). There continues to be a low uptake of the flu vaccine and commencement of antiviral treatment for pregnant women.

  13. Oseltamivir-resistant seasonal A(H1N1) and A(H1N1)pdm09 influenza viruses from the 2007/2008 to 2012/2013 season in Nara Prefecture, Japan.

    PubMed

    Yoneda, Masaki; Okayama, Akiko; Kitahori, Yoshiteru

    2014-01-01

    We examined the incidence of oseltamivir-resistant seasonal A(H1N1) and A(H1N1)pdm09 influenza viruses from the 2007/2008 to 2012/2013 season in Nara Prefecture, Japan. To detect the oseltamivir resistance marker in neuraminidase (NA), 365 influenza viruses (60 seasonal A(H1N1) and 305 A(H1N1)pdm09) were sequenced. The H275Y mutation in the NA gene, which confers resistance to oseltamivir, was identified in 93.8% (30/32) of seasonal A(H1N1) viruses that were circulating during the 2008/2009 season. Moreover, the detection rate of oseltamivir-resistant A(H1N1)pdm09 viruses was 4.1% (3/74) and 2.8% (5/180) in the 2009/2010 and 2010/2011 season, respectively. Four cases of oseltamivir-resistant A(H1N1)pdm09 virus infection occurred in the same hematology ward during the 2010/2011 season. Our data show a low frequency of oseltamivir-resistant A(H1N1)pdm09 virus in Nara Prefecture but suggested the possibility of human-to-human transmission of this virus.

  14. 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…

  15. Characterization of H1N1 swine influenza viruses circulating in Canadian pigs in 2009

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The 2009 pandemic H1N1 (pH1N1), of apparent swine origin, may have evolved in pigs unnoticed because of insufficient surveillance. Consequently, the need for surveillance of influenza viruses circulating in pigs has received added attention. In this study we characterized H1N1 viruses isolated from ...

  16. Pandemic H1N1 influenza virus in Chilean commercial turkeys with genetic and serologic comparisons to U.S. H1N1 avian influenza vaccine isolates.

    PubMed

    Kapczynski, Darrell R; Gonder, Eric; Tilley, Becky; Hernandez, Andres; Hodgson, Jorge; Wojcinski, Helen; Jiang, Haijun; Suarez, David L

    2011-12-01

    Beginning in April 2009, a novel H1N1 influenza virus caused acute respiratory disease in humans, first in Mexico and then around the world. The resulting pandemic influenza A H1N1 2009 (pH1N1) virus was isolated in swine in Canada in June 2009 and later in breeder turkeys in Chile, Canada, and the United States. The pH1N1 virus consists of gene segments of avian, human, and swine influenza origin and has the potential for infection in poultry following exposure to infected humans or swine. We examined the clinical events following the initial outbreak of pH1N1 in turkeys and determined the relatedness of the hemagglutinin (HA) gene segments from the pH1N1 to two H1N1 avian influenza (AI) isolates used in commercial turkey inactivated vaccines. Overall, infection of turkey breeder hens with pH1N1 resulted in -50% reduction of egg production over 3-4 weeks. Genetic analysis indicated one H1N1 AI vaccine isolate (Alturkey/North Carolina/17026/1988) contained approximately 92% nucleotide sequence similarity to the pH1N1 virus (A/Mexico/4109/2009); whereas, a more recent AI vaccine isolate (A/ swine/North Carolina/00573/2005) contained 75.9% similarity. Comparison of amino acids found at antigenic sites of the HA protein indicated conserved epitopes at the Sa site; however, major differences were found at the Ca2 site between pH1N1 and A/ turkey/North Carolina/127026/1988. Hemagglutinin-inhibition (HI) tests were conducted with sera produced in vaccinated turkeys in North Carolina to determine if protection would be conferred using U.S. AI vaccine isolates. HI results indicate positive reactivity (HI titer > or = 5 log2) against the vaccine viruses over the course of study. However, limited cross-reactivity to the 2009 pH1N1 virus was observed, with positive titers in a limited number of birds (6 out of 20) beginning only after a third vaccination. Taken together, these results demonstrate that turkeys treated with these vaccines would likely not be protected against pH

  17. rapidSTRIPE H1N1 test for detection of the pandemic swine origin influenza A (H1N1) virus.

    PubMed

    Patel, Pranav; Graser, Elmara; Robst, Stephan; Hillert, Roger; Meye, Axel; Hillebrand, Timo; Niedrig, Matthias

    2011-04-01

    The rapidSTRIPE H1N1 test, based on a nucleic acid lateral-flow assay, has been developed for diagnosis of a swine-origin influenza A (H1N1) virus. This test is simple and cost-effective and allows specific detection of the S-OIV A (H1N1) virus from swab sampling to final detection on a lateral-flow stripe within 2 to 3 h.

  18. 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…

  19. Novel route of exposure explains outbreaks of pH1N1 influenza in turkeys

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The presence of avian and swine influenza virus genes in the 2009 novel H1N1 pandemic virus (pH1N1) raises the potential for infection in poultry following exposure to infected humans or swine. This is especially true for turkeys because of their known susceptibility to type A influenza viruses and...

  20. Absence of Pandemic H1N1 Influenza A Virus in Fresh Pork

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pigs experimentally infected with pandemic 2009 H1N1 influenza A virus developed respiratory disease; however, there was no evidence for systemic disease to suggest that pork from pigs infected with H1N1 influenza would contain infectious virus. These findings support the WHO recommendation that po...

  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. 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.

  4. Epidemiological survey on pandemic influenza A (H1N1) virus infection in Kurdistan province, Islamic Republic of Iran, 2009.

    PubMed

    Afrasiabian, S; Mohsenpour, B; Bagheri, K H; Barari, M; Ghaderi, E; Hashemi, R; Garibi, F

    2014-04-03

    This study evaluated the epidemiology of suspected cases of pandemic influenza A (H1N1) virus infection in 2009-2010 in Kurdistan province, a frontier province of the Islamic Republic of Iran. A questionnaire covering demographic characteristics, clinical presentation and outcome, and history of exposure and travel was completed by patients attending health centres and hospitals in the province. Nasal and throat swabs were analysed by RT-PCR. A total of 1059 suspected cases were assessed; H1N1 influenza A was confirmed in 157 (14.8%). The highest proportion of confirmed cases was 30.0%, among children aged < 1 year. In multivariate analysis, previous contact with symptomatic influenza patients (OR = 2.17) and hospitalization (OR = 3.88) were the only significant risk factors for confirmed H1N1 infection. Age, sex, residency, presenting symptoms and history of national or international travel were not significant. Influenza A (H1N1) virus has spread in Islamic Republic of Iran; probably transmitted by travellers to Kurdistan.

  5. 2009 Pandemic Influenza A (H1N1): Diagnosis, Management, and Prevention- Lessons Learned.

    PubMed

    Swedish, Kristin A

    2011-04-01

    The 2009 pandemic influenza A (H1N1) was responsible for the first influenza pandemic of the 21st century. The virus- a previously unknown triple-reassortant virus containing segments of avian, human, and swine origins- generally caused mild disease. Unlike seasonal influenza, 2009 pandemic influenza A (H1N1) primarily affected adults 18 to 64 years of age. During the course of the pandemic, public health officials tried to facilitate diagnostic procedures and share information about treatment modalities globally. Efforts to contain the spread of 2009 pandemic influenza A (H1N1) included personal protective mechanisms and the 2009 H1N1 vaccine, which was not produced quickly enough or in large enough quantities. The lessons learned from this pandemic should be applied to ensure better preparedness in case of future pandemics.

  6. 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.

  7. 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.

  8. Influenza A(H1N1)pdm09 and postpandemic influenza in Lithuania

    PubMed Central

    Ambrozaitis, Arvydas; Radzišauskienė, Daiva; Kuprevičienė, Nerija; Gravenstein, Stefan; Jančorienė, Ligita

    2016-01-01

    Abstract The objective of this study is to describe the clinical and epidemiological characteristics of patients hospitalized in Lithuania who are infected with influenza A(H1N1)pdm09 and to compare pandemic A(H1N1) pdm09 infection with postpandemic. In total, 146 subjects hospitalized with influenza A(H1N1) pdm09 were identified from 2009–2011. There were 53 during the initial pandemic wave in the summer of 2009, 69 during the peak pandemic period, and 24 during the “postpandemic” period that we included in this study. There were 22 subjects who died after laboratory confirmation of influenza A(H1N1)pdm09. No deaths were documented during the first wave. Subjects presenting during the peak of pandemic influenza had a greater incidence of fever (100% vs 77.4%; p<0.001), dry cough (95.7% vs 82.7%; p=0.01), and vomiting (26.1% vs 1.9%, p<0.001) as compared with patients infected during the first wave. The rate of bacterial pneumonia was 18.8% (13/69) during the peak pandemic period and 12.5% (3/24, p=0.754) during the postpandemic period. None of the postpandemic influenza subjects’ intensive care unit stays were due to pneumonia. The hospitalized early 2009 H1N1 pandemic cases and postpandemic cases were milder compared with those at the peak of pandemic activity. PMID:28352819

  9. Influenza vaccination coverage among pregnant women--National 2009 H1N1 Flu Survey (NHFS).

    PubMed

    Ding, Helen; Santibanez, Tammy A; Jamieson, Denise J; Weinbaum, Cindy M; Euler, Gary L; Grohskopf, Lisa A; Lu, Peng-Jun; Singleton, James A

    2011-06-01

    We sought to describe vaccination with influenza A (H1N1) 2009 monovalent (2009 H1N1) and trivalent seasonal (seasonal) vaccines among pregnant women during the 2009 through 2010 influenza season. A national H1N1 flu survey was conducted April through June 2010. The 2009 H1N1 and seasonal vaccination coverage estimates were 45.7% and 32.1%, respectively, among pregnant women aged 18-49 years. Receipt of a health care provider's recommendation for vaccination, perceived effectiveness of influenza vaccinations, and perceived high chance of influenza infection were independently associated with higher 2009 H1N1 and seasonal vaccination coverage. Pregnancy during October 2009 through January 2010 was independently associated with higher 2009 H1N1 vaccination coverage. The 2009 H1N1 vaccination level among pregnant women was higher than the seasonal vaccination level during the 2009 through 2010 season; it was also higher than vaccination among nonpregnant women with and without high-risk conditions. Health care providers and public health messaging played important roles in influencing vaccination behavior.

  10. [Virological characteristics of pandemic (H1N1) 2009 influenza virus].

    PubMed

    Horimoto, Taisuke; Yamada, Shinya; Kawaoka, Yoshihiro

    2010-06-01

    In the spring of 2009, a novel swine-origin H1N1 virus, whose antigenicity is quite different from those of seasonal human H1N1 strains, emerged in Mexico and readily transmitted and spread among humans, resulting in the first influenza pandemic in the 21st century. This novel H1N1 virus was shown to be a triple reassortant comprising genes derived from avian, human, and swine viruses. Here, we review our current knowledge of this pandemic influenza virus and discuss future aspects of the pandemic.

  11. Effect of priming with H1N1 influenza viruses of variable antigenic distances on challenge with 2009 pandemic H1N1 virus.

    PubMed

    O'Donnell, Christopher D; Wright, Amber; Vogel, Leatrice N; Wei, Chih-Jen; Nabel, Gary J; Subbarao, Kanta

    2012-08-01

    Compared to seasonal influenza viruses, the 2009 pandemic H1N1 (pH1N1) virus caused greater morbidity and mortality in children and young adults. People over 60 years of age showed a higher prevalence of cross-reactive pH1N1 antibodies, suggesting that they were previously exposed to an influenza virus or vaccine that was antigenically related to the pH1N1 virus. To define the basis for this cross-reactivity, ferrets were infected with H1N1 viruses of variable antigenic distance that circulated during different decades from the 1930s (Alaska/35), 1940s (Fort Monmouth/47), 1950s (Fort Warren/50), and 1990s (New Caledonia/99) and challenged with 2009 pH1N1 virus 6 weeks later. Ferrets primed with the homologous CA/09 or New Jersey/76 (NJ/76) virus served as a positive control, while the negative control was an influenza B virus that should not cross-protect against influenza A virus infection. Significant protection against challenge virus replication in the respiratory tract was observed in ferrets primed with AK/35, FM/47, and NJ/76; FW/50-primed ferrets showed reduced protection, and NC/99-primed ferrets were not protected. The hemagglutinins (HAs) of AK/35, FM/47, and FW/50 differ in the presence of glycosylation sites. We found that the loss of protective efficacy observed with FW/50 was associated with the presence of a specific glycosylation site. Our results suggest that changes in the HA occurred between 1947 and 1950, such that prior infection could no longer protect against 2009 pH1N1 infection. This provides a mechanistic understanding of the nature of serological cross-protection observed in people over 60 years of age during the 2009 H1N1 pandemic.

  12. Effect of Priming with H1N1 Influenza Viruses of Variable Antigenic Distances on Challenge with 2009 Pandemic H1N1 Virus

    PubMed Central

    O'Donnell, Christopher D.; Wright, Amber; Vogel, Leatrice N.; Wei, Chih-Jen; Nabel, Gary J.

    2012-01-01

    Compared to seasonal influenza viruses, the 2009 pandemic H1N1 (pH1N1) virus caused greater morbidity and mortality in children and young adults. People over 60 years of age showed a higher prevalence of cross-reactive pH1N1 antibodies, suggesting that they were previously exposed to an influenza virus or vaccine that was antigenically related to the pH1N1 virus. To define the basis for this cross-reactivity, ferrets were infected with H1N1 viruses of variable antigenic distance that circulated during different decades from the 1930s (Alaska/35), 1940s (Fort Monmouth/47), 1950s (Fort Warren/50), and 1990s (New Caledonia/99) and challenged with 2009 pH1N1 virus 6 weeks later. Ferrets primed with the homologous CA/09 or New Jersey/76 (NJ/76) virus served as a positive control, while the negative control was an influenza B virus that should not cross-protect against influenza A virus infection. Significant protection against challenge virus replication in the respiratory tract was observed in ferrets primed with AK/35, FM/47, and NJ/76; FW/50-primed ferrets showed reduced protection, and NC/99-primed ferrets were not protected. The hemagglutinins (HAs) of AK/35, FM/47, and FW/50 differ in the presence of glycosylation sites. We found that the loss of protective efficacy observed with FW/50 was associated with the presence of a specific glycosylation site. Our results suggest that changes in the HA occurred between 1947 and 1950, such that prior infection could no longer protect against 2009 pH1N1 infection. This provides a mechanistic understanding of the nature of serological cross-protection observed in people over 60 years of age during the 2009 H1N1 pandemic. PMID:22674976

  13. Predicting the antigenic structure of the pandemic (H1N1) 2009 influenza virus hemagglutinin.

    PubMed

    Igarashi, Manabu; Ito, Kimihito; Yoshida, Reiko; Tomabechi, Daisuke; Kida, Hiroshi; Takada, Ayato

    2010-01-01

    The pandemic influenza virus (2009 H1N1) was recently introduced into the human population. The hemagglutinin (HA) gene of 2009 H1N1 is derived from "classical swine H1N1" virus, which likely shares a common ancestor with the human H1N1 virus that caused the pandemic in 1918, whose descendant viruses are still circulating in the human population with highly altered antigenicity of HA. However, information on the structural basis to compare the HA antigenicity among 2009 H1N1, the 1918 pandemic, and seasonal human H1N1 viruses has been lacking. By homology modeling of the HA structure, here we show that HAs of 2009 H1N1 and the 1918 pandemic virus share a significant number of amino acid residues in known antigenic sites, suggesting the existence of common epitopes for neutralizing antibodies cross-reactive to both HAs. It was noted that the early human H1N1 viruses isolated in the 1930s-1940s still harbored some of the original epitopes that are also found in 2009 H1N1. Interestingly, while 2009 H1N1 HA lacks the multiple N-glycosylations that have been found to be associated with an antigenic change of the human H1N1 virus during the early epidemic of this virus, 2009 H1N1 HA still retains unique three-codon motifs, some of which became N-glycosylation sites via a single nucleotide mutation in the human H1N1 virus. We thus hypothesize that the 2009 H1N1 HA antigenic sites involving the conserved amino acids will soon be targeted by antibody-mediated selection pressure in humans. Indeed, amino acid substitutions predicted here are occurring in the recent 2009 H1N1 variants. The present study suggests that antibodies elicited by natural infection with the 1918 pandemic or its early descendant viruses play a role in specific immunity against 2009 H1N1, and provides an insight into future likely antigenic changes in the evolutionary process of 2009 H1N1 in the human population.

  14. Predicting the Antigenic Structure of the Pandemic (H1N1) 2009 Influenza Virus Hemagglutinin

    PubMed Central

    Igarashi, Manabu; Ito, Kimihito; Yoshida, Reiko; Tomabechi, Daisuke; Kida, Hiroshi; Takada, Ayato

    2010-01-01

    The pandemic influenza virus (2009 H1N1) was recently introduced into the human population. The hemagglutinin (HA) gene of 2009 H1N1 is derived from “classical swine H1N1” virus, which likely shares a common ancestor with the human H1N1 virus that caused the pandemic in 1918, whose descendant viruses are still circulating in the human population with highly altered antigenicity of HA. However, information on the structural basis to compare the HA antigenicity among 2009 H1N1, the 1918 pandemic, and seasonal human H1N1 viruses has been lacking. By homology modeling of the HA structure, here we show that HAs of 2009 H1N1 and the 1918 pandemic virus share a significant number of amino acid residues in known antigenic sites, suggesting the existence of common epitopes for neutralizing antibodies cross-reactive to both HAs. It was noted that the early human H1N1 viruses isolated in the 1930s–1940s still harbored some of the original epitopes that are also found in 2009 H1N1. Interestingly, while 2009 H1N1 HA lacks the multiple N-glycosylations that have been found to be associated with an antigenic change of the human H1N1 virus during the early epidemic of this virus, 2009 H1N1 HA still retains unique three-codon motifs, some of which became N-glycosylation sites via a single nucleotide mutation in the human H1N1 virus. We thus hypothesize that the 2009 H1N1 HA antigenic sites involving the conserved amino acids will soon be targeted by antibody-mediated selection pressure in humans. Indeed, amino acid substitutions predicted here are occurring in the recent 2009 H1N1 variants. The present study suggests that antibodies elicited by natural infection with the 1918 pandemic or its early descendant viruses play a role in specific immunity against 2009 H1N1, and provides an insight into future likely antigenic changes in the evolutionary process of 2009 H1N1 in the human population. PMID:20049332

  15. Characterization of H1N1 swine influenza viruses circulating in Canadian pigs in 2009.

    PubMed

    Nfon, Charles K; Berhane, Yohannes; Hisanaga, Tamiko; Zhang, Shunzhen; Handel, Katherine; Kehler, Helen; Labrecque, Olivia; Lewis, Nicola S; Vincent, Amy L; Copps, John; Alexandersen, Soren; Pasick, John

    2011-09-01

    The 2009 pandemic H1N1 (pH1N1), of apparent swine origin, may have evolved in pigs unnoticed because of insufficient surveillance. Consequently, the need for surveillance of influenza viruses circulating in pigs has received added attention. In this study we characterized H1N1 viruses isolated from Canadian pigs in 2009. Isolates from May 2009 were comprised of hemagglutinin and neuraminidase (NA) genes of classical SIV origin in combination with the North American triple-reassortant internal gene (TRIG) cassette, here termed contemporary SIV (conSIV) H1N1. These conSIV H1N1 viruses were contiguous with the North American αH1 cluster, which was distinct from the pH1N1 isolates that were antigenically more related to the γH1 cluster. After the initial isolation of pH1N1 from an Alberta pig farm in early May 2009, pH1N1 was found several times in Canadian pigs. These pH1N1 isolates were genetically and antigenically homogeneous. In addition, H1N1 viruses bearing seasonal human H1 and N1 genes together with the TRIG cassette and an NA encoding an oseltamivir-resistance marker were isolated from pigs. The NS gene of one of these seasonal human-like SIV (shSIV) H1N1 isolates was homologous to pH1N1 NS, implicating reassortment between the two strains. Antigenic cross-reactivity was observed between pH1N1 and conSIV but not with shSIV H1N1. In summary, although there was cocirculation of pH1N1 with conSIV and shSIV H1N1 in Canadian pigs after May 2009, there was no evidence supporting the presence of pH1N1 in pigs prior to May 2009. The possibility for further reassortants being generated exists and should be closely monitored.

  16. Classical swine H1N1 influenza viruses confer cross protection from swine-origin 2009 pandemic H1N1 influenza virus infection in mice and ferrets.

    PubMed

    Min, Ji-Young; Chen, Grace L; Santos, Celia; Lamirande, Elaine W; Matsuoka, Yumiko; Subbarao, Kanta

    2010-12-05

    The hemagglutinin of the 2009 pandemic H1N1 influenza virus is a derivative of and is antigenically related to classical swine but not to seasonal human H1N1 viruses. We compared the A/California/7/2009 (CA/7/09) virus recommended by the WHO as the reference virus for vaccine development, with two classical swine influenza viruses A/swine/Iowa/31 (sw/IA/31) and A/New Jersey/8/1976 (NJ/76) to establish the extent of immunologic cross-reactivity and cross-protection in animal models. Primary infection with 2009 pandemic or NJ/76 viruses elicited antibodies against the CA/7/09 virus and provided complete protection from challenge with this virus in ferrets; the response in mice was variable and conferred partial protection. Although ferrets infected with sw/IA/31 virus developed low titers of cross-neutralizing antibody, they were protected from pulmonary replication of the CA/7/09 virus. The data suggest that prior exposure to antigenically related H1N1 viruses of swine-origin provide some protective immunity against the 2009 pandemic H1N1 virus.

  17. 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...

  18. Pandemic H1N1 influenza virus infection in a Canadian cat

    PubMed Central

    Knight, Cameron G.; Davies, Jennifer L.; Joseph, Tomy; Ondrich, Sarah; Rosa, Brielle V.

    2016-01-01

    A cat was presented for necropsy after being found dead at home. Histologic findings suggested viral pneumonia. Polymerase chain reaction and viral typing revealed influenza A(H1N1)pdm09. This is the first report of influenza in a Canadian cat and highlights the importance of considering influenza virus in the differential diagnosis for feline respiratory distress. PMID:27152036

  19. Influenza A(H1N1)pdm09 Virus Infection in Giant Pandas, China

    PubMed Central

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

    2014-01-01

    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

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. 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.

  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. Structural basis of preexisting immunity to the 2009 H1N1 pandemic influenza virus.

    PubMed

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

    2010-04-16

    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.

  7. 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.

  8. 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.

  9. Transplantation of solid organs procured from influenza A H1N1 infected donors.

    PubMed

    Cockbain, Andrew J; Jacob, Matthew; Ecuyer, Clare; Hostert, Lutz; Ahmad, Niaz

    2011-12-01

    Following the influenza A H1N1 (swine flu) pandemic, there remains little evidence informing the safety of transplanting organs from donors suspected or diagnosed with H1N1. Limited guidelines from the major transplant societies leave the use of such organs at the discretion of individual transplant centres, and practice varies considerably both nationally and internationally. We present the largest published series of outcome following transplantation of organs from H1N1 positive donors and demonstrate that these organs can be transplanted safely and with good short-term outcome. We discuss our local policy for treatment of recipients with Oseltamivir.

  10. Influenza A(H1N1)pdm09 virus in pigs, Réunion Island.

    PubMed

    Cardinale, Eric; Pascalis, Hervé; Temmam, Sarah; Hervé, Séverine; Saulnier, Aure; Turpin, Magali; Barbier, Nicolas; Hoarau, Johny; Quéguiner, Stéphane; Gorin, Stéphane; Foray, Coralie; Roger, Matthieu; Porphyre, Vincent; André, Paul; Thomas, Thierry; de Lamballerie, Xavier; Dellagi, Koussay; Simon, Gaëlle

    2012-10-01

    During 2009, pandemic influenza A(H1N1)pdm09 virus affected humans on Réunion Island. Since then, the virus has sustained circulation among local swine herds, raising concerns about the potential for genetic evolution of the virus and possible retransmission back to humans of variants with increased virulence. Continuous surveillance of A(H1N1)pdm09 infection in pigs is recommended.

  11. 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.

  12. Pandemic influenza A (H1N1) 2009 vaccine: an update.

    PubMed

    Goel, M K; Goel, M; Khanna, P; Mittal, K

    2011-01-01

    The world witnessed a the first influenza pandemic in this century and fourth overall since first flu pandemic was reported during the World War I. The past experiences with influenza viruses and this pandemic of H1N1 place a consider-able strain on health services and resulted in serious illnesses and a large number of deaths. Develop-ing countries were declared more likely to be at risk from the pandemic effects, as they faced the dual problem of highly vulnerable populations and limited resources to respond H1N1. The public health experts agreed that vaccination is the most effective ways to mitigate the negative effects of the pandemic. The vaccines for H1N1 virus have been used in over 40 countries and administered to over 200 million people helped in a great way and on August 10, 2010, World Health Organization (WHO) announced H1N1 to be in postpandemic period. But based on knowledge about past pandemics, the H1N1 (2009) virus is expected to continue to circulate as a seasonal virus and may undergo some agenic-variation. As WHO strongly recommends vaccination, vigilance for regular updating of the composition of influenza vaccines, based on an assessment of the future impact of circulating viruses along with safety surveillance of the vaccines is necessary. This review has been done to take a stock of the currently available H1N1 vaccines and their possible use as public health intervention in the postpandemic period.

  13. 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.

  14. 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...

  15. 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.

  16. Clinical Presentation of Novel Influenza A (H1N1) in Hospitalized Children

    PubMed Central

    Soleimani, Gholamreza; Akbarpour, Marzieh

    2011-01-01

    Objective Human pandemic influenza H1N1 virus as the cause of febrile respiratory infection ranging from self-limited to severe illness has spread globally during 2009. Signs and symptoms of upper and lower respiratory tract involvement, fever, sore throat, rhinitis, myalgia, malaise, headache, chills and fatigue are common. In this article we report the clinical presentation of Influenza A (H1N1) in our hospitalized children. Methods Between September and October 2009, all children requiring hospitalization for suspected H1N1 infection were transferred to Pediatric Infectious Diseases ward. For all patients the throat swab was taken for PCR testing to confirm or exclude the diagnosis of H1N1 Influenza A. Case patients consisted of H1N1-positive patients. Age, sex, symptoms, signs, laboratory data, CXR changes, details of therapy, duration of admission and patient outcome were documented. Findings Twenty patients were H1N1 positive. Mean age of the patients was 65.50±9.8 months. Fever and coughs were with 55% the most commonly reported symptoms. Other presentations included vomiting (55%), abdominal pain (25%), cyanosis and dyspnea (5%), body ache (40%), rhinorrhea (80%), sore throat (35%), head stiffness (5%) and loss of conciousness (5%). The median temperature of the patients was 38.5°C. Chest X-Ray changes were noted in 13 out of 20 patients (65%). Mean leukocyte and platelet was 6475 and 169000 respectively. Seventeen (85%) patients were treated with Oseltamivir, 3 patients received adjuvant antibiotics. The mean duration of admission was 3 days. Three patients required intensive care support and all of them expired due to superinfection. Conclusion Our data confirm that the presentation of influenza in children is variable and 2009 H1N1 influenza may cause leucopenia and thrombocytopenia. PMID:23056790

  17. [Pandemic influenza A(H1N1): the experience of the Spanish Laboratories of Influenza Network (ReLEG)].

    PubMed

    Cuevas González-Nicolás, María Teresa; Ledesma Moreno, Juan; Pozo Sánchez, Francisco; Casas Flecha, Inmaculada; Pérez-Breña, Pilar

    2010-01-01

    There are three types of influenza viruses: A, B, C. These viruses evolves constantly due to two main characteristics: the first one is the lack of the correction ability of the viral polymerase which causes the accumulation of single nucleotide mutations in the viral genes introduced by an error-prone viral RNA polymerase, (antigenic shift). The second one is the nature of their genome, formed by eight segments, which allows the interchange of genes between two different viral strains (antigenic drift). This viral plasticity, has allowed to the influenza A viruses to infect new host species and to cause infections with a pandemic characteristics. The Spanish influenza surveillance system, SVGE (its Spanish acronym), arises as a response to the possibility of facing a pandemic situation, especially after the transmission of avian influenza viruses to humans. This surveillance system is formed by sixteen physician and paediatrics network, nineteen epidemiological services coordinated by the National Epidemiological Centre (CNE) and eighteen laboratories , the Spanish Laboratories of Influenza network (ReLEG), coordinated by the National Centre of Microbiology. The aim of this article is to show the action of the ReLEG, in the pandemic caused by the influenza virus A(H1N1) during the season 2009-2010. The main objective of this network is the surveillance of the circulating viruses by means of their detection and their subsequent antigenic and genetic characterization, including the detection of resistance mutations against the main drugs, such as Oseltamivir.

  18. Initial incursion of pandemic (H1N1) 2009 influenza A virus into European pigs.

    PubMed

    Welsh, M D; Baird, P M; Guelbenzu-Gonzalo, M P; Hanna, A; Reid, S M; Essen, S; Russell, C; Thomas, S; Barrass, L; McNeilly, F; McKillen, J; Todd, D; Harkin, V; McDowell, S; Choudhury, B; Irvine, R M; Borobia, J; Grant, J; Brown, I H

    2010-05-22

    The initial incursion of pandemic (H1N1) 2009 influenza A virus (pH1N1) into a European pig population is reported. Diagnosis of swine influenza caused by pandemic virus was made during September 2009 following routine submission of samples for differential diagnosis of causative agents of respiratory disease, including influenza A virus. All four pigs (aged six weeks) submitted for investigation from a pig herd of approximately 5000 animals in Northern Ireland, experiencing acute-onset respiratory signs in finishing and growing pigs, were positive by immunofluorescence for influenza A. Follow-up analysis of lung tissue homogenates by real-time RT-PCR confirmed the presence of pH1N1. The virus was subsequently detected on two other premises in Northern Ireland; on one premises, detection followed the pre-export health certification testing of samples from pigs presumed to be subclinically infected as no clinical signs were apparent. None of the premises was linked to another epidemiologically. Sequencing of the haemagglutinin and neuraminidase genes revealed high nucleotide identity (>99.4 per cent) with other pH1N1s isolated from human beings. Genotypic analyses revealed all gene segments to be most closely related to those of contemporary pH1N1 viruses in human beings. It is concluded that all three outbreaks occurred independently, potentially as a result of transmission of the virus from human beings to pigs.

  19. Tracking the 2009 H1N1 influenza virus in the Italian region Campania.

    PubMed

    Esposito, Ciro; Di Spirito, Antimo; Cuomo, Nunzia; Di Nicuolo, Giuseppe; Flaminio, Giovanni; Altamura, Fabiana; Ambrosino, Daniele; Cantalupo, Federich; Costa, Caterina; Pentimalli, Francesca; Tarro, Giulio

    2012-07-01

    A novel swine-origin influenza A (H1N1) virus affecting humans was detected in April 2009 in Mexico, Canada, and USA. The S-OIV infection caused a mild to severe febrile respiratory disease throughout the world. Here, we briefly review the main features of influenza A viruses, which caused also other pandemics in the past, and focus in particular on the epidemiology data of the H1N1 influenza in the Italian region Campania, which resulted the most affected by the S-OIV and the one with more lethal cases. In Campania, the peak of influenza preceded of about 2 weeks the incidence peak at the national level. Moreover, the percentage of H1N1-positive patients was much higher in the main town Naples, compared to the other Campania provinces. The age group from 7 months to 17 years was the most affected by the H1N1 infection (43.45%), similarly to what reported at the national level. Here, we discuss the possible reasons of the high H1N1 incidence in Campania and the implications that these findings could have on the future prevention campaigns.

  20. 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.

  1. 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

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

    PubMed

    Faverio, Paola; Aliberti, Stefano; Ezekiel, Clinton; 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.

  3. Full-Genome Sequence of a Reassortant H1N1 Swine Influenza Virus Isolated from Pigs in Italy.

    PubMed

    Chiapponi, Chiara; Baioni, Laura; Luppi, Andrea; Moreno, Ana; Castellan, Alberto; Foni, Emanuela

    2013-10-03

    In this study, the full-genome sequence of a novel reassortant H1N1 swine influenza virus (SIV) is reported. The isolate has a hemagglutinin (HA) gene of the pandemic H1N1 influenza virus, but it carries the seven genome segments of the avian-origin H1N1 SIV currently circulating in European pig farms.

  4. Full-Genome Sequence of a Reassortant H1N1 Swine Influenza Virus Isolated from Pigs in Italy

    PubMed Central

    Chiapponi, Chiara; Baioni, Laura; Luppi, Andrea; Moreno, Ana; Castellan, Alberto

    2013-01-01

    In this study, the full-genome sequence of a novel reassortant H1N1 swine influenza virus (SIV) is reported. The isolate has a hemagglutinin (HA) gene of the pandemic H1N1 influenza virus, but it carries the seven genome segments of the avian-origin H1N1 SIV currently circulating in European pig farms. PMID:24092781

  5. Safety and efficacy of a novel live attenuated influenza vaccine against pandemic H1N1 in swine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    On June 11, 2009 the World Health Organization (WHO) declared that the outbreaks caused by novel swine-origin influenza A (H1N1) virus had reached pandemic proportions. The pandemic H1N1 (H1N1pdm) is the predominant influenza strain in the human population. It has also crossed the species barriers a...

  6. Genome Stability of Pandemic Influenza A (H1N1) 2009 Based on Analysis of Hemagglutinin and Neuraminidase Genes.

    PubMed

    Espínola, Emilio E

    2012-01-01

    Influenza A virus (H1N1), which arose in 2009, constituted the fourth pandemic after the cases of 1918, 1957, and 1968. This new variant was formed by a triple reassortment, with genomic segments from swine, avian, and human influenza origins. The objective of this study was to analyze sequences of hemagglutinin (n=2038) and neuraminidase (n=1273) genes, in order to assess the extent of diversity among circulating 2009-2010 strains, estimate if these genes evolved through positive, negative, or neutral selection models of evolution during the pandemic phase, and analyze the worldwide percentage of detection of important amino acid mutations that could enhance the viral performance, such as transmissibility or resistance to drugs. A continuous surveillance by public health authorities will be critical to monitor the appearance of new influenza variants, especially in animal reservoirs such as swine and birds, in order to prevent the potential animal-human transmission of viruses with pandemic potential.

  7. Melting muscles: novel H1N1 influenza A associated rhabdomyolysis.

    PubMed

    D'Silva, Dimple; Hewagama, Saliya; Doherty, Richard; Korman, Tony M; Buttery, Jim

    2009-12-01

    We report the first case of myositis and rhabdomyolysis after infection with novel influenza A (H1N1/09) virus. The case demonstrates the novel virus' capacity for causing significant disease. Myositis and the possibility of rhabdomyolysis should be considered in any individual presenting with influenza-like symptoms in which severe myalgia or muscle weakness is apparent. It is likely that we will see severe clinical manifestations of infection with this novel influenza virus in the coming respiratory virus season.

  8. Influenza A(H1N1)pdm09 during air travel.

    PubMed

    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

    2013-01-01

    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.

  9. 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

  10. 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

  11. Novel H1N1 influenza A viral infection complicated by alveolar hemorrhage.

    PubMed

    Gilbert, Christopher R; Vipul, Kumar; Baram, Michael

    2010-05-01

    We report a complication of the novel H1N1 influenza A viral infection not yet described during this 2007-2009 pandemic. Pulmonary hemorrhage is a known complication of influenza pneumonia, including well documented reports from previous pandemics. A 57-year-old African American female presented with fevers, progressive shortness of breath, and cough. After being admitted with an initial diagnosis of myocardial infarction, hemoptysis developed. Nasopharyngeal swabs rapid testing was negative for influenza A and B antigen, but a polymerase chain reaction test for influenza A type H1N1 was positive. A fiberoptic bronchoscopy for ongoing hemoptysis demonstrated diffuse erythema and bleeding, and bronchoalveolar lavage was consistent with alveolar hemorrhage. Progressive hypoxemic respiratory failure ensued, eventually leading to her demise. Our case highlights one of the more feared complications that may have been more common in prior outbreaks, such as the 1918 "Spanish Flu." Autopsy studies from the 1918 influenza pandemic found severe tracheobronchitis (oftentimes hemorrhagic), septal edema, necrotizing bronchiolitis, alveolitis, and extensive hemorrhage, as opposed to the more benign laryngitis and tracheobronchitis that is commonplace in other influenza infections. Similar pathology appearances, including pulmonary hemorrhage, have also been described in H5N1 outbreaks in China and Thailand. It is crucial for pandemic preparedness planning that additional careful and complete autopsy study of this present pandemic influenza infection be performed and reported to answer questions regarding the natural history, pathology, and pathogenesis of this novel H1N1 influenza.

  12. 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…

  13. Differential influenza H1N1-specific humoral and cellular response kinetics in kidney transplant patients.

    PubMed

    Rambal, Vinay; Müller, Karin; Dang-Heine, Chantip; Sattler, Arne; Dziubianau, Mikalai; Weist, Benjamin; Luu, Si-Hong; Stoyanova, Alexandra; Nickel, Peter; Thiel, Andreas; Neumann, Avidan; Schweiger, Brunhilde; Reinke, Petra; Babel, Nina

    2014-02-01

    Renal transplant recipients (RTR) are considered at high risk for influenza-associated complications due to immunosuppression. The efficacy of standard influenza vaccination in RTRs is unclear. Hence, we evaluated activation of the adaptive immunity by the pandemic influenza A(H1N1) 2009 (A(H1N1)pdm09) vaccine in RTRs as compared to healthy controls. To determine cross-reactivity and/or bystander activation, seasonal trivalent influenza vaccine and tetanus/diphteria toxoid (TT/DT) vaccine-specific T cells along with allospecific T cells were quantified before and after A(H1N1)pdm09 vaccination. Vaccination-induced alloimmunity was additionally determined by quantifying serum creatinine and proinflammatory protein IP-10. Contrary to healthy controls, RTRs required a booster vaccination to achieve seroconversion (13.3 % day 21; 90 % day 90). In contrast to humoral immunity, sufficient A(H1N1)pdm09-specific T-cell responses were mounted in RTRs already after the first immunization with a magnitude comparable with healthy controls. Interestingly, vaccination simultaneously boosted T cells reacting to seasonal flu but not to TT/DT, suggesting cross-activation. No alloimmune effects were recorded. In conclusion, protective antibody responses required booster vaccination. However, sufficient cellular immunity is established already after the first vaccination, demonstrating differential kinetics of humoral and cellular immunity.

  14. Travel and age of influenza A (H1N1) 2009 virus infection.

    PubMed

    Nishiura, Hiroshi

    2010-01-01

    Age distribution of 4,986 cases of influenza A (H1N1) 2009 in Japan was analyzed. Cases with a travel history within 10 days preceding the illness onset were significantly older than indigenous cases (p < 0.01) reflecting age-specific travel patterns. Border controls should account for the high frequency of infection among adults.

  15. 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.

  16. Infrarenal Aorta Thrombosis Associated with H1N1 Influenza A Virus Infection

    PubMed Central

    Saglam, Mustafa; Arıkan, Ali; Doner, Barıs; Akıncı, Gulay

    2016-01-01

    Influenza viruses are members of the Orthomyxoviridae family, of which influenza A, B, and C viruses constitute three separate genera. Arterial thrombosis associated with H1N1 influenza A virus infection has rarely been reported. A Turkish man aged 28 years was admitted to our emergency department with dyspnea, bilateral lower extremity insensitivity, and cold. He reported symptoms of fever, myalgia, and cough, which he had had for fifteen days before being admitted to our hospital. The patient was tested for pandemic influenza A (H1N1) virus using polymerase chain reaction (PCR) tests, which were positive. Abdominal computerized tomography with contrast revealed a large occlusive thrombus within the infrarenal aorta. PMID:27872775

  17. [Rhabdomyolysis and acute renal failure in human influenza A H1N1 mediated infection].

    PubMed

    Carrillo-Esper, Raúl; Ornelas-Arroyo, Sofía; Pérez-Bustos, Estela; Sánchez-Zúñiga, Jesús; Uribe-Esquivel, Misael

    2009-01-01

    Rabdomiolysis and acute renal failure secondary to influenza infection are rare. Up to now, few cases have been reported and most of them are primarily among children. Myositis associated to influenza infection is caused by the toxic effect of the virus in the muscular fiber, dysregulation of inflammatory cytokines and a cross reaction between the muscle fiber and the viral particles. We present the case of a 57 year old male with a diagnosis of H1N1 influenza who developed polyuria, oligoanuria, elevation of lactic dehydrogenase, myoglobin, creatinin phosphokinase and an electromyography with a myopathic pattern. The diagnosis of rabdomyolisis and acute renal failure were made, hemodyalisis was started and the patient improved satisfactorily. This is the first report of a patient with radmoyolisis and acute renal failure secondary to A H1N1 influenza treated during the Mexico epidemic.

  18. Molecular character of influenza A/H1N1 2009: Implications for spread and control.

    PubMed

    Aras, Siddhesh; Aiyar, Ashok; Amedee, Angela M; Gallaher, William R

    2009-12-01

    The world is experiencing a pandemic of influenza that emerged in March 2009, due to a novel strain designated influenza A/H1N1 2009. This strain is closest in molecular sequence to swine influenza viruses, but differs from all previously known influenza by a minimum of 6.1%, and from prior "seasonal" H1N1 by 27.2%, giving it great potential for widespread human infection. While spread into India was delayed for two months by an aggressive interdiction program, since 1 August 2009 most cases in India have been indigenous. H1N1 2009 has differentially struck younger patients who are naïve susceptibles to its antigenic subtype, while sparing those >60 who have crossreactive antibody from prior experience with influenza decades ago and the 1977 "swine flu" vaccine distributed in the United States. It also appears to more severely affect pregnant women. It emanated from a single source in central Mexico, but its precise geographical and circumstantial origins, from either Eurasia or the Americas, remain uncertain. While currently a mild pandemic by the standard of past pandemics, the seriousness of H1N1 2009 especially among children should not be underestimated. There is potential for the virus, which continues to adapt to humans, to change over time into a more severe etiologic agent by any of several foreseeable mutations. Mass acceptance of the novel H1N1 2009 vaccine worldwide will be essential to its control. Having spread globally in a few months, affecting millions of people, it is likely to remain circulating in the human population for a decade or more.

  19. Receptor recognition mechanism of human influenza A H1N1 (1918), avian influenza A H5N1 (2004), and pandemic H1N1 (2009) neuraminidase.

    PubMed

    Jongkon, Nipa; Sangma, Chak

    2012-01-01

    Influenza A neuraminidase (NA) is a target for anti-influenza drugs. The function of this enzyme is to cleave a glycosidic linkage of a host cell receptor that links sialic acid (Sia) to galactose (Gal), to allow the virus to leave an infected cell and propagate. The receptor is an oligosaccharide on the host cell surface. There are two types of oligosaccharide receptor; the first, which is found mainly on avian epithelial cell surfaces, links Sia with Gal by an α2,3 glycosidic linkage; in the second, found mainly on human epithelial cell surfaces, linkage is via an α2,6 linkage. Some researchers believe that NAs from different viruses show selectivity for each type of linkage, but there is limited information available to confirm this hypothesis. To see if the linkage type is more specific to any particular NA, a number of NA-receptor complexes of human influenza A H1N1 (1918), avian influenza A H5N1 (2004), and a pandemic strain of H1N1 (2009) were constructed using homology modeling and molecular dynamics simulation. The results show that the two types of receptor analogues bound to NAs use different mechanisms. Moreover, it was found that a residue unique to avian virus NA is responsible for the recognition of the Siaα2,3Gal receptor, and a residue unique to human virus NA is responsible for the recognition of Siaα2,6Gal. We believe that this finding could explain how NAs of different virus origins always possess some unique residues.

  20. 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.

  1. 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.

  2. Pandemic 2009 H1N1 vaccine protects against 1918 Spanish influenza virus.

    PubMed

    Medina, Rafael A; Manicassamy, Balaji; Stertz, Silke; Seibert, Christopher W; Hai, Rong; Belshe, Robert B; Frey, Sharon E; Basler, Christopher F; Palese, Peter; García-Sastre, Adolfo

    2010-06-15

    The 1918 influenza A virus caused the most devastating pandemic, killing approximately 50 million people worldwide. Immunization with 1918-like and classical swine H1N1 virus vaccines results in cross-protective antibodies against the 2009 H1N1 pandemic influenza, indicating antigenic similarities among these viruses. In this study, we demonstrate that vaccination with the 2009 pandemic H1N1 vaccine elicits 1918 virus cross-protective antibodies in mice and humans, and that vaccination or passive transfer of human-positive sera reduced morbidity and conferred full protection from lethal challenge with the 1918 virus in mice. The spread of the 2009 H1N1 influenza virus in the population worldwide, in addition to the large number of individuals already vaccinated, suggests that a large proportion of the population now have cross-protective antibodies against the 1918 virus, greatly alleviating concerns and fears regarding the accidental exposure/release of the 1918 virus from the laboratory and the use of the virus as a bioterrorist agent.

  3. 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

  4. 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.

  5. 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...

  6. Oseltamivir-Resistant Influenza Virus A (H1N1), Europe, 2007–08 Season

    PubMed Central

    Lackenby, Angie; Hungnes, Olav; Lina, Bruno; van der Werf, Sylvie; Schweiger, Brunhilde; Opp, Matthias; Paget, John; van de Kassteele, Jan; Hay, Alan; Zambon, Maria

    2009-01-01

    In Europe, the 2007–08 winter season was dominated by influenza virus A (H1N1) circulation through week 7, followed by influenza B virus from week 8 onward. Oseltamivir-resistant influenza viruses A (H1N1) (ORVs) with H275Y mutation in the neuraminidase emerged independently of drug use. By country, the proportion of ORVs ranged from 0% to 68%, with the highest proportion in Norway. The average weighted prevalence of ORVs across Europe increased gradually over time, from near 0 in week 40 of 2007 to 56% in week 19 of 2008 (mean 20%). Neuraminidase genes of ORVs possessing the H275Y substitution formed a homogeneous subgroup closely related to, but distinguishable from, those of oseltamivir-sensitive influenza viruses A (H1N1). Minor variants of ORVs emerged independently, indicating multiclonal ORVs. Overall, the clinical effect of ORVs in Europe, measured by influenza-like illness or acute respiratory infection, was unremarkable and consistent with normal seasonal activity. PMID:19331731

  7. 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.

  8. 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.

  9. Epidemiological characteristics of Pandemic Influenza A (H1N1-2009) in Zhanjiang, China

    PubMed Central

    Fu, JinJian; Chen, SiDong; Chen, JiaLin; Wang, Jie; Ling, ChenWen

    2011-01-01

    Background A novel influenza A virus strain (H1N1-2009) spread first in Mexico and the United Stated in late April 2009, leading to the first influenza pandemic of the 21st century. The objective of this study was to determine the epidemiological and virological characteristics of the pandemic influenza A (H1N1-2009) in Zhanjiang, China. Methods The case and outbreak reports of influenza-like illness (ILI) were collected from the Chinese information system of disease control and prevention and the influenza surveillance system of Zhanjiang city. Real-time RT-PCR was conducted, and epidemic and virological characteristics of the virus were analyzed using descriptive epidemiological methods and Chi-square trend tests. Results A total of 276 reported cases were confirmed from July 16, 2009 to June 30, 2010. The attack rate of outbreak was from 1.1% to 6.0%. The disease peak occurred in December 2009, after which the outbreak subsided gradually. The last case was confirmed in April 2010. Conclusion The main population struck by the H1N1-2009 virus was young adults, youths and children. The outbreaks most frequently occurred in schools, and most cases were acquired locally PMID:22384300

  10. 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

  11. Antigenic and genetic analyses of H1N1 influenza A viruses from European pigs.

    PubMed

    Brown, I H; Ludwig, S; Olsen, C W; Hannoun, C; Scholtissek, C; Hinshaw, V S; Harris, P A; McCauley, J W; Strong, I; Alexander, D J

    1997-03-01

    H1N1 influenza A viruses isolated from pigs in Europe since 1981 were examined both antigenically and genetically and compared with H1N1 viruses from other sources. H1N1 viruses from pigs and birds could be divided into three groups: avian, classical swine and 'avian-like' swine viruses. Low or no reactivity of 'avian-like' swine viruses in HI tests with monoclonal antibodies raised against classical swine viruses was associated with amino acid substitutions within antigenic sites of the haemagglutinin (HA). Phylogenetic analysis of the HA gene revealed that classical swine viruses from European pigs are most similar to each other and are closely related to North American swine strains, whilst the 'avian-like' swine viruses cluster with avian viruses. 'Avian-like' viruses introduced into pigs in the UK in 1992 apparently originated directly from strains in pigs in continental Europe at that time. The HA genes of the swine viruses examined had undergone limited variation in antigenic sites and also contained fewer potential glycosylation sites compared to human H1N1 viruses. The HA exhibited antigenic drift which was more marked in 'avian-like' swine viruses than in classical swine strains. Genetic analyses of two recent 'avian-like' swine viruses indicated that all the RNA segments are related most closely to those of avian influenza A viruses.

  12. H1N1 Influenza Pandemic in Italy Revisited: Has the Willingness to Get Vaccinated Suffered in the Long Run?

    PubMed Central

    Ludolph, Ramona; Nobile, Marta; Hartung, Uwe; Castaldi, Silvana; Schulz, Peter J.

    2015-01-01

    Background The aim of the study is to assess the long-term secondary effects of personal experience with the H1N1 pandemic of 2009/2010 and the perception of the institutional reaction to it on Italians’ willingness to get vaccinated in case of a novel influenza pandemic. Design and Methods We conducted 140 face-to-face interviews in the Registry Office of the Municipality of Milan, Italy, from October to December 2012. Results Willingness to get vaccinated during a novel influenza pandemic was best predicted by having been vaccinated against the seasonal flu in the past (OR=5.18; 95%CI: 1.40 to 19.13) and fear of losing one’s life in case of an infection with H1N1 (OR=4.09; 95%CI: 1.68 to 9.97). It was unaffected by the assessment of institutional performance. Conclusions The findings of this study do not point to long-term secondary effects of the institutional handling of the H1N1 pandemic. The results highlight the fact that behavioural intention is not the same as behaviour, and that the former cannot simply be taken as an indicator of the latter. Significance for public health Whereas influenza pandemics occurred rather rarely in the last centuries, their frequency can be expected to increase in the future due to the enhanced globalisation and still raising importance of air travelling. Recent examples (Ebola, H1N1, SARS, avian influenza) demonstrate that initially local disease outbreaks often become worldwide health threats of international concern. National and international health authorities are consequently urged to present preparedness plans on how to manage such health crises. However, their success highly depends on their acceptance by the public. To ensure the public compliance with recommended actions, effective communication is needed. Since communication is most successful when it meets the needs of the target audience, a full understanding of the audience is crucial. This study can help public health experts to better understand the

  13. 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

  14. 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

  15. Novel pandemic A (H1N1) influenza vaccination among pregnant women: motivators and barriers.

    PubMed

    Steelfisher, Gillian K; Blendon, Robert J; Bekheit, Mark M; Mitchell, Elizabeth W; Williams, Jennifer; Lubell, Keri; Peugh, Jordon; DiSogra, Charles A

    2011-06-01

    We sought to examine motivators and barriers related to monovalent 2009 influenza A (H1N1) vaccination among pregnant women. We conducted a national poll of pregnant women using a random online sample (237) and opt-in supplement (277). In all, 42% of pregnant women reported getting the vaccine. Vaccination was positively associated with attitudinal factors including believing the vaccine is very safe or benefits the baby, and with provider recommendations. Women in racial/ethnic minority groups, women with less education, and women <35 years were less likely to get the vaccine and had differing views and experiences. Despite H1N1 vaccination rates that are higher than past seasonal influenza rates, barriers like safety concerns may persist in a pandemic. Messaging from providers that encourages women to believe the vaccine is very safe and benefits their baby may be compelling. Messaging and outreach during future pandemics may require customization to increase vaccination among high-risk groups.

  16. Diversity of influenza viruses in swine and the emergence of a novel human pandemic influenza A (H1N1).

    PubMed

    Brockwell-Staats, Christy; Webster, Robert G; Webby, Richard J

    2009-09-01

    The novel H1N1 influenza virus that emerged in humans in Mexico in early 2009 and transmitted efficiently in the human population with global spread has been declared a pandemic strain. Here we review influenza infections in swine since 1918 and the introduction of different avian and human influenza virus genes into swine influenza viruses of North America and Eurasia. These introductions often result in viruses of increased fitness for pigs that occasionally transmit to humans. The novel virus affecting humans is derived from a North American swine influenza virus that has acquired two gene segments [Neuraminidase (NA) and Matrix (M)] from the European swine lineages. This reassortant appears to have increased fitness in humans. The potential for increased virulence in humans and of further reassortment between the novel H1N1 influenza virus and oseltamivir resistant seasonal H1N1 or with highly pathogenic H5N1 influenza stresses the need for urgent pandemic planning.

  17. 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

  18. Extreme evolutionary conservation of functionally important regions in H1N1 influenza proteome.

    PubMed

    Warren, Samantha; Wan, Xiu-Feng; Conant, Gavin; Korkin, Dmitry

    2013-01-01

    The H1N1 subtype of influenza A virus has caused two of the four documented pandemics and is responsible for seasonal epidemic outbreaks, presenting a continuous threat to public health. Co-circulating antigenically divergent influenza strains significantly complicates vaccine development and use. Here, by combining evolutionary, structural, functional, and population information about the H1N1 proteome, we seek to answer two questions: (1) do residues on the protein surfaces evolve faster than the protein core residues consistently across all proteins that constitute the influenza proteome? and (2) in spite of the rapid evolution of surface residues in influenza proteins, are there any protein regions on the protein surface that do not evolve? To answer these questions, we first built phylogenetically-aware models of the patterns of surface and interior substitutions. Employing these models, we found a single coherent pattern of faster evolution on the protein surfaces that characterizes all influenza proteins. The pattern is consistent with the events of inter-species reassortment, the worldwide introduction of the flu vaccine in the early 80's, as well as the differences caused by the geographic origins of the virus. Next, we developed an automated computational pipeline to comprehensively detect regions of the protein surface residues that were 100% conserved over multiple years and in multiple host species. We identified conserved regions on the surface of 10 influenza proteins spread across all avian, swine, and human strains; with the exception of a small group of isolated strains that affected the conservation of three proteins. Surprisingly, these regions were also unaffected by genetic variation in the pandemic 2009 H1N1 viral population data obtained from deep sequencing experiments. Finally, the conserved regions were intrinsically related to the intra-viral macromolecular interaction interfaces. Our study may provide further insights towards the

  19. 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.

  20. Predictors of symptoms of posttraumatic stress in Chinese university students during the 2009 H1N1 influenza pandemic

    PubMed Central

    Xu, Jiahong; Zheng, Yayuan; Wang, Mingmin; Zhao, Jiangmin; Zhan, Qing; Fu, Mingxu; Wang, Qianyi; Xiao, Junjie; Cheng, Yan

    2011-01-01

    Summary Background The university environment poses a high risk of spreading infectious diseases, particularly the 2009 pandemic influenza H1N1, as it is a mass gathering place for youth. This study aimed to evaluate the predictors of stress symptoms among Chinese university students during the 2009 H1N1 influenza pandemic. Material/Methods We used a self-reported questionnaire, the PTSD (posttraumatic stress disorder) Checklist-Civilian Version (PCL-C) to evaluate the stress symptoms among Chinese university students from Heilongjiang (n=455), Beijing (n=106), Shanghai (n=419) and Sichuan (n=102). We then analyzed the predictors of stress symptoms. Results The proportion of university students enrolled in this study who met symptomatic criteria for PTSD was 2% (22 students). The mean PCL-C total score in the sample was 22.09±8.01. The correlational analyses revealed a significant positive relationship between the PCL-C total score and area, and university grade (P<0.01). Moreover, a negative relationship was found between the PCL-C total score and gender, having H1N1 influenza, having family members, friends or acquaintances having H1N1 influenza, and being afraid of H1N1 influenza (P<0.01). The regression analyses showed that in North China, female gender, having H1N1 influenza, having family members or acquaintances with H1N1 influenza, and being afraid of H1N1 influenza were significant predictors of the stress symptoms. Conclusions In North China, female gender, having H1N1 influenza, having family members, friends, or acquaintances with H1N1 influenza, and being afraid of H1N1 influenza were significant predictors of the stress symptoms. PMID:21709644

  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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...

  6. 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…

  7. Improving influenza vaccine distribution in preparation for an H1N1 influenza pandemic: lessons from the field.

    PubMed

    Wahlen, Mongeon Kari J; Bessette, Richard R; Bernard, Matthew E; Springer, Donna J; Benson, Catherine A

    2010-01-01

    Vaccine distribution is an essential component of any healthcare organization's pandemic influenza plan. Variables surrounding distribution in these circumstances are often difficult to anticipate and require careful consideration. The 2009 H1N1 influenza pandemic provided organizations with an opportunity to test current models and overall organizational readiness for the next influenza pandemic. This article describes the experiences at a large, midwestern, multispecialty medical system in responding to the unique circumstances surrounding distribution of the 2009 H1N1 influenza vaccine. We discuss challenges, variables to consider when choosing a vaccine distribution model, institutional response, and lessons learned.

  8. 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

  9. Characterization of triple reassortant H1N1 influenza A viruses from swine in Ohio.

    PubMed

    Yassine, H M; Khatri, M; Zhang, Y J; Lee, C W; Byrum, B A; O'Quin, J; Smith, K A; Saif, Y M

    2009-10-20

    An H1N1 influenza A virus, A/swine/Ohio/24366/07, was isolated from pigs in an Ohio county fair. Twenty-six people who came in contact with the infected pigs developed respiratory disease and two of these people were laboratory confirmed as H1N1 by the Centers for Disease Control and Prevention (CDC). The A/swine/Ohio/24366/07 virus we isolated from swine was shown at the CDC to have 100% identical genome sequence to the human virus associated with the county fair. This prompted us to characterize three swine and two human origin H1N1 influenza A viruses isolated at different time points in the State of Ohio. The three swine viruses were shown to be triple reassortant viruses harboring genes of human (PB1), swine (HA, NA, NP, M, and NS), and avian (PB2 and PA) lineage viruses. Although viruses evaluated in this study were isolated during a short time interval (3 years), genetic drift was observed within the HA and NA genes, including changes at the receptor binding and antigenic sites of HA1 protein. Nevertheless, all viruses exhibited antigenic similarity as evaluated with hemagglutination inhibition and virus neutralizing tests. Internal genes were similar to other reassortant viruses of various subtypes currently circulating in the United States. Interestingly, two of the swine viruses including the 2007 isolate replicated well in human airway epithelial cells, however, another virus isolated in 2006 showed very little replication.

  10. H1N1 Influenza Patient Saved by Extracorporeal Membrane Oxygenation: First Report from Iran

    PubMed Central

    Jahangirifard, Alireza; Hossein Ahmadi, Zargham; Golestani Eraghi, Majid; Tabarsi, Payam; Marjani, Majid; Moniri, Afshin; Nadji, Seyed Ali Reza; Hashemian, Seyed Mohammad Reza; Velayati, Ali Akbar

    2016-01-01

    Respiratory failure is a serious complication of H1N1 influenza that, if not properly managed, can cause death. When mechanical ventilation is not effective, the only way to save the patient’s life is extracorporeal membrane oxygenation (ECMO). A prolonged type of cardiopulmonary bypass, ECMO is a high-cost management modality compared to other conventional types and its maintenance requires skilled personnel. Such staff usually comprises the members of open-heart surgical teams. Herein, we describe a patient with H1N1 influenza and severe respiratory failure not improved by mechanical ventilation who was admitted to Masih Daneshvari Medical Center in March 2015. She was placed on ECMO, from which she was successfully weaned 9 days later. The patient was discharged from the hospital after 52 days. Follow-up till 11 months after discharge revealed completely active life with no problem. There should be a close collaboration among infectious disease specialists, cardiac anesthetists, cardiac surgeons, and intensivists for the correct timing of ECMO placement, subsequent weaning, and care of the patient. This team work was the key to our success story. This is the first patient to survive H1N1 with the use of ECMO in Iran. PMID:27956916

  11. 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.

  12. On the spread of the novel influenza A (H1N1) virus in Mexico.

    PubMed

    López-Cervantes, Malaquías; Venado, Aida; Moreno, Andrés; Pacheco-Domínguez, Reyna L; Ortega-Pierres, Guadalupe

    2009-06-01

    A novel influenza A H1N1 virus of swine origin is responsible for the influenza epidemic affecting Mexico, the United States of America (USA), and 39 other countries. While the origin of this emerging pathogen remains uncertain, an increase in the reported incidence of respiratory diseases was noted during March 2009 at the town of La Gloria, in the southeastern state of Veracruz, Mexico. So far, this is the first community in which a case of novel influenza A H1N1 virus has been identified. Further cases were rapidly detected in other areas of Mexico and elsewhere. Initially, the atypical respiratory disease outbreak caused great uncertainty posing a challenge to the Mexican health system. Control measures such as social distancing, timely medical care, and personal hygiene have so far proven effective in containing the outbreak, resulting in a decline of the number of new cases. To the best of our knowledge, it appears that the virus might not be as virulent or contagious as previously thought. Here we provide a description of the influenza epidemic spread in Mexico. As the virus disseminates worldwide, there is concern about the possibility of a new reassortment resulting in a more pathogenic strain that will pose a threat for every country. The influenza epidemic provided lessons that underscore the importance of epidemiologic surveillance and preparedness. Further investigation to address questions about this new virus and conditions for its spread is warranted.

  13. 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.

  14. [Epidemic of influenza A(H1N1) 2009 in Reunion Island: epidemiological data].

    PubMed

    Renault, P; Thouillot, F; Do, C; Baroux, N; Cadivel, A; Balleydier, E; Brottet, E; Kermarec, F; D'Ortenzio, E; Filleul, L

    2011-05-01

    In Reunion Island, a French subtropical island located in the southern hemisphere, the monitoring of the epidemiological dynamics of the epidemic linked to the emergence of pandemic virus A(H1N1) 2009 was achieved through the regular influenza surveillance system which has been reinforced on that occasion. It was mainly based on a network of sentinel physicians, combined with virologic monitoring, and on surveillance of severe cases and deaths. The data were analyzed and retroinformation was distributed according to a weekly frequency. The first imported case was confirmed on July 5, 2009 in a traveler arriving from Australia, whereas the first autochthonous cases were reported on July 23. The epidemic peak was reached in five weeks and the duration of the whole epidemic episode was 9 weeks. Pandemic virus has quickly supplanted seasonal viruses that had begun to circulate. The estimated attack rate for symptomatic cases of infection with virus influenza A(H1N1) 2009 was 12.85%. The hospitalization rate was 32 per 10,000 estimated cases, and 24 people had a serious form requiring care in ICU. Among death certificates received at the regional office for health and social affairs, 14 mentioned the influenza, including 7 in whom the pandemic virus has been laboratory confirmed. These deaths occurred in patients significantly younger than usually observed in Reunion Island during the seasonal influenza epidemics. Overall, the epidemic intensity and severity have been similar to those of seasonal influenza in Reunion Island.

  15. Fitness of Pandemic H1N1 and Seasonal influenza A viruses during Co-infection: Evidence of competitive advantage of pandemic H1N1 influenza versus seasonal influenza.

    PubMed

    Perez, Daniel Roberto; Sorrell, Erin; Angel, Matthew; Ye, Jianqiang; Hickman, Danielle; Pena, Lindomar; Ramirez-Nieto, Gloria; Kimble, Brian; Araya, Yonas

    2009-08-24

    On June 11, 2009 the World Health Organization (WHO) declared a new H1N1 influenza pandemic. This pandemic strain is as transmissible as seasonal H1N1 and H3N2 influenza A viruses. Major concerns facing this pandemic are whether the new virus will replace, co-circulate and/or reassort with seasonal H1N1 and/or H3N2 human strains. Using the ferret model, we investigated which of these three possibilities were most likely favored. Our studies showed that the current pandemic virus is more transmissible than, and has a biological advantage over, prototypical seasonal H1 or H3 strains.

  16. [Influenza A/H1N1 virus--old and new].

    PubMed

    Bodas, Moran; Davidovich, Nadav; Balicer, Ran D

    2009-08-01

    Swine influenza is a disease known since 1918. Four decades Later, scientists were already isolating the disease-causing agent and learning more about its ability to infect humans. Generally, swine influenza viruses, similarly to avian influenza viruses, do not easily infect humans; however, the viruses' ability to undergo substantial genetic re-assortment enhances the emergence of novel influenza viruses, better capable of infecting and transmitting between humans. Pigs also form good "mixing vessels" for human and avian origin influenza viruses, enabling the emergence of highly virulent influenza strains. Human infection with swine influenza has been recorded in the past, both as sporadic infections and as outbreaks. The best known human swine influenza outbreak took place in Fort Dix (USA) in 1976, concluding in the immunization of almost 45 million U.S. citizens, in a highly controversial immunization program. The current H1N1 (S-OIV) Influenza outbreak was declared by the WHO as an influenza pandemic, setting to rest the lately popular question "when will the next pandemic occur?" and laying the foundations for the evaluation of preparedness plans. There is great importance in data collection and subsequent updating of current procedures and doctrines.

  17. Racial and ethnic disparities in uptake and location of vaccination for 2009-H1N1 and seasonal influenza.

    PubMed

    Uscher-Pines, Lori; Maurer, Jurgen; Harris, Katherine M

    2011-07-01

    To learn more about racial and ethnic disparities in influenza vaccination during the 2009-H1N1 pandemic, we examined nationally representative survey data of US adults. We found disparities in 2009-H1N1 vaccine uptake between Blacks and Whites (13.8% vs 20.4%); Whites and Hispanics had similar 2009-H1N1 vaccination rates. Physician offices were the dominant location for 2009-H1N1 and seasonal influenza vaccinations, especially among minorities. Our results highlight the need for a better understanding of how communication methods and vaccine distribution strategies affect vaccine uptake within minority communities.

  18. 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.

  19. 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

  20. [Epidemiology of influenza A (H1N1) worldwide and in Spain].

    PubMed

    Vaqué, Josep

    2010-03-01

    On June 11, 2009, the World Health Organization declared an established pandemic due to a new influenza virus A (H1N1) of swine origin. Initial cases were detected in Mexico in March and within 6 weeks the virus had spread worldwide. The transmissibility of influenza A (H1NA) is slightly higher than that of the seasonal virus, but its pathogenicity and virulence are low. The main target groups of this new virus have been children and young adults under 30 years old. Mortality has affected mainly persons aged between 20 and 50 years old. In areas with temperate climates, two epidemic waves have occurred. The first one, from mid-April to mid-August, affected Mexico, the United States and, consecutively, Spain, England, Japan, and other countries in the northern hemisphere. A few weeks later, coinciding with the beginning of the influenza season, the H1N1 epidemic started in the southern hemisphere countries, especially Argentina, Chile, Australia and New Zealand; in these countries, the epidemic finished at the end of September or October. The second wave affected the northern hemisphere, starting in the United States and Mexico at the beginning of September, and a few weeks later in European countries. In mid-December, this wave was considered to have ended, although some influenza activity persists. The intensity of this second wave was higher compared to the first one.

  1. Cross-reactive CD8+ T-cell immunity between the pandemic H1N1-2009 and H1N1-1918 influenza A viruses.

    PubMed

    Gras, Stephanie; Kedzierski, Lukasz; Valkenburg, Sophie A; Laurie, Karen; Liu, Yu Chih; Denholm, Justin T; Richards, Michael J; Rimmelzwaan, Guus F; Kelso, Anne; Doherty, Peter C; Turner, Stephen J; Rossjohn, Jamie; Kedzierska, Katherine

    2010-07-13

    Preexisting T-cell immunity directed at conserved viral regions promotes enhanced recovery from influenza virus infections, with there being some evidence of cross-protection directed at variable peptides. Strikingly, many of the immunogenic peptides derived from the current pandemic A(H1N1)-2009 influenza virus are representative of the catastrophic 1918 "Spanish flu" rather than more recent "seasonal" strains. We present immunological and structural analyses of cross-reactive CD8(+) T-cell-mediated immunity directed at a variable (although highly cross-reactive) immunodominant NP(418-426) peptide that binds to a large B7 family (HLA-B*3501/03/0702) found throughout human populations. Memory CD8(+) T-cell specificity was probed for 12 different NP(418) mutants that emerged over the 9 decades between the 1918 and 2009 pandemics. Although there is evidence of substantial cross-reactivity among seasonal NP(418) mutants, current memory T-cell profiles show no preexisting immunity to the 2009-NP(418) variant or the 1918-NP(418) variant. Natural infection with the A(H1N1)-2009 virus, however, elicits CD8(+) T cells specific for the 2009-NP(418) and 1918-NP(418) epitopes. This analysis points to the potential importance of cross-reactive T-cell populations that cover the possible spectrum of T-cell variants and suggests that the identification of key residues/motifs that elicit cross-reactive T-cell sets could facilitate the evolution of immunization protocols that provide a measure of protection against unpredicted pandemic influenza viruses. Thus, it is worth exploring the potential of vaccines that incorporate peptide variants with a proven potential for broader immunogenicity, especially to those that are not recognized by the current memory T-cell pool generated by exposure to influenza variants that cause successive seasonal epidemics.

  2. 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.

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

    PubMed Central

    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

  4. 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.

  5. 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

  6. 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.

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

    PubMed

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

    2014-06-03

    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.

  8. Pathology of the swine-origin influenza A (H1N1) flu.

    PubMed

    Calore, E E; Uip, D E; Perez, N M

    2011-02-15

    Pathological studies would aid in finding the real causes of death and in outlining adequate strategies for treatment regarding patients with poor clinical outcome of influenza A H1N1 swine flu. We describe the autopsy findings of six cases of influenza A H1N1 swine flu. The lungs in these cases had an alveolitis with hyaline membranes. Immunohistochemistry for influenza was positive only in lungs (in pneumocytes, in macrophages, in some multinucleate cells in alveoli, and in blood vessel walls) of two cases. Disseminated petechial brain hemorrhage was observed in four of the cases and focally in one case. Focal myocarditis was observed in one case. Coagulation infarcts (ischemic) were observed in the pancreas of two cases and in the spleen of two cases. Our results indicate that there was marked replication of the virus in alveoli in the more recently infected cases, which could explain the extensive diffuse alveolar damage. In our cases, there were important vascular phenomena that resulted in hemorrhage and thrombosis, but without marked decrease of platelet count and coagulation cascade disruptions. This would be attributed to hemodynamic disruption. However, it is possible that the hemorrhagic petechial lesions in the brain are due to vascular lesions or to an increase of endothelial permeability.

  9. Epidemiological aspects of 2009 H1N1 influenza: the accumulating experience from the Northern Hemisphere.

    PubMed

    Falagas, M E; Cholevas, N V; Kapaskelis, A M; Vouloumanou, E K; Michalopoulos, A; Rafailidis, P I

    2010-11-01

    Preliminary data regarding the experience of countries of the Northern Hemisphere with pandemic 2009 A(H1N1) influenza have already appeared in the literature. We aimed to evaluate the available published literature describing the epidemiological features of pandemic influenza. We searched PubMed; 35 studies (14 referred to European countries, eight to the USA, five to Mexico, four to Canada, two to Japan, one to Colombia, and one reviewed relevant data reported worldwide) were included. Considerably high hospitalization, intensive care unit (ICU) admission, and fatality rates (up to 93.8, 36.4, and 38.5%, respectively) among the evaluated cases were reported across studies with available relevant data. Young and middle-aged adults constituted the majority of the evaluated pandemic cases, with different disease severity (as indicated by the level of care and outcome). Yet, substantial percentages of elderly individuals were reported among more severely afflicted cases. Otherwise healthy patients constituted substantial percentages among evaluated cases with different disease severity. Pregnant women, obese, and morbidly obese patients also constituted substantial percentages of the cases involved in the included studies. The evaluation of the currently available published evidence contributes to the clarification of the epidemiological features of pandemic 2009 A(H1N1) influenza, which is useful in terms of the individual and public health perspectives.

  10. 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.

  11. Adaptation of pandemic H1N1 influenza viruses in mice.

    PubMed

    Ilyushina, Natalia A; Khalenkov, Alexey M; Seiler, Jon P; Forrest, Heather L; Bovin, Nicolai V; Marjuki, Henju; Barman, Subrata; Webster, Robert G; Webby, Richard J

    2010-09-01

    The molecular mechanism by which pandemic 2009 influenza A viruses were able to sufficiently adapt to humans is largely unknown. Subsequent human infections with novel H1N1 influenza viruses prompted an investigation of the molecular determinants of the host range and pathogenicity of pandemic influenza viruses in mammals. To address this problem, we assessed the genetic basis for increased virulence of A/CA/04/09 (H1N1) and A/TN/1-560/09 (H1N1) isolates, which are not lethal for mice, in a new mammalian host by promoting their mouse adaptation. The resulting mouse lung-adapted variants showed significantly enhanced growth characteristics in eggs, extended extrapulmonary tissue tropism, and pathogenicity in mice. All mouse-adapted viruses except A/TN/1-560/09-MA2 grew faster and to higher titers in cells than the original strains. We found that 10 amino acid changes in the ribonucleoprotein (RNP) complex (PB2 E158G/A, PA L295P, NP D101G, and NP H289Y) and hemagglutinin (HA) glycoprotein (K119N, G155E, S183P, R221K, and D222G) controlled enhanced mouse virulence of pandemic isolates. HA mutations acquired during adaptation affected viral receptor specificity by enhancing binding to alpha2,3 together with decreasing binding to alpha2,6 sialyl receptors. PB2 E158G/A and PA L295P amino acid substitutions were responsible for the significant enhancement of transcription and replication activity of the mouse-adapted H1N1 variants. Taken together, our findings suggest that changes optimizing receptor specificity and interaction of viral polymerase components with host cellular factors are the major mechanisms that contribute to the optimal competitive advantage of pandemic influenza viruses in mice. These modulators of virulence, therefore, may have been the driving components of early evolution, which paved the way for novel 2009 viruses in mammals.

  12. Cytotoxic T lymphocytes established by seasonal human influenza cross-react against 2009 pandemic H1N1 influenza virus.

    PubMed

    Tu, Wenwei; Mao, Huawei; Zheng, Jian; Liu, Yinping; Chiu, Susan S; Qin, Gang; Chan, Ping-Lung; Lam, Kwok-Tai; Guan, Jing; Zhang, Lijuan; Guan, Yi; Yuen, Kwok-Yung; Peiris, J S Malik; Lau, Yu-Lung

    2010-07-01

    While few children and young adults have cross-protective antibodies to the pandemic H1N1 2009 (pdmH1N1) virus, the illness remains mild. The biological reasons for these epidemiological observations are unclear. In this study, we demonstrate that the bulk memory cytotoxic T lymphocytes (CTLs) established by seasonal influenza viruses from healthy individuals who have not been exposed to pdmH1N1 can directly lyse pdmH1N1-infected target cells and produce gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha). Using influenza A virus matrix protein 1 (M1(58-66)) epitope-specific CTLs isolated from healthy HLA-A2(+) individuals, we further found that M1(58-66) epitope-specific CTLs efficiently killed both M1(58-66) peptide-pulsed and pdmH1N1-infected target cells ex vivo. These M1(58-66)-specific CTLs showed an effector memory phenotype and expressed CXCR3 and CCR5 chemokine receptors. Of 94 influenza A virus CD8 T-cell epitopes obtained from the Immune Epitope Database (IEDB), 17 epitopes are conserved in pdmH1N1, and more than half of these conserved epitopes are derived from M1 protein. In addition, 65% (11/17) of these epitopes were 100% conserved in seasonal influenza vaccine H1N1 strains during the last 20 years. Importantly, seasonal influenza vaccination could expand the functional M1(58-66) epitope-specific CTLs in 20% (4/20) of HLA-A2(+) individuals. Our results indicated that memory CTLs established by seasonal influenza A viruses or vaccines had cross-reactivity against pdmH1N1. These might explain, at least in part, the unexpected mild pdmH1N1 illness in the community and also might provide some valuable insights for the future design of broadly protective vaccines to prevent influenza, especially pandemic influenza.

  13. Subtype identification of the novel A H1N1 and other human influenza A viruses using an oligonucleotide microarray.

    PubMed

    Kang, Xiaoping; Li, Yongqiang; Sun, Honghe; Wu, Weili; Liu, Hong; Lin, Fang; Qing, Chenfeng; Chang, Guohui; Zhu, Qingyu; Chen, Weijun; Yang, Yinhui

    2010-01-01

    A novel strain of influenza A (H1N1) virus was isolated in Mexico and the US in March and April 2009. This novel virus spread to many countries and regions in a few months, and WHO raised the level of pandemic alert from phase 5 to phase 6 on June 11, 2009. The accurate identification of H1N1 virus and other human seasonal influenza A viruses is very important for further treatment and control of their infections. In this study, we developed an oligonucleotide microarray to subtype human H1N1, H3N2 and H5N1 influenza viruses, which could distinguish the novel H1N1 from human seasonal H1N1 influenza viruses and swine H1N1 influenza viruses. The microarray utilizes a panel of primers for multiplex PCR amplification of the hemagglutinin (HA), neuraminidase (NA) and matrix (MP) genes of human influenza A viruses. The 59-mer oligonucleotides were designed to distinguish different subtypes of human influenza A viruses. With this microarray, we accurately identified and correctly subtyped the reference virus strains. Moreover, we confirmed 4 out of 39 clinical throat swab specimens from suspected cases of novel H1N1.

  14. 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

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. Changes in the Viral Distribution Pattern after the Appearance of the Novel Influenza A H1N1 (pH1N1) Virus in Influenza-Like Illness Patients in Peru

    PubMed Central

    Laguna-Torres, Victor Alberto; Gómez, Jorge; Aguilar, Patricia V.; Ampuero, Julia S.; Munayco, Cesar; Ocaña, Víctor; Pérez, Juan; Gamero, María E.; Arrasco, Juan Carlos; Paz, Irmia; Chávez, Edward; Cruz, Rollin; Chavez, Jaime; Mendocilla, Silvia; Gomez, Elizabeth; Antigoni, Juana; Gonzalez, Sofía; Tejada, Cesar; Chowell, Gerardo; Kochel, Tadeusz J.

    2010-01-01

    Background We describe the temporal variation in viral agents detected in influenza like illness (ILI) patients before and after the appearance of the ongoing pandemic influenza A (H1N1) (pH1N1) in Peru between 4-January and 13-July 2009. Methods At the health centers, one oropharyngeal swab was obtained for viral isolation. From epidemiological week (EW) 1 to 18, at the US Naval Medical Research Center Detachment (NMRCD) in Lima, the specimens were inoculated into four cell lines for virus isolation. In addition, from EW 19 to 28, the specimens were also analyzed by real time-polymerase-chain-reaction (rRT-PCR). Results We enrolled 2,872 patients: 1,422 cases before the appearance of the pH1N1 virus, and 1,450 during the pandemic. Non-pH1N1 influenza A virus was the predominant viral strain circulating in Peru through (EW) 18, representing 57.8% of the confirmed cases; however, this predominance shifted to pH1N1 (51.5%) from EW 19–28. During this study period, most of pH1N1 cases were diagnosed in the capital city (Lima) followed by other cities including Cusco and Trujillo. In contrast, novel influenza cases were essentially absent in the tropical rain forest (jungle) cities during our study period. The city of Iquitos (Jungle) had the highest number of influenza B cases and only one pH1N1 case. Conclusions The viral distribution in Peru changed upon the introduction of the pH1N1 virus compared to previous months. Although influenza A viruses continue to be the predominant viral pathogen, the pH1N1 virus predominated over the other influenza A viruses. PMID:20668548

  20. 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.

  1. 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…

  2. 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

  3. Pandemic influenza A(H1N1) 2009 virus in pregnancy.

    PubMed

    Liu, She-Lan; Wang, Jing; Yang, Xu-Hui; Chen, Jin; Huang, Ren-Jie; Ruan, Bing; He, Hong-Xuan; Wang, Cheng-Min; Zhang, Hong-Mei; Sun, Zhou; Xie, Li; Zhuang, Hui

    2013-01-01

    Two hundred fourteen abstracts and 87 full texts regarding pregnant women infected with pandemic influenza A(H1N1) 2009 virus were systematically reviewed by using a PubMed search and assessing pandemic, clinical, laboratory test, vaccine, and control experiences. Both policy and health education were excluded. This review counted the total number of pregnant cases from different countries and analyzed their epidemic features, including trimester distribution, morbidity, hospitalization, intensive care unit admissions, maternal mortality, underlying diseases, complications, high-risk factors for death, pregnancy outcome, and clinical symptoms compared with the previous pandemic seasonal influenza A/H1N1 as compared with the general population. Early identification and treatment were the most important factors in different countries and areas examined. The vaccine and antiviral drugs that have been the most efficient means to control the novel virus appear to be safe but require more extensive study. In the future, the focus should be placed on understanding vertical transmission and the severe mechanisms.

  4. 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.

  5. 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.

  6. 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.

  7. Comparison of the clinical symptoms and the effectiveness of neuraminidase inhibitors for patients with pandemic influenza H1N1 2009 or seasonal H1N1 influenza in the 2007-2008 and 2008-2009 seasons.

    PubMed

    Kawai, Naoki; Ikematsu, Hideyuki; Tanaka, Osame; Matsuura, Shinro; Maeda, Tetsunari; Yamauchi, Satoshi; Hirotsu, Nobuo; Nishimura, Mika; Iwaki, Norio; Kashiwagi, Seizaburo

    2011-06-01

    The clinical symptoms and effectiveness of neuraminidase inhibitors (NAI) have not been adequately compared among pandemic H1N1 2009 patients, seasonal H1N1 patients, and patients with H1N1 with the H275Y mutation. The data of 68 seasonal H1N1 patients in 2007-2008, 193 seasonal H1N1 patients in 2008-2009, and 361 pandemic H1N1 2009 patients diagnosed by PCR who received an NAI were analyzed. The duration of fever (body temperature ≥ 37.5 ºC) after the first dose of NAI and from onset was calculated. The H275Y neuraminidase mutation status was determined for 166 patients. Significantly lower mean age (18.4 ± 13.2 years) and a higher percentage of teenagers (53.7%) were found for pandemic 2009 influenza than for seasonal influenza (P < 0.001). The peak body temperature was equivalent (mean, 39.0 ºC) in the three seasons, and the frequency of symptoms was the same or lower for pandemic influenza compared with seasonal H1N1. None of the 34 analyzed pandemic H1N1 virus isolates contained the H275Y mutation, which was commonly detected in the 2008-2009 season. The duration of fever after the start of oseltamivir therapy was significantly shorter for patients with pandemic (23.0 ± 11.6 h) than with seasonal H1N1 in both the 2008-2009 (49.7 ± 32.3 h) and 2007-2008 seasons (32.0 ± 18.9 h). The mean duration of fever after the first dose of zanamivir was not different among the three seasons (26.9-31.5 h). Clinical symptoms were the same or somewhat milder, and oseltamivir was more effective, for pandemic 2009 than for seasonal H1N1 influenza with or without H275Y mutation.

  8. 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

  9. Fatal cases associated with pandemic influenza A (H1N1) reported in Greece.

    PubMed Central

    Athanasiou, Maria; Lytras, Theodore; Spala, Georgia; Triantafyllou, Eleni; Gkolfinopoulou, Kassiani; Theocharopoulos, Georgios; Patrinos, Stavros; Danis, Kostas; Detsis, Marios; Tsiodras, Sotirios; Bonovas, Stefanos; Panagiotopoulos, Takis

    2010-01-01

    ABSTRACT Between 18 May 2009 and 3 May 2010, a total of 149 fatal cases associated with pandemic influenza A (H1N1) were reported in Greece. Detailed case-based epidemiological information was available for the large majority of fatal cases. The time distribution follows an epidemic curve with a peak in the beginning of December 2009 and a second peak one month later. This is similar to that of laboratory confirmed cases and influenza-like illness cases from our sentinel surveillance system, with two weeks delay. The most commonly reported underlying conditions were chronic cardiovascular disease and immunosuppression, while the most frequently identified risk factor was obesity. These findings should be taken into consideration, when vaccination strategies are employed. PMID:21085493

  10. Aliphatic and alicyclic camphor imines as effective inhibitors of influenza virus H1N1.

    PubMed

    Sokolova, Anastasiya S; Yarovaya, Оlga I; Baev, Dmitry S; Shernyukov, Аndrey V; Shtro, Anna A; Zarubaev, Vladimir V; Salakhutdinov, Nariman F

    2017-02-15

    A series of camphor derived imines was synthesised and evaluated in vitro for antiviral activity. Theoretical evaluations of ADME properties were also carried out. Most of these compounds exhibited significant activity against the drug-resistant strains of influenza A virus. Especially, compounds 2 (SI = 632) and 3 (SI = 417) presented high inhibition against influenza subtypes A/Puerto Rico/8/34 and A/California/07/09 of H1N1pdm09. Analysis of the structure-activity relationship showed that the activity was strongly dependent on the length of the aliphatic chain: derivatives with a shorter chain possessed higher activity, while the suppressing action of compounds with long aliphatic chains was lower.

  11. 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.

  12. Induction of cell surface human leukocyte antigen-G expression in pandemic H1N1 2009 and seasonal H1N1 influenza virus-infected patients.

    PubMed

    Chen, Hai-Xiao; Chen, Bao-Guo; Shi, Wei-Wu; Zhen, Rui; Xu, Dan-Ping; Lin, Aifen; Yan, Wei-Hua

    2011-02-01

    A novel H1N1 virus of swine origin (H1N1v) recently caused a pandemic; however, knowledge of immunologic aspects of the virus infection are limited. Human leukocyte antigen-G (HLA-G) was speculated to play critical roles in viral infection, although its clinical relevance in H1N1 infection remains unknown. In this study, HLA-G expression in peripheral T lymphocytes, monocytes, and CD4(+) CD25(+) FoxP3+ regulatory T (Treg) cells (in 50 H1N1v-infected and 41 seasonal H1N1-infected patients and 27 control subjects) were analyzed by flow cytometry. Plasma-soluble HLA-G (sHLA-G, in 28 H1N1v-infected, 29 seasonal H1N1-infected patients and 85 control subjects) were determined with enzyme-linked immunosorbent assay. The percentage of HLA-G-positive T lymphocytes and monocytes among patients with H1N1v and seasonal H1N1 infections was dramatically increased compared with controls (all p < 0.001). Treg was markedly increased among H1N1v- infected patients compared with normal controls (p = 0.041), but not for the seasonal H1N1-infected patients. Meanwhile, no significant difference was observed for sHLA-G levels between the groups. Together, cell surface HLA-G expression was markedly induced in H1N1v-infected and seasonal H1N1-infected patients, and increased Treg was observed only in H1N1v-infected patients. Given its immune-suppressive property, elevated cell surface HLA-G expression may help to explain the virus escaping from host immune responses.

  13. 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

  14. Peptide Sharing Between Influenza A H1N1 Hemagglutinin and Human Axon Guidance Proteins

    PubMed Central

    Kanduc, Darja

    2014-01-01

    Epidemiologic data suggest that maternal microbial infections may cause fetal neurodevelopmental disorders, potentially increasing susceptibility to heavy psychopathologies such as schizophrenia, schizophreniform disorder, autism, pervasive developmental disorders, bipolar disorders, psychosis, epilepsy, language and speech disorders, and cognitive impairment in adult offspring. However, the molecular pathomechanisms underlying such a relationship are not clear. Here we analyze the potential role of the maternal immune response to viral infection in determining fetal brain injuries that increase the risk of neurological disorders in the adult. We use influenza infection as a disease model and human axon guidance pathway, a key process in the formation of neural network during midgestation, as a potential fetal target of immune insults. Specifically, we examined influenza A H1N1 hemagglutinin (HA), an antigenic viral protein, for amino acid sequence similarity to a random library of 188 axon guidance proteins. We obtain the results that (1) contrary to any theoretical expectations, 45 viral pentapeptide matches are distributed throughout a subset of 36 guidance molecules; (2) in 24 guidance proteins, the peptide sharing with HA antigen involves already experimentally validated influenza HA epitopes; and (3) most of the axon guidance vs HA peptide overlap is conserved among influenza A viral strains and subsets. Taken together, our data indicate that immune cross-reactivity between influenza HA and axon guidance molecules is possible and may well represent a pathologic mechanism capable of determining neurodevelopmental disruption in the fetus. PMID:23378012

  15. 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.

  16. Recurrent plastic bronchitis in a child with 2009 influenza A (H1N1) and influenza B virus infection.

    PubMed

    Kim, Sun; Cho, Hwa Jin; Han, Dong Kyun; Choi, Yoo Duk; Yang, Eun Seok; Cho, Young Kuk; Ma, Jae Sook

    2012-09-01

    Plastic bronchitis is an uncommon disorder characterized by the formation of bronchial casts. It is associated with congenital heart disease or pulmonary disease. In children with underlying conditions such as allergy or asthma, influenza can cause severe plastic bronchitis resulting in respiratory failure. A review of the literature showed nine cases of plastic bronchitis with H1N1 including this case. We report a case of a child with recurrent plastic bronchitis with eosinophilic cast associated with influenza B infection, who had recovered from plastic bronchitis associated with an influenza A (H1N1) virus infection 5 months previously. To the best of our knowledge, this is the first case of recurrent plastic bronchitis related to influenza viral infection. If patients with influenza virus infection manifest acute respiratory distress with total lung atelectasis, clinicians should consider plastic bronchitis and early bronchoscopy should be intervened. In addition, management for underlying disease may prevent from recurrence of plastic bronchitis.

  17. [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.

  18. Guidance for Testing and Labeling Claims against Pandemic 2009 H1N1 Influenza A Virus (Formerly called Swine Flu )

    EPA Pesticide Factsheets

    This document provides guidance labeling and testing for antimicrobial pesticides in several forms that are used to treat hard non-porous surfaces in healthcare facilities and other settings against Pandemic 2009 H1N1 influenza A Virus.

  19. A novel monoclonal antibody effective against lethal challenge with swine-lineage and 2009 pandemic H1N1 influenza viruses in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The HA protein of the 2009 pandemic H1N1viruses (14 H1N1pdm) is antigenically closely related to the HA of classical North American swine H1N1 influenza viruses (cH1N1). Since 1998, through reassortment and incorporation of HA genes from human H3N2 and H1N1 influenza viruses, swine influenza strains...

  20. Pandemic response lessons from influenza H1N1 2009 in Asia.

    PubMed

    Fisher, Dale; Hui, David S; Gao, Zhancheng; Lee, Christopher; Oh, Myoung-Don; Cao, Bin; Hien, Tran Tinh; Patlovich, Krista; Farrar, Jeremy

    2011-08-01

    During April 2009, a novel H1N1 influenza A virus strain was identified in Mexico and the USA. Within weeks the virus had spread globally and the first pandemic of the 21st Century had been declared. It is unlikely to be the last and it is crucial that real lessons are learned from the experience. Asia is considered a hot spot for the emergence of new pathogens including past influenza pandemics. On this occasion while preparing for an avian, highly virulent influenza virus (H5N1 like) originating in Asia in fact the pandemic originated from swine, and was less virulent. This discrepancy between what was planned for and what emerged created its own challenges. The H1N1 pandemic has tested national health-care infrastructures and exposed shortcomings in our preparedness as a region. Key health challenges include communication throughout the region, surge capacity, access to reliable information and access to quality care, health-care worker skills, quality, density and distribution, access to essential medicines and lack of organizational infrastructure for emergency response. Despite years of preparation the public health and clinical research community were not ready to respond and opportunities for an immediate research response were missed. Despite warm words and pledges efforts to engage the international community to ensure equitable sharing of limited resources such as antivirals and vaccines fell short and stockpiles in the main remained in the rich world. This manuscript with authors from across the region describes some of the major challenges faced by Asia in response to the pandemic and draws lessons for the future.

  1. Origin and fate of A/H1N1 influenza in Scotland during 2009

    PubMed Central

    Lycett, Samantha; McLeish, Nigel J.; Robertson, Christopher; Carman, William; Baillie, Gregory; McMenamin, James; Rambaut, Andrew; Simmonds, Peter; Woolhouse, Mark

    2012-01-01

    The spread of influenza has usually been described by a ‘density’ model, where the largest centres of population drive the epidemic within a country. An alternative model emphasizing the role of air travel has recently been developed. We have examined the relative importance of the two in the context of the 2009 H1N1 influenza epidemic in Scotland. We obtained genome sequences of 70 strains representative of the geographical and temporal distribution of H1N1 influenza during the summer and winter phases of the pandemic in 2009. We analysed these strains, together with another 128 from the rest of the UK and 292 globally distributed strains, using maximum-likelihood phylogenetic and Bayesian phylogeographical methods. This revealed strikingly different epidemic patterns within Scotland in the early and late parts of 2009. The summer epidemic in Scotland was characterized by multiple independent introductions from both international and other UK sources, followed by major local expansion of a single clade that probably originated in Birmingham. The winter phase, in contrast, was more diverse genetically, with several clades of similar size in different locations, some of which had no particularly close phylogenetic affinity to strains sampled from either Scotland or England. Overall there was evidence to support both models, with significant links demonstrated between North American sequences and those from England, and between England and East Asia, indicating that major air-travel routes played an important role in the pattern of spread of the pandemic, both within the UK and globally. PMID:22337637

  2. 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.

  3. 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.

  4. Dialysis for acute kidney injury associated with influenza a (H1N1) infection.

    PubMed

    Vallejos, Augusto; Arias, Marcelo; Cusumano, Ana; Coste, Eduardo; Simon, Miguel; Martinez, Ricardo; Mendez, Sandra; Raño, Miguel; Sintado, Luis; Lococo, Bruno; Blanco, Carlos; Cestari, Jorge

    2013-05-01

    In June 2009, the World Health Organization declared a novel influenza A, S-OIV (H1N1), pandemic. We observed 44 consecutive patients during the "first wave" of the pandemic. 70.5% of them showed co-morbidities (hypertension, obesity, chronic respiratory diseases, chronic renal disease, diabetes, pregnancy). Serious cases were admitted to the intensive care unit (ICU), particularly those with severe acute respiratory failure. Some of them developed acute kidney injury (AKI) and required renal replacement therapy (RRT). The average time between admission to the ICU and initiation of RRT was 3.16 ± 2.6 days. At initiation of RRT, most patients required mechanical ventilation. No relationship was found with creatinine-kinase levels. Seventy-five percent of the cases were observed during a 3-week period and mortality, related to respiratory failure, doubling of alanine amino transferase and use of inotropics was 81.8%. In conclusion, the H1N1-infected patients who developed RRT-requiring AKI, in the context of multi-organ failure, showed a high mortality rate. Thus, it is mandatory that elaborate strategies aimed at anticipating potential renal complications associated to future pandemics are implemented.

  5. 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.

  6. Safety of the Pandemic H1N1 Influenza Vaccine among Pregnant U.S. Military Women and Their Newborns

    DTIC Science & Technology

    2013-03-01

    Naval Health Research Center Safety of the Pandemic H1N1 Influenza Vaccine among Pregnant Women and Their Newborns Ava M.S. Conlin Anna...Safety of the Pandemic H1N1 Influenza Vaccine Among Pregnant U.S. Military Women and Their Newborns Ava Marie S. Conlin, DO, MPH, Anna T. Bukowinski...active-duty U.S. military women who received pandemic H1N1 vaccine during pregnancy as well as adverse health outcomes among the newborns resulting from

  7. 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...

  8. 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...

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

    PubMed

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

    2009-09-28

    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.

  10. Rapid control of pandemic H1N1 influenza by targeting NKT-cells

    PubMed Central

    Artiaga, Bianca L.; Yang, Guan; Hutchinson, Tarun E.; Loeb, Julia C.; Richt, Jürgen A.; Lednicky, John A.; Salek-Ardakani, Shahram; Driver, John P.

    2016-01-01

    Swine influenza A viruses (IAV) are a major cause of respiratory disease in pigs and humans. Currently approved anti-influenza therapies directly target the virus, but these approaches are losing effectiveness as new viral strains quickly develop drug resistance. To over come this challenge, there is an urgent need for more effective antiviral drugs. Here we tested the anti-influenza efficacy of the invariant natural killer T (NKT) cell superagonist, α-galactosylceramide (α-GalCer), which stimulates a wide array of anti-viral immune responses. We show that intranasal but not systemic administration of α-GalCer to piglets infected with pandemic A/California/04/2009 (CA04) H1N1 IAV ameliorated disease symptoms and resulted in the restoration of weight gain to the level of uninfected pigs. Correspondingly, viral titers in the upper-and lower-respiratory tract were reduced only in piglets that had received intranasal α-GalCer. Most significantly, lung inflammation as a consequence of virus persistence was largely prevented when NKT-cells were targeted via the respiratory route. Thus, targeting mucosal NKT-cells may provide a novel and potent platform for improving the course of disease in swine infected with seasonal and pandemic influenza viruses, and leads to the suggestion that this may also be true in humans and therefore deserves further study. PMID:27897246

  11. Detection of novel influenza A(H1N1) virus by real-time RT-PCR.

    PubMed

    Whiley, David M; Bialasiewicz, Seweryn; Bletchly, Cheryl; Faux, Cassandra E; Harrower, Bruce; Gould, Allan R; Lambert, Stephen B; Nimmo, Graeme R; Nissen, Michael D; Sloots, Theo P

    2009-07-01

    Accurate and rapid diagnosis of novel influenza A(H1N1) infection is critical for minimising further spread through timely implementation of antiviral treatment and other public health based measures. In this study we developed two TaqMan-based reverse transcription PCR (RT-PCR) methods for the detection of novel influenza A(H1N1) virus targeting the haemagglutinin and neuraminidase genes. The assays were validated using 152 clinical respiratory samples, including 61 Influenza A positive samples, collected in Queenland, Australia during the years 2008 to 2009 and a further 12 seasonal H1N1 and H3N2 influenza A isolates collected from years 2000 to 2002. A wildtype swine H1N1 isolate was also tested. RNA from an influenza A(H1N1) virus isolate (Auckland, 2009) was used as a positive control. Overall, the results showed that the RT-PCR methods were suitable for sensitive and specific detection of novel influenza A(H1N1) RNA in human samples.

  12. 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

  13. [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.

  14. Outbreaks of 2009 pandemic influenza A (H1N1) among long-term-care facility residents - three states, 2009.

    PubMed

    2010-01-29

    Hospitalization and death from seasonal influenza are more common among older adults and in long-term--care facilities (LTCFs). Early data from the 2009 pandemic influenza A (H1N1) outbreak indicated that attack rates among persons aged >or=65 years were lower than in other age groups, and anti-influenza A antibodies that cross-react with 2009 H1N1 could be detected in up to one third of healthy adults aged >60 years. Based on these early data and anticipation of limited initial supplies of 2009 H1N1 vaccine, the Advisory Committee on Immunization Practices (ACIP) identified priority groups for vaccination, which did not include persons aged >or=65 years who did not have higher risk for influenza or its complications. During October and November 2009, CDC received reports of 2009 H1N1 outbreaks in LTCFs in Colorado, Maine, and New York. This report summarizes the three outbreaks, which involved facilities primarily housing older patients. These outbreaks illustrate that, despite the lower risk for infection with 2009 H1N1 among persons aged >or=65 years compared with seasonal influenza, 2009 H1N1 outbreaks still can occur in LTCFs. These outbreaks also underscore the importance of respiratory illness surveillance and recommended infection-control procedures in LTCFs. All health-care personnel should be vaccinated against seasonal influenza and 2009 H1N1. LTCF residents should receive seasonal influenza vaccination, and should be vaccinated against 2009 H1N1 after assessment of vaccine availability at the local level indicates that demand for vaccine among younger age groups is being met.

  15. 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

  16. Fatal 2009 pandemic influenza A (H1N1) in a bone marrow transplant recipient.

    PubMed

    Abdo, Anselmo; Alfonso, Carlos; Diaz, Guillermo; Wilford, Mario; Rocha, Maykel; Verdecia, Niurka

    2011-03-02

    Conditions characterized by immunosuppression have been recently reported as risk factors for severe novel swine-origin influenza A (H1N1) virus (S-OIV) infection during the current 2009 pandemic.  We report clinical and virological findings, antiviral therapy, and post-mortem study of S-OIV in an adult bone marrow transplant recipient. The viral genome was amplified by real time reverse transcriptase polymerase chain reaction (RT-PCR) from a nasopharyngeal swab specimen. The patient developed acute respiratory distress syndrome, septic shock, and eventually succumbed with a severe pulmonary haemorrhage. To the best of our knowledge, the entire clinical/therapy management and pathological examination in a transplant recipient infected with the S-OIV has not been previously documented. The fatal ending in this bone marrow transplant recipient supports recommendations that call for education measures, S-OIV vaccination, early diagnosis and aggressive treatment in the transplant population.

  17. Possible computational filter to detect proteins associated to influenza A subtype H1N1.

    PubMed

    Polanco, Carlos; Buhse, Thomas; Castañón-González, Jorge Alberto; Samaniego, José Lino

    2014-01-01

    The design of drugs with bioinformatics methods to identify proteins and peptides with a specific toxic action is increasingly recurrent. Here, we identify toxic proteins towards the influenza A virus subtype H1N1 located at the UniProt database. Our quantitative structure-activity relationship (QSAR) approach is based on the analysis of the linear peptide sequence with the so-called Polarity Index Method that shows an efficiency of 90% for proteins from the Uniprot Database. This method was exhaustively verified with the APD2, CPPsite, Uniprot, and AmyPDB databases as well as with the set of antibacterial peptides studied by del Rio et al. and Oldfield et al.

  18. Lessons Learned from Influenza A(H1N1)pdm09 Pandemic Response in Thailand

    PubMed Central

    Sawanpanyalert, Pathom; Hanchoworakul, Wanna; Sawanpanyalert, Narumol; Maloney, Susan A.; Brown, Richard Clive; Birmingham, Maureen Elizabeth; Chusuttiwat, Supamit

    2012-01-01

    In 2009, Thailand experienced rapid spread of the pandemic influenza A(H1N1)pdm09 virus. The national response came under intense public scrutiny as the number of confirmed cases and associated deaths increased. Thus, during July–December 2009, the Ministry of Public Health and the World Health Organization jointly reviewed the response efforts. The review found that the actions taken were largely appropriate and proportionate to need. However, areas needing improvement were surveillance, laboratory capacity, hospital infection control and surge capacity, coordination and monitoring of guidelines for clinical management and nonpharmaceutical interventions, risk communications, and addressing vulnerabilities of non-Thai displaced and migrant populations. The experience in Thailand may be applicable to other countries and settings, and the lessons learned may help strengthen responses to other pandemics or comparable prolonged public health emergencies. PMID:22709628

  19. 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.

  20. Reassortant Eurasian Avian-Like Influenza A(H1N1) Virus from a Severely Ill Child, Hunan Province, China, 2015

    PubMed Central

    Zhu, Wenfei; Zhang, Hong; Xiang, Xingyu; Zhong, Lili; Yang, Lei; Guo, Junfeng; Xie, Yiran; Li, Fangcai; Deng, Zhihong; Feng, Hong; Huang, Yiwei; Hu, Shixiong; Xu, Xin; Zou, Xiaohui; Li, Xiaodan; Bai, Tian; Chen, Yongkun; Li, Zi

    2016-01-01

    In 2015, a novel influenza A(H1N1) virus was isolated from a boy in China who had severe pneumonia. The virus was a genetic reassortant of Eurasian avian-like influenza A(H1N1) (EA-H1N1) virus. The hemagglutinin, neuraminidase, and matrix genes of the reassortant virus were highly similar to genes in EA-H1N1 swine influenza viruses, the polybasic 1 and 2, polymerase acidic, and nucleoprotein genes originated from influenza A(H1N1)pdm09 virus, and the nonstructural protein gene derived from classical swine influenza A(H1N1) (CS H1N1) virus. In a mouse model, the reassortant virus, termed influenza A/Hunan/42443/2015(H1N1) virus, showed higher infectivity and virulence than another human EA-H1N1 isolate, influenza A/Jiangsu/1/2011(H1N1) virus. In the respiratory tract of mice, virus replication by influenza A/Hunan/42443/2015(H1N1) virus was substantially higher than that by influenza A/Jiangsu/1/2011(H1N1) virus. Human-to-human transmission of influenza A/Hunan/42443/2015(H1N1) virus has not been detected; however, given the circulation of novel EA-H1N1 viruses in pigs, enhanced surveillance should be instituted among swine and humans. PMID:27767007

  1. 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

  2. Population modeling of influenza A/H1N1 virus kinetics and symptom dynamics.

    PubMed

    Canini, Laetitia; Carrat, Fabrice

    2011-03-01

    Influenza virus kinetics (VK) is used as a surrogate of infectiousness, while the natural history of influenza is described by symptom dynamics (SD). We used an original virus kinetics/symptom dynamics (VKSD) model to characterize human influenza virus infection and illness, based on a population approach. We combined structural equations and a statistical model to describe intra- and interindividual variability. The structural equations described influenza based on the target epithelial cells, the virus, the innate host response, and systemic symptoms. The model was fitted to individual VK and SD data obtained from 44 volunteers experimentally challenged with influenza A/H1N1 virus. Infection and illness parameters were calculated from best-fitted model estimates. We predicted that the cytokine level and NK cell activity would peak at days 2.2 and 4.2 after inoculation, respectively. Infectiousness, measured as the area under the VK curve above a viral titer threshold, lasted between 7.0 and 1.3 days and was 15 times lower in participants without systemic symptoms than in those with systemic symptoms (P < 0.001). The latent period, defined as the time between inoculation and infectiousness, varied from 0.7 to 1.9 days. The incubation period, defined as the time from inoculation to first symptoms, varied from 1.0 to 2.4 days. Our approach extends previous work by including the innate response and providing realistic estimates of infection and illness parameters, taking into account the strong interindividual variability. This approach could help to optimize studies of influenza VK and SD and to predict the effect of antivirals on infectiousness and symptoms.

  3. 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

  4. 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.

  5. Perspectives from Spanish infectious diseases professionals on 2009 A (H1N1) influenza: the third half.

    PubMed

    Paño-Pardo, J R; Martín-Quirós, A; Romero-Gómez, M; Maldonado, J; Martín-Vega, A; Rico-Nieto, A; Mora-Rillo, M; Grill, F; García-Rodríguez, J; Arribas, J R; Carratalá, J; Rodríguez-Baño, J

    2011-06-01

    The first influenza pandemic in more than 40 years was declared in 2009. We aimed to evaluate the beliefs of Spanish infectious diseases professionals regarding several aspects of 2009 A (H1N1) influenza once the epidemic waned. An online survey was designed and distributed among members of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC). The survey considered hospital organization and preparedness planning and conduct, as well as the opinion of the infectious diseases professionals regarding several key issues. Between 7 March and 22 March 2010, 303 responses, corresponding to 12.8% of the SEIMC membership, were received. Of the respondents, 48.2% were microbiologists and 42.3% were clinicians dealing with infectious diseases. Forty-one per cent of respondents did not believe that 2009 A (H1N1) influenza had a more severe presentation than other seasonal influenzas. Only 5% fully agreed that 2009 A (H1N1) influenza had a more severe presentation. Influenza planning was available in 69.7% of represented institutions before the arrival of 2009 A (H1N1) influenza, and was considered to be useful, to different extents, by most professionals. In most institutions (88.3%), a multidisciplinary team was created to coordinate local pandemic influenza actions. The most successful protocols were those provided by regional healthcare authorities, followed by those from the CDC. The most problematic issues regarding 2009 A (H1N1) influenza were the management of patients in the emergency room and the vaccination and awareness of healthcare professionals (HCPs) regarding infection control. Microbiological diagnosis and the availability of antivirals were the least problematic areas. Although the majority of surveyed infectious diseases professionals did not believe that 2009 A (H1N1) influenza had an especially severe presentation, most of them agreed with the way that this epidemic was managed in their institutions.

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. Relationship between population configuration and the spatial pattern of pandemic influenza A (H1N1) 2009 in Hong Kong.

    PubMed

    Lee, S S; Wong, N S

    2012-08-01

    OBJECTIVE. To investigate the association between population structure and the pandemic influenza A (H1N1) 2009 epidemic in a spatial context. DESIGN. A retrospective case-report series study. SETTING. Hong Kong. PATIENTS. Laboratory-confirmed cases of human influenza A (H1N1) 2009 reported to the Centre for Health Protection between May and September 2009. MAIN OUTCOME MEASURES. A geo-referenced database was established comprising age, gender, and residence location of all influenza A (H1N1) 2009 cases reported in the first 5 months of the Kong Kong epidemic's first wave in 2009. They were divided into four age categories: infant, student, adult, and elderly. Correlation coefficients and odds ratios were calculated to explore the association of H1N1 cases with population configurations in 400 District Council Constituency Areas. RESULTS. Of the 24 414 H1N1 cases reported, students accounted for the highest proportion (54.6%), followed by adults (33.4%), infants (11.1%), and the elderly (0.9%). Transmission was initially concentrated in students which then extended to infants and adults. Except for the elderly, the total population size and that of each age category were significantly associated with the H1N1 cases spatially. Mobility indicators as reflected by the number of students studying outside and adults working outside residential District Council Constituency Areas were also positively associated with H1N1 cases. CONCLUSIONS. Local population structure and mobility were associated with the spatial distribution of the H1N1 epidemic, despite the small size of the territory of Hong Kong. If an influenza epidemic hits again, an examination of these factors spatially would be useful in supporting the planning of interventions.

  14. Prospective evaluation of epidemiological, clinical, and microbiological features of pandemic influenza A (H1N1) virus infection in Italy.

    PubMed

    Fabbiani, Massimiliano; Sali, Michela; Di Cristo, Valentina; Pignataro, Giulia; Prete, Valentina; Farina, Salvatore; D'Avino, Alessandro; Manzara, Stefania; Dal Verme, Lorenzo Zileri; Silveri, Nicolò Gentiloni; Cauda, Roberto; Delogu, Giovanni; Fadda, Giovanni; Di Giambenedetto, Simona

    2011-12-01

    Since several characteristics of pandemic influenza A (H1N1) virus infection remain to be determined, this study aimed to describe clinical features and complications of patients infected with H1N1. Subjects affected by influenza-like illnesses and a control group of asymptomatic patients were enrolled prospectively at an Emergency Department from October 2009 to April 2010. At enrollment, clinical data and nasopharyngeal swabs for virological analyses were obtained. Ill subjects were followed until recovery and swabs were collected weekly in patients infected with H1N1. Of 318 patients enrolled, 92 (28.9%) were positive to H1N1. Patients infected with H1N1 were mainly young adults and complained classic influenza-like symptoms. Fever was observed for a median time of 5 (IQR 3-7) days. Hospitalization occurred in 27.7% with 2% requiring intensive care unit admission: median length of hospitalization was 6 days (IQR 5-9). Pneumonia was diagnosed in 19.6% of patients. A similar proportion of lower airways involvement and of clinical complications was observed in subjects testing positive or negative for H1N1. However, patients infected with H1N1 were younger and hospitalized for a shorter period as compared to the control group (P = 0.002 and P = 0.045, respectively). Older age, asthma/chronic obstructive pulmonary disease and hypertension were associated with an increased risk of pneumonia. Viral shedding was observed for at least 1 week in 21.3% of patients. Asymptomatic infection was uncommon (1.1%). Respiratory syndromes caused by H1N1 and factors associated with disease severity were investigated and compared to influenza-like illnesses of other origin. Such findings might contribute to improve clinical and epidemiological management of the disease.

  15. 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.

  16. 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

  17. Computational model for analyzing the evolutionary patterns of the neuraminidase gene of influenza A/H1N1.

    PubMed

    Ahn, Insung; Son, Hyeon Seok

    2012-02-01

    In this study, we performed computer simulations to evaluate the changes of selection potentials of codons in influenza A/H1N1 from 1999 to 2009. We artificially generated the sequences by using the transition matrices of positively selected codons over time, and their similarities against the database of influenzavirus A genus were determined by BLAST search. This is the first approach to predict the evolutionary direction of influenza A virus (H1N1) by simulating the codon substitutions over time. We observed that the BLAST results showed the high similarities with pandemic influenza A/H1N1 in 2009, suggesting that the classical human-origin influenza A/H1N1 isolated before 2009 might contain some selection potentials of swine-origin viruses. Computer simulations using the time series codon substitution patterns resulted dramatic changes of BLAST results in influenza A/H1N1, providing a possibility of developing a method for predicting the viral evolution in silico.

  18. 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.

  19. 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.

  20. Asparagine substitution at PB2 residue 701 enhances the replication, pathogenicity, and transmission of the 2009 pandemic H1N1 influenza A virus.

    PubMed

    Zhou, Bin; Pearce, Melissa B; Li, Yan; Wang, Jieru; Mason, Robert J; Tumpey, Terrence M; Wentworth, David E

    2013-01-01

    The 2009/2010 pandemic influenza virus (H1N1pdm) contains an avian-lineage PB2 gene that lacks E627K and D701N substitutions important in the pathogenesis and transmission of avian-origin viruses in humans or other mammals. Previous studies have shown that PB2-627K is not necessary because of a compensatory Q591R substitution. The role that PB2-701N plays in the H1N1pdm phenotype is not well understood. Therefore, PB2-D701N was introduced into an H1N1pdm virus (A/New York/1682/2009 (NY1682)) and analyzed in vitro and in vivo. Mini-genome replication assay, in vitro replication characteristics in cell lines, and analysis in the mouse and ferret models demonstrated that PB2-D701N increased virus replication rates and resulted in more severe pathogenicity in mice and more efficient transmission in ferrets. In addition, compared to the NY1682-WT virus, the NY1682-D701N mutant virus induced less IFN-λ and replicated to a higher titer in primary human alveolar epithelial cells. These findings suggest that the acquisition of the PB2-701N substitution by H1N1pdm viruses may result in more severe disease or increase transmission in humans.

  1. Generalized anhidrosis in a child following presumptive H1N1 influenza.

    PubMed

    Ghosh, Partha S; Mitra, Sudeshna; Fealey, Robert D

    2012-04-01

    We report an 8-year-old girl who developed generalized anhidrosis following presumptive H1N1 infection. Pure autonomic dysfunction is an unusual complication following H1N1 infection and specially generalized anhidrosis without other autonomic dysfunction have not been reported before.

  2. 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

  3. 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.

  4. 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

  5. RATE AND INFLUENCE OF RESPIRATORY VIRUS CO-INFECTION ON PANDEMIC (H1N1) INFLUENZA DISEASE

    PubMed Central

    Esper, Frank P.; Spahlinger, Timothy; Zhou, Lan

    2011-01-01

    Objectives Many patients with influenza have more than one viral agent with co-infection frequencies reported as high as 20%. The impact of respiratory virus copathogens on influenza disease is unclear. We sought to determine if respiratory virus co-infection with pandemic H1N1 altered clinical disease. Methods Respiratory samples from 229 and 267 patients identified with and without H1N1 influenza respectively were screened for the presence of 13 seasonal respiratory viruses by multiplex RT-PCR. Disease severity between coinfected and monoinfected H1N1 patients were quantified using a standardized clinical severity scale. Influenza viral load was calculated by quantitative RT-PCR. Results Thirty (13.1%) influenza samples screened positive for the presence of 31 viral copathogens. The most prominent copathogens included rhinovirus (61.3%), and coronaviruses (16.1%). Median clinical severity of both monoinfected and co-infected groups were 1. Patients coinfected with rhinovirus tended to have lower clinical severity (median 0), whereas non rhinovirus co-infections had substantially higher clinical severity (median 2). No difference in H1N1 viral load was observed between co-infected and mono infected groups. Conclusions Respiratory viruses co-infect patients with influenza disease. Patients coinfected with rhinovirus had less severe disease while non-rhinovirus co-infections were associated with substantially higher severity without changes in influenza viral titer. PMID:21546090

  6. Challenge and polymorphism analysis of the novel A (H1N1) influenza virus to normal animals.

    PubMed

    Bao, Linlin; Xu, Lili; Zhan, Lingjun; Deng, Wei; Zhu, Hua; Gao, Hong; Sun, Huihui; Ma, Chunmei; Lv, Qi; Li, Fengdi; Chen, Honglin; Zhang, Lianfeng; Qin, Chuan

    2010-07-01

    The novel influenza A (H1N1) virus that emerged from April 2009 in Mexico has spread rapidly to many countries and initiated a human pandemic. It is important to determine whether the virus has existed in, or will spread to, normal household animals, and whether A (H1N1)-like viruses derived from the animal is able to proliferate in cell lines derived from human. In this current paper, familiar animals, including pigs, chickens, ducks, cats, dogs, rats, mice, and Brandt's voles were challenged with the novel influenza A (H1N1) virus, and genetic variations of the viral genome were analyzed after three passages in the susceptible animals. To further determine the virulence of these animals derived influenza A (H1N1)-like viruses, viral replication dynamic curves were monitored after inoculation in MDCK cells and human A549 cells. Our results indicated that pigs, BALB/c mice, and Brandt's voles, but not chickens, ducks, cats, dogs, and rats, could be infected by the novel influenza A (H1N1) virus. Genome sequence alignment results showed that there was one genetic variation (G408T) in the HA gene of Brandt's vole derived virus and another one (C194A) in the NA gene of BALB/c mice derived virus, and the virulence of these two viruses in MDCK and A549 cells was significantly lower than the virus originally derived from human beings.

  7. "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.

  8. 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.

  9. 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

  10. A child with influenza A (H1N1)-associated myocarditis rescued by extracorporeal membrane oxygenation.

    PubMed

    Oda, Takeshi; Yasunaga, Hiroshi; Tsutsumi, Yoshimitsu; Shojima, Takahiro; Zaima, Yasuyuki; Nishino, Hiroshi; Ito, Shinichi; Todo, Kageshige

    2010-12-01

    A 6-year-old boy had cold-like symptoms and was diagnosed with influenza A at a clinic. Administration of oseltamivir and azithromycin did not improve the symptoms. He was referred to our hospital and was diagnosed with H1N1 pneumonia. The patient required ventilator support. However, hypoxia and hypercapnia were uncontrollable. To oxygenate and reduce the carbon dioxide concentration, veno-venous extracorporeal membrane oxygenation (ECMO) was applied 24 h after admission. We established outflow via the right internal jugular vein and inflow via the right femoral vein. Six hours later, an electrical storm of ventricular fibrillation occurred, probably due to influenza myocarditis. Chest compression was started immediately. Both cardioversion and medication were ineffective in treating the electrical storm. Therefore, we decided to switch the veno-venous ECMO to veno-arterial ECMO to maintain systemic flow. During chest compression, a 6-mm graft was anastomosed to the left common femoral artery, and an outflow tube was connected to the graft. Consequently, veno-arterial ECMO was established via outflow through the left common femoral artery and inflow through both the right jugular vein and right femoral vein. Veno-arterial ECMO terminated the electrical storm, and cardiac output improved. Veno-arterial ECMO was provided for 107 h, and was then replaced by veno-venous ECMO. Forty-three hours later, veno-venous ECMO was discontinued. The patient was successfully weaned from the mechanical ventilator on the 9th day after admission. Unfortunately, spinal infarction appeared as a complication. The patient was discharged from the hospital on the 86th day, and has now returned to primary school.

  11. Characteristics of outpatients with pandemic H1N1/09 influenza in a tertiary care university hospital in Korea.

    PubMed

    Park, Kyung Sun; Park, Tae Sung; Suh, Jin Tae; Nam, You Sun; Lee, Mi Suk; Lee, Hee Joo

    2012-01-01

    The pandemic H1N1/09 emerged rapidly in Korea. Here, we describe the clinical characteristics of outpatients in Seoul, Korea who were infected in the 2009 H1N1 pandemic. We reviewed the cases of outpatients with pandemic H1N1/09 who visited a tertiary care teaching hospital between September 1 and December 31, 2009. Infection with pandemic H1N1/09 was confirmed by molecular tests. Of a total of 7,182 tests, 3,020 (42.0%) were positive. Compared with 473 cases of influenza- like illness (ILI), the 586 confirmed cases of pandemic H1N1/09 differed in age [odds ratio (OR) 0.975] and fulfilling at least one of the following factors: age < 5 or ≥ 65 years, history of contact with other pandemic H1N1/09-infected individuals (OR 0.611), fever ≥ 37.8°C (OR 3.567), cough (OR 2.290), and myalgia (OR 1.559). The sensitivity of the best criteria, "fever (≥ 37.8°C) plus cough" (41.03%) in this study was lower than that of the Korea Centers for Disease Control and Prevention (KCDC) criteria (47.95%), whereas the positive likelihood ratio (3.55) and positive predictive value (81.6) of this criteria was higher than those of the KCDC criteria (2.98 and 78.7, respectively). The clinical characteristics of pandemic H1N1/09 are, in many regards, indistinguishable from those of ILI. Moreover, the accuracy and predictability of criteria which include only symptoms or signs were not sufficient to diagnose pandemic H1N1/09 infection. Therefore, use of a combination of symptoms with confirmatory laboratory testing is necessary for accurate diagnosis of pandemic H1N1/09.

  12. 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.

  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. Selecting Nonpharmaceutical Strategies to Minimize Influenza Spread: The 2009 Influenza A (H1N1) Pandemic and Beyond

    PubMed Central

    Koonin, Lisa M.; Kohl, Katrin S.; Cetron, Martin

    2012-01-01

    Shortly after the influenza A (H1N1) 2009 pandemic began, the U.S. government provided guidance to state and local authorities to assist decision-making for the use of nonpharmaceutical strategies to minimize influenza spread. This guidance included recommendations for flexible decision-making based on outbreak severity, and it allowed for uncertainty and course correction as the pandemic progressed. These recommendations build on a foundation of local, collaborative planning and posit a series of questions regarding epidemiology, the impact on the health-care system, and locally determined feasibility and acceptability of nonpharmaceutical strategies. This article describes -recommendations and key questions for decision makers. PMID:23115381

  15. [Outbreak of human A (H1N1) influenza in turkeys of a commercial poultry farm, Valparaiso, Chile: August 2009].

    PubMed

    Pedroni, Elena; Muñoz, Ximena; Sotomayor, Viviana; Muñoz, Juan C; Arenas, Myriam; Fasce, Rodrigo; Olea, Andrea

    2012-08-01

    The Chilean Ministry of Health (MINSAL) led an investigation to identify associated factors to human influenza A (H1N1) infection in turkeys from poultry farms, Valparaíso. The Agriculture and Livestock Farming Service (SAG) informed the detection of influenza A (low pathogenicity) in turkeys and the Public Health Institute (ISP) confirmed influenza A (H1N1).The study included 100% of operative wards: 31% presented positive event (influenza A (H1N1)); 60% if considered only reproductive wards. Dissemination and dispersion velocity of 13 wards in 18 days evidenced a continuous common source. Interviews were performed to 89% of workers of whom 20% presented influenza-like disease: 26% from reproductive wards and 4% from raising and rearing farms. Of15 risk factors studied insemination and age in females showed statistically significant RR in low oviposition index wards. A man-bird transmission is proposed, through direct transmission of saliva during manual insemination or indirect transmission through contaminated semen. To the authors, this is the first turkey 2009 influenza H1N1 outbreak detected worldwide,in this case with a documented cloacal transmission path.

  16. 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

  17. Different evolutionary trajectories of European avian-like and classical swine H1N1 influenza A viruses.

    PubMed

    Dunham, Eleca J; Dugan, Vivien G; Kaser, Emilee K; Perkins, Sarah E; Brown, Ian H; Holmes, Edward C; Taubenberger, Jeffery K

    2009-06-01

    In 1979, a lineage of avian-like H1N1 influenza A viruses emerged in European swine populations independently from the classical swine H1N1 virus lineage that had circulated in pigs since the Spanish influenza pandemic of 1918. To determine whether these two distinct lineages of swine-adapted A/H1N1 viruses evolved from avian-like A/H1N1 ancestors in similar ways, as might be expected given their common host species and origin, we compared patterns of nucleotide and amino acid change in whole genome sequences of both groups. An analysis of nucleotide compositional bias across all eight genomic segments for the two swine lineages showed a clear lineage-specific bias, although a segment-specific effect was also apparent. As such, there appears to be only a relatively weak host-specific selection pressure. Strikingly, despite each lineage evolving in the same species of host for decades, amino acid analysis revealed little evidence of either parallel or convergent changes. These findings suggest that although adaptation due to evolutionary lineages can be distinguished, there are functional and structural constraints on all gene segments and that the evolutionary trajectory of each lineage of swine A/H1N1 virus has a strong historical contingency. Thus, in the context of emergence of an influenza A virus strain via a host switch event, it is difficult to predict what specific polygenic changes are needed for mammalian adaptation.

  18. 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

    2015-05-05

    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

  19. Performance of rapid-test kits for the detection of the pandemic influenza A/H1N1 virus.

    PubMed

    Tsao, Kuo-Chien; Kuo, Yung-Bin; Huang, Chung-Guei; Chau, Shao-Wen; Chan, Err-Cheng

    2011-05-01

    The early detection of pandemic influenza strains is a key factor for clinicians in treatment decisions and infection control practices. The aims of this study were to determine the analytical sensitivity and clinical performance of the commercially available influenza rapid tests in Taiwan. Four rapid tests for influenza virus (BinaxNow test, QuickVue test, TRU test, and Formosa Rapid test) were evaluated for their detection limit against four influenza viruses (the 2009 pandemic influenza A virus H1N1, seasonal influenza virus H1N1, H3N2, and influenza B virus) circulating in Taiwan. The viral load of these isolates were quantified by rtRT-PCR and then diluted 2-fold serially for the comparison. The lowest detectable viral load of the pandemic influenza A virus H1N1 by the Formosa Rapid test, QuickVue test, TRU test, and Binax Now test was 5.3×10(4), 1.0×10(5), 1.0×10(5), and 4.2×10(5)copies/μL, respectively. Of these four tests, the two most sensitive tests (the QuickVue test and the Formosa Rapid test) were chosen to evaluate 62 nasopharyngeal specimens from patients who were suspected of infection with pandemic influenza A virus H1N1. The positive rate for the Formosa Rapid test and the QuickVue test were 53.2% (33/62) and 45.2% (28/62) (McNemar's test, P=0.125), respectively. In conclusion, the Formosa Rapid test was the most sensitive test in the present study for the detection of influenza antigens and its clinical performance was similar to that of the QuickVue test (Kappa=0.776). This suggests that the Formosa Rapid test could be used to aid clinical decision making in primary health care settings during outbreaks of influenza.

  20. Validation of a polymerase chain reaction-oligochromatography test for detection of influenza A (H1N1) 2009 virus.

    PubMed

    Fuenzalida, Loreto; Prat, Cristina; Blanco, Silvia; Bas, Albert; Domínguez, M J; Hernández, M Ángeles; Rodrigo, Carlos; Ausina, Vicente

    2012-02-01

    The outbreak of pandemic influenza A (H1N1) 2009 virus caused the first influenza pandemic disease of the 21st century. In August 2010, the pandemic moved into the post-pandemic period. However, localized outbreaks of various magnitudes continued with a higher rate of disease severity. The aim of this study was to assess a new polymerase chain reaction (PCR)-oligochromatographic assay (Speed-Oligo) in the diagnosis of novel influenza A (H1N1) 2009. A total of 405 nasopharyngeal aspirate specimens from 400 pediatric and adults patients with suspected infection of pandemic influenza A (H1N1) 2009 were analyzed. The sensitivity and specificity values of the Speed-Oligo assay in comparison to reverse transcriptase-PCR assay developed by the Centers for Disease Control and Prevention were 86.5% and 92.2%, respectively. The new assay is simple, rapid, and provides a good sensitivity for detection of influenza A (H1N1) 2009. This assay might be a good alternative to real-time PCR assays for laboratories not equipped with real-time PCR instruments.

  1. Outbreaks of pandemic (H1N1) 2009 and seasonal influenza A (H3N2) on cruise ship.

    PubMed

    Ward, Kate A; Armstrong, Paul; McAnulty, Jeremy M; Iwasenko, Jenna M; Dwyer, Dominic E

    2010-11-01

    To determine the extent and pattern of influenza transmission and effectiveness of containment measures, we investigated dual outbreaks of pandemic (H1N1) 2009 and influenza A (H3N2) that had occurred on a cruise ship in May 2009. Of 1,970 passengers and 734 crew members, 82 (3.0%) were infected with pandemic (H1N1) 2009 virus, 98 (3.6%) with influenza A (H3N2) virus, and 2 (0.1%) with both. Among 45 children who visited the ship's childcare center, infection rate for pandemic (H1N1) 2009 was higher than that for influenza A (H3N2) viruses. Disembarked passengers reported a high level of compliance with isolation and quarantine recommendations. We found 4 subsequent cases epidemiologically linked to passengers but no evidence of sustained transmission to the community or passengers on the next cruise. Among this population of generally healthy passengers, children seemed more susceptible to pandemic (H1N1) 2009 than to influenza (H3N2) viruses. Intensive disease control measures successfully contained these outbreaks.

  2. 2009 H1N1 influenza: a twenty-first century pandemic with roots in the early twentieth century.

    PubMed

    Farley, Monica M

    2010-09-01

    A swine-origin H1N1 triple-reassortant influenza A virus found to be a distant relative of the 1918 "Spanish flu" virus emerged in April 2009 to give rise to the first influenza pandemic of the 21st century. Although disease was generally mild and similar to seasonal influenza, severe manifestations including respiratory failure were noted in some, particularly those with underlying conditions such as asthma, pregnancy and immunosuppression. Children and younger adults accounted for most cases, hospitalizations and deaths. A reverse transcriptase-polymerase chain reaction assay was superior to antigen-based rapid tests for diagnosis. All 2009 H1N1 pandemic influenza strains were susceptible to 1 or more neuraminidase inhibitors. Monovalent, unadjuvanted 2009 H1N1 vaccines were licensed in the United States in September 2009 and initially targeted to younger individuals, pregnant women, caretakers of infants and healthcare providers. The 2009 H1N1 pandemic highlights the need for modernization of influenza vaccines, improved diagnostics and more rigorous evaluation of mitigation strategies.

  3. Adamantane- and Oseltamivir-Resistant Seasonal A (H1N1) and Pandemic A (H1N1) 2009 Influenza Viruses in Guangdong, China, during 2008 and 2009 ▿

    PubMed Central

    Zhou, Jie; Zou, Lirong; Zhang, Xin; Liao, Jiazheng; Ni, Hanzhong; Hou, Nianmei; Wang, Yajing; Li, Hui; Wu, Jie; Jonges, Marcel; Meijer, Adam; Koopmans, Marion; Ke, Changwen

    2011-01-01

    Adamantane and oseltamivir resistance among influenza viruses is a major concern to public health officials. To determine the prevalence of antiviral-resistant influenza viruses in Guangdong, China, 244 seasonal A (H1N1) and 222 pandemic A (H1N1) 2009 viruses were screened for oseltamivir resistance by a fluorescence-based neuraminidase (NA) inhibition assay along with NA gene sequencing. Also, 147 seasonal A (H1N1) viruses were sequenced to detect adamantane resistance markers in M2. Adamantane-resistant seasonal A (H1N1) viruses clustering to clade 2C were dominant in 2008, followed by oseltamivir-resistant seasonal A (H1N1) viruses, clustering to clade 2B during January and May 2009. In June 2009, a lineage of double-resistant seasonal A (H1N1) viruses emerged, until it was replaced by the pandemic A (H1N1) 2009 viruses. The lineage most likely resulted from reassortment under the pressure of the overuse of adamantanes. As all viruses were resistant to at least one of the two types of antiviral agents, the need for close monitoring of the prevalence of antiviral resistance is stressed. PMID:21593267

  4. 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.

  5. Reassortment between swine influenza A viruses increased their adaptation to humans in pandemic H1N1/09.

    PubMed

    Furuse, Yuki; Suzuki, Akira; Oshitani, Hitoshi

    2010-05-01

    In April 2009, pandemic H1N1/09 influenza, which originated from swine influenza, appeared in North America, and it has since spread globally among humans. It is important to know how swine influenza A virus broke the host barrier to cause a pandemic. We analyzed 673 strains of human, avian, and swine influenza viruses and assessed the internal genes PB2, PB1, PA, NP, M, and NS. Here we found accumulation of mutations in segments that were retained as well as introduced due to genetic reassortment of viruses. The retained segments may have to mutate to accommodate new segments. The mutations caused by interaction among segments retained and introduced due to reassortment between swine influenza viruses may have increased the adaptation of the virus to humans, leading to pandemic H1N1/09. We indicate the sites that probably contributed to the acquisition of efficient human-to-human transmission.

  6. Serologic cross reactivity of avian influenza H1 vaccinated commercial U.S. turkeys to the emergent H1N1 influenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recently, the 2009 human H1N1 influenza virus was identified in turkey breeders in Chile, Canada and the U.S. resulting in infection and production losses. In these studies sera from turkeys vaccinated against avian influenza H1 were tested against the recent human pandemic H1N1 virus. Genetic ana...

  7. A Metagenomic Analysis of Pandemic Influenza A (2009 H1N1) Infection in Patients from North America

    PubMed Central

    Greninger, Alexander L.; Chen, Eunice C.; Sittler, Taylor; Scheinerman, Alex; Roubinian, Nareg; Yu, Guixia; Kim, Edward; Pillai, Dylan R.; Guyard, Cyril; Mazzulli, Tony; Isa, Pavel; Arias, Carlos F.; Hackett, John; Schochetman, Gerald; Miller, Steve; Tang, Patrick; Chiu, Charles Y.

    2010-01-01

    Although metagenomics has been previously employed for pathogen discovery, its cost and complexity have prevented its use as a practical front-line diagnostic for unknown infectious diseases. Here we demonstrate the utility of two metagenomics-based strategies, a pan-viral microarray (Virochip) and deep sequencing, for the identification and characterization of 2009 pandemic H1N1 influenza A virus. Using nasopharyngeal swabs collected during the earliest stages of the pandemic in Mexico, Canada, and the United States (n = 17), the Virochip was able to detect a novel virus most closely related to swine influenza viruses without a priori information. Deep sequencing yielded reads corresponding to 2009 H1N1 influenza in each sample (percentage of aligned sequences corresponding to 2009 H1N1 ranging from 0.0011% to 10.9%), with up to 97% coverage of the influenza genome in one sample. Detection of 2009 H1N1 by deep sequencing was possible even at titers near the limits of detection for specific RT-PCR, and the percentage of sequence reads was linearly correlated with virus titer. Deep sequencing also provided insights into the upper respiratory microbiota and host gene expression in response to 2009 H1N1 infection. An unbiased analysis combining sequence data from all 17 outbreak samples revealed that 90% of the 2009 H1N1 genome could be assembled de novo without the use of any reference sequence, including assembly of several near full-length genomic segments. These results indicate that a streamlined metagenomics detection strategy can potentially replace the multiple conventional diagnostic tests required to investigate an outbreak of a novel pathogen, and provide a blueprint for comprehensive diagnosis of unexplained acute illnesses or outbreaks in clinical and public health settings. PMID:20976137

  8. CD206+ Cell Number Differentiates Influenza A (H1N1)pdm09 from Seasonal Influenza A Virus in Fatal Cases

    PubMed Central

    Rodriguez-Ramirez, Heidi G.; Salinas-Carmona, Mario C.; Barboza-Quintana, Oralia; Melo-de la Garza, Americo; Ceceñas-Falcon, Luis Angel; Rangel-Martinez, Lilia M.; Rosas-Taraco, Adrian G.

    2014-01-01

    In 2009, a new influenza A (H1N1) virus affected many persons around the world. There is an urgent need for finding biomarkers to distinguish between influenza A (H1N1)pdm09 and seasonal influenza virus. We investigated these possible biomarkers in the lung of fatal cases of confirmed influenza A (H1N1)pdm09. Cytokines (inflammatory and anti-inflammatory) and cellular markers (macrophages and lymphocytes subpopulation markers) were analyzed in lung tissue from both influenza A (H1N1)pdm09 and seasonal influenza virus. High levels of IL-17, IFN-γ, and TNF-α positive cells were identical in lung tissue from the influenza A (H1N1)pdm09 and seasonal cases when compared with healthy lung tissue (P < 0.05). Increased IL-4+ cells, and CD4+ and CD14+ cells were also found in high levels in both influenza A (H1N1)pdm09 and seasonal influenza virus (P < 0.05). Low levels of CD206+ cells (marker of alternatively activated macrophages marker in lung) were found in influenza A (H1N1)pdm09 when compared with seasonal influenza virus (P < 0.05), and the ratio of CD206/CD14+ cells was 2.5-fold higher in seasonal and noninfluenza group compared with influenza A (H1N1)pdm09 (P < 0.05). In conclusion, CD206+ cells differentiate between influenza A (H1N1)pdm09 and seasonal influenza virus in lung tissue of fatal cases. PMID:25614715

  9. 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

    2014-01-05

    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.

  10. Bayesian coalescent analysis of pandemic H1N1 influenza A virus circulating in the South American region.

    PubMed

    Goñi, Natalia; Moratorio, Gonzalo; Coppola, Leticia; Ramas, Viviana; Comas, Victoria; Soñora, Martin; Chiparelli, Hector; Cristina, Juan

    2012-12-01

    The first influenza pandemic of this century was declared in April of 2009, with the emergence of a novel H1N1 influenza A virus strain (H1N1pdm). Understanding the evolution of H1N1pdm populations within the South American region is essential for studying global diversification, emergence, resistance and vaccine efficacy. In order to gain insight into these matters, we have performed a Bayesian coalescent Markov Chain Monte Carlo analysis of hemagglutinin (HA) and neuraminidase (NA) gene sequences of all available and comparable HA and NA sequences obtained from H1N1pdm IAV circulating in the South American region. High evolutionary rates and fast population growths characterize the population dynamics of H1N1pdm strains in this region of the world. A significant contribution of first codon position to the mean evolutionary rate was found for both genes studied, revealing a high contribution of non-synonymous substitutions to the mean substitution rate. In the 178days period covered by these studies, substitutions in all HA epitope regions can be observed. HA substitutions D239G/N and Q310H have been observed only in Brazilian patients. While substitution D239G/N is not particularly associated to a specific genetic lineage, all strains bearing substitution Q310H were assigned to clade 6, suggesting a founder effect. None of the substitutions found in the NA proteins of H1N1pdm strains isolated in South America appears sufficiently close to affect the drug binding pocket for the three NA inhibitor antivirals tested. A more detailed analysis of NA proteins revealed epitope differences among 2010 vaccine and H1N1pdm IAV strains circulating in the South American region.

  11. Molecular Dynamics Analysis of Antibody Recognition and Escape by Human H1N1 Influenza Hemagglutinin

    PubMed Central

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

    2015-01-01

    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

  12. 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.

  13. The relationship between tuberculosis and influenza death during the influenza (H1N1) pandemic from 1918-19.

    PubMed

    Oei, Welling; Nishiura, Hiroshi

    2012-01-01

    The epidemiological mechanisms behind the W-shaped age-specific influenza mortality during the Spanish influenza (H1N1) pandemic 1918-19 have yet to be fully clarified. The present study aimed to develop a formal hypothesis: tuberculosis (TB) was associated with the W-shaped influenza mortality from 1918-19. Three pieces of epidemiological information were assessed: (i) the epidemic records containing the age-specific numbers of cases and deaths of influenza from 1918-19, (ii) an outbreak record of influenza in a Swiss TB sanatorium during the pandemic, and (iii) the age-dependent TB mortality over time in the early 20th century. Analyzing the data (i), we found that the W-shaped pattern was not only seen in mortality but also in the age-specific case fatality ratio, suggesting the presence of underlying age-specific risk factor(s) of influenza death among young adults. From the data (ii), TB was shown to be associated with influenza death (P = 0.09), and there was no influenza death among non-TB controls. The data (iii) were analyzed by employing the age-period-cohort model, revealing harvesting effect in the period function of TB mortality shortly after the 1918-19 pandemic. These findings suggest that it is worthwhile to further explore the role of TB in characterizing the age-specific risk of influenza death.

  14. 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

  15. Contact Tracing for Influenza A(H1N1)pdm09 Virus–infected Passenger on International Flight

    PubMed Central

    Shankar, Ananda G.; Janmohamed, Kulsum; Smith, Gillian E.; Hogan, Angela H.; De Souza, Valerie; Wallensten, Anders; Oliver, Isabel; Blatchford, Oliver; Cleary, Paul; Ibbotson, Sue

    2014-01-01

    In April 2009, influenza A(H1N1)pdm09 virus infection was confirmed in a person who had been symptomatic while traveling on a commercial flight from Mexico to the United Kingdom. Retrospective public health investigation and contact tracing led to the identification of 8 additional confirmed cases among passengers and community contacts of passengers. PMID:24377724

  16. 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.

  17. Diagnosis of 2009 Pandemic Influenza A (pH1N1) and Seasonal Influenza Using Rapid Influenza Antigen Tests, San Antonio, Texas, April-June 2009

    DTIC Science & Technology

    2009-01-01

    CDC Atlanta US. CDC protocol of realtime RTPCR for influenza A(H1N1) revision 1. 30 April 2009. Available at: http://www.who.int/ csr / resources...2009; 325:483–7. 24. Munster VJ, de Wit E, van den Brand JM, et al. Pathogenesis and Transmission of Swine-Origin 2009 A(H1N1) Influenza Virus in Fer

  18. [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.

  19. Influenza pathogenesis: lessons learned from animal studies with H5N1, H1N1 Spanish, and pandemic H1N1 2009 influenza.

    PubMed

    Meunier, Isabelle; Pillet, Stéphane; Simonsen, J Neil; von Messling, Veronika

    2010-04-01

    Because cases of highly pathogenic influenza are rare, no systematic clinical studies have evaluated different therapeutic approaches. Instead, treatment recommendations are aimed at the alleviation of clinical signs and symptoms, especially the restoration of respiratory function, and at the inhibition of virus replication, assuming viral load is responsible for disease phenotype. Studies of highly pathogenic influenza in different animal models, especially nonhuman primates and ferrets, reproduce many of the key observations from clinical cases. Host-response kinetics reveal a delayed but broad activation of genes involved in the innate and acquired immune responses (innate responses produce inflammatory responses), which continue after the virus has been cleared and may contribute importantly to the clinical signs observed. Experimental animal models point to an important role for immune dysregulation in the pathogenesis of highly pathogenic influenza. The use of these models to develop and validate therapeutic approaches is just beginning, but published studies reveal the importance of early treatment with antivirals and show the potential and limitations of approaches aimed at the host response.

  20. Porcine mast cells infected with H1N1 influenza virus release histamine and inflammatory cytokines and chemokines.

    PubMed

    Lee, In Hong; Kim, Hyun Soo; Seo, Sang Heui

    2017-04-01

    Mast cells reside in many tissues, including the lungs, and might play a role in enhancing influenza virus infections in animals. In this study, we cultured porcine mast cells from porcine bone marrow cells with IL-3 and stem cell factor to study the infectivity and activation of the 2009 pandemic H1N1 influenza virus of swine origin. Porcine mast cells were infected with H1N1 influenza virus, without the subsequent production of infectious viruses but were activated, as indicated by the release of histamines. Inflammatory cytokine- and chemokine-encoding genes, including IL-1α, IL-6, CXCL9, CXCL10, and CXCL11, were upregulated in the infected porcine mast cells. Our results suggest that mast cells could be involved in enhancing influenza-virus-mediated disease in infected animals.

  1. 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

  2. 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

  3. Research update on avian influenza viruses and H1N1 influenza virus in poultry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza (AI) remains an economic threat to commercial poultry throughout the world by negatively impacting animal health and trade. Southeast Poultry Research Laboratory conducts research on many areas related to AI including pathogenesis and transmission studies, use of vaccination, virus ...

  4. An Analysis of 332 Fatalities Infected with Pandemic 2009 Influenza A (H1N1) in Argentina

    PubMed Central

    Balanzat, Ana M.; Hertlein, Christian; Apezteguia, Carlos; Bonvehi, Pablo; Cámera, Luis; Gentile, Angela; Rizzo, Oscar; Gómez-Carrillo, Manuel; Coronado, Fatima; Azziz-Baumgartner, Eduardo; Chávez, Pollyanna R.; Widdowson, Marc-Alain

    2012-01-01

    Background The apparent high number of deaths in Argentina during the 2009 pandemic led to concern that the influenza A H1N1pdm disease was different there. We report the characteristics and risk factors for influenza A H1N1pdm fatalities. Methods We identified laboratory-confirmed influenza A H1N1pdm fatalities occurring during June-July 2009. Physicians abstracted data on age, sex, time of onset of illness, medical history, clinical presentation at admission, laboratory, treatment, and outcomes using standardize questionnaires. We explored the characteristics of fatalities according to their age and risk group. Results Of 332 influenza A H1N1pdm fatalities, 226 (68%) were among persons aged <50 years. Acute respiratory failure was the leading cause of death. Of all cases, 249 (75%) had at least one comorbidity as defined by Advisory Committee on Immunization Practices. Obesity was reported in 32% with data and chronic pulmonary disease in 28%. Among the 40 deaths in children aged <5 years, chronic pulmonary disease (42%) and neonatal pathologies (35%) were the most common co-morbidities. Twenty (6%) fatalities were among pregnant or postpartum women of which only 47% had diagnosed co-morbidities. Only 13% of patients received antiviral treatment within 48 hours of symptom onset. None of children aged <5 years or the pregnant women received antivirals within 48 h of symptom onset. As the pandemic progressed, the time from symptom-onset to medical care and to antiviral treatment decreased significantly among case-patients who subsequently died (p<0.001). Conclusion Persons with co-morbidities, pregnant and who received antivirals late were over-represented among influenza A H1N1pdm deaths in Argentina, though timeliness of antiviral treatment improved during the pandemic. PMID:22506006

  5. Intensive care adult patients with severe respiratory failure caused by Influenza A (H1N1)v in Spain

    PubMed Central

    2009-01-01

    Introduction Patients with influenza A (H1N1)v infection have developed rapidly progressive lower respiratory tract disease resulting in respiratory failure. We describe the clinical and epidemiologic characteristics of the first 32 persons reported to be admitted to the intensive care unit (ICU) due to influenza A (H1N1)v infection in Spain. Methods We used medical chart reviews to collect data on ICU adult patients reported in a standardized form. Influenza A (H1N1)v infection was confirmed in specimens using real-time reverse transcriptase-polymerase-chain-reaction (RT PCR) assay. Results Illness onset of the 32 patients occurred between 23 June and 31 July, 2009. The median age was 36 years (IQR = 31 - 52). Ten (31.2%) were obese, 2 (6.3%) pregnant and 16 (50%) had pre-existing medical complications. Twenty-nine (90.6%) had primary viral pneumonitis, 2 (6.3%) exacerbation of structural respiratory disease and 1 (3.1%) secondary bacterial pneumonia. Twenty-four patients (75.0%) developed multiorgan dysfunction, 7 (21.9%) received renal replacement techniques and 24 (75.0%) required mechanical ventilation. Six patients died within 28 days, with two additional late deaths. Oseltamivir administration delay ranged from 2 to 8 days after illness onset, 31.2% received high-dose (300 mg/day), and treatment duration ranged from 5 to 10 days (mean 8.0 ± 3.3). Conclusions Over a 5-week period, influenza A (H1N1)v infection led to ICU admission in 32 adult patients, with frequently observed severe hypoxemia and a relatively high case-fatality rate. Clinicians should be aware of pulmonary complications of influenza A (H1N1)v infection, particularly in pregnant and young obese but previously healthy persons. PMID:19747383

  6. 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

  7. Seroincidence of Influenza Among HIV-infected and HIV-uninfected Men During the 2009 H1N1 Influenza Pandemic, Bangkok, Thailand.

    PubMed

    Garg, Shikha; Olsen, Sonja J; Fernandez, Stefan; Muangchana, Charung; Rungrojcharoenkit, Kamonthip; Prapasiri, Prabda; Katz, Jacqueline M; Curlin, Marcel E; Gibbons, Robert V; Holtz, Timothy H; Chitwarakorn, Anupong; Dawood, Fatimah S

    2014-12-01

    Among 368 Thai men who have sex with men with paired serum samples collected before and during the 2009 H1N1 influenza pandemic, we determined influenza A (H1N1)pdm09 seroconversion rates (≥4-fold rise in antibody titers by hemagglutination inhibition or microneutralization assays). Overall, 66 of 232 (28%) participants seroconverted after the first year of A(H1N1)pdm09 activity, and 83 of 234 (35%) participants seroconverted after the second year. Influenza A(H1N1)pdm09 seroconversion did not differ between human immunodeficiency virus (HIV)-infected (55 of 2157 [35%]) and HIV-uninfected (71 of 2211 [34%]) participants (P = .78). Influenza A(H1N1)pdm09 seroconversion occurred in approximately one third of our Thai study population and was similar among HIV-infected and HIV-uninfected participants.

  8. 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

  9. 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.

  10. 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

  11. 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

  12. 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.

  13. Genetic Characterization of Circulating 2015 A(H1N1)pdm09 Influenza Viruses from Eastern India

    PubMed Central

    Mukherjee, Anupam; Nayak, Mukti Kant; Dutta, Shanta; Panda, Samiran; Satpathi, Biswa Ranjan; Chawla-Sarkar, Mamta

    2016-01-01

    In 2015, the swine derived A(H1N1)pdm09 pandemic strain outbreak became widespread throughout the different states of India. The reported cases and deaths in 2015 surpassed the previous years with more than 39000 laboratory confirmed cases and a death toll of more than 2500 people. There are relatively limited complete genetic sequences available for this virus from Asian countries. In this study, we describe the full genome analysis of influenza 2015 A(H1N1)pdm09 viruses isolated from West Bengal between January through December 2015. The phylogenetic analysis of the haemagglutinin sequence revealed clustering with globally circulating strains of genogroup 6B. This was further confirmed by the constructed concatenated tree using all eight complete gene segments of Kolkata A(H1N1)pdm09 isolates with the other strains from different timeline and lineages. A study from Massachusetts Institute of Technology (MIT) in 2015 reported novel mutations T200A and D225N in haemagglutinin gene of a 2014 Indian strain (A/India/6427/2014). However, in all the pandemic strains of 2014–2015 reported from India, so far including A(H1N1)pdm09 strains from Kolkata, D225N mutation was not observed, though the T200A mutation was found to be conserved. Neuraminidase gene of the analyzed strains did not show any oseltamivir resistant mutation H275Y suggesting continuation of Tamiflu® as drug of choice. The amino acid sequences of the all gene segments from 2015 A(H1N1)pdm09 isolates identified several new mutations compared to the 2009 A(H1N1)pdm09 strains, which may have contributed towards enhanced virulence, compared to 2009 A(H1N1)pdm09 strains. PMID:27997573

  14. A Two-Year Surveillance of 2009 Pandemic Influenza A (H1N1) in Guangzhou, China: From Pandemic to Seasonal Influenza?

    PubMed Central

    Yang, Zhicong; Wang, Yulin; Li, Meixia; Lu, Jianyun; Chen, Yiyun; Lu, Enjie; Geng, Jinmei; Hu, Wensui; Dong, Zhiqiang; Li, Meng-feng; Zheng, Bo-Jian; Cao, Kai-yuan; Wang, Ming

    2011-01-01

    In this two-years surveillance of 2009 pandemic influenza A (H1N1) (pH1N1) in Guangzhou, China, we reported here that the scale and duration of pH1N1 outbreaks, severe disease and fatality rates of pH1N1 patients were significantly lower or shorter in the second epidemic year (May 2010-April 2011) than those in the first epidemic year (May 2009-April 2010) (P<0.05), but similar to those of seasonal influenza (P>0.05). Similar to seasonal influenza, pre-existing chronic pulmonary diseases was a risk factor associated with fatal cases of pH1N1 influenza. Different from seasonal influenza, which occurred in spring/summer seasons annually, pH1N1 influenza mainly occurred in autumn/winter seasons in the first epidemic year, but prolonged to winter/spring season in the second epidemic year. The information suggests a tendency that the epidemics of pH1N1 influenza may probably further shift to spring/summer seasons and become a predominant subtype of seasonal influenza in coming years in Guangzhou, China. PMID:22125653

  15. T cell-mediated protection against lethal 2009 pandemic H1N1 influenza virus infection in a mouse model.

    PubMed

    Guo, Hailong; Santiago, Félix; Lambert, Kris; Takimoto, Toru; Topham, David J

    2011-01-01

    Genetic mutation and reassortment of influenza virus gene segments, in particular those of hemagglutinin (HA) and neuraminidase (NA), that lead to antigenic drift and shift are the major strategies for influenza virus to escape preexisting immunity. The most recent example of such phenomena is the first pandemic of H1N1 influenza of the 21st century, which started in 2009. Cross-reactive antibodies raised against H1N1 viruses circulating before 1930 show protective activity against the 2009 pandemic virus. Cross-reactive T-cell responses can also contribute to protection, but in vivo support of this view is lacking. To explore the protection mechanisms in vivo, we primed mice with H1 and H3 influenza virus isolates and rechallenged them with a virus derived from the 2009 H1N1 A/CA/04/09 virus, named CA/E3/09. We found that priming with influenza viruses of both H1 and H3 homo- and heterosubtypes protected against lethal CA/E3/09 virus challenge. Convalescent-phase sera from these primed mice conferred no neutralization activity in vitro and no protection in vivo. However, T-cell depletion studies suggested that both CD4 and CD8 T cells contributed to the protection. Taken together, these results indicate that cross-reactive T cells established after initial priming with distally related viruses can be a vital component for prevention of disease and control of pandemic H1N1 influenza virus infection. Our results highlight the importance of establishing cross-reactive T-cell responses for protecting against existing or newly emerging pandemic influenza viruses.

  16. 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

  17. Virus-Like Particle Vaccine Containing Hemagglutinin Confers Protection against 2009 H1N1 Pandemic Influenza

    PubMed Central

    Hossain, M. Jaber; Bourgeois, Melissa; Quan, Fu-Shi; Lipatov, Aleksandr S.; Song, Jae-Min; Chen, Li-Mei; Compans, Richard W.; York, Ian; Kang, Sang-Moo; Donis, Ruben O.

    2011-01-01

    Immunization of the world population before an influenza pandemic such as the 2009 H1N1 virus spreads globally is not possible with current vaccine production platforms. New influenza vaccine technologies, such as virus-like-particles (VLPs), offer a promising alternative. Here, we tested the immunogenicity and protective efficacy of a VLP vaccine containing hemagglutinin (HA) and M1 from the 2009 pandemic H1N1 influenza virus (H1N1pdm) in ferrets and compared intramuscular (i.m.) and intranasal (i.n.) routes of immunization. Vaccination of ferrets with VLPs containing the M1 and HA proteins from A/California/04/2009 (H1N1pdm) induced high antibody titers and conferred significant protection against virus challenge. VLP-vaccinated animals lost less weight, shed less virus in nasal washes, and had markedly lower virus titers in all organs tested than naïve controls. A single dose of VLPs, either i.m. or i.n., induced higher levels of antibody than did two doses of commercial split vaccine. Ferrets vaccinated with split vaccine were incompletely protected against challenge; these animals had lower virus titers in olfactory bulbs, tonsils, and intestines, but lost weight and shed virus in nasal washes to a similar extent as naïve controls. Challenge with heterologous A/Brisbane/59/07 (H1N1) virus revealed that the VLPs conferred minimal cross-protection to heterologous infection, as revealed by the lack of reduction in nasal wash and lung virus titers and slightly higher weight loss relative to controls. In summary, these experiments demonstrate the strong immunogenicity and protective efficacy of VLPs compared to the split vaccine and show that i.n. vaccination with VLPs has the potential for highly efficacious vaccination against influenza. PMID:22030367

  18. 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.

  19. Rapid differentiation of seasonal and pandemic H1N1 influenza through proteotyping of viral neuraminidase with mass spectrometry.

    PubMed

    Schwahn, Alexander B; Wong, Jason W H; Downard, Kevin M

    2010-06-01

    Signature peptides of the neuraminidase antigen across all common circulating human subtypes of type A and B influenza are identified through the bioinformatic alignment of translated gene sequences. The detection of these peptides within the high-resolution mass spectra of whole antigen, virus, and vaccine digests enables the strains to be rapidly and directly typed and subtyped. Importantly, unique signature peptides for pandemic (H1N1) 2009 influenza are identified and detected that enable pandemic strains to be rapidly and directly differentiated from seasonal type A (H1N1) influenza strains. The detection of these peptides can enable the origins of the neuraminidase gene to be monitored in the case of reassorted strains.

  20. 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

  1. 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.

  2. Modelling influenza A(H1N1) 2009 epidemics using a random network in a distributed computing environment.

    PubMed

    González-Parra, Gilberto; Villanueva, Rafael-J; Ruiz-Baragaño, Javier; Moraño, Jose-A

    2015-03-01

    In this paper we propose the use of a random network model for simulating and understanding the epidemics of influenza A(H1N1). The proposed model is used to simulate the transmission process of influenza A(H1N1) in a community region of Venezuela using distributed computing in order to accomplish many realizations of the underlying random process. These large scale epidemic simulations have recently become an important application of high-performance computing. The network model proposed performs better than the traditional epidemic model based on ordinary differential equations since it adjusts better to the irregularity of the real world data. In addition, the network model allows the consideration of many possibilities regarding the spread of influenza at the population level. The results presented here show how well the SEIR model fits the data for the AH1N1 time series despite the irregularity of the data and returns parameter values that are in good agreement with the medical data regarding AH1N1 influenza virus. This versatile network model approach may be applied to the simulation of the transmission dynamics of several epidemics in human networks. In addition, the simulation can provide useful information for the understanding, prediction and control of the transmission of influenza A(H1N1) epidemics.

  3. Seroepidemiologic Investigation of an Outbreak of Pandemic Influenza A H1N1 2009 Aboard a U.S. Navy Vessel - San Diego, 2009

    DTIC Science & Technology

    2013-01-01

    Naval Health Research Center Seroepidemiologic Investigation of An Outbreak of Pandemic Influenza A H1N1 2009 Aboard A US Navy Vessell – San...Journal Article 3. DATES COVERED (from – to) 2009 4. TITLE Seroepidemiologic Investigation of an Outbreak of Pandemic Influenza A H1N1 2009...outbreaks. 15. SUBJECT TERMS Adolescent; adult; Disease Outbreaks; H1N1 Subtype/genetics; epidemiology; Influenza A Virus; military personnel 16

  4. 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.

  5. Novel Virus Influenza A (H1N1sw) in South-Eastern France, April-August 2009

    PubMed Central

    Zandotti, Christine; Salez, Nicolas; Mantey, Karine; Resseguier, Noémie; Gazin, Céline; Raoult, Didier; Charrel, Rémi N.; de Lamballerie, Xavier

    2010-01-01

    Background In April 2009, the first cases of pandemic (H1N1)-2009 influenza [H1N1sw] virus were detected in France. Virological surveillance was undertaken in reference laboratories of the seven French Defence Zones. Methodology/Principal Findings We report results of virological analyses performed in the Public Hospitals of Marseille during the first months of the outbreak. (i) Nasal swabs were tested using rapid influenza diagnostic test (RIDT) and two RT-PCR assays. Epidemiological characteristics of the 99 first suspected cases were analyzed, including detection of influenza virus and 18 other respiratory viruses. During three months, a total of 1,815 patients were tested (including 236 patients infected H1N1sw virus) and distribution in age groups and results of RIDT were analyzed. (ii) 600 sera received before April 2009 and randomly selected from in-patients were tested by a standard hemagglutination inhibition assay for antibody to the novel H1N1sw virus. (iii) One early (May 2009) and one late (July 2009) viral isolates were characterized by sequencing the complete hemagglutinine and neuraminidase genes. (iiii) Epidemiological characteristics of a cluster of cases that occurred in July 2009 in a summer camp were analyzed. Conclusions/Significance This study presents new virological and epidemiological data regarding infection by the pandemic A/H1N1 virus in Europe. Distribution in age groups was found to be similar to that previously reported for seasonal H1N1. The first seroprevalence data made available for a European population suggest a previous exposure of individuals over 40 years old to influenza viruses antigenically related to the pandemic (H1N1)-2009 virus. Genomic analysis indicates that strains harbouring a new amino-acid pattern in the neuraminidase gene appeared secondarily and tended to supplant the first strains. Finally, in contrast with previous reports, our data support the use of RIDT for the detection of infection in children

  6. Virulence determinants of pandemic A(H1N1)2009 influenza virus in a mouse model.

    PubMed

    Uraki, Ryuta; Kiso, Maki; Shinya, Kyoko; Goto, Hideo; Takano, Ryo; Iwatsuki-Horimoto, Kiyoko; Takahashi, Kazuo; Daniels, Rod S; Hungnes, Olav; Watanabe, Tokiko; Kawaoka, Yoshihiro

    2013-02-01

    A novel swine-origin H1N1 influenza virus [A(H1N1)pdm09 virus] caused the 2009 influenza pandemic. Most patients exhibited mild symptoms similar to seasonal influenza, but some experienced severe clinical signs and, in the worst cases, died. Such differences in symptoms are generally associated with preexisting medical conditions, but recent reports indicate the possible involvement of viral factors in clinical severity. To better understand the mechanism of pathogenicity of the A(H1N1)pdm09 virus, here, we compared five viruses that are genetically similar but were isolated from patients with either severe or mild symptoms. In a mouse model, A/Norway/3487/2009 (Norway3487) virus exhibited greater pathogenicity than did A/Osaka/164/2009 (Osaka164) virus. By exploiting reassortant viruses between these two viruses, we found that viruses possessing the hemagglutinin (HA) gene of Norway3487 in the genetic background of Osaka164 were more pathogenic in mice than other reassortant viruses, indicating a role for HA in the high virulence of Norway3487 virus. Intriguingly, a virus possessing HA, NA, and NS derived from Norway3487 exhibited greater pathogenicity in mice in concert with PB2 and PB1 derived from Osaka164 than did the parental Norway3487 virus. These findings demonstrate that reassortment between A(H1N1)pdm09 viruses can lead to increased pathogenicity and highlight the need for continued surveillance of A(H1N1)pdm09 viruses.

  7. Indication for a role of regulatory T cells for the advent of influenza A (H1N1)-related pneumonia

    PubMed Central

    Raftogiannis, M; Antonopoulou, A; Baziaka, F; Spyridaki, A; Koutoukas, P; Tsaganos, T; Savva, A; Pistiki, A; Georgitsi, M; Giamarellos-Bourboulis, E J

    2010-01-01

    Regulatory T cells (Tregs) have an anti-inflammatory role. A former study in a limited number of patients found that absolute counts of Tregs increase when infection by the new influenza H1N1 virus is complicated with pneumonia. These results generate the question if H1N1-related pneumonia is associated with a state of hypo-inflammation. A total of 135 patients were enrolled with blood sampling within less than 24 h from diagnosis; 23 with flu-like syndrome; 69 with uncomplicated H1N1-infection; seven with bacterial pneumonia; and 36 with H1N1-related pneumonia. Tregs and CD14/HLA-DR co-expression were estimated by flow cytometry; concentrations of tumour necrosis factor-alpha (TNF-α), of interleukin (IL)-6 and of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) by an enzyme immunoassay; those of procalcitonin (PCT) by immuno-time-resolved amplified cryptate technology assay. Expression of human leucocyte antigen D-related (HLA-DR) on monocytes was similar between groups; absolute Treg counts were greater among patients with H1N1-related pneumonia than flu-like syndrome or H1N1-uncomplicated infection. Serum TNF-α of patients with bacterial pneumonia was greater than those of other groups, but IL-10 was similar between groups. Serum PCT was greater among patients with H1N1-related pneumonia and sTREM-1 among those with H1N1-related pneumonia. Regression analysis revealed that the most important factors related with the advent of pneumonia were the existence of underlying illnesses (P = 0·006) and of Tregs equal to or above 16 mm3 (P = 0·013). It is concluded that the advent of H1N1-related pneumonia is related to an early increase of the absolute Treg counts. This increase is probably not part of a hypo-inflammatory state of the host. PMID:20646008

  8. 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

  9. 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

  10. 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.

  11. Identification and characterization of a highly virulent triple reassortant H1N1 swine influenza virus in the United States.

    PubMed

    Ma, Wenjun; Vincent, Amy L; Lager, Kelly M; Janke, Bruce H; Henry, Steven C; Rowland, Raymond R R; Hesse, Richard A; Richt, Jürgen A

    2010-02-01

    A highly virulent H1N1 influenza A virus, A/Swine/Kansas/77778/2007 (KS07), which caused approximately 10% mortality in finishing pigs, was isolated from herds in the Midwestern United States. Molecular and phylogenic analysis revealed this swine isolate was a triple reassortant virus, similar to an H1N1 virus that infected humans and pigs at an Ohio county fair in August 2007. A pig challenge model was developed to evaluate the pathogenicity and transmission capacity of the KS07 virus. The results confirmed that the KS07 virus is highly virulent in pigs and easily transmitted to sentinel animals. The KS07 virus failed to cross-react with a panel of H1-specific swine sera. Interestingly, the KS07 virus shed for a prolonged period up to 7 days in infected pigs, indicating that this virus can spread efficiently between animals. The highly virulent H1N1 swine influenza virus is further evidence of reassortment among avian, human and swine influenza viruses and justifies the need for continued surveillance of influenza viruses in swine.

  12. Increased prevalence of a rare mutant of pandemic H1N1 influenza virus in a Eurasian region.

    PubMed

    Yang, Ting-Ting; Wang, Zhao-Guo; Li, Shan-Peng; Liu, Xiao-Lin; Yi, Ying; Yang, Yu; Yu, Ping; Chen, Ji-Ming

    2011-01-01

    In 2009, a novel swine-origin H1N1 influenza virus sparked an influenza pandemic. The emergence of mutations in the viral genome is therefore of ongoing concern. In this study, the hemagglutinin (HA) gene sequences of 3444 pandemic H1N1 influenza viruses reported to the GenBank database and the sequences of 48 pandemic H1N1 influenza viruses detected in the Chinese city of Qingdao were analyzed. Among the 3492 viruses, 101 carried a serine to proline substitution at position 128 (S128P) in the viral HA gene. All the 101 S128P mutants belonged to Clade 7 which has become dominant worldwide since the summer of 2009. Among the 3492 viruses, 1646 were collected before July 25, 2009, and none of these viruses carried the S128P mutation. Furthermore, after July 25, 2009, the prevalence of the S128P mutant was 33.56% (99/295) in a region of Eurasia including Russia, Mongolia, mainland China and South Korea, but only 0.11% (2/1846) in the rest of the world. The data suggested that the originally rare S128P mutant has become prevalent in the Eurasia region, indicating that the S128P mutant likely transmitted more efficiently than other strains of the virus. Therefore, it is of significance to observe whether the S128P mutant will be more dominant worldwide in the coming future and investigate the exact effects of the S128P mutation.

  13. The 2009 Influenza A(H1N1) ’Swine Flu’ Outbreak: An Overview

    DTIC Science & Technology

    2009-05-20

    Tamiflu and Relenza, respiratory protection devices, and other medical supplies, from the Strategic National Stockpile (SNS), to help states respond to... medical visits, and other measures. One CDC official commented that reported cases of H1N1 flu probably represent only a fraction of actual cases...with good hygienic practices recommended by the WHO, FAO, Codex Alimentarius Commission and the OIE, will not be a source of infection. To date there

  14. Transmission of pandemic A/H1N1 2009 influenza on passenger aircraft: retrospective cohort study

    PubMed Central

    Thornley, Craig N; Mills, Clair; Roberts, Sally; Perera, Shanika; Peters, Julia; Kelso, Anne; Barr, Ian; Wilson, Nick

    2010-01-01

    Objectives To assess the risk of transmission of pandemic A/H1N1 2009 influenza (pandemic A/H1N1) from an infected high school group to other passengers on an airline flight and the effectiveness of screening and follow-up of exposed passengers. Design Retrospective cohort investigation using a questionnaire administered to passengers and laboratory investigation of those with symptoms. Setting Auckland, New Zealand, with national and international follow-up of passengers. Participants Passengers seated in the rear section of a Boeing 747-400 long haul flight that arrived on 25 April 2009, including a group of 24 students and teachers and 97 (out of 102) other passengers in the same section of the plane who agreed to be interviewed. Main outcome measures Laboratory confirmed pandemic A/H1N1 infection in susceptible passengers within 3.2 days of arrival; sensitivity and specificity of influenza symptoms for confirmed infection; and completeness and timeliness of contact tracing. Results Nine members of the school group were laboratory confirmed cases of pandemic A/H1N1 infection and had symptoms during the flight. Two other passengers developed confirmed pandemic A/H1N1 infection, 12 and 48 hours after the flight. They reported no other potential sources of infection. Their seating was within two rows of infected passengers, implying a risk of infection of about 3.5% for the 57 passengers in those rows. All but one of the confirmed pandemic A/H1N1 infected travellers reported cough, but more complex definitions of influenza cases had relatively low sensitivity. Rigorous follow-up by public health workers located 93% of passengers, but only 52% were contacted within 72 hours of arrival. Conclusions A low but measurable risk of transmission of pandemic A/H1N1 exists during modern commercial air travel. This risk is concentrated close to infected passengers with symptoms. Follow-up and screening of exposed passengers is slow and difficult once they have left the

  15. 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.

  16. Detection of Extensive Cross-Neutralization between Pandemic and Seasonal A/H1N1 Influenza Viruses Using a Pseudotype Neutralization Assay

    PubMed Central

    Labrosse, Béatrice; Tourdjman, Mathieu; Porcher, Raphaël; LeGoff, Jérôme; de Lamballerie, Xavier; Simon, François; Molina, Jean-Michel; Clavel, François

    2010-01-01

    Background Cross-immunity between seasonal and pandemic A/H1N1 influenza viruses remains uncertain. In particular, the extent that previous infection or vaccination by seasonal A/H1N1 viruses can elicit protective immunity against pandemic A/H1N1 is unclear. Methodology/Principal Findings Neutralizing titers against seasonal A/H1N1 (A/Brisbane/59/2007) and against pandemic A/H1N1 (A/California/04/2009) were measured using an HIV-1-based pseudovirus neutralization assay. Using this highly sensitive assay, we found that a large fraction of subjects who had never been exposed to pandemic A/H1N1 express high levels of pandemic A/H1N1 neutralizing titers. A significant correlation was seen between neutralization of pandemic A/H1N1 and neutralization of a standard seasonal A/H1N1 strain. Significantly higher pandemic A/H1N1 neutralizing titers were measured in subjects who had received vaccination against seasonal influenza in 2008–2009. Higher pandemic neutralizing titers were also measured in subjects over 60 years of age. Conclusions/Significance Our findings reveal that the extent of protective cross-immunity between seasonal and pandemic A/H1N1 influenza viruses may be more important than previously estimated. This cross-immunity could provide a possible explanation of the relatively mild profile of the recent influenza pandemic. PMID:20543954

  17. 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.

  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. 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.

  20. An Experimental Investigation of the Performance of a Collison Nebulizer Generating H1N1 Influenza Aerosols

    DTIC Science & Technology

    2015-04-04

    virus preparation in egg allantoic fluid was diluted in sterile deionized water to a concentration of 3.4 £ 106 TCID50/mL. The virus suspension was...of the virus upon generation. An H1N1 influenza virus preparation in egg allantoic fluid was diluted in sterile deionized water to a concentration of... bacteria , fungi, atmospheric environmental pollu- tants and pulmonary drug particles suspended in air or another gas.[1] Their generation has numerous

  1. Seasonal Influenza Vaccine and Protection against Pandemic (H1N1) 2009-Associated Illness Among US Military Personnel

    DTIC Science & Technology

    2010-05-01

    severe) outcomes and warrants further investigation. Our findings further complement recent reports among civilian populations in Mexico [13,14] and among...et al. (2009) Infection and death from influenza A H1N1 virus in Mexico : a retrospective analysis. Lancet 374: 2072–2079. 14. Garcia-Garcia L...Valdespino-Gomez JL, Lazcano-Ponce E, Jimenez-Corona A, Higuera- Iglesias A, et al. (2009) Partial protection of seasonal trivalent inactivated vaccine

  2. 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.

  3. Screening of ethnic medicinal plants of South India against influenza (H1N1) and their antioxidant activity

    PubMed Central

    Maria John, K.M.; Enkhtaivan, Gansukh; Ayyanar, Muniappan; Jin, Kijoun; Yeon, Jin Bong; Kim, Doo Hwan

    2014-01-01

    Antiviral activity against H1N1 influenza was studied using ethnic medicinal plants of South India. Results revealed that Wrightia tinctoria (2.25 μg/ml) was one of the best antidotes against H1N1 virus in terms of inhibitory concentration of 50% (IC50) whereas the control drug Oseltamivir showed 6.44 μg/ml. Strychnos minor, Diotacanthus albiflorus and Cayratia pedata showed low cytotoxicity (>100) to the MDCK (Malin darby canine kidney) cells by cytotoxicity concentration of 50% (CC50) and possessed antiviral activity suggesting that these plants can be used as herbal capsules for H1N1 virus. W. tinctoria and S. minor showed high therapeutic indexes (TI) such as 12.67 and 21.97 suggesting that those plants can be used for anti-viral drug development. The CC50 values of Eugenia singampattiana (0.3 μg/ml), Vitex altissima (42 μg/ml), Salacia oblonga (7.32 μg/ml) and Salacia reticulata (7.36 μg/ml) resulted in cytotoxicity of the MDCK cells, due to their high phenolic content. Findings from this study state that the plant W. tinctoria can be a potent source for third generation anti-viral drug development against H1N1. PMID:25737652

  4. 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.

  5. Antibody-Dependent Cell-Mediated Cytotoxicity Epitopes on the Hemagglutinin Head Region of Pandemic H1N1 Influenza Virus Play Detrimental Roles in H1N1-Infected Mice

    PubMed Central

    Ye, Zi-Wei; Yuan, Shuofeng; Poon, Kwok-Man; Wen, Lei; Yang, Dong; Sun, Zehua; Li, Cun; Hu, Meng; Shuai, Huiping; Zhou, Jie; Zhang, Mei-Yun; Zheng, Bo-Jian; Chu, Hin; Yuen, Kwok-Yung

    2017-01-01

    Engaging the antibody-dependent cell-mediated cytotoxicity (ADCC) for killing of virus-infected cells and secretion of antiviral cytokines and chemokines was incorporated as one of the important features in the design of universal influenza vaccines. However, investigation of the ADCC epitopes on the highly immunogenic influenza hemagglutinin (HA) head region has been rarely reported. In this study, we determined the ADCC and antiviral activities of two putative ADCC epitopes, designated E1 and E2, on the HA head of a pandemic H1N1 influenza virus in vitro and in a lethal mouse model. Our data demonstrated that sera from the E1-vaccinated mice could induce high ADCC activities. Importantly, the induction of ADCC response modestly decreased viral load in the lungs of H1N1-infected mice. However, the elevated ADCC significantly increased mouse alveolar damage and mortality than that of the PBS-vaccinated group (P < 0.0001). The phenotype was potentially due to an exaggerated inflammatory cell infiltration triggered by ADCC, as an upregulated release of cytotoxic granules (perforin) was observed in the lung tissue of E1-vaccinated mice after H1N1 influenza virus challenge. Overall, our data suggested that ADCC elicited by certain domains of HA head region might have a detrimental rather than protective effect during influenza virus infection. Thus, future design of universal influenza vaccine shall strike a balance between the induction of protective immunity and potential side effects of ADCC. PMID:28377769

  6. Productive infection of human skeletal muscle cells by pandemic and seasonal influenza A(H1N1) viruses.

    PubMed

    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.

  7. Transmission characteristics of the 2009 H1N1 influenza pandemic: comparison of 8 Southern hemisphere countries.

    PubMed

    Opatowski, Lulla; Fraser, Christophe; Griffin, Jamie; de Silva, Eric; Van Kerkhove, Maria D; Lyons, Emily J; Cauchemez, Simon; Ferguson, Neil M

    2011-09-01

    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, R(0), 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.

  8. Modelling during an emergency: the 2009 H1N1 influenza pandemic.

    PubMed

    Lee, B Y; Haidari, L A; Lee, M S

    2013-11-01

    During the 2009 H1N1 pandemic, decision-makers had access to mathematical and computational models that were not available in previous pandemics in 1918, 1957, and 1968. How did models contribute to policy and action during the 2009 H1N1 pandemic? Modelling encountered six primary challenges: (i) expectations of modelling were not clearly defined; (ii) appropriate real-time data were not readily available; (iii) modelling results were not generated, shared, or disseminated in time; (iv) decision-makers could not always decipher the structure and assumptions of the models; (v) modelling studies varied in intervention representations and reported results; and (vi) modelling studies did not always present the results or outcomes that are useful to decision-makers. However, there were also seven general successes: (i) modelling characterized the role of social distancing measures such as school closure; (ii) modelling helped to guide data collection; (iii) modelling helped to justify the value of the vaccination programme; (iv) modelling helped to prioritize target populations for vaccination; (v) modelling addressed the use of antiviral medications; (vi) modelling helped with health system preparedness planning; and (vii) modellers and decision-makers gained a better understanding of how to work with each other. In many ways, the 2009 pandemic served as practice and a learning opportunity for both modellers and decision-makers. Modellers can continue working with decision-makers and other stakeholders to help overcome these challenges, to be better prepared when the next emergency inevitably arrives.

  9. Real-time reverse transcription-PCR assay for differentiating the Pandemic H1N1 2009 influenza virus from swine influenza viruses.

    PubMed

    Hiromoto, Yasuaki; Uchida, Yuko; Takemae, Nobuhiro; Hayashi, Tsuyoshi; Tsuda, Tomoyuki; Saito, Takehiko

    2010-12-01

    Since the Pandemic H1N1 2009 (H1N1pdm) influenza virus emerged in human in 2009, H1N1pdm, classical swine H1, Eurasian avian-like H1, human-like H1 and human-like H3 swine influenza viruses have circulated in pig populations, and avian H9N2 viruses have been isolated in pigs as well. In this study, TaqMan single-step real-time reverse transcription-PCR (rtRT-PCR) assays targeting the hemagglutinin gene were developed to differentiate H1N1pdm from other genetic lineages of the H1 subtype and other subtypes of influenza viruses circulating in human and pig populations for veterinary use. H1N1pdm rtRT-PCR detected H1N1pdm RNA and did not cross-react with classical swine H1, Eurasian avian-like H1, human-like H1, human-like H3 swine and avian H9 influenza viruses RNA. Classical swine H1, Eurasian avian-like H1, human-like H1 and H3 and avian H9 rtRT-PCR were reacted exclusively with viral RNA of their respective lineages and subtypes. The results demonstrate that these assays are useful for the diagnosis of the H1N1pdm virus in both human- and animal-health-related fields.

  10. [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.

  11. 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.

  12. Recipients of vaccine against the 1976 "swine flu" have enhanced neutralization responses to the 2009 novel H1N1 influenza virus.

    PubMed

    McCullers, Jonathan A; Van De Velde, Lee-Ann; Allison, Kim J; Branum, Kristen C; Webby, Richard J; Flynn, Patricia M

    2010-06-01

    BACKGROUND. The world is facing a novel H1N1 influenza pandemic. A pandemic scare with a similar influenza virus in 1976 resulted in the vaccination of nearly 45 million persons. We hypothesized that prior receipt of the 1976 "swine flu" vaccine would enhance immune responses to the 2009 novel H1N1 influenza strain. METHODS. A prospective, volunteer sample of employees aged > or = 55 years at a children's cancer hospital in August 2009 was assessed for antibody responses to the 2009 pandemic H1N1 influenza virus and the 2008-2009 seasonal H1N1 influenza virus. RESULTS. Antibody responses by hemagglutination-inhibition assay were high against both the seasonal influenza virus (89.7% had a titer considered seroprotective) and pandemic H1N1 influenza virus (88.8% had a seroprotective titer). These antibodies were effective at neutralizing the seasonal H1N1 influenza virus in 68.1% of participants (titer > or = 40), but only 18.1% had detectable neutralizing titers against the pandemic H1N1 influenza virus. Of 116 participants, 46 (39.7%) received the 1976 "swine flu" vaccine. Receipt of this vaccine significantly enhanced neutralization responses; 8 (17.4%) of 46 vaccine recipients had titers > or = 160, compared with only 3 (4.3%) of 70 who did not receive the vaccine (P = .018 by chi(2) test). CONCLUSIONS. In this cohort, persons aged > or = 55 years had evidence of robust immunity to the 2008-2009 seasonal H1N1 influenza virus. These antibodies were cross-reactive but nonneutralizing against the 2009 pandemic H1N1 influenza strain. Receipt of a vaccine to a related virus significantly enhanced the neutralization capacity of these responses, suggesting homologous vaccination against the 2009 pandemic H1N1 influenza virus would have a similar effect.

  13. The 2009 Influenza A(H1N1) "Swine Flu" Outbreak: An Overview

    DTIC Science & Technology

    2009-05-05

    Table 1. WHO Influenza Pandemic Phases (Current alert level is highlighted) Phase Description Phase 1 No animal influenza virus circulating among... animals has been reported to cause infection in humans. Phase 2 An animal influenza virus circulating in domesticated or wild animals is known to have...community-level outbreaks. Phase 4 Human-to-human transmission of an animal or human- animal influenza reassortant a virus able to sustain community

  14. 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.

  15. One-Step Real-Time RT-PCR for Pandemic Influenza A Virus (H1N1) 2009 Matrix Gene Detection in Swine Samples

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the spring of 2009, a novel H1N1 influenza A virus began to spread among humans worldwide. The genomic features of the new pandemic H1N1 were immediately identified: it contained gene segments with ancestors in North American and Eurasian swine influenza virus (SIV) lineages providing the virus a...

  16. Genetic and Antigenic Characterization of H1 Influenza Viruses from United States Swine Prior to the Emergence of the 2009 Pandemic H1N1

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Swine play a role for the evolution of influenza A viruses. Prior to the introduction of the 2009 pandemic H1N1 virus from humans into pigs, four phylogenetic clusters of the hemagglutinin (HA) gene from H1 influenza viruses could be found in U.S. swine. Viruses from the classical H1N1 swine lineage...

  17. Oseltamivir-Resistant Influenza Viruses A (H1N1) during 2007–2009 Influenza Seasons, Japan

    PubMed Central

    Ujike, Makoto; Shimabukuro, Kozue; Mochizuki, Kiku; Obuchi, Masatsugu; Kageyama, Tsutomu; Shirakura, Masayuki; Kishida, Noriko; Yamashita, Kazuyo; Horikawa, Hiroshi; Kato, Yumiko; Fujita, Nobuyuki; Tashiro, Masato

    2010-01-01

    To monitor oseltamivir-resistant influenza viruses A (H1N1) (ORVs) with H275Y in neuraminidase (NA) in Japan during 2 influenza seasons, we analyzed 3,216 clinical samples by NA sequencing and/or NA inhibition assay. The total frequency of ORVs was 2.6% (45/1,734) during the 2007–08 season and 99.7% (1,477/1,482) during the 2008–09 season, indicating a marked increase in ORVs in Japan during 1 influenza season. The NA gene of ORVs in the 2007–08 season fell into 2 distinct lineages by D354G substitution, whereas that of ORVs in the 2008–09 season fell into 1 lineage. NA inhibition assay and M2 sequencing showed that almost all the ORVs were sensitive to zanamivir and amantadine. The hemagglutination inhibition test showed that ORVs were antigenetically similar to the 2008–09 vaccine strain A/Brisbane/59/2007. Our data indicate that the current vaccine or zanamivir and amantadine are effective against recent ORVs, but continuous surveillance remains necessary. PMID:20507742

  18. 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.

  19. Modelling the transmission dynamics and control of the novel 2009 swine influenza (H1N1) pandemic.

    PubMed

    Sharomi, O; Podder, C N; Gumel, A B; Mahmud, S M; Rubinstein, E

    2011-03-01

    The paper presents a deterministic compartmental model for the transmission dynamics of swine influenza (H1N1) pandemic in a population in the presence of an imperfect vaccine and use of drug therapy for confirmed cases. Rigorous analysis of the model, which stratifies the infected population in terms of their risk of developing severe illness, reveals that it exhibits a vaccine-induced backward bifurcation when the associated reproduction number is less than unity. The epidemiological consequence of this result is that the effective control of H1N1, when the reproduction number is less than unity, in the population would then be dependent on the initial sizes of the subpopulations of the model. For the case where the vaccine is perfect, it is shown that having the reproduction number less than unity is necessary and sufficient for effective control of H1N1 in the population (in such a case, the associated disease-free equilibrium is globally asymptotically stable). The model has a unique endemic equilibrium when the reproduction number exceeds unity. Numerical simulations of the model, using data relevant to the province of Manitoba, Canada, show that it reasonably mimics the observed H1N1 pandemic data for Manitoba during the first (Spring) wave of the pandemic. Further, it is shown that the timely implementation of a mass vaccination program together with the size of the Manitoban population that have preexisting infection-acquired immunity (from the first wave) are crucial to the magnitude of the expected burden of disease associated with the second wave of the H1N1 pandemic. With an estimated vaccine efficacy of approximately 80%, it is projected that at least 60% of Manitobans need to be vaccinated in order for the effective control or elimination of the H1N1 pandemic in the province to be feasible. Finally, it is shown that the burden of the second wave of H1N1 is expected to be at least three times that of the first wave, and that the second wave would last

  20. 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.

  1. 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

  2. Immunogenicity and safety of pandemic influenza A (H1N1) 2009 vaccine: systematic review and meta‐analysis

    PubMed Central

    Yin, J. Kevin; Khandaker, Gulam; Rashid, Harunor; Heron, Leon; Ridda, Iman; Booy, Robert

    2011-01-01

    Please cite this paper as: Yin et al. (2011) Immunogenicity and safety of pandemic influenza A (H1N1) 2009 vaccine: systematic review and meta‐analysis. Influenza and Other Respiratory Viruses 5(5), 299–305. 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

  3. 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

    2015-08-13

    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.

  4. 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.

  5. The tree shrew provides a useful alternative model for the study of influenza H1N1 virus

    PubMed Central

    2013-01-01

    Background The influenza pandemics have resulted in significant morbidity and mortality worldwide. Animal models are useful in the study of influenza virus pathogenesis. Because of various limitations in current laboratory animal models, it is essential to develop new alternative animal models for influenza virus research aimed at understanding the viral and host factors that contribute to virus infection in human. Method We investigated the replicative efficiency of influenza H1N1 virus (classic strain (Influenza A/PR/8/34), seasonal influenza isolate (A/Guangzhou/GIRD/02/09) and swine-origin human influenza virus (A/Guangzhou/GIRD/07/09)) at Day1,2,4,6 and 9 p.i. using TCID50 and qPCR assay in tree shrew model. Body temperature was monitored in the morning and evening for 3 days before infection and for 14 days. Seroconversion was detected by determining the neutralizing antibody titers against the challenge viruses in the pre- and exposure serum samples collected before infection and at 14 days p.i., respectively. Lungs and tracheas of tree shews were collected at day 14 post p.i. for histopathological analysis. Lectinhistochemistry analysis was conducted to identify the distribution of SAα2,3 Gal and SAα2,6 Gal receptors in the lung and trachea. Results The infected tree shrew displayed mild or moderate systemic and respiratory symptoms and pathological changes in respiratory tracts. The human H1N1 influenza virus may replicate in the upper respiratory tract of tree shrews. Analysis of the receptors distribution in the respiratory tract of tree shrews by lectinhistochemistry showed that sialic acid (SA)α2,6-Gal receptors were widely distributed in the trachea and nasal mucosa, whereas (SA)α2,3-Gal receptor was the main receptor in the lung tissue. Conclusions Based on these findings, tree shrew seemed to mimic well influenza virus infection in humans. We propose that tree shrews could be a useful alternative mammalian model to study pathogenesis of

  6. 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

  7. In-Silico screening of Pleconaril and its novel substituted derivatives with Neuraminidase of H1N1 Influenza strain

    PubMed Central

    2012-01-01

    Background Neuraminidase (NA) is a prominent surface antigen of Influenza viruses, which helps in release of viruses from the host cells after replication. Anti influenza drugs such as Oseltamivir target a highly conserved active site of NA, which comprises of 8 functional residues (R118, D151, R152, R224, E276, R292, R371 and Y406) to restrict viral release from host cells, thus inhibiting its ability to cleave sialic acid residues on the cell membrane. Reports on the emergence of Oseltamivir resistant strains of H1N1 Influenza virus necessitated a search for alternative drug candidates. Pleconaril is a novel antiviral drug being developed by Schering-Plough to treat Picornaviridae infections, and is in its late clinical trials stage. Since, Pleconaril was designed to bind the highly conserved hydrophobic binding site on VP1 protein of Picorna viruses, the ability of Pleconaril and its novel substituted derivatives to bind highly conserved hydrophobic active site of H1N1 Neuraminidase, targeting which oseltamivir has been designed was investigated. Result 310 novel substituted variants of Pleconaril were designed using Chemsketch software and docked into the highly conserved active site of NA using arguslab software. 198 out of 310 Pleconaril variants analyzed for docking with NA active site were proven effective, based on their free binding energy. Conclusion Pleconaril variants with F, Cl, Br, CH3, OH and aromatic ring substitutions were shown to be effective alternatives to Oseltamivir as anti influenza drugs. PMID:22340192

  8. [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.

  9. Evidence of reassortment of pandemic H1N1 influenza virus in swine in Argentina: are we facing the expansion of potential epicenters of influenza emergence?

    PubMed Central

    Pereda, Ariel; Rimondi, Agustina; Cappuccio, Javier; Sanguinetti, Ramon; Angel, Matthew; Ye, Jianqiang; Sutton, Troy; Dibárbora, Marina; Olivera, Valeria; Craig, Maria I.; Quiroga, Maria; Machuca, Mariana; Ferrero, Andrea; Perfumo, Carlos; Perez, Daniel R.

    2011-01-01

    Please cite this paper as: Pereda et al. (2011) Evidence of reassortment of pandemic H1N1 influenza virus in swine in Argentina: are we facing the expansion of potential epicenters of influenza emergence? Influenza and Other Respiratory Viruses 5(6), 409–412. In this report, we describe the occurrence of two novel swine influenza viruses (SIVs) in pigs in Argentina. These viruses are the result of two independent reassortment events between the H1N1 pandemic influenza virus (H1N1pdm) and human‐like SIVs, showing the constant evolution of influenza viruses at the human–swine interface and the potential health risk of H1N1pdm as it appears to be maintained in the swine population. It must be noted that because of the lack of information regarding the circulation of SIVs in South America, we cannot discard the possibility that ancestors of the H1N1pdm or other SIVs have been present in this part of the world. More importantly, these findings suggest an ever‐expanding geographic range of potential epicenters of influenza emergence with public health risks. PMID:21668680

  10. Pandemic H1N1 influenza: zoonoses are a two-way street

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Influenza is a zoonotic viral disease representing a worldwide health and economic threat to humans and animals. Swine influenza was first recognized clinically in pigs in the Midwestern United States in 1918 concurrent with the Spanish flu human pandemic. Since the first report that flu was caused ...

  11. 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

  12. Heterovariant Cross-Reactive B-Cell Responses Induced by the 2009 Pandemic Influenza Virus A Subtype H1N1 Vaccine

    PubMed Central

    He, Xiao-Song; Sasaki, Sanae; Baer, Jane; Khurana, Surender; Golding, Hana; Treanor, John J.; Topham, David J.; Sangster, Mark Y.; Jin, Hong; Dekker, Cornelia L.; Subbarao, Kanta; Greenberg, Harry B.

    2013-01-01

    Background. The generation of heterovariant immunity is a highly desirable feature of influenza vaccines. The goal of this study was to compare the heterovariant B-cell response induced by the monovalent inactivated 2009 pandemic influenza A virus subtype H1N1 (A[H1N1]pdm09) vaccine with that induced by the 2009 seasonal trivalent influenza vaccine (sTIV) containing a seasonal influenza A virus subtype H1N1 (A[H1N1]) component in young and elderly adults. Methods. Plasmablast-derived polyclonal antibodies (PPAb) from young and elderly recipients of A(H1N1)pdm09 vaccine or sTIV were tested for binding activity to various influenza antigens. Results. In A(H1N1)pdm09 recipients, the PPAb titers against homotypic A(H1N1)pdm09 vaccine were similar to those against the heterovariant seasonal A(H1N1) vaccine and were similar between young and elderly subjects. The PPAb avidity was higher among elderly individuals, compared with young individuals. In contrast, the young sTIV recipients had 10-fold lower heterovariant PPAb titers against the A(H1N1)pdm09 vaccine than against the homotypic seasonal A(H1N1) vaccine. In binding assays with recombinant head and stalk domains of hemagglutinin, PPAb from the A(H1N1)pdm09 recipients but not PPAb from the sTIV recipients bound to the conserved stalk domain. Conclusion. The A(H1N1)pdm09 vaccine induced production of PPAb with heterovariant reactivity, including antibodies targeting the conserved hemagglutinin stalk domain. PMID:23107783

  13. Intent to receive influenza A (H1N1) 2009 monovalent and seasonal influenza vaccines - two counties, North Carolina, August 2009.

    PubMed

    2009-12-25

    On September 15, 2009, the Food and Drug Administration approved the manufacture of four influenza A (H1N1) 2009 monovalent vaccines. Before release of the first batches of the vaccine on September 30, intent to receive the vaccine was estimated at 50% among selected U.S. adult populations and as high as 70% for children. However, studies in previous years of seasonal influenza vaccination in children, who might require 2 doses based on age and prior vaccination status, have indicated poor compliance with recommendations. To measure intent to receive H1N1 and seasonal influenza vaccines among children and adults, during August 28-29, 2009, the North Carolina Center for Public Health Preparedness, with state and local public health officials, conducted a community assessment in two counties. This report summarizes the results of that assessment, which determined that 64% of adults reported intent to receive H1N1 vaccine. In addition, 65% of parents reported intent to have all their children (aged 6 months to <18 years) vaccinated with H1N1 vaccine, and 51% said they would have all their children vaccinated with both H1N1 and seasonal influenza vaccines. The most commonly reported reasons for not intending to receive H1N1 vaccine were belief in a low likelihood of infection (18%) and concern over vaccine side effects (14%); 85% of participants said they received their H1N1 information from television. To increase coverage with H1N1 and seasonal influenza vaccines, public health departments should use television to focus public health messages on the risks for infection and severe illness and the safety profile of the vaccine.

  14. Glycosylation on Hemagglutinin Affects the Virulence and Pathogenicity of Pandemic H1N1/2009 Influenza A Virus in Mice

    PubMed Central

    Li, Yongtao; Bradley, Konrad C.; Cao, Jiyue; Chen, Huanchun; Jin, Meilin; Zhou, Hongbo

    2013-01-01

    The two glycosylation sites (Asn142 and Asn177) were observed in the HA of most human seasonal influenza A/H1N1 viruses, while none in pandemic H1N1/2009 influenza A (pH1N1) viruses. We investigated the effect of the two glycosylation sites on viral virulence and pathogenicity in mice using recombinant pH1N1. The H1N1/144 and H1N1/177 mutants which gained potential glycosylation sites Asn142 and Asn177 on HA respectively were generated from A/Mexico/4486/2009(H1N1) by site-directed mutagenesis and reverse genetics, the same as the H1N1/144+177 gained both glycosylation sites Asn142 and Asn177. The biological characteristics and antigenicity of the mutants were compared with wild-type pH1N1. The virulence and pathogenicity of recombinants were also detected in mice. Our results showed that HA antigenicity and viral affinity for receptor may change with introduction of the glycosylation sites. Compared with wild-type pH1N1, the mutant H1N1/177 displayed an equivalent virus titer in chicken embryos and mice, and increased virulence and pathogenicity in mice. The H1N1/144 displayed the highest virus titer in mice lung. However, the H1N1/144+177 displayed the most serious alveolar inflammation and pathogenicity in infected mice. The introduction of the glycosylation sites Asn144 and Asn177 resulted in the enhancement on virulence and pathogenicity of pH1N1 in mice, and was also associated with the change of HA antigenicity and the viral affinity for receptor. PMID:23637827

  15. Oseltamivir for the treatment of H1N1 influenza during pregnancy.

    PubMed

    Beigi, R H; Pillai, V C; Venkataramanan, R; Caritis, S N

    2015-10-01

    Pregnancy heightens the risk of adverse outcomes from influenza infections. This is true for both seasonal epidemics as well as occasional pandemics. Seasonal influenza vaccines are the focus of disease prevention and are recommended for all pregnant women in any trimester of pregnancy and postpartum. Oseltamivir (Tamiflu) is currently the recommended and most commonly used pharmaceutical agent for influenza prophylaxis and treatment. Oseltamivir has been demonstrated to prevent disease after exposure, treat infected individuals, as well as lessen the likelihood of complications. The physiologic adaptations of pregnancy alter the pharmacokinetics of this important drug. Evidence of these alterations, knowledge gaps, and future investigative directions to fill these knowledge gaps are highlighted.

  16. 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

  17. The 2009 H1N1 influenza pandemic and Minnesota's K-12 schools: public health lessons learned.

    PubMed

    Como-Sabetti, Kathryn; Livingston, Franci; Gahr, Pamala; Nagle, Kayla; Martin, Karen; Morin, Craig; Parilla, Elizabeth

    2010-09-01

    Prior to 2009, influenza pandemic planners had primarily planned for a virus that would originate in a location other than North America, giving public health officials in the United States time to determine its severity before widespread disease occurred here. Thus, response plans for schools focused on closure in the case of a severe pandemic and potential closure in the event of a moderate one. The 2009 H1N1 pandemic, however, presented a different scenario. The severity of 2009 H1N1 was initially unknown and later was determined to be mild to moderate. Thus, as the pandemic unfolded, state and national public health entities found themselves adapting their recommendations for school closure. This article reviews Minnesota's experience with 2009 H1N1, focusing on the pandemic among school-aged children during the spring (April to August 2009) and fall (September 2009 to April 2010), and it chronicles how outbreak surveillance policies and recommendations for K-12 schools changed over the course of the pandemic.

  18. 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.

  19. 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

  20. Antigenic drift of the pandemic 2009 A(H1N1) influenza virus in A ferret model.

    PubMed

    Guarnaccia, Teagan; Carolan, Louise A; Maurer-Stroh, Sebastian; Lee, Raphael T C; Job, Emma; Reading, Patrick C; Petrie, Stephen; McCaw, James M; McVernon, Jodie; Hurt, Aeron C; Kelso, Anne; Mosse, Jennifer; Barr, Ian G; Laurie, Karen L

    2013-01-01

    Surveillance data indicate that most circulating A(H1N1)pdm09 influenza viruses have remained antigenically similar since they emerged in humans in 2009. However, antigenic drift is likely to occur in the future in response to increasing population immunity induced by infection or vaccination. In this study, sequential passaging of A(H1N1)pdm09 virus by contact transmission through two independent series of suboptimally vaccinated ferrets resulted in selection of variant viruses with an amino acid substitution (N156K, H1 numbering without signal peptide; N159K, H3 numbering without signal peptide; N173K, H1 numbering from first methionine) in a known antigenic site of the viral HA. The N156K HA variant replicated and transmitted efficiently between naïve ferrets and outgrew wildtype virus in vivo in ferrets in the presence and absence of immune pressure. In vitro, in a range of cell culture systems, the N156K variant rapidly adapted, acquiring additional mutations in the viral HA that also potentially affected antigenic properties. The N156K escape mutant was antigenically distinct from wildtype virus as shown by binding of HA-specific antibodies. Glycan binding assays demonstrated the N156K escape mutant had altered receptor binding preferences compared to wildtype virus, which was supported by computational modeling predictions. The N156K substitution, and culture adaptations, have been detected in human A(H1N1)pdm09 viruses with N156K preferentially reported in sequences from original clinical samples rather than cultured isolates. This study demonstrates the ability of the A(H1N1)pdm09 virus to undergo rapid antigenic change to evade a low level vaccine response, while remaining fit in a ferret transmission model of immunization and infection. Furthermore, the potential changes in receptor binding properties that accompany antigenic changes highlight the importance of routine characterization of clinical samples in human A(H1N1)pdm09 influenza surveillance.

  1. The PB2-E627K mutation attenuates viruses containing the 2009 H1N1 influenza pandemic polymerase.

    PubMed

    Jagger, Brett W; Memoli, Matthew J; Sheng, Zong-Mei; Qi, Li; Hrabal, Rachel J; Allen, Genevieve L; Dugan, Vivien G; Wang, Ruixue; Digard, Paul; Kash, John C; Taubenberger, Jeffery K

    2010-05-18

    The swine-origin H1N1 influenza A virus emerged in early 2009 and caused the first influenza pandemic in 41 years. The virus has spread efficiently to both the Northern and the Southern Hemispheres and has been associated with over 16,000 deaths. Given the virus's recent zoonotic origin, there is concern that the virus could acquire signature mutations associated with the enhanced pathogenicity of previous pandemic viruses or H5N1 viruses with pandemic potential. We tested the hypothesis that mutations in the polymerase PB2 gene at residues 627 and 701 would enhance virulence but found that influenza viruses containing these mutations in the context of the pandemic virus polymerase complex are attenuated in cell culture and mice.

  2. [Effects of school closure during influenza A/H1N1 pandemic in 2009 in Japan].

    PubMed

    Uchida, Mitsuo; Kaneko, Minoru; Yamamoto, Hiroshi; Honda, Takayuki; Kawa, Shigeyuki

    2013-01-01

    Schools were closed worldwide during the 2009 influenza A/H1N1 pandemic to prevent the viral spread; however, to date, there has been insufficient evidence to conclude that the closures were beneficial. Therefore, in the present review, we evaluated the effects of school closure during the 2009 influenza A/H1N1 pandemic in Japan. A search of PubMed and Japanese journals identified 24 articles that evaluated the effects of school closure using the following methods: descriptive epidemiology, changes in absenteeism rate, a simulation model, and reproductive number. Almost all of the retrieved studies showed that school closure effectively reduced the number of new infections and thus subsequently suppressed the epidemic. On the other hand, two major sets of confounding variables were identified. First, the effect of school closure was confounded by the methods used to measure, viral infectivity, subject characteristics, increased immunization rates, nonpharmaceutical interventions, antiviral administration, student contact patterns during school closure, and individual household environments. Secondly, school closure implementation was affected by differences between proactive and reactive closures, differences between seasonal and pandemic influenza, decision factors regarding school closure, socioeconomic cost, and ethics of imposing restrictions on individuals. Therefore, a comprehensive, longitudinal study is necessary to clarify the effects of school closure during viral pandemics.

  3. 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.

  4. 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.

  5. 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

  6. A novel monoclonal antibody effective against lethal challenge with swine-lineage and 2009 pandemic H1N1 influenza viruses in mice.

    PubMed

    Shao, Hongxia; Ye, Jianqiang; Vincent, Amy L; Edworthy, Nicole; Ferrero, Andrea; Qin, Aijian; Perez, Daniel R

    2011-09-01

    The HA protein of the 2009 pandemic H1N1 viruses (H1N1pdm) is antigenically closely related to the HA of classical North American swine H1N1 influenza viruses (cH1N1). Since 1998, through mutation and reassortment of HA genes from human H3N2 and H1N1 influenza viruses, swine influenza strains are undergoing substantial antigenic drift and shift. In this report we describe the development of a novel monoclonal antibody (S-OIV-3B2) that shows high hemagglutination inhibition (HI) and neutralization titers not only against H1N1pdm, but also against representatives of the α, β, and γ clusters of swine-lineage H1 influenza viruses. Mice that received a single intranasal dose of S-OIV-3B2 were protected against lethal challenge with either H1N1pdm or cH1N1 virus. These studies highlight the potential use of S-OIV-3B2 as effective intranasal prophylactic or therapeutic antiviral treatment for swine-lineage H1 influenza virus infections.

  7. Protection of human influenza vaccines against a reassortant swine influenza virus of pandemic H1N1 origin using a pig model.

    PubMed

    Arunorat, Jirapat; Charoenvisal, Nataya; Woonwong, Yonlayong; Kedkovid, Roongtham; Jittimanee, Supattra; Sitthicharoenchai, Panchan; Kesdangsakonwut, Sawang; Poolperm, Pariwat; Thanawongnuwech, Roongroje

    2017-02-28

    Since the pandemic H1N1 emergence in 2009 (pdmH1N1), many reassortant pdmH1N1 viruses emerged and found circulating in the pig population worldwide. Currently, commercial human subunit vaccines are used commonly to prevent the influenza symptom based on the WHO recommendation. In case of current reassortant swine influenza viruses transmitting from pigs to humans, the efficacy of current human influenza vaccines is of interest. In this study, influenza A negative pigs were vaccinated with selected commercial human subunit vaccines and challenged with rH3N2. All sera were tested with both HI and SN assays using four representative viruses from the surveillance data in 2012 (enH1N1, pdmH1N1, rH1N2 and rH3N2). The results showed no significant differences in clinical signs and macroscopic and microscopic findings among groups. However, all pig sera from vaccinated groups had protective HI titers to the enH1N1, pdmH1N1 and rH1N2 at 21DPV onward and had protective SN titers only to pdmH1N1and rH1N2 at 21DPV onward. SN test results appeared more specific than those of HI tests. All tested sera had no cross-reactivity against the rH3N2. Both studied human subunit vaccines failed to protect and to stop viral shedding with no evidence of serological reaction against rH3N2. SIV surveillance is essential for monitoring a novel SIV emergence potentially for zoonosis.

  8. 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

  9. Seasonal Influenza A H1N1pdm09 Virus and Severe Outcomes: A Reason for Broader Vaccination in Non-Elderly, At-Risk People

    PubMed Central

    Omeñaca, Manuel; Panadero, Carolina; Royo, Laura; Vengoechea, Jose J.; Fandos, Sergio; de Pablo, Francisco; Bello, Salvador

    2016-01-01

    Background Recent pandemics of influenza A H1N1pdm09 virus have caused severe illness, especially in young people. Very few studies on influenza A H1N1pdm09 in post-pandemic periods exist, and there is no information on the severity of both seasonal influenza A(H1N1) and A(H3N2) from the same season, adjusting for potential confounders, including vaccine. Methods and Results We performed a retrospective observational study of adults hospitalized during the 2014 season with influenza A(H1N1) or A(H3N2). All patients underwent the same diagnostic and therapeutic protocol in a single hospital, including early Oseltamivir therapy. We included 234 patients: 146 (62.4%) influenza A(H1N1) and 88 (37.6%) A(H3N2). A(H1N1) patients were younger (p<0.01), developed more pneumonia (p<0.01), respiratory complications (p = 0.015), ARDS (p = 0.047), and septic shock (p = 0.049), were more frequently admitted to the ICU (p = 0.022), required IMV (p = 0.049), and were less frequently vaccinated (p = 0.008). After adjusting for age, comorbidities, time from onset of illness, and vaccine status, influenza A(H1N1) (OR, 2.525), coinfection (OR, 2.821), and no vaccination (OR, 3.086) were independent risk factors for severe disease. Conclusions Hospitalized patients with influenza A(H1N1) were more than twice as likely to have severe influenza. They were younger and most had not received the vaccine. Our findings suggest that seasonal influenza A(H1N1) maintains some features of pandemic viruses, and recommend wider use of vaccination in younger adult high-risk patients. PMID:27832114

  10. Psychogenic illness following vaccination: exploratory study of mass vaccination against pandemic influenza A (H1N1) in 2009 in South Korea

    PubMed Central

    2017-01-01

    Purpose Adverse events during mass vaccination campaigns have had a profoundly negative impact on vaccine coverage rates. The objective of the study was to identify the characteristics of reported psychogenic illness cases following mass vaccination that needed further interventions of the national immunization program. Materials and Methods We collected documents that were submitted to the Korea Centers for Disease Control and Prevention for vaccine injury compensation, and analyzed cases of psychogenic illness following pandemic influenza A (H1N1) vaccination in 2009 which were confirmed by the Korean Advisory Committee on Vaccine Injury Compensation. Results During the 2009-2010 influenza season, 13 million Koreans were vaccinated against pandemic influenza. Of 28 reported psychogenic illness cases following immunization, 25 were vaccinated through school-located mass immunization. Significant numbers of them were female adolescents (68%) or had underlying vulnerable conditions or emotional life stressors (36%). They required lengthy hospitalization (median, 7 days) and high medical costs (median, US $1,582 per case). Conclusion Health authorities and organizers of future mass vaccinations should be well aware of the possible occurrence of psychogenic illness, acknowledge their detailed characteristics, and take its economic burden into account to mitigate the risk of transmission of infectious diseases efficiently. PMID:28168171

  11. 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

  12. 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.

  13. Challenge of Pigs with Natural Immunity to H1 and H3 Swine Influenza Virus with Pandemic 2009 H1N1 Influenza Virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction. The emergence of the pandemic 2009 human H1N1 influenza A virus raised many questions about the implications for this virus in swine (1). One such question is, does prior exposure to influenza virus confer any protection against the new virus? This report describes a study to evaluate ...

  14. Serologic cross reactivity of serum samples from avian influenza vaccinated commercial U.S. turkeys to the emergent H1N1 influenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recently, the 2009 human H1N1 influenza virus was identified in turkey breeders in Chile and Canada resulting in infection and egg production losses. In the U.S., vaccination of turkeys against avian influenza may include H1 and H3 viruses also isolated from swine. We tested whether sera from turk...

  15. 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

    2012-07-06

    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.

  16. Evolution of human receptor binding affinity of H1N1 hemagglutinins from 1918 to 2009 pandemic influenza A virus.

    PubMed

    Nunthaboot, Nadtanet; Rungrotmongkol, Thanyada; Malaisree, Maturos; Kaiyawet, Nopporn; Decha, Panita; Sompornpisut, Pornthep; Poovorawan, Yong; Hannongbua, Supot

    2010-08-23

    The recent outbreak of the novel 2009 H1N1 influenza in humans has focused global attention on this virus, which could potentially have introduced a more dangerous pandemic of influenza flu. In the initial step of the viral attachment, hemagglutinin (HA), a viral glycoprotein surface, is responsible for the binding to the human SIA alpha2,6-linked sialopentasaccharide host cell receptor (hHAR). Dynamical and structural properties, based on molecular dynamics simulations of the four different HAs of Spanish 1918 (H1-1918), swine 1930 (H1-1930), seasonal 2005 (H1-2005), and a novel 2009 (H1-2009) H1N1 bound to the hHAR were compared. In all four HA-hHAR complexes, major interactions with the receptor binding were gained from HA residue Y95 and the conserved HA residues of the 130-loop, 190-helix, and 220-loop. However, introduction of the charged HA residues K145 and E227 in the 2009 HA binding pocket was found to increase the HA-hHAR binding efficiency in comparison to the three previously recognized H1N1 strains. Changing of the noncharged HA G225 residue to a negatively charged D225 provides a larger number of hydrogen-bonding interactions. The increase in hydrophilicity of the receptor binding region is apparently an evolution of the current pandemic flu from the 1918 Spanish, 1930 swine, and 2005 seasonal strains. Detailed analysis could help the understanding of how different HAs effectively attach and bind with the hHAR.

  17. 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

  18. 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

  19. Implication of inflammatory macrophages, nuclear receptors and interferon regulatory factors in increased virulence of pandemic 2009 H1N1 influenza A virus after host adaptation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    While pandemic 2009 H1N1 influenza A viruses were responsible for numerous severe infections in humans, these viruses do not typically cause corresponding severe disease in mammalian models. However, the generation of a virulent 2009 H1N1 virus following serial lung passage in mice has allowed for...

  20. In silico modification of oseltamivir as neuraminidase inhibitor of influenza A virus subtype H1N1

    PubMed Central

    Tambunan, Usman Sumo Friend; Rachmania, Rizky Archintya; Parikesit, Arli Aditya

    2015-01-01

    Abstract This research focused on the modification of the functional groups of oseltamivir as neuraminidase inhibitor against influenza A virus subtype H1N1. Interactions of three of the best ligands were evaluated in the hydrated state using molecular dynamics simulation at two different temperatures. The docking result showed that AD3BF2D ligand (N-[(1S,6R)-5-amino-5-{[(2R,3S,4S)-3,4-dihydroxy-4-(hydroxymethyl) tetrahydrofuran-2-yl]oxy}-4-formylcyclohex-3-en-1-yl]acetamide-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate) had better binding energy values than standard oseltamivir. AD3BF2D had several interactions, including hydrogen bonds, with the residues in the catalytic site of neuraminidase as identified by molecular dynamics simulation. The results showed that AD3BF2D ligand can be used as a good candidate for neuraminidase inhibitor to cope with influenza A virus subtype H1N1. PMID:25859271

  1. The hemagglutinin of the influenza A(H1N1)pdm09 is mutating towards stability

    PubMed Central

    Castelán-Vega, Juan A; Magaña-Hernández, Anastasia; Jiménez-Alberto, Alicia; Ribas-Aparicio, Rosa María

    2014-01-01

    The last influenza A pandemic provided an excellent opportunity to study the adaptation of the influenza A(H1N1)pdm09 virus to the human host. Particularly, due to the availability of sequences taken from isolates since the beginning of the pandemic until date, we could monitor amino acid changes that occurred in the hemagglutinin (HA) as the virus spread worldwide and became the dominant H1N1 strain. HA is crucial to viral infection because it binds to sialidated cell-receptors and mediates fusion of cell and viral membranes; because antibodies that bind to HA may block virus entry to the cell, this protein is subjected to high selective pressure. Multiple alignment analysis of sequences of the HA from isolates taken since 2009 to date allowed us to find amino acid changes that were positively selected as the pandemic progressed. We found nine changes that became prevalent: HA1 subunits D104N, K166Q, S188T, S206T, A259T, and K285E; and HA2 subunits E47K, S124N, and E172K. Most of these changes were located in areas involved in inter- and intrachain interactions, while only two (K166Q and S188T) were located in known antigenic sites. We conclude that selective pressure on HA was aimed to improve its functionality and hence virus fitness, rather than at avoidance of immune recognition. PMID:25328411

  2. [NP gene of pandemic H1N1 virus attenuates virulence of mouse-adapted human influenza virus].

    PubMed

    Zhirnov, O P; Syrtsev, V V; Schwalm, F; Klenk, H D

    2011-01-01

    The authors studied a possible role of the caspase cleavage motif located in the nucleoprotein (NP) of pandemic influenza virus H1N1 in the regulation of viral virulence properties. A reverse genetics method was used to obtain chimeric seasonal-like mouse-adapted influenza virus hvA/PE/8/34 (H1N10) carrying either the NP gene of wild type pandemic virus with incomplete caspase motif ETGC or mutated pandemic NP with natural caspase cleavage site of human type ETDG. The wild-type NP gene of the pandemic virus was found to poorly fit to the gene pattern of closely related seasonal-like hvA/PR/8/34 virus (H1N1) and did not rescue mature virus production whereas a mutated NP with human-type caspase cleavage site maintained gene fitness, giving rise to a chimeric virus. The generated chimeric virus hvA/PR/8/34 carrying the mutated pandemic NP successfully replicated in the murine lung, but was attenuated and did not reach the virulence level of seasonal-like mouse-adapted virus hvA/PR/8/34. The findings indicate that the NP caspase cleavage site plays a role in viral adaptation and viral virulence in mammals.

  3. [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.

  4. 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

  5. Revealing the True Incidence of Pandemic A(H1N1)pdm09 Influenza in Finland during the First Two Seasons - An Analysis Based on a Dynamic Transmission Model.

    PubMed

    Shubin, Mikhail; Lebedev, Artem; Lyytikäinen, Outi; Auranen, Kari

    2016-03-01

    The threat of the new pandemic influenza A(H1N1)pdm09 imposed a heavy burden on the public health system in Finland in 2009-2010. An extensive vaccination campaign was set up in the middle of the first pandemic season. However, the true number of infected individuals remains uncertain as the surveillance missed a large portion of mild infections. We constructed a transmission model to simulate the spread of influenza in the Finnish population. We used the model to analyse the two first years (2009-2011) of A(H1N1)pdm09 in Finland. Using data from the national surveillance of influenza and data on close person-to-person (social) contacts in the population, we estimated that 6% (90% credible interval 5.1 - 6.7%) of the population was infected with A(H1N1)pdm09 in the first pandemic season (2009/2010) and an additional 3% (2.5 - 3.5%) in the second season (2010/2011). Vaccination had a substantial impact in mitigating the second season. The dynamic approach allowed us to discover how the proportion of detected cases changed over the course of the epidemic. The role of time-varying reproduction number, capturing the effects of weather and changes in behaviour, was important in shaping the epidemic.

  6. 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.

  7. Hemagglutinin protein of Asian strains of human influenza virus A H1N1 binds to sialic acid--a major component of human airway receptors.

    PubMed

    Chua, K H; Chai, H C

    2012-03-16

    Hemagglutinin (HA) protein plays an important role in binding the influenza virus to infected cells and therefore mediates infection. Deposited HA sequences of 86 Asian strains of influenza A (H1N1) viruses during the first outbreak were obtained from the NCBI database and compared. Interaction of the HA protein of influenza A (H1N1) virus with the human sialic acid receptor was also studied using bioinformatics. Overall, not more than three single-point amino acid variants/changes were observed in the HA protein region of influenza A (H1N1) virus from Asian countries when a selected group sequence comparison was made. The bioinformatics study showed that the HA protein of influenza A (H1N1) binds to the sialic acid receptor in human airway receptors, possibly key to air-borne infection in humans.

  8. Pandemic influenza A (H1N1) virus infection and avian influenza A (H5N1) virus infection: a comparative analysis.

    PubMed

    Korteweg, Christine; Gu, Jiang

    2010-08-01

    The 2009 H1N1 and H5N1 influenza viruses are newly (re-) emerged influenza A viruses (2009 A(H1N1) and A(H5N1), respectively) that have recently posed tremendous health threats in many regions worldwide. With the 2009 outbreak of H1N1 influenza A, the world witnessed the first influenza pandemic of the 21st century. The disease has rapidly spread across the entire globe, and has resulted in hundreds of thousands of cases with confirmed infection. Although characterized by high transmissibility, the virulence and fatality of the 2009 A(H1N1) influenza virus have thus far remained relatively low. The reverse holds true for A(H5N1) influenza; at a fatality rate that exceeds 60%, it is known to cause severe damage to the human respiratory system, but is not presently capable of efficient transmission from human to human. Apart from the clear differences between the two types of influenza, there are some significant similarities that warrant attention. In particular, the more severe and fatal 2009 A(H1N1) influenza cases have shown symptoms similar to those reported in cases of A(H5N1) influenza. Histopathological findings for these cases, to the extent available, also appear to have similarities for both diseases in terms of damage and severity. Here we review important recent publications in this area, and we discuss some of the key commonalities and contrasts between the two influenza A types in terms of their biology, origins, clinical features, pathology and pathogenesis, and receptors and transmissibility.

  9. Investigating the effect of high spring incidence of pandemic influenza A(H1N1) on early autumn incidence.

    PubMed

    Burkom, H; Kniss, K; Meltzer, M; Brammer, L; Elbert, Y; Finelli, L; Swerdlow, D

    2012-12-01

    A pandemic H1N1 infection wave in the USA occurred during spring 2009. Some hypothesized that for regions affected by the spring wave, an autumn outbreak would be less likely or delayed compared to unaffected regions because of herd immunity. We investigated this hypothesis using the Outpatient Influenza-like Illness (ILI) Network, a collaboration among the Centers for Disease Control and Prevention, health departments, and care providers. We evaluated the likelihood of high early autumn incidence given high spring incidence in core-based statistical areas (CBSAs). Using a surrogate incidence measure based on influenza-related illness ratios, we calculated the odds of high early autumn incidence given high spring incidence. CBSAs with high spring ILI ratios proved more likely than unaffected CBSAs to have high early autumn ratios, suggesting that elevated spring illness did not protect against early autumn increases. These novel methods are applicable to planning and studies involving other infectious diseases.

  10. [Clinical characteristics of pediatric patients treated for influenza A (H1N1). The 2009 pandemic in Mexico].

    PubMed

    Fuentes-Pacheco, Yazmín Carmen; Flores-Ruiz, Eric Moisés; Solórzano-Santos, Fortino; Meza-Chávez, Abigail; Zamudio-Lugo, Irma; Vázquez-Rosales, José Guillermo; Miranda-Novales, María Guadalupe

    2014-01-01

    INTRODUCCIÓN: en abril de 2009 se informó por primera vez del virus pandémico de la influenza A H1N1. El objetivo del presente estudio es describir el curso clínico de los pacientes atendidos con enfermedad tipo influenza en un hospital pediátrico de tercer nivel. MÉTODOS: estudio transversal analítico que comprendió el periodo de abril de 2009 a marzo de 2010. La información clínica y demográfica se obtuvo de los expedientes clínicos. El análisis de los datos se llevó a cabo mediante estadística descriptiva e inferencial, para lo cual se aplicó análisis univariado mediante chi cuadrada, prueba exacta de Fisher y U de Mann-Whitney para las variables cuantitativas.

  11. Emergence of a new swine H3N2 and pandemic (H1N1) 2009 influenza A virus reassortant in two Canadian animal populations, mink and swine.

    PubMed

    Tremblay, Donald; Allard, Véronique; Doyon, Jean-François; Bellehumeur, Christian; Spearman, J Grant; Harel, Josée; Gagnon, Carl A

    2011-12-01

    A swine H3N2 (swH3N2) and pandemic (H1N1) 2009 (pH1N1) influenza A virus reassortant (swH3N2/pH1N1) was detected in Canadian swine at the end of 2010. Simultaneously, a similar virus was also detected in Canadian mink based on partial viral genome sequencing. The origin of the new swH3N2/pH1N1 viral genes was related to the North American swH3N2 triple-reassortant cluster IV (for hemagglutinin [HA] and neuraminidase [NA] genes) and to pH1N1 for all the other genes (M, NP, NS, PB1, PB2, and PA). Data indicate that the swH3N2/pH1N1 virus can be found in several pigs that are housed at different locations.

  12. Prevalence, genetics, and transmissibility in ferrets of Eurasian avian-like H1N1 swine influenza viruses.

    PubMed

    Yang, Huanliang; Chen, Yan; Qiao, Chuanling; He, Xijun; Zhou, Hong; Sun, Yu; Yin, Hang; Meng, Shasha; Liu, Liping; Zhang, Qianyi; Kong, Huihui; Gu, Chunyang; Li, Chengjun; Bu, Zhigao; Kawaoka, Yoshihiro; Chen, Hualan

    2016-01-12

    Pigs are important intermediate hosts for generating novel influenza viruses. The Eurasian avian-like H1N1 (EAH1N1) swine influenza viruses (SIVs) have circulated in pigs since 1979, and human cases associated with EAH1N1 SIVs have been reported in several countries. However, the biologic properties of EAH1N1 SIVs are largely unknown. Here, we performed extensive influenza surveillance in pigs in China and isolated 228 influenza viruses from 36,417 pigs. We found that 139 of the 228 strains from pigs in 10 provinces in China belong to the EAH1N1 lineage. These viruses formed five genotypes, with two distinct antigenic groups, represented by A/swine/Guangxi/18/2011 and A/swine/Guangdong/104/2013, both of which are antigenically and genetically distinct from the current human H1N1 viruses. Importantly, the EAH1N1 SIVs preferentially bound to human-type receptors, and 9 of the 10 tested viruses transmitted in ferrets by respiratory droplet. We found that 3.6% of children (≤10 y old), 0% of adults, and 13.4% of elderly adults (≥60 y old) had neutralization antibodies (titers ≥40 in children and ≥80 in adults) against the EAH1N1 A/swine/Guangxi/18/2011 virus, but none of them had such neutralization antibodies against the EAH1N1 A/swine/Guangdong/104/2013 virus. Our study shows the potential of EAH1N1 SIVs to transmit efficiently in humans and suggests that immediate action is needed to prevent the efficient transmission of EAH1N1 SIVs to humans.

  13. Events supposedly attributable to vaccination or immunization during pandemic influenza A (H1N1) vaccination campaigns in Latin America and the Caribbean.

    PubMed

    Ropero-Álvarez, A M; Whittembury, A; Bravo-Alcántara, P; Kurtis, H J; Danovaro-Holliday, M C; Velandia-González, M

    2015-01-01

    As part of the vaccination activities against influenza A[H1N1]pdm vaccine in 2009-2010, countries in Latin American and the Caribbean (LAC) implemented surveillance of events supposedly attributable to vaccines and immunization (ESAVI). We describe the serious ESAVI reported in LAC in order to further document the safety profile of this vaccine and highlight lessons learned. We reviewed data from serious H1N1 ESAVI cases from LAC countries reported to the Pan American Health Organization/World Health Organization. We estimated serious ESAVI rates by age and target group, as well as by clinical diagnosis, and completed descriptive analyses of final outcomes and classifications given in country. A total of 1000 serious ESAVI were reported by 18 of the 29 LAC countries that vaccinated against A[H1N1]pdm. The overall reporting rate in LAC was 6.91 serious ESAVI per million doses, with country reporting rates ranging from 0.77 to 64.68 per million doses. Rates were higher among pregnant women (16.25 per million doses) when compared to health care workers (13.54 per million doses) and individuals with chronic disease (4.03 per million doses). The top three most frequent diagnoses were febrile seizures (12.0%), Guillain-Barré Syndrome (10.5%) and acute pneumonia (8.0%). Almost half (49.1%) of the serious ESAVI were reported among children aged <18 years of age; within this group, the highest proportion of cases was reported among those aged <2 years (53.1%). Of all serious ESAVI reported, 37.8% were classified as coincidental, 35.3% as related to vaccine components, 26.4% as non-conclusive and 0.5% as a programmatic error. This regional overview of A[H1N1]pdm vaccine safety data in LAC estimated the rate of serious ESAVI at lower levels than other studies. However, the ESAVI diagnosis distribution is comparable to the published literature. Lessons learned can be applied in the response to future pandemics.

  14. Psychological response of family members of patients hospitalised for influenza A/H1N1 in Oaxaca, Mexico

    PubMed Central

    2010-01-01

    Background The A/H1N1 pandemic originated in Mexico in April 2009, amid high uncertainty, social and economic disruption, and media reports of panic. The aim of this research project was to evaluate the psychological response of family primary caregivers of patients hospitalised in the Intensive Care Unit (ICU) with suspected influenza A/H1N1 to establish whether there was empirical evidence of high adverse psychological response, and to identify risk factors for such a response. If such evidence was found, a secondary aim was to develop a specific early intervention of psychological support for these individuals, to reduce distress and possibly lessen the likelihood of post-traumatic stress disorder (PTSD) in the longer term. Methods Psychological assessment questionnaires were administered to the family primary caregivers of patients hospitalised in the ICU in the General Hospital of Zone 1 of the Mexican Institute for Social Security (IMSS), Oaxaca, Mexico with suspected influenza A/H1N1, during the month of November 2009. The main outcome measures were ratings of reported perceived stress (PSS-10), depression (CES-D), and death anxiety (DAQ). Data were subjected to simple and multiple linear regression analysis to identify risk factors for adverse psychological response. Results Elevated levels of perceived stress and depression, compared to population normative data, and moderate levels of death anxiety were noted. Levels of depression were similar to those found in comparable studies of family members of ICU patients admitted for other conditions. Multiple regression analysis indicated that increasing age and non-spousal family relationship were significantly associated with depression and perceived stress. Female gender, increasing age, and higher levels of education were significantly associated with high death anxiety. Comparisons with data collected in previous studies in the same hospital ICU with groups affected by a range of other medical conditions

  15. H1N1 influenza viruses varying widely in hemagglutinin stability transmit efficiently from swine to swine and to ferrets

    PubMed Central

    Yang, Guohua; Marinova-Petkova, Atanaska; Kaplan, Bryan S.; Webby, Richard J.

    2017-01-01

    A pandemic-capable influenza virus requires a hemagglutinin (HA) surface glycoprotein that is immunologically unseen by most people and is capable of supporting replication and transmission in humans. HA stabilization has been linked to 2009 pH1N1 pandemic potential in humans and H5N1 airborne transmissibility in the ferret model. Swine have served as an intermediate host for zoonotic influenza viruses, yet the evolutionary pressure exerted by this host on HA stability was unknown. For over 70 contemporary swine H1 and H3 isolates, we measured HA activation pH to range from pH 5.1 to 5.9 for H1 viruses and pH 5.3 to 5.8 for H3 viruses. Thus, contemporary swine isolates vary widely in HA stability, having values favored by both avian (pH >5.5) and human and ferret (pH ≤5.5) species. Using an early 2009 pandemic H1N1 (pH1N1) virus backbone, we generated three viruses differing by one HA residue that only altered HA stability: WT (pH 5.5), HA1-Y17H (pH 6.0), and HA2-R106K (pH 5.3). All three replicated in pigs and transmitted from pig-to-pig and pig-to-ferret. WT and R106 viruses maintained HA genotype and phenotype after transmission. Y17H (pH 6.0) acquired HA mutations that stabilized the HA protein to pH 5.8 after transmission to pigs and 5.5 after transmission to ferrets. Overall, we found swine support a broad range of HA activation pH for contact transmission and many recent swine H1N1 and H3N2 isolates have stabilized (human-like) HA proteins. This constitutes a heightened pandemic risk and underscores the importance of ongoing surveillance and control efforts for swine viruses. PMID:28282440

  16. Evaluation of the Cepheid Xpert Flu Assay for Rapid Identification and Differentiation of Influenza A, Influenza A 2009 H1N1, and Influenza B Viruses

    PubMed Central

    Marlowe, E. M.; Poulter, M.; Dwyer, D.; Speers, D.; Rawlinson, W.; Baleriola, C.; Robinson, C. C.

    2012-01-01

    The Xpert Flu Assay cartridge is a next-generation nucleic acid amplification system that provides multiplexed PCR detection of the influenza A, influenza A 2009 H1N1, and influenza B viruses in approximately 70 min with minimal hands-on time. Six laboratories participated in a clinical trial comparing the results of the new Cepheid Xpert Flu Assay to those of culture or real-time PCR with archived and prospectively collected nasal aspirate-wash (NA-W) specimens and nasopharyngeal (NP) swabs from children and adults. Discrepant results were resolved by DNA sequence analysis. After discrepant-result analysis, the sensitivities of the Xpert Flu Assay for prospective NA-W specimens containing the influenza A, influenza A 2009 H1N1, and influenza B viruses compared to those of culture were 90.0%, 100%, and 100%, respectively, while the sensitivities of the assay for prospective NP swabs compared to those of culture were 100%, 100%, and 100%, respectively. The sensitivities of the Xpert Flu Assay for archived NA-W specimens compared to those of Gen-Probe ProFlu+ PCR for the influenza A, influenza A 2009 H1N1, and influenza B viruses were 99.4%, 98.4%, and 100%, respectively, while the sensitivities of the Xpert Flu Assay for archived NP swabs compared to those of ProFlu+ were 98.1%, 100%, and 93.8%, respectively. The sensitivities of the Xpert Flu Assay with archived NP specimens compared to those of culture for the three targets were 97.5%, 100%, and 93.8%, respectively. We conclude that the Cepheid Xpert Flu Assay is an accurate and rapid method that is suitable for on-demand testing for influenza viral infection. PMID:22378908

  17. Evaluation of the Cepheid Xpert Flu Assay for rapid identification and differentiation of influenza A, influenza A 2009 H1N1, and influenza B viruses.

    PubMed

    Novak-Weekley, S M; Marlowe, E M; Poulter, M; Dwyer, D; Speers, D; Rawlinson, W; Baleriola, C; Robinson, C C

    2012-05-01

    The Xpert Flu Assay cartridge is a next-generation nucleic acid amplification system that provides multiplexed PCR detection of the influenza A, influenza A 2009 H1N1, and influenza B viruses in approximately 70 min with minimal hands-on time. Six laboratories participated in a clinical trial comparing the results of the new Cepheid Xpert Flu Assay to those of culture or real-time PCR with archived and prospectively collected nasal aspirate-wash (NA-W) specimens and nasopharyngeal (NP) swabs from children and adults. Discrepant results were resolved by DNA sequence analysis. After discrepant-result analysis, the sensitivities of the Xpert Flu Assay for prospective NA-W specimens containing the influenza A, influenza A 2009 H1N1, and influenza B viruses compared to those of culture were 90.0%, 100%, and 100%, respectively, while the sensitivities of the assay for prospective NP swabs compared to those of culture were 100%, 100%, and 100%, respectively. The sensitivities of the Xpert Flu Assay for archived NA-W specimens compared to those of Gen-Probe ProFlu+ PCR for the influenza A, influenza A 2009 H1N1, and influenza B viruses were 99.4%, 98.4%, and 100%, respectively, while the sensitivities of the Xpert Flu Assay for archived NP swabs compared to those of ProFlu+ were 98.1%, 100%, and 93.8%, respectively. The sensitivities of the Xpert Flu Assay with archived NP specimens compared to those of culture for the three targets were 97.5%, 100%, and 93.8%, respectively. We conclude that the Cepheid Xpert Flu Assay is an accurate and rapid method that is suitable for on-demand testing for influenza viral infection.

  18. Structural Characterization of the Hemagglutinin Receptor Specificity from the 2009 H1N1 Influenza Pandemic

    SciTech Connect

    Xu, Rui; McBride, Ryan; Nycholat, Corwin M.; Paulson, James C.; Wilson, Ian A.

    2012-02-13

    Influenza virus hemagglutinin (HA) is the viral envelope protein that mediates viral attachment to host cells and elicits membrane fusion. The HA receptor-binding specificity is a key determinant for the host range and transmissibility of influenza viruses. In human pandemics of the 20th century, the HA normally has acquired specificity for human-like receptors before widespread infection. Crystal structures of the H1 HA from the 2009 human pandemic (A/California/04/2009 [CA04]) in complex with human and avian receptor analogs reveal conserved recognition of the terminal sialic acid of the glycan ligands. However, favorable interactions beyond the sialic acid are found only for {alpha}2-6-linked glycans and are mediated by Asp190 and Asp225, which hydrogen bond with Gal-2 and GlcNAc-3. For {alpha}2-3-linked glycan receptors, no specific interactions beyond the terminal sialic acid are observed. Our structural and glycan microarray analyses, in the context of other high-resolution HA structures with {alpha}2-6- and {alpha}2-3-linked glycans, now elucidate the structural basis of receptor-binding specificity for H1 HAs in human and avian viruses and provide a structural explanation for the preference for {alpha}2-6 siaylated glycan receptors for the 2009 pandemic swine flu virus.

  19. Planning and response to the influenza A (H1N1) pandemic: ethics, equity and justice.

    PubMed

    Devnani, Mahesh; Gupta, Anil Kumar; Devnani, Bharti

    2011-01-01

    This paper aims to highlight three ethical considerations related to influenza pandemic planning and response: ethical allocation of scarce resources; obligations and duties of healthcare workers to treat patients, and the balance between conflicting individual and community interests. Among these, perhaps the most challenging question facing bioethics is how to allocate scarce, life-saving resources given the devastating social and economic ramifications of a pandemic. In such situations, the identification of clear overall goals for pandemic planning is essential in making difficult choices. The dilemma between the duty to save patients and the right to protect the healthcare personnel's own life and health is a key issue. During the course of a pandemic, civil liberties may also be threatened, requiring limits on individual freedom to protect individuals as well as entire communities. Yet, individual liberty should be restricted with great care, and only when alternative approaches are not effective. Pandemic influenza planning and response should be a cooperative and shared responsibility that balances community and individual interests.

  20. Association of swine influenza H1N1 pandemic virus (SIV-H1N1p) with porcine respiratory disease complex in sows from commercial pig farms in Colombia.

    PubMed

    Jiménez, Luisa Fernanda Mancipe; Ramírez Nieto, Gloria; Alfonso, Victor Vera; Correa, Jairo Jaime

    2014-08-01

    Porcine respiratory disease complex (PRDC) is a serious health problem that mainly affects growing and finishing pigs. PRDC is caused by a combination of viral and bacterial agents, such as porcine reproductive and respiratory syndrome virus (PRRSV), swine influenza virus (SIV), Mycoplasma hyopneumoniae (Myh), Actinobacillus pleuropneumoniae (APP), Pasteurella multocida and Porcine circovirus 2 (PCV2). To characterize the specific role of swine influenza virus in PRDC presentation in Colombia, 11 farms from three major production regions in Colombia were examined in this study. Nasal swabs, bronchial lavage and lung tissue samples were obtained from animals displaying symptoms compatible with SIV. Isolation of SIV was performed in 9-day embryonated chicken eggs or Madin-Darby Canine Kidney (MDCK) cells. Positive isolates, identified via the hemagglutination inhibition test, were further analyzed using PCR. Overall, 7 of the 11 farms were positive for SIV. Notably, sequencing of the gene encoding the hemagglutinin (HA) protein led to grouping of strains into circulating viruses identified during the human outbreak of 2009, classified as pandemic H1N1-2009. Serum samples from 198 gilts and multiparous sows between 2008 and 2009 were obtained to determine antibody presence of APP, Myh, PCV2 and PRRSV in both SIV-H1N1p-negative and -positive farms, but higher levels were recorded for SIV-H1N1p-positive farms. Odds ratio (OR) and P values revealed statistically significant differences (p<0.05) in PRDC presentation in gilts and multiparous sows of farms positive for SIV-H1N1p. Our findings indicate that positive farms have increased risk of PRDC presentation, in particular, PCV2, APP and Myh.