Science.gov

Sample records for influenza survival transmission

  1. Household Transmission of Influenza Virus.

    PubMed

    Tsang, Tim K; Lau, Lincoln L H; Cauchemez, Simon; Cowling, Benjamin J

    2016-02-01

    Human influenza viruses cause regular epidemics and occasional pandemics with a substantial public health burden. Household transmission studies have provided valuable information on the dynamics of influenza transmission. We reviewed published studies and found that once one household member is infected with influenza, the risk of infection in a household contact can be up to 38%, and the delay between onset in index and secondary cases is around 3 days. Younger age was associated with higher susceptibility. In the future, household transmission studies will provide information on transmission dynamics, including the correlation of virus shedding and symptoms with transmission, and the correlation of new measures of immunity with protection against infection.

  2. Influenza viruses: transmission between species.

    PubMed

    Webster, R G; Hinshaw, V S; Bean, W J; Sriram, G

    1980-02-25

    The only direct evidence for transmission of influenza viruses between species comes from studies on swine influenza viruses. Antigenically and genetically identical Hsw1N1 influenza viruses were isolated from pigs and man on the same farm in Wisconsin, U.S.A. The isolation of H3N2 influenza viruses from a wide range of lower animals and birds suggests that influenza viruses of man can spread to the lower orders. Under some conditions the H3N2 viruses can persist for a number of years in some species. The isolation, from aquatic birds, of a large number of influenza A viruses that possess surface proteins antigenically similar to the viruses isolated from man, pigs and horses provides indirect evidence for inter-species transmission. There is now a considerable body of evidence which suggests that influenza viruses of lower animals and birds may play a role in the origin of some of the pandemic strains of influenza A viruses. There is no direct evidence that the influenza viruses in aquatic birds are transmitted to man, but they may serve as a genetic pool from which some genes may be introduced into humans by recombination. Preliminary evidence suggests that the molecular basis of host range and virulence may be related to the RNA segments coding for one of the polymerase proteins (P3) and for the nucleoprotein (NP).

  3. Transmission of influenza A viruses.

    PubMed

    Neumann, Gabriele; Kawaoka, Yoshihiro

    2015-05-01

    Influenza A viruses cause respiratory infections that range from asymptomatic to deadly in humans. Widespread outbreaks (pandemics) are attributable to 'novel' viruses that possess a viral hemagglutinin (HA) gene to which humans lack immunity. After a pandemic, these novel viruses form stable virus lineages in humans and circulate until they are replaced by other novel viruses. The factors and mechanisms that facilitate virus transmission among hosts and the establishment of novel lineages are not completely understood, but the HA and basic polymerase 2 (PB2) proteins are thought to play essential roles in these processes by enabling avian influenza viruses to infect mammals and replicate efficiently in their new host. Here, we summarize our current knowledge of the contributions of HA, PB2, and other viral components to virus transmission and the formation of new virus lineages.

  4. Transmission of Influenza A Viruses

    PubMed Central

    Neumann, Gabriele; Kawaoka, Yoshihiro

    2015-01-01

    Influenza A viruses cause respiratory infections that range from asymptomatic to deadly in humans. Widespread outbreaks (pandemics) are attributable to ‘novel’ viruses that possess a viral hemagglutinin (HA) gene to which humans lack immunity. After a pandemic, these novel viruses form stable virus lineages in humans and circulate until they are replaced by other novel viruses. The factors and mechanisms that facilitate virus transmission among hosts and the establishment of novel lineages are not completely understood, but the HA and basic polymerase 2 (PB2) proteins are thought to play essential roles in these processes by enabling avian influenza viruses to infect mammals and replicate efficiently in their new host. Here, we summarize our current knowledge of the contributions of HA, PB2, and other viral components to virus transmission and the formation of new virus lineages. PMID:25812763

  5. Influenza Burden and Transmission in the Tropics.

    PubMed

    Ng, Sophia; Gordon, Aubree

    Each year, influenza causes substantial mortality and morbidity worldwide. It is important to understand influenza in the tropics because of the significant burden in the region and its relevance to global influenza circulation. In this review, influenza burden, transmission dynamics, and their determinants in the tropics are discussed. Environmental, cultural, and social conditions in the tropics are very diverse and often differ from those of temperate regions. Theories that account for and predict influenza dynamics in temperate regions do not fully explain influenza epidemic patterns observed in the tropics. Routine surveillance and household studies have been useful in understanding influenza dynamics in the tropics, but these studies have been limited to only some regions; there is still a lack of information regarding influenza burden and transmission dynamics in many tropical countries. Further studies in the tropics will provide useful insight on many questions that remain.

  6. Review Article: Influenza Transmission on Aircraft

    PubMed Central

    Adlhoch, Cornelia

    2016-01-01

    Background: Air travel is associated with the spread of influenza through infected passengers and potentially through in-flight transmission. Contact tracing after exposure to influenza is not performed systematically. We performed a systematic literature review to evaluate the evidence for influenza transmission aboard aircraft. Methods: Using PubMed and EMBASE databases, we identified and critically appraised identified records to assess the evidence of such transmission to passengers seated in close proximity to the index cases. We also developed a bias assessment tool to evaluate the quality of evidence provided in the retrieved studies. Results: We identified 14 peer-reviewed publications describing contact tracing of passengers after possible exposure to influenza virus aboard an aircraft. Contact tracing during the initial phase of the influenza A(H1N1)pdm09 pandemic was described in 11 publications. The studies describe the follow-up of 2,165 (51%) of 4,252 traceable passengers. Altogether, 163 secondary cases were identified resulting in an overall secondary attack rate among traced passengers of 7.5%. Of these secondary cases, 68 (42%) were seated within two rows of the index case. Conclusion: We found an overall moderate quality of evidence for transmission of influenza virus aboard an aircraft. The major limiting factor was the comparability of the studies. A majority of secondary cases was identified at a greater distance than two rows from the index case. A standardized approach for initiating, conducting, and reporting contact tracing could help to increase the evidence base for better assessing influenza transmission aboard aircraft. PMID:27253070

  7. [Transmissibility and pathogenicity of influenza viruses].

    PubMed

    Horimoto, Taisuke; Yamada, Shinya; Kawaoka, Yoshihiro

    2010-09-01

    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. Molecular analyses of the pandemic H1N1 2009 viruses indicate low-pathogenic features for humans, although worldwide transmission of the virus and a considerable numbers of lethal cases with acute pneumonia have been observed in the first wave of the current pandemic. Here, we review our current molecular knowledge of transmissibility and pathogenicity of influenza viruses and discuss the future aspects of the pandemic virus.

  8. Can Antiviral Drugs Contain Pandemic Influenza Transmission?

    PubMed Central

    Becker, Niels G.; Wang, Dingcheng

    2011-01-01

    Antiviral drugs dispensed during the 2009 influenza pandemic generally failed to contain transmission. This poses the question of whether preparedness for a future pandemic should include plans to use antiviral drugs to mitigate transmission. Simulations using a standard transmission model that allows for infected arrivals and delayed vaccination show that attempts to contain transmission require relatively few antiviral doses. In contrast, persistent use of antiviral drugs when the reproduction number remains above 1 use very many doses and are unlikely to reduce the eventual attack rate appreciably unless the stockpile is very large. A second model, in which the community has a household structure, shows that the effectiveness of a strategy of dispensing antiviral drugs to infected households decreases rapidly with time delays in dispensing the antivirals. Using characteristics of past pandemics it is estimated that at least 80% of primary household cases must present upon show of symptoms to have a chance of containing transmission by dispensing antiviral drugs to households. To determine data needs, household outbreaks were simulated with 50% receiving antiviral drugs early and 50% receiving antiviral drugs late. A test to compare the size of household outbreaks indicates that at least 100–200 household outbreaks need to be monitored to find evidence that antiviral drugs can mitigate transmission of the newly emerged virus. Use of antiviral drugs in an early attempt to contain transmission should be part of preparedness plans for a future influenza pandemic. Data on the incidence of the first 350 cases and the eventual attack rates of the first 200 hundred household outbreaks should be used to estimate the initial reproduction number R and the effectiveness of antiviral drugs to mitigate transmission. Use of antiviral drugs to mitigate general transmission should cease if these estimates indicate that containment of transmission is unlikely. PMID:21464934

  9. Quantifying the transmission potential of pandemic influenza

    NASA Astrophysics Data System (ADS)

    Chowell, Gerardo; Nishiura, Hiroshi

    2008-03-01

    This article reviews quantitative methods to estimate the basic reproduction number of pandemic influenza, a key threshold quantity to help determine the intensity of interventions required to control the disease. Although it is difficult to assess the transmission potential of a probable future pandemic, historical epidemiologic data is readily available from previous pandemics, and as a reference quantity for future pandemic planning, mathematical and statistical analyses of historical data are crucial. In particular, because many historical records tend to document only the temporal distribution of cases or deaths (i.e. epidemic curve), our review focuses on methods to maximize the utility of time-evolution data and to clarify the detailed mechanisms of the spread of influenza. First, we highlight structured epidemic models and their parameter estimation method which can quantify the detailed disease dynamics including those we cannot observe directly. Duration-structured epidemic systems are subsequently presented, offering firm understanding of the definition of the basic and effective reproduction numbers. When the initial growth phase of an epidemic is investigated, the distribution of the generation time is key statistical information to appropriately estimate the transmission potential using the intrinsic growth rate. Applications of stochastic processes are also highlighted to estimate the transmission potential using similar data. Critically important characteristics of influenza data are subsequently summarized, followed by our conclusions to suggest potential future methodological improvements.

  10. Influenza transmission during extreme indoor conditions in a low-resource tropical setting

    NASA Astrophysics Data System (ADS)

    Tamerius, James; Ojeda, Sergio; Uejio, Christopher K.; Shaman, Jeffrey; Lopez, Brenda; Sanchez, Nery; Gordon, Aubree

    2017-04-01

    Influenza transmission occurs throughout the planet across wide-ranging environmental conditions. However, our understanding of the environmental factors mediating transmission is evaluated using outdoor environmental measurements, which may not be representative of the indoor conditions where influenza is transmitted. In this study, we examined the relationship between indoor environment and influenza transmission in a low-resource tropical population. We used a case-based ascertainment design to enroll 34 households with a suspected influenza case and then monitored households for influenza, while recording indoor temperature and humidity data in each household. We show that the indoor environment is not commensurate with outdoor conditions and that the relationship between indoor and outdoor conditions varies significantly across homes. We also show evidence of influenza transmission in extreme indoor environments. Specifically, our data suggests that indoor environments averaged 29 °C, 18 g/kg specific humidity, and 68 % relative humidity across 15 transmission events observed. These indoor settings also exhibited significant temporal variability with temperatures as high as 39 °C and specific and relative humidity increasing to 22 g/kg and 85 %, respectively, during some transmission events. However, we were unable to detect differences in the transmission efficiency by indoor temperature or humidity conditions. Overall, these results indicate that laboratory studies investigating influenza transmission and virus survival should increase the range of environmental conditions that they assess and that observational studies investigating the relationship between environment and influenza activity should use caution using outdoor environmental measurements since they can be imprecise estimates of the conditions that mediate transmission indoors.

  11. Influenza transmission during extreme indoor conditions in a low-resource tropical setting

    NASA Astrophysics Data System (ADS)

    Tamerius, James; Ojeda, Sergio; Uejio, Christopher K.; Shaman, Jeffrey; Lopez, Brenda; Sanchez, Nery; Gordon, Aubree

    2016-08-01

    Influenza transmission occurs throughout the planet across wide-ranging environmental conditions. However, our understanding of the environmental factors mediating transmission is evaluated using outdoor environmental measurements, which may not be representative of the indoor conditions where influenza is transmitted. In this study, we examined the relationship between indoor environment and influenza transmission in a low-resource tropical population. We used a case-based ascertainment design to enroll 34 households with a suspected influenza case and then monitored households for influenza, while recording indoor temperature and humidity data in each household. We show that the indoor environment is not commensurate with outdoor conditions and that the relationship between indoor and outdoor conditions varies significantly across homes. We also show evidence of influenza transmission in extreme indoor environments. Specifically, our data suggests that indoor environments averaged 29 °C, 18 g/kg specific humidity, and 68 % relative humidity across 15 transmission events observed. These indoor settings also exhibited significant temporal variability with temperatures as high as 39 °C and specific and relative humidity increasing to 22 g/kg and 85 %, respectively, during some transmission events. However, we were unable to detect differences in the transmission efficiency by indoor temperature or humidity conditions. Overall, these results indicate that laboratory studies investigating influenza transmission and virus survival should increase the range of environmental conditions that they assess and that observational studies investigating the relationship between environment and influenza activity should use caution using outdoor environmental measurements since they can be imprecise estimates of the conditions that mediate transmission indoors.

  12. Mapping influenza transmission in the ferret model to transmission in humans.

    PubMed

    Buhnerkempe, Michael G; Gostic, Katelyn; Park, Miran; Ahsan, Prianna; Belser, Jessica A; Lloyd-Smith, James O

    2015-09-02

    The controversy surrounding 'gain-of-function' experiments on high-consequence avian influenza viruses has highlighted the role of ferret transmission experiments in studying the transmission potential of novel influenza strains. However, the mapping between influenza transmission in ferrets and in humans is unsubstantiated. We address this gap by compiling and analyzing 240 estimates of influenza transmission in ferrets and humans. We demonstrate that estimates of ferret secondary attack rate (SAR) explain 66% of the variation in human SAR estimates at the subtype level. Further analysis shows that ferret transmission experiments have potential to identify influenza viruses of concern for epidemic spread in humans, though small sample sizes and biological uncertainties prevent definitive classification of human transmissibility. Thus, ferret transmission experiments provide valid predictions of pandemic potential of novel influenza strains, though results should continue to be corroborated by targeted virological and epidemiological research.

  13. Mapping influenza transmission in the ferret model to transmission in humans

    PubMed Central

    Buhnerkempe, Michael G; Gostic, Katelyn; Park, Miran; Ahsan, Prianna; Belser, Jessica A; Lloyd-Smith, James O

    2015-01-01

    The controversy surrounding 'gain-of-function' experiments on high-consequence avian influenza viruses has highlighted the role of ferret transmission experiments in studying the transmission potential of novel influenza strains. However, the mapping between influenza transmission in ferrets and in humans is unsubstantiated. We address this gap by compiling and analyzing 240 estimates of influenza transmission in ferrets and humans. We demonstrate that estimates of ferret secondary attack rate (SAR) explain 66% of the variation in human SAR estimates at the subtype level. Further analysis shows that ferret transmission experiments have potential to identify influenza viruses of concern for epidemic spread in humans, though small sample sizes and biological uncertainties prevent definitive classification of human transmissibility. Thus, ferret transmission experiments provide valid predictions of pandemic potential of novel influenza strains, though results should continue to be corroborated by targeted virological and epidemiological research. DOI: http://dx.doi.org/10.7554/eLife.07969.001 PMID:26329460

  14. Replication and transmission of influenza viruses in Japanese quail

    PubMed Central

    Makarova, Natalia V.; Ozaki, Hiroishi; Kida, Hiroshi; Webster, Robert G.; Perez, Daniel R.

    2015-01-01

    Quail have emerged as a potential intermediate host in the spread of avian influenza A viruses in poultry in Hong Kong. To better understand this possible role, we tested the replication and transmission in quail of influenza A viruses of all 15 HA subtypes. Quail supported the replication of at least 14 subtypes. Influenza A viruses replicated predominantly in the respiratory tract. Transmission experiments suggested that perpetuation of avian influenza viruses in quail requires adaptation. Swine influenza viruses were isolated from the respiratory tract of quail at low levels. There was no evidence of human influenza A or B virus replication. Interestingly, a human–avian recombinant containing the surface glycoprotein genes of a quail virus and the internal genes of a human virus replicated and transmitted readily in quail; therefore, quail could function as amplifiers of influenza virus reassortants that have the potential to infect humans and/or other mammalian species. PMID:12788625

  15. Avian Influenza spread and transmission dynamics

    USGS Publications Warehouse

    Bourouiba, Lydia; Gourley, Stephen A.; Liu, Rongsong; Takekawa, John Y.; Wu, Jianhong; Chen, Dongmei; Moulin, Bernard; Wu, Jianhong

    2015-01-01

    The spread of highly pathogenic avian influenza (HPAI) viruses of type A of subtype H5N1 has been a serious threat to global public health. Understanding the roles of various (migratory, wild, poultry) bird species in the transmission of these viruses is critical for designing and implementing effective control and intervention measures. Developing appropriate models and mathematical techniques to understand these roles and to evaluate the effectiveness of mitigation strategies have been a challenge. Recent development of the global health surveillance (especially satellite tracking and GIS techniques) and the mathematical theory of dynamical systems combined have gradually shown the promise of some cutting-edge methodologies and techniques in mathematical biology to meet this challenge.

  16. Transmission of influenza B viruses in the guinea pig.

    PubMed

    Pica, Natalie; Chou, Yi-Ying; Bouvier, Nicole M; Palese, Peter

    2012-04-01

    Epidemic influenza is typically caused by infection with viruses of the A and B types and can result in substantial morbidity and mortality during a given season. Here we demonstrate that influenza B viruses can replicate in the upper respiratory tract of the guinea pig and that viruses of the two main lineages can be transmitted with 100% efficiency between inoculated and naïve animals in both contact and noncontact models. Our results also indicate that, like in the case for influenza A virus, transmission of influenza B viruses is enhanced at colder temperatures, providing an explanation for the seasonality of influenza epidemics in temperate climates. We therefore present, for the first time, a small animal model with which to study the underlying mechanisms of influenza B virus transmission.

  17. Estimating parameter of influenza transmission using regularized least square

    NASA Astrophysics Data System (ADS)

    Nuraini, N.; Syukriah, Y.; Indratno, S. W.

    2014-02-01

    Transmission process of influenza can be presented in a mathematical model as a non-linear differential equations system. In this model the transmission of influenza is determined by the parameter of contact rate of the infected host and susceptible host. This parameter will be estimated using a regularized least square method where the Finite Element Method and Euler Method are used for approximating the solution of the SIR differential equation. The new infected data of influenza from CDC is used to see the effectiveness of the method. The estimated parameter represents the contact rate proportion of transmission probability in a day which can influence the number of infected people by the influenza. Relation between the estimated parameter and the number of infected people by the influenza is measured by coefficient of correlation. The numerical results show positive correlation between the estimated parameters and the infected people.

  18. Influenza Virus Transmission from Horses to Dogs, Australia

    PubMed Central

    Finlaison, Deborah S.; Crispe, Ellie; Hurt, Aeron C.

    2010-01-01

    During the 2007 equine influenza outbreak in Australia, respiratory disease in dogs in close contact with infected horses was noted; influenza (H3N8) virus infection was confirmed. Nucleotide sequence of the virus from dogs was identical to that from horses. No evidence of dog-to-dog transmission or virus persistence in dogs was found. PMID:20350392

  19. Modes of Transmission of Influenza B Virus in Households

    PubMed Central

    Cowling, Benjamin J.; Ip, Dennis K. M.; Fang, Vicky J.; Suntarattiwong, Piyarat; Olsen, Sonja J.; Levy, Jens; Uyeki, Timothy M.; Leung, Gabriel M.; Peiris, J. S. Malik; Chotpitayasunondh, Tawee; Nishiura, Hiroshi; Simmerman, J. Mark

    2014-01-01

    Introduction While influenza A and B viruses can be transmitted via respiratory droplets, the importance of small droplet nuclei “aerosols” in transmission is controversial. Methods and Findings In Hong Kong and Bangkok, in 2008–11, subjects were recruited from outpatient clinics if they had recent onset of acute respiratory illness and none of their household contacts were ill. Following a positive rapid influenza diagnostic test result, subjects were randomly allocated to one of three household-based interventions: hand hygiene, hand hygiene plus face masks, and a control group. Index cases plus their household contacts were followed for 7–10 days to identify secondary infections by reverse transcription polymerase chain reaction (RT-PCR) testing of respiratory specimens. Index cases with RT-PCR-confirmed influenza B were included in the present analyses. We used a mathematical model to make inferences on the modes of transmission, facilitated by apparent differences in clinical presentation of secondary infections resulting from aerosol transmission. We estimated that approximately 37% and 26% of influenza B virus transmission was via the aerosol mode in households in Hong Kong and Bangkok, respectively. In the fitted model, influenza B virus infections were associated with a 56%–72% risk of fever plus cough if infected via aerosol route, and a 23%–31% risk of fever plus cough if infected via the other two modes of transmission. Conclusions Aerosol transmission may be an important mode of spread of influenza B virus. The point estimates of aerosol transmission were slightly lower for influenza B virus compared to previously published estimates for influenza A virus in both Hong Kong and Bangkok. Caution should be taken in interpreting these findings because of the multiple assumptions inherent in the model, including that there is limited biological evidence to date supporting a difference in the clinical features of influenza B virus infection by

  20. The influence of meteorology on the spread of influenza: survival analysis of an equine influenza (A/H3N8) outbreak.

    PubMed

    Firestone, Simon M; Cogger, Naomi; Ward, Michael P; Toribio, Jenny-Ann L M L; Moloney, Barbara J; Dhand, Navneet K

    2012-01-01

    The influences of relative humidity and ambient temperature on the transmission of influenza A viruses have recently been established under controlled laboratory conditions. The interplay of meteorological factors during an actual influenza epidemic is less clear, and research into the contribution of wind to epidemic spread is scarce. By applying geostatistics and survival analysis to data from a large outbreak of equine influenza (A/H3N8), we quantified the association between hazard of infection and air temperature, relative humidity, rainfall, and wind velocity, whilst controlling for premises-level covariates. The pattern of disease spread in space and time was described using extraction mapping and instantaneous hazard curves. Meteorological conditions at each premises location were estimated by kriging daily meteorological data and analysed as time-lagged time-varying predictors using generalised Cox regression. Meteorological covariates time-lagged by three days were strongly associated with hazard of influenza infection, corresponding closely with the incubation period of equine influenza. Hazard of equine influenza infection was higher when relative humidity was <60% and lowest on days when daily maximum air temperature was 20-25°C. Wind speeds >30 km hour(-1) from the direction of nearby infected premises were associated with increased hazard of infection. Through combining detailed influenza outbreak and meteorological data, we provide empirical evidence for the underlying environmental mechanisms that influenced the local spread of an outbreak of influenza A. Our analysis supports, and extends, the findings of studies into influenza A transmission conducted under laboratory conditions. The relationships described are of direct importance for managing disease risk during influenza outbreaks in horses, and more generally, advance our understanding of the transmission of influenza A viruses under field conditions.

  1. The Influence of Meteorology on the Spread of Influenza: Survival Analysis of an Equine Influenza (A/H3N8) Outbreak

    PubMed Central

    Firestone, Simon M.; Cogger, Naomi; Ward, Michael P.; Toribio, Jenny-Ann L. M. L.; Moloney, Barbara J.; Dhand, Navneet K.

    2012-01-01

    The influences of relative humidity and ambient temperature on the transmission of influenza A viruses have recently been established under controlled laboratory conditions. The interplay of meteorological factors during an actual influenza epidemic is less clear, and research into the contribution of wind to epidemic spread is scarce. By applying geostatistics and survival analysis to data from a large outbreak of equine influenza (A/H3N8), we quantified the association between hazard of infection and air temperature, relative humidity, rainfall, and wind velocity, whilst controlling for premises-level covariates. The pattern of disease spread in space and time was described using extraction mapping and instantaneous hazard curves. Meteorological conditions at each premises location were estimated by kriging daily meteorological data and analysed as time-lagged time-varying predictors using generalised Cox regression. Meteorological covariates time-lagged by three days were strongly associated with hazard of influenza infection, corresponding closely with the incubation period of equine influenza. Hazard of equine influenza infection was higher when relative humidity was <60% and lowest on days when daily maximum air temperature was 20–25°C. Wind speeds >30 km hour−1 from the direction of nearby infected premises were associated with increased hazard of infection. Through combining detailed influenza outbreak and meteorological data, we provide empirical evidence for the underlying environmental mechanisms that influenced the local spread of an outbreak of influenza A. Our analysis supports, and extends, the findings of studies into influenza A transmission conducted under laboratory conditions. The relationships described are of direct importance for managing disease risk during influenza outbreaks in horses, and more generally, advance our understanding of the transmission of influenza A viruses under field conditions. PMID:22536366

  2. Animal Models for Influenza Virus Pathogenesis and Transmission

    PubMed Central

    Bouvier, Nicole M.; Lowen, Anice C.

    2010-01-01

    Influenza virus infection of humans results in a respiratory disease that ranges in severity from sub-clinical infection to primary viral pneumonia that can result in death. The clinical effects of infection vary with the exposure history, age and immune status of the host, and also the virulence of the influenza strain. In humans, the virus is transmitted through either aerosol or contact-based transfer of infectious respiratory secretions. As is evidenced by most zoonotic influenza virus infections, not all strains that can infect humans are able to transmit from person-to-person. Animal models of influenza are essential to research efforts aimed at understanding the viral and host factors that contribute to the disease and transmission outcomes of influenza virus infection in humans. These models furthermore allow the pre-clinical testing of antiviral drugs and vaccines aimed at reducing morbidity and mortality in the population through amelioration of the virulence or transmissibility of influenza viruses. Mice, ferrets, guinea pigs, cotton rats, hamsters and macaques have all been used to study influenza viruses and therapeutics targeting them. Each model presents unique advantages and disadvantages, which will be discussed herein. PMID:21442033

  3. Influenza transmission in households during the 1918 pandemic.

    PubMed

    Fraser, Christophe; Cummings, Derek A T; Klinkenberg, Don; Burke, Donald S; Ferguson, Neil M

    2011-09-01

    Analysis of historical data has strongly shaped our understanding of the epidemiology of pandemic influenza and informs analysis of current and future epidemics. Here, the authors analyzed previously unpublished documents from a large household survey of the "Spanish" H1N1 influenza pandemic, conducted in 1918, for the first time quantifying influenza transmissibility at the person-to-person level during that most lethal of pandemics. The authors estimated a low probability of person-to-person transmission relative to comparable estimates from seasonal influenza and other directly transmitted infections but similar to recent estimates from the 2009 H1N1 pandemic. The authors estimated a very low probability of asymptomatic infection, a previously unknown parameter for this pandemic, consistent with an unusually virulent virus. The authors estimated a high frequency of prior immunity that they attributed to a largely unreported influenza epidemic in the spring of 1918 (or perhaps to cross-reactive immunity). Extrapolating from this finding, the authors hypothesize that prior immunity partially protected some populations from the worst of the fall pandemic and helps explain differences in attack rates between populations. Together, these analyses demonstrate that the 1918 influenza virus, though highly virulent, was only moderately transmissible and thus in a modern context would be considered controllable.

  4. Influenza Transmission in Households During the 1918 Pandemic

    PubMed Central

    Fraser, Christophe; Cummings, Derek A. T.; Klinkenberg, Don; Burke, Donald S.; Ferguson, Neil M.

    2011-01-01

    Analysis of historical data has strongly shaped our understanding of the epidemiology of pandemic influenza and informs analysis of current and future epidemics. Here, the authors analyzed previously unpublished documents from a large household survey of the “Spanish” H1N1 influenza pandemic, conducted in 1918, for the first time quantifying influenza transmissibility at the person-to-person level during that most lethal of pandemics. The authors estimated a low probability of person-to-person transmission relative to comparable estimates from seasonal influenza and other directly transmitted infections but similar to recent estimates from the 2009 H1N1 pandemic. The authors estimated a very low probability of asymptomatic infection, a previously unknown parameter for this pandemic, consistent with an unusually virulent virus. The authors estimated a high frequency of prior immunity that they attributed to a largely unreported influenza epidemic in the spring of 1918 (or perhaps to cross-reactive immunity). Extrapolating from this finding, the authors hypothesize that prior immunity partially protected some populations from the worst of the fall pandemic and helps explain differences in attack rates between populations. Together, these analyses demonstrate that the 1918 influenza virus, though highly virulent, was only moderately transmissible and thus in a modern context would be considered controllable. PMID:21749971

  5. Vaccination of influenza a virus decreases transmission rates in pigs.

    PubMed

    Romagosa, Anna; Allerson, Matt; Gramer, Marie; Joo, Han Soo; Deen, John; Detmer, Susan; Torremorell, Montserrat

    2011-12-20

    Limited information is available on the transmission and spread of influenza virus in pig populations with differing immune statuses. In this study we assessed differences in transmission patterns and quantified the spread of a triple reassortant H1N1 influenza virus in naïve and vaccinated pig populations by estimating the reproduction ratio (R) of infection (i.e. the number of secondary infections caused by an infectious individual) using a deterministic Susceptible-Infectious-Recovered (SIR) model, fitted on experimental data. One hundred and ten pigs were distributed in ten isolated rooms as follows: (i) non-vaccinated (NV), (ii) vaccinated with a heterologous vaccine (HE), and (iii) vaccinated with a homologous inactivated vaccine (HO). The study was run with multiple replicates and for each replicate, an infected non-vaccinated pig was placed with 10 contact pigs for two weeks and transmission of influenza evaluated daily by analyzing individual nasal swabs by RT-PCR. A statistically significant difference between R estimates was observed between vaccinated and non-vaccinated pigs (p < 0.05). A statistically significant reduction in transmission was observed in the vaccinated groups where R (95%CI) was 1 (0.39-2.09) and 0 for the HE and the HO groups respectively, compared to an Ro value of 10.66 (6.57-16.46) in NV pigs (p < 0.05). Transmission in the HE group was delayed and variable when compared to the NV group and transmission could not be detected in the HO group. Results from this study indicate that influenza vaccines can be used to decrease susceptibility to influenza infection and decrease influenza transmission.

  6. Vaccination of influenza a virus decreases transmission rates in pigs

    PubMed Central

    2011-01-01

    Limited information is available on the transmission and spread of influenza virus in pig populations with differing immune statuses. In this study we assessed differences in transmission patterns and quantified the spread of a triple reassortant H1N1 influenza virus in naïve and vaccinated pig populations by estimating the reproduction ratio (R) of infection (i.e. the number of secondary infections caused by an infectious individual) using a deterministic Susceptible-Infectious-Recovered (SIR) model, fitted on experimental data. One hundred and ten pigs were distributed in ten isolated rooms as follows: (i) non-vaccinated (NV), (ii) vaccinated with a heterologous vaccine (HE), and (iii) vaccinated with a homologous inactivated vaccine (HO). The study was run with multiple replicates and for each replicate, an infected non-vaccinated pig was placed with 10 contact pigs for two weeks and transmission of influenza evaluated daily by analyzing individual nasal swabs by RT-PCR. A statistically significant difference between R estimates was observed between vaccinated and non-vaccinated pigs (p < 0.05). A statistically significant reduction in transmission was observed in the vaccinated groups where R (95%CI) was 1 (0.39-2.09) and 0 for the HE and the HO groups respectively, compared to an Ro value of 10.66 (6.57-16.46) in NV pigs (p < 0.05). Transmission in the HE group was delayed and variable when compared to the NV group and transmission could not be detected in the HO group. Results from this study indicate that influenza vaccines can be used to decrease susceptibility to influenza infection and decrease influenza transmission. PMID:22185601

  7. The Role of Environmental Transmission in Recurrent Avian Influenza Epidemics

    PubMed Central

    Breban, Romulus; Drake, John M.; Stallknecht, David E.; Rohani, Pejman

    2009-01-01

    Avian influenza virus (AIV) persists in North American wild waterfowl, exhibiting major outbreaks every 2–4 years. Attempts to explain the patterns of periodicity and persistence using simple direct transmission models are unsuccessful. Motivated by empirical evidence, we examine the contribution of an overlooked AIV transmission mode: environmental transmission. It is known that infectious birds shed large concentrations of virions in the environment, where virions may persist for a long time. We thus propose that, in addition to direct fecal/oral transmission, birds may become infected by ingesting virions that have long persisted in the environment. We design a new host–pathogen model that combines within-season transmission dynamics, between-season migration and reproduction, and environmental variation. Analysis of the model yields three major results. First, environmental transmission provides a persistence mechanism within small communities where epidemics cannot be sustained by direct transmission only (i.e., communities smaller than the critical community size). Second, environmental transmission offers a parsimonious explanation of the 2–4 year periodicity of avian influenza epidemics. Third, very low levels of environmental transmission (i.e., few cases per year) are sufficient for avian influenza to persist in populations where it would otherwise vanish. PMID:19360126

  8. Effect of the One-Child Policy on Influenza Transmission in China: A Stochastic Transmission Model

    PubMed Central

    Liu, Fengchen; Enanoria, Wayne T. A.; Ray, Kathryn J.; Coffee, Megan P.; Gordon, Aubree; Aragón, Tomás J.; Yu, Guowei; Cowling, Benjamin J.; Porco, Travis C.

    2014-01-01

    Background China's one-child-per-couple policy, introduced in 1979, led to profound demographic changes for nearly a quarter of the world's population. Several decades later, the consequences include decreased fertility rates, population aging, decreased household sizes, changes in family structure, and imbalanced sex ratios. The epidemiology of communicable diseases may have been affected by these changes since the transmission dynamics of infectious diseases depend on demographic characteristics of the population. Of particular interest is influenza because China and Southeast Asia lie at the center of a global transmission network of influenza. Moreover, changes in household structure may affect influenza transmission. Is it possible that the pronounced demographic changes that have occurred in China have affected influenza transmission? Methods and Findings To address this question, we developed a continuous-time, stochastic, individual-based simulation model for influenza transmission. With this model, we simulated 30 years of influenza transmission and compared influenza transmission rates in populations with and without the one-child policy control. We found that the average annual attack rate is reduced by 6.08% (SD 2.21%) in the presence of the one-child policy compared to a population in which no demographic changes occurred. There was no discernible difference in the secondary attack rate, −0.15% (SD 1.85%), between the populations with and without a one-child policy. We also forecasted influenza transmission over a ten-year time period in a population with a two-child policy under a hypothesis that a two-child-per-couple policy will be carried out in 2015, and found a negligible difference in the average annual attack rate compared to the population with the one-child policy. Conclusions This study found that the average annual attack rate is slightly lowered in a population with a one-child policy, which may have resulted from a decrease in household

  9. Animal models for influenza virus transmission studies: A historical perspective

    PubMed Central

    Bouvier, Nicole M.

    2015-01-01

    Animal models are used to simulate, under experimental conditions, the complex interactions among host, virus, and environment that affect the person-to-person spread of influenza viruses. The three species that have been most frequently employed, both past and present, as influenza virus transmission models -- ferrets, mice, and guinea pigs -- have each provided unique insights into the factors governing the efficiency with which these viruses pass from an infected host to a susceptible one. This review will highlight a few of these noteworthy discoveries, with a particular focus on the historical contexts in which each model was developed and the advantages and disadvantages of each species with regard to the study of influenza virus transmission among mammals. PMID:26126082

  10. Global transmission of influenza viruses from humans to swine

    PubMed Central

    Gramer, Marie R.; Vincent, Amy L.; Holmes, Edward C.

    2012-01-01

    To determine the extent to which influenza viruses jump between human and swine hosts, we undertook a large-scale phylogenetic analysis of pandemic A/H1N1/09 (H1N1pdm09) influenza virus genome sequence data. From this, we identified at least 49 human-to-swine transmission events that occurred globally during 2009–2011, thereby highlighting the ability of the H1N1pdm09 virus to transmit repeatedly from humans to swine, even following adaptive evolution in humans. Similarly, we identified at least 23 separate introductions of human seasonal (non-pandemic) H1 and H3 influenza viruses into swine globally since 1990. Overall, these results reveal the frequency with which swine are exposed to human influenza viruses, indicate that humans make a substantial contribution to the genetic diversity of influenza viruses in swine, and emphasize the need to improve biosecurity measures at the human–swine interface, including influenza vaccination of swine workers. PMID:22791604

  11. Predictors of indoor absolute humidity and estimated effects on influenza virus survival in grade schools.

    PubMed

    Koep, Tyler H; Enders, Felicity T; Pierret, Chris; Ekker, Stephen C; Krageschmidt, Dale; Neff, Kevin L; Lipsitch, Marc; Shaman, Jeffrey; Huskins, W Charles

    2013-02-05

    Low absolute humidity (AH) has been associated with increased influenza virus survival and transmissibility and the onset of seasonal influenza outbreaks. Humidification of indoor environments may mitigate viral transmission and may be an important control strategy, particularly in schools where viral transmission is common and contributes to the spread of influenza in communities. However, the variability and predictors of AH in the indoor school environment and the feasibility of classroom humidification to levels that could decrease viral survival have not been studied. Automated sensors were used to measure temperature, humidity and CO2 levels in two Minnesota grade schools without central humidification during two successive winters. Outdoor AH measurements were derived from the North American Land Data Assimilation System. Variability in indoor AH within classrooms, between classrooms in the same school, and between schools was assessed using concordance correlation coefficients (CCC). Predictors of indoor AH were examined using time-series Auto-Regressive Conditional Heteroskedasticity models. Classroom humidifiers were used when school was not in session to assess the feasibility of increasing indoor AH to levels associated with decreased influenza virus survival, as projected from previously published animal experiments. AH varied little within classrooms (CCC >0.90) but was more variable between classrooms in the same school (CCC 0.81 for School 1, 0.88 for School 2) and between schools (CCC 0.81). Indoor AH varied widely during the winter (range 2.60 to 10.34 millibars [mb]) and was strongly associated with changes in outdoor AH (p < 0.001). Changes in indoor AH on school weekdays were strongly associated with CO2 levels (p < 0.001). Over 4 hours, classroom humidifiers increased indoor AH by 4 mb, an increase sufficient to decrease projected 1-hour virus survival by an absolute value of 30% during winter months. During winter, indoor AH in non

  12. Predictors of indoor absolute humidity and estimated effects on influenza virus survival in grade schools

    PubMed Central

    2013-01-01

    Background Low absolute humidity (AH) has been associated with increased influenza virus survival and transmissibility and the onset of seasonal influenza outbreaks. Humidification of indoor environments may mitigate viral transmission and may be an important control strategy, particularly in schools where viral transmission is common and contributes to the spread of influenza in communities. However, the variability and predictors of AH in the indoor school environment and the feasibility of classroom humidification to levels that could decrease viral survival have not been studied. Methods Automated sensors were used to measure temperature, humidity and CO2 levels in two Minnesota grade schools without central humidification during two successive winters. Outdoor AH measurements were derived from the North American Land Data Assimilation System. Variability in indoor AH within classrooms, between classrooms in the same school, and between schools was assessed using concordance correlation coefficients (CCC). Predictors of indoor AH were examined using time-series Auto-Regressive Conditional Heteroskedasticity models. Classroom humidifiers were used when school was not in session to assess the feasibility of increasing indoor AH to levels associated with decreased influenza virus survival, as projected from previously published animal experiments. Results AH varied little within classrooms (CCC >0.90) but was more variable between classrooms in the same school (CCC 0.81 for School 1, 0.88 for School 2) and between schools (CCC 0.81). Indoor AH varied widely during the winter (range 2.60 to 10.34 millibars [mb]) and was strongly associated with changes in outdoor AH (p < 0.001). Changes in indoor AH on school weekdays were strongly associated with CO2 levels (p < 0.001). Over 4 hours, classroom humidifiers increased indoor AH by 4 mb, an increase sufficient to decrease projected 1-hour virus survival by an absolute value of 30% during winter months

  13. The risk of airborne influenza transmission in passenger cars.

    PubMed

    Knibbs, L D; Morawska, L; Bell, S C

    2012-03-01

    Travel in passenger cars is a ubiquitous aspect of the daily activities of many people. During the 2009 influenza A(H1N1) pandemic a case of probable transmission during car travel was reported in Australia, to which spread via the airborne route may have contributed. However, there are no data to indicate the likely risks of such events, and how they may vary and be mitigated. To address this knowledge gap, we estimated the risk of airborne influenza transmission in two cars (1989 model and 2005 model) by employing ventilation measurements and a variation of the Wells-Riley model. Results suggested that infection risk can be reduced by not recirculating air; however, estimated risk ranged from 59% to 99·9% for a 90-min trip when air was recirculated in the newer vehicle. These results have implications for interrupting in-car transmission of other illnesses spread by the airborne route.

  14. Complexities in Ferret Influenza Virus Pathogenesis and Transmission Models

    PubMed Central

    Eckert, Alissa M.; Tumpey, Terrence M.; Maines, Taronna R.

    2016-01-01

    SUMMARY Ferrets are widely employed to study the pathogenicity, transmissibility, and tropism of influenza viruses. However, inherent variations in inoculation methods, sampling schemes, and experimental designs are often overlooked when contextualizing or aggregating data between laboratories, leading to potential confusion or misinterpretation of results. Here, we provide a comprehensive overview of parameters to consider when planning an experiment using ferrets, collecting data from the experiment, and placing results in context with previously performed studies. This review offers information that is of particular importance for researchers in the field who rely on ferret data but do not perform the experiments themselves. Furthermore, this review highlights the breadth of experimental designs and techniques currently available to study influenza viruses in this model, underscoring the wide heterogeneity of protocols currently used for ferret studies while demonstrating the wealth of information which can benefit risk assessments of emerging influenza viruses. PMID:27412880

  15. Survival of influenza A virus on contaminated student clothing.

    PubMed

    Ikeda, Keiko; Tsujimoto, Kazuko; Suzuki, Yukiko; Koyama, Augustine Hajime

    2015-04-01

    The role of contaminated clothing in the transmission of influenza A virus during an epidemic period was investigated by examining the recovery of infectious influenza virus from experimentally virus-contaminated clothing, which had been subejected to routine wearing and washing for several months or years. The amount of infectious virus recovered from the nine types of clothing decreased with time and was shown to differ widely between clothing samples, when the contaminated clothing samples were maintained in uncovered glass Petri dishes in a safety cabinet under air blowing. These results indicate a dependence of virus transmissibility on the nature of the contaminated clothes. The difference in recovery was shown to have no significant correlation with the thickness or the materials of the clothing; however, a correlation was observed with the residual amount of water in the deposited virus preparation on the test clothing.

  16. Increased survival after gemfibrozil treatment of severe mouse influenza.

    PubMed

    Budd, Alison; Alleva, Lisa; Alsharifi, Mohammed; Koskinen, Aulikki; Smythe, Victoria; Müllbacher, Arno; Wood, Jeff; Clark, Ian

    2007-08-01

    Gemfibrozil, an agent that inhibits production of proinflammatory cytokines in addition to its clinically useful lipid-lowering activity, increased survival in BALB/c mice that were already ill from infection by influenza virus A/Japan/305/57 (H2N2). Gemfibrozil was administered intraperitoneally once daily from days 4 to 10 after intranasal exposure to the virus. Survival increased from 26% in vehicle-treated mice (n = 50) to 52% in mice given gemfibrozil at 60 mg/kg/day (n = 46) (P = 0.0026). If this principle translates to patients, a drug already approved for human use, albeit by a different route for another purpose, might be adapted relatively fast for use against influenza, conceivably including human infection with a derivative of the avian H5N1 strain.

  17. Contrasting the epidemiological and evolutionary dynamics of influenza spatial transmission

    PubMed Central

    Viboud, Cécile; Nelson, Martha I.; Tan, Yi; Holmes, Edward C.

    2013-01-01

    In the past decade, rapid increases in the availability of high-resolution molecular and epidemiological data, combined with developments in statistical and computational methods to simulate and infer migration patterns, have provided key insights into the spatial dynamics of influenza A viruses in humans. In this review, we contrast findings from epidemiological and molecular studies of influenza virus transmission at different spatial scales. We show that findings are broadly consistent in large-scale studies of inter-regional or inter-hemispheric spread in temperate regions, revealing intense epidemics associated with multiple viral introductions, followed by deep troughs driven by seasonal bottlenecks. However, aspects of the global transmission dynamics of influenza viruses are still debated, especially with respect to the existence of tropical source populations experiencing high levels of genetic diversity and the extent of prolonged viral persistence between epidemics. At the scale of a country or community, epidemiological studies have revealed spatially structured diffusion patterns in seasonal and pandemic outbreaks, which were not identified in molecular studies. We discuss the role of sampling issues in generating these conflicting results, and suggest strategies for future research that may help to fully integrate the epidemiological and evolutionary dynamics of influenza virus over space and time. PMID:23382422

  18. Inference of seasonal and pandemic influenza transmission dynamics

    PubMed Central

    Yang, Wan; Lipsitch, Marc; Shaman, Jeffrey

    2015-01-01

    The inference of key infectious disease epidemiological parameters is critical for characterizing disease spread and devising prevention and containment measures. The recent emergence of surveillance records mined from big data such as health-related online queries and social media, as well as model inference methods, permits the development of new methodologies for more comprehensive estimation of these parameters. We use such data in conjunction with Bayesian inference methods to study the transmission dynamics of influenza. We simultaneously estimate key epidemiological parameters, including population susceptibility, the basic reproductive number, attack rate, and infectious period, for 115 cities during the 2003–2004 through 2012–2013 seasons, including the 2009 pandemic. These estimates discriminate key differences in the epidemiological characteristics of these outbreaks across 10 y, as well as spatial variations of influenza transmission dynamics among subpopulations in the United States. In addition, the inference methods appear to compensate for observational biases and underreporting inherent in the surveillance data. PMID:25730851

  19. Spatial Transmission of 2009 Pandemic Influenza in the US

    PubMed Central

    Gog, Julia R.; Ballesteros, Sébastien; Viboud, Cécile; Simonsen, Lone; Bjornstad, Ottar N.; Shaman, Jeffrey; Chao, Dennis L.; Khan, Farid; Grenfell, Bryan T.

    2014-01-01

    The 2009 H1N1 influenza pandemic provides a unique opportunity for detailed examination of the spatial dynamics of an emerging pathogen. In the US, the pandemic was characterized by substantial geographical heterogeneity: the 2009 spring wave was limited mainly to northeastern cities while the larger fall wave affected the whole country. Here we use finely resolved spatial and temporal influenza disease data based on electronic medical claims to explore the spread of the fall pandemic wave across 271 US cities and associated suburban areas. We document a clear spatial pattern in the timing of onset of the fall wave, starting in southeastern cities and spreading outwards over a period of three months. We use mechanistic models to tease apart the external factors associated with the timing of the fall wave arrival: differential seeding events linked to demographic factors, school opening dates, absolute humidity, prior immunity from the spring wave, spatial diffusion, and their interactions. Although the onset of the fall wave was correlated with school openings as previously reported, models including spatial spread alone resulted in better fit. The best model had a combination of the two. Absolute humidity or prior exposure during the spring wave did not improve the fit and population size only played a weak role. In conclusion, the protracted spread of pandemic influenza in fall 2009 in the US was dominated by short-distance spatial spread partially catalysed by school openings rather than long-distance transmission events. This is in contrast to the rapid hierarchical transmission patterns previously described for seasonal influenza. The findings underline the critical role that school-age children play in facilitating the geographic spread of pandemic influenza and highlight the need for further information on the movement and mixing patterns of this age group. PMID:24921923

  20. Quantifying influenza virus diversity and transmission in humans.

    PubMed

    Poon, Leo L M; Song, Timothy; Rosenfeld, Roni; Lin, Xudong; Rogers, Matthew B; Zhou, Bin; Sebra, Robert; Halpin, Rebecca A; Guan, Yi; Twaddle, Alan; DePasse, Jay V; Stockwell, Timothy B; Wentworth, David E; Holmes, Edward C; Greenbaum, Benjamin; Peiris, Joseph S M; Cowling, Benjamin J; Ghedin, Elodie

    2016-02-01

    Influenza A virus is characterized by high genetic diversity. However, most of what is known about influenza evolution has come from consensus sequences sampled at the epidemiological scale that only represent the dominant virus lineage within each infected host. Less is known about the extent of within-host virus diversity and what proportion of this diversity is transmitted between individuals. To characterize virus variants that achieve sustainable transmission in new hosts, we examined within-host virus genetic diversity in household donor-recipient pairs from the first wave of the 2009 H1N1 pandemic when seasonal H3N2 was co-circulating. Although the same variants were found in multiple members of the community, the relative frequencies of variants fluctuated, with patterns of genetic variation more similar within than between households. We estimated the effective population size of influenza A virus across donor-recipient pairs to be approximately 100-200 contributing members, which enabled the transmission of multiple lineages, including antigenic variants.

  1. What Transmission Precautions Best Control Influenza Spread in a Hospital?

    PubMed

    Blanco, Natalia; Eisenberg, Marisa C; Stillwell, Terri; Foxman, Betsy

    2016-06-01

    Influenza is a significant problem within hospitals, leading to extended hospital stays, excess morbidity and mortality, and economic loss. Prevention and control strategies are generally "bundled"; therefore, the individual effects of particular strategies and the value of combined strategies cannot be determined directly, making it difficult to discern the optimal strategy. To quantify the individual and joint effectiveness of several known influenza infection control measures used in general hospitals, we simulated influenza transmission at a hypothetical hospital in Ann Arbor, Michigan, during a 1-year seasonal epidemic (June 2012-June 2013), using a susceptible-exposed-infected-recovered (SEIR) compartmental model. The hospital population comprised patients and health-care workers, interacting with its larger community population. Parameter ranges and values were determined from the literature (both national and local to Ann Arbor) and took into account coverage levels and effects of vaccination. The most effective individual strategies, based on percent reduction of cases, were: hand-washing (11%-27%), health-care worker vaccination (6%-19%), prevaccination of patients (4%-17%), patient isolation (5%-16%), antiviral treatment (4%-14%), and use of face masks (3%-10%). Use of all strategies together with ideal levels of compliance could potentially halve the number of observed hospital cases of influenza; under a more realistic scenario, an almost 40% reduction could be achieved. A multifaceted approach is imperative to control and prevent nosocomial influenza in health-care settings. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. A nice day for an infection? Weather conditions and social contact patterns relevant to influenza transmission.

    PubMed

    Willem, Lander; Van Kerckhove, Kim; Chao, Dennis L; Hens, Niel; Beutels, Philippe

    2012-01-01

    Although there is no doubt that significant morbidity and mortality occur during annual influenza epidemics, the role of contextual circumstances, which catalyze seasonal influenza transmission, remains unclear. Weather conditions are believed to affect virus survival, efficiency of transmission and host immunity, but seasonality may also be driven by a tendency of people to congregate indoors during periods of bad weather. To test this hypothesis, we combined data from a social contact survey in Belgium with local weather data. In the absence of a previous in-depth weather impact analysis of social contact patterns, we explored the possibilities and identified pitfalls. We found general dominance of day-type (weekend, holiday, working day) over weather conditions, but nonetheless observed an increase in long duration contacts ([Formula: see text]1 hour) on regular workdays with low temperatures, almost no precipitation and low absolute humidity of the air. Interestingly, these conditions are often assumed to be beneficial for virus survival and transmission. Further research is needed to establish the impact of the weather on social contacts. We recommend that future studies sample over a broad spectrum of weather conditions and day types and include a sufficiently large proportion of holiday periods and weekends.

  3. A Nice Day for an Infection? Weather Conditions and Social Contact Patterns Relevant to Influenza Transmission

    PubMed Central

    Willem, Lander; Van Kerckhove, Kim; Chao, Dennis L.; Hens, Niel; Beutels, Philippe

    2012-01-01

    Although there is no doubt that significant morbidity and mortality occur during annual influenza epidemics, the role of contextual circumstances, which catalyze seasonal influenza transmission, remains unclear. Weather conditions are believed to affect virus survival, efficiency of transmission and host immunity, but seasonality may also be driven by a tendency of people to congregate indoors during periods of bad weather. To test this hypothesis, we combined data from a social contact survey in Belgium with local weather data. In the absence of a previous in-depth weather impact analysis of social contact patterns, we explored the possibilities and identified pitfalls. We found general dominance of day-type (weekend, holiday, working day) over weather conditions, but nonetheless observed an increase in long duration contacts (1 hour) on regular workdays with low temperatures, almost no precipitation and low absolute humidity of the air. Interestingly, these conditions are often assumed to be beneficial for virus survival and transmission. Further research is needed to establish the impact of the weather on social contacts. We recommend that future studies sample over a broad spectrum of weather conditions and day types and include a sufficiently large proportion of holiday periods and weekends. PMID:23155399

  4. The Timeline of Influenza Virus Shedding in Children and Adults in a Household Transmission Study of Influenza in Managua, Nicaragua

    PubMed Central

    Ng, Sophia; Lopez, Roger; Kuan, Guillermina; Gresh, Lionel; Balmaseda, Angel; Harris, Eva; Gordon, Aubree

    2016-01-01

    In a household transmission study in Nicaragua, children under 6 years of age had a longer duration of pre-symptomatic influenza virus shedding than adults. The duration of post-symptomatic influenza virus shedding was longest in children 0–5 years of age, followed by children 6-15 years of age and adults. PMID:26910589

  5. Transmission of avian H9N2 influenza viruses in a murine model.

    PubMed

    Wu, Rui; Sui, Zhiwei; Liu, Zewen; Liang, Wangwang; Yang, Keli; Xiong, Zhongliang; Xu, Diping

    2010-05-19

    Avian H9N2 influenza viruses have circulated widely in domestic poultry around the world, resulting in occasional transmission of virus from infected poultry to humans. However, it is unknown whether H9N2 influenza virus has acquired the ability to be transmitted from human to human. Here, we report that mouse-adapted H9N2 influenza viruses can replicate efficiently and are lethal for several strains of mice. To evaluate the transmissibility of mouse-adapted H9N2 influenza viruses, we carried out transmission studies in mice using both contact and respiratory droplet routes. Our results indicate that mouse-adapted H9N2 influenza viruses can replicate efficiently and be transmitted between mice. This suggests that once H9N2 influenza viruses adapt to new host, they should present potential public health risks, therefore, urgent attention should be paid to H9N2 influenza viruses.

  6. Transmission of Influenza on International Flights, May 2009

    PubMed Central

    Foxwell, A. Ruth; Roberts, Leslee; Lokuge, Kamalini

    2011-01-01

    Understanding the dynamics of influenza transmission on international flights is necessary for prioritizing public health response to pandemic incursions. A retrospective cohort study to ascertain in-flight transmission of pandemic (H1N1) 2009 and influenza-like illness (ILI) was undertaken for 2 long-haul flights entering Australia during May 2009. Combined results, including survey responses from 319 (43%) of 738 passengers, showed that 13 (2%) had an ILI in flight and an ILI developed in 32 (5%) passengers during the first week post arrival. Passengers were at 3.6% increased risk of contracting pandemic (H1N1) 2009 if they sat in the same row as or within 2 rows of persons who were symptomatic preflight. A closer exposed zone (2 seats in front, 2 seats behind, and 2 seats either side) increased the risk for postflight disease to 7.7%. Efficiency of contact tracing without compromising the effectiveness of the public health intervention might be improved by limiting the exposed zone. PMID:21762571

  7. Assessing coughing-induced influenza droplet transmission and implications for infection risk control.

    PubMed

    Cheng, Y-H; Wang, C-H; You, S-H; Hsieh, N-H; Chen, W-Y; Chio, C-P; Liao, C-M

    2016-01-01

    Indoor transmission of respiratory droplets bearing influenza within humans poses high risks to respiratory function deterioration and death. Therefore, we aimed to develop a framework for quantifying the influenza infection risk based on the relationships between inhaled/exhaled respiratory droplets and airborne transmission dynamics in a ventilated airspace. An experiment was conducted to measure the size distribution of influenza-containing droplets produced by coughing for a better understanding of potential influenza spread. Here we integrated influenza population transmission dynamics, a human respiratory tract model, and a control measure approach to examine the indoor environment-virus-host interactions. A probabilistic risk model was implemented to assess size-specific infection risk for potentially transmissible influenza droplets indoors. Our results found that there was a 50% probability of the basic reproduction number (R0) exceeding 1 for small-size influenza droplets of 0·3-0·4 µm, implicating a potentially high indoor infection risk to humans. However, a combination of public health interventions with enhanced ventilation could substantially contain indoor influenza infection. Moreover, the present dynamic simulation and control measure assessment provide insights into why indoor transmissible influenza droplet-induced infection is occurring not only in upper lung regions but also in the lower respiratory tract, not normally considered at infection risk.

  8. Influenza A virus survival in water is influenced by the origin species of the host cell

    PubMed Central

    Shigematsu, Sayuri; Dublineau, Amélie; Sawoo, Olivier; Batéjat, Christophe; Matsuyama, Toshifumi; Leclercq, India; Manuguerra, Jean-Claude

    2014-01-01

    Background Influenza A viruses have an envelope made of a lipid bilayer and two surface glycoproteins, the hemagglutinin and the neuraminidase. The structure of the virus is directly dependent on the genetic makeup of the viral genome except the glycosylation moieties and the composition of the lipid bilayer. They both depend on the host cell and are in direct contact with the environment, such as air or water. Virus survival is important for virus transmission from contaminated waters in the case of wild aquatic birds or from contaminated surface or air for humans. Objective The objective of this study was to check whether the origin species of the host cell has an influence on influenza A virus survival. Method The persistence in water at 35°C of viruses grown on either mammalian cells or avian cells and belonging to two different subtypes H1N1 and H5N1 was compared. Results Both H5N1 and H1N1 viruses remained infectious for periods of time as long as 19–25 days, respectively. However, within the same subtype, viruses grown on mammalian cells were more stable in water at 35°C than their counterparts grown on avian cells, even for viruses sharing the same genetic background. Conclusions This difference in virus stability outside the host is probably connected to the nature of the lipid bilayer taken from the cell or to the carbohydrate side chains of the virus surface glycoproteins. Moreover, the long-lasting survival time might have a critical role in the ecology of influenza viruses, especially for avian viruses. PMID:24112132

  9. Network information analysis reveals risk perception transmission in a behaviour-influenza dynamics system.

    PubMed

    Liao, C-M; You, S-H; Cheng, Y-H

    2015-01-01

    Influenza poses a significant public health burden worldwide. Understanding how and to what extent people would change their behaviour in response to influenza outbreaks is critical for formulating public health policies. We incorporated the information-theoretic framework into a behaviour-influenza (BI) transmission dynamics system in order to understand the effects of individual behavioural change on influenza epidemics. We showed that information transmission of risk perception played a crucial role in the spread of health-seeking behaviour throughout influenza epidemics. Here a network BI model provides a new approach for understanding the risk perception spread and human behavioural change during disease outbreaks. Our study allows simultaneous consideration of epidemiological, psychological, and social factors as predictors of individual perception rates in behaviour-disease transmission systems. We suggest that a monitoring system with precise information on risk perception should be constructed to effectively promote health behaviours in preparation for emerging disease outbreaks.

  10. Pathogenicity, Transmission and Antigenic Variation of H5N1 Highly Pathogenic Avian Influenza Viruses.

    PubMed

    Jiao, Peirong; Song, Hui; Liu, Xiaoke; Song, Yafen; Cui, Jin; Wu, Siyu; Ye, Jiaqi; Qu, Nanan; Zhang, Tiemin; Liao, Ming

    2016-01-01

    H5N1 highly pathogenic avian influenza (HPAI) was one of the most important avian diseases in poultry production of China, especially in Guangdong province. In recent years, new H5N1 highly pathogenic avian influenza viruses (HPAIV) still emerged constantly, although all poultry in China were immunized with H5N1 vaccinations compulsorily. To better understand the pathogenicity and transmission of dominant clades of the H5N1 HPAIVs in chicken from Guangdong in 2012, we chose a clade 7.2 avian influenza virus named A/Chicken/China/G2/2012(H5N1) (G2) and a clade 2.3.2.1 avian influenza virus named A/Duck/China/G3/2012(H5N1) (G3) in our study. Our results showed that the chickens inoculated with 10(3) EID50 of G2 or G3 viruses all died, and the titers of virus replication detected in several visceral organs were high but different. In the naive contact groups, virus shedding was not detected in G2 group and all chickens survived, but virus shedding was detected in G3 group and all chickens died. These results showed that the two clades of H5N1 HPAIVs had high pathogenicity in chickens and the contact transmission of them was different in chickens. The results of cross reactive HI assay showed that antigens of G2 and G3 were very different from those of current commercial vaccines isolates (Re-4, Re-6, and D7). And to evaluate the protective efficacy of three vaccines against most isolates form Guangdong belonging to clade 2.3.2.1 in 2012, G3 was chosen to challenge the three vaccines such as Re-4, Re-6, and D7. First, chickens were immunized with 0.3 ml Re-4, Re-6, and D7 inactivated vaccines by intramuscular injection, respectively, and then challenged with 10(6) EID50 of G3 on day 28 post-vaccination. The D7 vaccine had 100% protection against G3 for chickens, the Re-6 vaccine had 88.9%, and the Re-4 vaccine only had 66.7%. Our results suggested that the D7 vaccine could prevent and control H5N1 virus outbreaks more effectively in Guangdong. From the above, it was

  11. Pathogenicity, Transmission and Antigenic Variation of H5N1 Highly Pathogenic Avian Influenza Viruses

    PubMed Central

    Jiao, Peirong; Song, Hui; Liu, Xiaoke; Song, Yafen; Cui, Jin; Wu, Siyu; Ye, Jiaqi; Qu, Nanan; Zhang, Tiemin; Liao, Ming

    2016-01-01

    H5N1 highly pathogenic avian influenza (HPAI) was one of the most important avian diseases in poultry production of China, especially in Guangdong province. In recent years, new H5N1 highly pathogenic avian influenza viruses (HPAIV) still emerged constantly, although all poultry in China were immunized with H5N1 vaccinations compulsorily. To better understand the pathogenicity and transmission of dominant clades of the H5N1 HPAIVs in chicken from Guangdong in 2012, we chose a clade 7.2 avian influenza virus named A/Chicken/China/G2/2012(H5N1) (G2) and a clade 2.3.2.1 avian influenza virus named A/Duck/China/G3/2012(H5N1) (G3) in our study. Our results showed that the chickens inoculated with 103 EID50 of G2 or G3 viruses all died, and the titers of virus replication detected in several visceral organs were high but different. In the naive contact groups, virus shedding was not detected in G2 group and all chickens survived, but virus shedding was detected in G3 group and all chickens died. These results showed that the two clades of H5N1 HPAIVs had high pathogenicity in chickens and the contact transmission of them was different in chickens. The results of cross reactive HI assay showed that antigens of G2 and G3 were very different from those of current commercial vaccines isolates (Re-4, Re-6, and D7). And to evaluate the protective efficacy of three vaccines against most isolates form Guangdong belonging to clade 2.3.2.1 in 2012, G3 was chosen to challenge the three vaccines such as Re-4, Re-6, and D7. First, chickens were immunized with 0.3 ml Re-4, Re-6, and D7 inactivated vaccines by intramuscular injection, respectively, and then challenged with 106 EID50 of G3 on day 28 post-vaccination. The D7 vaccine had 100% protection against G3 for chickens, the Re-6 vaccine had 88.9%, and the Re-4 vaccine only had 66.7%. Our results suggested that the D7 vaccine could prevent and control H5N1 virus outbreaks more effectively in Guangdong. From the above, it was

  12. Animal models for influenza virus pathogenesis, transmission, and immunology

    PubMed Central

    Thangavel, Rajagowthamee R.; Bouvier, Nicole M.

    2014-01-01

    In humans, infection with an influenza A or B virus manifests typically as an acute and self-limited upper respiratory tract illness characterized by fever, cough, sore throat, and malaise. However, influenza can present along a broad spectrum of disease, ranging from sub-clinical or even asymptomatic infection to a severe primary viral pneumonia requiring advanced medical supportive care. Disease severity depends upon the virulence of the influenza virus strain and the immune competence and previous influenza exposures of the patient. Animal models are used in influenza research not only to elucidate the viral and host factors that affect influenza disease outcomes in and spread among susceptible hosts, but also to evaluate interventions designed to prevent or reduce influenza morbidity and mortality in man. This review will focus on the three animal models currently used most frequently in influenza virus research -- mice, ferrets, and guinea pigs -- and discuss the advantages and disadvantages of each. PMID:24709389

  13. Probable Tiger-to-Tiger Transmission of Avian Influenza H5N1

    PubMed Central

    Thanawongnuwech, Roongroje; Amonsin, Alongkorn; Tantilertcharoen, Rachod; Damrongwatanapokin, Sudarat; Theamboonlers, Apiradee; Payungporn, Sunchai; Nanthapornphiphat, Kamonchart; Ratanamungklanon, Somchuan; Tunak, Eakchai; Songserm, Thaweesak; Vivatthanavanich, Veravit; Lekdumrongsak, Thawat; Kesdangsakonwut, Sawang; Tunhikorn, Schwann

    2005-01-01

    During the second outbreak of avian influenza H5N1 in Thailand, probable horizontal transmission among tigers was demonstrated in the tiger zoo. Sequencing and phylogenetic analysis of those viruses showed no differences from the first isolate obtained in January 2004. This finding has implications for influenza virus epidemiology and pathogenicity in mammals. PMID:15890122

  14. Modeling and predicting seasonal influenza transmission in warm regions using climatological parameters.

    PubMed

    Soebiyanto, Radina P; Adimi, Farida; Kiang, Richard K

    2010-03-01

    Influenza transmission is often associated with climatic factors. As the epidemic pattern varies geographically, the roles of climatic factors may not be unique. Previous in vivo studies revealed the direct effect of winter-like humidity on air-borne influenza transmission that dominates in regions with temperate climate, while influenza in the tropics is more effectively transmitted through direct contact. Using time series model, we analyzed the role of climatic factors on the epidemiology of influenza transmission in two regions characterized by warm climate: Hong Kong (China) and Maricopa County (Arizona, USA). These two regions have comparable temperature but distinctly different rainfall. Specifically we employed Autoregressive Integrated Moving Average (ARIMA) model along with climatic parameters as measured from ground stations and NASA satellites. Our studies showed that including the climatic variables as input series result in models with better performance than the univariate model where the influenza cases depend only on its past values and error signal. The best model for Hong Kong influenza was obtained when Land Surface Temperature (LST), rainfall and relative humidity were included as input series. Meanwhile for Maricopa County we found that including either maximum atmospheric pressure or mean air temperature gave the most improvement in the model performances. Our results showed that including the environmental variables generally increases the prediction capability. Therefore, for countries without advanced influenza surveillance systems, environmental variables can be used for estimating influenza transmission at present and in the near future.

  15. Modeling and Predicting Seasonal Influenza Transmission in Warm Regions Using Climatological Parameters

    PubMed Central

    Soebiyanto, Radina P.; Adimi, Farida; Kiang, Richard K.

    2010-01-01

    Background Influenza transmission is often associated with climatic factors. As the epidemic pattern varies geographically, the roles of climatic factors may not be unique. Previous in vivo studies revealed the direct effect of winter-like humidity on air-borne influenza transmission that dominates in regions with temperate climate, while influenza in the tropics is more effectively transmitted through direct contact. Methodology/Principal Findings Using time series model, we analyzed the role of climatic factors on the epidemiology of influenza transmission in two regions characterized by warm climate: Hong Kong (China) and Maricopa County (Arizona, USA). These two regions have comparable temperature but distinctly different rainfall. Specifically we employed Autoregressive Integrated Moving Average (ARIMA) model along with climatic parameters as measured from ground stations and NASA satellites. Our studies showed that including the climatic variables as input series result in models with better performance than the univariate model where the influenza cases depend only on its past values and error signal. The best model for Hong Kong influenza was obtained when Land Surface Temperature (LST), rainfall and relative humidity were included as input series. Meanwhile for Maricopa County we found that including either maximum atmospheric pressure or mean air temperature gave the most improvement in the model performances. Conclusions/Significance Our results showed that including the environmental variables generally increases the prediction capability. Therefore, for countries without advanced influenza surveillance systems, environmental variables can be used for estimating influenza transmission at present and in the near future. PMID:20209164

  16. Transmission of SARS and MERS coronaviruses and influenza virus in healthcare settings: the possible role of dry surface contamination.

    PubMed

    Otter, J A; Donskey, C; Yezli, S; Douthwaite, S; Goldenberg, S D; Weber, D J

    2016-03-01

    Viruses with pandemic potential including H1N1, H5N1, and H5N7 influenza viruses, and severe acute respiratory syndrome (SARS)/Middle East respiratory syndrome (MERS) coronaviruses (CoV) have emerged in recent years. SARS-CoV, MERS-CoV, and influenza virus can survive on surfaces for extended periods, sometimes up to months. Factors influencing the survival of these viruses on surfaces include: strain variation, titre, surface type, suspending medium, mode of deposition, temperature and relative humidity, and the method used to determine the viability of the virus. Environmental sampling has identified contamination in field-settings with SARS-CoV and influenza virus, although the frequent use of molecular detection methods may not necessarily represent the presence of viable virus. The importance of indirect contact transmission (involving contamination of inanimate surfaces) is uncertain compared with other transmission routes, principally direct contact transmission (independent of surface contamination), droplet, and airborne routes. However, influenza virus and SARS-CoV may be shed into the environment and be transferred from environmental surfaces to hands of patients and healthcare providers. Emerging data suggest that MERS-CoV also shares these properties. Once contaminated from the environment, hands can then initiate self-inoculation of mucous membranes of the nose, eyes or mouth. Mathematical and animal models, and intervention studies suggest that contact transmission is the most important route in some scenarios. Infection prevention and control implications include the need for hand hygiene and personal protective equipment to minimize self-contamination and to protect against inoculation of mucosal surfaces and the respiratory tract, and enhanced surface cleaning and disinfection in healthcare settings.

  17. Recombinant IgA Is Sufficient To Prevent Influenza Virus Transmission in Guinea Pigs

    PubMed Central

    Seibert, Christopher W.; Rahmat, Saad; Krause, Jens C.; Eggink, Dirk; Albrecht, Randy A.; Goff, Peter H.; Krammer, Florian; Duty, J. Andrew; Bouvier, Nicole M.; García-Sastre, Adolfo

    2013-01-01

    A serum hemagglutination inhibition (HAI) titer of 40 or greater is thought to be associated with reduced influenza virus pathogenesis in humans and is often used as a correlate of protection in influenza vaccine studies. We have previously demonstrated that intramuscular vaccination of guinea pigs with inactivated influenza virus generates HAI titers greater than 300 but does not protect vaccinated animals from becoming infected with influenza virus by transmission from an infected cage mate. Only guinea pigs intranasally inoculated with a live influenza virus or a live attenuated virus vaccine, prior to challenge, were protected from transmission (A. C. Lowen et al., J. Virol. 83:2803–2818, 2009.). Because the serum HAI titer is mostly determined by IgG content, these results led us to speculate that prevention of viral transmission may require IgA antibodies or cellular immune responses. To evaluate this hypothesis, guinea pigs and ferrets were administered a potent, neutralizing mouse IgG monoclonal antibody, 30D1 (Ms 30D1 IgG), against the A/California/04/2009 (H1N1) virus hemagglutinin and exposed to respiratory droplets from animals infected with this virus. Even though HAI titers were greater than 160 1 day postadministration, Ms 30D1 IgG did not prevent airborne transmission to passively immunized recipient animals. In contrast, intramuscular administration of recombinant 30D1 IgA (Ms 30D1 IgA) prevented transmission to 88% of recipient guinea pigs, and Ms 30D1 IgA was detected in animal nasal washes. Ms 30D1 IgG administered intranasally also prevented transmission, suggesting the importance of mucosal immunity in preventing influenza virus transmission. Collectively, our data indicate that IgG antibodies may prevent pathogenesis associated with influenza virus infection but do not protect from virus infection by airborne transmission, while IgA antibodies are more important for preventing transmission of influenza viruses. PMID:23698296

  18. Recombinant IgA is sufficient to prevent influenza virus transmission in guinea pigs.

    PubMed

    Seibert, Christopher W; Rahmat, Saad; Krause, Jens C; Eggink, Dirk; Albrecht, Randy A; Goff, Peter H; Krammer, Florian; Duty, J Andrew; Bouvier, Nicole M; García-Sastre, Adolfo; Palese, Peter

    2013-07-01

    A serum hemagglutination inhibition (HAI) titer of 40 or greater is thought to be associated with reduced influenza virus pathogenesis in humans and is often used as a correlate of protection in influenza vaccine studies. We have previously demonstrated that intramuscular vaccination of guinea pigs with inactivated influenza virus generates HAI titers greater than 300 but does not protect vaccinated animals from becoming infected with influenza virus by transmission from an infected cage mate. Only guinea pigs intranasally inoculated with a live influenza virus or a live attenuated virus vaccine, prior to challenge, were protected from transmission (A. C. Lowen et al., J. Virol. 83:2803-2818, 2009.). Because the serum HAI titer is mostly determined by IgG content, these results led us to speculate that prevention of viral transmission may require IgA antibodies or cellular immune responses. To evaluate this hypothesis, guinea pigs and ferrets were administered a potent, neutralizing mouse IgG monoclonal antibody, 30D1 (Ms 30D1 IgG), against the A/California/04/2009 (H1N1) virus hemagglutinin and exposed to respiratory droplets from animals infected with this virus. Even though HAI titers were greater than 160 1 day postadministration, Ms 30D1 IgG did not prevent airborne transmission to passively immunized recipient animals. In contrast, intramuscular administration of recombinant 30D1 IgA (Ms 30D1 IgA) prevented transmission to 88% of recipient guinea pigs, and Ms 30D1 IgA was detected in animal nasal washes. Ms 30D1 IgG administered intranasally also prevented transmission, suggesting the importance of mucosal immunity in preventing influenza virus transmission. Collectively, our data indicate that IgG antibodies may prevent pathogenesis associated with influenza virus infection but do not protect from virus infection by airborne transmission, while IgA antibodies are more important for preventing transmission of influenza viruses.

  19. Hemagglutinin Stalk Immunity Reduces Influenza Virus Replication and Transmission in Ferrets

    PubMed Central

    Nachbagauer, Raffael; Miller, Matthew S.; Hai, Rong; Ryder, Alex B.; Rose, John K.; Palese, Peter; García-Sastre, Adolfo

    2015-01-01

    We assessed whether influenza virus hemagglutinin stalk-based immunity protects ferrets against aerosol-transmitted H1N1 influenza virus infection. Immunization of ferrets by a universal influenza virus vaccine strategy based on viral vectors expressing chimeric hemagglutinin constructs induced stalk-specific antibody responses. Stalk-immunized ferrets were cohoused with H1N1-infected ferrets under conditions that permitted virus transmission. Hemagglutinin stalk-immunized ferrets had lower viral titers and delayed or no virus replication at all following natural exposure to influenza virus. PMID:26719251

  20. Aerosol influenza transmission risk contours: A study of humid tropics versus winter temperate zone

    PubMed Central

    2010-01-01

    Background In recent years, much attention has been given to the spread of influenza around the world. With the continuing human outbreak of H5N1 beginning in 2003 and the H1N1 pandemic in 2009, focus on influenza and other respiratory viruses has been increased. It has been accepted for decades that international travel via jet aircraft is a major vector for global spread of influenza, and epidemiological differences between tropical and temperate regions observed. Thus we wanted to study how indoor environmental conditions (enclosed locations) in the tropics and winter temperate zones contribute to the aerosol spread of influenza by travelers. To this end, a survey consisting of 632 readings of temperature (T) versus relative humidity (RH) in 389 different enclosed locations air travelers are likely to visit in 8 tropical nations were compared to 102 such readings in 2 Australian cities, including ground transport, hotels, shops, offices and other publicly accessible locations, along with 586 time course readings from aircraft. Results An influenza transmission risk contour map was developed for T versus RH. Empirical equations were created for estimating: 1. risk relative to temperature and RH, and 2. time parameterized influenza transmission risk. Using the transmission risk contours and equations, transmission risk for each country's locations was compared with influenza reports from the countries. Higher risk enclosed locations in the tropics included new automobile transport, luxury buses, luxury hotels, and bank branches. Most temperate locations were high risk. Conclusion Environmental control is recommended for public health mitigation focused on higher risk enclosed locations. Public health can make use of the methods developed to track potential vulnerability to aerosol influenza. The methods presented can also be used in influenza modeling. Accounting for differential aerosol transmission using T and RH can potentially explain anomalies of influenza

  1. Construction of the influenza A virus transmission tree in a college-based population: co-transmission and interactions between influenza A viruses.

    PubMed

    Zhang, Xu-Sheng; De Angelis, Daniela

    2016-01-29

    Co-infection of different influenza A viruses is known to occur but how viruses interact within co-infection remains unknown. An outbreak in a college campus during the 2009 pandemic involved two subtypes of influenza A: persons infected with pandemic A/H1N1; persons infected with seasonal A/H3N2 viruses; and persons infected with both at the same time (co-infection). This provides data to analyse the possible interaction between influenza A viruses within co-infection. We extend a statistical inference method designed for outbreaks caused by one virus to that caused by two viruses. The method uses knowledge of which subtype each case is infected with (and whether they were co-infected), contact information and symptom onset date of each case in the influenza outbreak. We then apply it to construct the most likely transmission tree during the outbreak in the college campus. Analysis of the constructed transmission tree shows that the simultaneous presence of the two influenza viruses increases the infectivity and the transmissibility of A/H1N1 virus but whether it changes the infectivity of A/H3N2 is unclear. The estimation also shows that co-transmission of both subtypes from co-infection is low and therefore co-infection cannot be sustained on its own. This study suggests that influenza A viruses within co-infected patients can interact in some ways rather than transmit independently, and this can enhance the spread of influenza A virus infection.

  2. Mucosal Immunization with a Candidate Universal Influenza Vaccine Reduces Virus Transmission in a Mouse Model

    PubMed Central

    Lo, Chia-Yun; Misplon, Julia A.; Epstein, Suzanne L.

    2014-01-01

    ABSTRACT Pandemic influenza is a major public health concern, but conventional strain-matched vaccines are unavailable early in a pandemic. Candidate “universal” vaccines targeting the viral antigens nucleoprotein (NP) and matrix 2 (M2), which are conserved among all influenza A virus strains and subtypes, could be manufactured in advance for use at the onset of a pandemic. These vaccines do not prevent infection but can reduce disease severity, deaths, and virus titers in the respiratory tract. We hypothesized that such immunization may reduce virus transmission from vaccinated, infected animals. To investigate this hypothesis, we studied mouse models for direct-contact and airborne transmission of H1N1 and H3N2 influenza viruses. We established conditions under which virus transmission occurs and showed that transmission efficiency is determined in part at the level of host susceptibility to infection. Our findings indicate that virus transmission between mice has both airborne and direct-contact components. Finally, we demonstrated that immunization with recombinant adenovirus vectors expressing NP and M2 significantly reduced the transmission of virus to cohoused, unimmunized mice in comparison to controls. These findings have broad implications for the impact of conserved-antigen vaccines, not only in protecting the vaccinated individual but also in protecting others by limiting influenza virus transmission and potentially reducing the size of epidemics. IMPORTANCE Using a mouse model of influenza A virus transmission, we demonstrate that a candidate “universal” influenza vaccine both protects vaccinated animals from lethal infection and reduces the transmission of virus from vaccinated to nonvaccinated mice. This vaccine induces immunity against proteins conserved among all known influenza A virus strains and subtypes, so it could be used early in a pandemic before conventional strain-matched vaccines are available and could potentially reduce the

  3. Determinants of Influenza Transmission in South East Asia: Insights from a Household Cohort Study in Vietnam

    PubMed Central

    Cauchemez, Simon; Ferguson, Neil M.; Fox, Annette; Mai, Le Quynh; Thanh, Le Thi; Thai, Pham Quang; Thoang, Dang Dinh; Duong, Tran Nhu; Minh Hoa, Le Nguyen; Tran Hien, Nguyen; Horby, Peter

    2014-01-01

    To guide control policies, it is important that the determinants of influenza transmission are fully characterized. Such assessment is complex because the risk of influenza infection is multifaceted and depends both on immunity acquired naturally or via vaccination and on the individual level of exposure to influenza in the community or in the household. Here, we analyse a large household cohort study conducted in 2007–2010 in Vietnam using innovative statistical methods to ascertain in an integrative framework the relative contribution of variables that influence the transmission of seasonal (H1N1, H3N2, B) and pandemic H1N1pdm09 influenza. Influenza infection was diagnosed by haemagglutination-inhibition (HI) antibody assay of paired serum samples. We used a Bayesian data augmentation Markov chain Monte Carlo strategy based on digraphs to reconstruct unobserved chains of transmission in households and estimate transmission parameters. The probability of transmission from an infected individual to another household member was 8% (95% CI, 6%, 10%) on average, and varied with pre-season titers, age and household size. Within households of size 3, the probability of transmission from an infected member to a child with low pre-season HI antibody titers was 27% (95% CI 21%–35%). High pre-season HI titers were protective against infection, with a reduction in the hazard of infection of 59% (95% CI, 44%–71%) and 87% (95% CI, 70%–96%) for intermediate (1∶20–1∶40) and high (≥1∶80) HI titers, respectively. Even after correcting for pre-season HI titers, adults had half the infection risk of children. Twenty six percent (95% CI: 21%, 30%) of infections may be attributed to household transmission. Our results highlight the importance of integrated analysis by influenza sub-type, age and pre-season HI titers in order to infer influenza transmission risks in and outside of the household. PMID:25144780

  4. The soft palate is an important site of adaptation for transmissible influenza viruses.

    PubMed

    Lakdawala, Seema S; Jayaraman, Akila; Halpin, Rebecca A; Lamirande, Elaine W; Shih, Angela R; Stockwell, Timothy B; Lin, Xudong; Simenauer, Ari; Hanson, Christopher T; Vogel, Leatrice; Paskel, Myeisha; Minai, Mahnaz; Moore, Ian; Orandle, Marlene; Das, Suman R; Wentworth, David E; Sasisekharan, Ram; Subbarao, Kanta

    2015-10-01

    Influenza A viruses pose a major public health threat by causing seasonal epidemics and sporadic pandemics. Their epidemiological success relies on airborne transmission from person to person; however, the viral properties governing airborne transmission of influenza A viruses are complex. Influenza A virus infection is mediated via binding of the viral haemagglutinin (HA) to terminally attached α2,3 or α2,6 sialic acids on cell surface glycoproteins. Human influenza A viruses preferentially bind α2,6-linked sialic acids whereas avian influenza A viruses bind α2,3-linked sialic acids on complex glycans on airway epithelial cells. Historically, influenza A viruses with preferential association with α2,3-linked sialic acids have not been transmitted efficiently by the airborne route in ferrets. Here we observe efficient airborne transmission of a 2009 pandemic H1N1 (H1N1pdm) virus (A/California/07/2009) engineered to preferentially bind α2,3-linked sialic acids. Airborne transmission was associated with rapid selection of virus with a change at a single HA site that conferred binding to long-chain α2,6-linked sialic acids, without loss of α2,3-linked sialic acid binding. The transmissible virus emerged in experimentally infected ferrets within 24 hours after infection and was remarkably enriched in the soft palate, where long-chain α2,6-linked sialic acids predominate on the nasopharyngeal surface. Notably, presence of long-chain α2,6-linked sialic acids is conserved in ferret, pig and human soft palate. Using a loss-of-function approach with this one virus, we demonstrate that the ferret soft palate, a tissue not normally sampled in animal models of influenza, rapidly selects for transmissible influenza A viruses with human receptor (α2,6-linked sialic acids) preference.

  5. Aerosol transmission is an important mode of influenza A virus spread

    PubMed Central

    Cowling, Benjamin J.; Ip, Dennis K. M.; Fang, Vicky J.; Suntarattiwong, Piyarat; Olsen, Sonja J.; Levy, Jens; Uyeki, Timothy M.; Leung, Gabriel M.; Malik Peiris, J. S.; Chotpitayasunondh, Tawee; Nishiura, Hiroshi; Simmerman, J. Mark

    2013-01-01

    Influenza A viruses are believed to spread between humans through contact, large respiratory droplets and small particle droplet nuclei (aerosols), but the relative importance of each of these modes of transmission is unclear. Volunteer studies suggest that infections via aerosol transmission may have a higher risk of febrile illness. Here we apply a mathematical model to data from randomized controlled trials of hand hygiene and surgical face masks in Hong Kong and Bangkok households. In these particular environments, inferences on the relative importance of modes of transmission are facilitated by information on the timing of secondary infections and apparent differences in clinical presentation of secondary infections resulting from aerosol transmission. We find that aerosol transmission accounts for approximately half of all transmission events. This implies that measures to reduce transmission by contact or large droplets may not be sufficient to control influenza A virus transmission in households. PMID:23736803

  6. Influenza A virus PB1-F2 protein prolongs viral shedding in chickens lengthening the transmission window

    PubMed Central

    James, Joe; Howard, Wendy; Iqbal, Munir; Nair, Venugopal K.; Barclay, Wendy S.

    2016-01-01

    Avian influenza is a significant economic burden on the poultry industry in geographical regions where it is enzootic. It also poses a public health concern when avian influenza subtypes infect humans, often with high mortality. Understanding viral genetic factors which positively contribute to influenza A virus (IAV) fitness – infectivity, spread and pathogenesis – is of great importance both for human and livestock health. PB1-F2 is a small accessory protein encoded by IAV and in mammalian hosts has been implicated in a wide range of functions that contribute to increased pathogenesis. In the avian host, the protein has been understudied despite high-level full-length conservation in avian IAV isolates, which is in contrast to the truncations of the PB1-F2 length frequently found in mammalian host isolates. Here we report that the presence of a full-length PB1-F2 protein, from a low pathogenicity H9N2 avian influenza virus, prolongs infectious virus shedding from directly inoculated chickens, thereby enhancing transmission of the virus by lengthening the transmission window to contact birds. As well as extending transmission, the presence of a full-length PB1-F2 suppresses pathogenicity evidenced by an increased minimum lethal dose in embryonated chicken eggs and increasing survival in directly infected birds when compared to a virus lacking an ORF for PB1-F2. We propose that there is a positive pressure to maintain a full-length functional PB1-F2 protein upon infection of avian hosts as it contributes to the effective transmission of IAV in the field. PMID:27558742

  7. One health, multiple challenges: The inter-species transmission of influenza A virus

    PubMed Central

    Short, Kirsty R.; Richard, Mathilde; Verhagen, Josanne H.; van Riel, Debby; Schrauwen, Eefje J. A.; van den Brand, Judith M. A.; Mänz, Benjamin; Bodewes, Rogier

    2015-01-01

    Influenza A viruses are amongst the most challenging viruses that threaten both human and animal health. Influenza A viruses are unique in many ways. Firstly, they are unique in the diversity of host species that they infect. This includes waterfowl (the original reservoir), terrestrial and aquatic poultry, swine, humans, horses, dog, cats, whales, seals and several other mammalian species. Secondly, they are unique in their capacity to evolve and adapt, following crossing the species barrier, in order to replicate and spread to other individuals within the new species. Finally, they are unique in the frequency of inter-species transmission events that occur. Indeed, the consequences of novel influenza virus strain in an immunologically naïve population can be devastating. The problems that influenza A viruses present for human and animal health are numerous. For example, influenza A viruses in humans represent a major economic and disease burden, whilst the poultry industry has suffered colossal damage due to repeated outbreaks of highly pathogenic avian influenza viruses. This review aims to provide a comprehensive overview of influenza A viruses by shedding light on interspecies virus transmission and summarising the current knowledge regarding how influenza viruses can adapt to a new host. PMID:26309905

  8. Attitudes of influenza‐vaccinated health care workers toward masks to prevent nosocomial transmission of influenza

    PubMed Central

    Brandt, Christian; Rabenau, Holger F.; Wicker, Sabine

    2010-01-01

    Please cite this paper as: Brandt et al. (2010) Attitudes of influenza‐vaccinated health care workers toward masks to prevent nosocomial transmission of influenza. . Influenza and Other Respiratory Viruses 5(1), 61–66. Background  Influenza viruses are highly contagious. Health care workers (HCWs) are at risk of occupational exposure to influenza and may transmit the infection to their patients and coworkers. Objectives  The aim of the study was to characterize the attitudes of HCWs regarding the use of surgical masks to prevent nosocomial influenza transmission. Furthermore, we assessed the informational needs of HCWs with regard to infection control measures. Methods  A survey was conducted among HCWs, using an anonymous questionnaire, at a German University Hospital during an influenza vaccination campaign. Results  Overall, 40·5% of the HCWs were vaccinated against seasonal influenza, and 35·2% were vaccinated against Influenza A/H1N1 (“swine flu”). In total, 1445 vaccinees completed the anonymous questionnaire. Of all respondents, 70·5% stated that the infection control recommendation “wearing a surgical” mask was appropriate to avoid influenza transmission. The percentage of HCWs who would like to have had more information about the infection control measures was 67·5%. Conclusions  Appropriate interventions ought to be taken to reduce the risk of exposure to influenza viruses among HCWs. Adherence to recommendations for the use of masks among HCWs needs to be evaluated. Further work is required to highlight the informational needs of HCWs to gain an appreciation of infection control measures. PMID:21138542

  9. Evidence of transmission and risk factors for influenza A virus in household dogs and their owners.

    PubMed

    Ramírez-Martínez, Luis A; Contreras-Luna, María; De la Luz, Jazmín; Manjarrez, María E; Rosete, Dora P; Rivera-Benitez, José F; Saavedra-Montañez, Manuel; Ramírez-Mendoza, Humberto

    2013-11-01

    The possible transmission of influenza A virus between dogs and humans is important, as in Mexico City there are approximately 1·2 million dogs. We present the first evidence of influenza A virus infection in household dogs in Mexico. The objective of this study was to identify the presence of antibodies against influenza A virus in dogs and their owners, as well as the presence of RNA of influenza A virus in nasal exudates of dogs and, thereby, assess the possible transmission of the virus between humans and dogs. Serum samples from household dogs and their owners were analyzed to detect the presence of antibodies against three subtypes of human influenza virus (H1N1pdm09, H1N1, and H3N2), as well as subtype H3N8 of equine influenza. We analyzed dog nasal exudates to detect influenza viral RNA. The relationship between the seropositivity of dogs and various factors (age, sex, constantly at home, and seropositivity of owners) was statistically analyzed. Seroprevalence for human influenza in dogs was 0·9% (1 of 113), and it was 4% (5 of 113) for equine influenza. In humans, seroprevalence was 22% for subtype H1N1pdm09, 20% for subtype H1N1, and 11% for subtype H3N2. No significant association (P>0·05) was found between seropositivity and any of the assessed factors. Furthermore, no viral RNA was detected in the nasal exudate samples. Results revealed seroprevalence of the influenza virus in household dogs in Mexico City. It can be assumed that dogs are currently becoming infected with different subtypes of influenza viruses. © 2013 John Wiley & Sons Ltd.

  10. Demographic distribution and transmission potential of influenza A and 2009 pandemic influenza A H1N1 in pilgrims.

    PubMed

    Ashshi, Ahmed; Azhar, Esam; Johargy, Ayman; Asghar, Atif; Momenah, Aiman; Turkestani, Abdulhafeez; Alghamdi, Saad; Memish, Ziad; Al-Ghamdi, Ahmed; Alawi, Maha; El-Kafrawy, Sherif; Farouk, Mohomed; Harakeh, Steve; Kumosani, Taha; Makhdoum, Hatim; Barbour, Elie K

    2014-09-12

    The World Health Organization's persistent reporting of global outbreaks of influenza A viruses, including the 2009 pandemic swine A H1N1 strain (H1N1pdm09), justified the targeted surveillance of pilgrims during their annual congregation that pools more than two million people from around 165 nations in a confined area of Makkah city in the Kingdom of Saudi Arabia (KSA). A total of 1,600 pilgrims were included in the targeted surveillance of influenza A and the 2009 pandemic swine H1N1 strain in the Hajj (pilgrimage) season of 2010. Each pilgrim responded to a demographic and health questionnaire. Collected oropharyngeal swabs were analyzed by real-time PCR for influenza A viruses, and positive samples were further analyzed for the presence of H1N1pdm09. Fisher's exact test was applied in the analysis of the significance of the distribution of influenza-positive pilgrims according to demographic characters. A total of 120 pilgrims (7.5%) tested positive for influenza A viruses by real-time PCR. Nine out of the 120 influenza-A-positive pilgrims (7.5%) were positive for H1N1pdm09. Demographics played a significant role in those pilgrims who tested positive for influenza A. The detection of H1N1pdm09 in pilgrims at their port of entry to the KSA was alarming, due to the high potential of trans-boundary transmission. This situation necessitates the implementation of specific prevention and control programs to limit infection by influenza A viruses.

  11. Highly Pathogenic Influenza A(H5N1) Virus Survival in Complex Artificial Aquatic Biotopes

    PubMed Central

    Horm, Viseth Srey; Gutiérrez, Ramona A.; Nicholls, John M.; Buchy, Philippe

    2012-01-01

    Background Very little is known regarding the persistence of Highly Pathogenic Avian Influenza (HPAI) H5N1 viruses in aquatic environments in tropical countries, although environmental materials have been suggested to play a role as reservoirs and sources of transmission for H5N1 viruses. Methodology/Principal Findings The survival of HPAI H5N1 viruses in experimental aquatic biotopes (water, mud, aquatic flora and fauna) relevant to field conditions in Cambodia was investigated. Artificial aquatic biotopes, including simple ones containing only mud and water, and complex biotopes involving the presence of aquatic flora and fauna, were set up. They were experimentally contaminated with H5N1 virus. The persistence of HPAI H5N1 virus (local avian and human isolates) was determined by virus isolation in embryonated chicken eggs and by real-time reverse-polymerase chain reaction. Persistence of infectious virus did not exceed 4 days, and was only identified in rain water. No infectious virus particles were detected in pond and lake water or mud even when high inoculum doses were used. However, viral RNA persisted up to 20 days in rain water and 7 days in pond or lake water. Viral RNA was also detected in mud samples, up to 14 days post-contamination in several cases. Infectious virus and viral RNA was detected in few cases in the aquatic fauna and flora, especially in bivalves and labyrinth fish, although these organisms seemed to be mostly passive carriers of the virus rather than host allowing virus replication. Conclusions/Significance Although several factors for the survival and persistence of HPAI viruses in the environment are still to be elucidated, and are particularly hard to control in laboratory conditions, our results, along with previous data, support the idea that environmental surveillance is of major relevance for avian influenza control programs. PMID:22514622

  12. Remote sensing and avian influenza: A review of image processing methods for extracting key variables affecting avian influenza virus survival in water from Earth Observation satellites

    NASA Astrophysics Data System (ADS)

    Tran, Annelise; Goutard, Flavie; Chamaillé, Lise; Baghdadi, Nicolas; Lo Seen, Danny

    2010-02-01

    Recent studies have highlighted the potential role of water in the transmission of avian influenza (AI) viruses and the existence of often interacting variables that determine the survival rate of these viruses in water; the two main variables are temperature and salinity. Remote sensing has been used to map and monitor water bodies for several decades. In this paper, we review satellite image analysis methods used for water detection and characterization, focusing on the main variables that influence AI virus survival in water. Optical and radar imagery are useful for detecting water bodies at different spatial and temporal scales. Methods to monitor the temperature of large water surfaces are also available. Current methods for estimating other relevant water variables such as salinity, pH, turbidity and water depth are not presently considered to be effective.

  13. Maternally-derived antibodies do not prevent transmission of swine influenza A virus between pigs.

    PubMed

    Cador, Charlie; Hervé, Séverine; Andraud, Mathieu; Gorin, Stéphane; Paboeuf, Frédéric; Barbier, Nicolas; Quéguiner, Stéphane; Deblanc, Céline; Simon, Gaëlle; Rose, Nicolas

    2016-08-17

    A transmission experiment involving 5-week-old specific-pathogen-free (SPF) piglets, with (MDA(+)) or without maternally-derived antibodies (MDA(-)), was carried out to evaluate the impact of passive immunity on the transmission of a swine influenza A virus (swIAV). In each group (MDA(+)/MDA(-)), 2 seeders were placed with 4 piglets in direct contact and 5 in indirect contact (3 replicates per group). Serological kinetics (ELISA) and individual viral shedding (RT-PCR) were monitored for 28 days after infection. MDA waning was estimated using a nonlinear mixed-effects model and survival analysis. Differential transmission rates were estimated depending on the piglets' initial serological status and contact structure (direct contact with pen-mates or indirect airborne contact). The time to MDA waning was 71.3 [52.8-92.1] days on average. The airborne transmission rate was 1.41 [0.64-2.63] per day. The compared shedding pattern between groups showed that MDA(+) piglets had mainly a reduced susceptibility to infection compared to MDA(-) piglets. The resulting reproduction number estimated in MDA(+) piglets (5.8 [1.4-18.9]), although 3 times lower than in MDA(-) piglets (14.8 [6.4-27.1]), was significantly higher than 1. Such an efficient and extended spread of swIAV at the population scale in the presence of MDAs could contribute to swIAV persistence on farms, given the fact that the period when transmission is expected to be impacted by the presence of MDAs can last up to 10 weeks.

  14. Transmission Potential of Influenza A(H7N9) Virus, China, 2013–2014

    PubMed Central

    Mills, Harriet L.; Donnelly, Christl A.; Riley, Steven

    2015-01-01

    To determine transmission potential of influenza A(H7N9) virus, we used symptom onset data to compare 2 waves of infection in China during 2013–2014. We found evidence of increased transmission potential in the second wave and showed that live bird market closure was significantly less effective in Guangdong than in other regions. PMID:25897624

  15. Transmission Potential of Influenza A(H7N9) Virus, China, 2013-2014.

    PubMed

    Kucharski, Adam J; Mills, Harriet L; Donnelly, Christl A; Riley, Steven

    2015-05-01

    To determine transmission potential of influenza A(H7N9) virus, we used symptom onset data to compare 2 waves of infection in China during 2013-2014. We found evidence of increased transmission potential in the second wave and showed that live bird market closure was significantly less effective in Guangdong than in other regions.

  16. Face masks to prevent transmission of influenza virus: a systematic review.

    PubMed

    Cowling, B J; Zhou, Y; Ip, D K M; Leung, G M; Aiello, A E

    2010-04-01

    Influenza viruses circulate around the world every year. From time to time new strains emerge and cause global pandemics. Many national and international health agencies recommended the use of face masks during the 2009 influenza A (H1N1) pandemic. We reviewed the English-language literature on this subject to inform public health preparedness. There is some evidence to support the wearing of masks or respirators during illness to protect others, and public health emphasis on mask wearing during illness may help to reduce influenza virus transmission. There are fewer data to support the use of masks or respirators to prevent becoming infected. Further studies in controlled settings and studies of natural infections in healthcare and community settings are required to better define the effectiveness of face masks and respirators in preventing influenza virus transmission.

  17. Quantifying the impact of immune escape on transmission dynamics of influenza.

    PubMed

    Park, Andrew W; Daly, Janet M; Lewis, Nicola S; Smith, Derek J; Wood, James L N; Grenfell, Bryan T

    2009-10-30

    Influenza virus evades prevailing natural and vaccine-induced immunity by accumulating antigenic change in the haemagglutinin surface protein. Linking amino acid substitutions in haemagglutinin epitopes to epidemiology has been problematic because of the scarcity of data connecting these scales. We use experiments on equine influenza virus to address this issue, quantifying how key parameters of viral establishment and shedding increase the probability of transmission with genetic distance between previously immunizing virus and challenge virus. Qualitatively similar patterns emerge from analyses based on antigenic distance and from a published human influenza study. Combination of the equine data and epidemiological models allows us to calculate the effective reproductive number of transmission as a function of relevant genetic change in the virus, illuminating the probability of influenza epidemics as a function of immunity.

  18. Inter-Seasonal Influenza is Characterized by Extended Virus Transmission and Persistence

    PubMed Central

    Patterson Ross, Zoe; Komadina, Naomi; Deng, Yi-Mo; Spirason, Natalie; Kelly, Heath A.; Sullivan, Sheena G.; Barr, Ian G.; Holmes, Edward C.

    2015-01-01

    The factors that determine the characteristic seasonality of influenza remain enigmatic. Current models predict that occurrences of influenza outside the normal surveillance season within a temperate region largely reflect the importation of viruses from the alternate hemisphere or from equatorial regions in Asia. To help reveal the drivers of seasonality we investigated the origins and evolution of influenza viruses sampled during inter-seasonal periods in Australia. To this end we conducted an expansive phylogenetic analysis of 9912, 3804, and 3941 hemagglutinnin (HA) sequences from influenza A/H1N1pdm, A/H3N2, and B, respectively, collected globally during the period 2009-2014. Of the 1475 viruses sampled from Australia, 396 (26.8% of Australian, or 2.2% of global set) were sampled outside the monitored temperate influenza surveillance season (1 May – 31 October). Notably, rather than simply reflecting short-lived importations of virus from global localities with higher influenza prevalence, we documented a variety of more complex inter-seasonal transmission patterns including “stragglers” from the preceding season and “heralds” of the forthcoming season, and which included viruses sampled from clearly temperate regions within Australia. We also provide evidence for the persistence of influenza B virus between epidemic seasons, in which transmission of a viral lineage begins in one season and continues throughout the inter-seasonal period into the following season. Strikingly, a disproportionately high number of inter-seasonal influenza transmission events occurred in tropical and subtropical regions of Australia, providing further evidence that climate plays an important role in shaping patterns of influenza seasonality. PMID:26107631

  19. Inter-Seasonal Influenza is Characterized by Extended Virus Transmission and Persistence.

    PubMed

    Patterson Ross, Zoe; Komadina, Naomi; Deng, Yi-Mo; Spirason, Natalie; Kelly, Heath A; Sullivan, Sheena G; Barr, Ian G; Holmes, Edward C

    2015-06-01

    The factors that determine the characteristic seasonality of influenza remain enigmatic. Current models predict that occurrences of influenza outside the normal surveillance season within a temperate region largely reflect the importation of viruses from the alternate hemisphere or from equatorial regions in Asia. To help reveal the drivers of seasonality we investigated the origins and evolution of influenza viruses sampled during inter-seasonal periods in Australia. To this end we conducted an expansive phylogenetic analysis of 9912, 3804, and 3941 hemagglutinnin (HA) sequences from influenza A/H1N1pdm, A/H3N2, and B, respectively, collected globally during the period 2009-2014. Of the 1475 viruses sampled from Australia, 396 (26.8% of Australian, or 2.2% of global set) were sampled outside the monitored temperate influenza surveillance season (1 May - 31 October). Notably, rather than simply reflecting short-lived importations of virus from global localities with higher influenza prevalence, we documented a variety of more complex inter-seasonal transmission patterns including "stragglers" from the preceding season and "heralds" of the forthcoming season, and which included viruses sampled from clearly temperate regions within Australia. We also provide evidence for the persistence of influenza B virus between epidemic seasons, in which transmission of a viral lineage begins in one season and continues throughout the inter-seasonal period into the following season. Strikingly, a disproportionately high number of inter-seasonal influenza transmission events occurred in tropical and subtropical regions of Australia, providing further evidence that climate plays an important role in shaping patterns of influenza seasonality.

  20. Role of receptor binding specificity in influenza A virus transmission and pathogenesis.

    PubMed

    de Graaf, Miranda; Fouchier, Ron A M

    2014-04-16

    The recent emergence of a novel avian A/H7N9 influenza virus in poultry and humans in China, as well as laboratory studies on adaptation and transmission of avian A/H5N1 influenza viruses, has shed new light on influenza virus adaptation to mammals. One of the biological traits required for animal influenza viruses to cross the species barrier that received considerable attention in animal model studies, in vitro assays, and structural analyses is receptor binding specificity. Sialylated glycans present on the apical surface of host cells can function as receptors for the influenza virus hemagglutinin (HA) protein. Avian and human influenza viruses typically have a different sialic acid (SA)-binding preference and only few amino acid changes in the HA protein can cause a switch from avian to human receptor specificity. Recent experiments using glycan arrays, virus histochemistry, animal models, and structural analyses of HA have added a wealth of knowledge on receptor binding specificity. Here, we review recent data on the interaction between influenza virus HA and SA receptors of the host, and the impact on virus host range, pathogenesis, and transmission. Remaining challenges and future research priorities are also discussed.

  1. Role of receptor binding specificity in influenza A virus transmission and pathogenesis

    PubMed Central

    de Graaf, Miranda; Fouchier, Ron A M

    2014-01-01

    The recent emergence of a novel avian A/H7N9 influenza virus in poultry and humans in China, as well as laboratory studies on adaptation and transmission of avian A/H5N1 influenza viruses, has shed new light on influenza virus adaptation to mammals. One of the biological traits required for animal influenza viruses to cross the species barrier that received considerable attention in animal model studies, in vitro assays, and structural analyses is receptor binding specificity. Sialylated glycans present on the apical surface of host cells can function as receptors for the influenza virus hemagglutinin (HA) protein. Avian and human influenza viruses typically have a different sialic acid (SA)-binding preference and only few amino acid changes in the HA protein can cause a switch from avian to human receptor specificity. Recent experiments using glycan arrays, virus histochemistry, animal models, and structural analyses of HA have added a wealth of knowledge on receptor binding specificity. Here, we review recent data on the interaction between influenza virus HA and SA receptors of the host, and the impact on virus host range, pathogenesis, and transmission. Remaining challenges and future research priorities are also discussed. PMID:24668228

  2. Transmission of avian influenza virus (H3N2) to dogs.

    PubMed

    Song, Daesub; Kang, Bokyu; Lee, Chulseung; Jung, Kwonil; Ha, Gunwoo; Kang, Dongseok; Park, Seongjun; Park, Bongkyun; Oh, Jinsik

    2008-05-01

    In South Korea, where avian influenza virus subtypes H3N2, H5N1, H6N1, and H9N2 circulate or have been detected, 3 genetically similar canine influenza virus (H3N2) strains of avian origin (A/canine/Korea/01/2007, A/canine/Korea/02/2007, and A/canine/Korea/03/2007) were isolated from dogs exhibiting severe respiratory disease. To determine whether the novel canine influenza virus of avian origin was transmitted among dogs, we experimentally infected beagles with this influenza virus (H3N2) isolate. The beagles shed virus through nasal excretion, seroconverted, and became ill with severe necrotizing tracheobronchitis and bronchioalveolitis with accompanying clinical signs (e.g., high fever). Consistent with histologic observation of lung lesions, large amounts of avian influenza virus binding receptor (SAalpha 2,3-gal) were identified in canine tracheal, bronchial, and bronchiolar epithelial cells, which suggests potential for direct transmission of avian influenza virus (H3N2) from poultry to dogs. Our data provide evidence that dogs may play a role in interspecies transmission and spread of influenza virus.

  3. Infection of dogs with equine influenza virus: evidence for transmission from horses during the Australian outbreak.

    PubMed

    Crispe, E; Finlaison, D S; Hurt, A C; Kirkland, P D

    2011-07-01

    During the equine influenza (EI) outbreak, respiratory disease was observed in dogs that were in close proximity to infected horses. Investigations were undertaken to exclude influenza virus infection. Of the 23 dogs that were seropositive in tests using the influenza A/Sydney/2007 virus as the test antigen, 10 showed clinical signs. EI virus appeared to be readily transmitted to dogs that were held in close proximity to infected horses, but there was no evidence of lateral transmission of the virus to other dogs that did not have contact with or were not held in close proximity to horses.

  4. Genetic data provide evidence for wind-mediated transmission of highly pathogenic avian influenza.

    PubMed

    Ypma, Rolf J F; Jonges, Marcel; Bataille, Arnaud; Stegeman, Arjan; Koch, Guus; van Boven, Michiel; Koopmans, Marion; van Ballegooijen, W Marijn; Wallinga, Jacco

    2013-03-01

    Outbreaks of highly pathogenic avian influenza in poultry can cause severe economic damage and represent a public health threat. Development of efficient containment measures requires an understanding of how these influenza viruses are transmitted between farms. However, the actual mechanisms of interfarm transmission are largely unknown. Dispersal of infectious material by wind has been suggested, but never demonstrated, as a possible cause of transmission between farms. Here we provide statistical evidence that the direction of spread of avian influenza A(H7N7) is correlated with the direction of wind at date of infection. Using detailed genetic and epidemiological data, we found the direction of spread by reconstructing the transmission tree for a large outbreak in the Netherlands in 2003. We conservatively estimate the contribution of a possible wind-mediated mechanism to the total amount of spread during this outbreak to be around 18%.

  5. Transmission and reassortment of avian influenza viruses at the Asian-North American interface

    USGS Publications Warehouse

    Ramey, Andrew M.; Pearce, John M.; Ely, Craig R.; Guy, Lisa M. Sheffield; Irons, David B.; Derksen, Dirk V.; Ip, Hon S.

    2010-01-01

    Twenty avian influenza viruses were isolated from seven wild migratory bird species sampled at St. Lawrence Island, Alaska. We tested predictions based on previous phylogenetic analyses of avian influenza viruses that support spatially dependent trans-hemispheric gene flow and frequent interspecies transmission at a location situated at the Asian–North American interface. Through the application of phylogenetic and genotypic approaches, our data support functional dilution by distance of trans-hemispheric reassortants and interspecific virus transmission. Our study confirms infection of divergent avian taxa with nearly identical avian influenza strains in the wild. Findings also suggest that H16N3 viruses may contain gene segments with unique phylogenetic positions and that further investigation of how host specificity may impact transmission of H13 and H16 viruses is warranted.

  6. Delayed transmission selects for increased survival of vesicular stomatitis virus.

    PubMed

    Wasik, Brian R; Bhushan, Ambika; Ogbunugafor, C Brandon; Turner, Paul E

    2015-01-01

    Life-history theory predicts that traits for survival and reproduction cannot be simultaneously maximized in evolving populations. For this reason, in obligate parasites such as infectious viruses, selection for improved between-host survival during transmission may lead to evolution of decreased within-host reproduction. We tested this idea using experimental evolution of RNA virus populations, passaged under differing transmission times in the laboratory. A single ancestral genotype of vesicular stomatitis virus (VSV), a negative-sense RNA Rhabdovirus, was used to found multiple virus lineages evolved in either ordinary 24-h cell-culture passage, or in delayed passages of 48 h. After 30 passages (120 generations of viral evolution), we observed that delayed transmission selected for improved extracellular survival, which traded-off with lowered viral fecundity (slower exponential population growth and smaller mean plaque size). To further examine the confirmed evolutionary trade-off, we obtained consensus whole-genome sequences of evolved virus populations, to infer phenotype-genotype associations. Results implied that increased virus survival did not occur via convergence; rather, improved virion stability was gained via independent mutations in various VSV structural proteins. Our study suggests that RNA viruses can evolve different molecular solutions for enhanced survival despite their limited genetic architecture, but suffer generalized reproductive trade-offs that limit overall fitness gains. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

  7. Influences on influenza transmission within terminal based on hierarchical structure of personal contact network.

    PubMed

    Shao, Quan; Jia, Meng

    2015-03-18

    Since the outbreak of pandemics, influenza has caused extensive attention in the field of public health. It is actually hard to distinguish what is the most effective method to control the influenza transmission within airport terminal. The purpose of this study was to quantitatively evaluate the influences of passenger source, immunity difference and social relation structure on the influenza transmission in terminal. A method combining hierarchical structure of personal contact network with agent-based SEIR model was proposed to analyze the characteristics of influenza diffusion within terminal. Based on the spatial distance between individuals, the hierarchical structure of personal contact network was defined to construct a complex relationship of passengers in the real world. Moreover, the agent-based SEIR model was improved by considering the individual level of influenza spread characteristics. To evaluate the method, this process was fused in simulation based on the constructed personal contact network. In the terminal we investigated, personal contact network was defined by following four layers: social relation structure, procedure partition, procedure area, and the whole terminal. With the growing of layer, the degree distribution curves move right. The value of degree distribution p(k) reached a peak at a specific value, and then back down. Besides, with the increase of layer α, the clustering coefficients presented a tendency to exponential decay. Based on the influenza transmission experiments, the main infected areas were concluded when considering different factors. Moreover, partition of passenger sources was found to impact a lot in departure, while social relation structure imposed a great influence in arrival. Besides, immunity difference exerted no obvious effect on the spread of influenza in the transmission process both in departure and arrival. The proposed method is efficient to reproduce the evolution process of influenza transmission

  8. [Interspecies transmission, adaptation to humans and pathogenicity of animal influenza viruses].

    PubMed

    Munier, S; Moisy, D; Marc, D; Naffakh, N

    2010-04-01

    The emergence in 2009 of a novel A(H1N1)v influenza virus of swine origin and the regular occurrence since 2003 of human cases of infection with A(H5N1) avian influenza viruses underline the zoonotic and pandemic potential of type A influenza viruses. Influenza viruses from the wild aquatic birds reservoir usually do not replicate efficiently in humans. Domestic poultry and swine can act as intermediate hosts for the acquisition of determinants that increase the potential of transmission and adaptation to humans, through the accumulation of mutations or by genetic reassortment. The rapid evolution of influenza viruses following interspecies transmission probably results from the selection of genetic variations that favor optimal interactions between viral proteins and cellular factors, leading to an increased multiplication potential and a better escape to the host antiviral response. Whereas influenza viruses usually cause asymptomatic infections in wild aquatic birds, they may be highly pathogenic in other species. Molecular determinants of host-specificity and pathogenesis have been identified in most viral genes, notably in genes that encode viral surface glycoproteins, proteins involved in the viral genome replication, and proteins that counteract the host immune response. However, our knowledge of these numerous and interdependant determinants remains incomplete, and the molecular mechanisms involved are still to be understood.

  9. A data-driven model for influenza transmission incorporating media effects.

    PubMed

    Mitchell, Lewis; Ross, Joshua V

    2016-10-01

    Numerous studies have attempted to model the effect of mass media on the transmission of diseases such as influenza; however, quantitative data on media engagement has until recently been difficult to obtain. With the recent explosion of 'big data' coming from online social media and the like, large volumes of data on a population's engagement with mass media during an epidemic are becoming available to researchers. In this study, we combine an online dataset comprising millions of shared messages relating to influenza with traditional surveillance data on flu activity to suggest a functional form for the relationship between the two. Using this data, we present a simple deterministic model for influenza dynamics incorporating media effects, and show that such a model helps explain the dynamics of historical influenza outbreaks. Furthermore, through model selection we show that the proposed media function fits historical data better than other media functions proposed in earlier studies.

  10. A data-driven model for influenza transmission incorporating media effects

    PubMed Central

    Ross, Joshua V.

    2016-01-01

    Numerous studies have attempted to model the effect of mass media on the transmission of diseases such as influenza; however, quantitative data on media engagement has until recently been difficult to obtain. With the recent explosion of ‘big data’ coming from online social media and the like, large volumes of data on a population’s engagement with mass media during an epidemic are becoming available to researchers. In this study, we combine an online dataset comprising millions of shared messages relating to influenza with traditional surveillance data on flu activity to suggest a functional form for the relationship between the two. Using this data, we present a simple deterministic model for influenza dynamics incorporating media effects, and show that such a model helps explain the dynamics of historical influenza outbreaks. Furthermore, through model selection we show that the proposed media function fits historical data better than other media functions proposed in earlier studies. PMID:27853563

  11. Contact transmission of influenza virus between ferrets imposes a looser bottleneck than respiratory droplet transmission allowing propagation of antiviral resistance

    PubMed Central

    Frise, Rebecca; Bradley, Konrad; van Doremalen, Neeltje; Galiano, Monica; Elderfield, Ruth A.; Stilwell, Peter; Ashcroft, Jonathan W.; Fernandez-Alonso, Mirian; Miah, Shahjahan; Lackenby, Angie; Roberts, Kim L.; Donnelly, Christl A.; Barclay, Wendy S.

    2016-01-01

    Influenza viruses cause annual seasonal epidemics and occasional pandemics. It is important to elucidate the stringency of bottlenecks during transmission to shed light on mechanisms that underlie the evolution and propagation of antigenic drift, host range switching or drug resistance. The virus spreads between people by different routes, including through the air in droplets and aerosols, and by direct contact. By housing ferrets under different conditions, it is possible to mimic various routes of transmission. Here, we inoculated donor animals with a mixture of two viruses whose genomes differed by one or two reverse engineered synonymous mutations, and measured the transmission of the mixture to exposed sentinel animals. Transmission through the air imposed a tight bottleneck since most recipient animals became infected by only one virus. In contrast, a direct contact transmission chain propagated a mixture of viruses suggesting the dose transferred by this route was higher. From animals with a mixed infection of viruses that were resistant and sensitive to the antiviral drug oseltamivir, resistance was propagated through contact transmission but not by air. These data imply that transmission events with a looser bottleneck can propagate minority variants and may be an important route for influenza evolution. PMID:27430528

  12. Role of environmental survival in transmission of Campylobacter jejuni.

    PubMed

    Bronowski, Christina; James, Chloe E; Winstanley, Craig

    2014-07-01

    Campylobacter species are the most common cause of bacterial gastroenteritis, with C. jejuni responsible for the majority of these cases. Although it is clear that livestock, and particularly poultry, are the most common source, it is likely that the natural environment (soil and water) plays a key role in transmission, either directly to humans or indirectly via farm animals. It has been shown using multilocus sequence typing that some clonal complexes (such as ST-45) are more frequently isolated from environmental sources such as water, suggesting that strains vary in their ability to survive in the environment. Although C. jejuni are fastidious microaerophiles generally unable to grow in atmospheric levels of oxygen, C. jejuni can adapt to survival in the environment, exhibiting aerotolerance and starvation survival. Biofilm formation, the viable but nonculturable state, and interactions with other microorganisms can all contribute to survival outside the host. By exploiting high-throughput technologies such as genome sequencing and RNA Seq, we are well placed to decipher the mechanisms underlying the variations in survival between strains in environments such as soil and water and to better understand the role of environmental persistence in the transmission of C. jejuni directly or indirectly to humans. © 2014 The Authors. FEMS Microbiology Letters published by John Wiley & Sons Ltd on behalf of Federation of European Microbiological Societies.

  13. Transmission of Equine Influenza Virus during an Outbreak Is Characterized by Frequent Mixed Infections and Loose Transmission Bottlenecks

    PubMed Central

    Hughes, Joseph; Allen, Richard C.; Baguelin, Marc; Hampson, Katie; Baillie, Gregory J.; Elton, Debra; Newton, J. Richard; Kellam, Paul; Wood, James L. N.; Holmes, Edward C.; Murcia, Pablo R.

    2012-01-01

    The ability of influenza A viruses (IAVs) to cross species barriers and evade host immunity is a major public health concern. Studies on the phylodynamics of IAVs across different scales – from the individual to the population – are essential for devising effective measures to predict, prevent or contain influenza emergence. Understanding how IAVs spread and evolve during outbreaks is critical for the management of epidemics. Reconstructing the transmission network during a single outbreak by sampling viral genetic data in time and space can generate insights about these processes. Here, we obtained intra-host viral sequence data from horses infected with equine influenza virus (EIV) to reconstruct the spread of EIV during a large outbreak. To this end, we analyzed within-host viral populations from sequences covering 90% of the infected yards. By combining gene sequence analyses with epidemiological data, we inferred a plausible transmission network, in turn enabling the comparison of transmission patterns during the course of the outbreak and revealing important epidemiological features that were not apparent using either approach alone. The EIV populations displayed high levels of genetic diversity, and in many cases we observed distinct viral populations containing a dominant variant and a number of related minor variants that were transmitted between infectious horses. In addition, we found evidence of frequent mixed infections and loose transmission bottlenecks in these naturally occurring populations. These frequent mixed infections likely influence the size of epidemics. PMID:23308065

  14. How much would closing schools reduce transmission during an influenza pandemic?

    PubMed

    Glass, Kathryn; Barnes, Belinda

    2007-09-01

    When deciding whether to close schools during an influenza pandemic, authorities must weigh the likely benefits against the expected social disruption. Although schools have been closed to slow the spread of influenza, there is limited evidence as to the impact on transmission of disease. To assess the benefits of closing schools for various pandemic scenarios, we used a stochastic mathematical model of disease transmission fitted to attack rates from past influenza pandemics. We compared these benefits with those achieved by other interventions targeted at children. Closing schools can reduce transmission among children considerably, but has only a moderate impact on average transmission rates among all individuals (both adults and children) under most scenarios. Much of the benefit of closing schools can be achieved if schools are closed by the time that 2% of children are infected; if the intervention is delayed until 20% of children are infected, there is little benefit. Immunization of all school children provides only a slight improvement over closing schools, indicating that schools are an important venue for transmission between children. Relative attack rates in adults and children provide a good indication of the likely benefit of closing schools, with the greatest impact seen for infections with high attack rates in children. Closing schools is effective at reducing transmission between children but has only a moderate effect on average transmission rates in the wider population unless children are disproportionately affected.

  15. Analysis of influenza transmission in the households of primary and junior high school students during the 2012-13 influenza season in Odate, Japan.

    PubMed

    Kamigaki, Taro; Mimura, Satoshi; Takahashi, Yoshihiro; Oshitani, Hitoshi

    2015-07-23

    Households are one of the major settings of influenza transmission in the community and transmission is frequently initiated by school-aged children. We surveyed households with primary school (PS) and/ or junior high school (JH) children for the 2012-13 influenza season in Odate, Japan then characterized the epidemiology of influenza household transmission as well as estimated the serial intervals. We delivered a self-reported questionnaire survey to households with PS and/or JH school children in Odate City, Japan. Influenza A (H3N2) virus predominantly circulated during the 2012-13 influenza season. We investigated the epidemiological characteristics of within-household transmission and calculated the serial intervals (SI). SIs were drew by a non-parametric model and compared with parametric models by the Akaike Information Criterion. The covariable contributions were investigated by the accelerated failure model. Household influenza transmission was identified in 255 out of 363 household respondents. Primary school (PS) children accounted for 45.1 % of primary cases, and disease transmission was most commonly observed between PS children and parents, followed by transmission from PS children to siblings. In primary cases of PS or JH children, younger age and longer absence from school were significantly associated with household transmission events. The mean SI was estimated as 2.8 days (95 % confidence interval 2.6-3.0 days) in the lognormal model. The estimated acceleration factors revealed that while secondary school age and the absence duration > 7 days were associated with shorter and longer SIs, respectively, antiviral prescriptions for primary cases made no contribution. High frequencies of household transmission from primary school with shorter SI were found. These findings contribute to the development of future mitigation strategies against influenza transmission in Japan.

  16. Role of Temperature, Humidity and Rainfall on Influenza Transmission in Guatemala, El Salvador and Panama

    NASA Technical Reports Server (NTRS)

    Soebiyanto, Radina P.; Bonilla, Luis; Jara, Jorge; McCracken, John; Azziz?-Baumgartner, Eduardo; Widdowson, Marc-Alain; Kiang, Richard

    2012-01-01

    Worldwide, seasonal influenza causes about 500,000 deaths and 5 million severe illnesses per year. The environmental drivers of influenza transmission are poorly understood especially in the tropics. We aimed to identify meteorological factors for influenza transmission in tropical Central America. We gathered laboratory-confirmed influenza case-counts by week from Guatemala City, San Salvador Department (El Salvador) and Panama Province from 2006 to 2010. The average total cases per year were: 390 (Guatemala), 99 (San Salvador) and 129 (Panama). Meteorological factors including daily air temperature, rainfall, relative and absolute humidity (RH, AH) were obtained from ground stations, NASA satellites and land models. For these factors, we computed weekly averages and their deviation from the 5-yr means. We assessed the relationship between the number of influenza case-counts and the meteorological factors, including effects lagged by 1 to 4 weeks, using Poisson regression for each site. Our results showed influenza in San Salvador would increase by 1 case within a week of every 1 day with RH>75% (Relative Risk (RR)= 1.32, p=.001) and every 1C increase in minimum temperature (RR=1.29, p=.007) but it would decrease by 1 case for every 1mm-above mean weekly rainfall (RR=0.93,p<.001) (model pseudo-R2=0.55). Within 2 weeks, influenza in Panama was increased by 1 case for every 1% increase in RH (RR=1.04, p=.003), and it was increased by 2 cases for every 1C increase of minimum temperature (RR=2.01, p<.001) (model pseudo-R2=0.4). Influenza counts in Guatemala had 1 case increase for every 1C increase in minimum temperature in the previous week (RR=1.21, p<.001), and for every 1mm/day-above normal increase of rainfall rate (RR=1.03, p=.03) (model pseudo-R2=0.54). Our findings that cases increase with temperature and humidity differ from some temperate-zone studies. But they indicate that climate parameters such as humidity and temperature could be predictive of influenza

  17. Hand hygiene to reduce community transmission of influenza and acute respiratory tract infection: a systematic review.

    PubMed

    Warren-Gash, Charlotte; Fragaszy, Ellen; Hayward, Andrew C

    2013-09-01

    Hand hygiene may be associated with modest protection against some acute respiratory tract infections, but its specific role in influenza transmission in different settings is unclear. We aimed to review evidence that improving hand hygiene reduces primary and secondary transmission of (i) influenza and (ii) acute respiratory tract infections in community settings. We searched Medline, Embase, Global Health and Cochrane databases up to 13 February 2012 for reports in any language of original research investigating the effect of hand hygiene on influenza or acute respiratory tract infection where aetiology was unspecified in community settings including institutions such as schools, and domestic residences. Data were presented and quality rated across outcomes according to the Grading of Recommendations Assessment, Development and Evaluation system. Sixteen articles met inclusion criteria. There was moderate to low-quality evidence of a reduction in both influenza and respiratory tract infection with hand hygiene interventions in schools, greatest in a lower-middle-income setting. There was high-quality evidence of a small reduction in respiratory infection in childcare settings. There was high-quality evidence for a large reduction in respiratory infection with a hand hygiene intervention in squatter settlements in a low-income setting. There was moderate- to high-quality evidence of no effect on secondary transmission of influenza in households that had already experienced an index case. While hand hygiene interventions have potential to reduce transmission of influenza and acute respiratory tract infections, their effectiveness varies depending on setting, context and compliance. © 2012 John Wiley & Sons Ltd.

  18. Estimating dynamic transmission model parameters for seasonal influenza by fitting to age and season-specific influenza-like illness incidence.

    PubMed

    Goeyvaerts, Nele; Willem, Lander; Van Kerckhove, Kim; Vandendijck, Yannick; Hanquet, Germaine; Beutels, Philippe; Hens, Niel

    2015-12-01

    Dynamic transmission models are essential to design and evaluate control strategies for airborne infections. Our objective was to develop a dynamic transmission model for seasonal influenza allowing to evaluate the impact of vaccinating specific age groups on the incidence of infection, disease and mortality. Projections based on such models heavily rely on assumed 'input' parameter values. In previous seasonal influenza models, these parameter values were commonly chosen ad hoc, ignoring between-season variability and without formal model validation or sensitivity analyses. We propose to directly estimate the parameters by fitting the model to age-specific influenza-like illness (ILI) incidence data over multiple influenza seasons. We used a weighted least squares (WLS) criterion to assess model fit and applied our method to Belgian ILI data over six influenza seasons. After exploring parameter importance using symbolic regression, we evaluated a set of candidate models of differing complexity according to the number of season-specific parameters. The transmission parameters (average R0, seasonal amplitude and timing of the seasonal peak), waning rates and the scale factor used for WLS optimization, influenced the fit to the observed ILI incidence the most. Our results demonstrate the importance of between-season variability in influenza transmission and our estimates are in line with the classification of influenza seasons according to intensity and vaccine matching.

  19. Avian biology, the human influence on global avian influenza transmission, and performing surveillance in wild birds.

    PubMed

    Gibbs, Samantha E J

    2010-06-01

    This paper takes a closer look at three interrelated areas of study: avian host biology, the role of human activities in virus transmission, and the surveillance activities centered on avian influenza in wild birds. There are few ecosystems in which birds are not found. Correspondingly, avian influenza viruses are equally global in distribution, relying on competent avian hosts. The immune systems, annual cycles, feeding behaviors, and migration patterns of these hosts influence the ecology of the disease. Decreased biodiversity has also been linked to heightened disease transmission in several disease systems, and it is evident that active destruction and modification of wetland environments for human use is impacting avian populations drastically. Legal and illegal trade in wild birds present a significant risk for introduction and maintenance of exotic diseases. After the emergence of HPAI H5N1 in Hong Kong in 1996 and the ensuing geographic spread of outbreaks after 2003, both infected countries and those at risk of introduction began intensifying avian influenza surveillance efforts. Several techniques for sampling wild birds for influenza viruses have been applied. Benefits, problems, and biases exist for each method. The wild bird avian influenza surveillance programs taking place across the continents are now scaling back due to the rise of other spending priorities; hopefully the lessons learned from this work will be preserved and will inform future research and disease outbreak response priorities.

  20. Amino acid substitutions in PB1 of avian influenza viruses influence pathogenicity and transmissibility in chickens.

    PubMed

    Suzuki, Yasushi; Uchida, Yuko; Tanikawa, Taichiro; Maeda, Naohiro; Takemae, Nobuhiro; Saito, Takehiko

    2014-10-01

    Amino acid substitutions were introduced into avian influenza virus PB1 in order to characterize the interaction between polymerase activity and pathogenicity. Previously, we used recombinant viruses containing the hemagglutinin (HA) and neuraminidase (NA) genes from the highly pathogenic avian influenza virus (HPAIV) H5N1 strain and other internal genes from two low-pathogenicity avian influenza viruses isolated from chicken and wild-bird hosts (LP and WB, respectively) to demonstrate that the pathogenicity of highly pathogenic avian influenza viruses (HPAIVs) of subtype H5N1 in chickens is regulated by the PB1 gene (Y. Uchida et al., J. Virol. 86:2686-2695, 2012, doi:http://dx.doi.org/10.1128/JVI.06374-11). In the present study, we introduced a C38Y substitution into WB PB1 and demonstrated that this substitution increased both polymerase activity in DF-1 cells in vitro and the pathogenicity of the recombinant viruses in chickens. The V14A substitution in LP PB1 reduced polymerase activity but did not affect pathogenicity in chickens. Interestingly, the V14A substitution reduced viral shedding and transmissibility. These studies demonstrate that increased polymerase activity correlates directly with enhanced pathogenicity, while decreased polymerase activity does not always correlate with pathogenicity and requires further analysis. We identified 2 novel amino acid substitutions in the avian influenza virus PB1 gene that affect the characteristics of highly pathogenic avian influenza viruses (HPAIVs) of the H5N1 subtype, such as viral replication and polymerase activity in vitro and pathogenicity and transmissibly in chickens. An amino acid substitution at residue 38 in PB1 directly affected pathogenicity in chickens and was associated with changes in polymerase activity in vitro. A substitution at residue 14 reduced polymerase activity in vitro, while its effects on pathogenicity and transmissibility depended on the constellation of internal genes. Copyright

  1. Phylogeny, Pathogenicity, and Transmission of H5N1 Avian Influenza Viruses in Chickens

    PubMed Central

    Cui, Jin; Qu, Nannan; Guo, Yang; Cao, Lan; Wu, Siyu; Mei, Kun; Sun, Hailiang; Lu, Yiliang; Qin, Zhifeng; Jiao, Peirong; Liao, Ming

    2017-01-01

    We analyzed five H5N1 avian influenza viruses (AIVs) isolated from different birds in 2012 in China. Based on whole-genome sequences, we divided the viruses into four genotypes. The DKE26, GSE43, and DKE53 viruses belonged to Genotypes 1–3, respectively. The CKE93 and CKE96 viruses were classified into Genotype 4. Genotypes 1–3 correspond to the viruses containing the HA gene of clade 2.3.2, and Genotype 4 is the virus that bears the HA gene of clade 7.2. To better understand the pathogenicity and transmission of the viruses, we infected chickens with 103 EID50/0.1 ml GSE43 (clade 2.3.2) or CKE93 (clade 7.2) virus. Our results revealed that 6 of 7 specific-pathogen-free (SPF) chickens inoculated with GSE43 virus were dead before 7-day post-infection, but all the SPF chickens inoculated with CKE93 virus survived the infection. Both the GSE43 and CKE93 viruses replicated systemically in chickens. The virus titers of GSE43 virus in tested organs were obviously higher than those of CKE93 virus. Our results revealed that the pathogenicity and replication of GSE43 in chickens was much higher than those of CKE93. The GSE43 virus could transmit between chickens, but the CKE93 could not transmit between chickens by naïve contact. Therefore, different clades of H5N1 AIVs possessed variable pathogenicities and transmission abilities among chickens. Our study contributes to knowledge of pathogenic variations of prevalent H5N1 viruses. PMID:28770175

  2. Phylogeny, Pathogenicity, and Transmission of H5N1 Avian Influenza Viruses in Chickens.

    PubMed

    Cui, Jin; Qu, Nannan; Guo, Yang; Cao, Lan; Wu, Siyu; Mei, Kun; Sun, Hailiang; Lu, Yiliang; Qin, Zhifeng; Jiao, Peirong; Liao, Ming

    2017-01-01

    We analyzed five H5N1 avian influenza viruses (AIVs) isolated from different birds in 2012 in China. Based on whole-genome sequences, we divided the viruses into four genotypes. The DKE26, GSE43, and DKE53 viruses belonged to Genotypes 1-3, respectively. The CKE93 and CKE96 viruses were classified into Genotype 4. Genotypes 1-3 correspond to the viruses containing the HA gene of clade 2.3.2, and Genotype 4 is the virus that bears the HA gene of clade 7.2. To better understand the pathogenicity and transmission of the viruses, we infected chickens with 10(3) EID50/0.1 ml GSE43 (clade 2.3.2) or CKE93 (clade 7.2) virus. Our results revealed that 6 of 7 specific-pathogen-free (SPF) chickens inoculated with GSE43 virus were dead before 7-day post-infection, but all the SPF chickens inoculated with CKE93 virus survived the infection. Both the GSE43 and CKE93 viruses replicated systemically in chickens. The virus titers of GSE43 virus in tested organs were obviously higher than those of CKE93 virus. Our results revealed that the pathogenicity and replication of GSE43 in chickens was much higher than those of CKE93. The GSE43 virus could transmit between chickens, but the CKE93 could not transmit between chickens by naïve contact. Therefore, different clades of H5N1 AIVs possessed variable pathogenicities and transmission abilities among chickens. Our study contributes to knowledge of pathogenic variations of prevalent H5N1 viruses.

  3. Avian influenza shedding patterns in waterfowl: implications for surveillance, environmental transmission, and disease spread

    USGS Publications Warehouse

    Viviane Henaux,; Samuel, Michael D.

    2011-01-01

    Despite the recognized importance of fecal/oral transmission of low pathogenic avian influenza (LPAI) via contaminated wetlands, little is known about the length, quantity, or route of AI virus shed by wild waterfowl. We used published laboratory challenge studies to evaluate the length and quantity of low pathogenic (LP) and highly pathogenic (HP) virus shed via oral and cloacal routes by AI-infected ducks and geese, and how these factors might influence AI epidemiology and virus detection. We used survival analysis to estimate the duration of infection (from virus inoculation to the last day virus was shed) and nonlinear models to evaluate temporal patterns in virus shedding. We found higher mean virus titer and longer median infectious period for LPAI-infected ducks (10–11.5 days in oral and cloacal swabs) than HPAI-infected ducks (5 days) and geese (7.5 days). Based on the median bird infectious dose, we found that environmental contamination is two times higher for LPAI- than HPAI-infectious ducks, which implies that susceptible birds may have a higher probability of infection during LPAI than HPAI outbreaks. Less environmental contamination during the course of infection and previously documented shorter environmental persistence for HPAI than LPAI suggest that the environment is a less favorable reservoir for HPAI. The longer infectious period, higher virus titers, and subclinical infections with LPAI viruses favor the spread of these viruses by migratory birds in comparison to HPAI. Given the lack of detection of HPAI viruses through worldwide surveillance, we suggest monitoring for AI should aim at improving our understanding of AI dynamics (in particular, the role of the environment and immunity) using long-term comprehensive live bird, serologic, and environmental sampling at targeted areas. Our findings on LPAI and HPAI shedding patterns over time provide essential information to parameterize environmental transmission and virus spread in predictive

  4. Optimal control of an influenza model with seasonal forcing and age-dependent transmission rates.

    PubMed

    Lee, Jeehyun; Kim, Jungeun; Kwon, Hee-Dae

    2013-01-21

    This study considers an optimal intervention strategy for influenza outbreaks. Variations in the SEIAR model are considered to include seasonal forcing and age structure, and control strategies include vaccination, antiviral treatment, and social distancing such as school closures. We formulate an optimal control problem by minimizing the incidence of influenza outbreaks while considering intervention costs. We examine the effects of delays in vaccine production, seasonal forcing, and age-dependent transmission rates on the optimal control and suggest some optimal strategies through numerical simulations.

  5. Disrupting the Transmission of Influenza A: Face Masks and Ultraviolet Light as Control Measures

    PubMed Central

    Weiss, Martin Meyer; Weiss, Peter D.; Weiss, Danielle E.; Weiss, Joseph B.

    2007-01-01

    In the event of an influenza pandemic, where effective vaccine and antiviral drugs may be lacking, disrupting environmental transmission of the influenza virus will be the only viable strategy to protect the public. We discuss 2 such modalities, respirators (face masks) and ultraviolet (UV) light. Largely overlooked, the potential utility of each is underappreciated. The effectiveness of disposable face masks may be increased by sealing the edges of the mask to the face. Reusable masks should be stockpiled, because the supply of disposable masks will likely prove inadequate. UV light, directed overhead, may be beneficial in hospitals and nursing homes. PMID:17413061

  6. Transmission potential of influenza A/H7N9, February to May 2013, China

    PubMed Central

    2013-01-01

    Background On 31 March 2013, the first human infections with the novel influenza A/H7N9 virus were reported in Eastern China. The outbreak expanded rapidly in geographic scope and size, with a total of 132 laboratory-confirmed cases reported by 3 June 2013, in 10 Chinese provinces and Taiwan. The incidence of A/H7N9 cases has stalled in recent weeks, presumably as a consequence of live bird market closures in the most heavily affected areas. Here we compare the transmission potential of influenza A/H7N9 with that of other emerging pathogens and evaluate the impact of intervention measures in an effort to guide pandemic preparedness. Methods We used a Bayesian approach combined with a SEIR (Susceptible-Exposed-Infectious-Removed) transmission model fitted to daily case data to assess the reproduction number (R) of A/H7N9 by province and to evaluate the impact of live bird market closures in April and May 2013. Simulation studies helped quantify the performance of our approach in the context of an emerging pathogen, where human-to-human transmission is limited and most cases arise from spillover events. We also used alternative approaches to estimate R based on individual-level information on prior exposure and compared the transmission potential of influenza A/H7N9 with that of other recent zoonoses. Results Estimates of R for the A/H7N9 outbreak were below the epidemic threshold required for sustained human-to-human transmission and remained near 0.1 throughout the study period, with broad 95% credible intervals by the Bayesian method (0.01 to 0.49). The Bayesian estimation approach was dominated by the prior distribution, however, due to relatively little information contained in the case data. We observe a statistically significant deceleration in growth rate after 6 April 2013, which is consistent with a reduction in A/H7N9 transmission associated with the preemptive closure of live bird markets. Although confidence intervals are broad, the estimated

  7. Survivability of Eurasian H5N1 highly pathogenic avian influenza viruses in water varies between strains

    USDA-ARS?s Scientific Manuscript database

    Aquatic habitats play critical role in the transmission and maintenance of low pathogenic avian influenza (LPAI) viruses in wild waterfowl; however the importance of these environments in the ecology of H5N1 highly pathogenic avian influenza (HPAI) viruses is unknown. In laboratory-based studies, L...

  8. Oseltamivir expands quasispecies of influenza virus through cell-to-cell transmission.

    PubMed

    Mori, Kotaro; Murano, Kensaku; Ohniwa, Ryosuke L; Kawaguchi, Atsushi; Nagata, Kyosuke

    2015-03-16

    The population of influenza virus consists of a huge variety of variants, called quasispecies, due to error-prone replication. Previously, we reported that progeny virions of influenza virus become infected to adjacent cells via cell-to-cell transmission pathway in the presence of oseltamivir. During cell-to-cell transmission, viruses become infected to adjacent cells at high multiplicity since progeny virions are enriched on plasma membrane between infected cells and their adjacent cells. Co-infection with viral variants may rescue recessive mutations with each other. Thus, it is assumed that the cell-to-cell transmission causes expansion of virus quasispecies. Here, we have demonstrated that temperature-sensitive mutations remain in progeny viruses even at non-permissive temperature by co-infection in the presence of oseltamivir. This is possibly due to a multiplex infection through the cell-to-cell transmission by the addition of oseltamivir. Further, by the addition of oseltamivir, the number of missense mutation introduced by error-prone replication in segment 8 encoding NS1 was increased in a passage-dependent manner. The number of missense mutation in segment 5 encoding NP was not changed significantly, whereas silent mutation was increased. Taken together, we propose that oseltamivir expands influenza virus quasispecies via cell-to-cell transmission, and may facilitate the viral evolution and adaptation.

  9. Influenza A virus transmission via respiratory aerosols or droplets as it relates to pandemic potential

    PubMed Central

    Richard, Mathilde; Fouchier, Ron A.M.

    2015-01-01

    Many respiratory viruses of humans originate from animals. For instance, there are now eight paramyxoviruses, four coronaviruses and four orthomxoviruses that cause recurrent epidemics in humans but were once confined to other hosts. In the last decade, several members of the same virus families have jumped the species barrier from animals to humans. Fortunately, these viruses have not become established in humans, because they lacked the ability of sustained transmission between humans. However, these outbreaks highlighted the lack of understanding of what makes a virus transmissible. In part triggered by the relatively high frequency of occurrence of influenza A virus zoonoses and pandemics, the influenza research community has started to investigate the viral genetic and biological traits that drive virus transmission via aerosols or respiratory droplets between mammals. Here we summarize recent discoveries on the genetic and phenotypic traits required for airborne transmission of zoonotic influenza viruses of subtypes H5, H7 and H9 and pandemic viruses of subtypes H1, H2 and H3. Increased understanding of the determinants and mechanisms of respiratory virus transmission is not only key from a basic scientific perspective, but may also aid in assessing the risks posed by zoonotic viruses to human health, and preparedness for such risks. PMID:26385895

  10. The impact of illness on social networks: implications for transmission and control of influenza.

    PubMed

    Van Kerckhove, Kim; Hens, Niel; Edmunds, W John; Eames, Ken T D

    2013-12-01

    We expect social networks to change as a result of illness, but social contact data are generally collected from healthy persons. Here we quantified the impact of influenza-like illness on social mixing patterns. We analyzed the contact patterns of persons from England measured when they were symptomatic with influenza-like illness during the 2009 A/H1N1pdm influenza epidemic (2009-2010) and again 2 weeks later when they had recovered. Illness was associated with a reduction in the number of social contacts, particularly in settings outside the home, reducing the reproduction number to about one-quarter of the value it would otherwise have taken. We also observed a change in the age distribution of contacts. By comparing the expected age distribution of cases resulting from transmission by (a)symptomatic persons with incidence data, we estimated the contribution of both groups to transmission. Using this, we calculated the fraction of transmission resulting from (a)symptomatic persons, assuming equal duration of infectiousness. We estimated that 66% of transmission was attributable to persons with symptomatic disease (95% confidence interval: 0.23, 1.00). This has important implications for control: Treating symptomatic persons with antiviral agents or encouraging home isolation would be expected to have a major impact on transmission, particularly since the reproduction number for this strain was low.

  11. Microstructure of atmospheric particles revealed by TXM and a new mode of influenza virus transmission

    NASA Astrophysics Data System (ADS)

    Bao, L. M.; Zhang, G. L.; Lei, Q. T.; Li, Y.; Li, X. L.; Hwu, Y. K.; Yi, J. M.

    2015-09-01

    For control of influenza, firstly it is important to find the real virus transmission media. Atmospheric aerosol particles are presumably one of the media. In this study, three typical atmospheric inhaled particles in Shanghai were studied by the synchrotron based transmission X-ray microscopes (TXM). Three dimensional microstructure of the particles reveals that there are many pores contained in, particularly the coal combustion fly particles which may be possible virus carrier. The particles can transport over long distance and cause long-range infections due to its light weight. We suggest a mode which is droplet combining with aerosol mode. By this mode the transmission of global and pandemic influenzas and infection between inland avian far from population and poultry or human living in cities along coast may be explained.

  12. [Role of the poultry red mite (Dermanyssus gallinae) in the transmission of avian influenza A virus].

    PubMed

    Sommer, D; Heffels-Redmann, U; Köhler, K; Lierz, M; Kaleta, E F

    2016-01-01

    The aim of this study was to investigate the role of the poultry red mite (Dermanyssus [D.] gallinae) in the horizontal transmission of avian influenza A virus (AIV) to chickens. This mite is the most common ectoparasite in poultry worldwide, and may play a role in the spread of infectious agents including AIV. Currently, the control of mites is difficult due to frequently developed resistance to many acaricides, their nocturnality and their ability to survive hidden without feeding for months. D. gallinae were collected in a commercial layer farm and housed in self-made fibreboard boxes. SPF chickens were intravenously infected with AIV strain A/turkey/Ontario/7732/1966 (H5N9). The viraemia in chickens was monitored and at an appropriate time point about 1000 mites were allowed to suck on the AIV infected chickens. Re-isolation of the virus from blood-filled mites was tried daily for 14 days using chicken embryo fibroblast cultures and embryonated chicken eggs. Subsequently, the virus containing mites were placed into boxes that contained naïve SPF chickens to enable virus transmission from mites to chickens. Possible transmission to the chickens was examined using clinical signs, serology, gross lesions, histopathology and immunohistochemistry. Chickens developed a dose-dependent viraemia one day after infection, therefore this day was chosen for the bloodmeal of the mites. AIV was detected in mites after bloodsucking on AIV-infected chickens over a 10-day period. Naïve SPF chickens were infected during bloodsucking of AIV carrying mites. AIV isolates in mites and in chickens were undistinguishable from the original AIV inoculum by RT-PCR. D. gallinae ingested AIV during bloodmeals on AIV infected chickens and are able to transmit AIV to SPF chickens. Therefore, mites serve as mechanical vector of AIV and may play a major role in the circulation of AIV within a facility or area although the life span of infectious virus in the mite is limited. The proven

  13. Influenza-Sediment Interactions

    NASA Astrophysics Data System (ADS)

    Trusiak, A.; Block, K. A.; Katz, A.; Gottlieb, P.; Alimova, A.; Galarza, J.; Wei, H.; Steiner, J. C.

    2013-12-01

    A typical water fowl can secrete 1012 influenza virions per day. Therefore it is not unexpected that influenza virions interact with sediments in the water column. The influence of sediments on avian influenza virions is not known. With the threat of avian influenza emerging into the human population, it is crucial to understand virus survivability and residence time in a body of water. Influenza and clay sediments are colloidal particles and thus aggregate as explained by DLVO (Derjaguin & Landau, Verwey & Overbeek) theory. Of great importance is an understanding of the types of particulate or macromolecular components that bind the virus particles, and whether the virus remains biologically active. We present results of hetero-aggregation and transmission electron microscopy experiments performed with influenza A/PR8/38. Influenza particles are suspended with sediment and minimal nutrients for several days, after which the components are evaluated to determine influenza concentration and survivability. Transmission electron microscopy results are reported on the influenza-sediment aggregates to elucidate structure and morphology of the components.

  14. Transmission of Eurasian avian H2 influenza virus to shorebirds in North America.

    PubMed

    Makarova, N V; Kaverin, N V; Krauss, S; Senne, D; Webster, R G

    1999-12-01

    Influenza A virus of the H2 subtype caused a serious pandemic in 1957 and may cause similar outbreaks in the future. To assess the evolution and the antigenic relationships of avian influenza H2 viruses, we sequenced the haemagglutinin (HA) genes of H2 isolates from shorebirds, ducks and poultry in North America and derived a phylogenetic tree to establish their interrelationships. This analysis confirmed the divergence of H2 HA into two geographical lineages, American and Eurasian. One group of viruses isolated from shorebirds in North America had HA belonging to the Eurasian lineage, indicating an interregional transmission of the H2 gene. Characterization of HA with a monoclonal antibody panel revealed that the antigenicity of the Delaware strains differed from the other avian strains analysed. The data emphasizes the importance of avian influenza surveillance.

  15. Pandemic A/H1N1 influenza: transmission of the first cases in Spain.

    PubMed

    Català, Laura; Rius, Cristina; García de Olalla, Patricia; Nelson, Jeanne L; Alvarez, Josep; Minguell, Sofía; Camps, Neus; Sala, María Rosa; Arias, Carlos; Barrabeig, Irene; Carol, Mónica; Torra, Roser; Cardeñosa, Neus; Pumarola, Tomas; Caylà, Joan A

    2012-02-01

    Pandemic A/H1N1 influenza emerged in Mexico at the end of March 2009. Since then, it is still important to provide evidences that contributed to the international spread of the virus and to ascertain the attack rate of this new strain of influenza among the first cases in Spain that led to identify the first transmission in Europe. Three pandemic A/H1N1 influenza groups related to an overseas flight were studied: 71 student group, 94 remaining passengers, and 68 contacts of confirmed cases. The attack rate with their 95% confidence interval (CI) among the student group and contacts was calculated. On April 26th, when the first cases were notified, strong preventive measures were implemented among the student group and the contacts of the confirmed cases. On 27th April, the first pandemic A/H1N1 influenza cases confirmed in Spain were three students that came back from Mexico by airplane. A student generated the first native case in Spain and one of the first cases in Europe. Similar attack rates were found between the student group (14.1%; CI: 12.1-16.1) and their contacts (13.2%; CI: 4.4-22.0), but no cases among remaining passengers were detected, suggesting low transmission risk during air travel. The first cases of pandemic A/H1N1 influenza in Spain were imported by airplane from Mexico. Preventive efforts to reduce the impact of the influenza influenced that primary and secondary rates were lower than first estimations by WHO. Copyright © 2011 Elsevier España, S.L. All rights reserved.

  16. The role of influenza in the severity and transmission of respiratory bacterial disease

    PubMed Central

    Mina, Michael J; Klugman, Keith P

    2016-01-01

    Infections with influenza viruses and respiratory bacteria each contribute substantially to the global burden of morbidity and mortality. Simultaneous or sequential infection with these pathogens manifests in complex and difficult-to-treat disease processes that need extensive antimicrobial therapy and cause substantial excess mortality, particularly during annual influenza seasons and pandemics. At the host level, influenza viruses prime respiratory mucosal surfaces for excess bacterial acquisition and this supports increased carriage density and dissemination to the lower respiratory tract, while greatly constraining innate and adaptive antibacterial defences. Driven by virus-mediated structural modifications, aberrant immunological responses to sequential infection, and excessive immunopathological responses, co-infections are noted by short-term and long-term departures from immune homoeostasis, inhibition of appropriate pathogen recognition, loss of tolerance to tissue damage, and general increases in susceptibility to severe bacterial disease. At the population level, these effects translate into increased horizontal bacterial transmission and excess use of antimicrobial therapies. With increasing concerns about future possible influenza pandemics, the past decade has seen rapid advances in our understanding of these interactions. In this Review, we discuss the epidemiological and clinical importance of influenza and respiratory bacterial co-infections, including the foundational efforts that laid the groundwork for today’s investigations, and detail the most important and current advances in our understanding of the structural and immunological mechanisms underlying the pathogenesis of co-infection. We describe and interpret what is known in sequence, from transmission and phenotypic shifts in bacterial dynamics to the immunological, cellular, and molecular modifications that underlie these processes, and propose avenues of further research that might be

  17. Transmission of influenza reflects seasonality of wild birds across the annual cycle

    USGS Publications Warehouse

    Hill, Nichola J.; Ma, Eric J.; Meixell, Brandt W.; Lindberg, Mark S.; Boyce, Walter M.; Runstadler, Jonathan A.

    2016-01-01

    Influenza A Viruses (IAV) in nature must overcome shifting transmission barriers caused by the mobility of their primary host, migratory wild birds, that change throughout the annual cycle. Using a phylogenetic network of viral sequences from North American wild birds (2008–2011) we demonstrate a shift from intraspecific to interspecific transmission that along with reassortment, allows IAV to achieve viral flow across successive seasons from summer to winter. Our study supports amplification of IAV during summer breeding seeded by overwintering virus persisting locally and virus introduced from a wide range of latitudes. As birds migrate from breeding sites to lower latitudes, they become involved in transmission networks with greater connectivity to other bird species, with interspecies transmission of reassortant viruses peaking during the winter. We propose that switching transmission dynamics may be a critical strategy for pathogens that infect mobile hosts inhabiting regions with strong seasonality.

  18. Environmental Conditions Affect Exhalation of H3N2 Seasonal and Variant Influenza Viruses and Respiratory Droplet Transmission in Ferrets

    PubMed Central

    Gustin, Kortney M.; Belser, Jessica A.; Veguilla, Vic; Zeng, Hui; Katz, Jacqueline M.; Tumpey, Terrence M.; Maines, Taronna R.

    2015-01-01

    The seasonality of influenza virus infections in temperate climates and the role of environmental conditions like temperature and humidity in the transmission of influenza virus through the air are not well understood. Using ferrets housed at four different environmental conditions, we evaluated the respiratory droplet transmission of two influenza viruses (a seasonal H3N2 virus and an H3N2 variant virus, the etiologic virus of a swine to human summertime infection) and concurrently characterized the aerosol shedding profiles of infected animals. Comparisons were made among the different temperature and humidity conditions and between the two viruses to determine if the H3N2 variant virus exhibited enhanced capabilities that may have contributed to the infections occurring in the summer. We report here that although increased levels of H3N2 variant virus were found in ferret nasal wash and exhaled aerosol samples compared to the seasonal H3N2 virus, enhanced respiratory droplet transmission was not observed under any of the environmental settings. However, overall environmental conditions were shown to modulate the frequency of influenza virus transmission through the air. Transmission occurred most frequently at 23°C/30%RH, while the levels of infectious virus in aerosols exhaled by infected ferrets agree with these results. Improving our understanding of how environmental conditions affect influenza virus infectivity and transmission may reveal ways to better protect the public against influenza virus infections. PMID:25969995

  19. Association of Oseltamivir Treatment With Virus Shedding, Illness, and Household Transmission of Influenza Viruses

    PubMed Central

    Cheung, Doug H.; Tsang, Tim K.; Fang, Vicky J.; Xu, Jiajing; Chan, Kwok-Hung; Ip, Dennis K. M.; Peiris, Joseph Sriyal Malik; Leung, Gabriel M.; Cowling, Benjamin J.

    2015-01-01

    In an observational study of 582 patients with laboratory-confirmed influenza virus infections and their household contacts, we found that the initiation of oseltamivir within 24 hours was associated with shorter duration of self-reported illness symptoms (56% reduction in duration; 95% confidence interval, 41%–67%). However, we did not find any association of oseltamivir treatment with duration of viral shedding by polymerase chain reaction or with the risk of household transmission. PMID:25646354

  20. Contemporary North American influenza H7 viruses possess human receptor specificity: Implications for virus transmissibility.

    PubMed

    Belser, Jessica A; Blixt, Ola; Chen, Li-Mei; Pappas, Claudia; Maines, Taronna R; Van Hoeven, Neal; Donis, Ruben; Busch, Julia; McBride, Ryan; Paulson, James C; Katz, Jacqueline M; Tumpey, Terrence M

    2008-05-27

    Avian H7 influenza viruses from both the Eurasian and North American lineage have caused outbreaks in poultry since 2002, with confirmed human infection occurring during outbreaks in The Netherlands, British Columbia, and the United Kingdom. The majority of H7 infections have resulted in self-limiting conjunctivitis, whereas probable human-to-human transmission has been rare. Here, we used glycan microarray technology to determine the receptor-binding preference of Eurasian and North American lineage H7 influenza viruses and their transmissibility in the ferret model. We found that highly pathogenic H7N7 viruses from The Netherlands in 2003 maintained the classic avian-binding preference for alpha2-3-linked sialic acids (SA) and are not readily transmissible in ferrets, as observed previously for highly pathogenic H5N1 viruses. However, H7N3 viruses isolated from Canada in 2004 and H7N2 viruses from the northeastern United States isolated in 2002-2003 possessed an HA with increased affinity toward alpha2-6-linked SA, the linkage type found prominently on human tracheal epithelial cells. We identified a low pathogenic H7N2 virus isolated from a man in New York in 2003, A/NY/107/03, which replicated efficiently in the upper respiratory tract of ferrets and was capable of transmission in this species by direct contact. These results indicate that H7 influenza viruses from the North American lineage have acquired sialic acid-binding properties that more closely resemble those of human influenza viruses and have the potential to spread to naïve animals.

  1. Influenza Virus Respiratory Infection and Transmission Following Ocular Inoculation in Ferrets

    PubMed Central

    Belser, Jessica A.; Gustin, Kortney M.; Maines, Taronna R.; Pantin-Jackwood, Mary J.; Katz, Jacqueline M.; Tumpey, Terrence M.

    2012-01-01

    While influenza viruses are a common respiratory pathogen, sporadic reports of conjunctivitis following human infection demonstrates the ability of this virus to cause disease outside of the respiratory tract. The ocular surface represents both a potential site of virus replication and a portal of entry for establishment of a respiratory infection. However, the properties which govern ocular tropism of influenza viruses, the mechanisms of virus spread from ocular to respiratory tissue, and the potential differences in respiratory disease initiated from different exposure routes are poorly understood. Here, we established a ferret model of ocular inoculation to explore the development of virus pathogenicity and transmissibility following influenza virus exposure by the ocular route. We found that multiple subtypes of human and avian influenza viruses mounted a productive virus infection in the upper respiratory tract of ferrets following ocular inoculation, and were additionally detected in ocular tissue during the acute phase of infection. H5N1 viruses maintained their ability for systemic spread and lethal infection following inoculation by the ocular route. Replication-independent deposition of virus inoculum from ocular to respiratory tissue was limited to the nares and upper trachea, unlike traditional intranasal inoculation which results in virus deposition in both upper and lower respiratory tract tissues. Despite high titers of replicating transmissible seasonal viruses in the upper respiratory tract of ferrets inoculated by the ocular route, virus transmissibility to naïve contacts by respiratory droplets was reduced following ocular inoculation. These data improve our understanding of the mechanisms of virus spread following ocular exposure and highlight differences in the establishment of respiratory disease and virus transmissibility following use of different inoculation volumes and routes. PMID:22396651

  2. Serological evidence of pig-to-human influenza virus transmission on Thai swine farms.

    PubMed

    Kitikoon, Pravina; Sreta, Donruethai; Tuanudom, Ranida; Amonsin, Alongkorn; Suradhat, Sanipa; Oraveerakul, Kanisak; Poovorawan, Yong; Thanawongnuwech, Roongroje

    2011-03-24

    We investigated influenza interspecies transmission in two commercial swine farms in Thailand. Sera from swine-exposed workers (n=78), age-matched non-swine-exposed healthy people (n=60) and swine populations in both farms (n=85) were studied. Hemagglutination-inhibition (HI) assay was performed on Thai swine H1 viruses (swH1N1 and swH1N2) isolated from both farms. Thai human H1N1 (huH1N1) and pandemic H1N1 2009 (pH1N1) were also used as test antigens. The hemagglutinin (HA) 1 genes of swH1N1 and swH1N2 viruses were sequenced and shown to be genetically distinct from the Thai huH1N1 and pH1N1 viruses. Evidence of pig-to-human influenza virus transmission was found in farm workers with increased odds of elevated antibody titers to both swH1N1 (OR 42.63, 95% CI, 14.65-124) and swH1N2 (OR 58, 95% CI, 13.12-256.3) viruses. No evidence of human-to-pig influenza virus transmission was detected in this study. Copyright © 2010 Elsevier B.V. All rights reserved.

  3. Human mobility and the spatial transmission of influenza in the United States

    PubMed Central

    Charu, Vivek; Zeger, Scott; Gog, Julia; Bjørnstad, Ottar N.; Simonsen, Lone; Grenfell, Bryan T.; Viboud, Cécile

    2017-01-01

    Seasonal influenza epidemics offer unique opportunities to study the invasion and re-invasion waves of a pathogen in a partially immune population. Detailed patterns of spread remain elusive, however, due to lack of granular disease data. Here we model high-volume city-level medical claims data and human mobility proxies to explore the drivers of influenza spread in the US during 2002–2010. Although the speed and pathways of spread varied across seasons, seven of eight epidemics likely originated in the Southern US. Each epidemic was associated with 1–5 early long-range transmission events, half of which sparked onward transmission. Gravity model estimates indicate a sharp decay in influenza transmission with the distance between infectious and susceptible cities, consistent with spread dominated by work commutes rather than air traffic. Two early-onset seasons associated with antigenic novelty had particularly localized modes of spread, suggesting that novel strains may spread in a more localized fashion than previously anticipated. PMID:28187123

  4. Influenza A Virus Acquires Enhanced Pathogenicity and Transmissibility after Serial Passages in Swine

    PubMed Central

    Wei, Kai; Sun, Honglei; Sun, Zhenhong; Sun, Yipeng; Kong, Weili; Pu, Juan; Ma, Guangpeng; Yin, Yanbo; Yang, Hanchun; Guo, Xin; Chang, Kin-Chow

    2014-01-01

    ABSTRACT Genetic and phylogenetic analyses suggest that the pandemic H1N1/2009 virus was derived from well-established swine influenza lineages; however, there is no convincing evidence that the pandemic virus was generated from a direct precursor in pigs. Furthermore, the evolutionary dynamics of influenza virus in pigs have not been well documented. Here, we subjected a recombinant virus (rH1N1) with the same constellation makeup as the pandemic H1N1/2009 virus to nine serial passages in pigs. The severity of infection sequentially increased with each passage. Deep sequencing of viral quasispecies from the ninth passage found five consensus amino acid mutations: PB1 A469T, PA 1129T, NA N329D, NS1 N205K, and NEP T48N. Mutations in the hemagglutinin (HA) protein, however, differed greatly between the upper and lower respiratory tracts. Three representative viral clones with the five consensus mutations were selected for functional evaluation. Relative to the parental virus, the three viral clones showed enhanced replication and polymerase activity in vitro and enhanced replication, pathogenicity, and transmissibility in pigs, guinea pigs, and ferrets in vivo. Specifically, two mutants of rH1N1 (PB1 A469T and a combination of NS1 N205K and NEP T48N) were identified as determinants of transmissibility in guinea pigs. Crucially, one mutant viral clone with the five consensus mutations, which also carried D187E, K211E, and S289N mutations in its HA, additionally was able to infect ferrets by airborne transmission as effectively as the pandemic virus. Our findings demonstrate that influenza virus can acquire viral characteristics that are similar to those of the pandemic virus after limited serial passages in pigs. IMPORTANCE We demonstrate here that an engineered reassortant swine influenza virus, with the same gene constellation pattern as the pandemic H1N1/2009 virus and subjected to only nine serial passages in pigs, acquired greatly enhanced virulence and

  5. Quantifying Transmission of Highly Pathogenic and Low Pathogenicity H7N1 Avian Influenza in Turkeys

    PubMed Central

    Saenz, Roberto A.; Essen, Steve C.; Brookes, Sharon M.; Iqbal, Munir; Wood, James L. N.; Grenfell, Bryan T.; McCauley, John W.; Brown, Ian H.; Gog, Julia R.

    2012-01-01

    Outbreaks of avian influenza in poultry can be devastating, yet many of the basic epidemiological parameters have not been accurately characterised. In 1999–2000 in Northern Italy, outbreaks of H7N1 low pathogenicity avian influenza virus (LPAI) were followed by the emergence of H7N1 highly pathogenic avian influenza virus (HPAI). This study investigates the transmission dynamics in turkeys of representative HPAI and LPAI H7N1 virus strains from this outbreak in an experimental setting, allowing direct comparison of the two strains. The fitted transmission rates for the two strains are similar: 2.04 (1.5–2.7) per day for HPAI, 2.01 (1.6–2.5) per day for LPAI. However, the mean infectious period is far shorter for HPAI (1.47 (1.3–1.7) days) than for LPAI (7.65 (7.0–8.3) days), due to the rapid death of infected turkeys. Hence the basic reproductive ratio, is significantly lower for HPAI (3.01 (2.2–4.0)) than for LPAI (15.3 (11.8–19.7)). The comparison of transmission rates and are critically important in relation to understanding how HPAI might emerge from LPAI. Two competing hypotheses for how transmission rates vary with population size are tested by fitting competing models to experiments with differing numbers of turkeys. A model with frequency-dependent transmission gives a significantly better fit to experimental data than density-dependent transmission. This has important implications for extrapolating experimental results from relatively small numbers of birds to the commercial poultry flock size, and for how control, including vaccination, might scale with flock size. PMID:23028760

  6. Viral kinetics and exhaled droplet size affect indoor transmission dynamics of influenza infection.

    PubMed

    Chen, S C; Chio, C P; Jou, L J; Liao, C M

    2009-10-01

    The purpose of this paper was to investigate the effects of viral kinetics and exhaled droplet size on indoor transmission dynamics of influenza infection. The target cell-limited model with delayed virus production was adopted to strengthen the inner mechanisms of virus infection on human epithelial cell. The particle number and volume involved in the viral kinetics were linked with Wells-Riley mathematical equation to quantify the infection risk. We investigated population dynamics in a specific elementary school by using the seasonal susceptible - exposed - infected - recovery (SEIR) model. We found that exhaled pulmonary bioaerosol of sneeze (particle diameter <10 microm) have 10(2)-fold estimate higher than that of cough. Sneeze and cough caused risk probabilities range from 0.075 to 0.30 and 0.076, respectively; whereas basic reproduction numbers (R(0)) estimates range from 4 to 17 for sneeze and nearly 4 for cough, indicating sneeze-posed higher infection risk. The viral kinetics and exhaled droplet size for sneeze affect indoor transmission dynamics of influenza infection since date post-infection 1-7. This study provides direct mechanistic support that indoor influenza virus transmission can be characterized by viral kinetics in human upper respiratory tracts that are modulated by exhaled droplet size. Practical Implications This paper provides a predictive model that can integrate the influenza viral kinetics (target cell-limited model), indoor aerosol transmission potential (Wells-Riley mathematical equation), and population dynamic model [susceptible - exposed - infected - recovery (SEIR) model] in a proposed susceptible population. Viral kinetics expresses the competed results of human immunity ability with influenza virus generation. By linking the viral kinetics and different exposure parameters and environmental factors in a proposed school setting with five age groups, the influenza infection risk can be estimated. On the other hand, we implicated

  7. Influenza virus contamination of common household surfaces during the 2009 influenza A (H1N1) pandemic in Bangkok, Thailand: implications for contact transmission.

    PubMed

    Simmerman, James Mark; Suntarattiwong, Piyarat; Levy, Jens; Gibbons, Robert V; Cruz, Christina; Shaman, Jeffrey; Jarman, Richard G; Chotpitayasunondh, Tawee

    2010-11-01

    Rational infection control guidance requires an improved understanding of influenza transmission. We studied households with an influenza-infected child to measure the prevalence of influenza contamination, the effect of hand washing, and associations with humidity and temperature. We identified children with influenza and randomly assigned their households to hand washing and control arms. Six common household surfaces and the fingertips of the index patient and symptomatic family members were swabbed. Specimens were tested by real-time reverse-transcription polymerase chain reaction (rRT-PCR), and specimens with positive results were placed on cell culture. A handheld psychrometer measured meteorological data. Sixteen (17.8%) of 90 households had influenza A-positive surfaces by rRT-PCR, but no viruses could be cultured. The fingertips of 15 (16.6%) of the index patients had results positive for influenza A, and 1 virus was cultured. Index patients with seasonal influenza infections shed more virus than did patients with pandemic influenza infection. Control households had a higher prevalence of surface contamination (11 [24.4%] of 45) than did hand washing households (5 [11.1%] of 45); prevalence risk difference (PRD), 13.3%; [95% confidence interval {CI}, −2.2% to 28.9%]; P = .09). Households in which the age of the index patient was ≤8 years had a significantly higher prevalence of contamination (PRD ,19.1%; 95% CI, 5.3% -32.9%; P = .02). Within the strata of households with secondary infections, an effect of lower absolute humidity is suggested (P = .07). We documented influenza virus RNA contamination on household surfaces and on the fingertips of ill children. Homes with younger children were more likely than homes of older children to have contaminated surfaces. Lower absolute humidity favors surface contamination in households with multiple infections. Increased hand washing can reduce influenza contamination in the home.

  8. Reviewing the History of Pandemic Influenza: Understanding Patterns of Emergence and Transmission

    PubMed Central

    Saunders-Hastings, Patrick R.; Krewski, Daniel

    2016-01-01

    For centuries, novel strains of influenza have emerged to produce human pandemics, causing widespread illness, death, and disruption. There have been four influenza pandemics in the past hundred years. During this time, globalization processes, alongside advances in medicine and epidemiology, have altered the way these pandemics are experienced. Drawing on international case studies, this paper provides a review of the impact of past influenza pandemics, while examining the evolution of our understanding of, and response to, these viruses. This review argues that pandemic influenza is in part a consequence of human development, and highlights the importance of considering outbreaks within the context of shifting global landscapes. While progress in infectious disease prevention, control, and treatment has improved our ability to respond to such outbreaks, globalization processes relating to human behaviour, demographics, and mobility have increased the threat of pandemic emergence and accelerated global disease transmission. Preparedness planning must continue to evolve to keep pace with this heightened risk. Herein, we look to the past for insights on the pandemic experience, underlining both progress and persisting challenges. However, given the uncertain timing and severity of future pandemics, we emphasize the need for flexible policies capable of responding to change as such emergencies develop. PMID:27929449

  9. Respiratory transmission of an avian H3N8 influenza virus isolated from a harbour seal

    USGS Publications Warehouse

    Karlsson, Erik A.; Ip, Hon S.; Hall, Jeffrey S.; Yoon, Sun W.; Johnson, Jordan; Beck, Melinda A.; Webby, Richard J.; Schultz-Cherry, Stacey

    2014-01-01

    The ongoing human H7N9 influenza infections highlight the threat of emerging avian influenza viruses. In 2011, an avian H3N8 influenza virus isolated from moribund New England harbour seals was shown to have naturally acquired mutations known to increase the transmissibility of highly pathogenic H5N1 influenza viruses. To elucidate the potential human health threat, here we evaluate a panel of avian H3N8 viruses and find that the harbour seal virus displays increased affinity for mammalian receptors, transmits via respiratory droplets in ferrets and replicates in human lung cells. Analysis of a panel of human sera for H3N8 neutralizing antibodies suggests that there is no population-wide immunity to these viruses. The prevalence of H3N8 viruses in birds and multiple mammalian species including recent isolations from pigs and evidence that it was a past human pandemic virus make the need for surveillance and risk analysis of these viruses of public health importance.

  10. Long-term evolution and transmission dynamics of swine influenza A virus.

    PubMed

    Vijaykrishna, Dhanasekaran; Smith, Gavin J D; Pybus, Oliver G; Zhu, Huachen; Bhatt, Samir; Poon, Leo L M; Riley, Steven; Bahl, Justin; Ma, Siu K; Cheung, Chung L; Perera, Ranawaka A P M; Chen, Honglin; Shortridge, Kennedy F; Webby, Richard J; Webster, Robert G; Guan, Yi; Peiris, J S Malik

    2011-05-26

    Swine influenza A viruses (SwIV) cause significant economic losses in animal husbandry as well as instances of human disease and occasionally give rise to human pandemics, including that caused by the H1N1/2009 virus. The lack of systematic and longitudinal influenza surveillance in pigs has hampered attempts to reconstruct the origins of this pandemic. Most existing swine data were derived from opportunistic samples collected from diseased pigs in disparate geographical regions, not from prospective studies in defined locations, hence the evolutionary and transmission dynamics of SwIV are poorly understood. Here we quantify the epidemiological, genetic and antigenic dynamics of SwIV in Hong Kong using a data set of more than 650 SwIV isolates and more than 800 swine sera from 12 years of systematic surveillance in this region, supplemented with data stretching back 34 years. Intercontinental virus movement has led to reassortment and lineage replacement, creating an antigenically and genetically diverse virus population whose dynamics are quantitatively different from those previously observed for human influenza viruses. Our findings indicate that increased antigenic drift is associated with reassortment events and offer insights into the emergence of influenza viruses with epidemic potential in swine and humans.

  11. Respiratory transmission of an avian H3N8 influenza virus isolated from a harbour seal

    PubMed Central

    Karlsson, Erik A.; Ip, Hon S.; Hall, Jeffrey S.; Yoon, Sun Woo; Johnson, Jordan; Beck, Melinda A.; Webby, Richard J.; Schultz-Cherry, Stacey

    2016-01-01

    The ongoing human H7N9 influenza infections highlight the threat of emerging avian influenza viruses. In 2011, an avian H3N8 influenza virus isolated from moribund New England harbour seals was shown to have naturally acquired mutations known to increase the transmissibility of highly pathogenic H5N1 influenza viruses. To elucidate the potential human health threat, here we evaluate a panel of avian H3N8 viruses and find that the harbour seal virus displays increased affinity for mammalian receptors, transmits via respiratory droplets in ferrets and replicates in human lung cells. Analysis of a panel of human sera for H3N8 neutralizing antibodies suggests that there is no population-wide immunity to these viruses. The prevalence of H3N8 viruses in birds and multiple mammalian species including recent isolations from pigs and evidence that it was a past human pandemic virus make the need for surveillance and risk analysis of these viruses of public health importance. PMID:25183346

  12. Transmissibility of the Influenza Virus during Influenza Outbreaks and Related Asymptomatic Infection in Mainland China, 2005-2013.

    PubMed

    Chen, Tao; Chen, Tianmu; Liu, Ruchun; Xu, Cuiling; Wang, Dayan; Chen, Faming; Zhu, Wenfei; Zhang, Xixing; Yang, Jing; Wang, Lijie; Xie, Zhi; Chen, Yongkun; Bai, Tian; Li, Yelan; Wang, Zhiyu; Zhang, Min; Chen, Shuilian; Shu, Yuelong

    2016-01-01

    We collected 2768 Influenza-like illness emergency public health incidents from April 1, 2005 to November 30, 2013reported in the Emergency Public Reporting System. After screening by strict inclusion and exclusion criteria, there were 613 outbreaks analyzed with susceptible-exposed-infectious/asymptomatic-removed model in order to estimate the proportion of asymptomatic individuals (p) and the effective reproduction number (Rt). The relation between Rt and viral subtypes, regions, outbreak sites, populations, and seasons were analyzed. The mean values of p of different subtypes ranged from 0.09 to 0.15, but could be as high as up to 0.94. Different subtypes, provinces, regions, and sites of outbreak had statistically significantly different Rt. In particular, the southern region also manifested different Rt by affected population size and seasonality. Our results provide China and also the rest of the world a reference to understand characteristics of transmission and develop prevention and control strategies.

  13. Transmissibility of the Influenza Virus during Influenza Outbreaks and Related Asymptomatic Infection in Mainland China, 2005-2013

    PubMed Central

    Liu, Ruchun; Xu, Cuiling; Wang, Dayan; Chen, Faming; Zhu, Wenfei; Zhang, Xixing; Yang, Jing; Wang, Lijie; Xie, Zhi; Chen, Yongkun; Bai, Tian; Li, Yelan; Wang, Zhiyu; Zhang, Min; Chen, Shuilian; Shu, Yuelong

    2016-01-01

    We collected 2768 Influenza-like illness emergency public health incidents from April 1, 2005 to November 30, 2013reported in the Emergency Public Reporting System. After screening by strict inclusion and exclusion criteria, there were 613 outbreaks analyzed with susceptible–exposed–infectious/asymptomatic–removed model in order to estimate the proportion of asymptomatic individuals (p) and the effective reproduction number (Rt). The relation between Rt and viral subtypes, regions, outbreak sites, populations, and seasons were analyzed. The mean values of p of different subtypes ranged from 0.09 to 0.15, but could be as high as up to 0.94. Different subtypes, provinces, regions, and sites of outbreak had statistically significantly different Rt. In particular, the southern region also manifested different Rt by affected population size and seasonality. Our results provide China and also the rest of the world a reference to understand characteristics of transmission and develop prevention and control strategies. PMID:27880774

  14. Genetic Adaptation of Influenza A Viruses in Domestic Animals and Their Potential Role in Interspecies Transmission: A Literature Review.

    PubMed

    Munoz, Olga; De Nardi, Marco; van der Meulen, Karen; van Reeth, Kristien; Koopmans, Marion; Harris, Kate; von Dobschuetz, Sophie; Freidl, Gudrun; Meijer, Adam; Breed, Andrew; Hill, Andrew; Kosmider, Rowena; Banks, Jill; Stärk, Katharina D C; Wieland, Barbara; Stevens, Kim; van der Werf, Sylvie; Enouf, Vincent; Dauphin, Gwenaelle; Dundon, William; Cattoli, Giovanni; Capua, Ilaria

    2016-03-01

    In December 2011, the European Food Safety Authority awarded a Grant for the implementation of the FLURISK project. The main objective of FLURISK was the development of an epidemiological and virological evidence-based influenza risk assessment framework (IRAF) to assess influenza A virus strains circulating in the animal population according to their potential to cross the species barrier and cause infections in humans. With the purpose of gathering virological data to include in the IRAF, a literature review was conducted and key findings are presented here. Several adaptive traits have been identified in influenza viruses infecting domestic animals and a significance of these adaptations for the emergence of zoonotic influenza, such as shift in receptor preference and mutations in the replication proteins, has been hypothesized. Nonetheless, and despite several decades of research, a comprehensive understanding of the conditions that facilitate interspecies transmission is still lacking. This has been hampered by the intrinsic difficulties of the subject and the complexity of correlating environmental, viral and host factors. Finding the most suitable and feasible way of investigating these factors in laboratory settings represents another challenge. The majority of the studies identified through this review focus on only a subset of species, subtypes and genes, such as influenza in avian species and avian influenza viruses adapting to humans, especially in the context of highly pathogenic avian influenza H5N1. Further research applying a holistic approach and investigating the broader influenza genetic spectrum is urgently needed in the field of genetic adaptation of influenza A viruses.

  15. Disparities in influenza mortality and transmission related to sociodemographic factors within Chicago in the pandemic of 1918

    PubMed Central

    Grantz, Kyra H.; Rane, Madhura S.; Salje, Henrik; Glass, Gregory E.; Schachterle, Stephen E.; Cummings, Derek A. T.

    2016-01-01

    Social factors have been shown to create differential burden of influenza across different geographic areas. We explored the relationship between potential aggregate-level social determinants and mortality during the 1918 influenza pandemic in Chicago using a historical dataset of 7,971 influenza and pneumonia deaths. Census tract-level social factors, including rates of illiteracy, homeownership, population, and unemployment, were assessed as predictors of pandemic mortality in Chicago. Poisson models fit with generalized estimating equations (GEEs) were used to estimate the association between social factors and the risk of influenza and pneumonia mortality. The Poisson model showed that influenza and pneumonia mortality increased, on average, by 32.2% for every 10% increase in illiteracy rate adjusted for population density, homeownership, unemployment, and age. We also found a significant association between transmissibility and population density, illiteracy, and unemployment but not homeownership. Lastly, analysis of the point locations of reported influenza and pneumonia deaths revealed fine-scale spatiotemporal clustering. This study shows that living in census tracts with higher illiteracy rates increased the risk of influenza and pneumonia mortality during the 1918 influenza pandemic in Chicago. Our observation that disparities in structural determinants of neighborhood-level health lead to disparities in influenza incidence in this pandemic suggests that disparities and their determinants should remain targets of research and control in future pandemics. PMID:27872284

  16. The role of different social contexts in shaping influenza transmission during the 2009 pandemic

    NASA Astrophysics Data System (ADS)

    Ajelli, Marco; Poletti, Piero; Melegaro, Alessia; Merler, Stefano

    2014-11-01

    Evaluating the relative importance of different social contexts in which infection transmission occurs is critical for identifying optimal intervention strategies. Nonetheless, an overall picture of influenza transmission in different social contexts has yet to emerge. Here we provide estimates of the fraction of infections generated in different social contexts during the 2009 H1N1 pandemic in Italy by making use of a highly detailed individual-based model accounting for time use data and parametrized on the basis of observed age-specific seroprevalence. We found that 41.6% (95%CI: 39-43.7%) of infections occurred in households, 26.7% (95%CI: 21-33.2) in schools, 3.3% (95%CI: 1.7-5%) in workplaces, and 28.4% (95%CI: 24.6-31.9%) in the general community. The above estimates strongly depend on the lower susceptibility to infection of individuals 19+ years old compared to younger ones, estimated to be 0.2 (95%CI 0.12-0.28). We also found that school closure over the weekends contributed to decrease the effective reproduction number of about 8% and significantly affected the pattern of transmission. These results highlight the pivotal role played by schools in the transmission of the 2009 H1N1 influenza. They may be relevant in the evaluation of intervention options and, hence, for informing policy decisions.

  17. Exhaled Aerosol Transmission of Pandemic and Seasonal H1N1 Influenza Viruses in the Ferret

    PubMed Central

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

    2012-01-01

    Person-to-person transmission of influenza viruses occurs by contact (direct and fomites) and non-contact (droplet and small particle aerosol) routes, but the quantitative dynamics and relative contributions of these routes are incompletely understood. The transmissibility of influenza strains estimated from secondary attack rates in closed human populations is confounded by large variations in population susceptibilities. An experimental method to phenotype strains for transmissibility in an animal model could provide relative efficiencies of transmission. We developed an experimental method to detect exhaled viral aerosol transmission between unanesthetized infected and susceptible ferrets, measured aerosol particle size and number, and quantified the viral genomic RNA in the exhaled aerosol. During brief 3-hour exposures to exhaled viral aerosols in airflow-controlled chambers, three strains of pandemic 2009 H1N1 strains were frequently transmitted to susceptible ferrets. In contrast one seasonal H1N1 strain was not transmitted in spite of higher levels of viral RNA in the exhaled aerosol. Among three pandemic strains, the two strains causing weight loss and illness in the intranasally infected ‘donor’ ferrets were transmitted less efficiently from the donor than the strain causing no detectable illness, suggesting that the mucosal inflammatory response may attenuate viable exhaled virus. Although exhaled viral RNA remained constant, transmission efficiency diminished from day 1 to day 5 after donor infection. Thus, aerosol transmission between ferrets may be dependent on at least four characteristics of virus-host relationships including the level of exhaled virus, infectious particle size, mucosal inflammation, and viral replication efficiency in susceptible mucosa. PMID:22509254

  18. Assessment of transmission, pathogenesis and adaptation of H2 subtype influenza viruses in ferrets.

    PubMed

    Pappas, Claudia; Yang, Hua; Carney, Paul J; Pearce, Melissa B; Katz, Jacqueline M; Stevens, James; Tumpey, Terrence M

    2015-03-01

    After their disappearance from the human population in 1968, influenza H2 viruses have continued to circulate in the natural avian reservoir. The isolation of this virus subtype from multiple bird species as well as swine highlights the need to better understand the potential of these viruses to spread and cause disease in humans. Here we analyzed the virulence, transmissibility and receptor-binding preference of two avian influenza H2 viruses (H2N2 and H2N3) and compared them to a swine H2N3 (A/swine/Missouri/2124514/2006 [swMO]), and a human H2N2 (A/England/10/1967 [Eng/67]) virus using the ferret model as a mammalian host. Both avian H2 viruses possessed the capacity to spread efficiently between cohoused ferrets, and the swine (swMO) and human (Eng/67) viruses transmitted to naïve ferrets by respiratory droplets. Further characterization of the swMO hemagglutinin (HA) by x-ray crystallography and glycan microarray array identified receptor-specific adaptive mutations. As influenza virus quasispecies dynamics during transmission have not been well characterized, we sequenced nasal washes collected during transmission studies to better understand experimental adaptation of H2 HA. The avian H2 viruses isolated from ferret nasal washes contained mutations in the HA1, including a Gln226Leu substitution, which is a mutation associated with α2,6 sialic acid (human-like) binding preference. These results suggest that the molecular structure of HA in viruses of the H2 subtype continue to have the potential to adapt to a mammalian host and become transmissible, after acquiring additional genetic markers.

  19. Contact heterogeneity, rather than transmission efficiency, limits the emergence and spread of canine influenza virus.

    PubMed

    Dalziel, Benjamin D; Huang, Kai; Geoghegan, Jemma L; Arinaminpathy, Nimalan; Dubovi, Edward J; Grenfell, Bryan T; Ellner, Stephen P; Holmes, Edward C; Parrish, Colin R

    2014-10-01

    Host-range shifts in influenza virus are a major risk factor for pandemics. A key question in the study of emerging zoonoses is how the evolution of transmission efficiency interacts with heterogeneity in contact patterns in the new host species, as this interplay influences disease dynamics and prospects for control. Here we use a synergistic mixture of models and data to tease apart the evolutionary and demographic processes controlling a host-range shift in equine H3N8-derived canine influenza virus (CIV). CIV has experienced 15 years of continuous transfer among dogs in the United States, but maintains a patchy distribution, characterized by sporadic short-lived outbreaks coupled with endemic hotspots in large animal shelters. We show that CIV has a high reproductive potential in these facilities (mean R(0) = 3.9) and that these hotspots act as refugia from the sparsely connected majority of the dog population. Intriguingly, CIV has evolved a transmission efficiency that closely matches the minimum required to persist in these refugia, leaving it poised on the extinction/invasion threshold of the host contact network. Corresponding phylogenetic analyses show strong geographic clustering in three US regions, and that the effective reproductive number of the virus (R(e)) in the general dog population is close to 1.0. Our results highlight the critical role of host contact structure in CIV dynamics, and show how host contact networks could shape the evolution of pathogen transmission efficiency. Importantly, efficient control measures could eradicate the virus, in turn minimizing the risk of future sustained transmission among companion dogs that could represent a potential new axis to the human-animal interface for influenza.

  20. Ionizing air affects influenza virus infectivity and prevents airborne-transmission

    PubMed Central

    Hagbom, Marie; Nordgren, Johan; Nybom, Rolf; Hedlund, Kjell-Olof; Wigzell, Hans; Svensson, Lennart

    2015-01-01

    By the use of a modified ionizer device we describe effective prevention of airborne transmitted influenza A (strain Panama 99) virus infection between animals and inactivation of virus (>97%). Active ionizer prevented 100% (4/4) of guinea pigs from infection. Moreover, the device effectively captured airborne transmitted calicivirus, rotavirus and influenza virus, with recovery rates up to 21% after 40 min in a 19 m3 room. The ionizer generates negative ions, rendering airborne particles/aerosol droplets negatively charged and electrostatically attracts them to a positively charged collector plate. Trapped viruses are then identified by reverse transcription quantitative real-time PCR. The device enables unique possibilities for rapid and simple removal of virus from air and offers possibilities to simultaneously identify and prevent airborne transmission of viruses. PMID:26101102

  1. Emergence and transmission of amantadine-resistant influenza A in a nursing home.

    PubMed

    Schilling, Margo; Gravenstein, Stefan; Drinka, Paul; Cox, Nancy; Krause, Peggy; Povinelli, Laura; Shult, Peter

    2004-12-01

    To prospectively detect amantadine-resistant influenza when amantadine was used for influenza A outbreak control. Prospective clinical surveillance and viral culture of all new respiratory illnesses during the course of amantadine prophylaxis. A 721-bed, 14-ward nursing home for veterans and spouses during an influenza A outbreak (1993-94). Residents of a veterans hospital and their spouses. Nasopharyngeal and throat viral culture. All residents with positive cultures who developed new respiratory symptoms while receiving or residing on a unit receiving amantadine prophylaxis had antiviral-resistance testing and polymerase chain reaction restriction analyses performed. Amantadine prophylaxis was administered sequentially on nine of 14 wards to all well residents for 14 to 31 days/ward to control influenza outbreaks between December 9, 1993, and January 28, 1994. Amantadine treatment was simultaneously provided to 29 ill residents. Between December 3, 1993, and January 22, 1994, 68 culture-positive cases of influenza A were detected. Twenty subjects were receiving or residing on units receiving amantadine prophylaxis. Amantadine sensitivity testing could be performed on 16 residents; 12 residents had amantadine resistant strains. Four of the 12 had not received any antiviral treatment. Illness onset ranged from 1 to 22 days after amantadine prophylaxis was begun on the individual's unit. Two ribonucleic acid (RNA) mutations in the gene coding the M2 protein transmembrane region were observed that were clustered in time and space. Isolates from two roommates, one receiving amantadine for 18 days and one on no antiviral, had identical RNA sequences. Antiviral resistance may be responsible for failure of prophylaxis in nursing home outbreaks. Strategies that use different classes of antivirals for prophylaxis and treatment may limit emergence and transmission of resistant virus.

  2. Possible role of aerosol transmission in a hospital outbreak of influenza.

    PubMed

    Wong, Bonnie C K; Lee, Nelson; Li, Yuguo; Chan, Paul K S; Qiu, Hong; Luo, Zhiwen; Lai, Raymond W M; Ngai, Karry L K; Hui, David S C; Choi, K W; Yu, Ignatius T S

    2010-11-15

    We examined the role of aerosol transmission of influenza in an acute ward setting. We investigated a seasonal influenza A outbreak that occurred in our general medical ward (with open bay ward layout) in 2008. Clinical and epidemiological information was collected in real time during the outbreak. Spatiotemporal analysis was performed to estimate the infection risk among patients. Airflow measurements were conducted, and concentrations of hypothetical virus-laden aerosols at different ward locations were estimated using computational fluid dynamics modeling. Nine inpatients were infected with an identical strain of influenza A/H3N2 virus. With reference to the index patient's location, the attack rate was 20.0% and 22.2% in the "same" and "adjacent" bays, respectively, but 0% in the "distant" bay (P = .04). Temporally, the risk of being infected was highest on the day when noninvasive ventilation was used in the index patient; multivariate logistic regression revealed an odds ratio of 14.9 (95% confidence interval, 1.7-131.3; P = .015). A simultaneous, directional indoor airflow blown from the "same" bay toward the "adjacent" bay was found; it was inadvertently created by an unopposed air jet from a separate air purifier placed next to the index patient's bed. Computational fluid dynamics modeling revealed that the dispersal pattern of aerosols originated from the index patient coincided with the bed locations of affected patients. Our findings suggest a possible role of aerosol transmission of influenza in an acute ward setting. Source and engineering controls, such as avoiding aerosol generation and improving ventilation design, may warrant consideration to prevent nosocomial outbreaks.

  3. Predicting transmission of avian influenza A viruses from avian to human by using informative physicochemical properties.

    PubMed

    Wang, Jia; Ma, Chuang; Kou, Zheng; Zhou, Yan-Hong; Liu, Huai-Lan

    2013-01-01

    Some strains of avian influenza A virus (AIV) can directly transmit from their natural hosts to humans. These avian-to-human transmissions have continuously been reported to cause human deaths worldwide since 1997. Predicting whether AIV strains can transmit from avian to human is valuable for early warning of AIV strains with human pandemic potential. In this study, we constructed a computational model to predict avian-to-human transmission of AIV based on physicochemical properties. Initially, ninety signature positions in the inner protein sequences were extracted with the entropy method. These positions were then encoded with 531 physicochemical features. Subsequently, the optimal subset of these physicochemical features was mined with several feature selection methods. Finally, a support vector machine (SVM) model named A2H was established to integrate the selected optimal features. The experimental results of cross-validation and an independent test show that A2H has the capability of predicting transmission of AIV from avian to human.

  4. Ecological dynamics of influenza A viruses: cross-species transmission and global migration

    PubMed Central

    Ren, Hongguang; Jin, Yuan; Hu, Mingda; Zhou, Jing; Song, Ting; Huang, Zhisong; Li, Beiping; Li, Kaiwu; Zhou, Wei; Dai, Hongmei; Shi, Weifeng; Yue, Junjie; Liang, Long

    2016-01-01

    A comprehensive study of cross-species transmission and inter-regional migration would provide insights into the global ecology of influenza A viruses (IAVs). To this end, we assembled 17,241 non-redundant IAV whole-genome sequences with complete epidemiological information. We hierarchically divided the movements of IAVs into the cross-species transmission in each region and the inter-regional migration driven by each host species. We then systematically identified the potential cross-species transmission and inter-regional migration events. Cross-species transmission networks were obtained for each gene segment of the IAVs. Waterfowl, domestic birds and swine showed higher degrees of connection than did other species in all of the transmission networks. East Asia and Southeast Asia were hot regions for avian-mammal transmissions. Swine and migratory birds were the dominant species for global virus delivery. The importance of swine was reemphasized because it has not only provided an environment for adaptive evolution during the avian-human transmission of IAVs (as incubators) but also served as a key species for the global dissemination of the viruses (as carriers). Therefore, monitoring the global live trade of swine and survey of migratory birds along flyways would be beneficial for the prevention and control of IAVs. PMID:27827462

  5. Evolutionary Analysis of Inter-Farm Transmission Dynamics in a Highly Pathogenic Avian Influenza Epidemic

    PubMed Central

    Bataille, Arnaud; van der Meer, Frank; Stegeman, Arjan; Koch, Guus

    2011-01-01

    Phylogenetic studies have largely contributed to better understand the emergence, spread and evolution of highly pathogenic avian influenza during epidemics, but sampling of genetic data has never been detailed enough to allow mapping of the spatiotemporal spread of avian influenza viruses during a single epidemic. Here, we present genetic data of H7N7 viruses produced from 72% of the poultry farms infected during the 2003 epidemic in the Netherlands. We use phylogenetic analyses to unravel the pathways of virus transmission between farms and between infected areas. In addition, we investigated the evolutionary processes shaping viral genetic diversity, and assess how they could have affected our phylogenetic analyses. Our results show that the H7N7 virus was characterized by a high level of genetic diversity driven mainly by a high neutral substitution rate, purifying selection and limited positive selection. We also identified potential reassortment in the three genes that we have tested, but they had only a limited effect on the resolution of the inter-farm transmission network. Clonal sequencing analyses performed on six farm samples showed that at least one farm sample presented very complex virus diversity and was probably at the origin of chronological anomalies in the transmission network. However, most virus sequences could be grouped within clearly defined and chronologically sound clusters of infection and some likely transmission events between farms located 0.8–13 Km apart were identified. In addition, three farms were found as most likely source of virus introduction in distantly located new areas. These long distance transmission events were likely facilitated by human-mediated transport, underlining the need for strict enforcement of biosafety measures during outbreaks. This study shows that in-depth genetic analysis of virus outbreaks at multiple scales can provide critical information on virus transmission dynamics and can be used to increase

  6. Replication and transmission of mammalian-adapted H9 subtype influenza virus in pigs and quail.

    PubMed

    Obadan, Adebimpe O; Kimble, Brian J; Rajao, Daniela; Lager, Kelly; Santos, Jefferson J S; Vincent, Amy; Perez, Daniel R

    2015-09-01

    Influenza A virus is a major pathogen of birds, swine and humans. Strains can jump between species in a process often requiring mutations and reassortment, resulting in outbreaks and, potentially, pandemics. H9N2 avian influenza is predominant in poultry across Asia and occasionally infects humans and swine. Pandemic H1N1 (H1N1pdm) is endemic in humans and swine and has a history of reassortment in pigs. Previous studies have shown the compatibility of H9N2 and H1N1pdm for reassortment in ferrets, a model for human infection and transmission. Here, the effects of ferret adaptation of H9 surface gene segments on the infectivity and transmission in at-risk natural hosts, specifically swine and quail, were analysed. Reassortant H9N1 and H9N2 viruses, carrying seven or six gene segments from H1N1pdm, showed infectivity and transmissibility in swine, unlike the wholly avian H9N2 virus with ferret-adapted surface genes. In quail, only the reassortant H9N2 with the six internal gene segments from the H1N1pdm strain was able to infect and transmit, although less efficiently than the wholly avian H9N2 virus with ferret-adapted surface genes. These results highlight that ferret-adapted mutations on the haemagglutinin of H9 subtype virus do not restrict the ability of the virus to infect swine and quail, and that the ability to transmit in these species depends on the context of the whole virus. As such, this study emphasizes the threat that H9N2 reassortant viruses pose to humans and agricultural species and the importance of the genetic constellation of the virus to its ability to replicate and transmit in natural hosts of influenza.

  7. Replication and transmission of mammalian-adapted H9 subtype influenza virus in pigs and quail

    PubMed Central

    Obadan, Adebimpe O.; Kimble, Brian J.; Rajao, Daniela; Lager, Kelly; Santos, Jefferson J. S.; Vincent, Amy

    2015-01-01

    Influenza A virus is a major pathogen of birds, swine and humans. Strains can jump between species in a process often requiring mutations and reassortment, resulting in outbreaks and, potentially, pandemics. H9N2 avian influenza is predominant in poultry across Asia and occasionally infects humans and swine. Pandemic H1N1 (H1N1pdm) is endemic in humans and swine and has a history of reassortment in pigs. Previous studies have shown the compatibility of H9N2 and H1N1pdm for reassortment in ferrets, a model for human infection and transmission. Here, the effects of ferret adaptation of H9 surface gene segments on the infectivity and transmission in at-risk natural hosts, specifically swine and quail, were analysed. Reassortant H9N1 and H9N2 viruses, carrying seven or six gene segments from H1N1pdm, showed infectivity and transmissibility in swine, unlike the wholly avian H9N2 virus with ferret-adapted surface genes. In quail, only the reassortant H9N2 with the six internal gene segments from the H1N1pdm strain was able to infect and transmit, although less efficiently than the wholly avian H9N2 virus with ferret-adapted surface genes. These results highlight that ferret-adapted mutations on the haemagglutinin of H9 subtype virus do not restrict the ability of the virus to infect swine and quail, and that the ability to transmit in these species depends on the context of the whole virus. As such, this study emphasizes the threat that H9N2 reassortant viruses pose to humans and agricultural species and the importance of the genetic constellation of the virus to its ability to replicate and transmit in natural hosts of influenza. PMID:25986634

  8. A mouse model for the study of contact-dependent transmission of influenza A virus and the factors that govern transmissibility.

    PubMed

    Edenborough, Kathryn M; Gilbertson, Brad P; Brown, Lorena E

    2012-12-01

    Influenza A virus transmission by direct contact is not well characterized. Here, we describe a mouse model for investigation of factors regulating contact-dependent transmission. Strains within the H3N2 but not H1N1 subtype of influenza virus were transmissible, and reverse-engineered viruses representing hybrids of these subtypes showed that the viral hemagglutinin is a determinant of the transmissible phenotype. Transmission to contact mice occurred within the first 6 to 54 h after cohousing with directly infected index mice, and the proportion of contacts infected within this period was reduced if the index mice had been preinfected with a heterologous subtype virus. A threshold level of virus present in the saliva of the index mice was identified, above which the likelihood of transmission was greatly increased. There was no correlation with transmission and viral loads in the nose or lung. This model could be useful for preclinical evaluation of antiviral and vaccine efficacy in combating contact-dependent transmission of influenza.

  9. Key transmission parameters of an institutional outbreak during the 1918 influenza pandemic estimated by mathematical modelling

    PubMed Central

    Sertsou, Gabriel; Wilson, Nick; Baker, Michael; Nelson, Peter; Roberts, Mick G

    2006-01-01

    Aim To estimate the key transmission parameters associated with an outbreak of pandemic influenza in an institutional setting (New Zealand 1918). Methods Historical morbidity and mortality data were obtained from the report of the medical officer for a large military camp. A susceptible-exposed-infectious-recovered epidemiological model was solved numerically to find a range of best-fit estimates for key epidemic parameters and an incidence curve. Mortality data were subsequently modelled by performing a convolution of incidence distribution with a best-fit incidence-mortality lag distribution. Results Basic reproduction number (R0) values for three possible scenarios ranged between 1.3, and 3.1, and corresponding average latent period and infectious period estimates ranged between 0.7 and 1.3 days, and 0.2 and 0.3 days respectively. The mean and median best-estimate incidence-mortality lag periods were 6.9 and 6.6 days respectively. This delay is consistent with secondary bacterial pneumonia being a relatively important cause of death in this predominantly young male population. Conclusion These R0 estimates are broadly consistent with others made for the 1918 influenza pandemic and are not particularly large relative to some other infectious diseases. This finding suggests that if a novel influenza strain of similar virulence emerged then it could potentially be controlled through the prompt use of major public health measures. PMID:17137517

  10. Epidemiology and transmission dynamics of the 1918-19 pandemic influenza in Florence, Italy.

    PubMed

    Rizzo, Caterina; Ajelli, Marco; Merler, Stefano; Pugliese, Andrea; Barbetta, Ilaria; Salmaso, Stefania; Manfredi, Piero

    2011-07-22

    To investigate the 1918/19 influenza pandemic daily number of new hospitalizations in the only hospital in Florence (Central Italy) were analyzed. In order to describe the transmission dynamics of the 1918/1919 pandemic influenza a compartmental epidemic model was used. Model simulations show a high level of agreement with the observed epidemic data. By assuming both latent and infectious period equal to 1.5 days, the estimated basic reproduction number was R(0)(1) = 1.03 (95% CI: 1.00-1.08) during the summer wave and R(0)(2) = 1.38 (95% CI: 1.32-1.48) during the fall wave. Varying the length of the generation time or the estimation method, R(0)(2) ranges from 1.32 to 1.71. The hospitalization rate was found significantly different between summer and fall waves. Notably, the estimated basic reproductive numbers are lower compared to those observed in other countries, while the age distribution of deaths resulted to be consistent with the patterns generally observed during of the 1918-1919 pandemic. Our knowledge on past pandemics, as for the 1918-19 Spanish influenza, would help improving mathematical modeling accuracy and understanding the mechanisms underlying the dynamics of future pandemics.

  11. Survival of the avian influenza virus (H6N2) after land disposal.

    PubMed

    Graiver, David A; Topliff, Christina L; Kelling, Clayton L; Bartelt-Hunt, Shannon L

    2009-06-01

    An integral component in preventing an avian influenza pandemic is containment and disposal of infected bird (poultry) carcasses. Disposal of carcasses in Subtitle D municipal solid waste (MSW) landfills may be an advantageous option due to their large capacities and facility distribution in the U.S. In this study, the survival of H6N2 avian influenza virus (AIV) was measured in a methanogenic landfill leachate and water as a function of temperature, conductivity, and pH. Elevated temperature and nonneutral pH resulted in the quickest inactivation times for AIV in both media, whereas conductivity did not have a significant influence on AIV survival. Media effects were significant and AIV inactivation in leachate was consistently the same or faster than AIV inactivation in water. Based on an initial titer of 10(5) TCID50/mL, calculated inactivation times ranged from 30 days to greater than 600 days, indicating that AIV will remain infectious during and after waste disposal. Disposal of infected carcasses in a MSW landfill may be an appropriate option as inactivation times are within the design life of required barrier systems at Subtitle D landfills.

  12. Influenza A virus acquires enhanced pathogenicity and transmissibility after serial passages in swine.

    PubMed

    Wei, Kai; Sun, Honglei; Sun, Zhenhong; Sun, Yipeng; Kong, Weili; Pu, Juan; Ma, Guangpeng; Yin, Yanbo; Yang, Hanchun; Guo, Xin; Chang, Kin-Chow; Liu, Jinhua

    2014-10-01

    Genetic and phylogenetic analyses suggest that the pandemic H1N1/2009 virus was derived from well-established swine influenza lineages; however, there is no convincing evidence that the pandemic virus was generated from a direct precursor in pigs. Furthermore, the evolutionary dynamics of influenza virus in pigs have not been well documented. Here, we subjected a recombinant virus (rH1N1) with the same constellation makeup as the pandemic H1N1/2009 virus to nine serial passages in pigs. The severity of infection sequentially increased with each passage. Deep sequencing of viral quasispecies from the ninth passage found five consensus amino acid mutations: PB1 A469T, PA 1129T, NA N329D, NS1 N205K, and NEP T48N. Mutations in the hemagglutinin (HA) protein, however, differed greatly between the upper and lower respiratory tracts. Three representative viral clones with the five consensus mutations were selected for functional evaluation. Relative to the parental virus, the three viral clones showed enhanced replication and polymerase activity in vitro and enhanced replication, pathogenicity, and transmissibility in pigs, guinea pigs, and ferrets in vivo. Specifically, two mutants of rH1N1 (PB1 A469T and a combination of NS1 N205K and NEP T48N) were identified as determinants of transmissibility in guinea pigs. Crucially, one mutant viral clone with the five consensus mutations, which also carried D187E, K211E, and S289N mutations in its HA, additionally was able to infect ferrets by airborne transmission as effectively as the pandemic virus. Our findings demonstrate that influenza virus can acquire viral characteristics that are similar to those of the pandemic virus after limited serial passages in pigs. Importance: We demonstrate here that an engineered reassortant swine influenza virus, with the same gene constellation pattern as the pandemic H1N1/2009 virus and subjected to only nine serial passages in pigs, acquired greatly enhanced virulence and transmissibility

  13. Molecular Mechanism of the Airborne Transmissibility of H9N2 Avian Influenza A Viruses in Chickens

    PubMed Central

    Zhong, Lei; Wang, Xiaoquan; Li, Qunhui; Liu, Dong; Chen, Hongzhi; Zhao, Mingjun; Gu, Xiaobing; He, Liang; Liu, Xiaowen; Gu, Min; Peng, Daxin

    2014-01-01

    ABSTRACT H9N2 avian influenza virus has been prevalent in poultry in many parts of the world since the 1990s and occasionally crosses the host barrier, transmitting to mammals, including humans. In recent years, these viruses have contributed genes to H5N1 and H7N9 influenza viruses, threatening public health. To explore the molecular mechanism for the airborne transmission of H9N2 virus, we compared two genetically close strains isolated from chickens in 2001, A/chicken/Shanghai/7/2001(SH7) and A/chicken/Shanghai/14/2001 (SH14). SH7 is airborne transmissible between chickens, whereas SH14 is not. We used reverse genetics and gene swapping to derive recombinant SH7 (rSH7), rSH14, and a panel of reassortant viruses. Among the reassortant viruses, we identified segments HA and PA as governing the airborne transmission among chickens. In addition, the NP and NS genes also contributed to a lesser extent. Furthermore, the mutational analyses showed the transmissibility phenotype predominantly mapped to the HA and PA genes, with HA-K363 and PA-L672 being important for airborne transmissibility among chickens. In addition, the viral infectivity and acid stability are related to the airborne transmissibility. Importantly, airborne transmission studies of 18 arbitrarily chosen H9N2 viruses from our collections confirmed the importance of both 363K in HA and 672L in PA in determining their levels of transmissibility. Our finding elucidates the genetic contributions to H9N2 transmissibility in chickens and highlights the importance of their prevalence in poultry. IMPORTANCE Our study investigates the airborne transmissibility of H9N2 viruses in chickens and the subsequent epidemic. H9N2 virus is the donor for several prevalent reassortant influenza viruses, such as H7N9/2013 and the H5N1 viruses. Poultry as the reservoir hosts of influenza virus is closely associated with human society. Airborne transmission is an efficient pathway for influenza virus transmission among

  14. Infectivity and Transmissibility of Avian H9N2 Influenza Viruses in Pigs

    PubMed Central

    Wang, Jia; Wu, Maocai; Hong, Wenshan; Fan, Xiaohui; Chen, Rirong; Zheng, Zuoyi; Zeng, Yu; Huang, Ren; Zhang, Yu; Lam, Tommy Tsan-Yuk; Smith, David K.

    2016-01-01

    ABSTRACT The H9N2 influenza viruses that are enzootic in terrestrial poultry in China pose a persistent pandemic threat to humans. To investigate whether the continuous circulation and adaptation of these viruses in terrestrial poultry increased their infectivity to pigs, we conducted a serological survey in pig herds with H9N2 viruses selected from the aquatic avian gene pool (Y439 lineage) and the enzootic terrestrial poultry viruses (G1 and Y280 lineages). We also compared the infectivity and transmissibility of these viruses in pigs. It was found that more than 15% of the pigs sampled from 2010 to 2012 in southern China were seropositive to either G1 or Y280 lineage viruses, but none of the sera were positive to the H9 viruses from the Y439 lineage. Viruses of the G1 and Y280 lineages were able to infect experimental pigs, with detectable nasal shedding of the viruses and seroconversion, whereas viruses of the Y439 lineage did not cause a productive infection in pigs. Thus, adaptation and prevalence in terrestrial poultry could lead to interspecies transmission of H9N2 viruses from birds to pigs. Although H9N2 viruses do not appear to be continuously transmissible among pigs, repeated introductions of H9 viruses to pigs naturally increase the risk of generating mammalian-adapted or reassorted variants that are potentially infectious to humans. This study highlights the importance of monitoring the activity of H9N2 viruses in terrestrial poultry and pigs. IMPORTANCE H9N2 subtype of influenza viruses has repeatedly been introduced into mammalian hosts, including humans and pigs, so awareness of their activity and evolution is important for influenza pandemic preparedness. However, since H9N2 viruses usually cause mild or even asymptomatic infections in mammalian hosts, they may be overlooked in influenza surveillance. Here, we found that the H9N2 viruses established in terrestrial poultry had higher infectivity in pigs than those from aquatic birds, which

  15. Unexpected Interfarm Transmission Dynamics during a Highly Pathogenic Avian Influenza Epidemic

    PubMed Central

    Tassoni, Luca; Milani, Adelaide; Hughes, Joseph; Salviato, Annalisa; Massi, Paola; Zamperin, Gianpiero; Bonfanti, Lebana; Marangon, Stefano; Cattoli, Giovanni; Monne, Isabella

    2016-01-01

    ABSTRACT Next-generation sequencing technology is now being increasingly applied to study the within- and between-host population dynamics of viruses. However, information on avian influenza virus evolution and transmission during a naturally occurring epidemic is still limited. Here, we use deep-sequencing data obtained from clinical samples collected from five industrial holdings and a backyard farm infected during the 2013 highly pathogenic avian influenza (HPAI) H7N7 epidemic in Italy to unravel (i) the epidemic virus population diversity, (ii) the evolution of virus pathogenicity, and (iii) the pathways of viral transmission between different holdings and sheds. We show a high level of genetic diversity of the HPAI H7N7 viruses within a single farm as a consequence of separate bottlenecks and founder effects. In particular, we identified the cocirculation in the index case of two viral strains showing a different insertion at the hemagglutinin cleavage site, as well as nine nucleotide differences at the consensus level and 92 minority variants. To assess interfarm transmission, we combined epidemiological and genetic data and identified the index case as the major source of the virus, suggesting the spread of different viral haplotypes from the index farm to the other industrial holdings, probably at different time points. Our results revealed interfarm transmission dynamics that the epidemiological data alone could not unravel and demonstrated that delay in the disease detection and stamping out was the major cause of the emergence and the spread of the HPAI strain. IMPORTANCE The within- and between-host evolutionary dynamics of a highly pathogenic avian influenza (HPAI) strain during a naturally occurring epidemic is currently poorly understood. Here, we perform for the first time an in-depth sequence analysis of all the samples collected during a HPAI epidemic and demonstrate the importance to complement outbreak investigations with genetic data to

  16. Extended transmission of two H5/H7 low pathogenic avian influenza viruses in chickens.

    PubMed

    Claes, G; Lambrecht, B; Dewulf, J; van den Berg, T; Marché, S

    2015-03-01

    Transmission experiments are useful for investigating the mechanisms of low pathogenic notifiable avian influenza virus (LPNAI) transmission. In this study, the hypothesis that inoculation-infected chickens are more infectious than contact-infected chickens was tested. To this end, extended transmission experiments with one H5N2 and one H7N1 LPAIV which had previously been characterized in a series of standard transmission experiments were conducted in specific pathogen-free (SPF) chickens. For the H5N2 LPAIV, the infectivity of contact-infected chickens was similar to the infectivity of inoculated chickens. Despite results from a previous study suggesting the H7N1 LPAIV strain to be similarly infectious to SPF chickens as the H5N2 LPAIV strain, the acquisition of contact-infected chickens proved more difficult for H7N1 LPAIV. It was assumed that this might have been a consequence of the length and timing of the exposure period. In conclusion, for LPNAIVs that first seemed equally infectious, short-term transmissibility may vary considerably.

  17. Reconstruction of disease transmission rates: Applications to measles, dengue, and influenza.

    PubMed

    Lange, Alexander

    2016-07-07

    Transmission rates are key in understanding the spread of infectious diseases. Using the framework of compartmental models, we introduce a simple method to reconstruct time series of transmission rates directly from incidence or disease-related mortality data. The reconstruction employs differential equations, which model the time evolution of infective stages and strains. Being sensitive to initial values, the method produces asymptotically correct solutions. The computations are fast, with time complexity being quadratic. We apply the reconstruction to data of measles (England and Wales, 1948-1967), dengue (Thailand, 1982-1999), and influenza (U.S., 1910-1927). The Measles example offers comparison with earlier work. Here we re-investigate reporting corrections, include and exclude demographic information. The dengue example deals with the failure of vector-control measures in reducing dengue hemorrhagic fever (DHF) in Thailand. Two competing mechanisms have been held responsible: strain interaction and demographic transitions. Our reconstruction reveals that both explanations are possible, showing that the increase in DHF cases is consistent with decreasing transmission rates resulting from reduced vector counts. The flu example focuses on the 1918/1919 pandemic, examining the transmission rate evolution for an invading strain. Our analysis indicates that the pandemic strain could have circulated in the population for many months before the pandemic was initiated by an event of highly increased transmission.

  18. Pathogenicity and transmission of a swine influenza A(H6N6) virus.

    PubMed

    Sun, Hailiang; Kaplan, Bryan S; Guan, Minhui; Zhang, Guihong; Ye, Jianqiang; Long, Li-Ping; Blackmon, Sherry; Yang, Chun-Kai; Chiang, Meng-Jung; Xie, Hang; Zhao, Nan; Cooley, Jim; Smith, David F; Liao, Ming; Cardona, Carol; Li, Lei; Wang, George Peng; Webby, Richard; Wan, Xiu-Feng

    2017-04-12

    Subtype H6 influenza A viruses (IAVs) are commonly detected in wild birds and domestic poultry and can infect humans. In 2010, a H6N6 virus emerged in southern China, and since then, it has caused sporadic infections among swine. We show that this virus binds to α2,6-linked and α2,3-linked sialic acids. Mutations at residues 222 (alanine to valine) and 228 (glycine to serine) of the virus hemagglutinin (HA) affected its receptor-binding properties. Experiments showed that the virus has limited transmissibility between ferrets through direct contact or through inhalation of infectious aerosolized droplets. The internal genes of the influenza A(H1N1)pdm09 virus, which is prevalent in swine worldwide, increases the replication efficiency of H6N6 IAV in the lower respiratory tract of ferrets but not its transmissibility between ferrets. These findings suggest H6N6 swine IAV (SIV) currently poses a moderate risk to public health, but its evolution and spread should be closely monitored.

  19. Swine-to-Human Transmission of Influenza A(H3N2) Virus at Agricultural Fairs, Ohio, USA, 2012

    PubMed Central

    Nelson, Sarah W.; Page, Shannon L.; Nolting, Jacqueline M.; Killian, Mary L.; Sreevatsan, Srinand; Slemons, Richard D.

    2014-01-01

    Agricultural fairs provide an opportunity for bidirectional transmission of influenza A viruses. We sought to determine influenza A virus activity among swine at fairs in the United States. As part of an ongoing active influenza A virus surveillance project, nasal swab samples were collected from exhibition swine at 40 selected Ohio agricultural fairs during 2012. Influenza A(H3N2) virus was isolated from swine at 10 of the fairs. According to a concurrent public health investigation, 7 of the 10 fairs were epidemiologically linked to confirmed human infections with influenza A(H3N2) variant virus. Comparison of genome sequences of the subtype H3N2 isolates recovered from humans and swine from each fair revealed nucleotide identities of >99.7%, confirming zoonotic transmission between swine and humans. All influenza A(H3N2) viruses isolated in this study, regardless of host species or fair, were >99.5% identical, indicating that 1 virus strain was widely circulating among exhibition swine in Ohio during 2012. PMID:25148572

  20. Swine-to-human transmission of influenza A(H3N2) virus at agricultural fairs, Ohio, USA, 2012.

    PubMed

    Bowman, Andrew S; Nelson, Sarah W; Page, Shannon L; Nolting, Jacqueline M; Killian, Mary L; Sreevatsan, Srinand; Slemons, Richard D

    2014-09-01

    Agricultural fairs provide an opportunity for bidirectional transmission of influenza A viruses. We sought to determine influenza A virus activity among swine at fairs in the United States. As part of an ongoing active influenza A virus surveillance project, nasal swab samples were collected from exhibition swine at 40 selected Ohio agricultural fairs during 2012. Influenza A(H3N2) virus was isolated from swine at 10 of the fairs. According to a concurrent public health investigation, 7 of the 10 fairs were epidemiologically linked to confirmed human infections with influenza A(H3N2) variant virus. Comparison of genome sequences of the subtype H3N2 isolates recovered from humans and swine from each fair revealed nucleotide identities of >99.7%, confirming zoonotic transmission between swine and humans. All influenza A(H3N2) viruses isolated in this study, regardless of host species or fair, were >99.5% identical, indicating that 1 virus strain was widely circulating among exhibition swine in Ohio during 2012.

  1. NADPH Oxidase 1 Is Associated with Altered Host Survival and T Cell Phenotypes after Influenza A Virus Infection in Mice

    PubMed Central

    Hofstetter, Amelia R.; De La Cruz, Juan A.; Cao, Weiping; Patel, Jenish; Belser, Jessica A.; McCoy, James; Liepkalns, Justine S.; Amoah, Samuel; Cheng, Guangjie; Ranjan, Priya; Diebold, Becky A.; Shieh, Wun-Ju; Zaki, Sherif; Katz, Jacqueline M.; Sambhara, Suryaprakash; Lambeth, J. David; Gangappa, Shivaprakash

    2016-01-01

    The role of the reactive oxygen species-producing NADPH oxidase family of enzymes in the pathology of influenza A virus infection remains enigmatic. Previous reports implicated NADPH oxidase 2 in influenza A virus-induced inflammation. In contrast, NADPH oxidase 1 (Nox1) was reported to decrease inflammation in mice within 7 days post-influenza A virus infection. However, the effect of NADPH oxidase 1 on lethality and adaptive immunity after influenza A virus challenge has not been explored. Here we report improved survival and decreased morbidity in mice with catalytically inactive NADPH oxidase 1 (Nox1*/Y) compared with controls after challenge with A/PR/8/34 influenza A virus. While changes in lung inflammation were not obvious between Nox1*/Y and control mice, we observed alterations in the T cell response to influenza A virus by day 15 post-infection, including increased interleukin-7 receptor-expressing virus-specific CD8+ T cells in lungs and draining lymph nodes of Nox1*/Y, and increased cytokine-producing T cells in lungs and spleen. Furthermore, a greater percentage of conventional and interstitial dendritic cells from Nox1*/Y draining lymph nodes expressed the co-stimulatory ligand CD40 within 6 days post-infection. Results indicate that NADPH oxidase 1 modulates the innate and adaptive cellular immune response to influenza virus infection, while also playing a role in host survival. Results suggest that NADPH oxidase 1 inhibitors may be beneficial as adjunct therapeutics during acute influenza infection. PMID:26910342

  2. Cost-effectiveness of seasonal quadrivalent versus trivalent influenza vaccination in the United States: A dynamic transmission modeling approach

    PubMed Central

    Brogan, Anita J.; Talbird, Sandra E.; Davis, Ashley E.; Thommes, Edward W.; Meier, Genevieve

    2017-01-01

    ABSTRACT Trivalent inactivated influenza vaccines (IIV3s) protect against 2 A strains and one B lineage; quadrivalent versions (IIV4s) protect against an additional B lineage. The objective was to assess projected health and economic outcomes associated with IIV4 versus IIV3 for preventing seasonal influenza in the US. A cost-effectiveness model was developed to interact with a dynamic transmission model. The transmission model tracked vaccination, influenza cases, infection-spreading interactions, and recovery over 10 y (2012–2022). The cost-effectiveness model estimated influenza-related complications, direct and indirect costs (2013–2014 US$), health outcomes, and cost-effectiveness. Inputs were taken from published/public sources or estimated using regression or calibration. Outcomes were discounted at 3% per year. Scenario analyses tested the reliability of the results. Seasonal vaccination with IIV4 versus IIV3 is predicted to reduce annual influenza cases by 1,973,849 (discounted; 2,325,644 undiscounted), resulting in 12–13% fewer cases and influenza-related complications and deaths. These reductions are predicted to translate into 18,485 more quality-adjusted life years (QALYs) accrued annually for IIV4 versus IIV3. Increased vaccine-related costs ($599 million; 5.7%) are predicted to be more than offset by reduced influenza treatment costs ($699 million; 12.2%), resulting in direct medical cost saving annually ($100 million; 0.6%). Including indirect costs, savings with IIV4 are predicted to be $7.1 billion (5.6%). Scenario analyses predict IIV4 to be cost-saving in all scenarios tested apart from low infectivity, where IIV4 is predicted to be cost-effective. In summary, seasonal influenza vaccination in the US with IIV4 versus IIV3 is predicted to improve health outcomes and reduce costs. PMID:27780425

  3. Transmissibility of Variant Influenza From Swine to Humans: A Modeling Approach

    PubMed Central

    Wong, Karen K.; Gambhir, Manoj; Finelli, Lyn; Swerdlow, David L.; Ostroff, Stephen; Reed, Carrie

    2015-01-01

    Background Respiratory illness was reported among humans and swine at an agricultural fair in 2011; 3 human infections with an influenza A(H3N2) variant (H3N2v) virus were confirmed. Using epidemiologic investigation data, we sought to estimate H3N2v transmissibility from swine to humans. Methods We developed a model of H3N2v transmission among swine and humans and fit it to data from a cohort of 100 agricultural club members reporting swine contact to estimate transmissibility. A sensitivity analysis was performed varying H3N2v prevalence in the club cohort. Using the best-fit transmission probability, we simulated the number of swine-acquired infections among all fair attendees. Results We estimated the best-fit probability of swine-to-human H3N2v transmission per minute of swine contact. Applying this probability to 14 910 people with swine contact at the fair, we estimate that there were 80 (95% confidence interval [CI], 40–133) H3N2v infections among persons aged <20 years and 58 (95% CI, 29–96) H3N2v infections among person aged ≥20 years. Conclusions Using early data from investigation of a new virus with unclear transmission properties, we estimated the transmissibility of H3N2v from swine to humans and the burden of H3N2v among fair attendees. Although the risk of H3N2v virus infection is small for fair attendees with minimal swine contact, large populations attend agricultural events each year, and human cases will likely occur when infected swine are present. PMID:23794727

  4. Pathogenicity and transmissibility of North American triple reassortant swine influenza A viruses in ferrets.

    PubMed

    Barman, Subrata; Krylov, Petr S; Fabrizio, Thomas P; Franks, John; Turner, Jasmine C; Seiler, Patrick; Wang, David; Rehg, Jerold E; Erickson, Gene A; Gramer, Marie; Webster, Robert G; Webby, Richard J

    2012-01-01

    North American triple reassortant swine (TRS) influenza A viruses have caused sporadic human infections since 2005, but human-to-human transmission has not been documented. These viruses have six gene segments (PB2, PB1, PA, HA, NP, and NS) closely related to those of the 2009 H1N1 pandemic viruses. Therefore, understanding of these viruses' pathogenicity and transmissibility may help to identify determinants of virulence of the 2009 H1N1 pandemic viruses and to elucidate potential human health threats posed by the TRS viruses. Here we evaluated in a ferret model the pathogenicity and transmissibility of three groups of North American TRS viruses containing swine-like and/or human-like HA and NA gene segments. The study was designed only to detect informative and significant patterns in the transmissibility and pathogenicity of these three groups of viruses. We observed that irrespective of their HA and NA lineages, the TRS viruses were moderately pathogenic in ferrets and grew efficiently in both the upper and lower respiratory tracts. All North American TRS viruses studied were transmitted between ferrets via direct contact. However, their transmissibility by respiratory droplets was related to their HA and NA lineages: TRS viruses with human-like HA and NA were transmitted most efficiently, those with swine-like HA and NA were transmitted minimally or not transmitted, and those with swine-like HA and human-like NA (N2) showed intermediate transmissibility. We conclude that the lineages of HA and NA may play a crucial role in the respiratory droplet transmissibility of these viruses. These findings have important implications for pandemic planning and warrant confirmation.

  5. Findings from a household randomized controlled trial of hand washing and face masks to reduce influenza transmission in Bangkok, Thailand.

    PubMed

    Simmerman, James M; Suntarattiwong, Piyarat; Levy, Jens; Jarman, Richard G; Kaewchana, Suchada; Gibbons, Robert V; Cowling, Ben J; Sanasuttipun, Wiwan; Maloney, Susan A; Uyeki, Timothy M; Kamimoto, Laurie; Chotipitayasunondh, Tawee

    2011-07-01

    Evidence is needed on the effectiveness of non-pharmaceutical interventions (NPIs) to reduce influenza transmission. We studied NPIs in households with a febrile, influenza-positive child. Households were randomized to control, hand washing (HW), or hand washing plus paper surgical face masks (HW + FM) arms. Study nurses conducted home visits within 24 hours of enrollment and on days 3, 7, and 21. Respiratory swabs and serum were collected from all household members and tested for influenza by RT-PCR or serology. Between April 2008 and August 2009, 991 (16·5%) of 5995 pediatric influenza-like illness patients tested influenza positive. Four hundred and forty-two index children with 1147 household members were enrolled, and 221 (50·0%) were aged <6 years. Three hundred and ninety-seven (89·8%) households reported that the index patient slept in the parents' bedroom. The secondary attack rate was 21·5%, and 56/345 (16·3%; 95% CI 12·4-20·2%) secondary cases were asymptomatic. Hand-washing subjects reported 4·7 washing episodes/day, compared to 4·9 times/day in the HW + FM arm and 3·9 times/day in controls (P = 0·001). The odds ratios (ORs) for secondary influenza infection were not significantly different in the HW arm (OR = 1·20; 95% CI 0·76-1·88; P-0.442), or the HW + FM arm (OR = 1·16; 95% CI .0·74-1·82; P = 0.525). Influenza transmission was not reduced by interventions to promote hand washing and face mask use. This may be attributable to transmission that occurred before the intervention, poor facemask compliance, little difference in hand-washing frequency between study groups, and shared sleeping arrangements. A prospective study design and a careful analysis of sociocultural factors could improve future NPI studies. © 2011 Blackwell Publishing Ltd.

  6. Replication and Transmission of the Novel Bovine Influenza D Virus in a Guinea Pig Model.

    PubMed

    Sreenivasan, Chithra; Thomas, Milton; Sheng, Zizhang; Hause, Ben M; Collin, Emily A; Knudsen, David E B; Pillatzki, Angela; Nelson, Eric; Wang, Dan; Kaushik, Radhey S; Li, Feng

    2015-12-01

    Influenza D virus (FLUDV) is a novel influenza virus that infects cattle and swine. The goal of this study was to investigate the replication and transmission of bovine FLUDV in guinea pigs. Following direct intranasal inoculation of animals, the virus was detected in nasal washes of infected animals during the first 7 days postinfection. High viral titers were obtained from nasal turbinates and lung tissues of directly inoculated animals. Further, bovine FLUDV was able to transmit from the infected guinea pigs to sentinel animals by means of contact and not by aerosol dissemination under the experimental conditions tested in this study. Despite exhibiting no clinical signs, infected guinea pigs developed seroconversion and the viral antigen was detected in lungs of animals by immunohistochemistry. The observation that bovine FLUDV replicated in the respiratory tract of guinea pigs was similar to observations described previously in studies of gnotobiotic calves and pigs experimentally infected with bovine FLUDV but different from those described previously in experimental infections in ferrets and swine with a swine FLUDV, which supported virus replication only in the upper respiratory tract and not in the lower respiratory tract, including lung. Our study established that guinea pigs could be used as an animal model for studying this newly emerging influenza virus. Influenza D virus (FLUDV) is a novel emerging pathogen with bovine as its primary host. The epidemiology and pathogenicity of the virus are not yet known. FLUDV also spreads to swine, and the presence of FLUDV-specific antibodies in humans could indicate that there is a potential for zoonosis. Our results showed that bovine FLUDV replicated in the nasal turbinate and lungs of guinea pigs at high titers and was also able to transmit from an infected animal to sentinel animals by contact. The fact that bovine FLUDV replicated productively in both the upper and lower respiratory tracts of guinea pigs

  7. Replication and Transmission of the Novel Bovine Influenza D Virus in a Guinea Pig Model

    PubMed Central

    Sreenivasan, Chithra; Thomas, Milton; Sheng, Zizhang; Hause, Ben M.; Collin, Emily A.; Knudsen, David E. B.; Pillatzki, Angela; Nelson, Eric; Wang, Dan; Kaushik, Radhey S.

    2015-01-01

    ABSTRACT Influenza D virus (FLUDV) is a novel influenza virus that infects cattle and swine. The goal of this study was to investigate the replication and transmission of bovine FLUDV in guinea pigs. Following direct intranasal inoculation of animals, the virus was detected in nasal washes of infected animals during the first 7 days postinfection. High viral titers were obtained from nasal turbinates and lung tissues of directly inoculated animals. Further, bovine FLUDV was able to transmit from the infected guinea pigs to sentinel animals by means of contact and not by aerosol dissemination under the experimental conditions tested in this study. Despite exhibiting no clinical signs, infected guinea pigs developed seroconversion and the viral antigen was detected in lungs of animals by immunohistochemistry. The observation that bovine FLUDV replicated in the respiratory tract of guinea pigs was similar to observations described previously in studies of gnotobiotic calves and pigs experimentally infected with bovine FLUDV but different from those described previously in experimental infections in ferrets and swine with a swine FLUDV, which supported virus replication only in the upper respiratory tract and not in the lower respiratory tract, including lung. Our study established that guinea pigs could be used as an animal model for studying this newly emerging influenza virus. IMPORTANCE Influenza D virus (FLUDV) is a novel emerging pathogen with bovine as its primary host. The epidemiology and pathogenicity of the virus are not yet known. FLUDV also spreads to swine, and the presence of FLUDV-specific antibodies in humans could indicate that there is a potential for zoonosis. Our results showed that bovine FLUDV replicated in the nasal turbinate and lungs of guinea pigs at high titers and was also able to transmit from an infected animal to sentinel animals by contact. The fact that bovine FLUDV replicated productively in both the upper and lower respiratory tracts

  8. Laboratory creation of a highly transmissible H5N1 influenza virus: balancing substantial risks and real benefits.

    PubMed

    Pavia, Andrew T

    2012-03-20

    Controversy erupted when influenza researchers announced that they had created an H5N1 influenza virus that was transmissible between ferrets. The controversy escalated when the National Science Advisory Board for Biosecurity (NSABB) recommended that the work be published but recommended significant voluntary redactions. The responses to the NSABB action and to the research itself have been polarized. A readily transmitted H5N1 virus could be extraordinarily lethal; therefore, the risk for accidental release is significant, and deliberate misuse of the data to create a biological weapon is possible. However, the knowledge gained by these and future experiments under appropriate safeguards is likely to allow critical understanding of influenza transmission and virulence. It would be irresponsible to adopt either extreme solution: to prevent and censor the research or to allow unlimited distribution without careful review by an independent group, such as the NSABB.

  9. Influenza A(H7N9) Virus Transmission between Finches and Poultry

    PubMed Central

    Jones, Jeremy C.; Sonnberg, Stephanie; Webby, Richard J.

    2015-01-01

    Low pathogenicity avian influenza A(H7N9) virus has been detected in poultry since 2013, and the virus has caused >450 infections in humans. The mode of subtype H7N9 virus transmission between avian species remains largely unknown, but various wild birds have been implicated as a source of transmission. H7N9 virus was recently detected in a wild sparrow in Shanghai, China, and passerine birds, such as finches, which share space and resources with wild migratory birds, poultry, and humans, can be productively infected with the virus. We demonstrate that interspecies transmission of H7N9 virus occurs readily between society finches and bobwhite quail but only sporadically between finches and chickens. Inoculated finches are better able to infect naive poultry than the reverse. Transmission occurs through shared water but not through the airborne route. It is therefore conceivable that passerine birds may serve as vectors for dissemination of H7N9 virus to domestic poultry. PMID:25811839

  10. Influenza A(H7N9) virus transmission between finches and poultry.

    PubMed

    Jones, Jeremy C; Sonnberg, Stephanie; Webby, Richard J; Webster, Robert G

    2015-04-01

    Low pathogenicity avian influenza A(H7N9) virus has been detected in poultry since 2013, and the virus has caused >450 infections in humans. The mode of subtype H7N9 virus transmission between avian species remains largely unknown, but various wild birds have been implicated as a source of transmission. H7N9 virus was recently detected in a wild sparrow in Shanghai, China, and passerine birds, such as finches, which share space and resources with wild migratory birds, poultry, and humans, can be productively infected with the virus. We demonstrate that interspecies transmission of H7N9 virus occurs readily between society finches and bobwhite quail but only sporadically between finches and chickens. Inoculated finches are better able to infect naive poultry than the reverse. Transmission occurs through shared water but not through the airborne route. It is therefore conceivable that passerine birds may serve as vectors for dissemination of H7N9 virus to domestic poultry.

  11. Transmission Characteristics of Different Students during a School Outbreak of (H1N1) pdm09 Influenza in China, 2009

    PubMed Central

    Wang, Ligui; Chu, Chenyi; Yang, Guang; Hao, Rongzhang; Li, Zhenjun; Cao, Zhidong; Qiu, Shaofu; Li, Peng; Wu, Zhihao; Yuan, Zhengquan; Xu, Yuanyong; Zeng, Dajun; Wang, Yong; Song, Hongbin

    2014-01-01

    Many outbreaks of A(H1N1)pdm09 influenza have occurred in schools with a high population density. Containment of school outbreaks is predicted to help mitigate pandemic influenza. Understanding disease transmission characteristics within the school setting is critical to implementing effective control measures. Based on a school outbreak survey, we found almost all (93.7%) disease transmission occurred within a single grade, only 6.3% crossed grades. Transmissions originating from freshmen exhibited a star-shaped network; other grades exhibited branch- or line-shaped networks, indicating freshmen have higher activity and are more likely to cause infection. R0 for freshmen, calculated as 2.04, estimated as 2.76, was greater than for other grades (P < 0.01). Without intervention, the estimated number of cases was much greater when the outbreak was initiated by freshmen than by other grades. Furthermore, the estimated number of cases required to be under quarantine and isolation for freshmen was less than that of equivalent other grades. So we concluded that different grades have different transmission mode. Freshmen were the main facilitators of the spread of A(H1N1)pdm09 influenza during this school outbreak, so control measures (e.g. close contact isolation) priority used for freshmen would likely have effectively reduced spread of influenza in school settings. PMID:25102240

  12. Multiannual patterns of influenza A transmission in Chinese live bird market systems

    PubMed Central

    Pepin, Kim M.; Wang, Jia; Webb, Colleen T.; Smith, Gavin J. D.; Poss, Mary; Hudson, Peter J.; Hong, Wenshan; Zhu, Huachen; Riley, Steven; Guan, Yi

    2012-01-01

    Please cite this paper as: Pepin et al. (2012) Multiannual patterns of influenza A transmission in Chinese live bird market systems. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750‐2659.2012.00354.x. Background  Avian influenza viruses (AIV) cause huge economic losses in poultry industries and pose a substantial threat to human health. However, predicting AIV epizootics and emergence in humans is confounded by insufficient empirical data on the ecology and dynamics of AIV in poultry systems. To address this gap, we quantified incidence patterns for 13 hemagglutinin subtypes of AIV using 6 years of surveillance data that were collected from ten different species of poultry and three different types of poultry holdings (contexts) – retail, wholesale, or farms. Methods  We collected 42 646 samples in Shantou, China between 2000 and 2006. We screened samples for hemagglutinin subtypes 1–13 of AIV and Avian Paramyxovirus‐type‐1 (APMV‐1) using monospecific antisera in hemagglutination inhibition tests. We analyzed the data to determine seasonality patterns, subtype–host, and subtype–subtype interactions as well as subtype bias in incidence in different contexts. Results  H3, H6, H9, and APMV‐1 were the most prevalent. No significant seasonality was found when all subtypes were considered together. For most AIV subtypes and APMV‐1, there was subtype specificity for host, context, and coinfection partner. H5 showed the most generalized host usage pattern, followed by H9 and H6. Conclusion  Subtype‐specific patterns because of host, context, and other subtypes suggest that risk assessments that exclude these details are likely inaccurate. Surveillance should include longitudinal sampling of multiple host species in multiple contexts. Quantitative models of control strategies must consider multiple subtypes, hosts, and source contexts to assess the effectiveness of interventions. PMID:22458429

  13. Nosocomial transmission of avian influenza A (H7N9) virus in China: epidemiological investigation

    PubMed Central

    Fang, Chun-Fu; Ma, Mai-Juan; Zhan, Bing-Dong; Lai, Shi-Ming; Hu, Yi; Yang, Xiao-Xian; Li, Jing; Zhou, Jing-Jing; Zhang, Jian-Min; Wang, Shuang-Qing; Hu, Xiao-Long; Li, Yin-Jun; Wang, Xiao-Xiao; Cheng, Wei; Yao, Hong-Wu; Li, Xin-Lou; Yi, Huai-Ming; Xu, Wei-Dong; Jiang, Jia-Fu; Gray, Gregory C; Fang, Li-Qun; Chen, En-Fu

    2015-01-01

    Study question Can avian influenza A (H7N9) virus be transmitted between unrelated individuals in a hospital setting? Methods An epidemiological investigation looked at two patients who shared a hospital ward in February 2015, in Quzhou, Zhejiang Province, China. Samples from the patients, close contacts, and local environments were examined by real time reverse transcriptase (rRT) polymerase chain reaction (PCR) and viral culture. Haemagglutination inhibition and microneutralisation assays were used to detect specific antibodies to the viruses. Primary outcomes were clinical data, infection source tracing, phylogenetic tree analysis, and serological results. Study answer and limitations A 49 year old man (index patient) became ill seven days after visiting a live poultry market. A 57 year old man (second patient), with a history of chronic obstructive pulmonary disease, developed influenza-like symptoms after sharing the same hospital ward as the index patient for five days. The second patient had not visited any poultry markets nor had any contact with poultry or birds within 15 days before the onset of illness. H7N9 virus was identified in the two patients, who both later died. Genome sequences of the virus isolated from both patients were nearly identical, and genetically similar to the virus isolated from the live poultry market. No specific antibodies were detected among 38 close contacts. Transmission between the patients remains unclear, owing to the lack of samples collected from their shared hospital ward. Although several environmental swabs were positive for H7N9 by rRT-PCR, no virus was cultured. Owing to delayed diagnosis and frequent hospital transfers, no serum samples were collected from the patients, and antibodies to H7N9 viruses could not be tested. What this study adds Nosocomial H7N9 transmission might be possible between two unrelated individuals. Surveillance on patients with influenza-like illness in hospitals as well as chickens in live

  14. Mapping risk of avian influenza transmission at the interface of domestic poultry and wild birds

    USGS Publications Warehouse

    Prosser, Diann J.; Hungerford, Laura L.; Erwin, R. Michael; Ottinger, Mary Ann; Takekawa, John Y.; Ellis, Erle C.

    2013-01-01

    Emergence of avian influenza viruses with high lethality to humans, such as the currently circulating highly pathogenic A(H5N1) (emerged in 1996) and A(H7N9) cause serious concern for the global economic and public health sectors. Understanding the spatial and temporal interface between wild and domestic populations, from which these viruses emerge, is fundamental to taking action. This information, however, is rarely considered in influenza risk models, partly due to a lack of data. We aim to identify areas of high transmission risk between domestic poultry and wild waterfowl in China, the epicenter of both viruses. Two levels of models were developed: one that predicts hotspots of novel virus emergence between domestic and wild birds, and one that incorporates H5N1 risk factors, for which input data exists. Models were produced at 1 and 30 km spatial resolution, and two temporal seasons. Patterns of risk varied between seasons with higher risk in the northeast, central-east, and western regions of China during spring and summer, and in the central and southeastern regions during winter. Monte-Carlo uncertainty analyses indicated varying levels of model confidence, with lowest errors in the densely populated regions of eastern and southern China. Applications and limitations of the models are discussed within.

  15. Interspecies transmission and limited persistence of low pathogenic avian influenza genomes among Alaska dabbling ducks

    USGS Publications Warehouse

    Reeves, Andrew B.; Pearce, John M.; Ramey, Andy M.; Meixell, Brandt; Runstadler, Jonathan A.

    2011-01-01

    The reassortment and geographic distribution of low pathogenic avian influenza (LPAI) virus genes are well documented, but little is known about the persistence of intact LPAI genomes among species and locations. To examine persistence of entire LPAI genome constellations in Alaska, we calculated the genetic identities among 161 full-genome LPAI viruses isolated across 4 years from five species of duck: northern pintail (Anas acuta), mallard (Anas platyrhynchos), American green-winged teal (Anas crecca), northern shoveler (Anas clypeata) and American wigeon (Anas Americana). Based on pairwise genetic distance, highly similar LPAI genomes (>99 percent identity) were observed within and between species and across a range of geographic distances (up to and >1000 km), but most often between isolates collected 0-10 km apart. Highly similar viruses were detected between years, suggesting inter-annual persistence, but these were rare in our data set with the majority occurring within 0-9 days of sampling. These results identify LPAI transmission pathways in the context of species, space and time, an initial perspective into the extent of regional virus distribution and persistence, and insight into why no completely Eurasian genomes have ever been detected in Alaska. Such information will be useful in forecasting the movement of foreign-origin avian influenza strains should they be introduced to North America.

  16. Interspecies transmission and limited persistence of low pathogenic avian influenza genomes among Alaska dabbling ducks

    USGS Publications Warehouse

    Reeves, A.B.; Pearce, J.M.; Ramey, A.M.; Meixell, B.W.; Runstadler, J.A.

    2011-01-01

    The reassortment and geographic distribution of low pathogenic avian influenza (LPAI) virus genes are well documented, but little is known about the persistence of intact LPAI genomes among species and locations. To examine persistence of entire LPAI genome constellations in Alaska, we calculated the genetic identities among 161 full-genome LPAI viruses isolated across 4. years from five species of duck: northern pintail (Anas acuta), mallard (Anas platyrhynchos), American green-winged teal (Anas crecca), northern shoveler (Anas clypeata) and American wigeon (Anas americana). Based on pairwise genetic distance, highly similar LPAI genomes (>99% identity) were observed within and between species and across a range of geographic distances (up to and >1000 km), but most often between isolates collected 0-10. km apart. Highly similar viruses were detected between years, suggesting inter-annual persistence, but these were rare in our data set with the majority occurring within 0-9. days of sampling. These results identify LPAI transmission pathways in the context of species, space and time, an initial perspective into the extent of regional virus distribution and persistence, and insight into why no completely Eurasian genomes have ever been detected in Alaska. Such information will be useful in forecasting the movement of foreign-origin avian influenza strains should they be introduced to North America. ?? 2011.

  17. Intraspecies and interspecies transmission of mink H9N2 influenza virus.

    PubMed

    Yong-Feng, Zhao; Fei-Fei, Diao; Jia-Yu, Yu; Feng-Xia, Zhang; Chang-Qing, Jiang; Jian-Li, Wang; Shou-Yu, Guo; Kai, Cui; Chuan-Yi, Liu; Xue-Hua, Wei; Jiang, Shi-Jin; Zhi-Jing, Xie

    2017-08-07

    H9N2 influenza A virus (IAV) causes low pathogenic respiratory disease and infects a wide range of hosts. In this study, six IAVs were isolated from mink and identified as H9N2 IAV. Sequence analysis revealed that the six isolates continued to evolve, and their PB2 genes shared high nucleotide sequence identity with H7N9 IAV. The six isolates contained an amino acid motif PSRSSR↓GL at the hemagglutinin cleavage site, which is a characteristic of low pathogenic influenza viruses. A serosurvey demonstrated that H9N2 IAV had spread widely in mink and was prevalent in foxes and raccoon dogs. Transmission experiments showed that close contact between H9N2-infected mink and naive mink, foxes and raccoon dogs resulted in spread of the virus to the contact animals. Furthermore, H9N2 challenge experiments in foxes and raccoon dogs showed that H9N2 IAV could infect these hosts. Virological and epidemiological surveillance of H9N2 IAV should be strengthened for the fur animal industry.

  18. Possible waterborne transmission and maintenance of influenza viruses in domestic ducks.

    PubMed Central

    Markwell, D D; Shortridge, K F

    1982-01-01

    Two duck farms in Hong Kong were examined monthly for 1 year for the occurrence and persistence of influenza viruses within the duck communities. The predominant virus in one community was H3N2, a virus antigenically related to the pandemic Hong Kong strain. This virus was isolated monthly throughout the year from feces or pond water or both, indicating a cycle of waterborne transmission. Viruses of the same antigenic combination were isolated 1 and 2 years after the last sampling occasion, implying persistence in the community. Infection was asymptomatic. Maintenance of virus appeared to be dependent upon the continual introduction of ducklings susceptible to infection onto virus-contaminated water; the feces of ducks 70 to 80 days old were generally free of detectable virus despite the exposure of the ducks to virus in pond water. In the second community, in which ducklings were not introduced after the initial sampling, the prevailing viruses, H7N1 and H7N2, also present asymptomatically, ceased to be detected once the ducks were 70 to 80 days old. The normal practice of raising ducks of different ages on the same farm, wherein the water supplies are shared, as typified by the first community, appears to be instrumental in maintaining a large reservoir of influenza viruses in the duck population of southern China. PMID:7055370

  19. Mapping Avian Influenza Transmission Risk at the Interface of Domestic Poultry and Wild Birds

    PubMed Central

    Prosser, Diann J.; Hungerford, Laura L.; Erwin, R. Michael; Ottinger, Mary Ann; Takekawa, John Y.; Ellis, Erle C.

    2013-01-01

    Emergence of avian influenza viruses with high lethality to humans, such as the currently circulating highly pathogenic A(H5N1) (emerged in 1996) and A(H7N9) cause serious concern for the global economic and public health sectors. Understanding the spatial and temporal interface between wild and domestic populations, from which these viruses emerge, is fundamental to taking action. This information, however, is rarely considered in influenza risk models, partly due to a lack of data. We aim to identify areas of high transmission risk between domestic poultry and wild waterfowl in China, the epicenter of both viruses. Two levels of models were developed: one that predicts hotspots of novel virus emergence between domestic and wild birds, and one that incorporates H5N1 risk factors, for which input data exists. Models were produced at 1 and 30 km spatial resolution, and two temporal seasons. Patterns of risk varied between seasons with higher risk in the northeast, central-east, and western regions of China during spring and summer, and in the central and southeastern regions during winter. Monte-Carlo uncertainty analyses indicated varying levels of model confidence, with lowest errors in the densely populated regions of eastern and southern China. Applications and limitations of the models are discussed within. PMID:24350197

  20. The transmissibility of highly pathogenic avian influenza in commercial poultry in industrialised countries.

    PubMed

    Garske, Tini; Clarke, Paul; Ghani, Azra C

    2007-04-04

    With the increased occurrence of outbreaks of H5N1 worldwide there is concern that the virus could enter commercial poultry farms with severe economic consequences. We analyse data from four recent outbreaks of highly pathogenic avian influenza (HPAI) in commercial poultry to estimate the farm-to-farm reproductive number for HPAI. The reproductive number is a key measure of the transmissibility of HPAI at the farm level because it can be used to evaluate the effectiveness of the control measures. In these outbreaks the mean farm-to-farm reproductive number prior to controls ranged from 1.1 to 2.4, with the maximum farm-based reproductive number in the range 2.2 to 3.2. Enhanced bio-security, movement restrictions and prompt isolation of the infected farms in all four outbreaks substantially reduced the reproductive number, but it remained close to the threshold value 1 necessary to ensure the disease will be eradicated. Our results show that depending on the particular situation in which an outbreak of avian influenza occurs, current controls might not be enough to eradicate the disease, and therefore a close monitoring of the outbreak is required. The method we used for estimating the reproductive number is straightforward to implement and can be used in real-time. It therefore can be a useful tool to inform policy decisions.

  1. Evolutionary and transmission dynamics of reassortant H5N1 influenza virus in Indonesia.

    PubMed

    Lam, Tommy Tsan-Yuk; Hon, Chung-Chau; Pybus, Oliver G; Kosakovsky Pond, Sergei L; Wong, Raymond Tze-Yeung; Yip, Chi-Wai; Zeng, Fanya; Leung, Frederick Chi-Ching

    2008-08-22

    H5N1 highly pathogenic avian influenza (HPAI) viruses have seriously affected the Asian poultry industry since their recurrence in 2003. The viruses pose a threat of emergence of a global pandemic influenza through point mutation or reassortment leading to a strain that can effectively transmit among humans. In this study, we present phylogenetic evidences for the interlineage reassortment among H5N1 HPAI viruses isolated from humans, cats, and birds in Indonesia, and identify the potential genetic parents of the reassorted genome segments. Parsimony analyses of viral phylogeography suggest that the reassortant viruses may have originated from greater Jakarta and surroundings, and subsequently spread to other regions in the West Java province. In addition, Bayesian methods were used to elucidate the genetic diversity dynamics of the reassortant strain and one of its genetic parents, which revealed a more rapid initial growth of genetic diversity in the reassortant viruses relative to their genetic parent. These results demonstrate that interlineage exchange of genetic information may play a pivotal role in determining viral genetic diversity in a focal population. Moreover, our study also revealed significantly stronger diversifying selection on the M1 and PB2 genes in the lineages preceding and subsequent to the emergence of the reassortant viruses, respectively. We discuss how the corresponding mutations might drive the adaptation and onward transmission of the newly formed reassortant viruses.

  2. 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.

  3. Genetic tuning of the novel avian influenza A(H7N9) virus during interspecies transmission, China, 2013.

    PubMed

    Wang, D; Yang, L; Gao, R; Zhang, X; Tan, Y; Wu, A; Zhu, W; Zhou, J; Zou, S; Li, Xiyan; Sun, Y; Zhang, Y; Liu, Y; Liu, T; Xiong, Y; Xu, J; Chen, L; Weng, Y; Qi, X; Guo, J; Li, Xiaodan; Dong, J; Huang, W; Zhang, Y; Dong, L; Zhao, X; Liu, L; Lu, J; Lan, Y; Wei, H; Xin, L; Chen, Y; Xu, C; Chen, T; Zhu, Y; Jiang, T; Feng, Z; Yang, W; Wang, Y; Zhu, H; Guan, Y; Gao, G F; Li, D; Han, J; Wang, S; Wu, G; Shu, Y

    2014-06-26

    A novel avian influenza A(H7N9) virus causing human infection emerged in February 2013 in China. To elucidate the mechanism of interspecies transmission, we compared the signature amino acids of avian influenza A(H7N9) viruses from human and non-human hosts and analysed the reassortants of 146 influenza A(H7N9) viruses with full genome sequences. We propose a genetic tuning procedure with continuous amino acid substitutions and reassorting that mediates host adaptation and interspecies transmission. When the early influenza A(H7N9) virus, containing ancestor haemagglutinin (HA) and neuraminidase (NA) genes similar to A/Shanghai/05 virus, circulated in waterfowl and transmitted to terrestrial poultry, it acquired an NA stalk deletion at amino acid positions 69 to 73. Then, receptor binding preference was tuned to increase the affinity to human-like receptors through HA G186V and Q226L mutations in terrestrial poultry. Additional mammalian adaptations such as PB2 E627K were selected in humans. The continual reassortation between H7N9 and H9N2 viruses resulted in multiple genotypes for further host adaptation. When we analysed a potential association of mutations and reassortants with clinical outcome, only the PB2 E627K mutation slightly increased the case fatality rate. Genetic tuning may create opportunities for further adaptation of influenza A(H7N9) and its potential to cause a pandemic.

  4. The use of masks and respirators to prevent transmission of influenza: a systematic review of the scientific evidence.

    PubMed

    Bin-Reza, Faisal; Lopez Chavarrias, Vicente; Nicoll, Angus; Chamberland, Mary E

    2012-07-01

    There are limited data on the use of masks and respirators to reduce transmission of influenza. A systematic review was undertaken to help inform pandemic influenza guidance in the United Kingdom. The initial review was performed in November 2009 and updated in June 2010 and January 2011. Inclusion criteria included randomised controlled trials and quasi-experimental and observational studies of humans published in English with an outcome of laboratory-confirmed or clinically-diagnosed influenza and other viral respiratory infections. There were 17 eligible studies. Six of eight randomised controlled trials found no significant differences between control and intervention groups (masks with or without hand hygiene; N95/P2 respirators). One household trial found that mask wearing coupled with hand sanitiser use reduced secondary transmission of upper respiratory infection/influenza-like illness/laboratory-confirmed influenza compared with education; hand sanitiser alone resulted in no reduction. One hospital-based trial found a lower rate of clinical respiratory illness associated with non-fit-tested N95 respirator use compared with medical masks. Eight of nine retrospective observational studies found that mask and/or respirator use was independently associated with a reduced risk of severe acute respiratory syndrome (SARS). Findings, however, may not be applicable to influenza and many studies were suboptimal. None of the studies established a conclusive relationship between mask/respirator use and protection against influenza infection. Some evidence suggests that mask use is best undertaken as part of a package of personal protection especially hand hygiene. The effectiveness of masks and respirators is likely linked to early, consistent and correct usage. © 2011 Blackwell Publishing Ltd.

  5. Modeling insights into Haemophilus influenzae type b disease, transmission, and vaccine programs.

    PubMed

    Jackson, Michael L; Rose, Charles E; Cohn, Amanda; Coronado, Fatima; Clark, Thomas A; Wenger, Jay D; Bulkow, Lisa; Bruce, Michael G; Messonnier, Nancy E; Hennessy, Thomas W

    2012-01-01

    In response to the 2007-2009 Haemophilus influenzae type b (Hib) vaccine shortage in the United States, we developed a flexible model of Hib transmission and disease for optimizing Hib vaccine programs in diverse populations and situations. The model classifies population members by age, colonization/disease status, and antibody levels, with movement across categories defined by differential equations. We implemented the model for the United States as a whole, England and Wales, and the Alaska Native population. This model accurately simulated Hib incidence in all 3 populations, including the increased incidence in England/Wales beginning in 1999 and the change in Hib incidence in Alaska Natives after switching Hib vaccines in 1996. The model suggests that a vaccine shortage requiring deferral of the booster dose could last 3 years in the United States before loss of herd immunity would result in increasing rates of invasive Hib disease in children <5 years of age.

  6. Modeling Insights into Haemophilus influenzae Type b Disease, Transmission, and Vaccine Programs

    PubMed Central

    Rose, Charles E.; Cohn, Amanda; Coronado, Fatima; Clark, Thomas A.; Wenger, Jay D.; Bulkow, Lisa; Bruce, Michael G.; Messonnier, Nancy E.; Hennessy, Thomas W.

    2012-01-01

    In response to the 2007–2009 Haemophilus influenzae type b (Hib) vaccine shortage in the United States, we developed a flexible model of Hib transmission and disease for optimizing Hib vaccine programs in diverse populations and situations. The model classifies population members by age, colonization/disease status, and antibody levels, with movement across categories defined by differential equations. We implemented the model for the United States as a whole, England and Wales, and the Alaska Native population. This model accurately simulated Hib incidence in all 3 populations, including the increased incidence in England/Wales beginning in 1999 and the change in Hib incidence in Alaska Natives after switching Hib vaccines in 1996. The model suggests that a vaccine shortage requiring deferral of the booster dose could last 3 years in the United States before loss of herd immunity would result in increasing rates of invasive Hib disease in children <5 years of age. PMID:22257582

  7. Transmission of avian influenza A viruses among species in an artificial barnyard.

    PubMed

    Achenbach, Jenna E; Bowen, Richard A

    2011-03-31

    Waterfowl and shorebirds harbor and shed all hemagglutinin and neuraminidase subtypes of influenza A viruses and interact in nature with a broad range of other avian and mammalian species to which they might transmit such viruses. Estimating the efficiency and importance of such cross-species transmission using epidemiological approaches is difficult. We therefore addressed this question by studying transmission of low pathogenic H5 and H7 viruses from infected ducks to other common animals in a quasi-natural laboratory environment designed to mimic a common barnyard. Mallards (Anas platyrhynchos) recently infected with H5N2 or H7N3 viruses were introduced into a room housing other mallards plus chickens, blackbirds, rats and pigeons, and transmission was assessed by monitoring virus shedding (ducks) or seroconversion (other species) over the following 4 weeks. Additional animals of each species were directly inoculated with virus to characterize the effect of a known exposure. In both barnyard experiments, virus accumulated to high titers in the shared water pool. The H5N2 virus was transmitted from infected ducks to other ducks and chickens in the room either directly or through environmental contamination, but not to rats or blackbirds. Ducks infected with the H7N2 virus transmitted directly or indirectly to all other species present. Chickens and blackbirds directly inoculated with these viruses shed significant amounts of virus and seroconverted; rats and pigeons developed antiviral antibodies, but, except for one pigeon, failed to shed virus.

  8. The contribution of social behaviour to the transmission of influenza A in a human population.

    PubMed

    Kucharski, Adam J; Kwok, Kin O; Wei, Vivian W I; Cowling, Benjamin J; Read, Jonathan M; Lessler, Justin; Cummings, Derek A; Riley, Steven

    2014-06-01

    Variability in the risk of transmission for respiratory pathogens can result from several factors, including the intrinsic properties of the pathogen, the immune state of the host and the host's behaviour. It has been proposed that self-reported social mixing patterns can explain the behavioural component of this variability, with simulated intervention studies based on these data used routinely to inform public health policy. However, in the absence of robust studies with biological endpoints for individuals, it is unclear how age and social behaviour contribute to infection risk. To examine how the structure and nature of social contacts influenced infection risk over the course of a single epidemic, we designed a flexible disease modelling framework: the population was divided into a series of increasingly detailed age and social contact classes, with the transmissibility of each age-contact class determined by the average contacts of that class. Fitting the models to serologically confirmed infection data from the 2009 Hong Kong influenza A/H1N1p pandemic, we found that an individual's risk of infection was influenced strongly by the average reported social mixing behaviour of their age group, rather than by their personal reported contacts. We also identified the resolution of social mixing that shaped transmission: epidemic dynamics were driven by intense contacts between children, a post-childhood drop in risky contacts and a subsequent rise in contacts for individuals aged 35-50. Our results demonstrate that self-reported social contact surveys can account for age-associated heterogeneity in the transmission of a respiratory pathogen in humans, and show robustly how these individual-level behaviours manifest themselves through assortative age groups. Our results suggest it is possible to profile the social structure of different populations and to use these aggregated data to predict their inherent transmission potential.

  9. 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

  10. Risks of Avian Influenza Transmission in Areas of Intensive Free-ranging Duck Production with wild waterfowl

    PubMed Central

    Cappelle, Julien; Zhao, Delong; Gilbert, Marius; Nelson, Martha I.; Newman, Scott H.; Takekawa, John Y.; Gaidet, Nicolas; Prosser, Diann J.; Liu, Ying; Li, Peng; Shu, Yuelong; Xiao, Xiangming

    2014-01-01

    For decades, southern China has been considered to be an important source for emerging influenza viruses since key hosts live together in high densities in areas with intensive agriculture. However, the underlying conditions of emergence and spread of avian influenza viruses (AIV) have not been studied in detail, particularly the complex spatiotemporal interplay of viral transmission between wild and domestic ducks, two major actors of AIV epidemiology. In this synthesis, we examine the risks of avian influenza spread in Poyang Lake, an area of intensive free-ranging duck production and large numbers of wild waterfowl. Our synthesis shows that farming of free-grazing domestic ducks is intensive in this area and synchronized with wild duck migration. The presence of juvenile domestic ducks in harvested paddy fields prior to the arrival and departure of migrant ducks in the same fields may amplify the risk of AIV circulation and facilitate the transmission between wild and domestic populations. We provide evidence associating wild ducks migration with the spread of H5N1 in the spring of 2008 from southern China to South Korea, Russia, and Japan, supported by documented wild duck movements and phylogenetic analyses of highly pathogenic avian influenza H5N1 sequences. We suggest that prevention measures based on a modification of agricultural practices may be implemented in these areas to reduce the intensity of AIV transmission between wild and domestic ducks. This would require involving all local stakeholders to discuss feasible and acceptable solutions. PMID:24652313

  11. Risks of avian influenza transmission in areas of intensive free-ranging duck production with wild waterfowl.

    PubMed

    Cappelle, Julien; Zhao, Delong; Gilbert, Marius; Nelson, Martha I; Newman, Scott H; Takekawa, John Y; Gaidet, Nicolas; Prosser, Diann J; Liu, Ying; Li, Peng; Shu, Yuelong; Xiao, Xiangming

    2014-01-01

    For decades, southern China has been considered to be an important source for emerging influenza viruses since key hosts live together in high densities in areas with intensive agriculture. However, the underlying conditions of emergence and spread of avian influenza viruses (AIV) have not been studied in detail, particularly the complex spatiotemporal interplay of viral transmission between wild and domestic ducks, two major actors of AIV epidemiology. In this synthesis, we examine the risks of avian influenza spread in Poyang Lake, an area of intensive free-ranging duck production and large numbers of wild waterfowl. Our synthesis shows that farming of free-grazing domestic ducks is intensive in this area and synchronized with wild duck migration. The presence of juvenile domestic ducks in harvested paddy fields prior to the arrival and departure of migrant ducks in the same fields may amplify the risk of AIV circulation and facilitate the transmission between wild and domestic populations. We provide evidence associating wild ducks migration with the spread of H5N1 in the spring of 2008 from southern China to South Korea, Russia, and Japan, supported by documented wild duck movements and phylogenetic analyses of highly pathogenic avian influenza H5N1 sequences. We suggest that prevention measures based on a modification of agricultural practices may be implemented in these areas to reduce the intensity of AIV transmission between wild and domestic ducks. This would require involving all local stakeholders to discuss feasible and acceptable solutions.

  12. Inducing Herd Immunity against Seasonal Influenza in Long-Term Care Facilities through Employee Vaccination Coverage: A Transmission Dynamics Model

    PubMed Central

    Wendelboe, Aaron M.; Grafe, Carl; McCumber, Micah; Anderson, Michael P.

    2015-01-01

    Introduction. Vaccinating healthcare workers (HCWs) in long-term care facilities (LTCFs) may effectively induce herd immunity and protect residents against influenza-related morbidity and mortality. We used influenza surveillance data from all LTCFs in New Mexico to validate a transmission dynamics model developed to investigate herd immunity induction. Material and Methods. We adjusted a previously published transmission dynamics model and used surveillance data from an active system among 76 LTCFs in New Mexico during 2006-2007 for model validation. We used a deterministic compartmental model with a stochastic component for transmission between residents and HCWs in each facility in order to simulate the random variation expected in such populations. Results. When outbreaks were defined as a dichotomous variable, our model predicted that herd immunity could be induced. When defined as an attack rate, the model demonstrated a curvilinear trend, but insufficiently strong to induce herd immunity. The model was sensitive to changes in the contact parameter β but was robust to changes in the visitor contact probability. Conclusions. These results further elucidate previous studies' findings that herd immunity may not be induced by vaccinating HCWs in LTCFs; however, increased influenza vaccination coverage among HCWs reduces the probability of influenza infection among residents. PMID:26101542

  13. Risks of avian influenza transmission in areas of intensive free-ranging duck production with wild waterfowl

    USGS Publications Warehouse

    Cappelle, Julien; Zhao, Delong; Gilbert, Marius; Newman, Scott H.; Takekawa, John Y.; Gaidet, Nicolas; Prosser, Diann J.; Liu, Ying; Li, Peng; Shu, Yuelong; Xiao, Xiangming

    2014-01-01

    For decades, southern China has been considered to be an important source for emerging influenza viruses since key hosts live together in high densities in areas with intensive agriculture. However, the underlying conditions of emergence and spread of avian influenza viruses (AIV) have not been studied in detail, particularly the complex spatiotemporal interplay of viral transmission between wild and domestic ducks, two major actors of AIV epidemiology. In this synthesis, we examine the risks of avian influenza spread in Poyang Lake, an area of intensive free-ranging duck production and large numbers of wild waterfowl. Our synthesis shows that farming of free-grazing domestic ducks is intensive in this area and synchronized with wild duck migration. The presence of juvenile domestic ducks in harvested paddy fields prior to the arrival and departure of migrant ducks in the same fields may amplify the risk of AIV circulation and facilitate the transmission between wild and domestic populations. We provide evidence associating wild ducks migration with the spread of H5N1 in the spring of 2008 from southern China to South Korea, Russia, and Japan, supported by documented wild duck movements and phylogenetic analyses of highly pathogenic avian influenza H5N1 sequences. We suggest that prevention measures based on a modification of agricultural practices may be implemented in these areas to reduce the intensity of AIV transmission between wild and domestic ducks. This would require involving all local stakeholders to discuss feasible and acceptable solutions.

  14. Tracking the Evolution of Polymerase Genes of Influenza A Viruses during Interspecies Transmission between Avian and Swine Hosts

    PubMed Central

    Karnbunchob, Nipawit; Omori, Ryosuke; Tessmer, Heidi L.; Ito, Kimihito

    2016-01-01

    Human influenza pandemics have historically been caused by reassortant influenza A viruses using genes from human and avian viruses. This genetic reassortment between human and avian viruses has been known to occur in swine during viral circulation, as swine are capable of circulating both avian and human viruses. Therefore, avian-to-swine transmission of viruses plays an important role in the emergence of new pandemic strains. The amino acids at several positions on PB2, PB1, and PA are known to determine the host range of influenza A viruses. In this paper, we track viral transmission between avian and swine to investigate the evolution on polymerase genes associated with their hosts. We traced viral transmissions between avian and swine hosts by using nucleotide sequences of avian viruses and swine viruses registered in the NCBI GenBank. Using BLAST and the reciprocal best hits technique, we found 32, 33, and 30 pairs of avian and swine nucleotide sequences that may be associated with avian-to-swine transmissions for PB2, PB1, and PA genes, respectively. Then, we examined the amino acid substitutions involved in these sporadic transmissions. On average, avian-to-swine transmission pairs had 5.47, 3.73, and 5.13 amino acid substitutions on PB2, PB1, and PA, respectively. However, amino acid substitutions were distributed over the positions, and few positions showed common substitutions in the multiple transmission events. Statistical tests on the number of repeated amino acid substitutions suggested that no specific positions on PB2 and PA may be required for avian viruses to infect swine. We also found that avian viruses that transmitted to swine tend to process I478V substitutions on PB2 before interspecies transmission events. Furthermore, most mutations occurred after the interspecies transmissions, possibly due to selective viral adaptation to swine. PMID:28082971

  15. Highly pathogenic avian influenza A(H5N1) mutants transmissible by air are susceptible to human and animal neutralizing antibodies.

    PubMed

    Du, Lanying; Li, Ye; Zhao, Guangyu; Wang, Lili; Zou, Peng; Lu, Lu; Zhou, Yusen; Jiang, Shibo

    2013-10-15

    A laboratory-generated reassortant H5 hemagglutinin (HA)/influenza A(H1N1) strain containing 4 mutations in influenza A(H5N1) HA has become transmissible by air among mammals. Here, we constructed 15 influenza A(H5N1) pseudoviruses containing a single mutation or a combination of mutations and showed that the pseudoviruses were susceptible to neutralizing antibodies from patients with influenza A(H5N1) infection and from mice immunized with a vaccine containing the conserved HA1 sequence of influenza A(H5N1). These results indicate that antibodies in patients currently infected by influenza A(H5N1) and antibodies induced by vaccines containing conserved sequences in HA1 of wild-type influenza A(H5N1) are highly effective in cross-neutralizing future influenza A(H5N1) mutants with airborne transmissibility, suggesting that human influenza pandemics caused by these influenza A(H5N1) variants can be prevented.

  16. Transmission Bottleneck Size Estimation from Pathogen Deep-Sequencing Data, with an Application to Human Influenza A Virus.

    PubMed

    Sobel Leonard, Ashley; Weissman, Daniel B; Greenbaum, Benjamin; Ghedin, Elodie; Koelle, Katia

    2017-07-15

    The bottleneck governing infectious disease transmission describes the size of the pathogen population transferred from the donor to the recipient host. Accurate quantification of the bottleneck size is particularly important for rapidly evolving pathogens such as influenza virus, as narrow bottlenecks reduce the amount of transferred viral genetic diversity and, thus, may decrease the rate of viral adaptation. Previous studies have estimated bottleneck sizes governing viral transmission by using statistical analyses of variants identified in pathogen sequencing data. These analyses, however, did not account for variant calling thresholds and stochastic viral replication dynamics within recipient hosts. Because these factors can skew bottleneck size estimates, we introduce a new method for inferring bottleneck sizes that accounts for these factors. Through the use of a simulated data set, we first show that our method, based on beta-binomial sampling, accurately recovers transmission bottleneck sizes, whereas other methods fail to do so. We then apply our method to a data set of influenza A virus (IAV) infections for which viral deep-sequencing data from transmission pairs are available. We find that the IAV transmission bottleneck size estimates in this study are highly variable across transmission pairs, while the mean bottleneck size of 196 virions is consistent with a previous estimate for this data set. Furthermore, regression analysis shows a positive association between estimated bottleneck size and donor infection severity, as measured by temperature. These results support findings from experimental transmission studies showing that bottleneck sizes across transmission events can be variable and influenced in part by epidemiological factors.IMPORTANCE The transmission bottleneck size describes the size of the pathogen population transferred from the donor to the recipient host and may affect the rate of pathogen adaptation within host populations. Recent

  17. Cultural Transmission and Survival in Contemporary Micmac Society

    ERIC Educational Resources Information Center

    Battiste, Marie

    1977-01-01

    The Micmacs of Canada have only had a couple of hundred years of contact with the white man and although at first glance their reserves appear acculturated, they are distinct cultural and linguistic entities who have survived the tortures, rigors, and challenges of Christianity and civilization. (JC)

  18. Cultural Transmission and Survival in Contemporary Micmac Society

    ERIC Educational Resources Information Center

    Battiste, Marie

    1977-01-01

    The Micmacs of Canada have only had a couple of hundred years of contact with the white man and although at first glance their reserves appear acculturated, they are distinct cultural and linguistic entities who have survived the tortures, rigors, and challenges of Christianity and civilization. (JC)

  19. Oral intake of Lactobacillus rhamnosus M21 enhances the survival rate of mice lethally infected with influenza virus.

    PubMed

    Song, Jeong Ah; Kim, Hee Joo; Hong, Seong Keun; Lee, Dong Hoon; Lee, Sang Won; Song, Chang Seon; Kim, Ki Taek; Choi, In Soo; Lee, Joong Bok; Park, Seung Yong

    2016-02-01

    Influenza viruses cause acute respiratory disease. Because of the high genetic variability of viruses, effective vaccines and antiviral agents are limited. Considering the fact that the site of influenza virus entry is the mucosa of the upper respiratory tract, probiotics that can enhance mucosal immunity as well as systemic immunity could be an important source of treatment against influenza infection. Mice were fed with Lactobacillus rhamnosus M21 or skim milk and were challenged with influenza virus. The resulting survival rate, lung inflammation, and changes in the cytokine and secretory immunoglobulin A (sIgA) levels were examined. Because of infection (influenza virus), all the mice in the control group and 60% of the mice in the L. rhamnosus M21 group died; however, the remaining 40% of the mice fed with L. rhamnosus M21 survived the infection. Pneumonia was severe in the control group but moderate in the group treated with L. rhamnosus M21. Although there were no significant changes in the proinflammatory cytokines in the lung lysates of mice collected from both groups, levels of interferon-γ and interleukin-2, which are representative cytokines of type I helper T cells, were significantly increased in the L. rhamnosus M21-treated group. An increase in sIgA as well as the diminution of inflammatory cells in bronchoalveolar lavage fluid was also observed in the L. rhamnosus M21-treated group. These results demonstrate that orally administered L. rhamnosus M21 activates humoral as well as cellular immune responses, conferring increased resistance to the host against influenza virus infection. Copyright © 2014. Published by Elsevier B.V.

  20. Haemophilus influenzae isolates survive for up to 20 years at -70 °C in skim milk tryptone glucose glycerol broth (STGGB) if thawing is avoided during re-culture.

    PubMed

    Hare, K M; Smith-Vaughan, H C; Beissbarth, J; Leach, A J

    2015-12-01

    Haemophilus influenzae remains a major cause of disease worldwide requiring continued study. Recently, isolates of Streptococcus pneumoniae and Moraxella catarrhalis, but not H. influenzae, were reported to survive long-term ultra-freeze storage in STGGB. We show that nontypeable H. influenzae isolates survive for up to 20 years when thawing is avoided.

  1. A highly pathogenic avian influenza virus H5N1 with 2009 pandemic H1N1 internal genes demonstrated increased replication and transmission in pigs

    USDA-ARS?s Scientific Manuscript database

    This study investigated the pathogenicity and transmissibility of a reverse-genetics derived highly pathogenic avian influenza (HPAI) H5N1 influenza A virus (IAV), A/Iraq/775/06, and a reassortant virus comprised of the HA and NA from A/Iraq/775/06 and the internal genes of a 2009 pandemic H1N1, A/N...

  2. Quantitative transmission characteristics of different H5 low pathogenic avian influenza viruses in Muscovy ducks.

    PubMed

    Niqueux, Éric; Picault, Jean-Paul; Amelot, Michel; Allée, Chantal; Lamandé, Josiane; Guillemoto, Carole; Pierre, Isabelle; Massin, Pascale; Blot, Guillaume; Briand, François-Xavier; Rose, Nicolas; Jestin, Véronique

    2014-01-10

    EU annual serosurveillance programs show that domestic duck flocks have the highest seroprevalence of H5 antibodies, demonstrating the circulation of notifiable avian influenza virus (AIV) according to OIE, likely low pathogenic (LP). Therefore, transmission characteristics of LPAIV within these flocks can help to understand virus circulation and possible risk of propagation. This study aimed at estimating transmission parameters of four H5 LPAIV (three field strains from French poultry and decoy ducks, and one clonal reverse-genetics strain derived from one of the former), using a SIR model to analyze data from experimental infections in SPF Muscovy ducks. The design was set up to accommodate rearing on wood shavings with a low density of 1.6 ducks/m(2): 10 inoculated ducks were housed together with 15 contact-exposed ducks. Infection was monitored by RNA detection on oropharyngeal and cloacal swabs using real-time RT-PCR with a cutoff corresponding to 2-7 EID50. Depending on the strain, the basic reproduction number (R0) varied from 5.5 to 42.7, confirming LPAIV could easily be transmitted to susceptible Muscovy ducks. The lowest R0 estimate was obtained for a H5N3 field strain, due to lower values of transmission rate and duration of infectious period, whereas reverse-genetics derived H5N1 strain had the highest R0. Frequency and intensity of clinical signs were also variable between strains, but apparently not associated with longer infectious periods. Further comparisons of quantitative transmission parameters may help to identify relevant viral genetic markers for early detection of potentially more virulent strains during surveillance of LPAIV. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Implications of within-farm transmission for network dynamics: Consequences for the spread of avian influenza

    PubMed Central

    Nickbakhsh, Sema; Matthews, Louise; Dent, Jennifer E.; Innocent, Giles T.; Arnold, Mark E.; Reid, Stuart W.J.; Kao, Rowland R.

    2013-01-01

    The importance of considering coupled interactions across multiple population scales has not previously been studied for highly pathogenic avian influenza (HPAI) in the British commercial poultry industry. By simulating the within-flock transmission of HPAI using a deterministic S-E-I-R model, and by incorporating an additional environmental class representing infectious faeces, we tracked the build-up of infectious faeces within a poultry house over time. A measure of the transmission risk (TR) was computed for each farm by linking the amount of infectious faeces present each day of an outbreak with data describing the daily on-farm visit schedules for a major British catching company. Larger flocks tended to have greater levels of these catching-team visits. However, where density-dependent contact was assumed, faster outbreak detection (according to an assumed mortality threshold) led to a decreased opportunity for catching-team visits to coincide with an outbreak. For this reason, maximum TR-levels were found for mid-range flock sizes (~25,000–35,000 birds). When assessing all factors simultaneously using multivariable linear regression on the simulated outputs, those related to the pattern of catching-team visits had the largest effect on TR, with the most important movement-related factor depending on the mode of transmission. Using social network analysis on a further database to inform a measure of between-farm connectivity, we identified a large fraction of farms (28%) that had both a high TR and a high potential impact at the between farm level. Our results have counter-intuitive implications for between-farm spread that could not be predicted based on flock size alone, and together with further knowledge of the relative importance of transmission risk and impact, could have implications for improved targeting of control measures. PMID:23746799

  4. Survival of H5N1 influenza virus in water and its inactivation by chemical methods.

    PubMed

    Mihai, Maria Elena; Tecu, Cristina; Ivanciuc, Alina Elena; Necula, Gheorghe; Lupulescu, Emilia; Onu, Adrian

    2011-01-01

    The ability of H5N1 Avian Influenza Virus (AIV) to survive in surface water has been assessed in experimental laboratory conditions, based on non-pathogenic avian reassortant model, by titration of infectivity (TCID50) at different time intervals, in three different types of water. The effect of different chemicals on AIV's survival was assessed using the same type of experimental model. After exposure to the chemical, followed by growth on a suitable substrate, the AIV was quantified by a real-time quantitative reverse transcriptase PCR (qRT-PCR). The reassortant virus persisted, and remained infective in aquatic environments, for 12 days at 22-35 degrees C and up to 20 days at 4 degrees C, irrespective of the type of water, supporting the hypothesis of a potential risk for transmitting the virus among birds and contaminating the household water via common sources of water. A significant decrease for AIV persistence models was recorded for sea water, after 12 days, at 35 degrees C. An effective inactivation has been shown when using commercially available products based on glutaraldehyde and penta potassium bis (peroxy mono sulphate) bis(sulphate), respectively. This rapid and safe method for decontamination, developed in this study, might be helpful in implementation of biosafety measures in laboratory and farms against AIV.

  5. Multiple estimates of transmissibility for the 2009 influenza pandemic based on influenza-like-illness data from small US military populations.

    PubMed

    Riley, Pete; Ben-Nun, Michal; Armenta, Richard; Linker, Jon A; Eick, Angela A; Sanchez, Jose L; George, Dylan; Bacon, David P; Riley, Steven

    2013-01-01

    Rapidly characterizing the amplitude and variability in transmissibility of novel human influenza strains as they emerge is a key public health priority. However, comparison of early estimates of the basic reproduction number during the 2009 pandemic were challenging because of inconsistent data sources and methods. Here, we define and analyze influenza-like-illness (ILI) case data from 2009-2010 for the 50 largest spatially distinct US military installations (military population defined by zip code, MPZ). We used publicly available data from non-military sources to show that patterns of ILI incidence in many of these MPZs closely followed the pattern of their enclosing civilian population. After characterizing the broad patterns of incidence (e.g. single-peak, double-peak), we defined a parsimonious SIR-like model with two possible values for intrinsic transmissibility across three epochs. We fitted the parameters of this model to data from all 50 MPZs, finding them to be reasonably well clustered with a median (mean) value of 1.39 (1.57) and standard deviation of 0.41. An increasing temporal trend in transmissibility ([Formula: see text], p-value: 0.013) during the period of our study was robust to the removal of high transmissibility outliers and to the removal of the smaller 20 MPZs. Our results demonstrate the utility of rapidly available - and consistent - data from multiple populations.

  6. Multiple Estimates of Transmissibility for the 2009 Influenza Pandemic Based on Influenza-like-Illness Data from Small US Military Populations

    PubMed Central

    Riley, Pete; Ben-Nun, Michal; Armenta, Richard; Linker, Jon A.; Eick, Angela A.; Sanchez, Jose L.; George, Dylan; Bacon, David P.; Riley, Steven

    2013-01-01

    Rapidly characterizing the amplitude and variability in transmissibility of novel human influenza strains as they emerge is a key public health priority. However, comparison of early estimates of the basic reproduction number during the 2009 pandemic were challenging because of inconsistent data sources and methods. Here, we define and analyze influenza-like-illness (ILI) case data from 2009–2010 for the 50 largest spatially distinct US military installations (military population defined by zip code, MPZ). We used publicly available data from non-military sources to show that patterns of ILI incidence in many of these MPZs closely followed the pattern of their enclosing civilian population. After characterizing the broad patterns of incidence (e.g. single-peak, double-peak), we defined a parsimonious SIR-like model with two possible values for intrinsic transmissibility across three epochs. We fitted the parameters of this model to data from all 50 MPZs, finding them to be reasonably well clustered with a median (mean) value of 1.39 (1.57) and standard deviation of 0.41. An increasing temporal trend in transmissibility (, p-value: 0.013) during the period of our study was robust to the removal of high transmissibility outliers and to the removal of the smaller 20 MPZs. Our results demonstrate the utility of rapidly available – and consistent – data from multiple populations. PMID:23696723

  7. 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

  8. Replication and transmission of mammalian-adapted H9 subtype influenza virus in pigs and quail

    USDA-ARS?s Scientific Manuscript database

    Influenza A is a major pathogen of birds, swine, and humans. Strains can jump from one species to another in a process that often requires genetic mutation and genome reassortment and results in outbreaks and, potentially, pandemics. H9N2 avian influenza is one of the most predominant influenza subt...

  9. Absolute Humidity and the Seasonality of Influenza (Invited)

    NASA Astrophysics Data System (ADS)

    Shaman, J. L.; Pitzer, V.; Viboud, C.; Grenfell, B.; Goldstein, E.; Lipsitch, M.

    2010-12-01

    Much of the observed wintertime increase of mortality in temperate regions is attributed to seasonal influenza. A recent re-analysis of laboratory experiments indicates that absolute humidity strongly modulates the airborne survival and transmission of the influenza virus. Here we show that the onset of increased wintertime influenza-related mortality in the United States is associated with anomalously low absolute humidity levels during the prior weeks. We then use an epidemiological model, in which observed absolute humidity conditions temper influenza transmission rates, to successfully simulate the seasonal cycle of observed influenza-related mortality. The model results indicate that direct modulation of influenza transmissibility by absolute humidity alone is sufficient to produce this observed seasonality. These findings provide epidemiological support for the hypothesis that absolute humidity drives seasonal variations of influenza transmission in temperate regions. In addition, we show that variations of the basic and effective reproductive numbers for influenza, caused by seasonal changes in absolute humidity, are consistent with the general timing of pandemic influenza outbreaks observed for 2009 A/H1N1 in temperate regions. Indeed, absolute humidity conditions correctly identify the region of the United States vulnerable to a third, wintertime wave of pandemic influenza. These findings suggest that the timing of pandemic influenza outbreaks is controlled by a combination of absolute humidity conditions, levels of susceptibility and changes in population mixing and contact rates.

  10. Pathogenicity and Transmission of H5 and H7 Highly Pathogenic Avian Influenza Viruses in Mallards

    PubMed Central

    Costa-Hurtado, Mar; Shepherd, Eric; DeJesus, Eric; Smith, Diane; Spackman, Erica; Kapczynski, Darrell R.; Suarez, David L.; Stallknecht, David E.; Swayne, David E.

    2016-01-01

    ABSTRACT Wild aquatic birds have been associated with the intercontinental spread of H5 subtype highly pathogenic avian influenza (HPAI) viruses of the A/goose/Guangdong/1/96 (Gs/GD) lineage during 2005, 2010, and 2014, but dispersion by wild waterfowl has not been implicated with spread of other HPAI viruses. To better understand why Gs/GD H5 HPAI viruses infect and transmit more efficiently in waterfowl than other HPAI viruses, groups of mallard ducks were challenged with one of 14 different H5 and H7 HPAI viruses, including a Gs/GD lineage H5N1 (clade 2.2) virus from Mongolia, part of the 2005 dispersion, and the H5N8 and H5N2 index HPAI viruses (clade 2.3.4.4) from the United States, part of the 2014 dispersion. All virus-inoculated ducks and contact exposed ducks became infected and shed moderate to high titers of the viruses, with the exception that mallards were resistant to Ck/Pennsylvania/83 and Ck/Queretaro/95 H5N2 HPAI virus infection. Clinical signs were only observed in ducks challenged with the H5N1 2005 virus, which all died, and with the H5N8 and H5N2 2014 viruses, which had decreased weight gain and fever. These three viruses were also shed in higher titers by the ducks, which could facilitate virus transmission and spread. This study highlights the possible role of wild waterfowl in the spread of HPAI viruses. IMPORTANCE The spread of H5 subtype highly pathogenic avian influenza (HPAI) viruses of the Gs/GD lineage by migratory waterfowl is a serious concern for animal and public health. H5 and H7 HPAI viruses are considered to be adapted to gallinaceous species (chickens, turkeys, quail, etc.) and less likely to infect and transmit in wild ducks. In order to understand why this is different with certain Gs/GD lineage H5 HPAI viruses, we compared the pathogenicity and transmission of several H5 and H7 HPAI viruses from previous poultry outbreaks to Gs/GD lineage H5 viruses, including H5N1 (clade 2.2), H5N8 and H5N2 (clade 2.3.4.4) viruses, in

  11. Adaptation and transmission of a duck-origin avian influenza virus in poultry species.

    PubMed

    Li, Jinling; zu Dohna, Heinrich; Anchell, Nichole L; Adams, Sean C; Dao, Nguyet T; Xing, Zheng; Cardona, Carol J

    2010-01-01

    A duck-origin avian influenza virus (AIV) was used to study viral adaptation and transmission patterns in chickens (Gallus gallus domesticus) and Pekin ducks (Anas platyrhynchos domesticus). Inoculated birds were housed with naïve birds of the same species and all birds were monitored for infection. The inoculating duck virus was transmitted effectively by contact in both species. Viruses recovered from infected birds showed mutations as early as 1 or 3 days after inoculation in chickens and ducks, respectively. Amino acid substitutions in hemagglutinin (HA) or deletions in neuraminidase (NA) stalk regions were identified in chicken isolates, but only substitutions in HA were identified in duck isolates. HA substitution-containing viruses replicated more efficiently than those with NA stalk deletions. NA deletion mutants were not recovered from contact chickens, suggesting inefficient transmission. Amino acid substitutions in HA proteins appeared in pairs in chickens, but were independent in ducks, indicating adaptation in chickens. In addition, our findings showed that a duck-origin virus can rapidly adapt to chickens, suggesting that the emergence of new epidemic AIV can be rapid.

  12. Ecological Routes of Avian Influenza Virus Transmission to a Common Mesopredator: An Experimental Evaluation of Alternatives

    PubMed Central

    Root, J. Jeffrey; Bentler, Kevin T.; Shriner, Susan A.; Mooers, Nicole L.; VanDalen, Kaci K.; Sullivan, Heather J.; Franklin, Alan B.

    2014-01-01

    Background Wild raccoons have been shown to be naturally exposed to avian influenza viruses (AIV). However, the mechanisms associated with these natural exposures are not well-understood. Methodology/Principal Findings We experimentally tested three alternative routes (water, eggs, and scavenged waterfowl carcasses) of AIV transmission that may explain how raccoons in the wild are exposed to AIV. Raccoons were exposed to 1) water and 2) eggs spiked with an AIV (H4N6), as well as 3) mallard carcasses experimentally inoculated with the same virus. Three of four raccoons exposed to the high dose water treatment yielded apparent nasal shedding of >102.0 PCR EID50 equivalent/mL. Little to no shedding was observed from the fecal route. The only animals yielding evidence of serologic activity during the study period were three animals associated with the high dose water treatment. Conclusions/Significance Overall, our results indicate that virus-laden water could provide a natural exposure route of AIV for raccoons and possibly other mammals associated with aquatic environments. However, this association appears to be related to AIV concentration in the water, which would constitute an infective dose. In addition, strong evidence of infection was only detected in three of four animals exposed to a high dose (e.g., 105.0 EID50/mL) of AIV in water. As such, water-borne transmission to raccoons may require repeated exposures to water with high concentrations of virus. PMID:25127468

  13. The impact of media coverage on the transmission dynamics of human influenza

    PubMed Central

    2011-01-01

    Background There is an urgent need to understand how the provision of information influences individual risk perception and how this in turn shapes the evolution of epidemics. Individuals are influenced by information in complex and unpredictable ways. Emerging infectious diseases, such as the recent swine flu epidemic, may be particular hotspots for a media-fueled rush to vaccination; conversely, seasonal diseases may receive little media attention, despite their high mortality rate, due to their perceived lack of newness. Methods We formulate a deterministic transmission and vaccination model to investigate the effects of media coverage on the transmission dynamics of influenza. The population is subdivided into different classes according to their disease status. The compartmental model includes the effect of media coverage on reporting the number of infections as well as the number of individuals successfully vaccinated. Results A threshold parameter (the basic reproductive ratio) is analytically derived and used to discuss the local stability of the disease-free steady state. The impact of costs that can be incurred, which include vaccination, education, implementation and campaigns on media coverage, are also investigated using optimal control theory. A simplified version of the model with pulse vaccination shows that the media can trigger a vaccinating panic if the vaccine is imperfect and simplified messages result in the vaccinated mixing with the infectives without regard to disease risk. Conclusions The effects of media on an outbreak are complex. Simplified understandings of disease epidemiology, propogated through media soundbites, may make the disease significantly worse. PMID:21356134

  14. Molecular basis of mammalian transmissibility of avian H1N1 influenza viruses and their pandemic potential.

    PubMed

    Zanin, Mark; Wong, Sook-San; Barman, Subrata; Kaewborisuth, Challika; Vogel, Peter; Rubrum, Adam; Darnell, Daniel; Marinova-Petkova, Atanaska; Krauss, Scott; Webby, Richard J; Webster, Robert G

    2017-09-05

    North American wild birds are an important reservoir of influenza A viruses, yet the potential of viruses in this reservoir to transmit and cause disease in mammals is not well understood. Our surveillance of avian influenza viruses (AIVs) at Delaware Bay, USA, revealed a group of similar H1N1 AIVs isolated in 2009, some of which were airborne-transmissible in the ferret model without prior adaptation. Comparison of the genomes of these viruses revealed genetic markers of airborne transmissibility in the Polymerase Basic 2 (PB2), PB1, PB1-F2, Polymerase Acidic-X (PA-X), Nonstructural Protein 1 (NS1), and Nuclear Export Protein (NEP) genes. We studied the role of NS1 in airborne transmission and found that NS1 mutants that were not airborne-transmissible caused limited tissue pathology in the upper respiratory tract (URT). Viral maturation was also delayed, evident as strong intranuclear staining and little virus at the mucosa. Our study of this naturally occurring constellation of genetic markers has provided insights into the poorly understood phenomenon of AIV airborne transmissibility by revealing a role for NS1 and characteristics of viral replication in the URT that were associated with airborne transmission. The transmissibility of these viruses further highlights the pandemic potential of AIVs in the wild bird reservoir and the need to maintain surveillance.

  15. Interspecies transmission and reassortment of influenza A viruses in pigs and turkeys in the United States.

    PubMed

    Wright, S M; Kawaoka, Y; Sharp, G B; Senne, D A; Webster, R G

    1992-08-15

    Genetic reassortment between influenza A viruses in humans and in animals and birds has been implicated in the appearance of new pandemics of human influenza. To determine whether such reassortment has occurred in the United States, the authors compared the genetic origins of gene segments of 73 swine influenza virus isolates (1976-1990), representing 11 states, and 11 turkey virus isolates (1980-1989), representing eight states. The host origin of gene segments encoding the internal proteins of H1N1 swine and turkey influenza viruses was identified by developing a dot-blot assay. All gene segments of swine influenza viruses were characteristic of influenza virus genes from that species, indicating that pigs may not be frequent participants in interspecies genetic exchange and reassortment of influenza viruses in the United States. In contrast, 73% of the turkey influenza virus isolates contained genes of swine origin. One turkey isolate was a reassortant having three genes characteristic of avian influenza virus and three of swine origin. These findings document a high degree of genetic exchange and reassortment of influenza A viruses in domestic turkeys in the United States. The molecular biologic techniques used by the authors should aid future epidemiologic studies of influenza pandemics.

  16. 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.

  17. Possible Role of Songbirds and Parakeets in Transmission of Influenza A(H7N9) Virus to Humans

    PubMed Central

    Jones, Jeremy C.; Sonnberg, Stephanie; Koçer, Zeynep A.; Shanmuganatham, Karthik; Seiler, Patrick; Shu, Yuelong; Zhu, Huachen; Guan, Yi; Peiris, Malik; Webby, Richard J.

    2014-01-01

    Avian-origin influenza A(H7N9) recently emerged in China, causing severe human disease. Several subtype H7N9 isolates contain influenza genes previously identified in viruses from finch-like birds. Because wild and domestic songbirds interact with humans and poultry, we investigated the susceptibility and transmissibility of subtype H7N9 in these species. Finches, sparrows, and parakeets supported replication of a human subtype H7N9 isolate, shed high titers through the oropharyngeal route, and showed few disease signs. Virus was shed into water troughs, and several contact animals seroconverted, although they shed little virus. Our study demonstrates that a human isolate can replicate in and be shed by such songbirds and parakeets into their environment. This finding has implications for these birds’ potential as intermediate hosts with the ability to facilitate transmission and dissemination of A(H7N9) virus. PMID:24572739

  18. Possible role of songbirds and parakeets in transmission of influenza A(H7N9) virus to humans.

    PubMed

    Jones, Jeremy C; Sonnberg, Stephanie; Koçer, Zeynep A; Shanmuganatham, Karthik; Seiler, Patrick; Shu, Yuelong; Zhu, Huachen; Guan, Yi; Peiris, Malik; Webby, Richard J; Webster, Robert G

    2014-03-01

    Avian-origin influenza A(H7N9) recently emerged in China, causing severe human disease. Several subtype H7N9 isolates contain influenza genes previously identified in viruses from finch-like birds. Because wild and domestic songbirds interact with humans and poultry, we investigated the susceptibility and transmissibility of subtype H7N9 in these species. Finches, sparrows, and parakeets supported replication of a human subtype H7N9 isolate, shed high titers through the oropharyngeal route, and showed few disease signs. Virus was shed into water troughs, and several contact animals seroconverted, although they shed little virus. Our study demonstrates that a human isolate can replicate in and be shed by such songbirds and parakeets into their environment. This finding has implications for these birds' potential as intermediate hosts with the ability to facilitate transmission and dissemination of A(H7N9) virus.

  19. A generic model of contagious disease and its application to human-to-human transmission of avian influenza.

    SciTech Connect

    Hirsch, Gary B.

    2007-03-01

    Modeling contagious diseases has taken on greater importance over the past several years as diseases such as SARS and avian influenza have raised concern about worldwide pandemics. Most models developed to consider projected outbreaks have been specific to a single disease. This paper describes a generic System Dynamics contagious disease model and its application to human-to-human transmission of a mutant version of avian influenza. The model offers the option of calculating rates of new infections over time based either on a fixed ''reproductive number'' that is traditional in contagious disease models or on contact rates for different sub-populations and likelihood of transmission per contact. The paper reports on results with various types of interventions. These results suggest the potential importance of contact tracing, limited quarantine, and targeted vaccination strategies as methods for controlling outbreaks, especially when vaccine supplies may initially be limited and the efficacy of anti-viral drugs uncertain.

  20. Genetics, Receptor Binding Property, and Transmissibility in Mammals of Naturally Isolated H9N2 Avian Influenza Viruses

    PubMed Central

    Deng, Guohua; Zhang, Qianyi; Wang, Jinliang; He, Xijun; Wang, Kaicheng; Chen, Jiming; Li, Yuanyuan; Fan, Jun; Kong, Huiui; Gu, Chunyang; Guan, Yuantao; Suzuki, Yasuo; Kawaoka, Yoshihiro; Liu, Liling; Jiang, Yongping; Tian, Guobin; Li, Yanbing; Bu, Zhigao; Chen, Hualan

    2014-01-01

    H9N2 subtype influenza viruses have been detected in different species of wild birds and domestic poultry in many countries for several decades. Because these viruses are of low pathogenicity in poultry, their eradication is not a priority for animal disease control in many countries, which has allowed them to continue to evolve and spread. Here, we characterized the genetic variation, receptor-binding specificity, replication capability, and transmission in mammals of a series of H9N2 influenza viruses that were detected in live poultry markets in southern China between 2009 and 2013. Thirty-five viruses represented 17 genotypes on the basis of genomic diversity, and one specific “internal-gene-combination” predominated among the H9N2 viruses. This gene combination was also present in the H7N9 and H10N8 viruses that have infected humans in China. All of the 35 viruses preferentially bound to the human-like receptor, although two also retained the ability to bind to the avian-like receptor. Six of nine viruses tested were transmissible in ferrets by respiratory droplet; two were highly transmissible. Some H9N2 viruses readily acquired the 627K or 701N mutation in their PB2 gene upon infection of ferrets, further enhancing their virulence and transmission in mammals. Our study indicates that the widespread dissemination of H9N2 viruses poses a threat to human health not only because of the potential of these viruses to cause an influenza pandemic, but also because they can function as “vehicles” to deliver different subtypes of influenza viruses from avian species to humans. PMID:25411973

  1. The impact of seasonal and year-round transmission regimes on the evolution of influenza A virus

    PubMed Central

    Adams, Ben; McHardy, Alice Carolyn

    2011-01-01

    Punctuated antigenic change is believed to be a key element in the evolution of influenza A; clusters of antigenically similar strains predominate worldwide for several years until an antigenically distant mutant emerges and instigates a selective sweep. It is thought that a region of East–Southeast Asia with year-round transmission acts as a source of antigenic diversity for influenza A and seasonal epidemics in temperate regions make little contribution to antigenic evolution. We use a mathematical model to examine how different transmission regimes affect the evolutionary dynamics of influenza over the lifespan of an antigenic cluster. Our model indicates that, in non-seasonal regions, mutants that cause significant outbreaks appear before the peak of the wild-type epidemic. A relatively large proportion of these mutants spread globally. In seasonal regions, mutants that cause significant local outbreaks appear each year before the seasonal peak of the wild-type epidemic, but only a small proportion spread globally. The potential for global spread is strongly influenced by the intensity of non-seasonal circulation and coupling between non-seasonal and seasonal regions. Results are similar if mutations are neutral, or confer a weak to moderate antigenic advantage. However, there is a threshold antigenic advantage, depending on the non-seasonal transmission intensity, beyond which mutants can escape herd immunity in the non-seasonal region and there is a global explosion in diversity. We conclude that non-seasonal transmission regions are fundamental to the generation and maintenance of influenza diversity owing to their epidemiology. More extensive sampling of viral diversity in such regions could facilitate earlier identification of antigenically novel strains and extend the critical window for vaccine development. PMID:21177678

  2. Molecular Evidence of Transmission of Influenza A/H1N1 2009 on a University Campus

    PubMed Central

    Virk, Ramandeep Kaur; Gunalan, Vithiagaran; Lee, Hong Kai; Inoue, Masafumi; Chua, Catherine; Tan, Boon-Huan; Tambyah, Paul Anantharajah

    2017-01-01

    Background In the recent years, the data on the molecular epidemiology of influenza viruses have expanded enormously because of the availability of cutting-edge sequencing technologies. However, much of the information is from the temperate regions with few studies from tropical regions such as South-east Asia. Despite the fact that influenza has been known to transmit rapidly within semi-closed communities, such as military camps and educational institutions, data are limited from these communities. Objectives To determine the phylogeography of influenza viruses on a university campus, we examined the spatial distribution of influenza virus on the National University of Singapore (NUS) campus. Methods Consenting students from the NUS who sought medical attention at the UHC provided two nasopharyngeal swabs and demographic data. PCR was used for detection of influenza viruses. 34 full-genomes of pH1N1/09 viruses were successfully sequenced by Sanger method and concatenated using Geneious R7. Phylogenetic analysis was conducted using these 34 sequences and 1518 global sequences. Phylogeographic analysis was done using BaTS software and Association index and Fitch parsimony scores were determined. Results Integrating whole genome sequencing data with epidemiological data, we found strong evidence of influenza transmission on campus as isolates from students residing on-campus were highly similar to each other (AI, P value = 0.009; PS, P value = 0.04). There was also evidence of multiple introductions from the community. Conclusions Such data are useful in formulating pandemic preparedness plans which can use these communities as sentinel sites for detection and monitoring of emerging respiratory viral infections. PMID:28060851

  3. Comparison of the Levels of Infectious Virus in Respirable Aerosols Exhaled by Ferrets Infected with Influenza Viruses Exhibiting Diverse Transmissibility Phenotypes

    PubMed Central

    Gustin, Kortney M.; Katz, Jacqueline M.; Tumpey, Terrence M.

    2013-01-01

    Influenza viruses pose a major public health burden to communities around the world by causing respiratory infections that can be highly contagious and spread rapidly through the population. Despite extensive research on influenza viruses, the modes of transmission occurring most often among humans are not entirely clear. Contributing to this knowledge gap is the lack of an understanding of the levels of infectious virus present in respirable aerosols exhaled from infected hosts. Here, we used the ferret model to evaluate aerosol shedding patterns and measure the amount of infectious virus present in exhaled respirable aerosols. By comparing these parameters among a panel of human and avian influenza viruses exhibiting diverse respiratory droplet transmission efficiencies, we are able to report that ferrets infected by highly transmissible influenza viruses exhale a greater number of aerosol particles and more infectious virus within respirable aerosols than ferrets infected by influenza viruses that do not readily transmit. Our findings improve our understanding of the ferret transmission model and provide support for the potential for influenza virus aerosol transmission. PMID:23658443

  4. The 1918 influenza pandemic in New York City: age-specific timing, mortality, and transmission dynamics

    PubMed Central

    Yang, Wan; Petkova, Elisaveta; Shaman, Jeffrey

    2014-01-01

    Background The 1918 influenza pandemic caused disproportionately high mortality among certain age groups. The mechanisms underlying these differences are not fully understood. Objectives To explore the dynamics of the 1918 pandemic and to identify potential age-specific transmission patterns. Methods We examined 1915–1923 daily mortality data in New York City (NYC) and estimated the outbreak duration and initial effective reproductive number (Re) for each 1-year age cohort. Results Four pandemic waves occurred from February 1918 to April 1920. The fractional mortality increase (i.e. ratio of excess mortality to baseline mortality) was highest among teenagers during the first wave. This peak shifted to 25- to 29-year-olds in subsequent waves. The distribution of age-specific mortality during the last three waves was strongly correlated (r = 0·94 and 0·86). With each wave, the pandemic appeared to spread with a comparable early growth rate but then attenuate with varying rates. For the entire population, Re estimates made assuming 2-day serial interval were 1·74 (1·27), 1·74 (1·43), 1·66 (1·25), and 1·86 (1·37), respectively, during the first week (first 3 weeks) of each wave. Using age-specific mortality, the average Re estimates over the first week of each wave were 1·62 (95% CI: 1·55–1·68), 1·68 (1·65–1·72), 1·67 (1·61–1·73), and 1·69 (1·63–1·74), respectively; Re was not significantly different either among age cohorts or between waves. Conclusions The pandemic generally caused higher mortality among young adults and might have spread mainly among school-aged children during the first wave. We propose mechanisms to explain the timing and transmission dynamics of the four NYC pandemic waves. PMID:24299150

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

    PubMed

    Belser, Jessica A; Gustin, Kortney M; Pearce, Melissa B; Maines, Taronna R; Zeng, Hui; Pappas, Claudia; Sun, Xiangjie; Carney, Paul J; Villanueva, Julie M; Stevens, James; Katz, Jacqueline M; Tumpey, Terrence M

    2013-09-26

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

  6. Vertical Transmission of H9N2 Avian Influenza Virus in Goose.

    PubMed

    Yu, Guanliu; Wang, Aihua; Tang, Yi; Diao, Youxiang

    2017-01-01

    During a study on high mortality cases of goose embryo in Shandong Province, China (2014-2015), we isolated an H9N2 avian influenza virus (AIV) strain (A/goose/Shandong/DP01/2014, DP01), which was supposedly the causative agent for goose embryo death. Sequence analysis revealed that DP01 shared 99.9% homology in the HA gene with a classic immune suppression strain SD06. To study the potential vertical transmission ability of the DP01 strain in breeder goose, a total of 105 Taizhou breeder geese, which were 360 days old, were equally divided into five groups (A, B, C, D, and E) for experimental infection. H9N2 AIV (DP01) was used for inoculating through intravenous (group A), intranasal instillation (group B), and throat inoculation (group C) routes, respectively. The geese in group D were inoculated with phosphate buffer solution (PBS) and those in group E were the non-treated group. At 24 h post inoculation, H9N2 viral RNA could be detected at vitelline membrane, embryos, and allantoic fluid of goose embryos from H9N2 inoculated groups. Furthermore, the HA gene of H9N2 virus from vitelline membrane, embryo, allantoic fluid, and gosling shared almost 100% homology with an H9N2 virus isolated from the ovary of breeder goose, which laid these eggs, indicating that H9N2 AIV can be vertically transmitted in goose. The present research study provides evidence that vertical transmission of H9N2 AIV from breeding goose to goslings is possible.

  7. Staying Alive: Vibrio cholerae's Cycle of Environmental Survival, Transmission, and Dissemination.

    PubMed

    Conner, Jenna G; Teschler, Jennifer K; Jones, Christopher J; Yildiz, Fitnat H

    2016-04-01

    Infectious diseases kill nearly 9 million people annually. Bacterial pathogens are responsible for a large proportion of these diseases, and the bacterial agents of pneumonia, diarrhea, and tuberculosis are leading causes of death and disability worldwide. Increasingly, the crucial role of nonhost environments in the life cycle of bacterial pathogens is being recognized. Heightened scrutiny has been given to the biological processes impacting pathogen dissemination and survival in the natural environment, because these processes are essential for the transmission of pathogenic bacteria to new hosts. This chapter focuses on the model environmental pathogen Vibrio cholerae to describe recent advances in our understanding of how pathogens survive between hosts and to highlight the processes necessary to support the cycle of environmental survival, transmission, and dissemination. We describe the physiological and molecular responses of V. cholerae to changing environmental conditions, focusing on its survival in aquatic reservoirs between hosts and its entry into and exit from human hosts.

  8. Staying alive: Vibrio cholerae’s cycle of environmental survival, transmission, and dissemination

    PubMed Central

    Jones, Christopher J.; Yildiz, Fitnat H.

    2015-01-01

    Infectious diseases kill nearly 9 million people annually. Bacterial pathogens are responsible for a large proportion of these diseases and the bacterial agents of pneumonia, diarrhea, and tuberculosis are leading causes of death and disability worldwide (1). Increasingly, the crucial role of non-host environments in the life cycle of bacterial pathogens is being recognized. Heightened scrutiny has been given to the biological processes impacting pathogen dissemination and survival in the natural environment, as these processes are essential for the transmission of pathogenic bacteria to new hosts. This chapter focuses on the model environmental pathogen, Vibrio cholerae, to describe recent advances in our understanding of how pathogens survive between hosts and highlight the processes necessary to support the cycle of environmental survival, transmission, and dissemination. We describe the physiological and molecular responses of V. cholerae to changing environmental conditions, focusing on its survival in aquatic reservoirs between hosts and its entry and exit from human hosts. PMID:27227302

  9. No evidence for zoonotic transmission of H3N8 canine influenza virus among US adults occupationally exposed to dogs.

    PubMed

    Krueger, Whitney S; Heil, Gary L; Yoon, Kyoung-Jin; Gray, Gregory C

    2014-01-01

    The zoonotic potential of H3N8 canine influenza virus (CIV) has not been previously examined; yet considering the popularity of dogs as a companion animal and the zoonotic capabilities of other influenza viruses, the public health implications are great. This study aimed to determine the seroprevalence of antibodies against CIV among a US cohort. A cross-sectional seroepidemiological study was conducted between 2007 and 2010. Recruitments primarily occurred in Iowa and Florida. Participants were enrolled at dog shows, or at their home or place of employment. Three hundred and four adults occupationally exposed to dogs and 101 non-canine-exposed participants completed a questionnaire and provided a blood sample. Microneutralization and neuraminidase inhibition assays were performed to detect human sera antibodies against A/Canine/Iowa/13628/2005(H3N8). An enzyme-linked lectin assay (ELLA) was adapted to detect antibodies against a recombinant N8 neuraminidase protein from A/Equine/Pennsylvania/1/2007(H3N8). For all assays, no significant difference in detectable antibodies was observed when comparing the canine-exposed subjects to the non-canine-exposed subjects. While these results do not provide evidence for cross-species CIV transmission, influenza is predictably unpredictable. People frequently exposed to ill dogs should continually be monitored for novel zoonotic CIV infections. © 2013 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.

  10. Low transmission rate of 2009 H1N1 Influenza during a long-distance bus trip.

    PubMed

    Piso, R J; Albrecht, Y; Handschin, P; Bassetti, S

    2011-04-01

    Current data on the risk of transmission of 2009 H1N1 Influenza in public transportation systems (e.g., public trains, busses, airplanes) are conflicting. The main transmission route of this virus is thought to be via droplets, but airborne transmission has not been completely ruled out. This is a contact tracing investigation of a young woman subsequently diagnosed with the 2009 H1N1 Influenza virus who was symptomatic during a long-distance bus trip from Spain to Switzerland. Fever and cough had begun 24 h earlier, 2 h before she stepped onto a bus for a long-distance trip. After the 2009 H1N1 virus had been confirmed in the patient, the other bus travellers were contacted by telephone on day 7 and 10 after the bus trip. Of the 72 individuals travelling on the bus with the H1N1-infected young woman, 52 (72%) could be contacted. Only one of these 52 developed fever, with onset of symptoms 3 days after the bus trip, and rRT-PCR analysis of the nasopharyngeal swab showed the infection to be caused by the 2009 H1N1 virus. One other person complained of coughing 1 day after the bus trip, but without fever, and no further investigation was carried out. All other passengers remained without fever, coughing, or arthralgia. The risk of transmission was calculated as 1.96% (95% confidence interval 0-5.76%). The transmission rate of 2009 H1N1 Influenza was low on a long-distance bus trip.

  11. Assessing the State of Knowledge Regarding the Effectiveness of Interventions to Contain Pandemic Influenza Transmission: A Systematic Review and Narrative Synthesis

    PubMed Central

    Reisman, Jane; Krewski, Daniel

    2016-01-01

    Background Influenza pandemics occur when a novel influenza strain, to which humans are immunologically naïve, emerges to cause infection and illness on a global scale. Differences in the viral properties of pandemic strains, relative to seasonal ones, can alter the effectiveness of interventions typically implemented to control seasonal influenza burden. As a result, annual control activities may not be sufficient to contain an influenza pandemic. Purpose This study seeks to inform pandemic policy and planning initiatives by reviewing the effectiveness of previous interventions to reduce pandemic influenza transmission and infection. Results will inform the planning and design of more focused in-depth systematic reviews for specific types of interventions, thus providing the most comprehensive and current understanding of the potential for alternative interventions to mitigate the burden of pandemic influenza. Methods A systematic review and narrative synthesis of existing systematic reviews and meta-analyses examining intervention effectiveness in containing pandemic influenza transmission was conducted using information collected from five databases (PubMed, Medline, Cochrane, Embase, and Cinahl/EBSCO). Two independent reviewers conducted study screening and quality assessment, extracting data related to intervention impact and effectiveness. Results and Discussion Most included reviews were of moderate to high quality. Although the degree of statistical heterogeneity precluded meta-analysis, the present systematic review examines the wide variety of interventions that can impact influenza transmission in different ways. While it appears that pandemic influenza vaccination provides significant protection against infection, there was insufficient evidence to conclude that antiviral prophylaxis, seasonal influenza cross-protection, or a range of non-pharmaceutical strategies would provide appreciable protection when implemented in isolation. It is likely that an

  12. Oral administration of Euglena gracilis Z and its carbohydrate storage substance provides survival protection against influenza virus infection in mice.

    PubMed

    Nakashima, Ayaka; Suzuki, Kengo; Asayama, Yuta; Konno, Makoto; Saito, Keita; Yamazaki, Noriyuki; Takimoto, Hiroaki

    2017-09-30

    Euglena gracilis Z is a micro-algae that is used as a food or nutritional supplement. Paramylon, the carbohydrate storage substance of Euglena gracilis Z has β-1, 3-glucan structure. Euglena gracilis Z and paramylon are reported to affect the immune system. In this study, we investigated the protective effects of Euglena gracilis Z and paramylon against influenza virus infection in mice. Euglena gracilis Z and paramylon were administered to mice as a 2% dietary mixture ad libitum. At 2 weeks after initiation of dietary administration, mice were infected intranasally with influenza virus A/PR/8/34 (H1N1). Survival rate was monitored 10 days after infection. In adition, we performed virus titer and cytokine profiles in the lung. High survival rates were observed for Euglena gracilis Z and paramylon-treated groups compared to the control group. Significantly lower virus titer in the lung was observed in the Euglena gracilis Z and paramylon-treated groups compared to the control group from day 1 after infection. Higher amount of IL-1β, IL-6, IL-12 (p70), IFN-γ, and IL-10 was observed in the paramylon groups compared to the control group. Our data therefore reveals a novel immunoregulatory role of the Euglena gracilis Z and paramylon which provides protection against influenza virus infection. Copyright © 2017. Published by Elsevier Inc.

  13. Zoonotic Risk, Pathogenesis, and Transmission of Avian-Origin H3N2 Canine Influenza Virus.

    PubMed

    Sun, Hailiang; Blackmon, Sherry; Yang, Guohua; Waters, Kaitlyn; Li, Tao; Tangwangvivat, Ratanaporn; Xu, Yifei; Shyu, Daniel; Wen, Feng; Cooley, Jim; Senter, Lucy; Lin, Xiaoxu; Jarman, Richard; Hanson, Larry; Webby, Richard; Wan, Xiu-Feng

    2017-08-16

    Two subtypes of influenza A virus (IAV), avian-origin canine influenza virus H3N2 (CIV-H3N2) and equine-origin CIV-H3N8, are enzootic in the canine population. Dogs have demonstrated seroconversion to diverse IAVs and naturally occurring reassortants of CIV-H3N2 and the 2009 H1N1 pandemic virus (pdmH1N1) have been isolated. We conducted a thorough phenotypic evaluation of CIV-H3N2 in order to assess its threat to human health. Using ferret-generated antisera we determined that CIV-H3N2 is antigenically distinct from contemporary human H3N2 IAVs, suggesting there may be minimal herd immunity in humans. We assessed the public health risk of CIV-H3N2×pdmH1N1 reassortants by characterizing in vitro genetic compatibility and in vivo pathogenicity and transmissibility. Using a luciferase minigenome assay, we quantified the polymerase activity of all possible 16 ribonucleoprotein (RNP) complexes (PB2, PB1, PA, NP) between CIV-H3N2 and pdmH1N1 identifying some combinations that were more active than either parental virus complex. Using reverse genetics, and fixing the CIV-H3N2 HA, we found that 51 of the 127 possible reassortant viruses were viable and able to be rescued. Nineteen of these reassortant viruses had high in vitro growth phenotypes and 13 of these replicated in mice lungs. A single reassortant with the NP and HA gene segments from CIV-H3N2 was selected for characterization in ferrets. The reassortant efficiently transmitted by contact but not airborne routes and was pathogenic in ferrets. Our results suggest that CIV-H3N2 reassortants may pose a moderate risk to public health and that the canine host should be monitored for emerging IAVs.Importance IAV pandemics are caused by the introduction of novel viruses that are capable of efficient and sustained human transmission into a human population with limited herd immunity. The dog, as a potential "mixing vessel" for avian and mammalian IAVs, represents a human health concern due to their susceptibility to

  14. Transmissibility of novel H7N9 and H9N2 avian influenza viruses between chickens and ferrets.

    PubMed

    Ku, Keun Bon; Park, Eun Hye; Yum, Jung; Kim, Heui Man; Kang, Young Myong; Kim, Jeong Cheol; Kim, Ji An; Kim, Hyun Soo; Seo, Sang Heui

    2014-02-01

    Previous studies have shown that the H7N9 avian influenza virus cannot be transmitted efficiently between ferrets via respiratory droplets. Here, we studied the infectivity of the H7N9 avian influenza virus in chickens and its transmissibility from infected to naïve chickens and ferrets. The H7N9 virus (A/Anhui/1/2013) replicated poorly in chickens and could not be transmitted efficiently from infected chickens to naïve chickens and ferrets. H7N9 virus was shed from chicken tracheae for only 2 days after infection and from chicken cloacae for only 1 day after infection, while the H9N2 avian influenza virus, which is endemic in chickens in many Asian countries, was shed from tracheae and cloacae for 8 days after infection. Taken together, our results suggest that chickens may be a poor agent of transmission for the H7N9 virus to other chickens and to mammals, including humans.

  15. Symbiont survival and host-symbiont disequilibria under differential vertical transmission.

    PubMed Central

    Sánchez, M S; Arnold, J; Asmussen, M A

    2000-01-01

    Interspecific genetic interactions in host-symbiont systems raise intriguing coevolutionary questions and may influence the effectiveness of public health and management policies. Here we present an analytical and numerical investigation of the effects of host genetic heterogeneity in the rate of vertical transmission of a symbiont. We consider the baseline case with a monomorphic symbiont and a single diallelic locus in its diploid host, where vertical transmission is the sole force. Our analysis introduces interspecific disequilibria to quantify nonrandom associations between host genotypes and alleles and symbiont presence/absence. The transient and equilibrium behavior is examined in simulations with randomly generated initial conditions and transmission parameters. Compared to the case where vertical transmission rates are uniform across host genotypes, differential transmission (i) increases average symbiont survival from 50% to almost 60%, (ii) dramatically reduces the minimum average transmission rate for symbiont survival from 0.5 to 0.008, and (iii) readily creates permanent host-symbiont disequilibria de novo, whereas uniform transmission can neither create nor maintain such associations. On average, heterozygotes are slightly more likely to carry and maintain the symbiont in the population and are more randomly associated with the symbiont. Results show that simple evolutionary forces can create substantial nonrandom associations between two species. PMID:10757775

  16. Antigenicity and transmissibility of a novel clade 2.3.2.1 avian influenza H5N1 virus.

    PubMed

    Xu, Lili; Bao, Linlin; Yuan, Jing; Li, Fengdi; Lv, Qi; Deng, Wei; Xu, Yanfeng; Yao, Yanfeng; Yu, Pin; Chen, Honglin; Yuen, Kwok-Yung; Qin, Chuan

    2013-12-01

    A genetic variant of the H5N1 influenza virus, termed subclade 2.3.2.1, was first identified in Bulgaria in 2010 and has subsequently been found in Vietnam and Laos. Several cases of human infections with this virus have been identified. Thus, it is important to understand the antigenic properties and transmissibility of this variant. Our results showed that, although it is phylogenetically closely related to other previously characterized clade 2.3 viruses, this novel 2.3.2.1 variant exhibited distinct antigenic properties and showed little cross-reactivity to sera raised against other H5N1 viruses. Like other H5N1 viruses, this variant bound preferentially to avian-type receptors, but contained substitutions at positions 190 and 158 of the haemagglutinin (HA) protein that have been postulated to facilitate HA binding to human-type receptors and to enhance viral transmissibility among mammals, respectively. However, this virus did not appear to have acquired the capacity for airborne transmission between ferrets. These findings highlight the challenges in selecting vaccine candidates for H5N1 influenza because these viruses continue to evolve rapidly in the field. It is important to note that some variants have obtained mutations that may gain transmissibility between model animals, and close surveillance of H5N1 viruses in poultry is warranted.

  17. Cost-Utility of Quadrivalent Versus Trivalent Influenza Vaccine in Germany, Using an Individual-Based Dynamic Transmission Model.

    PubMed

    Dolk, Christiaan; Eichner, Martin; Welte, Robert; Anastassopoulou, Anastassia; Van Bellinghen, Laure-Anne; Poulsen Nautrup, Barbara; Van Vlaenderen, Ilse; Schmidt-Ott, Ruprecht; Schwehm, Markus; Postma, Maarten

    2016-12-01

    Seasonal influenza infection is primarily caused by circulation of two influenza A strain subtypes and strains from two B lineages that vary each year. Trivalent influenza vaccine (TIV) contains only one of the two B-lineage strains, resulting in mismatches between vaccine strains and the predominant circulating B lineage. Quadrivalent influenza vaccine (QIV) includes both B-lineage strains. The objective was to estimate the cost-utility of introducing QIV to replace TIV in Germany. An individual-based dynamic transmission model (4Flu) using German data was used to provide realistic estimates of the impact of TIV and QIV on age-specific influenza infections. Cases were linked to health and economic outcomes to calculate the cost-utility of QIV versus TIV, from both a societal and payer perspective. Costs and effects were discounted at 3.0 and 1.5 % respectively, with 2014 as the base year. Univariate and probabilistic sensitivity analyses were conducted. Using QIV instead of TIV resulted in additional quality-adjusted life-years (QALYs) and cost savings from the societal perspective (i.e. it represents the dominant strategy) and an incremental cost-utility ratio (ICUR) of €14,461 per QALY from a healthcare payer perspective. In all univariate analyses, QIV remained cost-effective (ICUR <€50,000). In probabilistic sensitivity analyses, QIV was cost-effective in >98 and >99 % of the simulations from the societal and payer perspective, respectively. This analysis suggests that QIV in Germany would provide additional health gains while being cost-saving to society or costing €14,461 per QALY gained from the healthcare payer perspective, compared with TIV.

  18. A topology for computer networks with good survivability characteristics and low transmission delays between node computers

    NASA Technical Reports Server (NTRS)

    Kelly, G. L.; Jiang, D. P.

    1984-01-01

    Various network topologies are developed which have not appeared in the literature before which result in minimum diameter graphs for computer networks having connectivity four. The topologies presented have good survivability characteristics and result in more topologies being available for computer network designers which achieve the minimum diameter resulting in small transmission delays.

  19. A topology for computer networks with good survivability characteristics and low transmission delays between node computers

    NASA Technical Reports Server (NTRS)

    Kelly, G. L.; Jiang, D. P.

    1984-01-01

    Various network topologies are developed which have not appeared in the literature before which result in minimum diameter graphs for computer networks having connectivity four. The topologies presented have good survivability characteristics and result in more topologies being available for computer network designers which achieve the minimum diameter resulting in small transmission delays.

  20. Eurasian-Origin Gene Segments Contribute to the Transmissibility, Aerosol Release, and Morphology of the 2009 Pandemic H1N1 Influenza Virus

    PubMed Central

    Lakdawala, Seema S.; Lamirande, Elaine W.; Suguitan, Amorsolo L.; Wang, Weijia; Santos, Celia P.; Vogel, Leatrice; Matsuoka, Yumiko; Lindsley, William G.; Jin, Hong; Subbarao, Kanta

    2011-01-01

    The epidemiological success of pandemic and epidemic influenza A viruses relies on the ability to transmit efficiently from person-to-person via respiratory droplets. Respiratory droplet (RD) transmission of influenza viruses requires efficient replication and release of infectious influenza particles into the air. The 2009 pandemic H1N1 (pH1N1) virus originated by reassortment of a North American triple reassortant swine (TRS) virus with a Eurasian swine virus that contributed the neuraminidase (NA) and M gene segments. Both the TRS and Eurasian swine viruses caused sporadic infections in humans, but failed to spread from person-to-person, unlike the pH1N1 virus. We evaluated the pH1N1 and its precursor viruses in a ferret model to determine the contribution of different viral gene segments on the release of influenza virus particles into the air and on the transmissibility of the pH1N1 virus. We found that the Eurasian-origin gene segments contributed to efficient RD transmission of the pH1N1 virus likely by modulating the release of influenza viral RNA-containing particles into the air. All viruses replicated well in the upper respiratory tract of infected ferrets, suggesting that factors other than viral replication are important for the release of influenza virus particles and transmission. Our studies demonstrate that the release of influenza viral RNA-containing particles into the air correlates with increased NA activity. Additionally, the pleomorphic phenotype of the pH1N1 virus is dependent upon the Eurasian-origin gene segments, suggesting a link between transmission and virus morphology. We have demonstrated that the viruses are released into exhaled air to varying degrees and a constellation of genes influences the transmissibility of the pH1N1 virus. PMID:22241979

  1. Environmental role in influenza virus outbreaks.

    PubMed

    Sooryanarain, Harini; Elankumaran, Subbiah

    2015-01-01

    The environmental drivers of influenza outbreaks are largely unknown. Despite more than 50 years of research, there are conflicting lines of evidence on the role of the environment in influenza A virus (IAV) survival, stability, and transmissibility. With the increasing and looming threat of pandemic influenza, it is important to understand these factors for early intervention and long-term control strategies. The factors that dictate the severity and spread of influenza would include the virus, natural and acquired hosts, virus-host interactions, environmental persistence, virus stability and transmissibility, and anthropogenic interventions. Virus persistence in different environments is subject to minor variations in temperature, humidity, pH, salinity, air pollution, and solar radiations. Seasonality of influenza is largely dictated by temperature and humidity, with cool-dry conditions enhancing IAV survival and transmissibility in temperate climates in high latitudes, whereas humid-rainy conditions favor outbreaks in low latitudes, as seen in tropical and subtropical zones. In mid-latitudes, semiannual outbreaks result from alternating cool-dry and humid-rainy conditions. The mechanism of virus survival in the cool-dry or humid-rainy conditions is largely determined by the presence of salts and proteins in the respiratory droplets. Social determinants of heath, including health equity, vaccine acceptance, and age-related illness, may play a role in influenza occurrence and spread.

  2. Genetic evolution of PB1 in the zoonotic transmission of influenza A(H1) virus.

    PubMed

    Gíria, Marta; Rebelo de Andrade, Helena

    2014-10-01

    The epidemiology of human infection with swine-origin influenza A(H1) viruses suggests that the virus must adapt to replicate and transmit within the human host. PB1 is essential to the replication process. The objective of this study was to identify whether PB1 retains genetic traces of interspecies transmission and adaptation. We have found that the evolutionary history of PB1 is traceable. Lineage appears to be distinguished by amino acid changes between the conserved motifs of the viral polymerase, which can have major impact in PB1 protein folding, and by changes in the expression of the Mitochondrial Targeting Sequence and in the predicted helical region, that putatively affect induction of cellular apoptosis by PB1-F2. Furthermore, we found genomic markers that possibly relate to viral adaptation to new hosts and to new cellular environment and, additionally, to an enhanced compatibility with HA. We found no specific trend in the amino acid substitutions. Viral fitness appears to be favored by less reactive amino acids in some positions, while in others more reactive ones are fixed. Also, more flexible conformations appear associated with higher protein stability in general, although often more restrictive conformations appear to have favored protein folding and binding. Several aspects of PB1 mapping domains and the specific roles and interaction of PB1, PB1-F2 and N40 with each other and with other viral proteins and host cellular molecules remain unclear. Tracing the genetic evolution is critical to further understand the mechanisms by which PB1 affects vital fitness and adaptation. This analysis now permits putative adaptive related polymorphisms to be experimentally evaluated for phenotypic impact.

  3. Pathogenicity and Transmission of H5 and H7 Highly Pathogenic Avian Influenza Viruses in Mallards.

    PubMed

    Pantin-Jackwood, Mary J; Costa-Hurtado, Mar; Shepherd, Eric; DeJesus, Eric; Smith, Diane; Spackman, Erica; Kapczynski, Darrell R; Suarez, David L; Stallknecht, David E; Swayne, David E

    2016-11-01

    Wild aquatic birds have been associated with the intercontinental spread of H5 subtype highly pathogenic avian influenza (HPAI) viruses of the A/goose/Guangdong/1/96 (Gs/GD) lineage during 2005, 2010, and 2014, but dispersion by wild waterfowl has not been implicated with spread of other HPAI viruses. To better understand why Gs/GD H5 HPAI viruses infect and transmit more efficiently in waterfowl than other HPAI viruses, groups of mallard ducks were challenged with one of 14 different H5 and H7 HPAI viruses, including a Gs/GD lineage H5N1 (clade 2.2) virus from Mongolia, part of the 2005 dispersion, and the H5N8 and H5N2 index HPAI viruses (clade 2.3.4.4) from the United States, part of the 2014 dispersion. All virus-inoculated ducks and contact exposed ducks became infected and shed moderate to high titers of the viruses, with the exception that mallards were resistant to Ck/Pennsylvania/83 and Ck/Queretaro/95 H5N2 HPAI virus infection. Clinical signs were only observed in ducks challenged with the H5N1 2005 virus, which all died, and with the H5N8 and H5N2 2014 viruses, which had decreased weight gain and fever. These three viruses were also shed in higher titers by the ducks, which could facilitate virus transmission and spread. This study highlights the possible role of wild waterfowl in the spread of HPAI viruses.

  4. The impact of ambient fine particles on influenza transmission and the modification effects of temperature in China: A multi-city study.

    PubMed

    Chen, Gongbo; Zhang, Wenyi; Li, Shanshan; Zhang, Yongming; Williams, Gail; Huxley, Rachel; Ren, Hongyan; Cao, Wei; Guo, Yuming

    2017-01-01

    There is good evidence that air pollution is a risk factor for adverse respiratory and vascular health outcomes. However, data are limited as to whether ambient fine particles contribute to the transmission of influenza and if so, how the association is modified by weather conditions. We examined the relationship between ambient PM2.5 and influenza incidence at the national level in China and explored the associations at different temperatures. Daily data on concentrations of particulate matter with aerodynamic diameter<2.5μm (PM2.5) and influenza incidence counts were collected in 47 Chinese cities. A Poisson regression model was used to estimate the city-specific PM2.5-influenza association, after controlling for potential confounders. Then, a random-effect meta-analysis was used to pool the effects at national level. In addition, stratified analyses were performed to examine modification effects of ambient temperature. For single lag models, the highest effect of ambient PM2.5 on influenza incidence appeared at lag day 2, with relative risk (RR) of 1.015 (95% confidence interval (CI): 1.004, 1.025) associated with a 10μg/m(3) increase in PM2.5. For moving average lag models, the significant association was found at lag 2-3days, with RR of 1.020 (95% CI: 1.006, 1.034). The RR of influenza transmission associated with PM2.5 was higher for cold compared with hot days. Overall, 10.7% of incident influenza cases may result from exposure to ambient PM2.5. Ambient PM2.5 may increase the risk of exposure to influenza in China especially on cooler days. Control measures to reduce PM2.5 concentrations could potentially also be of benefit in lowering the risk of exposure and subsequent transmission of influenza in China. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Molecular Infectious Disease Epidemiology: Survival Analysis and Algorithms Linking Phylogenies to Transmission Trees.

    PubMed

    Kenah, Eben; Britton, Tom; Halloran, M Elizabeth; Longini, Ira M

    2016-04-01

    Recent work has attempted to use whole-genome sequence data from pathogens to reconstruct the transmission trees linking infectors and infectees in outbreaks. However, transmission trees from one outbreak do not generalize to future outbreaks. Reconstruction of transmission trees is most useful to public health if it leads to generalizable scientific insights about disease transmission. In a survival analysis framework, estimation of transmission parameters is based on sums or averages over the possible transmission trees. A phylogeny can increase the precision of these estimates by providing partial information about who infected whom. The leaves of the phylogeny represent sampled pathogens, which have known hosts. The interior nodes represent common ancestors of sampled pathogens, which have unknown hosts. Starting from assumptions about disease biology and epidemiologic study design, we prove that there is a one-to-one correspondence between the possible assignments of interior node hosts and the transmission trees simultaneously consistent with the phylogeny and the epidemiologic data on person, place, and time. We develop algorithms to enumerate these transmission trees and show these can be used to calculate likelihoods that incorporate both epidemiologic data and a phylogeny. A simulation study confirms that this leads to more efficient estimates of hazard ratios for infectiousness and baseline hazards of infectious contact, and we use these methods to analyze data from a foot-and-mouth disease virus outbreak in the United Kingdom in 2001. These results demonstrate the importance of data on individuals who escape infection, which is often overlooked. The combination of survival analysis and algorithms linking phylogenies to transmission trees is a rigorous but flexible statistical foundation for molecular infectious disease epidemiology.

  6. Molecular Infectious Disease Epidemiology: Survival Analysis and Algorithms Linking Phylogenies to Transmission Trees

    PubMed Central

    Kenah, Eben; Britton, Tom; Halloran, M. Elizabeth; Longini, Ira M.

    2016-01-01

    Recent work has attempted to use whole-genome sequence data from pathogens to reconstruct the transmission trees linking infectors and infectees in outbreaks. However, transmission trees from one outbreak do not generalize to future outbreaks. Reconstruction of transmission trees is most useful to public health if it leads to generalizable scientific insights about disease transmission. In a survival analysis framework, estimation of transmission parameters is based on sums or averages over the possible transmission trees. A phylogeny can increase the precision of these estimates by providing partial information about who infected whom. The leaves of the phylogeny represent sampled pathogens, which have known hosts. The interior nodes represent common ancestors of sampled pathogens, which have unknown hosts. Starting from assumptions about disease biology and epidemiologic study design, we prove that there is a one-to-one correspondence between the possible assignments of interior node hosts and the transmission trees simultaneously consistent with the phylogeny and the epidemiologic data on person, place, and time. We develop algorithms to enumerate these transmission trees and show these can be used to calculate likelihoods that incorporate both epidemiologic data and a phylogeny. A simulation study confirms that this leads to more efficient estimates of hazard ratios for infectiousness and baseline hazards of infectious contact, and we use these methods to analyze data from a foot-and-mouth disease virus outbreak in the United Kingdom in 2001. These results demonstrate the importance of data on individuals who escape infection, which is often overlooked. The combination of survival analysis and algorithms linking phylogenies to transmission trees is a rigorous but flexible statistical foundation for molecular infectious disease epidemiology. PMID:27070316

  7. Inferring patterns of influenza transmission in swine from multiple streams of surveillance data.

    PubMed

    Strelioff, Christopher C; Vijaykrishna, Dhanasekaran; Riley, Steven; Guan, Yi; Peiris, J S Malik; Lloyd-Smith, James O

    2013-07-07

    Swine populations are known to be an important source of new human strains of influenza A, including those responsible for global pandemics. Yet our knowledge of the epidemiology of influenza in swine is dismayingly poor, as highlighted by the emergence of the 2009 pandemic strain and the paucity of data describing its origins. Here, we analyse a unique dataset arising from surveillance of swine influenza at a Hong Kong abattoir from 1998 to 2010. We introduce a state-space model that estimates disease exposure histories by joint inference from multiple modes of surveillance, integrating both virological and serological data. We find that an observed decrease in virus isolation rates is not due to a reduction in the regional prevalence of influenza. Instead, a more likely explanation is increased infection of swine in production farms, creating greater immunity to disease early in life. Consistent with this, we find that the weekly risk of exposure on farms equals or exceeds the exposure risk during transport to slaughter. We discuss potential causes for these patterns, including competition between influenza strains and shifts in the Chinese pork industry, and suggest opportunities to improve knowledge and reduce prevalence of influenza in the region.

  8. Serial killers, spiders and cybersex: Social and survival information bias in the transmission of urban legends.

    PubMed

    Stubbersfield, Joseph M; Tehrani, Jamshid J; Flynn, Emma G

    2015-05-01

    This study uses urban legends to examine the effects of the social information bias and survival information bias on cultural transmission across three phases of transmission: the choose-to-receive phase, the encode-and-retrieve phase, and the choose-to-transmit phase. In line with previous research into content biases, a linear transmission chain design with 60 participants aged 18-52 was used to examine the encode-and-retrieve phase, while participants were asked to rank their interest in reading the story behind a headline and passing a story on for the other two phases. Legends which contained social information (Social Type), legends which contained survival information (Survival Type), and legends which contained both forms of information (Combined Type) were all recalled with significantly greater accuracy than control material, while Social and Combined Type legends were recalled with significantly greater accuracy than Survival Type legends. In another study with 30 participants aged 18-22, no significant differences were found between legend types in either the choose-to-receive phase or the choose-to-transmit phase.

  9. Interregional transmission of the internal protein genes of H2 influenza virus in migratory ducks from North America to Eurasia.

    PubMed

    Liu, Jin-Hua; Okazaki, Katsunori; Bai, Gui-Rong; Shi, Wei-Min; Mweene, Aaron; Kida, Hiroshi

    2004-08-01

    H2 influenza virus caused a pandemic in 1957 and has the possibility to cause outbreaks in the future. To assess the evolutionary characteristics of H2 influenza viruses isolated from migratory ducks that congregate in Hokkaido, Japan, on their flyway of migration from Siberia in 2001, we investigated the phylogenetic relationships among these viruses and avian and human viruses described previously. Phylogenetic analysis showed that the PB2 gene of Dk/Hokkaido/107/01 (H2N3) and the PA gene of Dk/Hokkaido/95/01 (H2N2) belonged to the American lineage of avian virus and that the other genes of the isolates belonged to the Eurasian lineage. These results indicate that the internal protein genes might be transmitted from American to Eurasian avian host. Thus, it is further confirmed that interregional transmission of influenza viruses occurred between the North American and Eurasian birds. The fact that reassortants could be generated in the migratory ducks between North American and Eurasian avian virus lineage further stresses the importance of global surveillance among the migratory ducks.

  10. Pandemic influenza and health system resource gaps in Bali: an analysis through a resource transmission dynamics model.

    PubMed

    Adisasmito, Wiku; Hunter, Benjamin M; Krumkamp, Ralf; Latief, Kamal; Rudge, James W; Hanvoravongchai, Piya; Coker, Richard J

    2015-03-01

    The failure to contain pandemic influenza A(H1N1) 2009 in Mexico has shifted global attention from containment to mitigation. Limited surveillance and reporting have, however, prevented detailed assessment of mitigation during the pandemic, particularly in low- and middle-income countries. To assess pandemic influenza case management capabilities in a resource-limited setting, the authors used a health system questionnaire and density-dependent, deterministic transmission model for Bali, Indonesia, determining resource gaps. The majority of health resources were focused in and around the provincial capital, Denpasar; however, gaps are found in every district for nursing staff, surgical masks, and N95 masks. A relatively low pathogenicity pandemic influenza virus would see an overall surplus for physicians, antivirals, and antimicrobials; however, a more pathogenic virus would lead to gaps in every resource except antimicrobials. Resources could be allocated more evenly across Bali. These, however, are in short supply universally and therefore redistribution would not fill resource gaps. © 2011 APJPH.

  11. No evidence for zoonotic transmission of H3N8 canine influenza virus among US adults occupationally exposed to dogs

    PubMed Central

    Krueger, Whitney S; Heil, Gary L; Yoon, Kyoung-Jin; Gray, Gregory C

    2014-01-01

    Objectives The zoonotic potential of H3N8 canine influenza virus (CIV) has not been previously examined; yet considering the popularity of dogs as a companion animal and the zoonotic capabilities of other influenza viruses, the public health implications are great. This study aimed to determine the seroprevalence of antibodies against CIV among a US cohort. Design A cross-sectional seroepidemiological study was conducted between 2007 and 2010. Setting Recruitments primarily occurred in Iowa and Florida. Participants were enrolled at dog shows, or at their home or place of employment. Sample Three hundred and four adults occupationally exposed to dogs and 101 non-canine-exposed participants completed a questionnaire and provided a blood sample. Main outcome measures Microneutralization and neuraminidase inhibition assays were performed to detect human sera antibodies against A/Canine/Iowa/13628/2005(H3N8). An enzyme-linked lectin assay (ELLA) was adapted to detect antibodies against a recombinant N8 neuraminidase protein from A/Equine/Pennsylvania/1/2007(H3N8). Results For all assays, no significant difference in detectable antibodies was observed when comparing the canine-exposed subjects to the non-canine-exposed subjects. Conclusion While these results do not provide evidence for cross-species CIV transmission, influenza is predictably unpredictable. People frequently exposed to ill dogs should continually be monitored for novel zoonotic CIV infections. PMID:24237615

  12. [Transmissibility and severity of the pandemic influenza A (H1N1) 2009 virus in Spain].

    PubMed

    Simón Méndez, Lorena; de Mateo Ontañón, Salvador; Larrauri Cámara, Amparo; Jiménez-Jorge, Silvia; Vaqué Rafart, Josep; Pérez Hoyos, Santiago

    2011-01-01

    To estimate the value of the basic reproduction number for the pandemic wave of influenza A (H1N1) 2009 in Spain and to assess its impact on morbidity and mortality in the Spanish population compared with those in the previous influenza season. Data on the incidence of influenza and viral detections were obtained from the Spanish Influenza Surveillance System. Deaths from pandemic influenza were obtained from the Coordinating Center for Health Alerts and Emergencies of the Spanish Ministry of Health and Social Policy, and deaths from seasonal influenza during the period 2003-2008 were obtained from the National Statistics Institute. The reproduction number was estimated by two methods: firstly, by using the growth rate of the cumulative incidence of influenza during the exponential growth phase of the pandemic wave, and secondly (maximum likelihood estimation), through analysis the dates of onset of symptoms observed in pairs of cases based on generation time distribution. We calculated the fatality rate and mortality from influenza by comparing potential years of life lost in the pandemic season with those in previous interpandemic seasons. The start of the pandemic wave occurred in Spain earlier in week 40/2009 (from 4 to 10 October), with an absolute predominance of the new strain in the pattern of circulating viruses. The value of R(0) in the growth phase of the wave was 1.29 (95% CI: 1.25-1.33), estimated with the first method, and was 1.01 (95% CI: 0.99-1.03) with the second method. During the pandemic season, there were 318 deaths from pandemic influenza, affecting younger age groups than in previous interpandemic seasons. Consequently, the number of potential years of life lost in the pandemic season (11,612) was estimated at six times the adjusted annual average of the interpandemic influenza seasons for comparison (1,802). The estimates of R(0) for the growth phase of the pandemic wave were in the lower range of estimates of this parameter in previous

  13. Using egg production data to quantify within-flock transmission of low pathogenic avian influenza virus in commercial layer chickens.

    PubMed

    Gonzales, J L; Elbers, A R W; van der Goot, J A; Bontje, D; Koch, G; de Wit, J J; Stegeman, J A

    2012-12-01

    Even though low pathogenic avian influenza viruses (LPAIv) affect the poultry industry of several countries in the world, information about their transmission characteristics in poultry is sparse. Outbreak reports of LPAIv in layer chickens have described drops in egg production that appear to be correlated with the virus transmission dynamics. The objective of this study was to use egg production data from LPAIv infected layer flocks to quantify the within-flock transmission parameters of the virus. Egg production data from two commercial layer chicken flocks which were infected with an H7N3 LPAIv were used for this study. In addition, an isolate of the H7N3 LPAIv causing these outbreaks was used in a transmission experiment. The field and experimental estimates showed that this is a virus with high transmission characteristics. Furthermore, with the field method, the day of introduction of the virus into the flock was estimated. The method here presented uses compartmental models that assume homogeneous mixing. This method is, therefore, best suited to study transmission in commercial flocks with a litter (floor-reared) housing system. It would also perform better, when used to study transmission retrospectively, after the outbreak has finished and there is egg production data from recovered chickens. This method cannot be used when a flock was affected with a LPAIv with low transmission characteristics (R(0)<2), since the drop in egg production would be low and likely to be confounded with the expected decrease in production due to aging of the flock. Because only two flocks were used for this analysis, this study is a preliminary basis for a proof of principle that transmission parameters of LPAIv infections in layer chicken flocks could be quantified using the egg production data from affected flocks. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. 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.

  15. Swine Influenza Virus (H1N2) Characterization and Transmission in Ferrets, Chile

    PubMed Central

    Bravo-Vasquez, Nicolás; Karlsson, Erik A.; Jimenez-Bluhm, Pedro; Meliopoulos, Victoria; Kaplan, Bryan; Marvin, Shauna; Cortez, Valerie; Freiden, Pamela; Beck, Melinda A.

    2017-01-01

    Phylogenetic analysis of the influenza hemagglutinin gene (HA) has suggested that commercial pigs in Chile harbor unique human seasonal H1-like influenza viruses, but further information, including characterization of these viruses, was unavailable. We isolated influenza virus (H1N2) from a swine in a backyard production farm in Central Chile and demonstrated that the HA gene was identical to that in a previous report. Its HA and neuraminidase genes were most similar to human H1 and N2 viruses from the early 1990s and internal segments were similar to influenza A(H1N1)pdm09 virus. The virus replicated efficiently in vitro and in vivo and transmitted in ferrets by respiratory droplet. Antigenically, it was distinct from other swine viruses. Hemagglutination inhibition analysis suggested that antibody titers to the swine Chilean H1N2 virus were decreased in persons born after 1990. Further studies are needed to characterize the potential risk to humans, as well as the ecology of influenza in swine in South America. PMID:28098524

  16. Failure of transmission of low-pathogenic avian influenza virus between Mallards and freshwater snails: an experimental evaluation.

    PubMed

    Oesterle, Paul T; Huyvaert, Kathryn P; Orahood, Darcy; Mooers, Nicole; Sullivan, Heather; Franklin, Alan B; Root, J Jeffrey

    2013-10-01

    In aquatic bird populations, the ability of avian influenza (AI) viruses to remain infectious in water for extended periods provides a mechanism that allows viral transmission to occur long after shedding birds have left the area. However, this also exposes other aquatic organisms, including freshwater invertebrates, to AI viruses. Previous researchers found that AI viral RNA can be sequestered in snail tissues. Using an experimental approach, we determined whether freshwater snails (Physa acuta and Physa gyrina) can infect waterfowl with AI viruses by serving as a means of transmission between infected and naïve waterfowl via ingestion. In our first experiment, we exposed 20 Physa spp. snails to an AI virus (H3N8) and inoculated embryonated specific pathogen-free (SPF) chicken eggs with the homogenized snail tissues. Sequestered AI viruses remain infectious in snail tissues; 10% of the exposed snail tissues infected SPF eggs. In a second experiment, we exposed snails to water contaminated with feces of AI virus-inoculated Mallards (Anas platyrhynchos) to evaluate whether ingestion of exposed freshwater snails was an alternate route of AI virus transmission to waterfowl. None of the immunologically naïve Mallards developed an infection, indicating that transmission via ingestion likely did not occur. Our results suggest that this particular trophic interaction may not play an important role in the transmission of AI viruses in aquatic habitats.

  17. An evaluation of transmission routes for low pathogenicity avian influenza virus among chickens sold in live bird markets.

    PubMed

    Yee, Karen S; Carpenter, Tim E; Farver, Thomas B; Cardona, Carol J

    2009-11-10

    Many theories about the modes of avian influenza virus (AIV) transmission have been proposed, but few have been quantified, and none within a flock or live bird market (LBM) setting where birds are often kept in stacked cages. We describe a novel experimental design and the results collected for the purpose of estimating transmission rates specific to the potential modes of AIV transmission within an LBM. Chickens of the strains and ages found in California LBMs were inoculated with low pathogenicity AIV H6N2. Aerosol exposure was found to be the most important route of transmission for this H6N2 AIV. The handling of infectious chickens resulted in the transmission of H6N2 AIV, though the virus was not detectible by rRT-PCR. Chickens with fecal exposure to infected birds (median=8.0 DPI) had detectable virus earlier than in those with aerosol exposure only (median=10.0 DPI). Changes in the hemagglutinin sequence were not found to be associated with oropharyngeal or cloacal shedding in this study.

  18. Economic factors influencing zoonotic disease dynamics: demand for poultry meat and seasonal transmission of avian influenza in Vietnam.

    PubMed

    Delabouglise, Alexis; Choisy, Marc; Phan, Thang D; Antoine-Moussiaux, Nicolas; Peyre, Marisa; Vu, Ton D; Pfeiffer, Dirk U; Fournié, Guillaume

    2017-07-19

    While climate is often presented as a key factor influencing the seasonality of diseases, the importance of anthropogenic factors is less commonly evaluated. Using a combination of methods - wavelet analysis, economic analysis, statistical and disease transmission modelling - we aimed to explore the influence of climatic and economic factors on the seasonality of H5N1 Highly Pathogenic Avian Influenza in the domestic poultry population of Vietnam. We found that while climatic variables are associated with seasonal variation in the incidence of avian influenza outbreaks in the North of the country, this is not the case in the Centre and the South. In contrast, temporal patterns of H5N1 incidence are similar across these 3 regions: periods of high H5N1 incidence coincide with Lunar New Year festival, occurring in January-February, in the 3 climatic regions for 5 out of the 8 study years. Yet, daily poultry meat consumption drastically increases during Lunar New Year festival throughout the country. To meet this rise in demand, poultry production and trade are expected to peak around the festival period, promoting viral spread, which we demonstrated using a stochastic disease transmission model. This study illustrates the way in which economic factors may influence the dynamics of livestock pathogens.

  19. Analysis of spatial distribution and transmission characters for highly pathogenic avian influenza in Chinese mainland in 2004

    NASA Astrophysics Data System (ADS)

    Liu, Y. L.; Wei, C. J.; Yan, L.; Chi, T. H.; Wu, X. B.; Xiao, C. S.

    2006-03-01

    After the outbreak of highly pathogenic Avian Influenza (HPAI) in South Korea in the end of year 2003, estimates of the impact of HPAI in affected countries vary greatly, the total direct losses are about 3 billion US dollars, and it caused 15 million birds and poultry flocks death. It is significant to understand the spatial distribution and transmission characters of HPAI for its prevention and control. According to 50 outbreak cases for HPAI in Chinese mainland during 2004, this paper introduces the approach of spatial distribution and transmission characters for HPAI and its results. Its approach is based on remote sensing and GIS techniques. Its supporting data set involves normalized difference vegetation index (NDVI) and land surface temperature (Ts) derived from a time-series of remote sensing data of 1 kilometer-resolution NOAA/AVHRR, birds' migration routes, topology geographic map, lake and wetland maps, and meteorological observation data. In order to analyze synthetically using these data, a supporting platform for analysis Avian Influenza epidemic situation (SPAS/AI) was developed. Supporting by SPAS/AI, the integrated information from multi-sources can be easily used to the analysis of the spatial distribution and transmission character of HPAI. The results show that the range of spatial distribution and transmission of HPAI in China during 2004 connected to environment factors NDVI, Ts and the distributions of lake and wetland, and especially to bird migration routes. To some extent, the results provide some suggestions for the macro-decision making for the prevention and control of HPAI in the areas of potential risk and reoccurrence.

  20. A spatial-temporal transmission model and early intervention policies of 2009 A/H1N1 influenza in South Korea.

    PubMed

    Lee, Jonggul; Jung, Eunok

    2015-09-07

    We developed a spatial-temporal model of the 2009 A/H1N1 influenza pandemic in the Seoul metropolitan area (SMA), which is located in the north-west of South Korea and is the second-most complex metropolitan area worldwide. This multi-patch influenza model consists of a SEIAR influenza transmission model and flow model between two districts. This model is based on the daily confirmed cases of A/H1N1 influenza collected by the Korea Center for Disease Control and Prevention from April 27 to September 15, 2009 and the daily commuting data from 33 districts of SMA reported in the 2010 Population and Housing Census (PHC). We analyzed the spread patterns of 2009 influenza in the SMA by the reproductive numbers and geographic information systems. During the early period of novel influenza pandemics, when pharmaceutical interventions are lacking, non-pharmaceutical public health interventions will be the most critical strategies for impeding the spread of influenza and delaying an epidemic. Using the spatial-temporal model developed herein, we also investigated the impact of non-pharmaceutical public health interventions, isolation and/or commuting restrictions, on the incidence reduction in various scenarios. Our model provides scientific evidence for predicting the spread of disease and preparedness for a future pandemic.

  1. Pathogen-Mediated Inhibition of Anorexia Promotes Host Survival and Transmission.

    PubMed

    Rao, Sheila; Schieber, Alexandria M Palaferri; O'Connor, Carolyn P; Leblanc, Mathias; Michel, Daniela; Ayres, Janelle S

    2017-01-26

    Sickness-induced anorexia is a conserved behavior induced during infections. Here, we report that an intestinal pathogen, Salmonella Typhimurium, inhibits anorexia by manipulating the gut-brain axis. Inhibition of inflammasome activation by the S. Typhimurium effector, SlrP, prevented anorexia caused by IL-1β-mediated signaling to the hypothalamus via the vagus nerve. Rather than compromising host defenses, pathogen-mediated inhibition of anorexia increased host survival. SlrP-mediated inhibition of anorexia prevented invasion and systemic infection by wild-type S. Typhimurium, reducing virulence while increasing transmission to new hosts, suggesting that there are trade-offs between transmission and virulence. These results clarify the complex and contextual role of anorexia in host-pathogen interactions and suggest that microbes have evolved mechanisms to modulate sickness-induced behaviors to promote health of their host and their transmission at the expense of virulence. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. A Novel, Molybdenum-Containing Methionine Sulfoxide Reductase Supports Survival of Haemophilus influenzae in an In vivo Model of Infection

    PubMed Central

    Dhouib, Rabeb; Othman, Dk. Seti Maimonah Pg; Lin, Victor; Lai, Xuanjie J.; Wijesinghe, Hewa G. S.; Essilfie, Ama-Tawiah; Davis, Amanda; Nasreen, Marufa; Bernhardt, Paul V.; Hansbro, Philip M.; McEwan, Alastair G.; Kappler, Ulrike

    2016-01-01

    Haemophilus influenzae is a host adapted human mucosal pathogen involved in a variety of acute and chronic respiratory tract infections, including chronic obstructive pulmonary disease and asthma, all of which rely on its ability to efficiently establish continuing interactions with the host. Here we report the characterization of a novel molybdenum enzyme, TorZ/MtsZ that supports interactions of H. influenzae with host cells during growth in oxygen-limited environments. Strains lacking TorZ/MtsZ showed a reduced ability to survive in contact with epithelial cells as shown by immunofluorescence microscopy and adherence/invasion assays. This included a reduction in the ability of the strain to invade human epithelial cells, a trait that could be linked to the persistence of H. influenzae. The observation that in a murine model of H. influenzae infection, strains lacking TorZ/MtsZ were almost undetectable after 72 h of infection, while ∼3.6 × 103 CFU/mL of the wild type strain were measured under the same conditions is consistent with this view. To understand how TorZ/MtsZ mediates this effect we purified and characterized the enzyme, and were able to show that it is an S- and N-oxide reductase with a stereospecificity for S-sulfoxides. The enzyme converts two physiologically relevant sulfoxides, biotin sulfoxide and methionine sulfoxide (MetSO), with the kinetic parameters suggesting that MetSO is the natural substrate of this enzyme. TorZ/MtsZ was unable to repair sulfoxides in oxidized Calmodulin, suggesting that a role in cell metabolism/energy generation and not protein repair is the key function of this enzyme. Phylogenetic analyses showed that H. influenzae TorZ/MtsZ is only distantly related to the Escherichia coli TorZ TMAO reductase, but instead is a representative of a new, previously uncharacterized clade of molybdenum enzyme that is widely distributed within the Pasteurellaceae family of pathogenic bacteria. It is likely that MtsZ/TorZ has a similar

  3. Laninamivir Octanoate and Artificial Surfactant Combination Therapy Significantly Increases Survival of Mice Infected with Lethal Influenza H1N1 Virus

    PubMed Central

    Fukushi, Masaya; Yamashita, Makoto; Miyoshi-Akiyama, Tohru; Kubo, Shuku; Yamamoto, Kenji; Kudo, Koichiro

    2012-01-01

    Background Patients with influenza virus infection can develop severe pneumonia and acute respiratory distress syndrome (ARDS) which have a high mortality. Influenza virus infection is treated worldwide mainly by neuraminidase inhibitors (NAIs). However, monotherapy with NAIs is insufficient for severe pneumonia secondary to influenza virus infection. We previously demonstrated that mice infected with a lethal dose of influenza virus develop diffuse alveolar damage (DAD) with alveolar collapse similar to that seen in ARDS in humans. Additionally, pulmonary surfactant proteins were gradually increased in mouse serum, suggesting a decrease in pulmonary surfactant in the lung. Therefore, the present study examined whether combination therapy of NAI with exogenous artificial surfactant affects mortality of influenza virus-infected mice. Methodology/Principal Findings BALB/c mice were inoculated with several viral doses of influenza A/Puerto Rico/8/34 (PR8) virus (H1N1). The mice were additionally administered exogenous artificial surfactant in the presence or absence of a new NAI, laninamivir octanoate. Mouse survival, body weight and general condition were observed for up to 20 days after inoculation. Viral titer and cytokine/chemokine levels in the lungs, lung weight, pathological analysis, and blood O2 and CO2 pressures were evaluated. Infected mice treated with combination therapy of laninamivir octanoate with artificial surfactant showed a significantly higher survival rate compared with those that received laninamivir octanoate monotherapy (p = 0.003). However, virus titer, lung weight and cytokine/chemokine responses were not different between the groups. Histopathological examination, a hydrostatic lung test and blood gas analysis showed positive results in the combination therapy group. Conclusions/Significance Combination therapy of laninamivir octanoate with artificial surfactant reduces lethality in mice infected with influenza virus, and eventually

  4. Assessing Potential Risks of Influenza A Virus Transmission at the Pig-Human Interface in Thai Small Pig Farms Using a Questionnaire Survey.

    PubMed

    Netrabukkana, P; Robertson, I D; Kasemsuwan, S; Wongsathapornchai, K; Fenwick, S

    2016-02-01

    Influenza A viruses pose a major public health threat worldwide, especially due to the potential for inter-species transmission. Farmers could be among the first people to be infected with a novel reassortant virus in a pig herd and may serve as a source of the virus for their communities. In this study, the pig production systems of smallholders in rural Thailand were examined to qualitatively evaluate the potential risks that may contribute to the spread of influenza A viruses. The investigation was based on questionnaire interviews regarding pig farmers' practices and trading activities. We found that extensive pig-human contacts, commingling of pigs and chickens and suboptimal biosecurity practices adopted by farmers and traders may constitute substantial risks for inter-species influenza virus transmission, thereby posing a threat to pig populations and human public health. The regular practices of using manure as field fertilizer, hiring boars from outside and trading activities could contribute to the potential spread of influenza viruses in the local community. To mitigate the potential risks of influenza A virus transmission and spread in the local community, it is recommended that appropriate public health strategies and disease prevention policies for farmers and traders should be developed including improving biosecurity, encouraging separation of animals raised on farms and minimizing the exposure between pigs and humans. Furthermore, surveillance systems for pig diseases should be targeted around the festival months, and on-farm identification of pigs should be promoted.

  5. Assessing the impact of public health interventions on the transmission of pandemic H1N1 influenza a virus aboard a Peruvian navy ship

    PubMed Central

    Vera, Delphis M; Hora, Ricardo A; Murillo, Anarina; Wong, Juan F; Torre, Armando J; Wang, David; Boulay, Darbi; Hancock, Kathy; Katz, Jacqueline M; Ramos, Mariana; Loayza, Luis; Quispe, Jose; Reaves, Erik J; Bausch, Daniel G; Chowell, Gerardo; Montgomery, Joel M

    2014-01-01

    Background Limited data exist on transmission dynamics and effectiveness of control measures for influenza in confined settings. Objectives To investigate the transmission dynamics of a 2009 pandemic H1N1 influenza A outbreak aboard a Peruvian Navy ship and quantify the effectiveness of the implemented control measures. Methods We used surveillance data and a simple stochastic epidemic model to characterize and evaluate the effectiveness of control interventions implemented during an outbreak of 2009 pandemic H1N1 influenza A aboard a Peruvian Navy ship. Results The serological attack rate for the outbreak was 49·1%, with younger cadets and low-ranking officers at greater risk of infection than older, higher-ranking officers. Our transmission model yielded a good fit to the daily time series of new influenza cases by date of symptom onset. We estimated a reduction of 54·4% in the reproduction number during the period of intense control interventions. Conclusion Our results indicate that the patient isolation strategy and other control measures put in place during the outbreak reduced the infectiousness of isolated individuals by 86·7%. Our findings support that early implementation of control interventions can limit the spread of influenza epidemics in confined settings. PMID:24506160

  6. Infectivity and transmissibility of H9N2 avian influenza virus in chickens and wild terrestrial birds

    PubMed Central

    2013-01-01

    Genetic changes in avian influenza viruses influence their infectivity, virulence and transmission. Recently we identified a novel genotype of H9N2 viruses in widespread circulation in poultry in Pakistan that contained polymerases (PB2, PB1 and PA) and non-structural (NS) gene segments identical to highly pathogenic H7N3 viruses. Here, we investigated the potential of these viruses to cause disease and assessed the transmission capability of the virus within and between poultry and wild terrestrial avian species. Groups of broilers, layers, jungle fowl, quail, sparrows or crows were infected with a representative strain (A/chicken/UDL-01/08) of this H9N2 virus and then mixed with naïve birds of the same breed or species, or different species to examine transmission. With the exception of crows, all directly inoculated and contact birds showed clinical signs, varying in severity with quail showing the most pronounced clinical signs. Virus shedding was detected in all infected birds, with quail showing the greatest levels of virus secretion, but only very low levels of virus were found in directly infected crow samples. Efficient virus intra-species transmission was observed within each group with the exception of crows in which no evidence of transmission was seen. Interspecies transmission was examined between chickens and sparrows and vice versa and efficient transmission was seen in either direction. These results highlight the ease of spread of this group of H9N2 viruses between domesticated poultry and sparrows and show that sparrows need to be considered as a high risk species for transmitting H9N2 viruses between premises. PMID:24134616

  7. Pathogenesis and transmission of H7N9 influenza virus in poultry

    USDA-ARS?s Scientific Manuscript database

    Background: The recent and ongoing outbreak of H7N9 influenza in China has resulted in many human cases with a high fatality rate. Poultry have been suspected as the source of infection based on sequence analysis and virus isolations from live bird markets; however it’s not clear which species of ...

  8. Pathogenesis and transmission of H7N9 influenza virus in poultry

    USDA-ARS?s Scientific Manuscript database

    The recent outbreaks of H7N9 influenza in China has resulted in many human cases with a high fatality rate. Poultry have been suspected as the source of infection based on sequence analysis and virus isolations from live bird markets, but it’s not clear which species of birds are most likely to be ...

  9. Airborne transmission of H5N1 high pathogenicity avian influenza viruses during simulated home slaughter

    USDA-ARS?s Scientific Manuscript database

    Most H5N1 human infections have occurred following exposure to H5N1 high pathogenicity avian influenza (HPAI) virus-infected poultry, especially when poultry are home slaughtered or slaughtered in live poultry markets. Previous studies have demonstrated that slaughter of clade 1 isolate A/Vietnam/1...

  10. Pathogenicity and transmission of H5 and H7 highly pathogenic avian influenza viruses in mallards

    USDA-ARS?s Scientific Manuscript database

    Wild aquatic birds have been associated with the intercontinental spread of H5 subtype highly pathogenic avian influenza (HPAI) viruses of the A/goose/Guangdong/1/96 (Gs/GD) lineage during 2005, 2010 and 2014, but dispersion by wild waterfowl has not been implicated with spread of other HPAI viruses...

  11. Pathogenesis and transmission studies: non-swine influenza A viruses in the swine host

    USDA-ARS?s Scientific Manuscript database

    Abstract Influenza A virus (IAV) causes disease in poultry, pigs, and people with wild waterfowl being the natural reservoir. IAV strains have been periodically transmitted between swine and humans in both directions and avian IAV have also sporadically infected swine. If an individual is infected w...

  12. Influenza virus respiratory infection and transmission following ocular inoculation in ferrets

    USDA-ARS?s Scientific Manuscript database

    While influenza viruses are a common respiratory pathogen, sporadic reports of conjunctivitis following human infection demonstrates the ability of this virus to cause disease outside of the respiratory tract. The ocular surface represents both a potential site of virus replication and a portal of e...

  13. Pathogenesis and transmission of highly pathogenic avian influenza H5Nx in swine

    USDA-ARS?s Scientific Manuscript database

    Introduction Influenza A viruses (IAV) periodically transmit between pigs, people, and birds. If two IAV strains infect the same host, genes can reassort to generate progeny virus with potential to be more infectious or avoid immunity. Pigs pose a risk for such reassortment. Highly pathogenic avian ...

  14. A Hypothesis: Supplementation with Mushroom-Derived Active Compound Modulates Immunity and Increases Survival in Response to Influenza Virus (H1N1) Infection

    PubMed Central

    Chunchao, Han; Guo, Jian-you

    2011-01-01

    We hypothesize that the mushroom-derived active compound may be a potential strategy for increasing survival in response to influenza virus (H1N1) infection through the stimulation of host innate immune response. The validity of the hypothesis can be tested by immune response to influenza infection as seen through survival percentage, virus clearance, weight loss, natural killer cell cytotoxicity, Tumor Necrosis Factor-α (TNF-α) and Interferon-gamma (IFN-γ) levels, lytic efficiency in the spleens of mice and inducible nitric oxide synthase mRNA expressions in RAW 264.7 murine macrophage cells. The hypothesis may improve people's quality of life, reduce the medical cost of our healthcare system and eliminate people's fears of influenza outbreak. PMID:21660092

  15. Predicting bat colony survival under controls targeting multiple transmission routes of white-nose syndrome.

    PubMed

    Meyer, A D; Stevens, D F; Blackwood, J C

    2016-11-21

    White-nose syndrome (WNS) is a lethal infection of bats caused by the psychrophilic fungus Pseudogymnoascus destructans (Pd). Since the first cases of WNS were documented in 2006, it is estimated that as many as 5.5million bats have succumbed in the United States-one of the fastest mammalian die-offs due to disease ever observed, and the first known sustained epizootic of bats. WNS is contagious between bats, and mounting evidence suggests that a persistent environmental reservoir of Pd plays a significant role in transmission as well. It is unclear, however, the relative contributions of bat-to-bat and environment-to-bat transmission to disease propagation within a colony. We analyze a mathematical model to investigate the consequences of both avenues of transmission on colony survival in addition to the efficacy of disease control strategies. Our model shows that selection of the most effective control strategies is highly dependent on the primary route of WNS transmission. Under all scenarios, however, generalized culling is ineffective and while targeted culling of infected bats may be effective under idealized conditions, it primarily has negative consequences. Thus, understanding the significance of environment-to-bat transmission is paramount to designing effective management plans. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Pathogenesis, Transmissibility, and Tropism of a Highly Pathogenic Avian Influenza A(H7N7) Virus Associated With Human Conjunctivitis in Italy, 2013.

    PubMed

    Belser, Jessica A; Creager, Hannah M; Zeng, Hui; Maines, Taronna R; Tumpey, Terrence M

    2017-09-15

    H7 subtype influenza viruses represent a persistent public health threat because of their continued detection in poultry and ability to cause human infection. An outbreak of highly pathogenic avian influenza H7N7 virus in Italy during 2013 resulted in 3 cases of human conjunctivitis. We determined the pathogenicity and transmissibility of influenza A/Italy/3/2013 virus in mouse and ferret models and examined the replication kinetics of this virus in several human epithelial cell types. The moderate virulence observed in mammalian models and the capacity for transmission in a direct contact model underscore the need for continued study of H7 subtype viruses. Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  17. Transmission by super-spreading event of pandemic A/H1N1 2009 influenza during road and train travel.

    PubMed

    Pestre, Vincent; Morel, Bruno; Encrenaz, Nathalie; Brunon, Amandine; Lucht, Frédéric; Pozzetto, Bruno; Berthelot, Philippe

    2012-03-01

    The investigation of clustered cases of pandemic A/H1N1 2009 influenza virus infection (21 children, 3 adults) during a summer camp, led to the identification of transportation as the circumstance of transmission. Results suggest that super-spreading of flu can occur in a confined space without sufficient air renewal.

  18. Contribution of Company Affiliation and Social Contacts to Risk Estimates of Between-Farm Transmission of Avian Influenza

    PubMed Central

    Leibler, Jessica H.; Carone, Marco; Silbergeld, Ellen K.

    2010-01-01

    Background Models of between-farm transmission of pathogens have identified service vehicles and social groups as risk factors mediating the spread of infection. Because of high levels of economic organization in much of the poultry industry, we examined the importance of company affiliation, as distinct from social contacts, in a model of the potential spread of avian influenza among broiler poultry farms in a poultry-dense region in the United States. The contribution of company affiliation to risk of between-farm disease transmission has not been previously studied. Methodology/Principal Findings We obtained data on the nature and frequency of business and social contacts through a national survey of broiler poultry growers in the United States. Daily rates of contact were estimated using Monte Carlo analysis. Stochastic modeling techniques were used to estimate the exposure risk posed by a single infectious farm to other farms in the region and relative risk of exposure for farms under different scenarios. The mean daily rate of vehicular contact was 0.82 vehicles/day. The magnitude of exposure risk ranged from <1% to 25% under varying parameters. Risk of between-farm transmission was largely driven by company affiliation, with farms in the same company group as the index farm facing as much as a 5-fold increase in risk compared to farms contracted with different companies. Employment of part-time workers contributed to significant increases in risk in most scenarios, notably for farms who hired day-laborers. Social visits were significantly less important in determining risk. Conclusions/Significance Biosecurity interventions should be based on information on industry structure and company affiliation, and include part-time workers as potentially unrecognized sources of viral transmission. Modeling efforts to understand pathogen transmission in the context of industrial food animal production should consider company affiliation in addition to geospatial

  19. Contribution of company affiliation and social contacts to risk estimates of between-farm transmission of avian influenza.

    PubMed

    Leibler, Jessica H; Carone, Marco; Silbergeld, Ellen K

    2010-03-25

    Models of between-farm transmission of pathogens have identified service vehicles and social groups as risk factors mediating the spread of infection. Because of high levels of economic organization in much of the poultry industry, we examined the importance of company affiliation, as distinct from social contacts, in a model of the potential spread of avian influenza among broiler poultry farms in a poultry-dense region in the United States. The contribution of company affiliation to risk of between-farm disease transmission has not been previously studied. We obtained data on the nature and frequency of business and social contacts through a national survey of broiler poultry growers in the United States. Daily rates of contact were estimated using Monte Carlo analysis. Stochastic modeling techniques were used to estimate the exposure risk posed by a single infectious farm to other farms in the region and relative risk of exposure for farms under different scenarios. The mean daily rate of vehicular contact was 0.82 vehicles/day. The magnitude of exposure risk ranged from <1% to 25% under varying parameters. Risk of between-farm transmission was largely driven by company affiliation, with farms in the same company group as the index farm facing as much as a 5-fold increase in risk compared to farms contracted with different companies. Employment of part-time workers contributed to significant increases in risk in most scenarios, notably for farms who hired day-laborers. Social visits were significantly less important in determining risk. Biosecurity interventions should be based on information on industry structure and company affiliation, and include part-time workers as potentially unrecognized sources of viral transmission. Modeling efforts to understand pathogen transmission in the context of industrial food animal production should consider company affiliation in addition to geospatial factors and pathogen characteristics. Restriction of social contacts

  20. Spatial Modeling of Wild Bird Risk Factors for Highly Pathogenic A(H5N1) Avian Influenza Virus Transmission.

    PubMed

    Prosser, Diann J; Hungerford, Laura L; Erwin, R Michael; Ottinger, Mary Ann; Takekawa, John Y; Newman, Scott H; Xiao, Xiangming; Ellis, Erle C

    2016-05-01

    One of the longest-persisting avian influenza viruses in history, highly pathogenic avian influenza virus (HPAIV) A(H5N1), continues to evolve after 18 yr, advancing the threat of a global pandemic. Wild waterfowl (family Anatidae) are reported as secondary transmitters of HPAIV and primary reservoirs for low-pathogenic avian influenza viruses, yet spatial inputs for disease risk modeling for this group have been lacking. Using geographic information software and Monte Carlo simulations, we developed geospatial indices of waterfowl abundance at 1 and 30 km resolutions and for the breeding and wintering seasons for China, the epicenter of H5N1. Two spatial layers were developed: cumulative waterfowl abundance (WAB), a measure of predicted abundance across species, and cumulative abundance weighted by H5N1 prevalence (WPR), whereby abundance for each species was adjusted based on prevalence values and then totaled across species. Spatial patterns of the model output differed between seasons, with higher WAB and WPR in the northern and western regions of China for the breeding season and in the southeast for the wintering season. Uncertainty measures indicated highest error in southeastern China for both WAB and WPR. We also explored the effect of resampling waterfowl layers from 1 to 30 km resolution for multiscale risk modeling. Results indicated low average difference (less than 0.16 and 0.01 standard deviations for WAB and WPR, respectively), with greatest differences in the north for the breeding season and southeast for the wintering season. This work provides the first geospatial models of waterfowl abundance available for China. The indices provide important inputs for modeling disease transmission risk at the interface of poultry and wild birds. These models are easily adaptable, have broad utility to both disease and conservation needs, and will be available to the scientific community for advanced modeling applications.

  1. Complete-proteome mapping of human influenza A adaptive mutations: implications for human transmissibility of zoonotic strains.

    PubMed

    Miotto, Olivo; Heiny, A T; Albrecht, Randy; García-Sastre, Adolfo; Tan, Tin Wee; August, J Thomas; Brusic, Vladimir

    2010-02-03

    There is widespread concern that H5N1 avian influenza A viruses will emerge as a pandemic threat, if they become capable of human-to-human (H2H) transmission. Avian strains lack this capability, which suggests that it requires important adaptive mutations. We performed a large-scale comparative analysis of proteins from avian and human strains, to produce a catalogue of mutations associated with H2H transmissibility, and to detect their presence in avian isolates. We constructed a dataset of influenza A protein sequences from 92,343 public database records. Human and avian sequence subsets were compared, using a method based on mutual information, to identify characteristic sites where human isolates present conserved mutations. The resulting catalogue comprises 68 characteristic sites in eight internal proteins. Subtype variability prevented the identification of adaptive mutations in the hemagglutinin and neuraminidase proteins. The high number of sites in the ribonucleoprotein complex suggests interdependence between mutations in multiple proteins. Characteristic sites are often clustered within known functional regions, suggesting their functional roles in cellular processes. By isolating and concatenating characteristic site residues, we defined adaptation signatures, which summarize the adaptive potential of specific isolates. Most adaptive mutations emerged within three decades after the 1918 pandemic, and have remained remarkably stable thereafter. Two lineages with stable internal protein constellations have circulated among humans without reassorting. On the contrary, H5N1 avian and swine viruses reassort frequently, causing both gains and losses of adaptive mutations. Human host adaptation appears to be complex and systemic, involving nearly all influenza proteins. Adaptation signatures suggest that the ability of H5N1 strains to infect humans is related to the presence of an unusually high number of adaptive mutations. However, these mutations appear

  2. Complete-Proteome Mapping of Human Influenza A Adaptive Mutations: Implications for Human Transmissibility of Zoonotic Strains

    PubMed Central

    Miotto, Olivo; Heiny, A. T.; Albrecht, Randy; García-Sastre, Adolfo; Tan, Tin Wee; August, J. Thomas; Brusic, Vladimir

    2010-01-01

    Background There is widespread concern that H5N1 avian influenza A viruses will emerge as a pandemic threat, if they become capable of human-to-human (H2H) transmission. Avian strains lack this capability, which suggests that it requires important adaptive mutations. We performed a large-scale comparative analysis of proteins from avian and human strains, to produce a catalogue of mutations associated with H2H transmissibility, and to detect their presence in avian isolates. Methodology/Principal Findings We constructed a dataset of influenza A protein sequences from 92,343 public database records. Human and avian sequence subsets were compared, using a method based on mutual information, to identify characteristic sites where human isolates present conserved mutations. The resulting catalogue comprises 68 characteristic sites in eight internal proteins. Subtype variability prevented the identification of adaptive mutations in the hemagglutinin and neuraminidase proteins. The high number of sites in the ribonucleoprotein complex suggests interdependence between mutations in multiple proteins. Characteristic sites are often clustered within known functional regions, suggesting their functional roles in cellular processes. By isolating and concatenating characteristic site residues, we defined adaptation signatures, which summarize the adaptive potential of specific isolates. Most adaptive mutations emerged within three decades after the 1918 pandemic, and have remained remarkably stable thereafter. Two lineages with stable internal protein constellations have circulated among humans without reassorting. On the contrary, H5N1 avian and swine viruses reassort frequently, causing both gains and losses of adaptive mutations. Conclusions Human host adaptation appears to be complex and systemic, involving nearly all influenza proteins. Adaptation signatures suggest that the ability of H5N1 strains to infect humans is related to the presence of an unusually high number of

  3. Treatment with the reactive oxygen species scavenger EUK-207 reduces lung damage and increases survival during 1918 influenza virus infection in mice.

    PubMed

    Kash, John C; Xiao, Yongli; Davis, A Sally; Walters, Kathie-Anne; Chertow, Daniel S; Easterbrook, Judith D; Dunfee, Rebecca L; Sandouk, Aline; Jagger, Brett W; Schwartzman, Louis M; Kuestner, Rolf E; Wehr, Nancy B; Huffman, Karl; Rosenthal, Rosalind A; Ozinsky, Adrian; Levine, Rodney L; Doctrow, Susan R; Taubenberger, Jeffery K

    2014-02-01

    The 1918 influenza pandemic caused over 40 million deaths worldwide, with 675,000 deaths in the United States alone. Studies in several experimental animal models showed that 1918 influenza virus infection resulted in severe lung pathology associated with dysregulated immune and cell death responses. To determine if reactive oxygen species produced by host inflammatory responses play a central role in promoting severity of lung pathology, we treated 1918 influenza virus-infected mice with the catalytic catalase/superoxide dismutase mimetic, salen-manganese complex EUK-207 beginning 3 days postinfection. Postexposure treatment of mice infected with a lethal dose of the 1918 influenza virus with EUK-207 resulted in significantly increased survival and reduced lung pathology without a reduction in viral titers. In vitro studies also showed that EUK-207 treatment did not affect 1918 influenza viral replication. Immunohistochemical analysis showed a reduction in the detection of the apoptosis marker cleaved caspase-3 and the oxidative stress marker 8-oxo-2'-deoxyguanosine in lungs of EUK-207-treated animals compared to vehicle controls. High-throughput sequencing and RNA expression microarray analysis revealed that treatment resulted in decreased expression of inflammatory response genes and increased lung metabolic and repair responses. These results directly demonstrate that 1918 influenza virus infection leads to an immunopathogenic immune response with excessive inflammatory and cell death responses that can be limited by treatment with the catalytic antioxidant EUK-207. Published by Elsevier Inc.

  4. Transmission of H7N9 Influenza Viruses with a Polymorphism at PB2 Residue 627 in Chickens and Ferrets

    PubMed Central

    Luk, Geraldine S. M.; Leung, Connie Y. H.; Sia, Sin Fun; Choy, Ka-Tim; Zhou, Jie; Ho, Candy C. K.; Cheung, Peter P. H.; Lee, Elaine F.; Wai, Chris K. L.; Li, Pamela C. H.; Ip, Sin-Ming; Poon, Leo L. M.; Lindsley, William G.

    2015-01-01

    ABSTRACT Poultry exposure is a major risk factor for human H7N9 zoonotic infections, for which the mode of transmission remains unclear. We studied the transmission of genetically related poultry and human H7N9 influenza viruses differing by four amino acids, including the host determinant PB2 residue 627. A/Silkie chicken/HK/1772/2014 (SCk1772) and A/HK/3263/14 (HK3263) replicated to comparable titers in chickens, with superior oropharyngeal over cloacal shedding; both viruses transmitted efficiently among chickens via direct contact but inefficiently via the airborne route. Interspecies transmission via the airborne route was observed for ferrets exposed to the SCk1772- or HK3263-infected chickens, while low numbers of copies of influenza viral genome were detected in the air, predominantly at particle sizes larger than 4 μm. In ferrets, the human isolate HK3263 replicated to higher titers and transmitted more efficiently via direct contact than SCk1772. We monitored “intrahost” and “interhost” adaptive changes at PB2 residue 627 during infection and transmission of the Sck1772 that carried E627 and HK3263 that carried V/K/E polymorphism at 60%, 20%, and 20%, respectively. For SCk1772, positive selection for K627 over E627 was observed in ferrets during the chicken-to-ferret or ferret-to-ferret transmission. For HK3263 that contained V/K/E polymorphism, mixed V627 and E627 genotypes were transmitted among chickens while either V627 or K627 was transmitted to ferrets with a narrow transmission bottleneck. Overall, our results suggest direct contact as the main mode for H7N9 transmission and identify the PB2-V627 genotype with uncompromised fitness and transmissibility in both avian and mammalian species. IMPORTANCE We studied the modes of H7N9 transmission, as this information is crucial for developing effective control measures for prevention. Using chicken (SCk1772) and human (HK3263) H7N9 isolates that differed by four amino acids, including the host

  5. Transmission of H7N9 Influenza Viruses with a Polymorphism at PB2 Residue 627 in Chickens and Ferrets.

    PubMed

    Luk, Geraldine S M; Leung, Connie Y H; Sia, Sin Fun; Choy, Ka-Tim; Zhou, Jie; Ho, Candy C K; Cheung, Peter P H; Lee, Elaine F; Wai, Chris K L; Li, Pamela C H; Ip, Sin-Ming; Poon, Leo L M; Lindsley, William G; Peiris, Malik; Yen, Hui-Ling

    2015-10-01

    Poultry exposure is a major risk factor for human H7N9 zoonotic infections, for which the mode of transmission remains unclear. We studied the transmission of genetically related poultry and human H7N9 influenza viruses differing by four amino acids, including the host determinant PB2 residue 627. A/Silkie chicken/HK/1772/2014 (SCk1772) and A/HK/3263/14 (HK3263) replicated to comparable titers in chickens, with superior oropharyngeal over cloacal shedding; both viruses transmitted efficiently among chickens via direct contact but inefficiently via the airborne route. Interspecies transmission via the airborne route was observed for ferrets exposed to the SCk1772- or HK3263-infected chickens, while low numbers of copies of influenza viral genome were detected in the air, predominantly at particle sizes larger than 4 μm. In ferrets, the human isolate HK3263 replicated to higher titers and transmitted more efficiently via direct contact than SCk1772. We monitored "intrahost" and "interhost" adaptive changes at PB2 residue 627 during infection and transmission of the Sck1772 that carried E627 and HK3263 that carried V/K/E polymorphism at 60%, 20%, and 20%, respectively. For SCk1772, positive selection for K627 over E627 was observed in ferrets during the chicken-to-ferret or ferret-to-ferret transmission. For HK3263 that contained V/K/E polymorphism, mixed V627 and E627 genotypes were transmitted among chickens while either V627 or K627 was transmitted to ferrets with a narrow transmission bottleneck. Overall, our results suggest direct contact as the main mode for H7N9 transmission and identify the PB2-V627 genotype with uncompromised fitness and transmissibility in both avian and mammalian species. We studied the modes of H7N9 transmission, as this information is crucial for developing effective control measures for prevention. Using chicken (SCk1772) and human (HK3263) H7N9 isolates that differed by four amino acids, including the host determinant PB2 residue 627

  6. Mechanism of Human Influenza Virus RNA Persistence and Virion Survival in Feces: Mucus Protects Virions From Acid and Digestive Juices.

    PubMed

    Hirose, Ryohei; Nakaya, Takaaki; Naito, Yuji; Daidoji, Tomo; Watanabe, Yohei; Yasuda, Hiroaki; Konishi, Hideyuki; Itoh, Yoshito

    2017-07-01

    Although viral RNA or infectious virions have been detected in the feces of individuals infected with human influenza A and B viruses (IAV/IBV), the mechanism of viral survival in the gastrointestinal tract remains unclear. We developed a model that attempts to recapitulate the conditions encountered by a swallowed virus. While IAV/IBV are vulnerable to simulated digestive juices (gastric acid and bile/pancreatic juice), highly viscous mucus protects viral RNA and virions, allowing the virus to retain its infectivity. Our results suggest that virions and RNA present in swallowed mucus are not inactivated or degraded by the gastrointestinal environment, allowing their detection in feces. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  7. Optimal design of studies of influenza transmission in households. II: comparison between cohort and case-ascertained studies.

    PubMed

    Klick, B; Nishiura, H; Leung, G M; Cowling, B J

    2014-04-01

    Both case-ascertained household studies, in which households are recruited after an 'index case' is identified, and household cohort studies, where a household is enrolled before the start of the epidemic, may be used to test and estimate the protective effect of interventions used to prevent influenza transmission. A simulation approach parameterized with empirical data from household studies was used to evaluate and compare the statistical power of four study designs: a cohort study with routine virological testing of household contacts of infected index case, a cohort study where only household contacts with acute respiratory illness (ARI) are sampled for virological testing, a case-ascertained study with routine virological testing of household contacts, and a case-ascertained study where only household contacts with ARI are sampled for virological testing. We found that a case-ascertained study with ARI-triggered testing would be the most powerful design while a cohort design only testing household contacts with ARI was the least powerful. Sensitivity analysis demonstrated that these conclusions varied by model parameters including the serial interval and the risk of influenza virus infection from outside the household.

  8. Using nonpharmaceutical interventions to prevent influenza transmission in elementary school children: parent and teacher perspectives.

    PubMed

    Stebbins, Samuel; Downs, Julie S; Vukotich, Charles J

    2009-01-01

    Schools act as "amplifying sites" for the spread of infectious diseases, outbreaks, and pandemics. This project assessed which nonpharmaceutical interventions (NPIs) are most acceptable to parents and teachers of school children in grades K-5 to K-8 in Pittsburgh public schools. During the spring of 2007, the Pittsburgh Influenza Prevention Project surveyed 134 teachers and 151 parents representing nine elementary schools regarding attitudes toward NPIs and their usage by adults and school children during seasonal influenza outbreaks. General etiquette practices such as covering coughs, handwashing, and using hand sanitizer were highly acceptable to both groups, while masks and gloves were not. The success of an NPI or a set of NPIs depends on both its efficacy and the feasibility of implementing it with relevant populations. If masks, gloves, and other more intrusive NPIs are to be used in community settings during a severe influenza season or pandemic, it is clear that there is significant preparatory work needed to increase acceptability on the part of the adults. Without such acceptance, it is highly unlikely that children and their supervising adults will participate.

  9. The impact of stratified immunity on the transmission dynamics of influenza.

    PubMed

    Yuan, Hsiang-Yu; Baguelin, Marc; Kwok, Kin O; Arinaminpathy, Nimalan; van Leeuwen, Edwin; Riley, Steven

    2017-03-12

    Although empirical studies show that protection against influenza infection in humans is closely related to antibody titres, influenza epidemics are often described under the assumption that individuals are either susceptible or not. Here we develop a model in which antibody titre classes are enumerated explicitly and mapped onto a variable scale of susceptibility in different age groups. Fitting only with pre- and post-wave serological data during 2009 pandemic in Hong Kong, we demonstrate that with stratified immunity, the timing and the magnitude of the epidemic dynamics can be reconstructed more accurately than is possible with binary seropositivity data. We also show that increased infectiousness of children relative to adults and age-specific mixing are required to reproduce age-specific seroprevalence observed in Hong Kong, while pre-existing immunity in the elderly is not. Overall, our results suggest that stratified immunity in an aged-structured heterogeneous population plays a significant role in determining the shape of influenza epidemics. Copyright © 2017. Published by Elsevier B.V.

  10. The ToxAvapA toxin-antitoxin locus contributes to the survival of nontypeable Haemophilus influenzae during infection.

    PubMed

    Ren, Dabin; Kordis, Alexis A; Sonenshine, Daniel E; Daines, Dayle A

    2014-01-01

    Nontypeable Haemophilus influenzae (NTHi) is an opportunistic pathogen that is a common cause of acute and recurrent mucosal infections. One uncharacterized NTHi toxin-antitoxin (TA) module, NTHI1912-1913, is a host inhibition of growth (higBA) homologue. We hypothesized that this locus, which we designated toxAvapA, contributed to NTHi survival during infection. We deleted toxAvapA and determined that growth of the mutant in defined media was not different from the parent strain. We tested the mutant for persistence during long-term in vitro co-culture with primary human respiratory tissues, which revealed that the ΔtoxAvapA mutant was attenuated for survival. We then performed challenge studies using the chinchilla model of otitis media and determined that mutant survival was also reduced in vivo. Following purification, the toxin exhibited ribonuclease activity on RNA in vitro, while the antitoxin did not. A microarray comparison of the transcriptome revealed that the tryptophan biosynthetic regulon was significantly repressed in the mutant compared to the parent strain. HPLC studies of conditioned medium confirmed that there was no significant difference in the concentration of tryptophan remaining in the supernatant, indicating that the uptake of tryptophan by the mutant was not affected. We conclude that the role of the NTHi toxAvapA TA module in persistence following stress is multifactorial and includes effects on essential metabolic pathways.

  11. From Exit to Entry: Long-term Survival and Transmission of Salmonella

    PubMed Central

    Waldner, Landon L.; MacKenzie, Keith D.; Köster,, Wolfgang; White, Aaron P.

    2012-01-01

    Salmonella spp. are a leading cause of human infectious disease worldwide and pose a serious health concern. While we have an improving understanding of pathogenesis and the host-pathogen interactions underlying the infection process, comparatively little is known about the survival of pathogenic Salmonella outside their hosts. This review focuses on three areas: (1) in vitro evidence that Salmonella spp. can survive for long periods of time under harsh conditions; (2) observations and conclusions about Salmonella persistence obtained from human outbreaks; and (3) new information revealed by genomic- and population-based studies of Salmonella and related enteric pathogens. We highlight the mechanisms of Salmonella persistence and transmission as an essential part of their lifecycle and a prerequisite for their evolutionary success as human pathogens. PMID:25436767

  12. Medfly Ceratitis capitata as Potential Vector for Fire Blight Pathogen Erwinia amylovora: Survival and Transmission.

    PubMed

    Ordax, Mónica; Piquer-Salcedo, Jaime E; Santander, Ricardo D; Sabater-Muñoz, Beatriz; Biosca, Elena G; López, María M; Marco-Noales, Ester

    2015-01-01

    Monitoring the ability of bacterial plant pathogens to survive in insects is required for elucidating unknown aspects of their epidemiology and for designing appropriate control strategies. Erwinia amylovora is a plant pathogenic bacterium that causes fire blight, a devastating disease in apple and pear commercial orchards. Studies on fire blight spread by insects have mainly focused on pollinating agents, such as honeybees. However, the Mediterranean fruit fly (medfly) Ceratitis capitata (Diptera: Tephritidae), one of the most damaging fruit pests worldwide, is also common in pome fruit orchards. The main objective of the study was to investigate whether E. amylovora can survive and be transmitted by the medfly. Our experimental results show: i) E. amylovora can survive for at least 8 days inside the digestive tract of the medfly and until 28 days on its external surface, and ii) medflies are able to transmit the bacteria from inoculated apples to both detached shoots and pear plants, being the pathogen recovered from lesions in both cases. This is the first report on E. amylovora internalization and survival in/on C. capitata, as well as the experimental transmission of the fire blight pathogen by this insect. Our results suggest that medfly can act as a potential vector for E. amylovora, and expand our knowledge on the possible role of these and other insects in its life cycle.

  13. Estimating transmission of avian influenza in wild birds from incomplete epizootic data: implications for surveillance and disease spreac

    USGS Publications Warehouse

    Viviane Henaux,; Jane Parmley,; Catherine Soos,; Samuel, Michael D.

    2013-01-01

    Synthesis and applications. Our study highlights the potential of integrating incomplete surveillance data with epizootic models to quantify disease transmission and immunity. This modelling approach provides an important tool to understand spatial and temporal epizootic dynamics and inform disease surveillance. Our findings suggest focusing highly pathogenic avian influenza virus (HPAIv) surveillance on postbreeding areas where mortality of immunologically naïve hatch-year birds is most likely to occur, and collecting serology to enhance HPAIv detection. Our modelling approach can integrate various types of disease data facilitating its use with data from other surveillance programs (as illustrated by the estimation of infection rate during an HPAIv outbreak in mute swansCygnus olor in Europe).

  14. Analysis of Influenza and RSV dynamics in the community using a ‘Local Transmission Zone’ approach

    PubMed Central

    Almogy, Gal; Stone, Lewi; Bernevig, B. Andrei; Wolf, Dana G.; Dorozko, Marina; Moses, Allon E.; Nir-Paz, Ran

    2017-01-01

    Understanding the dynamics of pathogen spread within urban areas is critical for the effective prevention and containment of communicable diseases. At these relatively small geographic scales, short-distance interactions and tightly knit sub-networks dominate the dynamics of pathogen transmission; yet, the effective boundaries of these micro-scale groups are generally not known and often ignored. Using clinical test results from hospital admitted patients we analyze the spatio-temporal distribution of Influenza Like Illness (ILI) in the city of Jerusalem over a period of three winter seasons. We demonstrate that this urban area is not a single, perfectly mixed ecology, but is in fact comprised of a set of more basic, relatively independent pathogen transmission units, which we term here Local Transmission Zones, LTZs. By identifying these LTZs, and using the dynamic pathogen-content information contained within them, we are able to differentiate between disease-causes at the individual patient level often with near-perfect predictive accuracy. PMID:28181554

  15. Analysis of Influenza and RSV dynamics in the community using a ‘Local Transmission Zone’ approach

    NASA Astrophysics Data System (ADS)

    Almogy, Gal; Stone, Lewi; Bernevig, B. Andrei; Wolf, Dana G.; Dorozko, Marina; Moses, Allon E.; Nir-Paz, Ran

    2017-02-01

    Understanding the dynamics of pathogen spread within urban areas is critical for the effective prevention and containment of communicable diseases. At these relatively small geographic scales, short-distance interactions and tightly knit sub-networks dominate the dynamics of pathogen transmission; yet, the effective boundaries of these micro-scale groups are generally not known and often ignored. Using clinical test results from hospital admitted patients we analyze the spatio-temporal distribution of Influenza Like Illness (ILI) in the city of Jerusalem over a period of three winter seasons. We demonstrate that this urban area is not a single, perfectly mixed ecology, but is in fact comprised of a set of more basic, relatively independent pathogen transmission units, which we term here Local Transmission Zones, LTZs. By identifying these LTZs, and using the dynamic pathogen-content information contained within them, we are able to differentiate between disease-causes at the individual patient level often with near-perfect predictive accuracy.

  16. A single vaccination of commercial broilers does not reduce transmission of H5N1 highly pathogenic avian influenza

    PubMed Central

    2011-01-01

    Vaccination of chickens has become routine practice in Asian countries in which H5N1 highly pathogenic avian influenza (HPAI) is endemically present. This mainly applies to layer and breeder flocks, but broilers are usually left unvaccinated. Here we investigate whether vaccination is able to reduce HPAI H5N1 virus transmission among broiler chickens. Four sets of experiments were carried out, each consisting of 22 replicate trials containing a pair of birds. Experiments 1-3 were carried out with four-week-old birds that were unvaccinated, and vaccinated at day 1 or at day 10 of age. Experiment 4 was carried out with unvaccinated day-old broiler chicks. One chicken in each trial was inoculated with H5N1 HPAI virus. One chicken in each trial was inoculated with virus. The course of the infection chain was monitored by serological analysis, and by virus isolation performed on tracheal and cloacal swabs. The analyses were based on a stochastic SEIR model using a Bayesian inferential framework. When inoculation was carried out at the 28th day of life, transmission was efficient in unvaccinated birds, and in birds vaccinated at first or tenth day of life. In these experiments estimates of the latent period (~1.0 day), infectious period (~3.3 days), and transmission rate parameter (~1.4 per day) were similar, as were estimates of the reproduction number (~4) and generation interval (~1.4 day). Transmission was significantly less efficient in unvaccinated chickens when inoculation was carried out on the first day of life. These results show that vaccination of broiler chickens does not reduce transmission, and suggest that this may be due to the interference of maternal immunity. PMID:21635732

  17. Survival of Highly Pathogenic Avian Influenza H5N1 Virus in Tissues Derived from Experimentally Infected Chickens.

    PubMed

    Yamamoto, Yu; Nakamura, Kikuyasu; Mase, Masaji

    2017-08-15

    Eurasian lineage highly pathogenic avian influenza (HPAI) H5N1 virus has been a severe threat to the poultry industry since its emergence in 1996. The carcass or tissues derived from infected birds may present the risk of the virus spreading to humans, animals, and the surrounding environment. In this study, we investigated the survival of the virus in feather, muscle, and liver tissues collected from six chickens (Gallus gallus) experimentally infected with HPAI H5N1 virus. The tissues were stored at +4°C or +20°C, and viral isolation was performed at different times for 360 days. The maximum periods for viral survival were observed in samples stored at +4°C in all tissue types and were 240 days in feather tissues, 160 days in muscle, and 20 days in liver. The viral infectivity at +20°C was maintained for a maximum of 30 days in the feather tissues, 20 days in muscle, and 3 days in liver. The viral inactivation rates partly overlapped in the feather and muscle tissues at the two temperatures. The virus was inactivated rapidly in the liver. Our experimental results indicate that the tissue type and temperature can greatly influence the survival of HPAI H5N1 virus in the tissues of infected chickens.IMPORTANCE Highly pathogenic avian influenza virus of the H5N1 subtype can cause massive losses of poultry, and people need to handle a large number of chicken carcasses contaminated with the virus at outbreak sites. This study evaluated how long the virus can keep its infectivity in the three types of tissues derived from chickens infected with the virus. Our experimental results indicate that the virus can survive in tissues for a specific period of time depending on the tissue type and temperature. Our results are valuable for better understanding of viral ecology in the environment and for reducing the risk of the virus spreading via bird tissues contaminated with the virus. Copyright © 2017 American Society for Microbiology.

  18. 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

  19. Variable effect of vaccination against highly pathogenic avian influenza (H7N7) virus on disease and transmission in pheasants and teals.

    PubMed

    van der Goot, Jeanet A; van Boven, Michiel; Koch, Guus; de Jong, Mart C M

    2007-11-28

    Highly pathogenic avian influenza viruses can affect many bird species, with disease symptoms ranging from severe morbidity and high mortality to mild transient illness. Much is known about infections in chickens, but for other captive birds the relations between disease symptoms, excretion patterns, and transmission, as well as the effect of vaccination on these relations are not clear. We report results from experimental transmission studies with a highly pathogenic H7N7 virus and two commonly kept bird species (ringed teals and golden pheasants). The results show that depending on the host species the virus can spread in unvaccinated birds with or without disease symptoms. Vaccination reduces disease symptoms markedly, but need not always reduce virus transmission. We discuss the implications for the control of highly pathogenic avian influenza.

  20. Impact of prior seasonal H3N2 influenza vaccination or infection on protection and transmission of emerging variants of influenza A(H3N2)v virus in ferrets.

    PubMed

    Houser, Katherine V; Pearce, Melissa B; Katz, Jacqueline M; Tumpey, Terrence M

    2013-12-01

    Influenza H3N2 A viruses continue to circulate in swine and occasionally infect humans, resulting in outbreaks of variant influenza H3N2 [A(H3N2)v] virus. It has been previously demonstrated in ferrets that A(H3N2)v viruses transmit as efficiently as seasonal influenza viruses, raising concern over the pandemic potential of these viruses. However, A(H3N2)v viruses have not acquired the ability to transmit efficiently among humans, which may be due in part to existing cross-reactive immunity to A(H3N2)v viruses. Although current seasonal H3N2 and A(H3N2)v viruses are antigenically distinct from one another, historical H3N2 viruses have some antigenic similarity to A(H3N2)v viruses and previous exposure to these viruses may provide a measure of immune protection sufficient to dampen A(H3N2)v virus transmission. Here, we evaluated whether prior seasonal H3N2 influenza virus vaccination or infection affects virus replication and transmission of A(H3N2)v virus in the ferret animal model. We found that the seasonal trivalent inactivated influenza virus vaccine (TIV) or a monovalent vaccine prepared from an antigenically related 1992 seasonal influenza H3N2 (A/Beijing/32/1992) virus failed to substantially reduce A(H3N2)v (A/Indiana/08/2011) virus shedding and subsequent transmission to naive hosts. Conversely, ferrets primed by seasonal H3N2 virus infection displayed reduced A(H3N2)v virus shedding following challenge, which blunted transmission to naive ferrets. A higher level of specific IgG and IgA antibody titers detected among infected versus vaccinated ferrets was associated with the degree of protection offered by seasonal H3N2 virus infection. The data demonstrate in ferrets that the efficiency of A(H3N2)v transmission is disrupted by preexisting immunity induced by seasonal H3N2 virus infection.

  1. Impact of Prior Seasonal H3N2 Influenza Vaccination or Infection on Protection and Transmission of Emerging Variants of Influenza A(H3N2)v Virus in Ferrets

    PubMed Central

    Houser, Katherine V.; Pearce, Melissa B.; Katz, Jacqueline M.

    2013-01-01

    Influenza H3N2 A viruses continue to circulate in swine and occasionally infect humans, resulting in outbreaks of variant influenza H3N2 [A(H3N2)v] virus. It has been previously demonstrated in ferrets that A(H3N2)v viruses transmit as efficiently as seasonal influenza viruses, raising concern over the pandemic potential of these viruses. However, A(H3N2)v viruses have not acquired the ability to transmit efficiently among humans, which may be due in part to existing cross-reactive immunity to A(H3N2)v viruses. Although current seasonal H3N2 and A(H3N2)v viruses are antigenically distinct from one another, historical H3N2 viruses have some antigenic similarity to A(H3N2)v viruses and previous exposure to these viruses may provide a measure of immune protection sufficient to dampen A(H3N2)v virus transmission. Here, we evaluated whether prior seasonal H3N2 influenza virus vaccination or infection affects virus replication and transmission of A(H3N2)v virus in the ferret animal model. We found that the seasonal trivalent inactivated influenza virus vaccine (TIV) or a monovalent vaccine prepared from an antigenically related 1992 seasonal influenza H3N2 (A/Beijing/32/1992) virus failed to substantially reduce A(H3N2)v (A/Indiana/08/2011) virus shedding and subsequent transmission to naive hosts. Conversely, ferrets primed by seasonal H3N2 virus infection displayed reduced A(H3N2)v virus shedding following challenge, which blunted transmission to naive ferrets. A higher level of specific IgG and IgA antibody titers detected among infected versus vaccinated ferrets was associated with the degree of protection offered by seasonal H3N2 virus infection. The data demonstrate in ferrets that the efficiency of A(H3N2)v transmission is disrupted by preexisting immunity induced by seasonal H3N2 virus infection. PMID:24089569

  2. Efficacy of inactivated and live-attenuated influenza virus vaccines in pigs against infection and transmission of emerging H3N2 similar to the 2011-2012 H3N2v

    USDA-ARS?s Scientific Manuscript database

    Vaccines provide a primary means to limit disease but may not be effective at blocking infection and pathogen transmission. The objective of the current study was to evaluate the efficacy of commercial inactivated swine influenza A virus (IAV) vaccines and experimental live-attenuated influenza viru...

  3. West Nile Virus in American White Pelican Chicks: Transmission, Immunity, and Survival

    PubMed Central

    Sovada, Marsha A.; Pietz, Pamela J.; Hofmeister, Erik K.; Bartos, Alisa J.

    2013-01-01

    West Nile virus (WNV) causes significant mortality of American White Pelican chicks at northern plains colonies. We tested oropharyngeal/cloacal swabs from moribund chicks for shed WNV. Such shedding could enable chick-to-chick transmission and help explain why WNV spreads rapidly in colonies. WNV was detected on swabs from 11% of chicks in 2006 and 52% of chicks in 2007; however, viral titers were low. Before onset of WNV mortality, we tested blood from < 3-week-old chicks for antibodies to WNV; 5% of chicks were seropositive, suggesting passive transfer of maternal antibodies. Among near-fledged chicks, 41% tested positive for anti-WNV antibodies, indicating that they survived infection. Among years and colonies, cumulative incidence of WNV in chicks varied from 28% to 81%, whereas the proportion of chicks surviving WNV (i.e., seropositive) was 64–75%. Our data revealed that WNV kills chicks that likely would fledge in the absence of WNV, that infection of chicks is pervasive, and that significant numbers of chicks survive infection. PMID:23530073

  4. West nile virus in American white pelican chicks: transmission, immunity, and survival

    USGS Publications Warehouse

    Sovada, Marsha A.; Pietz, Pamela J.; Hofmeister, Erik K.; Bartos, Alisa J.

    2013-01-01

    West Nile virus (WNV) causes significant mortality of American White Pelican chicks at northern plains colonies. We tested oropharyngeal/cloacal swabs from moribund chicks for shed WNV. Such shedding could enable chick-to-chick transmission and help explain why WNV spreads rapidly in colonies. WNV was detected on swabs from 11% of chicks in 2006 and 52% of chicks in 2007; however, viral titers were low. Before onset of WNV mortality, we tested blood from < 3-week-old chicks for antibodies to WNV; 5% of chicks were seropositive, suggesting passive transfer of maternal antibodies. Among near-fledged chicks, 41% tested positive for anti-WNV antibodies, indicating that they survived infection. Among years and colonies, cumulative incidence of WNV in chicks varied from 28% to 81%, whereas the proportion of chicks surviving WNV (i.e., seropositive) was 64–75%. Our data revealed that WNV kills chicks that likely would fledge in the absence of WNV, that infection of chicks is pervasive, and that significant numbers of chicks survive infection.

  5. West Nile virus in American White Pelican chicks: transmission, immunity, and survival.

    PubMed

    Sovada, Marsha A; Pietz, Pamela J; Hofmeister, Erik K; Bartos, Alisa J

    2013-06-01

    West Nile virus (WNV) causes significant mortality of American White Pelican chicks at northern plains colonies. We tested oropharyngeal/cloacal swabs from moribund chicks for shed WNV. Such shedding could enable chick-to-chick transmission and help explain why WNV spreads rapidly in colonies. WNV was detected on swabs from 11% of chicks in 2006 and 52% of chicks in 2007; however, viral titers were low. Before onset of WNV mortality, we tested blood from < 3-week-old chicks for antibodies to WNV; 5% of chicks were seropositive, suggesting passive transfer of maternal antibodies. Among near-fledged chicks, 41% tested positive for anti-WNV antibodies, indicating that they survived infection. Among years and colonies, cumulative incidence of WNV in chicks varied from 28% to 81%, whereas the proportion of chicks surviving WNV (i.e., seropositive) was 64-75%. Our data revealed that WNV kills chicks that likely would fledge in the absence of WNV, that infection of chicks is pervasive, and that significant numbers of chicks survive infection.

  6. Avian influenza virus (H5N1); effects of physico-chemical factors on its survival.

    PubMed

    Shahid, Muhammad Akbar; Abubakar, Muhammad; Hameed, Sajid; Hassan, Shamsul

    2009-03-28

    Present study was performed to determine the effects of physical and chemical agents on infective potential of highly pathogenic avian influenza (HPAI) H5N1 (local strain) virus recently isolated in Pakistan during 2006 outbreak. H5N1 virus having titer 10(8.3) ELD(50)/ml was mixed with sterilized peptone water to get final dilution of 4HA units and then exposed to physical (temperature, pH and ultraviolet light) and chemical (formalin, phenol crystals, iodine crystals, CID 20, virkon-S, zeptin 10%, KEPCIDE 300, KEPCIDE 400, lifebuoy, surf excel and caustic soda) agents. Harvested amnio-allantoic fluid (AAF) from embryonated chicken eggs inoculated with H5N1 treated virus (0.2 ml/egg) was subjected to haemagglutination (HA) and haemagglutination inhibition (HI) tests. H5N1 virus lost infectivity after 30 min at 56 degrees C, after 1 day at 28 degrees C but remained viable for more than 100 days at 4 degrees C. Acidic pH (1, 3) and basic pH (11, 13) were virucidal after 6 h contact time; however virus retained infectivity at pH 5 (18 h), 7 and 9 (more than 24 h). UV light was proved ineffectual in inactivating virus completely even after 60 min. Soap (lifebuoy), detergent (surf excel) and alkali (caustic soda) destroyed infectivity after 5 min at 0.1, 0.2 and 0.3% dilution. All commercially available disinfectants inactivated virus at recommended concentrations. Results of present study would be helpful in implementing bio-security measures at farms/hatcheries levels in the wake of avian influenza virus (AIV) outbreak.

  7. Avian influenza virus (H5N1); effects of physico-chemical factors on its survival

    PubMed Central

    Shahid, Muhammad Akbar; Abubakar, Muhammad; Hameed, Sajid; Hassan, Shamsul

    2009-01-01

    Present study was performed to determine the effects of physical and chemical agents on infective potential of highly pathogenic avian influenza (HPAI) H5N1 (local strain) virus recently isolated in Pakistan during 2006 outbreak. H5N1 virus having titer 108.3 ELD50/ml was mixed with sterilized peptone water to get final dilution of 4HA units and then exposed to physical (temperature, pH and ultraviolet light) and chemical (formalin, phenol crystals, iodine crystals, CID 20, virkon®-S, zeptin 10%, KEPCIDE 300, KEPCIDE 400, lifebuoy, surf excel and caustic soda) agents. Harvested amnio-allantoic fluid (AAF) from embryonated chicken eggs inoculated with H5N1 treated virus (0.2 ml/egg) was subjected to haemagglutination (HA) and haemagglutination inhibition (HI) tests. H5N1 virus lost infectivity after 30 min at 56°C, after 1 day at 28°C but remained viable for more than 100 days at 4°C. Acidic pH (1, 3) and basic pH (11, 13) were virucidal after 6 h contact time; however virus retained infectivity at pH 5 (18 h), 7 and 9 (more than 24 h). UV light was proved ineffectual in inactivating virus completely even after 60 min. Soap (lifebuoy®), detergent (surf excel®) and alkali (caustic soda) destroyed infectivity after 5 min at 0.1, 0.2 and 0.3% dilution. All commercially available disinfectants inactivated virus at recommended concentrations. Results of present study would be helpful in implementing bio-security measures at farms/hatcheries levels in the wake of avian influenza virus (AIV) outbreak. PMID:19327163

  8. D701N mutation in the PB2 protein contributes to the pathogenicity of H5N1 avian influenza viruses but not transmissibility in guinea pigs.

    PubMed

    Jiao, Peirong; Wei, Liangmeng; Song, Yafen; Cui, Jin; Song, Hui; Cao, Lan; Yuan, Runyu; Luo, Kaijian; Liao, Ming

    2014-01-01

    H5N1 highly pathogenic avian influenza virus (HPAIV) of clade 2.3.2 has been circulating in waterfowl in Southern China since 2003. Our previous studies showed that certain H5N1 HPAIV isolates within clade 2.3.2 from Southern China had high pathogenicity in different birds. Guinea pigs have been successfully used as models to evaluate the transmissibility of AIVs and other species of influenza viruses in mammalian hosts. However, few studies have reported pathogenicity and transmissibility of H5N1 HPAIVs of this clade in guinea pigs. In this study, we selected an H5N1 HPAIV isolate, A/duck/Guangdong/357/2008, to investigate the pathogenicity and transmissibility of the virus in guinea pigs. The virus had high pathogenicity in mice; additionally, it only replicated in some tissues of the guinea pigs without production of clinical signs, but was transmissible among guinea pigs. Interestingly, virus isolates from co-caged guinea pigs had the D701N mutation in the PB2 protein. These mutant viruses showed higher pathogenicity in mice and higher replication capability in guinea pigs but did not demonstrate enhanced the transmissibility among guinea pigs. These findings indicate the transmission of the H5N1 virus between mammals could induce virus mutations, and the mutant viruses might have higher pathogenicity in mammals without higher transmissibility. Therefore, the continued evaluation of the pathogenicity and transmissibility of avian influenza virus (AIVs) in mammals is critical to the understanding of the evolutionary characteristics of AIVs and the emergence of potential pandemic strains.

  9. Genetics, Receptor Binding, Replication, and Mammalian Transmission of H4 Avian Influenza Viruses Isolated from Live Poultry Markets in China

    PubMed Central

    Liang, Libin; Deng, Guohua; Shi, Jianzhong; Wang, Shuai; Zhang, Qianyi; Kong, Huihui; Gu, Chunyang; Guan, Yuntao; Suzuki, Yasuo; Li, Yanbing; Jiang, Yongping; Tian, Guobin; Liu, Liling

    2015-01-01

    ABSTRACT H4 avian influenza virus (AIV) is one of the most prevalent influenza virus subtypes in the world. However, whether H4 AIVs pose a threat to public health remains largely unclear. Here, we analyzed the phylogenetic relationships, receptor binding properties, replication, and transmissibility in mammals of H4 AIVs isolated from live poultry markets in China between 2009 and 2012. Genomic sequence analysis of 36 representative H4 viruses revealed 32 different genotypes, indicating that these viruses are undergoing complex and frequent reassortment events. All 32 viruses tested could replicate in the respiratory organs of infected mice without prior adaptation. Receptor binding analysis demonstrated that the H4 AIVs bound to α-2,6-linked glycans, although they retained the binding preference for α-2,3-linked glycans. When we tested the direct-contact transmission of 10 H4 viruses in guinea pigs, we found that three viruses did not transmit to any of the contact animals, one virus transmitted to one of three contact animals, and six viruses transmitted to all three contact animals. When we further tested the respiratory droplet transmissibility of four of the viruses that transmitted efficiently via direct contact, we found that three of them could transmit to one or two of the five exposed animals. Our study demonstrates that the current circulating H4 AIVs can infect, replicate in, and transmit to mammalian hosts, thereby posing a potential threat to human health. These findings emphasize the continual need for enhanced surveillance of H4 AIVs. IMPORTANCE Numerous surveillance studies have documented the wide distribution of H4 AIVs throughout the world, yet the biological properties of H4 viruses have not been well studied. In this study, we found that multiple genotypes of H4 viruses are cocirculating in the live poultry markets of China and that H4 viruses can replicate in mice, possess human-type receptor binding specificity, and transmit between

  10. Mammalian Pathogenesis and Transmission of H7N9 Influenza Viruses from Three Waves, 2013-2015

    PubMed Central

    Belser, Jessica A.; Creager, Hannah M.; Sun, Xiangjie; Gustin, Kortney M.; Jones, Tara; Shieh, Wun-Ju; Maines, Taronna R.

    2016-01-01

    ABSTRACT Three waves of human infection with H7N9 influenza viruses have concluded to date, but only viruses within the first wave (isolated between March and September 2013) have been extensively studied in mammalian models. While second- and third-wave viruses remain closely linked phylogenetically and antigenically, even subtle molecular changes can impart critical shifts in mammalian virulence. To determine if H7N9 viruses isolated from humans during 2013 to 2015 have maintained the phenotype first identified among 2013 isolates, we assessed the ability of first-, second-, and third-wave H7N9 viruses isolated from humans to cause disease in mice and ferrets and to transmit among ferrets. Similar to first-wave viruses, H7N9 viruses from 2013 to 2015 were highly infectious in mice, with lethality comparable to that of the well-studied A/Anhui/1/2013 virus. Second- and third-wave viruses caused moderate disease in ferrets, transmitted efficiently to cohoused, naive contact animals, and demonstrated limited transmissibility by respiratory droplets. All H7N9 viruses replicated efficiently in human bronchial epithelial cells, with subtle changes in pH fusion threshold identified between H7N9 viruses examined. Our results indicate that despite increased genetic diversity and geographical distribution since their initial detection in 2013, H7N9 viruses have maintained a pathogenic phenotype in mammals and continue to represent an immediate threat to public health. IMPORTANCE H7N9 influenza viruses, first isolated in 2013, continue to cause human infection and represent an ongoing public health threat. Now entering the fourth wave of human infection, H7N9 viruses continue to exhibit genetic diversity in avian hosts, necessitating continuous efforts to monitor their pandemic potential. However, viruses isolated post-2013 have not been extensively studied, limiting our understanding of potential changes in virus-host adaptation. In order to ensure that current research

  11. Mammalian Pathogenesis and Transmission of H7N9 Influenza Viruses from Three Waves, 2013-2015.

    PubMed

    Belser, Jessica A; Creager, Hannah M; Sun, Xiangjie; Gustin, Kortney M; Jones, Tara; Shieh, Wun-Ju; Maines, Taronna R; Tumpey, Terrence M

    2016-05-01

    Three waves of human infection with H7N9 influenza viruses have concluded to date, but only viruses within the first wave (isolated between March and September 2013) have been extensively studied in mammalian models. While second- and third-wave viruses remain closely linked phylogenetically and antigenically, even subtle molecular changes can impart critical shifts in mammalian virulence. To determine if H7N9 viruses isolated from humans during 2013 to 2015 have maintained the phenotype first identified among 2013 isolates, we assessed the ability of first-, second-, and third-wave H7N9 viruses isolated from humans to cause disease in mice and ferrets and to transmit among ferrets. Similar to first-wave viruses, H7N9 viruses from 2013 to 2015 were highly infectious in mice, with lethality comparable to that of the well-studied A/Anhui/1/2013 virus. Second- and third-wave viruses caused moderate disease in ferrets, transmitted efficiently to cohoused, naive contact animals, and demonstrated limited transmissibility by respiratory droplets. All H7N9 viruses replicated efficiently in human bronchial epithelial cells, with subtle changes in pH fusion threshold identified between H7N9 viruses examined. Our results indicate that despite increased genetic diversity and geographical distribution since their initial detection in 2013, H7N9 viruses have maintained a pathogenic phenotype in mammals and continue to represent an immediate threat to public health. H7N9 influenza viruses, first isolated in 2013, continue to cause human infection and represent an ongoing public health threat. Now entering the fourth wave of human infection, H7N9 viruses continue to exhibit genetic diversity in avian hosts, necessitating continuous efforts to monitor their pandemic potential. However, viruses isolated post-2013 have not been extensively studied, limiting our understanding of potential changes in virus-host adaptation. In order to ensure that current research with first-wave H7N9

  12. When fur and feather occur together: interclass transmission of avian influenza A virus from mammals to birds through common resources.

    PubMed

    Root, J Jeffrey; Shriner, Susan A; Ellis, Jeremy W; VanDalen, Kaci K; Sullivan, Heather J; Franklin, Alan B

    2015-09-24

    The potential role of wild mammals in avian influenza A virus (IAV) transmission cycles has received some attention in recent years and cases where birds have transmitted IAV to mammals have been documented. However, the contrasting cycle, wherein a mammal could transmit an avian IAV to birds, has been largely overlooked. We experimentally tested the abilities of two mammalian species to transmit avian IAV to mallards (Anas platyrhynchos) in simulated natural environments. Results suggested that striped skunks (Mephitis mephitis) can successfully transmit avian IAV to mallards through indirect contact with shared resources, as transmission was noted in 1 of 4 of the mallards tested. Cottontail rabbits (Sylvilagus sp.) exhibited a similar pattern, as one of five cottontail rabbits successfully transmitted IAV to a mallard, likely through environmental contamination. For each mammalian species tested, the mallards that became infected were those paired with the individual mammals with the lowest shedding levels but were anecdotally observed to be the most active animals. Mammals associated with and around poultry rearing facilities should be taken into consideration in biosecurity plans.

  13. When fur and feather occur together: interclass transmission of avian influenza A virus from mammals to birds through common resources

    PubMed Central

    Jeffrey Root, J.; Shriner, Susan A.; Ellis, Jeremy W.; VanDalen, Kaci K.; Sullivan, Heather J.; Franklin, Alan B.

    2015-01-01

    The potential role of wild mammals in avian influenza A virus (IAV) transmission cycles has received some attention in recent years and cases where birds have transmitted IAV to mammals have been documented. However, the contrasting cycle, wherein a mammal could transmit an avian IAV to birds, has been largely overlooked. We experimentally tested the abilities of two mammalian species to transmit avian IAV to mallards (Anas platyrhynchos) in simulated natural environments. Results suggested that striped skunks (Mephitis mephitis) can successfully transmit avian IAV to mallards through indirect contact with shared resources, as transmission was noted in 1 of 4 of the mallards tested. Cottontail rabbits (Sylvilagus sp.) exhibited a similar pattern, as one of five cottontail rabbits successfully transmitted IAV to a mallard, likely through environmental contamination. For each mammalian species tested, the mallards that became infected were those paired with the individual mammals with the lowest shedding levels but were anecdotally observed to be the most active animals. Mammals associated with and around poultry rearing facilities should be taken into consideration in biosecurity plans. PMID:26400374

  14. A Single-Amino-Acid Substitution at Position 225 in HA Alters the Transmissibility of Eurasian Avian-like H1N1 Swine Influenza Virus in Guinea Pigs.

    PubMed

    Wang, Zeng; Yang, Huanliang; Chen, Yan; Tao, Shiyu; Liu, Liling; Kong, Huihui; Ma, Shujie; Meng, Fei; Suzuki, Yasuo; Qiao, Chuanling; Chen, Hualan

    2017-08-16

    Efficient transmission from human to human is the prerequisite for an influenza virus to cause a pandemic; however, the molecular determinants of influenza virus transmission are still largely unknown. In this study, we explored the molecular basis for transmission of Eurasian avian-like H1N1 (EAH1N1) swine influenza viruses by comparing two viruses that are genetically similar but differ in their transmissibility in guinea pigs: the A/swine/Guangxi/18/2011 virus (GX/18) is highly transmissible by respiratory droplet in guinea pigs, whereas the A/swine/Heilongjiang/27/2012 virus (HLJ/27) does not transmit in this animal model. We used reverse genetics to generate a series of reassortants and mutants in the GX/18 background and tested their transmissibility in guinea pigs. We found that a single amino acid substitution of glycine (G) for glutamic acid (E) at position 225 (E225G) in the HA1 protein completely abolished the respiratory droplet transmission of GX/18, whereas the substitution of E for G at the same position (G225E) in HA1 enabled HLJ/27 to transmit in guinea pigs. We investigated the underlying mechanism and found that viruses bearing 225E in HA1 replicated more rapidly than viruses bearing 225G due to differences in assembly and budding efficiency. Our study indicates that the amino acid 225E in HA1 plays a key role in EAH1N1 swine influenza virus transmission and provides important information for evaluating the pandemic potential of field influenza strains.IMPORTANCE Efficient transmission among humans is a prerequisite for a novel influenza virus to cause a human pandemic. Transmissibility of influenza viruses is a polygenic trait, and understanding the genetic determinants for transmissibility will provide useful insights for evaluating the pandemic potential of influenza viruses in the field. Several amino acids in the hemagglutinin (HA) protein of influenza viruses have been shown to be important for transmissibility, usually by increasing virus

  15. Introduction of 2009 Pandemic Influenza A Virus Subtype H1N1 Into South Africa: Clinical Presentation, Epidemiology, and Transmissibility of the First 100 Cases

    PubMed Central

    Archer, Brett N.; Timothy, Geraldine A.; Cohen, Cheryl; Tempia, Stefano; Huma, Mmampedi; Blumberg, Lucille; Naidoo, Dhamari; Cengimbo, Ayanda; Schoub, Barry D.

    2012-01-01

    Background. We documented the introduction of 2009 pandemic influenza A virus subtype H1N1 (A[H1N1]pdm09) into South Africa and describe its clinical presentation, epidemiology, and transmissibility. Methods. We conducted a prospective descriptive study of the first 100 laboratory-confirmed cases of A(H1N1)pdm09 infections identified through active case finding and surveillance. Infected patients and the attending clinicians were interviewed, and close contacts were followed up to investigate household transmission. Findings. The first case was confirmed on 14 June 2009, and by 15 July 2009, 100 cases were diagnosed. Forty-two percent of patients reported international travel within 7 days prior to onset of illness. Patients ranged in age from 4 to 70 years (median age, 21.5 years). Seventeen percent of household contacts developed influenza-like illness, and 10% of household contacts had laboratory-confirmed A(H1N1)pdm09 infection. We found a mean serial interval (± SD) of 2.3 ± 1.3 days (range, 1–5 days) between successive laboratory-confirmed cases in the transmission chain. Conclusions. A(H1N1)pdm09 established itself rapidly in South Africa. Transmissibility of the virus was comparable to observations from outside of Africa and to seasonal influenza virus strains. PMID:23169962

  16. 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.

  17. The origin of novel avian influenza A (H7N9) and mutation dynamics for its human-to-human transmissible capacity.

    PubMed

    Peng, Jin; Yang, Hao; Jiang, Hua; Lin, Yi-xiao; Lu, Charles Damien; Xu, Ya-wei; Zeng, Jun

    2014-01-01

    In February 2013, H7N9 (A/H7N9/2013_China), a novel avian influenza virus, broke out in eastern China and caused human death. It is a global priority to discover its origin and the point in time at which it will become transmittable between humans. We present here an interdisciplinary method to track the origin of H7N9 virus in China and to establish an evolutionary dynamics model for its human-to-human transmission via mutations. After comparing influenza viruses from China since 1983, we established an A/H7N9/2013_China virus evolutionary phylogenetic tree and found that the human instances of virus infection were of avian origin and clustered into an independent line. Comparing hemagglutinin (HA) and neuraminidase (NA) gene sequences of A/H7N9/2013_China viruses with all human-to-human, avian, and swine influenza viruses in China in the past 30 years, we found that A/H7N9/2013_China viruses originated from Baer's Pochard H7N1 virus of Hu Nan Province 2010 (HA gene, EPI: 370846, similarity with H7N9 is 95.5%) and duck influenza viruses of Nanchang city 2000 (NA gene, EPI: 387555, similarity with H7N9 is 97%) through genetic re-assortment. HA and NA gene sequence comparison indicated that A/H7N9/2013_China virus was not similar to human-to-human transmittable influenza viruses. To simulate the evolution dynamics required for human-to-human transmission mutations of H7N9 virus, we employed the Markov model. The result of this calculation indicated that the virus would acquire properties for human-to-human transmission in 11.3 years (95% confidence interval (CI): 11.2-11.3, HA gene).

  18. Lack of transmission of a human influenza virus with avian receptor specificity between ferrets is not due to decreased virus shedding but rather a lower infectivity in vivo.

    PubMed

    Roberts, Kim L; Shelton, Holly; Scull, Margaret; Pickles, Raymond; Barclay, Wendy S

    2011-08-01

    Influenza virus attaches to host cells by sialic acid (SA). Human influenza viruses show preferential affinity for α2,6-linked SA, whereas avian influenza viruses bind α2,3-linked SA. In this study, mutation of the haemagglutinin receptor-binding site of a human H3N2 influenza A virus to switch binding to α2,3-linked SA did not eliminate infection of ferrets but prevented transmission, even in a co-housed model. The mutant virus was shed from the noses of ferrets directly inoculated with virus in the same amounts and for the same length of time as wild-type virus. Mutant virus infection was localized to the same anatomical regions of the upper respiratory tract of directly inoculated animals. Interestingly, wild-type virus was more readily neutralized than the mutant virus in vitro by ferret nasal washes containing mucus. Moreover after inoculation of equal doses, the mutant virus grew poorly in ex vivo ferret nasal turbinate tissue compared with wild-type virus. The dose of mutant virus required to establish infection in the directly inoculated ferrets was 40-fold higher than for wild-type virus. It was concluded that minimum infectious dose is a predictor of virus transmissibility and it is suggested that, as virus passes from one host to another through stringent environmental conditions, viruses with a preference for α2,3-linked SA are unlikely to inoculate a new mammalian host in sufficient quantities to initiate a productive infection.

  19. Equine influenza virus.

    PubMed

    Landolt, Gabriele A

    2014-12-01

    For decades the horse has been viewed as an isolated or "dead-end" host for influenza A viruses, with equine influenza virus being considered as relatively stable genetically. Although equine influenza viruses are genetically more stable than those of human lineage, they are by no means in evolutionary stasis. Moreover, recent transmission of equine-lineage influenza viruses to dogs also challenges the horse's status as a dead-end host. This article reviews recent developments in the epidemiology and evolution of equine influenza virus. In addition, the clinical presentation of equine influenza infection, diagnostic techniques, and vaccine recommendations are briefly summarized.

  20. Modeling highly pathogenic avian influenza transmission in wild birds and poultry in West Bengal, India.

    PubMed

    Pandit, Pranav S; Bunn, David A; Pande, Satish A; Aly, Sharif S

    2013-01-01

    Wild birds are suspected to have played a role in highly pathogenic avian influenza (HPAI) H5N1 outbreaks in West Bengal. Cluster analysis showed that H5N1 was introduced in West Bengal at least 3 times between 2008 and 2010. We simulated the introduction of H5N1 by wild birds and their contact with poultry through a stochastic continuous-time mathematical model. Results showed that reducing contact between wild birds and domestic poultry, and increasing the culling rate of infected domestic poultry communities will reduce the probability of outbreaks. Poultry communities that shared habitat with wild birds or those indistricts with previous outbreaks were more likely to suffer an outbreak. These results indicate that wild birds can introduce HPAI to domestic poultry and that limiting their contact at shared habitats together with swift culling of infected domestic poultry can greatly reduce the likelihood of HPAI outbreaks.

  1. Modeling highly pathogenic avian influenza transmission in wild birds and poultry in West Bengal, India

    PubMed Central

    Pandit, Pranav S.; Bunn, David A.; Pande, Satish A.; Aly, Sharif S.

    2013-01-01

    Wild birds are suspected to have played a role in highly pathogenic avian influenza (HPAI) H5N1 outbreaks in West Bengal. Cluster analysis showed that H5N1 was introduced in West Bengal at least 3 times between 2008 and 2010. We simulated the introduction of H5N1 by wild birds and their contact with poultry through a stochastic continuous-time mathematical model. Results showed that reducing contact between wild birds and domestic poultry, and increasing the culling rate of infected domestic poultry communities will reduce the probability of outbreaks. Poultry communities that shared habitat with wild birds or those indistricts with previous outbreaks were more likely to suffer an outbreak. These results indicate that wild birds can introduce HPAI to domestic poultry and that limiting their contact at shared habitats together with swift culling of infected domestic poultry can greatly reduce the likelihood of HPAI outbreaks. PMID:23846233

  2. Frequent inter-species transmission and geographic subdivision in avian influenza viruses from wild birds.

    PubMed

    Chen, Rubing; Holmes, Edward C

    2009-01-05

    Revealing the factors that shape the genetic structure of avian influenza viruses (AIVs) in wild bird populations is essential to understanding their evolution. However, the relationship between epidemiological dynamics and patterns of genetic diversity in AIV is not well understood, especially at the continental scale. To address this question, we undertook a phylogeographic analysis of complete genome sequences of AIV sampled from wild birds in North America. In particular, we asked whether host species, geographic location or sampling time played the major role in shaping patterns of viral genetic diversity. Strikingly, our analysis revealed no strong species effect, yet a significant viral clustering by time and place of sampling, as well as the circulation of multiple viral lineages in single locations. These results suggest that AIVs can readily infect many of the bird species that share breeding/feeding areas.

  3. Bayesian uncertainty quantification for transmissibility of influenza, norovirus and Ebola using information geometry

    PubMed Central

    Ford, Ashley; Lan, Shiwei; Bilson, Samuel; Buckingham-Jeffery, Elizabeth; Girolami, Mark

    2016-01-01

    Infectious diseases exert a large and in many contexts growing burden on human health, but violate most of the assumptions of classical epidemiological statistics and hence require a mathematically sophisticated approach. Viral shedding data are collected during human studies—either where volunteers are infected with a disease or where existing cases are recruited—in which the levels of live virus produced over time are measured. These have traditionally been difficult to analyse due to strong, complex correlations between parameters. Here, we show how a Bayesian approach to the inverse problem together with modern Markov chain Monte Carlo algorithms based on information geometry can overcome these difficulties and yield insights into the disease dynamics of two of the most prevalent human pathogens—influenza and norovirus—as well as Ebola virus disease. PMID:27558850

  4. Continuing evolution and interspecies transmission of influenza viruses in live bird markets in Korea.

    PubMed

    Lee, Hyun-Jeong; Kwon, Ji-Sun; Lee, Dong-Hun; Lee, Yu-Na; Youn, Ha-Na; Lee, Youn-Jeong; Kim, Min-Chul; Jeong, Ok-Mi; Kang, Hyun-Mi; Kwon, Jun-Hun; Lee, Joong-Bok; Park, Seung-Yong; Choi, In-Soo; Song, Chang-Seon

    2010-03-01

    Live bird markets (LBMs) provide an ideal environment for the evolution and interspecies transfer of avian influenza viruses (AIVs). In this study, we analyzed AIVs present in LBMs in Korea during the winter seasons of 2006-08. Sixty-five AIVs that belong to four hemagglutination (HA) subtypes ofAIV (H3, H4, H6, and H9) were isolated from 644 pooled tissue or swab samples collected in LBMs. Most H9 subtypes of AIVs were isolated from Galliformes (chickens, silky fowls, pheasants, and guinea fowls), and other subtypes were isolated from Anseriformes (Pekin ducks and mallards). In addition, we obtained a single H3N2 virus from nasal swabs of dogs sold in LBMs, and the virus was genetically identical to the canine influenza virus (CIV) isolated from pet dogs in Korea. Phylogenetic analysis suggests that the Korean H9N2 viruses prevalent in chickens have provided their gene segments to AIVs circulating in ducks. These gene transfers facilitated reassortment events among AIVs and likely generated the ancestors of CIV in Korea. An animal challenge study using chickens, quail, mice, and dogs had shown that the H4 and H6 subtypes could replicate in mice and that some H4 and H6 viruses could replicate in chickens without preadaptation. In addition, two H3 subtype viruses (H3N2 and H3N8) induced interstitial pneumonia that accompanied clinical signs and seroconversion in dogs. Our findings indicate that the newly evolved AIVs have been continuously generated by reassortment in ducks, and these reassortments could result in expanding the host range of AIVs.

  5. Poultry food products--a source of avian influenza virus transmission to humans?

    PubMed

    Harder, T C; Buda, S; Hengel, H; Beer, M; Mettenleiter, T C

    2016-02-01

    Global human mobility and intercontinental connectivity, expansion of livestock production and encroachment of wildlife habitats by invasive agricultural land use contribute to shape the complexity of influenza epidemiology. The OneHealth approach integrates these and further elements into considerations to improve disease control and prevention. Food of animal origin for human consumption is another integral aspect; if produced from infected livestock such items may act as vehicles of spread of animal pathogens, and, in case of zoonotic agents, as a potential human health hazard. Notifiable zoonotic avian influenza viruses (AIV) have become entrenched in poultry populations in several Asian and northern African countries since 2003. Highly pathogenic (HP) AIV (e.g. H5N1) cause extensive poultry mortality and severe economic losses. HPAIV and low pathogenic AIV (e.g. H7N9) with zoonotic propensities pose risks for human health. More than 1500 human cases of AIV infection have been reported, mainly from regions with endemically infected poultry. Intense human exposure to AIV-infected poultry, e.g. during rearing, slaughtering or processing of poultry, is a major risk factor for acquiring AIV infection. In contrast, human infections through consumption of AIV-contaminated food have not been substantiated. Heating poultry products according to kitchen standards (core temperatures ≥70°C, ≥10 s) rapidly inactivates AIV infectivity and renders fully cooked products safe. Nevertheless, concerted efforts must ensure that poultry products potentially contaminated with zoonotic AIV do not reach the food chain. Stringent and sustained OneHealth measures are required to better control and eventually eradicate, HPAIV from endemic regions. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  6. Pathogenesis and Transmission Assessments of Two H7N8 Influenza A Viruses Recently Isolated from Turkey Farms in Indiana Using Mouse and Ferret Models.

    PubMed

    Sun, Xiangjie; Belser, Jessica A; Pulit-Penaloza, Joanna A; Zeng, Hui; Lewis, Amanda; Shieh, Wun-Ju; Tumpey, Terrence M; Maines, Taronna R

    2016-12-01

    Avian influenza A H7 viruses have caused multiple outbreaks in domestic poultry throughout North America, resulting in occasional infections of humans in close contact with affected birds. In early 2016, the presence of H7N8 highly pathogenic avian influenza (HPAI) viruses and closely related H7N8 low-pathogenic avian influenza (LPAI) viruses was confirmed in commercial turkey farms in Indiana. These H7N8 viruses represent the first isolation of this subtype in domestic poultry in North America, and their virulence in mammalian hosts and the potential risk for human infection are largely unknown. In this study, we assessed the ability of H7N8 HPAI and LPAI viruses to replicate in vitro in human airway cells and in vivo in mouse and ferret models. Both H7N8 viruses replicated efficiently in vitro and in vivo, but they exhibited substantial differences in disease severity in mammals. In mice, while the H7N8 LPAI virus largely remained avirulent, the H7N8 HPAI virus exhibited greater infectivity, virulence, and lethality. Both H7N8 viruses replicated similarly in ferrets, but only the H7N8 HPAI virus caused moderate weight loss, lethargy, and mortality. The H7N8 LPAI virus displayed limited transmissibility in ferrets placed in direct contact with an inoculated animal, while no transmission of H7N8 HPAI virus was detected. Our results indicate that the H7N8 avian influenza viruses from Indiana are able to replicate in mammals and cause severe disease but with limited transmission. The recent appearance of H7N8 viruses in domestic poultry highlights the need for continued influenza surveillance in wild birds and close monitoring of the potential risk to human health. H7 influenza viruses circulate in wild birds in the United States, but when the virus emerges in domestic poultry populations, the frequency of human exposure and the potential for human infections increases. An H7N8 highly pathogenic avian influenza (HPAI) virus and an H7N8 low-pathogenic avian influenza

  7. Pathogenesis and Transmission Assessments of Two H7N8 Influenza A Viruses Recently Isolated from Turkey Farms in Indiana Using Mouse and Ferret Models

    PubMed Central

    Sun, Xiangjie; Belser, Jessica A.; Pulit-Penaloza, Joanna A.; Zeng, Hui; Lewis, Amanda; Shieh, Wun-Ju; Tumpey, Terrence M.

    2016-01-01

    ABSTRACT Avian influenza A H7 viruses have caused multiple outbreaks in domestic poultry throughout North America, resulting in occasional infections of humans in close contact with affected birds. In early 2016, the presence of H7N8 highly pathogenic avian influenza (HPAI) viruses and closely related H7N8 low-pathogenic avian influenza (LPAI) viruses was confirmed in commercial turkey farms in Indiana. These H7N8 viruses represent the first isolation of this subtype in domestic poultry in North America, and their virulence in mammalian hosts and the potential risk for human infection are largely unknown. In this study, we assessed the ability of H7N8 HPAI and LPAI viruses to replicate in vitro in human airway cells and in vivo in mouse and ferret models. Both H7N8 viruses replicated efficiently in vitro and in vivo, but they exhibited substantial differences in disease severity in mammals. In mice, while the H7N8 LPAI virus largely remained avirulent, the H7N8 HPAI virus exhibited greater infectivity, virulence, and lethality. Both H7N8 viruses replicated similarly in ferrets, but only the H7N8 HPAI virus caused moderate weight loss, lethargy, and mortality. The H7N8 LPAI virus displayed limited transmissibility in ferrets placed in direct contact with an inoculated animal, while no transmission of H7N8 HPAI virus was detected. Our results indicate that the H7N8 avian influenza viruses from Indiana are able to replicate in mammals and cause severe disease but with limited transmission. The recent appearance of H7N8 viruses in domestic poultry highlights the need for continued influenza surveillance in wild birds and close monitoring of the potential risk to human health. IMPORTANCE H7 influenza viruses circulate in wild birds in the United States, but when the virus emerges in domestic poultry populations, the frequency of human exposure and the potential for human infections increases. An H7N8 highly pathogenic avian influenza (HPAI) virus and an H7N8 low

  8. Pathogenicity and transmission of triple reassortant H3N2 swine influenza A viruses is attenuated following Turkey embryo propagation.

    PubMed

    Raghunath, Shobana; Pudupakam, Raghavendra Sumanth; Deventhiran, Jagadeeswaran; Tevatia, Rahul; Leroith, Tanya

    2017-03-01

    Genetic lineages of swine influenza A viruses (SIVs) have recently been established in Turkeys in the United States. To identify molecular determinants that are involved in virulence and transmission of SIVs to Turkeys, we sequentially passaged two triple reassortant H3N2 SIV isolates from Minnesota in ten day old specific-pathogen free (SPF) Turkey embryos and tested them in seven-day old Turkey poults. We found that SIV replication in Turkey embryos led to minimal mutations in and around the receptor binding and antigenic sites of the HA molecule, while other gene segments were unchanged. The predominant changes associated with Turkey embryo passage were A223V, V226A and T248I mutations in the receptor-binding and glycosylation sites of the HA molecule. Furthermore, Turkey embryo propagation altered receptor specificity in SIV strain 07-1145. Embryo passaged 07-1145 virus showed a decrease in α2, 6 sialic acid receptor binding compared to the wild type virus. Intranasal infection of wild type SIVs in one-week-old Turkey poults resulted in persistent diarrhea and all the infected birds seroconverted at ten days post infection. The 07-1145 wild type virus also transmitted to age matched in-contact birds introduced one-day post infection. Turkeys infected with embryo passaged viruses displayed no clinical signs and were not transmitted to in-contact poults. Our results suggest that Turkey embryo propagation attenuates recent TR SIVs for infectivity and transmission in one week old Turkeys. Our findings will have important implications in identifying molecular determinants that control the transmission and virulence of TR SIVs in Turkeys and other species. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Enhanced Mammalian Transmissibility of Seasonal Influenza A/H1N1 Viruses Encoding an Oseltamivir-Resistant Neuraminidase

    PubMed Central

    Rahmat, Saad; Pica, Natalie

    2012-01-01

    Between 2007 and 2009, oseltamivir resistance developed among seasonal influenza A/H1N1 (sH1N1) virus isolates at an exponential rate, without a corresponding increase in oseltamivir usage. We hypothesized that the oseltamivir-resistant neuraminidase (NA), in addition to being relatively insusceptible to the antiviral effect of oseltamivir, might confer an additional fitness advantage on these viruses by enhancing their transmission efficiency among humans. Here we demonstrate that an oseltamivir-resistant clinical isolate, an A/Brisbane/59/2007(H1N1)-like virus isolated in New York State in 2008, transmits more efficiently among guinea pigs than does a highly similar, contemporaneous oseltamivir-sensitive isolate. With reverse genetics reassortants and point mutants of the two clinical isolates, we further show that expression of the oseltamivir-resistant NA in the context of viral proteins from the oseltamivir-sensitive virus (a 7:1 reassortant) is sufficient to enhance transmissibility. In the guinea pig model, the NA is the critical determinant of transmission efficiency between oseltamivir-sensitive and -resistant Brisbane/59-like sH1N1 viruses, independent of concurrent drift mutations that occurred in other gene products. Our data suggest that the oseltamivir-resistant NA (specifically, one or both of the companion mutations, H275Y and D354G) may have allowed resistant Brisbane/59-like viruses to outtransmit sensitive isolates. These data provide in vivo evidence of an evolutionary mechanism that would explain the rapidity with which oseltamivir resistance achieved fixation among sH1N1 isolates in the human reservoir. PMID:22532693

  10. Blow Flies Were One of the Possible Candidates for Transmission of Highly Pathogenic H5N1 Avian Influenza Virus during the 2004 Outbreaks in Japan

    PubMed Central

    Sawabe, Kyoko; Hoshino, Keita; Isawa, Haruhiko; Sasaki, Toshinori; Kim, Kyeong Soon; Hayashi, Toshihiko; Tsuda, Yoshio; Kurahashi, Hiromu; Kobayashi, Mutsuo

    2011-01-01

    The 2003-2004 H5N1 highly pathogenic avian influenza (HPAI) outbreaks in Japan were the first such outbreaks in 79 years in Japan. Epidemic outbreaks have been occurring in Southeast Asia, with the most recent in 2010. Knowledge of the transmission route responsible for the HPAI outbreaks in these countries remains elusive. Our studies strongly suggested that field and laboratory studies focusing on mechanical transmission by blow flies should be considered to control H5N1 avian influenza outbreaks, in particular in epidemic areas, where there are high densities of different fly species throughout the year. In this paper, we review these field and laboratory entomological studies and discuss the possibility of blow flies transmitting H5N1 viruses. PMID:23074659

  11. Impact of live poultry market closure in reducing bird-to-human transmission of avian influenza A(H7N9) virus: an ecological study

    PubMed Central

    Yu, Hongjie; Wu, Joseph T.; Cowling, Benjamin J.; Liao, Qiaohong; Fang, Vicky J.; Zhou, Sheng; Wu, Peng; Zhou, Hang; Lau, Eric H. Y.; Guo, Danhuai; Ni, Michael Y.; Peng, Zhibin; Feng, Luzhao; Jiang, Hui; Luo, Huiming; Li, Qun; Feng, Zijian; Wang, Yu; Yang, Weizhong; Leung, Gabriel M.

    2014-01-01

    Background A novel influenza A(H7N9) virus has emerged in China during the past few months. Inter-species zoonotic transmission appears to be the predominant route of spread. Live poultry markets (LPMs) in the major cities of Shanghai, Hangzhou, Huzhou and Nanjing, where the majority of cases have occurred, were swiftly closed as a precautionary public health measure. Our objective was to quantify the impact of LPM closure in reducing bird-to-human transmission of avian influenza A(H7N9) virus. Methods We used data on the illness onset dates and geographical locations of laboratory-confirmed influenza A(H7N9) cases that were officially announced by 7 June 2013. We constructed a statistical model to explain the patterns in incident cases reported in each city based on the assumption of a constant force of infection prior to closure, and a different constant force of infection after closure. We fitted the model using Markov chain Monte Carlo methods. Findings There were 85 confirmed influenza A(H7N9) cases in Shanghai, Hangzhou, Huzhou and Nanjing out of a total of 130 confirmed cases in mainland China by 7 June 2013. Closure of LPMs in those four cities reduced the risk of human infections by 97%–99% (range 68%–100%) in each city. Given that LPMs were the predominant source of influenza A(H7N9) exposure in those locations, we estimated the mean incubation period to be 3.3 days. Interpretation LPM closures were extremely effective in controlling human risk of influenza A(H7N9). If the influenza A(H7N9) epizootic/epidemic continues, LPM closure should be sustained in at-risk areas and implemented in any urban areas where influenza A(H7N9) reappears in future. In the longer term, evidence-based discussions and deliberations about the role of central slaughtering of all live poultry should be renewed. Funding Ministry of Science and Technology, China; Research Fund for the Control of Infectious Disease and University Grants Committee, Hong Kong Special

  12. Influenza Transmission in the Mother-Infant Dyad Leads to Severe Disease, Mammary Gland Infection, and Pathogenesis by Regulating Host Responses.

    PubMed

    Paquette, Stéphane G; Banner, David; Huang, Stephen S H; Almansa, Raquel; Leon, Alberto; Xu, Luoling; Bartoszko, Jessica; Kelvin, David J; Kelvin, Alyson A

    2015-10-01

    Seasonal influenza viruses are typically restricted to the human upper respiratory tract whereas influenza viruses with greater pathogenic potential often also target extra-pulmonary organs. Infants, pregnant women, and breastfeeding mothers are highly susceptible to severe respiratory disease following influenza virus infection but the mechanisms of disease severity in the mother-infant dyad are poorly understood. Here we investigated 2009 H1N1 influenza virus infection and transmission in breastfeeding mothers and infants utilizing our developed infant-mother ferret influenza model. Infants acquired severe disease and mortality following infection. Transmission of the virus from infants to mother ferrets led to infection in the lungs and mother mortality. Live virus was also found in mammary gland tissue and expressed milk of the mothers which eventually led to milk cessation. Histopathology showed destruction of acini glandular architecture with the absence of milk. The virus was localized in mammary epithelial cells of positive glands. To understand the molecular mechanisms of mammary gland infection, we performed global transcript analysis which showed downregulation of milk production genes such as Prolactin and increased breast involution pathways indicated by a STAT5 to STAT3 signaling shift. Genes associated with cancer development were also significantly increased including JUN, FOS and M2 macrophage markers. Immune responses within the mammary gland were characterized by decreased lymphocyte-associated genes CD3e, IL2Ra, CD4 with IL1β upregulation. Direct inoculation of H1N1 into the mammary gland led to infant respiratory infection and infant mortality suggesting the influenza virus was able to replicate in mammary tissue and transmission is possible through breastfeeding. In vitro infection studies with human breast cells showed susceptibility to H1N1 virus infection. Together, we have shown that the host-pathogen interactions of influenza virus

  13. Influenza Transmission in the Mother-Infant Dyad Leads to Severe Disease, Mammary Gland Infection, and Pathogenesis by Regulating Host Responses

    PubMed Central

    Huang, Stephen S. H.; Almansa, Raquel; Leon, Alberto; Xu, Luoling; Bartoszko, Jessica; Kelvin, David J.; Kelvin, Alyson A.

    2015-01-01

    Seasonal influenza viruses are typically restricted to the human upper respiratory tract whereas influenza viruses with greater pathogenic potential often also target extra-pulmonary organs. Infants, pregnant women, and breastfeeding mothers are highly susceptible to severe respiratory disease following influenza virus infection but the mechanisms of disease severity in the mother-infant dyad are poorly understood. Here we investigated 2009 H1N1 influenza virus infection and transmission in breastfeeding mothers and infants utilizing our developed infant-mother ferret influenza model. Infants acquired severe disease and mortality following infection. Transmission of the virus from infants to mother ferrets led to infection in the lungs and mother mortality. Live virus was also found in mammary gland tissue and expressed milk of the mothers which eventually led to milk cessation. Histopathology showed destruction of acini glandular architecture with the absence of milk. The virus was localized in mammary epithelial cells of positive glands. To understand the molecular mechanisms of mammary gland infection, we performed global transcript analysis which showed downregulation of milk production genes such as Prolactin and increased breast involution pathways indicated by a STAT5 to STAT3 signaling shift. Genes associated with cancer development were also significantly increased including JUN, FOS and M2 macrophage markers. Immune responses within the mammary gland were characterized by decreased lymphocyte-associated genes CD3e, IL2Ra, CD4 with IL1β upregulation. Direct inoculation of H1N1 into the mammary gland led to infant respiratory infection and infant mortality suggesting the influenza virus was able to replicate in mammary tissue and transmission is possible through breastfeeding. In vitro infection studies with human breast cells showed susceptibility to H1N1 virus infection. Together, we have shown that the host-pathogen interactions of influenza virus

  14. Climate change and avian influenza

    PubMed Central

    Slingenbergh, J.; Xiao, X.

    2009-01-01

    Summary This paper discusses impacts of climate change on the ecology of avian influenza viruses (AI viruses), which presumably co-evolved with migratory water birds, with virus also persisting outside the host in subarctic water bodies. Climate change would almost certainly alter bird migration, influence the AI virus transmission cycle and directly affect virus survival outside the host. The joint, net effects of these changes are rather unpredictable, but it is likely that AI virus circulation in water bird populations will continue with endless adaptation and evolution. In domestic poultry, too little is known about the direct effect of environmental factors on highly pathogenic avian influenza transmission and persistence to allow inference about the possible effect of climate change. However, possible indirect links through changes in the distribution of duck-crop farming are discussed. PMID:18819672

  15. Scavenging Ducks and Transmission of Highly Pathogenic Avian Influenza, Java, Indonesia

    PubMed Central

    Wibawa, Hendra; Morton, John; Usman, Tri Bhakti; Junaidi, Akhmad; Meers, Joanne

    2010-01-01

    In Java, Indonesia, during March 2007–March 2008, 96 farms with scavenging ducks that were not vaccinated against highly pathogenic avian influenza (HPAI) were monitored bimonthly. Bird-level (prevalence among individual birds) H5 seroprevalence was 2.6% for ducks and 0.5% for chickens in contact with ducks. At least 1 seropositive bird was detected during 19.5% and 2.0% of duck- and chicken-flock visits, respectively. Duck flocks were 12.4× more likely than chicken flocks to have seropositive birds. During 21.4% of farm visits, ≥1 sampled duck was H5 seropositive when all sampled in-contact chickens were seronegative. Subtype H5 virus was detected during 2.5% of duck-flock visits and 1.5% of chicken-flock visits. When deaths from HPAI infection occurred, H5 virus shedding occurred in apparently healthy birds on 68.8% of farms. Of 180 poultry deaths investigated, 43.9% were attributed to H5 virus. These longitudinal study results indicate that ducks are a source of infection for chickens and, potentially, for humans. PMID:20678318

  16. Scavenging ducks and transmission of highly pathogenic avian influenza, Java, Indonesia.

    PubMed

    Henning, Joerg; Wibawa, Hendra; Morton, John; Usman, Tri Bhakti; Junaidi, Akhmad; Meers, Joanne

    2010-08-01

    In Java, Indonesia, during March 2007-March 2008, 96 farms with scavenging ducks that were not vaccinated against highly pathogenic avian influenza (HPAI) were monitored bimonthly. Bird-level (prevalence among individual birds) H5 seroprevalence was 2.6% for ducks and 0.5% for chickens in contact with ducks. At least 1 seropositive bird was detected during 19.5% and 2.0% of duck- and chicken-flock visits, respectively. Duck flocks were 12.4x more likely than chicken flocks to have seropositive birds. During 21.4% of farm visits,

  17. 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.

  18. Highly pathogenic avian influenza (H7N7): vaccination of zoo birds and transmission to non-poultry species.

    PubMed

    Philippa, Joost D W; Munster, Vincent J; Bolhuis, Hester van; Bestebroer, Theo M; Schaftenaar, Willem; Beyer, Walter E P; Fouchier, Ron A M; Kuiken, Thijs; Osterhaus, Albert D M E

    2005-12-30

    In 2003 an outbreak of highly pathogenic avian influenza virus (H7N7) struck poultry in The Netherlands. A European Commission directive made vaccination of valuable species in zoo collections possible under strict conditions. We determined pre- and post-vaccination antibody titres in 211 birds by haemagglutination inhibition test as a measure of vaccine efficacy. After booster vaccination, 81.5% of vaccinated birds developed a titre of > or =40, while overall geometric mean titre (GMT) was 190 (95% CI: 144-251). Birds of the orders Anseriformes, Galliformes and Phoenicopteriformes showed higher GMT, and larger percentages developed titres > or =40 than those of the other orders. Antibody response decreased with increasing mean body weight in birds > or =1.5 kg body weight. In the vicinity of the outbreak, H7N7 was detected by RT-PCR in wild species (mallards and mute swans) kept in captivity together with infected poultry, illustrating the potential threat of transmission from poultry into other avian species, and the importance of protecting valuable avian species by means of vaccination.

  19. Early Characterization of the Severity and Transmissibility of Pandemic Influenza Using Clinical Episode Data from Multiple Populations

    PubMed Central

    Riley, Pete; Ben-Nun, Michal; Linker, Jon A.; Cost, Angelia A.; Sanchez, Jose L.; George, Dylan; Bacon, David P.; Riley, Steven

    2015-01-01

    The potential rapid availability of large-scale clinical episode data during the next influenza pandemic suggests an opportunity for increasing the speed with which novel respiratory pathogens can be characterized. Key intervention decisions will be determined by both the transmissibility of the novel strain (measured by the basic reproductive number R 0) and its individual-level severity. The 2009 pandemic illustrated that estimating individual-level severity, as described by the proportion p C of infections that result in clinical cases, can remain uncertain for a prolonged period of time. Here, we use 50 distinct US military populations during 2009 as a retrospective cohort to test the hypothesis that real-time encounter data combined with disease dynamic models can be used to bridge this uncertainty gap. Effectively, we estimated the total number of infections in multiple early-affected communities using the model and divided that number by the known number of clinical cases. Joint estimates of severity and transmissibility clustered within a relatively small region of parameter space, with 40 of the 50 populations bounded by: p C, 0.0133–0.150 and R 0, 1.09–2.16. These fits were obtained despite widely varying incidence profiles: some with spring waves, some with fall waves and some with both. To illustrate the benefit of specific pairing of rapidly available data and infectious disease models, we simulated a future moderate pandemic strain with p C approximately ×10 that of 2009; the results demonstrating that even before the peak had passed in the first affected population, R 0 and p C could be well estimated. This study provides a clear reference in this two-dimensional space against which future novel respiratory pathogens can be rapidly assessed and compared with previous pandemics. PMID:26402446

  20. Understanding the failure of a behavior change intervention to reduce risk behaviors for avian influenza transmission among backyard poultry raisers in rural Bangladesh: a focused ethnography.

    PubMed

    Rimi, Nadia Ali; Sultana, Rebeca; Ishtiak-Ahmed, Kazi; Rahman, Md Zahidur; Hasin, Marufa; Islam, M Saiful; Azziz-Baumgartner, Eduardo; Nahar, Nazmun; Gurley, Emily S; Luby, Stephen P

    2016-08-24

    The spread of the highly pathogenic avian influenza (HPAI) H5N1 virus among poultry and humans has raised global concerns and has motivated government and public health organizations to initiate interventions to prevent the transmission of HPAI. In Bangladesh, H5N1 became endemic in poultry and seven human H5N1 cases have been reported since 2007, including one fatality. This study piloted messages to increase awareness about avian influenza and its prevention in two rural communities, and explored change in villagers' awareness and behaviors attributable to the intervention. During 2009-10, a research team implemented the study in two rural villages in two districts of Bangladesh. The team used a focused ethnographic approach for data collection, including informal interviews and observations to provide detailed contextual information about community response to a newly emerging disease. They collected pre-intervention qualitative data for one month. Then another team disseminated preventive messages focused on safe slaughtering methods, through courtyard meetings and affixed posters in every household. After dissemination, the research team collected post-intervention data for one month. More villagers reported hearing about 'bird flu' after the intervention compared to before the intervention. After the intervention, villagers commonly recalled changes in the color of combs and shanks of poultry as signs of avian influenza, and perceived zoonotic transmission of avian influenza through direct contact and through inhalation. Consequently the villagers valued covering the nose and mouth while handling sick and dead poultry as a preventive measure. Nevertheless, the team did not observe noticeable change in villagers' behavior after the intervention. Villagers reported not following the recommended behaviors because of the perceived absence of avian influenza in their flocks, low risk of avian influenza, cost, inconvenience, personal discomfort, fear of being

  1. Molecular signatures associated with Mx-1 mediated resistance to highlyl pathogenic influenza virus infections: mechanisms of survival

    USDA-ARS?s Scientific Manuscript database

    Understanding the role of host factors during lethal influenza virus infection is critical to deciphering the events that will determine the fate of the host. One such factor is encoded by the Mx1 gene, which confers resistance to influenza virus infection. Here, we compared pathology and global g...

  2. Experimental transmission of avian-like swine H1N1 influenza virus between immunologically naïve and vaccinated pigs.

    PubMed

    Lloyd, Lucy E; Jonczyk, Magdalena; Jervis, Carley M; Flack, Deborah J; Lyall, John; Foote, Alasdair; Mumford, Jennifer A; Brown, Ian H; Wood, James L; Elton, Debra M

    2011-09-01

    Infection of pigs with swine influenza has been studied experimentally and in the field; however, little information is available on the natural transmission of this virus in pigs. Two studies in an experimental transmission model are presented here, one in immunologically naïve and one in a combination of vaccinated and naïve pigs. To investigate the transmission of a recent 'avian-like' swine H1N1 influenza virus in naive piglets, to assess the antibody response to a commercially available vaccine and to determine the efficiency of transmission in pigs after vaccination. Transmission chains were initiated by intranasal challenge of two immunologically naïve pigs. Animals were monitored daily for clinical signs and virus shedding. Pairs of pigs were sequentially co-housed, and once virus was detected in recipients, prior donors were removed. In the vaccination study, piglets were vaccinated and circulating antibody levels were monitored by haemagglutination inhibition assay. To study transmission in vaccinates, a pair of infected immunologically naïve animals was co-housed with vaccinated recipient pigs and further pairs of vaccinates were added sequentially as above. The chain was completed by the addition of naive pigs. Transmission of the H1N1 virus was achieved through a chain of six pairs of naïve piglets and through four pairs of vaccinated animals. Transmission occurred with minimal clinical signs and, in vaccinates, at antibody levels higher than previously reported to protect against infection. © 2011 Blackwell Publishing Ltd.

  3. Different transmission patterns in the early stages of the influenza A(H1N1)v pandemic: a comparative analysis of 12 European countries.

    PubMed

    Flasche, Stefan; Hens, Niel; Boëlle, Pierre-Yves; Mossong, Joël; van Ballegooijen, W Marijn; Nunes, Baltazar; Rizzo, Caterina; Popovici, Florin; Santa-Olalla, Patricia; Hrubá, Frantiska; Parmakova, Kremena; Baguelin, Marc; van Hoek, Albert Jan; Desenclos, Jean-Claude; Bernillon, Pascale; Cámara, Amparro Larrauri; Wallinga, Jacco; Asikainen, Tommi; White, Peter J; Edmunds, W John

    2011-06-01

    Following the emergence of a novel strain of influenza A(H1N1) in Mexico and the United States in April 2009, its epidemiology in Europe during the summer was limited to sporadic and localised outbreaks. Only the United Kingdom experienced widespread transmission declining with school holidays in late July. Using statistical modelling where applicable we explored the following causes that could explain this surprising difference in transmission dynamics: extinction by chance, differences in the susceptibility profile, age distribution of the imported cases, differences in contact patterns, mitigation strategies, school holidays and weather patterns. No single factor was able to explain the differences sufficiently. Hence an additive mixed model was used to model the country-specific weekly estimates of the effective reproductive number using the extinction probability, school holidays and weather patterns as explanatory variables. The average extinction probability, its trend and the trend in absolute humidity were found to be significantly negatively correlated with the effective reproduction number - although they could only explain about 3% of the variability in the model. By comparing the initial epidemiology of influenza A (H1N1) across different European countries, our analysis was able to uncover a possible role for the timing of importations (extinction probability), mixing patterns and the absolute humidity as underlying factors. However, much uncertainty remains. With better information on the role of these epidemiological factors, the control of influenza could be improved.

  4. Evolution of 2009 H1N1 influenza viruses during the pandemic correlates with increased viral pathogenicity and transmissibility in the ferret model

    PubMed Central

    Otte, Anna; Marriott, Anthony C.; Dreier, Carola; Dove, Brian; Mooren, Kyra; Klingen, Thorsten R.; Sauter, Martina; Thompson, Katy-Anne; Bennett, Allan; Klingel, Karin; van Riel, Debby; McHardy, Alice C.; Carroll, Miles W.; Gabriel, Gülsah

    2016-01-01

    There is increasing evidence that 2009 pandemic H1N1 influenza viruses have evolved after pandemic onset giving rise to severe epidemics in subsequent waves. However, it still remains unclear which viral determinants might have contributed to disease severity after pandemic initiation. Here, we show that distinct mutations in the 2009 pandemic H1N1 virus genome have occurred with increased frequency after pandemic declaration. Among those, a mutation in the viral hemagglutinin was identified that increases 2009 pandemic H1N1 virus binding to human-like α2,6-linked sialic acids. Moreover, these mutations conferred increased viral replication in the respiratory tract and elevated respiratory droplet transmission between ferrets. Thus, our data show that 2009 H1N1 influenza viruses have evolved after pandemic onset giving rise to novel virus variants that enhance viral replicative fitness and respiratory droplet transmission in a mammalian animal model. These findings might help to improve surveillance efforts to assess the pandemic risk by emerging influenza viruses. PMID:27339001

  5. Pathogenesis in Eurasian tree sparrows inoculated with H5N1 highly pathogenic avian influenza virus and experimental virus transmission from tree sparrows to chickens.

    PubMed

    Yamamoto, Yu; Nakamura, Kikuyasu; Yamada, Manabu; Mase, Masaji

    2013-06-01

    Small wild birds that routinely enter poultry farms may be possible vectors of Asian lineage H5N1 highly pathogenic avian influenza virus. In this study, we conducted experimental infections using wild-caught Eurasian tree sparrows (Passer montanus) to evaluate their possible epidemiological involvement in virus transmission. When tree sparrows were intranasally inoculated with the virus at a low or high dose, all sparrows excluding euthanatized birds died within 11 days after inoculation. Viruses were frequently isolated from the drinking water, oral swabs, and visceral organs of the sparrows. Immunohistochemical analysis revealed that the virus replicated strongly in the central nervous system, heart, and adrenal gland following primary infection in the upper respiratory tract and a probable subsequent viremic stage. In the contact infection study using virus-inoculated sparrows and untreated contact chickens, more than half of all chickens died from viral infection. In the virus transmission study in which chickens were given drinking water collected from virus-inoculated sparrows, mortality due to viral infection was observed in chickens. Our data suggest that Eurasian tree sparrows could be biological vectors of the H5N1 highly pathogenic avian influenza virus. In addition to frequent virus detection in the drinking water of sparrows, the results of the virus transmission study suggest that waterborne pathways could be important for viral transmission from tree sparrows to poultry.

  6. Perinatal survival and health after maternal influenza A(H1N1)pdm09 vaccination: A cohort study of pregnancies stratified by trimester of vaccination.

    PubMed

    Baum, Ulrike; Leino, Tuija; Gissler, Mika; Kilpi, Terhi; Jokinen, Jukka

    2015-09-11

    Large cohort studies demonstrated the safety of vaccination with the AS03 adjuvanted pandemic influenza vaccine, but data on first trimester vaccination safety are limited. We conducted a nationwide register-based retrospective cohort study in Finland, included singleton pregnancies present on 01 November 2009 and followed them from 01 November 2009 until delivery. Pregnancies with abortive outcome, pregnancies that started before 01 February 2009 and pregnancies of women, who received the AS03 adjuvanted pandemic influenza vaccine prior to the onset of pregnancy, were excluded. Our main outcome measures were hazard ratios comparing the risk of stillbirth, early neonatal death, moderately preterm birth, very preterm birth, moderately low birth weight, very low birth weight, and being small for gestational age between pregnancies exposed and unexposed to maternal influenza A(H1N1)pdm09 vaccination. The study population comprised 43,604 pregnancies; 34,241 (78.5%) women were vaccinated at some stage during pregnancy. The rates of stillbirth, early neonatal death, moderately preterm birth, and moderately low birth weight were similar between pregnant women exposed and unexposed to influenza A(H1N1)pdm09 vaccination. After adjusting for known risk factors, the relative rates were 0.90 (95% confidence interval 0.55-1.45) for very preterm birth, 0.84 (0.61-1.16) for very low birth weight, and 1.17 (0.98-1.40) for being small for gestational age. Also, in the subanalysis of 7839 women vaccinated during the first trimester, the rates did not indicate that maternal vaccination during the first trimester had any adverse impact on perinatal survival and health. The risk of adverse pregnancy outcomes was not associated with the exposure to the AS03 adjuvanted pandemic influenza vaccine. This study adds reassuring evidence on the safety of AS03 adjuvanted influenza vaccines when given in the first trimester and supports the recommendation of influenza vaccination to all

  7. Transmission dynamics of the 2009 influenza A (H1N1) pandemic in India: the impact of holiday-related school closure.

    PubMed

    Ali, Sheikh Taslim; Kadi, A S; Ferguson, Neil M

    2013-12-01

    The role of social-distancing measures, such as school closures, is a controversial aspect of pandemic mitigation planning. However, the timing of 2009 pandemic provides a natural experiment for evaluating the impact of school closure during holidays on influenza transmission. To quantify the transmission intensity of the influenza A (H1N1) pdm'09 in India, by estimating the time varying reproduction number (Rt) and correlating the temporal changes in the estimates of Rt for different regions of India with the timing of school holidays. We used daily lab-confirmed case reports of influenza A (H1N1) pdm'09 in India (during 17 May'09 to 17 May'10), stratified by regions. We estimated the transmissibility of the pandemic for different regions from these time-series, using Bayesian methods applied to a branching process model of disease spread and correlated the resulting estimates with the timing of school holidays in each region. The North-west region experienced two notable waves, with the peak of the first wave coinciding with the start of a 4 week school holiday (September-October'09). In the southern region the two waves were less clear cut, though again the first peak of the first wave coincided with the start of school holidays--albeit of less than 2 weeks duration (August'09). Our analysis suggests that the school holidays had a significant influence on the epidemiology of the 2009 pandemic in India. We estimate that school holidays reduced the reproduction number by 14-27% in different regions of India, relative to levels seen outside holiday periods. The estimates of the reproduction number obtained (with peak R values below 1.5) are compatible with those reported from other regions of the world. This work reinforces past studies showing the significant impact of school holidays on spread of 2009 pandemic virus, and by inference the role of contact patterns in children on transmission.

  8. Transmission dynamics of the 2009 influenza A (H1N1) pandemic in India: The impact of holiday-related school closure

    PubMed Central

    Taslim Ali, Sheikh; Kadi, A. S.; Ferguson, Neil M.

    2014-01-01

    The role of social-distancing measures, such as school closures, is a controversial aspect of pandemic mitigation planning. However, the timing of 2009 pandemic provides a natural experiment for evaluating the impact of school closure during holidays on influenza transmission. To quantify the transmission intensity of the influenza A (H1N1) pdm’09 in India, by estimating the time varying reproduction number (Rt) and correlating the temporal changes in the estimates of Rt for different regions of India with the timing of school holidays. We used daily lab-confirmed case reports of influenza A (H1N1) pdm’09 in India (during 17 May’09 to 17 May’10), stratified by regions. We estimated the transmissibility of the pandemic for different regions from these time-series, using Bayesian methods applied to a branching process model of disease spread and correlated the resulting estimates with the timing of school holidays in each region. The North-west region experienced two notable waves, with the peak of the first wave coinciding with the start of a 4 week school holiday (September-October’09). In the southern region the two waves were less clear cut, though again the first peak of the first wave coincided with the start of school holidays – albeit of less than 2 weeks duration (August’09). Our analysis suggests that the school holidays had a significant influence on the epidemiology of the 2009 pandemic in India. We estimate that school holidays reduced the reproduction number by 14%–27% in different regions of India, relative to levels seen outside holiday periods. The estimates of the reproduction number obtained (with peak R values below 1.5) are compatible with those reported from other regions of the world. This work reinforces past studies showing the significant impact of school holidays on spread of 2009 pandemic virus, and by inference the role of contact patterns in children on transmission. PMID:24267871

  9. Identification of a key amino acid in hemagglutinin that increases human-type receptor binding and transmission of an H6N2 avian influenza virus.

    PubMed

    Qu, Zhiyuan; Ma, Shujie; Kong, Huihui; Deng, Guohua; Shi, Jianzhong; Liu, Liling; Suzuki, Yasuo; Chen, Hualan

    2017-09-23

    Binding exclusively to human-type receptors is a prerequisite for avian influenza viruses to transmit from human to human. We previously reported that 34% of H6 avian influenza viruses recognize the human-type receptor, but their affinity for the avian-type receptor remains higher than that for the human-type receptor. Here, we found that a single amino acid change from glutamine to leucine at position 226 of hemagglutinin caused a switch in receptor-binding preference from avian-type to human-type receptors and rendered A/chicken/Guangdong/S1312/2010(H6N2) capable of respiratory droplet transmission in guinea pigs. Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  10. Persistence of Highly Pathogenic Avian Influenza Viruses in Natural Ecosystems

    PubMed Central

    Feare, Chris J.; Renaud, François; Thomas, Frédéric; Gauthier-Clerc, Michel

    2010-01-01

    Understanding of ecologic factors favoring emergence and maintenance of highly pathogenic avian influenza (HPAI) viruses is limited. Although low pathogenic avian influenza viruses persist and evolve in wild populations, HPAI viruses evolve in domestic birds and cause economically serious epizootics that only occasionally infect wild populations. We propose that evolutionary ecology considerations can explain this apparent paradox. Host structure and transmission possibilities differ considerably between wild and domestic birds and are likely to be major determinants of virulence. Because viral fitness is highly dependent on host survival and dispersal in nature, virulent forms are unlikely to persist in wild populations if they kill hosts quickly or affect predation risk or migratory performance. Interhost transmission in water has evolved in low pathogenic influenza viruses in wild waterfowl populations. However, oropharyngeal shedding and transmission by aerosols appear more efficient for HPAI viruses among domestic birds. PMID:20587174

  11. Effect of closure of live poultry markets on poultry-to-person transmission of avian influenza A H7N9 virus: an ecological study.

    PubMed

    Yu, Hongjie; Wu, Joseph T; Cowling, Benjamin J; Liao, Qiaohong; Fang, Vicky J; Zhou, Sheng; Wu, Peng; Zhou, Hang; Lau, Eric H Y; Guo, Danhuai; Ni, Michael Y; Peng, Zhibin; Feng, Luzhao; Jiang, Hui; Luo, Huiming; Li, Qun; Feng, Zijian; Wang, Yu; Yang, Weizhong; Leung, Gabriel M

    2014-02-08

    Transmission of the novel avian influenza A H7N9 virus seems to be predominantly between poultry and people. In the major Chinese cities of Shanghai, Hangzhou, Huzhou, and Nanjing--where most human cases of infection have occurred--live poultry markets (LPMs) were closed in April, 2013, soon after the initial outbreak, as a precautionary public health measure. Our objective was to quantify the effect of LPM closure in these cities on poultry-to-person transmission of avian influenza A H7N9 virus. We obtained information about every laboratory-confirmed human case of avian influenza A H7N9 virus infection reported in the four cities by June 7, 2013, from a database built by the Chinese Center for Disease Control and Prevention. We used data for age, sex, location, residence type (rural or urban area), and dates of illness onset. We obtained information about LPMs from official sources. We constructed a statistical model to explain the patterns in incidence of cases reported in each city on the basis of the assumption of a constant force of infection before LPM closure, and a different constant force of infection after closure. We fitted the model with Markov chain Monte Carlo methods. 85 human cases of avian influenza A H7N9 virus infection were reported in Shanghai, Hangzhou, Huzhou, and Nanjing by June 7, 2013, of which 60 were included in our main analysis. Closure of LPMs reduced the mean daily number of infections by 99% (95% credibility interval 93-100%) in Shanghai, by 99% (92-100%) in Hangzhou, by 97% (68-100%) in Huzhou, and by 97% (81-100%) in Nanjing. Because LPMs were the predominant source of exposure to avian influenza A H7N9 virus for confirmed cases in these cities, we estimated that the mean incubation period was 3·3 days (1·4-5·7). LPM closures were effective in the control of human risk of avian influenza A H7N9 virus infection in the spring of 2013. In the short term, LPM closure should be rapidly implemented in areas where the virus is

  12. Genetic evidence for avian influenza H5N1 viral transmission along the Black Sea-Mediterranean Flyway.

    PubMed

    Zhou, Sen; Tian, Huaiyu; Wu, Xiaoxu; Xu, Bo; Yang, Jing; Chan, Karen Kie Yan; Huang, Shanqian; Dong, Lu; Brownstein, John; Xu, Bing

    2016-09-01

    The current epidemic of highly pathogenic avian influenza H5N1 virus is considered to pose a significant threat to the health of wild and domestic avian species, and even to human beings. The Black Sea-Mediterranean Flyway is one of the most important epidemic areas of H5N1. However, the epidemic along this flyway has not been fully explored. To better understand the role of hosts in the spread and evolution of H5N1 virus along the flyway, a phylogeographic study was conducted using haemagglutinin (HA) gene sequences obtained during 2005-2013. To infer phylodynamic spread in time and space, we used a flexible Bayesian statistical framework and modelled viral spatial diffusion as a continuous-time Markov-chain process along time-measured genealogies. Our results revealed that H5N1 virus isolated from wild birds showed an increase in genetic variation of HA gene from 2005-2007. The mean genetic distance of viruses isolated from poultry reached its peak in 2010, and dropped in 2011, increasing again in 2012-2013. The reconstruction of virus circulation revealed a different viral-migration network of H5N1 virus by different hosts. Western Russia constituted a link in viral migration from Russia to Europe and Africa. Cross-species transmission of H5N1 viruses predominated in the migration network of the Black Sea-Mediterranean Flyway. This might be due to the migration of birds across long distances and interaction between local poultry and migratory birds. Additionally, the short-distance spread of H5N1 viruses among poultry followed local transportation networks. Such findings will aid in developing effective disease control and prevention strategies.

  13. Effects of climatological parameters in modeling and forecasting seasonal influenza transmission in Abidjan, Cote d'Ivoire.

    PubMed

    N'gattia, A K; Coulibaly, D; Nzussouo, N Talla; Kadjo, H A; Chérif, D; Traoré, Y; Kouakou, B K; Kouassi, P D; Ekra, K D; Dagnan, N S; Williams, T; Tiembré, I

    2016-09-13

    In temperate regions, influenza epidemics occur in the winter and correlate with certain climatological parameters. In African tropical regions, the effects of climatological parameters on influenza epidemics are not well defined. This study aims to identify and model the effects of climatological parameters on seasonal influenza activity in Abidjan, Cote d'Ivoire. We studied the effects of weekly rainfall, humidity, and temperature on laboratory-confirmed influenza cases in Abidjan from 2007 to 2010. We used the Box-Jenkins method with the autoregressive integrated moving average (ARIMA) process to create models using data from 2007-2010 and to assess the predictive value of best model on data from 2011 to 2012. The weekly number of influenza cases showed significant cross-correlation with certain prior weeks for both rainfall, and relative humidity. The best fitting multivariate model (ARIMAX (2,0,0) _RF) included the number of influenza cases during 1-week and 2-weeks prior, and the rainfall during the current week and 5-weeks prior. The performance of this model showed an increase of >3 % for Akaike Information Criterion (AIC) and 2.5 % for Bayesian Information Criterion (BIC) compared to the reference univariate ARIMA (2,0,0). The prediction of the weekly number of influenza cases during 2011-2012 with the best fitting multivariate model (ARIMAX (2,0,0) _RF), showed that the observed values were within the 95 % confidence interval of the predicted values during 97 of 104 weeks. Including rainfall increases the performances of fitted and predicted models. The timing of influenza in Abidjan can be partially explained by rainfall influence, in a setting with little change in temperature throughout the year. These findings can help clinicians to anticipate influenza cases during the rainy season by implementing preventive measures.

  14. Unifying viral genetics and human transportation data to predict the global transmission dynamics of human influenza H3N2.

    PubMed

    Lemey, Philippe; Rambaut, Andrew; Bedford, Trevor; Faria, Nuno; Bielejec, Filip; Baele, Guy; Russell, Colin A; Smith, Derek J; Pybus, Oliver G; Brockmann, Dirk; Suchard, Marc A

    2014-02-01

    Information on global human movement patterns is central to spatial epidemiological models used to predict the behavior of influenza and other infectious diseases. Yet it remains difficult to test which modes of dispersal drive pathogen spread at various geographic scales using standard epidemiological data alone. Evolutionary analyses of pathogen genome sequences increasingly provide insights into the spatial dynamics of influenza viruses, but to date they have largely neglected the wealth of information on human mobility, mainly because no statistical framework exists within which viral gene sequences and empirical data on host movement can be combined. Here, we address this problem by applying a phylogeographic approach to elucidate the global spread of human influenza subtype H3N2 and assess its ability to predict the spatial spread of human influenza A viruses worldwide. Using a framework that estimates the migration history of human influenza while simultaneously testing and quantifying a range of potential predictive variables of spatial spread, we show that the global dynamics of influenza H3N2 are driven by air passenger flows, whereas at more local scales spread is also determined by processes that correlate with geographic distance. Our analyses further confirm a central role for mainland China and Southeast Asia in maintaining a source population for global influenza diversity. By comparing model output with the known pandemic expansion of H1N1 during 2009, we demonstrate that predictions of influenza spatial spread are most accurate when data on human mobility and viral evolution are integrated. In conclusion, the global dynamics of influenza viruses are best explained by combining human mobility data with the spatial information inherent in sampled viral genomes. The integrated approach introduced here offers great potential for epidemiological surveillance through phylogeographic reconstructions and for improving predictive models of disease control.

  15. Transmission of highly pathogenic avian influenza H5N1 virus in Pekin ducks is significantly reduced by a genetically distant H5N2 vaccine.

    PubMed

    van der Goot, Jeanet A; van Boven, Michiel; Stegeman, Arjan; van de Water, Sandra G P; de Jong, Mart C M; Koch, Guus

    2008-12-05

    Domestic ducks play an important role in the epidemiology of H5N1 avian influenza. Although it is known that vaccines that have a high homology with the challenge virus are able to prevent infection in ducks, little is yet known about the ability of genetically more distant vaccines in preventing infection, disease, and transmission. Here we study the effect of a widely used H5N2 vaccine (A/Chicken/Mexico/232/94/CPA) on the transmission of H5N1 virus (A/Chicken/China/1204/04) in ducks. The quantitative analyses show that despite the low level of homology between the virus and vaccine strain transmission was significantly reduced two weeks after a single or double vaccination. Mortality and disease rates were reduced markedly already one week after a single vaccination.

  16. Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets.

    PubMed

    Imai, Masaki; Watanabe, Tokiko; Hatta, Masato; Das, Subash C; Ozawa, Makoto; Shinya, Kyoko; Zhong, Gongxun; Hanson, Anthony; Katsura, Hiroaki; Watanabe, Shinji; Li, Chengjun; Kawakami, Eiryo; Yamada, Shinya; Kiso, Maki; Suzuki, Yasuo; Maher, Eileen A; Neumann, Gabriele; Kawaoka, Yoshihiro

    2012-05-02

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

  17. 2009 Pandemic Influenza A Virus Subtype H1N1 in Morocco, 2009–2010: Epidemiology, Transmissibility, and Factors Associated With Fatal Cases

    PubMed Central

    Barakat, Amal; Ihazmad, Hassan; El Falaki, Fatima; Tempia, Stefano; Cherkaoui, Imad; El Aouad, Rajae

    2012-01-01

    Background. Following the emergence of 2009 pandemic influenza A virus subtype H1N1 (A[H1N1]pdm09) in the United States and Mexico in April 2009, A(H1N1)pdm09 spread rapidly all over the world. There is a dearth of information about the epidemiology of A(H1N1)pdm09 in Africa, including Morocco. We describe the epidemiologic characteristics of the A(H1N1)pdm09 epidemic in Morocco during 2009–2010, including transmissibility and risk factors associated with fatal disease. Methods. We implemented influenza surveillance for patients presenting with influenza-like illness (ILI) at 136 private and public clinics for patients with severe acute respiratory illness (SARI) at 16 regional public hospitals from June 2009 through February 2010. Respiratory samples and structured questionnaires were collected from all enrolled patients, and samples were tested by real-time reverse-transcription polymerase chain reaction for influenza viruses. We estimated the risk factors associated with fatal disease as well as the basic reproduction number (R0) and the serial interval of the pandemic virus. Results. From June 2009 through February 2010, we obtained 3937 specimens, of which 1452 tested positive for influenza virus. Of these, 1398 (96%) were A(H1N1)pdm09. Forty percent of specimens from ILI cases (1056 of 2646) and 27% from SARI cases (342 of 1291) were positive for A(H1N1)pdm09. Sixty-four deaths occurred among laboratory-confirmed A(H1N1)pdm09 SARI cases. Among these cases, those who had hypertension (age-adjusted odd ratio [aOR], 28.2; 95% confidence interval [CI], 2.0–398.7), had neurological disorders (aOR, 7.5; 95% CI, 1.5–36.4), or were obese (aOR, 7.1; 95% CI, 1.6–31.1), as well as women of gestational age who were pregnant (aOR, 2.5; 95% CI, 1.1–5.6), were at increased risk of death. Across the country, elevated numbers of locally acquired infections were detected 4 months after the detection of the first laboratory-confirmed case and coincided with the

  18. Plant viruses in aqueous environment - survival, water mediated transmission and detection.

    PubMed

    Mehle, Nataša; Ravnikar, Maja

    2012-10-15

    The presence of plant viruses outside their plant host or insect vectors has not been studied intensively. This is due, in part, to the lack of effective detection methods that would enable their detection in difficult matrixes and in low titres, and support the search for unknown viruses. Recently, new and sensitive methods for detecting viruses have resulted in a deeper insight into plant virus movement through, and transmission between, plants. In this review, we have focused on plant viruses found in environmental waters and their detection. Infectious plant pathogenic viruses from at least 7 different genera have been found in aqueous environment. The majority of the plant pathogenic viruses so far recovered from environmental waters are very stable, they can infect plants via the roots without the aid of a vector and often have a wide host range. The release of such viruses from plants can lead to their dissemination in streams, lakes, and rivers, thereby ensuring the long-distance spread of viruses that otherwise, under natural conditions, would remain restricted to limited areas. The possible sources and survival of plant viruses in waters are therefore discussed. Due to the widespread use of hydroponic systems and intensive irrigation in horticulture, the review is focused on the possibility and importance of spreading viral infection by water, together with measures for preventing the spread of viruses. The development of new methods for detecting multiple plant viruses at the same time, like microarrays or new generation sequencing, will facilitate the monitoring of environmental waters and waters used for irrigation and in hydroponic systems. It is reasonable to expect that the list of plant viruses found in waters will thereby be expanded considerably. This will emphasize the need for further studies to determine the biological significance of water-mediated transport.

  19. Pathogenicity and Transmissibility of Novel Reassortant H3N2 Influenza Viruses with 2009 Pandemic H1N1 Genes in Pigs

    PubMed Central

    Ma, Jingjiao; Shen, Huigang; Liu, Qinfang; Bawa, Bhupinder; Qi, Wenbao; Duff, Michael; Lang, Yuekun; Lee, Jinhwa; Yu, Hai; Bai, Jianfa; Tong, Guangzhi; Hesse, Richard A.; Richt, Jürgen A.

    2014-01-01

    ABSTRACT At least 10 different genotypes of novel reassortant H3N2 influenza viruses with 2009 pandemic H1N1 [A(H1N1)pdm09] gene(s) have been identified in U.S. pigs, including the H3N2 variant with a single A(H1N1)pdm09 M gene, which has infected more than 300 people. To date, only three genotypes of these viruses have been evaluated in animal models, and the pathogenicity and transmissibility of the other seven genotype viruses remain unknown. Here, we show that three H3N2 reassortant viruses that contain 3 (NP, M, and NS) or 5 (PA, PB2, NP, M, and NS) genes from A(H1N1)pdm09 were pathogenic in pigs, similar to the endemic H3N2 swine virus. However, the reassortant H3N2 virus with 3 A(H1N1)pdm09 genes and a recent human influenza virus N2 gene was transmitted most efficiently among pigs, whereas the reassortant H3N2 virus with 5 A(H1N1)pdm09 genes was transmitted less efficiently than the endemic H3N2 virus. Interestingly, the polymerase complex of reassortant H3N2 virus with 5 A(H1N1)pdm09 genes showed significantly higher polymerase activity than those of endemic and reassortant H3N2 viruses with 3 A(H1N1)pdm09 genes. Further studies showed that an avian-like glycine at position 228 at the hemagglutinin (HA) receptor binding site is responsible for inefficient transmission of the reassortant H3N2 virus with 5 A(H1N1)pdm09 genes. Taken together, our results provide insights into the pathogenicity and transmissibility of novel reassortant H3N2 viruses in pigs and suggest that a mammalian-like serine at position 228 in the HA is critical for the transmissibility of these reassortant H3N2 viruses. IMPORTANCE Swine influenza is a highly contagious zoonotic disease that threatens animal and public health. Introduction of 2009 pandemic H1N1 virus [A(H1N1)pdm09] into swine herds has resulted in novel reassortant influenza viruses in swine, including H3N2 and H1N2 variants that have caused human infections in the United States. We showed that reassortant H3N2 influenza

  20. Transmission and immunopathology of the avian influenza virus A/Anhui/1/2013 (H7N9) human isolate in three commonly commercialized avian species.

    PubMed

    Vidaña, B; Dolz, R; Busquets, N; Ramis, A; Sánchez, R; Rivas, R; Valle, R; Cordón, I; Solanes, D; Martínez, J; Majó, N

    2017-09-14

    H7N9 virus infection is a global concern, given that it can cause severe infection and mortality in humans. However, the understanding of H7N9 epidemiology, animal reservoir species and zoonotic risk remains limited. This work evaluates the pathogenicity, transmissibility and local innate immune response of three avian species harbouring different respiratory distribution of α2,6 and α2,3 SA receptors. Muscovy ducks, European quails and SPF chickens were intranasally inoculated with 10(5) embryo infectious dose (EID)50 of the human H7N9 (A/Anhui/1/2013) influenza isolate. None of the avian species showed clinical signs or macroscopic lesions, and only mild microscopic lesions were observed in the upper respiratory tract of quail and chickens. Quail presented more severe histopathologic lesions and avian influenza virus (AIV) positivity by immunohistochemistry (IHC), which correlated with higher IL-6 responses. In contrast, Muscovy ducks were resistant to disease and presented higher IFNα and TLR7 response. In all species, viral shedding was higher in the respiratory than in the digestive tract. Higher viral shedding was observed in quail, followed by chicken and ducks, which presented similar viral titres. Efficient transmission was observed in all contact quail and half of the Muscovy ducks, while no transmission was observed between chicken. All avian species showed viral shedding in drinking water throughout infection. © 2017 Blackwell Verlag GmbH.

  1. The mouse model is suitable for the study of viral factors governing transmission and pathogenesis of highly pathogenic avian influenza (HPAI) viruses in mammals

    PubMed Central

    Rigoni, Michela; Toffan, Anna; Viale, Elisabetta; Mancin, Marzia; Cilloni, Filippo; Bertoli, Elena; Salomoni, Angela; Marciano, Sabrina; Milani, Adelaide; Zecchin, Bianca; Capua, Ilaria; Cattoli, Giovanni

    2010-01-01

    Highly pathogenic avian influenza (HPAI) viruses of the H5 and H7 subtype pose a major public health threat due to their capacity to cross the species barrier and infect mammals, for example dogs, cats and humans. In the present study we tested the capacity of selected H7 and H5 HPAI viruses to infect and to be transmitted from infected BALB/c mice to contact sentinels. Previous experiments have shown that viruses belonging to both H5 and H7 subtypes replicate in the respiratory tract and central nervous system of experimentally infected mice. In this study we show that selected H7N1 and H5N1 HPAI viruses can be transmitted from mouse-to-mouse by direct contact, and that in experimentally infected animals they exhibit a different pattern of replication and transmission. Our results can be considered as a starting point for transmission experiments involving other influenza A viruses with α 2-3 receptor affinity in order to better understand the viral factors influencing transmissibility of these viruses in selected mammalian species. PMID:20546698

  2. Prospective of Genomics in Revealing Transmission, Reassortment and Evolution of Wildlife-Borne Avian Influenza A (H5N1) Viruses

    PubMed Central

    Lei, Fumin; Shi, Weifeng

    2011-01-01

    The outbreak of highly pathogenic avian influenza (HPAI) H5N1 disease has led to significant loss of poultry and wild life and case fatality rates in humans of 60%. Wild birds are natural hosts for all avian influenza virus subtypes and over120 bird species have been reported with evidence of H5N1 infection. Influenza A viruses possess a segmented RNA genome and are characterized by frequently occurring genetic reassortment events, which play a very important role in virus evolution and the spread of novel gene constellations in immunologically naïve human and animal populations. Phylogenetic analysis of whole genome or sub-genomic sequences is a standard means for delineating genetic variation, novel reassortment events, and surveillance to trace the global transmission pathways. In this paper, special emphasis is given to the transmission and circulation of H5N1 among wild life populations, and to the reassortment events that are associated with inter-host transmission of the H5N1 viruses when they infect different hosts, such as birds, pigs and humans. In addition, we review the inter-subtype reassortment of the viral segments encoding inner proteins between the H5N1 viruses and viruses of other subtypes, such as H9N2 and H6N1. Finally, we highlight the usefulness of genomic sequences in molecular epidemiological analysis of HPAI H5N1 and the technical limitations in existing analytical methods that hinder them from playing a greater role in virological research. PMID:22547954

  3. Phylogenetic Exploration of Nosocomial Transmission Chains of 2009 Influenza A/H1N1 among Children Admitted at Red Cross War Memorial Children's Hospital, Cape Town, South Africa in 2011.

    PubMed

    Valley-Omar, Ziyaad; Nindo, Fredrick; Mudau, Maanda; Hsiao, Marvin; Martin, Darren Patrick

    2015-01-01

    Traditional modes of investigating influenza nosocomial transmission have entailed a combination of confirmatory molecular diagnostic testing and epidemiological investigation. Common hospital-acquired infections like influenza require a discerning ability to distinguish between viral isolates to accurately identify patient transmission chains. We assessed whether influenza hemagglutinin sequence phylogenies can be used to enrich epidemiological data when investigating the extent of nosocomial transmission over a four-month period within a paediatric Hospital in Cape Town South Africa. Possible transmission chains/channels were initially determined through basic patient admission data combined with Maximum likelihood and time-scaled Bayesian phylogenetic analyses. These analyses suggested that most instances of potential hospital-acquired infections resulted from multiple introductions of Influenza A into the hospital, which included instances where virus hemagglutinin sequences were identical between different patients. Furthermore, a general inability to establish epidemiological transmission linkage of patients/viral isolates implied that identified isolates could have originated from asymptomatic hospital patients, visitors or hospital staff. In contrast, a traditional epidemiological investigation that used no viral phylogenetic analyses, based on patient co-admission into specific wards during a particular time-frame, suggested that multiple hospital acquired infection instances may have stemmed from a limited number of identifiable index viral isolates/patients. This traditional epidemiological analysis by itself could incorrectly suggest linkage between unrelated cases, underestimate the number of unique infections and may overlook the possible diffuse nature of hospital transmission, which was suggested by sequencing data to be caused by multiple unique introductions of influenza A isolates into individual hospital wards. We have demonstrated a functional

  4. Phylogenetic Exploration of Nosocomial Transmission Chains of 2009 Influenza A/H1N1 among Children Admitted at Red Cross War Memorial Children’s Hospital, Cape Town, South Africa in 2011

    PubMed Central

    Hsiao, Marvin; Martin, Darren Patrick

    2015-01-01

    Traditional modes of investigating influenza nosocomial transmission have entailed a combination of confirmatory molecular diagnostic testing and epidemiological investigation. Common hospital-acquired infections like influenza require a discerning ability to distinguish between viral isolates to accurately identify patient transmission chains. We assessed whether influenza hemagglutinin sequence phylogenies can be used to enrich epidemiological data when investigating the extent of nosocomial transmission over a four-month period within a paediatric Hospital in Cape Town South Africa. Possible transmission chains/channels were initially determined through basic patient admission data combined with Maximum likelihood and time-scaled Bayesian phylogenetic analyses. These analyses suggested that most instances of potential hospital-acquired infections resulted from multiple introductions of Influenza A into the hospital, which included instances where virus hemagglutinin sequences were identical between different patients. Furthermore, a general inability to establish epidemiological transmission linkage of patients/viral isolates implied that identified isolates could have originated from asymptomatic hospital patients, visitors or hospital staff. In contrast, a traditional epidemiological investigation that used no viral phylogenetic analyses, based on patient co-admission into specific wards during a particular time-frame, suggested that multiple hospital acquired infection instances may have stemmed from a limited number of identifiable index viral isolates/patients. This traditional epidemiological analysis by itself could incorrectly suggest linkage between unrelated cases, underestimate the number of unique infections and may overlook the possible diffuse nature of hospital transmission, which was suggested by sequencing data to be caused by multiple unique introductions of influenza A isolates into individual hospital wards. We have demonstrated a functional

  5. Southward autumn migration of waterfowl facilitates cross-continental transmission of the highly pathogenic avian influenza H5N1 virus

    PubMed Central

    Xu, Yanjie; Gong, Peng; Wielstra, Ben; Si, Yali

    2016-01-01

    The highly pathogenic avian influenza subtype H5N1 (HPAI H5N1) is a worldwide zoonotic infectious disease, threatening humans, poultry and wild birds. The role of wild birds in the spread of HPAI H5N1 has previously been investigated by comparing disease spread patterns with bird migration routes. However, the different roles that the southward autumn and northward spring migration might play in virus transmission have hardly been explored. Using direction analysis, we analyze HPAI H5N1 transmission directions and angular concentration of currently circulating viral clades, and compare these with waterfowl seasonal migration directions along major waterfowl flyways. Out of 22 HPAI H5N1 transmission directions, 18 had both a southward direction and a relatively high concentration. Differences between disease transmission and waterfowl migration directions were significantly smaller for autumn than for spring migration. The four northward transmission directions were found along Asian flyways, where the initial epicenter of the virus was located. We suggest waterfowl first picked up the virus from East Asia, then brought it to the north via spring migration, and then spread it to other parts of world mainly by autumn migration. We emphasize waterfowl autumn migration plays a relatively important role in HPAI H5N1 transmission compared to spring migration. PMID:27507581

  6. Amino acid substitutions in the neuraminidase protein of an H9N2 avian influenza virus affect its airborne transmission in chickens.

    PubMed

    Lv, Jing; Wei, Liangmeng; Yang, Yan; Wang, Bingxiao; Liang, Wei; Gao, Yuwei; Xia, Xianzhu; Gao, Lili; Cai, Yumei; Hou, Peiqiang; Yang, Huili; Wang, Airong; Huang, Rong; Gao, Jing; Chai, Tongjie

    2015-04-18

    Cases of H9N2 avian influenza virus (AIV) in poultry are increasing throughout many Eurasian countries, and co-infections with other pathogens have resulted in high morbidity and mortality in poultry. Few studies have investigated the genetic factors of virus airborne transmission which determine the scope of this epidemic. In this study, we used specific-pathogen-free chickens housed in isolators to investigate the airborne transmissibility of five recombinant H9N2 AIV rescued by reverse genetic technology. The results show that airborne transmission of A/Chicken/Shandong/01/2008 (SD01) virus was related to the neuraminidase (NA) gene, and four amino acid mutations (D368E, S370L, E313K and G381D) within the head region of the SD01 NA, reduced virus replication in the respiratory tract of chickens, reduced virus NA activity, and resulted in a loss of airborne transmission ability in chickens. Similarly, reverse mutations of these four amino acids in the NA protein of r01/NASS virus, conferred an airborne transmission ability to the recombinant virus. We conclude that these four NA residues may be significant genetic markers for evaluating potential disease outbreak of H9N2 AIV, and propose that immediate attention should be paid to the airborne transmission of this virus.

  7. Household transmissibility of avian influenza A (H7N9) virus, China, February to May 2013 and October 2013 to March 2014.

    PubMed

    Yang, Y; Zhang, Y; Fang, L; Halloran, M E; Ma, M; Liang, S; Kenah, E; Britton, T; Chen, E; Hu, J; Tang, F; Cao, W; Feng, Z; Longini, I M

    2015-03-12

    To study human-to-human transmissibility of the avian influenza A (H7N9) virus in China, household contact information was collected for 125 index cases during the spring wave (February to May 2013), and for 187 index cases during the winter wave (October 2013 to March 2014). Using a statistical model, we found evidence for human-to-human transmission, but such transmission is not sustainable. Under plausible assumptions about the natural history of disease and the relative transmission frequencies in settings other than household, we estimate the household secondary attack rate (SAR) among humans to be 1.4% (95% CI: 0.8 to 2.3), and the basic reproductive number R0 to be 0.08 (95% CI: 0.05 to 0.13). The estimates range from 1.3% to 2.2% for SAR and from 0.07 to 0.12 for R0 with reasonable changes in the assumptions. There was no significant change in the human-to-human transmissibility of the virus between the two waves, although a minor increase was observed in the winter wave. No sex or age difference in the risk of infection from a human source was found. Human-to-human transmissibility of H7N9 continues to be limited, but it needs to be closely monitored for potential increase via genetic reassortment or mutation.

  8. Household transmissibility of avian influenza A (H7N9) virus, China, February to May 2013 and October 2013 to March 2014

    PubMed Central

    Yang, Y; Zhang, Y; Fang, L; Halloran, M E; Ma, M; Liang, S; Kenah, E; Britton, T; Chen, E; Hu, J; Tang, F; Cao, W; Feng, Z; Longini, I M

    2015-01-01

    To study human-to-human transmissibility of the avian influenza A (H7N9) virus in China, household contact information was collected for 125 index cases during the spring wave (February to May 2013), and for 187 index cases during the winter wave (October 2013 to March 2014). Using a statistical model, we found evidence for human-to-human transmission, but such transmission is not sustainable. Under plausible assumptions about the natural history of disease and the relative transmission frequencies in settings other than household, we estimate the household secondary attack rate (SAR) among humans to be 1.4% (95% CI: 0.8 to 2.3), and the basic reproductive number R0 to be 0.08 (95% CI: 0.05 to 0.13). The estimates range from 1.3% to 2.2% for SAR and from 0.07 to 0.12 for R0 with reasonable changes in the assumptions. There was no significant change in the human-to-human transmissibility of the virus between the two waves, although a minor increase was observed in the winter wave. No sex or age difference in the risk of infection from a human source was found. Human-to-human transmissibility of H7N9 continues to be limited, but it needs to be closely monitored for potential increase via genetic reassortment or mutation. PMID:25788253

  9. Southward autumn migration of waterfowl facilitates cross-continental transmission of the highly pathogenic avian influenza H5N1 virus

    NASA Astrophysics Data System (ADS)

    Xu, Yanjie; Gong, Peng; Wielstra, Ben; Si, Yali

    2016-08-01

    The highly pathogenic avian influenza subtype H5N1 (HPAI H5N1) is a worldwide zoonotic infectious disease, threatening humans, poultry and wild birds. The role of wild birds in the spread of HPAI H5N1 has previously been investigated by comparing disease spread patterns with bird migration routes. However, the different roles that the southward autumn and northward spring migration might play in virus transmission have hardly been explored. Using direction analysis, we analyze HPAI H5N1 transmission directions and angular concentration of currently circulating viral clades, and compare these with waterfowl seasonal migration directions along major waterfowl flyways. Out of 22 HPAI H5N1 transmission directions, 18 had both a southward direction and a relatively high concentration. Differences between disease transmission and waterfowl migration directions were significantly smaller for autumn than for spring migration. The four northward transmission directions were found along Asian flyways, where the initial epicenter of the virus was located. We suggest waterfowl first picked up the virus from East Asia, then brought it to the north via spring migration, and then spread it to other parts of world mainly by autumn migration. We emphasize waterfowl autumn migration plays a relatively important role in HPAI H5N1 transmission compared to spring migration.

  10. Southward autumn migration of waterfowl facilitates cross-continental transmission of the highly pathogenic avian influenza H5N1 virus.

    PubMed

    Xu, Yanjie; Gong, Peng; Wielstra, Ben; Si, Yali

    2016-08-10

    The highly pathogenic avian influenza subtype H5N1 (HPAI H5N1) is a worldwide zoonotic infectious disease, threatening humans, poultry and wild birds. The role of wild birds in the spread of HPAI H5N1 has previously been investigated by comparing disease spread patterns with bird migration routes. However, the different roles that the southward autumn and northward spring migration might play in virus transmission have hardly been explored. Using direction analysis, we analyze HPAI H5N1 transmission directions and angular concentration of currently circulating viral clades, and compare these with waterfowl seasonal migration directions along major waterfowl flyways. Out of 22 HPAI H5N1 transmission directions, 18 had both a southward direction and a relatively high concentration. Differences between disease transmission and waterfowl migration directions were significantly smaller for autumn than for spring migration. The four northward transmission directions were found along Asian flyways, where the initial epicenter of the virus was located. We suggest waterfowl first picked up the virus from East Asia, then brought it to the north via spring migration, and then spread it to other parts of world mainly by autumn migration. We emphasize waterfowl autumn migration plays a relatively important role in HPAI H5N1 transmission compared to spring migration.

  11. A Small Community Model for the Transmission of Infectious Diseases: Comparison of School Closure as an Intervention in Individual-Based Models of an Influenza Pandemic

    PubMed Central

    Milne, George J.; Kelso, Joel K.; Kelly, Heath A.; Huband, Simon T.; McVernon, Jodie

    2008-01-01

    Background In the absence of other evidence, modelling has been used extensively to help policy makers plan for a potential future influenza pandemic. Method We have constructed an individual based model of a small community in the developed world with detail down to exact household structure obtained from census collection datasets and precise simulation of household demographics, movement within the community and individual contact patterns. We modelled the spread of pandemic influenza in this community and the effect on daily and final attack rates of four social distancing measures: school closure, increased case isolation, workplace non-attendance and community contact reduction. We compared the modelled results of final attack rates in the absence of any interventions and the effect of school closure as a single intervention with other published individual based models of pandemic influenza in the developed world. Results We showed that published individual based models estimate similar final attack rates over a range of values for R0 in a pandemic where no interventions have been implemented; that multiple social distancing measures applied early and continuously can be very effective in interrupting transmission of the pandemic virus for R0 values up to 2.5; and that different conclusions reached on the simulated benefit of school closure in published models appear to result from differences in assumptions about the timing and duration of school closure and flow-on effects on other social contacts resulting from school closure. Conclusion Models of the spread and control of pandemic influenza have the potential to assist policy makers with decisions about which control strategies to adopt. However, attention needs to be given by policy makers to the assumptions underpinning both the models and the control strategies examined. PMID:19104659

  12. On avian influenza epidemic models with time delay.

    PubMed

    Liu, Sanhong; Ruan, Shigui; Zhang, Xinan

    2015-12-01

    After the outbreak of the first avian influenza A virus (H5N1) in Hong Kong in 1997, another avian influenza A virus (H7N9) crossed the species barrier in mainland China in 2013 and 2014 and caused more than 400 human cases with a death rate of nearly 40%. In this paper, we take account of the incubation periods of avian influenza A virus and construct a bird-to-human transmission model with different time delays in the avian and human populations combining the survival probability of the infective avian and human populations at the latent time. By analyzing the dynamical behavior of the model, we obtain a threshold value for the prevalence of avian influenza and investigate local and global asymptotical stability of equilibria of the system.

  13. 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

  14. Contact structures in the poultry industry in Great Britain: Exploring transmission routes for a potential avian influenza virus epidemic

    PubMed Central

    Dent, Jennifer E; Kao, Rowland R; Kiss, Istvan Z; Hyder, Kieran; Arnold, Mark

    2008-01-01

    Background The commercial poultry industry in United Kingdom (UK) is worth an estimated £3.4 billion at retail value, producing over 174 million birds for consumption per year. An epidemic of any poultry disease with high mortality or which is zoonotic, such as avian influenza virus (AIV), would result in the culling of significant numbers of birds, as seen in the Netherlands in 2003 and Italy in 2000. Such an epidemic would cost the UK government millions of pounds in compensation costs, with further economic losses through reduction of international and UK consumption of British poultry. In order to better inform policy advisers and makers on the potential for a large epidemic in GB, we investigate the role that interactions amongst premises within the British commercial poultry industry could play in promoting an AIV epidemic, given an introduction of the virus in a specific part of poultry industry in Great Britain (GB). Results Poultry premises using multiple slaughterhouses lead to a large number of premises being potentially connected, with the resultant potential for large and sometimes widespread epidemics. Catching companies can also potentially link a large proportion of the poultry population. Critical to this is the maximum distance traveled by catching companies between premises and whether or not between-species transmission could occur within individual premises. Premises closely linked by proximity may result in connections being formed between different species and or sectors within the industry. Conclusion Even quite well-contained epidemics have the potential for geographically widespread dissemination, potentially resulting in severe logistical problems for epidemic control, and with economic impact on a large part of the country. Premises sending birds to multiple slaughterhouses or housing multiple species may act as a bridge between otherwise separate sectors of the industry, resulting in the potential for large epidemics. Investment into

  15. Contact structures in the poultry industry in Great Britain: exploring transmission routes for a potential avian influenza virus epidemic.

    PubMed

    Dent, Jennifer E; Kao, Rowland R; Kiss, Istvan Z; Hyder, Kieran; Arnold, Mark

    2008-07-23

    The commercial poultry industry in United Kingdom (UK) is worth an estimated 3.4 billion pounds sterling at retail value, producing over 174 million birds for consumption per year. An epidemic of any poultry disease with high mortality or which is zoonotic, such as avian influenza virus (AIV), would result in the culling of significant numbers of birds, as seen in the Netherlands in 2003 and Italy in 2000. Such an epidemic would cost the UK government millions of pounds in compensation costs, with further economic losses through reduction of international and UK consumption of British poultry. In order to better inform policy advisers and makers on the potential for a large epidemic in GB, we investigate the role that interactions amongst premises within the British commercial poultry industry could play in promoting an AIV epidemic, given an introduction of the virus in a specific part of poultry industry in Great Britain (GB). Poultry premises using multiple slaughterhouses lead to a large number of premises being potentially connected, with the resultant potential for large and sometimes widespread epidemics. Catching companies can also potentially link a large proportion of the poultry population. Critical to this is the maximum distance traveled by catching companies between premises and whether or not between-species transmission could occur within individual premises. Premises closely linked by proximity may result in connections being formed between different species and or sectors within the industry. Even quite well-contained epidemics have the potential for geographically widespread dissemination, potentially resulting in severe logistical problems for epidemic control, and with economic impact on a large part of the country. Premises sending birds to multiple slaughterhouses or housing multiple species may act as a bridge between otherwise separate sectors of the industry, resulting in the potential for large epidemics. Investment into further data

  16. Avian influenza virus.

    PubMed

    Lee, Chang-Won; Saif, Yehia M

    2009-07-01

    Avian influenza viruses do not typically replicate efficiently in humans, indicating direct transmission of avian influenza virus to humans is unlikely. However, since 1997, several cases of human infections with different subtypes (H5N1, H7N7, and H9N2) of avian influenza viruses have been identified and raised the pandemic potential of avian influenza virus in humans. Although circumstantial evidence of human to human transmission exists, the novel avian-origin influenza viruses isolated from humans lack the ability to transmit efficiently from person-to-person. However, the on-going human infection with avian-origin H5N1 viruses increases the likelihood of the generation of human-adapted avian influenza virus with pandemic potential. Thus, a better understanding of the biological and genetic basis of host restriction of influenza viruses is a critical factor in determining whether the introduction of a novel influenza virus into the human population will result in a pandemic. In this article, we review current knowledge of type A influenza virus in which all avian influenza viruses are categorized.

  17. Influenza in Children.

    PubMed

    Kumar, Virendra

    2017-02-01

    In children, influenza is one among the commonest causes of acute respiratory illness and loss of school days. Influenza A, B, and C are 3 types of viruses responsible for illness. Type A virus has many subtypes based on antigens but Type B and Type C viruses have no known subtypes. Currently, influenza A/H1N1, A/H3N2, and influenza type B viruses are circulating in humans. Transmission of influenza occurs through droplets from infected person or through direct contact with person or fomites. Clinically, influenza is characterized by acute onset fever, chills, running nose, cough, sore throat, headache and myalgia. Mostly, febrile illness lasts for 3-4 d with resolution of disease in 7-10 d. Confirmation of influenza can be done either by virus culture, RT-PCR or specific neutralizing antibodies in blood. Basic principles of management include prompt institution of infection control measures, early identification of children at higher risk, supportive care and antiviral drugs. Vaccine and chemoprophylaxis are two commonly used methods for prevention of influenza. Currently, inactivated influenza vaccine (IIV) and live attenuated influenza vaccine (LAIV) are available for use with good efficacy. Cough etiquette, use of face masks and hand hygiene are the most important measures to reduce the risk of infection transmission from person to person.

  18. Experimentally Infected Domestic Ducks Show Efficient Transmission of Indonesian H5N1 Highly Pathogenic Avian Influenza Virus, but Lack Persistent Viral Shedding

    PubMed Central

    Wibawa, Hendra; Bingham, John; Nuradji, Harimurti; Lowther, Sue; Payne, Jean; Harper, Jenni; Junaidi, Akhmad; Middleton, Deborah; Meers, Joanne

    2014-01-01

    Ducks are important maintenance hosts for avian influenza, including H5N1 highly pathogenic avian influenza viruses. A previous study indicated that persistence of H5N1 viruses in ducks after the development of humoral immunity may drive viral evolution following immune selection. As H5N1 HPAI is endemic in Indonesia, this mechanism may be important in understanding H5N1 evolution in that region. To determine the capability of domestic ducks to maintain prolonged shedding of Indonesian clade 2.1 H5N1 virus, two groups of Pekin ducks were inoculated through the eyes, nostrils and oropharynx and viral shedding and transmission investigated. Inoculated ducks (n = 15), which were mostly asymptomatic, shed infectious virus from the oral route from 1 to 8 days post inoculation, and from the cloacal route from 2–8 dpi. Viral ribonucleic acid was detected from 1–15 days post inoculation from the oral route and 1–24 days post inoculation from the cloacal route (cycle threshold <40). Most ducks seroconverted in a range of serological tests by 15 days post inoculation. Virus was efficiently transmitted during acute infection (5 inoculation-infected to all 5 contact ducks). However, no evidence for transmission, as determined by seroconversion and viral shedding, was found between an inoculation-infected group (n = 10) and contact ducks (n = 9) when the two groups only had contact after 10 days post inoculation. Clinical disease was more frequent and more severe in contact-infected (2 of 5) than inoculation-infected ducks (1 of 15). We conclude that Indonesian clade 2.1 H5N1 highly pathogenic avian influenza virus does not persist in individual ducks after acute infection. PMID:24392085

  19. Experimentally infected domestic ducks show efficient transmission of Indonesian H5N1 highly pathogenic avian influenza virus, but lack persistent viral shedding.

    PubMed

    Wibawa, Hendra; Bingham, John; Nuradji, Harimurti; Lowther, Sue; Payne, Jean; Harper, Jenni; Junaidi, Akhmad; Middleton, Deborah; Meers, Joanne

    2014-01-01

    Ducks are important maintenance hosts for avian influenza, including H5N1 highly pathogenic avian influenza viruses. A previous study indicated that persistence of H5N1 viruses in ducks after the development of humoral immunity may drive viral evolution following immune selection. As H5N1 HPAI is endemic in Indonesia, this mechanism may be important in understanding H5N1 evolution in that region. To determine the capability of domestic ducks to maintain prolonged shedding of Indonesian clade 2.1 H5N1 virus, two groups of Pekin ducks were inoculated through the eyes, nostrils and oropharynx and viral shedding and transmission investigated. Inoculated ducks (n = 15), which were mostly asymptomatic, shed infectious virus from the oral route from 1 to 8 days post inoculation, and from the cloacal route from 2-8 dpi. Viral ribonucleic acid was detected from 1-15 days post inoculation from the oral route and 1-24 days post inoculation from the cloacal route (cycle threshold <40). Most ducks seroconverted in a range of serological tests by 15 days post inoculation. Virus was efficiently transmitted during acute infection (5 inoculation-infected to all 5 contact ducks). However, no evidence for transmission, as determined by seroconversion and viral shedding, was found between an inoculation-infected group (n = 10) and contact ducks (n = 9) when the two groups only had contact after 10 days post inoculation. Clinical disease was more frequent and more severe in contact-infected (2 of 5) than inoculation-infected ducks (1 of 15). We conclude that Indonesian clade 2.1 H5N1 highly pathogenic avian influenza virus does not persist in individual ducks after acute infection.

  20. Virulence and transmissibility of H1N2 influenza virus in ferrets imply the continuing threat of triple-reassortant swine viruses.

    PubMed

    Pascua, Philippe Noriel Q; Song, Min-Suk; Lee, Jun Han; Baek, Yun Hee; Kwon, Hyeok-il; Park, Su-Jin; Choi, Eun Hye; Lim, Gyo-Jin; Lee, Ok-Jun; Kim, Si-Wook; Kim, Chul-Joong; Sung, Moon Hee; Kim, Myung Hee; Yoon, Sun-Woo; Govorkova, Elena A; Webby, Richard J; Webster, Robert G; Choi, Young-Ki

    2012-09-25

    Efficient worldwide swine surveillance for influenza A viruses is urgently needed; the emergence of a novel reassortant pandemic H1N1 (pH1N1) virus in 2009 demonstrated that swine can be the direct source of pandemic influenza and that the pandemic potential of viruses prevalent in swine populations must be monitored. We used the ferret model to assess the pathogenicity and transmissibility of predominant Korean triple-reassortant swine (TRSw) H1N2 and H3N2 influenza viruses genetically related to North American strains. Although most of the TRSw viruses were moderately pathogenic, one [A/Swine/Korea/1204/2009; Sw/1204 (H1N2)] was virulent in ferrets, causing death within 10 d of inoculation, and was efficiently transmitted to naive contact ferrets via respiratory droplets. Although molecular analysis did not reveal known virulence markers, the Sw/1204 virus acquired mutations in hemagglutinin (HA) (Asp-225-Gly) and neuraminidase (NA) (Ser-315-Asn) proteins during the single ferret passage. The contact-Sw/1204 virus became more virulent in mice, replicated efficiently in vitro, extensively infected human lung tissues ex vivo, and maintained its ability to replicate and transmit in swine. Reverse-genetics studies further indicated that the HA(225G) and NA(315N) substitutions contributed substantially in altering virulence and transmissibility. These findings support the continuing threat of some field TRSw viruses to human and animal health, reviving concerns on the capacity of pigs to create future pandemic viruses. Apart from warranting continued and enhanced global surveillance, this study also provides evidence on the emerging roles of HA(225G) and NA(315N) as potential virulence markers in mammals.

  1. Insight into live bird markets of Bangladesh: an overview of the dynamics of transmission of H5N1 and H9N2 avian influenza viruses.

    PubMed

    Turner, Jasmine C M; Feeroz, Mohammed M; Hasan, M Kamrul; Akhtar, Sharmin; Walker, David; Seiler, Patrick; Barman, Subrata; Franks, John; Jones-Engel, Lisa; McKenzie, Pamela; Krauss, Scott; Webby, Richard J; Kayali, Ghazi; Webster, Robert G

    2017-03-08

    Highly pathogenic avian influenza (HPAI) H5N1 and low pathogenic avian influenza (LPAI) H9N2 viruses have been recognized as threats to public health in Bangladesh since 2007. Although live bird markets (LBMs) have been implicated in the transmission, dissemination, and circulation of these viruses, an in-depth analysis of the dynamics of avian transmission of H5N1 and H9N2 viruses at the human-animal interface has been lacking. Here we present and evaluate epidemiological findings from active surveillance conducted among poultry in various production sectors in Bangladesh from 2008 to 2016. Overall, the prevalence of avian influenza viruses (AIVs) in collected samples was 24%. Our data show that AIVs are more prevalent in domestic birds within LBMs (30.4%) than in farms (9.6%). Quail, chickens and ducks showed a high prevalence of AIVs (>20%). The vast majority of AIVs detected (99.7%) have come from apparently healthy birds and poultry drinking water served as a reservoir of AIVs with a prevalence of 32.5% in collected samples. HPAI H5N1 was more frequently detected in ducks while H9N2 was more common in chickens and quail. LBMs, particularly wholesale markets, have become a potential reservoir for various types of AIVs, including HPAI H5N1 and LPAI H9N2. The persistence of AIVs in LBMs is of great concern to public health, and this study highlights the importance of regularly reviewing and implementing infection control procedures as a means of reducing the exposure of the general public to AIVs.Emerging Microbes & Infections (2017) 6, e12; doi:10.1038/emi.2016.142; published online 8 March 2017.

  2. Insight into live bird markets of Bangladesh: an overview of the dynamics of transmission of H5N1 and H9N2 avian influenza viruses

    PubMed Central

    Turner, Jasmine C M; Feeroz, Mohammed M; Hasan, M Kamrul; Akhtar, Sharmin; Walker, David; Seiler, Patrick; Barman, Subrata; Franks, John; Jones-Engel, Lisa; McKenzie, Pamela; Krauss, Scott; Webby, Richard J; Kayali, Ghazi; Webster, Robert G

    2017-01-01

    Highly pathogenic avian influenza (HPAI) H5N1 and low pathogenic avian influenza (LPAI) H9N2 viruses have been recognized as threats to public health in Bangladesh since 2007. Although live bird markets (LBMs) have been implicated in the transmission, dissemination, and circulation of these viruses, an in-depth analysis of the dynamics of avian transmission of H5N1 and H9N2 viruses at the human–animal interface has been lacking. Here we present and evaluate epidemiological findings from active surveillance conducted among poultry in various production sectors in Bangladesh from 2008 to 2016. Overall, the prevalence of avian influenza viruses (AIVs) in collected samples was 24%. Our data show that AIVs are more prevalent in domestic birds within LBMs (30.4%) than in farms (9.6%). Quail, chickens and ducks showed a high prevalence of AIVs (>20%). The vast majority of AIVs detected (99.7%) have come from apparently healthy birds and poultry drinking water served as a reservoir of AIVs with a prevalence of 32.5% in collected samples. HPAI H5N1 was more frequently detected in ducks while H9N2 was more common in chickens and quail. LBMs, particularly wholesale markets, have become a potential reservoir for various types of AIVs, including HPAI H5N1 and LPAI H9N2. The persistence of AIVs in LBMs is of great concern to public health, and this study highlights the importance of regularly reviewing and implementing infection control procedures as a means of reducing the exposure of the general public to AIVs. PMID:28270655

  3. The neuraminidase and matrix genes of the 2009 pandemic influenza H1N1 virus cooperate functionally to facilitate efficient replication and transmissibility in pigs

    PubMed Central

    Liu, Qinfang; Bawa, Bhupinder; Qiao, Chuanling; Qi, Wenbao; Shen, Huigang; Chen, Ying; Ma, Jingqun; Li, Xi; Webby, Richard J.; García-Sastre, Adolfo

    2012-01-01

    The 2009 pandemic H1N1 virus (pH1N1) contains neuraminidase (NA) and matrix (M) genes from Eurasian avian-like swine influenza viruses (SIVs), with the remaining six genes from North American triple-reassortant SIVs. To characterize the role of the pH1N1 NA and M genes in pathogenesis and transmission, their impact was evaluated in the background of an H1N1 triple-reassortant (tr1930) SIV in which the HA (H3) and NA (N2) of influenza A/swine/Texas/4199-2/98 virus were replaced with those from the classical H1N1 A/swine/Iowa/15/30 (1930) virus. The laboratory-adapted 1930 virus did not shed nor transmit in pigs, but tr1930 was able to shed in infected pigs. The NA, M or both genes of the tr1930 virus were then substituted by those of pH1N1. The resulting virus with both NA and M from pH1N1 grew to significantly higher titre in cell cultures than the viruses with single NA or M from pH1N1. In a pig model, only the virus containing both NA and M from pH1N1 was transmitted to and infected sentinels, whereas the viruses with single NA or M from pH1N1 did not. These results demonstrate that the right combination of NA and M genes is critical for the replication and transmissibility of influenza viruses in pigs. PMID:22337640

  4. Extracting transmission networks from phylogeographic data for epidemic and endemic diseases: Ebola virus in Sierra Leone, 2009 H1N1 pandemic influenza and polio in Nigeria.

    PubMed

    Famulare, Michael; Hu, Hao

    2015-03-01

    Phylogeography improves our understanding of spatial epidemiology. However, application to practical problems requires choices among computational tools to balance statistical rigor, computational complexity, sensitivity to sampling strategy and interpretability. We introduce a fast, heuristic algorithm to reconstruct partially-observed transmission networks (POTN) that combines features of phylogenetic and transmission tree approaches. We compare the transmission network generated by POTN with existing algorithms (BEAST and SeqTrack), and discuss the benefits and challenges of phylogeographic analysis on examples of epidemic and endemic diseases: Ebola virus, H1N1 pandemic influenza and polio. For the 2014 Sierra Leone Ebola virus outbreak and the 2009 H1N1 outbreak, all three methods provide similarly plausible transmission histories but differ in detail. For polio in northern Nigeria, we discuss performance trade-offs between the POTN and discrete phylogeography in BEAST and conclude that spatial history reconstruction is limited by under-sampling. POTN is complementary to available tools on densely-sampled data, fails gracefully on under-sampled data and is scalable to accommodate larger datasets. We provide further evidence for the utility of phylogeography for understanding transmission networks of rapidly evolving epidemics. We propose simple heuristic criteria to identify how sampling rates and disease dynamics interact to determine fundamental limitations of phylogeographic inference. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.

  5. Extracting transmission networks from phylogeographic data for epidemic and endemic diseases: Ebola virus in Sierra Leone, 2009 H1N1 pandemic influenza and polio in Nigeria

    PubMed Central

    Famulare, Michael; Hu, Hao

    2015-01-01

    Background Phylogeography improves our understanding of spatial epidemiology. However, application to practical problems requires choices among computational tools to balance statistical rigor, computational complexity, sensitivity to sampling strategy and interpretability. Methods We introduce a fast, heuristic algorithm to reconstruct partially-observed transmission networks (POTN) that combines features of phylogenetic and transmission tree approaches. We compare the transmission network generated by POTN with existing algorithms (BEAST and SeqTrack), and discuss the benefits and challenges of phylogeographic analysis on examples of epidemic and endemic diseases: Ebola virus, H1N1 pandemic influenza and polio. Results For the 2014 Sierra Leone Ebola virus outbreak and the 2009 H1N1 outbreak, all three methods provide similarly plausible transmission histories but differ in detail. For polio in northern Nigeria, we discuss performance trade-offs between the POTN and discrete phylogeography in BEAST and conclude that spatial history reconstruction is limited by under-sampling. Conclusions POTN is complementary to available tools on densely-sampled data, fails gracefully on under-sampled data and is scalable to accommodate larger datasets. We provide further evidence for the utility of phylogeography for understanding transmission networks of rapidly evolving epidemics. We propose simple heuristic criteria to identify how sampling rates and disease dynamics interact to determine fundamental limitations of phylogeographic inference. PMID:25733563

  6. Detection of Oseltamivir-Resistant Pandemic Influenza A(H1N1)pdm2009 in Brazil: Can Community Transmission Be Ruled Out?

    PubMed Central

    Souza, Thiago Moreno L.; Resende, Paola C.; Fintelman-Rodrigues, Natalia; Gregianini, Tatiana Schaffer; Ikuta, Nilo; Fernandes, Sandra Bianchini; Cury, Ana Luisa Furtado; Rosa, Maria do Carmo Debur; Siqueira, Marilda M.

    2013-01-01

    Although surveillance efforts that monitor the emergence of drug-resistant strains of influenza are critical, systematic analysis is overlooked in most developing countries. We report on the occurrence of strains of pandemic influenza A(H1N1)pdm09 with resistance and decreased susceptibility to oseltamivir (OST) in Brazil in 2009, 2011 and 2012. We found 7 mutant viruses, 2 with the mutation S247N and other 5 with the mutation H275Y. Most of these viruses were from samples concentrated in the southern region of Brazil. Some of these resistant viruses were detected prior to the initiation of OST treatment, suggesting that community transmission of mutant viruses may exist. Moreover, we show that one of these OST-resistant (H275Y) strains of A(H1N1)pdm09 was discovered in the tri-border region between Brazil, Argentina and Paraguay, highlighting that this strain could also be found in other Latin American countries. Our findings reinforce the importance of enhanced antiviral resistance surveillance in Brazil and in other Latin American countries to confirm or rule out the community transmission of OST-resistant strains of A(H1N1)pdm09. PMID:24244615

  7. Transmission dynamics of pandemic influenza A(H1N1)pdm09 virus in humans and swine in backyard farms in Tumbes, Peru.

    PubMed

    Tinoco, Yeny O; Montgomery, Joel M; Kasper, Mathew R; Nelson, Martha I; Razuri, Hugo; Guezala, Maria C; Azziz-Baumgartner, Eduardo; Widdowson, Marc-Alain; Barnes, John; Gilman, Robert H; Bausch, Daniel G; Gonzalez, Armando E

    2016-01-01

    We aimed to determine the frequency of pH1N1 transmission between humans and swine on backyard farms in Tumbes, Peru. Two-year serial cross-sectional study comprising four sampling periods: March 2009 (pre-pandemic), October 2009 (peak of the pandemic in Peru), April 2010 (1st post-pandemic period), and October 2011 (2nd post-pandemic period). Backyard swine serum, tracheal swabs, and lung sample were collected during each sampling period. We assessed current and past pH1N1 infection in swine through serological testing, virus culture, and RT-PCR and compared the results with human incidence data from a population-based active surveillance cohort study in Peru. Among 1303 swine sampled, the antibody prevalence to pH1N1 was 0% pre-pandemic, 8% at the peak of the human pandemic (October 2009), and 24% in April 2010 and 1% in October 2011 (post-pandemic sampling periods). Trends in swine seropositivity paralleled those seen in humans in Tumbes. The pH1N1 virus was isolated from three pigs during the peak of the pandemic. Phylogenetic analysis revealed that these viruses likely represent two separate human-to-swine transmission events in backyard farm settings. Our findings suggest that human-to-swine pH1N1 transmission occurred during the pandemic among backyard farms in Peru, emphasizing the importance of interspecies transmission in backyard pig populations. Continued surveillance for influenza viruses in backyard farms is warranted. © 2015 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

  8. HIV prevention is not enough: child survival in the context of prevention of mother to child HIV transmission

    PubMed Central

    2009-01-01

    Clinical and epidemiologic research has identified increasingly effective interventions to reduce mother to child HIV transmission in resource-limited settings These scientific breakthroughs have been implemented in some programmes, although much remains to be done to improve coverage and quality of these programmes. But prevention of HIV transmission is not enough. It is necessary also to consider ways to improve maternal health and protect child survival. A win-win approach is to ensure that all pregnant and lactating women with CD4 counts of <350 cells/mm3 have access to antiretroviral therapy. On its own, this approach will substantially improve maternal health and markedly reduce mother to child HIV transmission during pregnancy and delivery and through breastfeeding. This approach can be combined with additional interventions for women with higher CD4 counts, either extended prophylaxis to infants or extended regimens of antiretroviral drugs to women, to reduce transmission even further. Attempts to encourage women to abstain from all breastfeeding or to shorten the optimal duration of breastfeeding have led to increases in mortality among both uninfected and infected children. A better approach is to support breastfeeding while strengthening programmes to provide antiretroviral therapy for pregnant and lactating women who need it and offering antiretroviral drug interventions through the duration of breastfeeding. This will lead to reduced HIV transmission and will protect the health of women without compromising the health and well-being of infants and young children. PMID:20015345

  9. Seasonal Influenza Epidemics and El Niños

    PubMed Central

    Oluwole, Olusegun Steven Ayodele

    2015-01-01

    Seasonal influenza epidemics occur annually during the winter in the northern and southern hemispheres, but timing of peaks and severity vary seasonally. Low humidity, which enhances survival and transmission of influenza virus, is the major risk factor. Both El Niño and La Niña phases of El Niño-southern oscillation (ENSO), which determine inter-annual variation of precipitation, are putative risk factors. This study was done to determine if seasonality, timing of peak, and severity of influenza epidemics are coupled to phases of ENSO. Monthly time series of positive specimens for influenza viruses and of multivariate El Niño-Southern Oscillation Index from January 2000 to August 2015 were analyzed. Seasonality, wavelet spectra, and cross-wavelet spectra analyses were performed. Of 31 countries in the dataset, 21 were in the northern hemisphere and 10 in the southern hemisphere. The highest number of influenza cases occurred in January in the northern hemisphere, but in July in the southern hemisphere, p < 0.0001. Seasonal influenza epidemic was coupled to El Niño, while low occurrence was coupled to La Niña. The moderate La Niña of 2010–2011 was followed by weak seasonal influenza epidemic. The influenza pandemic of 2009–2010 followed the moderate El Niño of 2009–2010, which had three peaks. Spectrograms showed time-varying periodicities of 6–48 months for ENSO, 6–24 months for influenza in the northern hemisphere, and 6–12 months for influenza in the southern hemisphere. Cross spectrograms showed time-varying periodicities at 6–36 months for ENSO and influenza in both hemispheres, p < 0.0001. Phase plots showed that influenza time series lagged ENSO in both hemispheres. Severity of seasonal influenza increases during El Niño, but decreases during La Niña. Coupling of seasonality, timing, and severity of influenza epidemics to the strength and waveform of ENSO indicate that forecast models of El Niño should be integrated

  10. Seasonal Influenza Epidemics and El Niños.

    PubMed

    Oluwole, Olusegun Steven Ayodele

    2015-01-01

    Seasonal influenza epidemics occur annually during the winter in the northern and southern hemispheres, but timing of peaks and severity vary seasonally. Low humidity, which enhances survival and transmission of influenza virus, is the major risk factor. Both El Niño and La Niña phases of El Niño-southern oscillation (ENSO), which determine inter-annual variation of precipitation, are putative risk factors. This study was done to determine if seasonality, timing of peak, and severity of influenza epidemics are coupled to phases of ENSO. Monthly time series of positive specimens for influenza viruses and of multivariate El Niño-Southern Oscillation Index from January 2000 to August 2015 were analyzed. Seasonality, wavelet spectra, and cross-wavelet spectra analyses were performed. Of 31 countries in the dataset, 21 were in the northern hemisphere and 10 in the southern hemisphere. The highest number of influenza cases occurred in January in the northern hemisphere, but in July in the southern hemisphere, p < 0.0001. Seasonal influenza epidemic was coupled to El Niño, while low occurrence was coupled to La Niña. The moderate La Niña of 2010-2011 was followed by weak seasonal influenza epidemic. The influenza pandemic of 2009-2010 followed the moderate El Niño of 2009-2010, which had three peaks. Spectrograms showed time-varying periodicities of 6-48 months for ENSO, 6-24 months for influenza in the northern hemisphere, and 6-12 months for influenza in the southern hemisphere. Cross spectrograms showed time-varying periodicities at 6-36 months for ENSO and influenza in both hemispheres, p < 0.0001. Phase plots showed that influenza time series lagged ENSO in both hemispheres. Severity of seasonal influenza increases during El Niño, but decreases during La Niña. Coupling of seasonality, timing, and severity of influenza epidemics to the strength and waveform of ENSO indicate that forecast models of El Niño should be integrated into

  11. Seroepidemiological evidence of avian H4, H5, and H9 influenza A virus transmission to pigs in southeastern China.

    PubMed

    Ninomiya, Ai; Takada, Ayato; Okazaki, Katsunori; Shortridge, Kennedy F; Kida, Hiroshi

    2002-08-25

    Pig serum samples collected in southeastern China were examined for antibodies to influenza A viruses. Since the hemagglutination inhibition (HI) test does not accurately detect antibodies to the hemagglutinins (HAs) of "avian" influenza viruses, we utilized the neutralization (NT) test to detect subtype-specific antibodies to the HA of avian viruses in pig sera. Neutralizing antibodies to H1, H3, H4, and H5 influenza viruses were detected in the serum samples collected in 1977-1982 and 1998, suggesting that pigs in China have been sporadically infected with avian H4 and H5 viruses in addition to swine and human H1 and H3 viruses. Antibodies to H9 virus, on the other hand, were found only in the sera collected in 1998, not in those collected in 1977-1982, correlating with the recent spread in poultry and subsequent isolation of H9N2 viruses from pigs and humans in 1998. The present results indicate that avian influenza viruses have been transmitted to pig populations in southeastern China.

  12. The avian-origin PB1 gene segment facilitated replication and transmissibility of the H3N2/1968 pandemic influenza virus.

    PubMed

    Wendel, Isabel; Rubbenstroth, Dennis; Doedt, Jennifer; Kochs, Georg; Wilhelm, Jochen; Staeheli, Peter; Klenk, Hans-Dieter; Matrosovich, Mikhail

    2015-04-01

    The H2N2/1957 and H3N2/1968 pandemic influenza viruses emerged via the exchange of genomic RNA segments between human and avian viruses. The avian hemagglutinin (HA) allowed the hybrid viruses to escape preexisting immunity in the human population. Both pandemic viruses further received the PB1 gene segment from the avian parent (Y. Kawaoka, S. Krauss, and R. G. Webster, J Virol 63:4603-4608, 1989), but the biological significance of this observation was not understood. To assess whether the avian-origin PB1 segment provided pandemic viruses with some selective advantage, either on its own or via cooperation with the homologous HA segment, we modeled by reverse genetics the reassortment event that led to the emergence of the H3N2/1968 pandemic virus. Using seasonal H2N2 virus A/California/1/66 (Cal) as a surrogate precursor human virus and pandemic virus A/Hong Kong/1/68 (H3N2) (HK) as a source of avian-derived PB1 and HA gene segments, we generated four reassortant recombinant viruses and compared pairs of viruses which differed solely by the origin of PB1. Replacement of the PB1 segment of Cal by PB1 of HK facilitated viral polymerase activity, replication efficiency in human cells, and contact transmission in guinea pigs. A combination of PB1 and HA segments of HK did not enhance replicative fitness of the reassortant virus compared with the single-gene PB1 reassortant. Our data suggest that the avian PB1 segment of the 1968 pandemic virus served to enhance viral growth and transmissibility, likely by enhancing activity of the viral polymerase complex. Despite the high impact of influenza pandemics on human health, some mechanisms underlying the emergence of pandemic influenza viruses still are poorly understood. Thus, it was unclear why both H2N2/1957 and H3N2/1968 reassortant pandemic viruses contained, in addition to the avian HA, the PB1 gene segment of the avian parent. Here, we addressed this long-standing question by modeling the emergence of the H3N2

  13. Role of vaccination-induced immunity and antigenic distance in the transmission dynamics of highly pathogenic avian influenza H5N1.

    PubMed

    Sitaras, Ioannis; Rousou, Xanthoula; Kalthoff, Donata; Beer, Martin; Peeters, Ben; de Jong, Mart C M

    2016-01-01

    Highly pathogenic avian influenza (HPAI) H5N1 epidemics in poultry cause huge economic losses as well as sporadic human morbidity and mortality. Vaccination in poultry has often been reported as being ineffective in preventing transmission and as a potential driving force in the selection of immune escape mutants. We conducted transmission experiments to evaluate the transmission dynamics of HPAI H5N1 strains in chickens vaccinated with high and low doses of immune escape mutants we have previously selected, and analysed the data using mathematical models. Remarkably, we demonstrate that the effect of antigenic distances between the vaccine and challenge strains used in this study is too small to influence the transmission dynamics of the strains used. This is because the effect of a sufficient vaccine dose on antibody levels against the challenge viruses is large enough to compensate for any decrease in antibody titres due to antigenic differences between vaccine and challenge strains. Our results show that at least under experimental conditions, vaccination will remain effective even after antigenic changes as may be caused by the initial selection in vaccinated birds.

  14. Role of vaccination-induced immunity and antigenic distance in the transmission dynamics of highly pathogenic avian influenza H5N1

    PubMed Central

    Rousou, Xanthoula; Kalthoff, Donata; Beer, Martin

    2016-01-01

    Highly pathogenic avian influenza (HPAI) H5N1 epidemics in poultry cause huge economic losses as well as sporadic human morbidity and mortality. Vaccination in poultry has often been reported as being ineffective in preventing transmission and as a potential driving force in the selection of immune escape mutants. We conducted transmission experiments to evaluate the transmission dynamics of HPAI H5N1 strains in chickens vaccinated with high and low doses of immune escape mutants we have previously selected, and analysed the data using mathematical models. Remarkably, we demonstrate that the effect of antigenic distances between the vaccine and challenge strains used in this study is too small to influence the transmission dynamics of the strains used. This is because the effect of a sufficient vaccine dose on antibody levels against the challenge viruses is large enough to compensate for any decrease in antibody titres due to antigenic differences between vaccine and challenge strains. Our results show that at least under experimental conditions, vaccination will remain effective even after antigenic changes as may be caused by the initial selection in vaccinated birds. PMID:26763336

  15. Differences in transmissibility and pathogenicity of reassortants between H9N2 and 2009 pandemic H1N1 influenza A viruses from humans and swine.

    PubMed

    He, Liang; Wu, Qiwen; Jiang, Kaijun; Duan, Zhiqiang; Liu, Jingjing; Xu, Haixu; Cui, Zhu; Gu, Min; Wang, Xiaoquan; Liu, Xiaowen; Liu, Xiufan

    2014-07-01

    Both H9N2 subtype avian influenza and 2009 pandemic H1N1 viruses (pH1N1) can infect humans and pigs, which provides the opportunity for virus reassortment, leading to the genesis of new strains with potential pandemic risk. In this study, we generated six reassortant H9 viruses in the background of three pH1N1 strains from different hosts (A/California/04/2009 [CA04], A/Swine/Jiangsu/48/2010 [JS48] and A/Swine/Jiangsu/285/2010 [JS285]) by replacing either the HA (H9N1-pH1N1) or both the HA and NA genes (H9N2-pH1N1) from an h9.4.2.5-lineage H9N2 subtype influenza virus, A/Swine/Taizhou/5/08 (TZ5). The reassortant H9 viruses replicated to higher titers in vitro and in vivo and gained both efficient transmissibility in guinea pigs and increased pathogenicity in mice compared with the parental H9N2 virus. In addition, differences in transmissibility and pathogenicity were observed among these reassortant H9 viruses. The H9N2-pH1N1viruses were transmitted more efficiently than the corresponding H9N1-pH1N1 viruses but showed significantly decreased pathogenicity. One of the reassortant H9 viruses that were generated, H9N-JS48, showed the highest virulence in mice and acquired respiratory droplet transmissibility between guinea pigs. These results indicate that coinfection of swine with H9N2 and pH1N1viruses may pose a threat for humans if reassortment occurs, emphasizing the importance of surveillance of these viruses in their natural hosts.

  16. Moraxella catarrhalis outer membrane vesicles carry β-lactamase and promote survival of Streptococcus pneumoniae and Haemophilus influenzae by inactivating amoxicillin.

    PubMed

    Schaar, Viveka; Nordström, Therése; Mörgelin, Matthias; Riesbeck, Kristian

    2011-08-01

    Moraxella catarrhalis is a common pathogen found in children with upper respiratory tract infections and in patients with chronic obstructive pulmonary disease during exacerbations. The bacterial species is often isolated together with Streptococcus pneumoniae and Haemophilus influenzae. Outer membrane vesicles (OMVs) are released by M. catarrhalis and contain phospholipids, adhesins, and immunomodulatory compounds such as lipooligosaccharide. We have recently shown that M. catarrhalis OMVs exist in patients upon nasopharyngeal colonization. As virtually all M. catarrhalis isolates are β-lactamase positive, the goal of this study was to investigate whether M. catarrhalis OMVs carry β-lactamase and to analyze if OMV consequently can prevent amoxicillin-induced killing. Recombinant β-lactamase was produced and antibodies were raised in rabbits. Transmission electron microscopy, flow cytometry, and Western blotting verified that OMVs carried β-lactamase. Moreover, enzyme assays revealed that M. catarrhalis OMVs contained active β-lactamase. OMVs (25 μg/ml) incubated with amoxicillin for 1 h completely hydrolyzed amoxicillin at concentrations up to 2.5 μg/ml. In functional experiments, preincubation of amoxicillin (10× MIC) with M. catarrhalis OMVs fully rescued amoxicillin-susceptible M. catarrhalis, S. pneumoniae, and type b or nontypeable H. influenzae from β-lactam-induced killing. Our results suggest that the presence of amoxicillin-resistant M. catarrhalis originating from β-lactamase-containing OMVs may pave the way for respiratory pathogens that by definition are susceptible to β-lactam antibiotics.

  17. Experimental infection of highly and low pathogenic avian influenza viruses to chickens, ducks, tree sparrows, jungle crows, and black rats for the evaluation of their roles in virus transmission.

    PubMed

    Hiono, Takahiro; Okamatsu, Masatoshi; Yamamoto, Naoki; Ogasawara, Kohei; Endo, Mayumi; Kuribayashi, Saya; Shichinohe, Shintaro; Motohashi, Yurie; Chu, Duc-Huy; Suzuki, Mizuho; Ichikawa, Takaya; Nishi, Tatsuya; Abe, Yuri; Matsuno, Keita; Tanaka, Kazuyuki; Tanigawa, Tsutomu; Kida, Hiroshi; Sakoda, Yoshihiro

    2016-01-01

    Highly pathogenic avian influenza viruses (HPAIVs) have spread in both poultry and wild birds. Determining transmission routes of these viruses during an outbreak is essential for the control of avian influenza. It has been widely postulated that migratory ducks play crucial roles in the widespread dissemination of HPAIVs in poultry by carrying viruses along with their migrations; however close contacts between wild migratory ducks and poultry are less likely in modern industrial poultry farming settings. Therefore, we conducted experimental infections of HPAIVs and low pathogenic avian influenza viruses (LPAIVs) to chickens, domestic ducks, tree sparrows, jungle crows, and black rats to evaluate their roles in virus transmission. The results showed that chickens, ducks, sparrows, and crows were highly susceptible to HPAIV infection. Significant titers of virus were recovered from the sparrows and crows infected with HPAIVs, which suggests that they potentially play roles of transmission of HPAIVs to poultry. In contrast, the growth of LPAIVs was limited in each of the animals tested compared with that of HPAIVs. The present results indicate that these common synanthropes play some roles in influenza virus transmission from wild birds to poultry. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Spatial modeling of wild bird risk factors to investigate highly pathogenic A(H5N1) avian influenza virus transmission

    USGS Publications Warehouse

    Prosser, Diann J.; Hungerford, Laura L.; Erwin, R. Michael; Ottinger, Mary Ann; Takekawa, John Y.; Newman, Scott H.; Xiao, Xianming; Ellis, Erie C.

    2016-01-01

    One of the longest-persisting avian influenza viruses in history, highly pathogenic avian influenza virus (HPAIV) A(H5N1), continues to evolve after 18 years, advancing the threat of a global pandemic. Wild waterfowl (family Anatidae), are reported as secondary transmitters of HPAIV, and primary reservoirs for low-pathogenic avian influenza viruses, yet spatial inputs for disease risk modeling for this group have been lacking. Using GIS and Monte Carlo simulations, we developed geospatial indices of waterfowl abundance at 1 and 30 km resolutions and for the breeding and wintering seasons for China, the epicenter of H5N1. Two spatial layers were developed: cumulative waterfowl abundance (WAB), a measure of predicted abundance across species, and cumulative abundance weighted by H5N1 prevalence (WPR), whereby abundance for each species was adjusted based on prevalence values then totaled across species. Spatial patterns of the model output differed between seasons, with higher WAB and WPR in the northern and western regions of China for the breeding season and in the southeast for the wintering season. Uncertainty measures indicated highest error in southeastern China for both WAB and WPR. We also explored the effect of resampling waterfowl layers from 1 km to 30 km resolution for multi-scale risk modeling. Results indicated low average difference (less than 0.16 and 0.01 standard deviations for WAB and WPR, respectively), with greatest differences in the north for the breeding season and southeast for the wintering season. This work provides the first geospatial models of waterfowl abundance available for China. The indices provide important inputs for modeling disease transmission risk at the interface of poultry and wild birds. These models are easily adaptable, have broad utility to both disease and conservation needs, and will be available to the scientific community for advanced modeling applications.

  19. Evaluation of oseltamivir prophylaxis regimens for reducing influenza virus infection, transmission and disease severity in a ferret model of household contact.

    PubMed

    Oh, Ding Yuan; Lowther, Sue; McCaw, James M; Sullivan, Sheena G; Leang, Sook-Kwan; Haining, Jessica; Arkinstall, Rachel; Kelso, Anne; Mcvernon, Jodie; Barr, Ian G; Middleton, Deborah; Hurt, Aeron C

    2014-09-01

    The emergence of the pandemic influenza A(H1N1)pdm09 virus in 2009 saw a significant increase in the therapeutic and prophylactic use of neuraminidase inhibitors (NAIs) to mitigate the impact of this highly transmissible virus. Prior to the pandemic, many countries stockpiled NAIs and developed pandemic plans for the use of antiviral drugs, based on either treatment of high-risk individuals and/or prophylaxis of contacts. However, to date there has been a lack of in vivo models to test the efficacy of treatment or prophylaxis with NAIs, for influenza-infected individuals or exposed contacts, in a household setting. A ferret model of household contact was developed to study the efficacy of different prophylaxis regimens in preventing infection in contact ferrets exposed to influenza A(H1N1)pdm09-infected index ferrets. Among the different prophylactic regimens, contact ferrets receiving oseltamivir prophylaxis twice daily showed better outcomes than those receiving oseltamivir once daily. Benefits included a significant delay in the time to secondary infection, lower weight loss and higher activity levels. The treatment of index ferrets at 36 h post-infection did not influence either secondary infection rates or clinical symptoms in exposed contact ferrets. Neither prophylaxis nor treatment prevented infection or reduced the duration of viral shedding, although clinical symptoms did improve in infected animals receiving prophylaxis. Different oseltamivir prophylaxis regimens did not prevent infections, but consistently resulted in a reduction in symptoms in infected ferrets. However, oseltamivir prophylaxis failed to reduce viral titres, which warrants further investigation in humans. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

  20. Evaluation of oseltamivir prophylaxis regimens for reducing influenza virus infection, transmission and disease severity in a ferret model of household contact

    PubMed Central

    Oh, Ding Yuan; Lowther, Sue; McCaw, James M.; Sullivan, Sheena G.; Leang, Sook-Kwan; Haining, Jessica; Arkinstall, Rachel; Kelso, Anne; Mcvernon, Jodie; Barr, Ian G.; Middleton, Deborah; Hurt, Aeron C.

    2014-01-01

    Objectives The emergence of the pandemic influenza A(H1N1)pdm09 virus in 2009 saw a significant increase in the therapeutic and prophylactic use of neuraminidase inhibitors (NAIs) to mitigate the impact of this highly transmissible virus. Prior to the pandemic, many countries stockpiled NAIs and developed pandemic plans for the use of antiviral drugs, based on either treatment of high-risk individuals and/or prophylaxis of contacts. However, to date there has been a lack of in vivo models to test the efficacy of treatment or prophylaxis with NAIs, for influenza-infected individuals or exposed contacts, in a household setting. Methods A ferret model of household contact was developed to study the efficacy of different prophylaxis regimens in preventing infection in contact ferrets exposed to influenza A(H1N1)pdm09-infected index ferrets. Results Among the different prophylactic regimens, contact ferrets receiving oseltamivir prophylaxis twice daily showed better outcomes than those receiving oseltamivir once daily. Benefits included a significant delay in the time to secondary infection, lower weight loss and higher activity levels. The treatment of index ferrets at 36 h post-infection did not influence either secondary infection rates or clinical symptoms in exposed contact ferrets. Neither prophylaxis nor treatment prevented infection or reduced the duration of viral shedding, although clinical symptoms did improve in infected animals receiving prophylaxis. Conclusions Different oseltamivir prophylaxis regimens did not prevent infections, but consistently resulted in a reduction in symptoms in infected ferrets. However, oseltamivir prophylaxis failed to reduce viral titres, which warrants further investigation in humans. PMID:24840623

  1. Reducing perinatal HIV transmission in developing countries through antenatal and delivery care, and breastfeeding: supporting infant survival by supporting women's survival.

    PubMed Central

    Berer, M.

    1999-01-01

    In 1998, a joint UNAIDS/UNICEF/WHO working group announced an initiative to pilot test an intervention to reduce perinatal transmission of human immunodeficiency virus (HIV), based on new guidelines on HIV and infant feeding. This intervention for developing countries includes short-course perinatal zidovudine (AZT) treatment and advice to HIV-positive women not to breastfeed their infants, where this can be done safely. The present paper raises questions about the extent of the public health benefit of this intervention, even though it may be cost-effective, due to the limited capacity of antenatal and delivery services to implement it fully. It argues that it is necessary to provide universal access to replacement feeding methods and support in their safe use, not only for women who have tested HIV-positive during pregnancy, but also for untested women who may also decide not to breastfeed, some of whom may be infected with HIV or may acquire HIV during the breastfeeding period. It further argues that additional funding, more staff, staff training, and improved capacity and resources are also needed to integrate this intervention successfully into antenatal and delivery care. The intervention will prevent some infants from getting HIV even in the absence of many of these changes. However, a comprehensive approach to HIV prevention and care in developing countries that includes both women and infants would promote better health and survival of women, which would in turn contribute to greater infant health and survival. If combination antiretroviral therapy in the latter part of pregnancy and/or during the breastfeeding period can be shown to be safe for infants, preliminary evidence suggests that it might reduce perinatal HIV transmission as effectively as the current intervention and, in addition, might allow the practice of breastfeeding to be preserved. PMID:10612882

  2. Oral Administration of Lactobacillus plantarum Strain AYA Enhances IgA Secretion and Provides Survival Protection against Influenza Virus Infection in Mice

    PubMed Central

    Kikuchi, Yosuke; Kunitoh-Asari, Ayami; Hayakawa, Katsuyuki; Imai, Shinjiro; Kasuya, Kenji; Abe, Kimio; Adachi, Yu; Fukudome, Shin-ichi; Takahashi, Yoshimasa; Hachimura, Satoshi

    2014-01-01

    The mucosal immune system provides the first line of defense against inhaled and ingested pathogenic microbacteria and viruses. This defense system, to a large extent, is mediated by the actions of secretory IgA. In this study, we screened 140 strains of lactic acid bacteria for induction of IgA production by murine Peyer’s patch cells. We selected one strain and named it Lactobacillus plantarum AYA. We found that L. plantarum AYA-induced production of IL-6 in Peyer’s patch dendritic cells, with this production promoting IgA+ B cells to differentiate into IgA-secreting plasma cells. We also observed that oral administration of L. plantarum AYA in mice caused an increase in IgA production in the small intestine and lung. This production of IgA correlated strongly with protective ability, with the treated mice surviving longer than the control mice after lethal influenza virus infection. Our data therefore reveals a novel immunoregulatory role of the L. plantarum AYA strain which enhances mucosal IgA production and provides protection against respiratory influenza virus infection. PMID:24466081

  3. Oral administration of Lactobacillus plantarum strain AYA enhances IgA secretion and provides survival protection against influenza virus infection in mice.

    PubMed

    Kikuchi, Yosuke; Kunitoh-Asari, Ayami; Hayakawa, Katsuyuki; Imai, Shinjiro; Kasuya, Kenji; Abe, Kimio; Adachi, Yu; Fukudome, Shin-Ichi; Takahashi, Yoshimasa; Hachimura, Satoshi

    2014-01-01

    The mucosal immune system provides the first line of defense against inhaled and ingested pathogenic microbacteria and viruses. This defense system, to a large extent, is mediated by the actions of secretory IgA. In this study, we screened 140 strains of lactic acid bacteria for induction of IgA production by murine Peyer's patch cells. We selected one strain and named it Lactobacillus plantarum AYA. We found that L. plantarum AYA-induced production of IL-6 in Peyer's patch dendritic cells, with this production promoting IgA(+) B cells to differentiate into IgA-secreting plasma cells. We also observed that oral administration of L. plantarum AYA in mice caused an increase in IgA production in the small intestine and lung. This production of IgA correlated strongly with protective ability, with the treated mice surviving longer than the control mice after lethal influenza virus infection. Our data therefore reveals a novel immunoregulatory role of the L. plantarum AYA strain which enhances mucosal IgA production and provides protection against respiratory influenza virus infection.

  4. Transmission of survival signals through Delta-like 1 on activated CD4+ T cells

    PubMed Central

    Furukawa, Takahiro; Ishifune, Chieko; Tsukumo, Shin-ichi; Hozumi, Katsuto; Maekawa, Yoichi; Matsui, Naoko; Kaji, Ryuji; Yasutomo, Koji

    2016-01-01

    Notch expressed on CD4+ T cells transduces signals that mediate their effector functions and survival. Although Notch signaling is known to be cis-inhibited by Notch ligands expressed on the same cells, the role of Notch ligands on T cells remains unclear. In this report we demonstrate that the CD4+ T cell Notch ligand Dll1 transduces signals required for their survival. Co-transfer of CD4+ T cells from Dll1−/− and control mice into recipient mice followed by immunization revealed a rapid decline of CD4+ T cells from Dll1−/− mice compared with control cells. Dll1−/− mice exhibited lower clinical scores of experimental autoimmune encephalitis than control mice. The expression of Notch target genes in CD4+ T cells from Dll1−/− mice was not affected, suggesting that Dll1 deficiency in T cells does not affect cis Notch signaling. Overexpression of the intracellular domain of Dll1 in Dll1-deficient CD4+ T cells partially rescued impaired survival. Our data demonstrate that Dll1 is an independent regulator of Notch-signaling important for the survival of activated CD4+ T cells, and provide new insight into the physiological roles of Notch ligands as well as a regulatory mechanism important for maintaining adaptive immune responses. PMID:27659682

  5. A NON-TRANSMISSIBLE CYTOPATHOGENIC EFFECT OF INFLUENZA VIRUS IN TISSUE CULTURE ACCOMPANIED BY FORMATION OF NON-INFECTIOUS HEMAGGLUTININS

    PubMed Central

    Henle, Gertrude; Girardi, Anthony; Henle, Werner

    1955-01-01

    Various strains of influenza virus produce a cytopathogenic effect in cultures of HeLa cells. The virus could not be passed in series. Virus partially or even completely inactivated with respect to infectivity by exposure to 37°C. or ultraviolet light retained some of its cytopathogenic effect. No evidence has been obtained of an increase in infectious virus in HeLa cultures, but an increase in hemagglutinins and in both viral and soluble complement-fixing antigens became detectable during incubation. These virus materials apparently were not released from these cells prior to their destruction. These results suggested that HeLa cells are capable of supporting an incomplete reproductive cycle of influenza virus. The fact that radioactive phosphorus was readily incorporated into the hemagglutinin supplies strong evidence for this interpretation. PMID:13211925

  6. Residue 41 of the Eurasian Avian-Like Swine Influenza A Virus Matrix Protein Modulates Virion Filament Length and Efficiency of Contact Transmission

    PubMed Central

    Campbell, Patricia J.; Kyriakis, Constantinos S.; Marshall, Nicolle; Suppiah, Suganthi; Seladi-Schulman, Jill; Danzy, Shamika; Lowen, Anice C.

    2014-01-01

    ABSTRACT Position 41 of the influenza A virus matrix protein encodes a highly conserved alanine in human and avian lineages. Nonetheless, strains of the Eurasian avian-like swine (Easw) lineage contain a change at this position: position 41 of A/swine/Spain/53207/04 (H1N1) (SPN04) encodes a proline. To assess the impact of this naturally occurring polymorphism on viral fitness, we utilized reverse genetics to produce recombinant viruses encoding wild-type M1 41P (rSPN04-P) and consensus 41A (rSPN04-A) residues. Relative to rSPN04-A, rSPN04-P virus displayed reduced growth in vitro. In the guinea pig model, rSPN04-P was transmitted to fewer contact animals than rSPN04-A and failed to infect guinea pigs that received a low-dose inoculum. Moreover, the P41A change altered virion morphology, reducing the number and length of filamentous virions, as well as reducing the neuraminidase activity of virions. The lab-adapted human isolate, A/PR/8/34 (H1N1) (PR8), is nontransmissible in the guinea pig model, making it a useful background in which to identify certain viral factors that enhance transmissibility. We assessed transmission in the context of single-, double-, and triple-reassortant viruses between PR8 and SPN04; PR8/SPN04 M, PR8/SPN04 M+NA, and PR8/SPN04 M+NA+HA, encoding either matrix 41 A or P, were generated. In each case, the virus possessing 41P transmitted less well than the corresponding 41A-encoding virus. In summary, we have identified a naturally occurring mutation in the influenza A virus matrix protein that impacts transmission efficiency and can alter virion morphology and neuraminidase activity. IMPORTANCE We have developed a practical model for examining the genetics underlying transmissibility of the Eurasian avian-like swine lineage viruses, which contributed M and NA segments to the 2009 pandemic strain. Here, we use our system to investigate the impact on viral fitness of a naturally occurring polymorphism at matrix (M1) position 41 in an Easw

  7. 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.

  8. Cationic amino acid transporters play key roles in the survival and transmission of apicomplexan parasites.

    PubMed

    Rajendran, Esther; Hapuarachchi, Sanduni V; Miller, Catherine M; Fairweather, Stephen J; Cai, Yeping; Smith, Nicholas C; Cockburn, Ian A; Bröer, Stefan; Kirk, Kiaran; van Dooren, Giel G

    2017-02-16

    Apicomplexans are obligate intracellular parasites that scavenge essential nutrients from their hosts via transporter proteins on their plasma membrane. The identities of the transporters that mediate amino acid uptake into apicomplexans are unknown. Here we demonstrate that members of an apicomplexan-specific protein family-the Novel Putative Transporters (NPTs)-play key roles in the uptake of cationic amino acids. We show that an NPT from Toxoplasma gondii (TgNPT1) is a selective arginine transporter that is essential for parasite survival and virulence. We also demonstrate that a homologue of TgNPT1 from the malaria parasite Plasmodium berghei (PbNPT1), shown previously to be essential for the sexual gametocyte stage of the parasite, is a cationic amino acid transporter. This reveals a role for cationic amino acid scavenging in gametocyte biology. Our study demonstrates a critical role for amino acid transporters in the survival, virulence and life cycle progression of these parasites.

  9. Cationic amino acid transporters play key roles in the survival and transmission of apicomplexan parasites

    PubMed Central

    Rajendran, Esther; Hapuarachchi, Sanduni V.; Miller, Catherine M.; Fairweather, Stephen J.; Cai, Yeping; Smith, Nicholas C.; Cockburn, Ian A.; Bröer, Stefan; Kirk, Kiaran; van Dooren, Giel G.

    2017-01-01

    Apicomplexans are obligate intracellular parasites that scavenge essential nutrients from their hosts via transporter proteins on their plasma membrane. The identities of the transporters that mediate amino acid uptake into apicomplexans are unknown. Here we demonstrate that members of an apicomplexan-specific protein family—the Novel Putative Transporters (NPTs)—play key roles in the uptake of cationic amino acids. We show that an NPT from Toxoplasma gondii (TgNPT1) is a selective arginine transporter that is essential for parasite survival and virulence. We also demonstrate that a homologue of TgNPT1 from the malaria parasite Plasmodium berghei (PbNPT1), shown previously to be essential for the sexual gametocyte stage of the parasite, is a cationic amino acid transporter. This reveals a role for cationic amino acid scavenging in gametocyte biology. Our study demonstrates a critical role for amino acid transporters in the survival, virulence and life cycle progression of these parasites. PMID:28205520

  10. Transmission characteristics of low pathogenic avian influenza virus of H7N7 and H5N7 subtypes in layer chickens.

    PubMed

    Gonzales, J L; Elbers, A R W; Bouma, A; Koch, G; de Wit, J J; Stegeman, J A

    2012-03-23

    Low pathogenic avian influenza virus (LPAIv) infections of H5 and H7 subtypes in poultry are notifiable to the OIE, hence surveillance programmes are implemented. The rate at which LPAIv strains spread within a flock determines the prevalence of infected birds and the time it takes to reach that prevalence and, consequently, optimal sample size and sampling frequency. The aim of this study was to investigate the transmission characteristics of an H7N7 and an H5N7 LPAIv in layer chickens. Two transmission experiments were performed, which consisted of 30 (first experiment) and 20 (second experiment) pairs of conventional layers, respectively. At the start of the experiments, one chicken per pair was inoculated with LPAIv and the other chicken was contact-exposed. Occurrence of infection was monitored by regularly collecting tracheal and cloacal swab samples, which were examined for the presence of virus RNA by RT-PCR. The results of the test were used to estimate the transmission rate parameter (β), the infectious period (T) and the basic reproduction ratio (R(0)). In addition, egg production and virus shedding patterns were quantified. For the H7N7 virus, the β, T and R(0) estimates were 0.10 (95% confidence interval (CI): 0.04-0.18) day(-1), 7.1 (95% CI: 6.5-7.8) days and 0.7 (95% CI: 0.0-1.7), respectively. With the H5N7 virus, only a few inoculated chickens (5 out of 20) became infected and no transmission was observed. This study shows that transmission characteristics of LPAIv strains may vary considerably, which has to be taken into account when designing surveillance programmes.

  11. Molecular epidemiological analysis of the transboundary transmission of 2003 highly pathogenic avian influenza H7N7 outbreaks between the Netherlands and Belgium.

    PubMed

    Van Borm, S; Jonges, M; Lambrecht, B; Koch, G; Houdart, P; van den Berg, T

    2014-02-01

    The 2003 outbreak of Highly pathogenic avian influenza (HPAI) A(H7N7) in the Netherlands, Belgium and Germany resulted in significant genetic diversification that proved informative for tracing transmission events. Building on previous investigations on the Dutch outbreak, we focused on the potential transnational transmissions between the Netherlands and Belgium. Although no clear epidemiological links could be identified from the tracing data, the transmission network based on concatenated HA-NA-PB2 sequences supports at least three independent introductions from the Netherlands to Belgium and suggests one possible introduction form Belgium back to the Netherlands. Two introductions in the Belgian province of Limburg occurred from nearby farms in the Dutch province of Limburg. One introduction resulted in three secondary infected farms, while a second introduction did not cause secondary infections. The third introduction into Belgium occurred in the north of the Antwerp province, very close to the national border, and originated from the North of the Dutch province Brabant (long distance transmission, >65 km). The virus spread to two additional Belgian farms, one of which may be the source of a secondarily infected farm in the Netherlands. One infected turkey farm in the province of Antwerp (Westmalle) was geographically close to the latter introduction, but genetically clustered with the first introduction event in the Limburg province. Epidemiological tracing data could neither confirm nor exclude whether this outbreak was a result from long distance contacts within Belgium or whether this farm presented a fourth independent transboundary introduction. These multiple transnational transmissions of HPAI in spite of reinforced biosecurity measures and trade restrictions illustrate the importance of international cooperation, legislation and standardization of tools to combat transboundary diseases. © 2012 Blackwell Verlag GmbH.

  12. Susceptibility to and transmission of H5N1 and H7N1 highly pathogenic avian influenza viruses in bank voles (Myodes glareolus).

    PubMed

    Romero Tejeda, Aurora; Aiello, Roberta; Salomoni, Angela; Berton, Valeria; Vascellari, Marta; Cattoli, Giovanni

    2015-05-13

    The study of influenza type A (IA) infections in wild mammals populations is a critical gap in our knowledge of how IA viruses evolve in novel hosts that could be in close contact with avian reservoir species and other wild animals. The aim of this study was to evaluate the susceptibility to infection, the nasal shedding and the transmissibility of the H7N1 and H5N1 highly pathogenic avian influenza (HPAI) viruses in the bank vole (Myodes glareolus), a wild rodent common throughout Europe and Asia. Two out of 24 H5N1-infected voles displayed evident respiratory distress, while H7N1-infected voles remained asymptomatic. Viable virus was isolated from nasal washes collected from animals infected with both HPAI viruses, and extra-pulmonary infection was confirmed in both experimental groups. Histopathological lesions were evident in the respiratory tract of infected animals, although immunohistochemistry positivity was only detected in lungs and trachea of two H7N1-infected voles. Both HPAI viruses were transmitted by direct contact, and seroconversion was confirmed in 50% and 12.5% of the asymptomatic sentinels in the H7N1 and H5N1 groups, respectively. Interestingly, viable virus was isolated from lungs and nasal washes collected from contact sentinels of both groups. The present study demonstrated that two non-rodent adapted HPAI viruses caused asymptomatic infection in bank voles, which shed high amounts of the viruses and were able to infect contact voles. Further investigations are needed to determine whether bank voles could be involved as silent hosts in the transmission of HPAI viruses to other mammals and domestic poultry.

  13. g-FLUA2H: a web-based application to study the dynamics of animal-to-human mutation transmission for influenza viruses.

    PubMed

    Sjaugi, Muhammad Farhan; Tan, Swan; Abd Raman, Hadia Syahirah; Lim, Wan Ching; Nik Mohamed, Nik Elena; August, J; Khan, Asif M

    2015-01-01

    g-FLUA2H is a web-based application focused on the analysis of the dynamics of influenza virus animal-to-human (A2H) mutation transmissions. The application only requires the viral protein sequences from both the animal and human host populations as input datasets. The comparative analyses between the co-aligned sequences of the two viral populations is based on a sliding window approach of size nine for statistical significance and data application to the major histocompatibility complex (MHC) and T-cell receptor (TCR) immune response mechanisms. The sequences at each of the aligned overlapping nonamer positions for the respective virus hosts are classified as four patterns of characteristic diversity motifs, as a basis for quantitative analyses: (i) "index", the most prevalent sequence; (ii) "major" variant, the second most common sequence and the single most prevalent variant of the index, with at least one amino acid mutation; (iii) "minor" variants, multiple different sequences, each with an incidence (percent occurrence) less than that of the major variant; and (iv) "unique" variants, each with only one occurrence in the alignment. The diversity motifs and their incidences at each of the nonamer positions allow evaluation of the mutation transmission dynamics and selectivity of the viral sequences in relation to the animal and the human hosts. g-FLUA2H is facilitated by a grid back-end for parallel processing of large sequence datasets. The web-application is publicly available at http://bioinfo.perdanauniversity.edu.my/g-FLUA2H. It can be used for a detailed characterization of the composition and incidence of mutations present in the proteomes of influenza viruses from animal and human host populations, for a better understanding of host tropism.

  14. g-FLUA2H: a web-based application to study the dynamics of animal-to-human mutation transmission for influenza viruses

    PubMed Central

    2015-01-01

    g-FLUA2H is a web-based application focused on the analysis of the dynamics of influenza virus animal-to-human (A2H) mutation transmissions. The application only requires the viral protein sequences from both the animal and human host populations as input datasets. The comparative analyses between the co-aligned sequences of the two viral populations is based on a sliding window approach of size nine for statistical significance and data application to the major histocompatibility complex (MHC) and T-cell receptor (TCR) immune response mechanisms. The sequences at each of the aligned overlapping nonamer positions for the respective virus hosts are classified as four patterns of characteristic diversity motifs, as a basis for quantitative analyses: (i) "index", the most prevalent sequence; (ii) "major" variant, the second most common sequence and the single most prevalent variant of the index, with at least one amino acid mutation; (iii) "minor" variants, multiple different sequences, each with an incidence (percent occurrence) less than that of the major variant; and (iv) "unique" variants, each with only one occurrence in the alignment. The diversity motifs and their incidences at each of the nonamer positions allow evaluation of the mutation transmission dynamics and selectivity of the viral sequences in relation to the animal and the human hosts. g-FLUA2H is facilitated by a grid back-end for parallel processing of large sequence datasets. The web-application is publicly available at http://bioinfo.perdanauniversity.edu.my/g-FLUA2H. It can be used for a detailed characterization of the composition and incidence of mutations present in the proteomes of influenza viruses from animal and human host populations, for a better understanding of host tropism. PMID:26680743

  15. Introduction of virulence markers in PB2 of pandemic swine-origin influenza virus does not result in enhanced virulence or transmission.

    PubMed

    Herfst, Sander; Chutinimitkul, Salin; Ye, Jianqiang; de Wit, Emmie; Munster, Vincent J; Schrauwen, Eefje J A; Bestebroer, Theo M; Jonges, Marcel; Meijer, Adam; Koopmans, Marion; Rimmelzwaan, Guus F; Osterhaus, Albert D M E; Perez, Daniel R; Fouchier, Ron A M

    2010-04-01

    In the first 6 months of the H1N1 swine-origin influenza virus (S-OIV) pandemic, the vast majority of infections were relatively mild. It has been postulated that mutations in the viral genome could result in more virulent viruses, leading to a more severe pandemic. Mutations E627K and D701N in the PB2 protein have previously been identified as determinants of avian and pandemic influenza virus virulence in mammals. These mutations were absent in S-OIVs detected early in the 2009 pandemic. Here, using reverse genetics, mutations E627K, D701N, and E677G were introduced into the prototype S-OIV A/Netherlands/602/2009, and their effects on virus replication, virulence, and transmission were investigated. Mutations E627K and D701N caused increased reporter gene expression driven by the S-OIV polymerase complex. None of the three mutations affected virus replication in vitro. The mutations had no major impact on virus replication in the respiratory tracts of mice and ferrets or on pathogenesis. All three mutant viruses were transmitted via aerosols or respiratory droplets in ferrets. Thus, the impact of key known virulence markers in PB2 in the context of current S-OIVs was surprisingly small. This study does not exclude the possibility of emergence of S-OIVs with other virulence-associated mutations in the future. We conclude that surveillance studies aimed at detecting S-OIVs with increased virulence or transmission should not rely solely on virulence markers identified in the past but should include detailed characterization of virus phenotypes, guided by genetic signatures of viruses detected in severe cases of disease in humans.

  16. Preferential transmission of the MTHFR 677 T allele to infants with Down syndrome: implications for a survival advantage.

    PubMed

    Hobbs, Charlotte A; Cleves, Mario A; Lauer, Ronald M; Burns, Trudy L; James, S Jill

    2002-11-15

    We have examined the transmission frequencies of the methylenetetrahydrofolate reductase (MTHFR) 677 T and C alleles from heterozygous parents to children with Down syndrome (trisomy 21) in 202 Caucasian families. Our results indicated that the MTHFR 677T allele was transmitted to children with Down syndrome at a significantly higher rate than would be expected based on Mendelian inheritance patterns, and the C allele was transmitted at a significantly lower rate (P < 0.009). Transmission frequencies were also examined independently for maternally and paternally transmitted alleles to assess potential parent-of-origin effects. Because the vast majority of conceptions with trisomy 21 end in pregnancy loss, we questioned whether the observed preferential transmission of the T allele to this population of liveborn infants with Down syndrome could reflect a survival advantage. A plausible biochemical interpretation of these results is presented based on a maternal-fetal MTHFR 677T allele interaction in the context of the constitutive overexpression of three copies of the cystathionine beta synthase gene in the trisomy 21 fetus. Published 2002 Wiley-Liss, Inc.

  17. Assessing Effectiveness of Ceiling-Ventilated Mock Airborne Infection Isolation Room in Preventing Hospital-Acquired Influenza Transmission to Health Care Workers.

    PubMed

    Thatiparti, Deepthi Sharan; Ghia, Urmila; Mead, Kenneth R

    2016-01-01

    Exposure to airborne influenza (or flu) from a patient's cough and exhaled air causes potential flu virus transmission to the persons located nearby. Hospital-acquired influenza is a major airborne disease that occurs to health care workers (HCW). This paper examines the airflow patterns and influenza-infected cough aerosol transport behavior in a ceiling-ventilated mock airborne infection isolation room (AIIR) and its effectiveness in mitigating HCW's exposure to airborne infection. The computational fluid dynamics (CFD) analysis of the airflow patterns and the flu virus dispersal behavior in a mock AIIR is conducted using the room geometries and layout (room dimensions, bathroom dimensions and details, placement of vents and furniture), ventilation parameters (flow rates at the inlet and outlet vents, diffuser design, thermal sources, etc.), and pressurization corresponding to that of a traditional ceiling-mounted ventilation arrangement observed in existing hospitals. The measured data shows that ventilation rates for the AIIR are about 12 air changes per hour(ach). However, the numerical results reveals incomplete air mixing and that not all of the room air is changed 12 times per hour. Two life-sized breathing human models are used to simulate a source patient and a receiving HCW. A patient cough cycle is introduced into the simulation and the airborne infection dispersal is tracked in time using a multiphase flow simulation approach. The results reveal air recirculation regions that diminished the effect of air filtration and prolong the presence of flu-contaminated air at the HCW's zone. Immediately after the patient coughs (0.51 s), the cough velocity from the patient's mouth drives the cough aerosols toward the HCW standing next to patient's bed. Within 0.7 s, the HCW is at risk of acquiring the infectious influenza disease, as a portion of these aerosols are inhaled by the HCW. As time progresses (5 s), the aerosols eventually spread throughout the entire

  18. Assessing Effectiveness of Ceiling-Ventilated Mock Airborne Infection Isolation Room in Preventing Hospital-Acquired Influenza Transmission to Health Care Workers

    PubMed Central

    Thatiparti, Deepthi Sharan; Ghia, Urmila; Mead, Kenneth R.

    2017-01-01

    Exposure to airborne influenza (or flu) from a patient's cough and exhaled air causes potential flu virus transmission to the persons located nearby. Hospital-acquired influenza is a major airborne disease that occurs to health care workers (HCW). This paper examines the airflow patterns and influenza-infected cough aerosol transport behavior in a ceiling-ventilated mock airborne infection isolation room (AIIR) and its effectiveness in mitigating HCW's exposure to airborne infection. The computational fluid dynamics (CFD) analysis of the airflow patterns and the flu virus dispersal behavior in a mock AIIR is conducted using the room geometries and layout (room dimensions, bathroom dimensions and details, placement of vents and furniture), ventilation parameters (flow rates at the inlet and outlet vents, diffuser design, thermal sources, etc.), and pressurization corresponding to that of a traditional ceiling-mounted ventilation arrangement observed in existing hospitals. The measured data shows that ventilation rates for the AIIR are about 12 air changes per hour(ach). However, the numerical results reveals incomplete air mixing and that not all of the room air is changed 12 times per hour. Two life-sized breathing human models are used to simulate a source patient and a receiving HCW. A patient cough cycle is introduced into the simulation and the airborne infection dispersal is tracked in time using a multiphase flow simulation approach. The results reveal air recirculation regions that diminished the effect of air filtration and prolong the presence of flu-contaminated air at the HCW's zone. Immediately after the patient coughs (0.51 s), the cough velocity from the patient's mouth drives the cough aerosols toward the HCW standing next to patient's bed. Within 0.7 s, the HCW is at risk of acquiring the infectious influenza disease, as a portion of these aerosols are inhaled by the HCW. As time progresses (5 s), the aerosols eventually spread throughout the entire

  19. Influenza Virus Infection of Marine Mammals.

    PubMed

    Fereidouni, Sasan; Munoz, Olga; Von Dobschuetz, Sophie; De Nardi, Marco

    2016-03-01

    Interspecies transmission may play a key role in the evolution and ecology of influenza A viruses. The importance of marine mammals as hosts or carriers of potential zoonotic pathogens such as highly pathogenic H5 and H7 influenza viruses is not well understood. The fact that influenza viruses are some of the few zoonotic pathogens known to have caused infection in marine mammals, evidence for direct transmission of influenza A virus H7N7 subtype from seals to man, transmission of pandemic H1N1 influenza viruses to seals and also limited evidence for long-term persistence of influenza B viruses in seal populations without significant genetic change, makes monitoring of influenza viruses in marine mammal populations worth being performed. In addition, such monitoring studies could be a great tool to better understand the ecology of influenza viruses in nature.

  20. Environmental Predictors of Seasonal Influenza Epidemics across Temperate and Tropical Climates

    PubMed Central

    Tamerius, James D.; Shaman, Jeffrey; Alonso, Wladmir J.; Bloom-Feshbach, Kimberly; Uejio, Christopher K.; Comrie, Andrew; Viboud, Cécile

    2013-01-01

    Human influenza infections exhibit a strong seasonal cycle in temperate regions. Recent laboratory and epidemiological evidence suggests that low specific humidity conditions facilitate the airborne survival and transmission of the influenza virus in temperate regions, resulting in annual winter epidemics. However, this relationship is unlikely to account for the epidemiology of influenza in tropical and subtropical regions where epidemics often occur during the rainy season or transmit year-round without a well-defined season. We assessed the role of specific humidity and other local climatic variables on influenza virus seasonality by modeling epidemiological and climatic information from 78 study sites sampled globally. We substantiated that there are two types of environmental conditions associated with seasonal influenza epidemics: “cold-dry” and “humid-rainy”. For sites where monthly average specific humidity or temperature decreases below thresholds of approximately 11–12 g/kg and 18–21°C during the year, influenza activity peaks during the cold-dry season (i.e., winter) when specific humidity and temperature are at minimal levels. For sites where specific humidity and temperature do not decrease below these thresholds, seasonal influenza activity is more likely to peak in months when average precipitation totals are maximal and greater than 150 mm per month. These findings provide a simple climate-based model rooted in empirical data that accounts for the diversity of seasonal influenza patterns observed across temperate, subtropical and tropical climates. PMID:23505366

  1. Environmental predictors of seasonal influenza epidemics across temperate and tropical climates.

    PubMed

    Tamerius, James D; Shaman, Jeffrey; Alonso, Wladimir J; Alonso, Wladmir J; Bloom-Feshbach, Kimberly; Uejio, Christopher K; Comrie, Andrew; Viboud, Cécile

    2013-03-01

    Human influenza infections exhibit a strong seasonal cycle in temperate regions. Recent laboratory and epidemiological evidence suggests that low specific humidity conditions facilitate the airborne survival and transmission of the influenza virus in temperate regions, resulting in annual winter epidemics. However, this relationship is unlikely to account for the epidemiology of influenza in tropical and subtropical regions where epidemics often occur during the rainy season or transmit year-round without a well-defined season. We assessed the role of specific humidity and other local climatic variables on influenza virus seasonality by modeling epidemiological and climatic information from 78 study sites sampled globally. We substantiated that there are two types of environmental conditions associated with seasonal influenza epidemics: "cold-dry" and "humid-rainy". For sites where monthly average specific humidity or temperature decreases below thresholds of approximately 11-12 g/kg and 18-21°C during the year, influenza activity peaks during the cold-dry season (i.e., winter) when specific humidity and temperature are at minimal levels. For sites where specific humidity and temperature do not decrease below these thresholds, seasonal influenza activity is more likely to peak in months when average precipitation totals are maximal and greater than 150 mm per month. These findings provide a simple climate-based model rooted in empirical data that accounts for the diversity of seasonal influenza patterns observed across temperate, subtropical and tropical climates.

  2. Peroxiredoxin-glutaredoxin and catalase promote resistance of nontypeable Haemophilus influenzae 86-028NP to oxidants and survival within neutrophil extracellular traps.

    PubMed

    Juneau, Richard A; Pang, Bing; Armbruster, Chelsie E; Murrah, Kyle A; Perez, Antonia C; Swords, W Edward

    2015-01-01

    Nontypeable Haemophilus influenzae (NTHI) is a common commensal and opportunistic pathogen of the human airways. For example, NTHI is a leading cause of otitis media and is the most common cause of airway infections associated with chronic obstructive pulmonary disease (COPD). These infections are often chronic/recurrent in nature and involve bacterial persistence within biofilm communities that are highly resistant to host clearance. Our previous work has shown that NTHI within biofilms has increased expression of factors associated with oxidative stress responses. The goal of this study was to define the roles of catalase (encoded by hktE) and a bifunctional peroxiredoxin-glutaredoxin (encoded by pdgX) in resistance of NTHI to oxidants and persistence in vivo. Isogenic NTHI strain 86-028NP mutants lacking hktE and pdgX had increased susceptibility to peroxide. Moreover, these strains had persistence defects in the chinchilla infection model for otitis media, as well as in a murine model for COPD. Additional work showed that pdgX and hktE were important determinants of NTHI survival within neutrophil extracellular traps (NETs), which we have shown to be an integral part of NTHI biofilms in vivo. Based on these data, we conclude that catalase and peroxiredoxin-glutaredoxin are determinants of bacterial persistence during chronic/recurrent NTHI infections that promote bacterial survival within NETs.

  3. 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.

  4. Spillback transmission of European H1N1 avian-like swine influenza viruses to turkeys: A strain-dependent possibility?

    PubMed

    Bonfante, Francesco; Fusaro, Alice; Tassoni, Luca; Patrono, Livia Victoria; Milani, Adelaide; Maniero, Silvia; Salviato, Annalisa; Terregino, Calogero

    2016-04-15

    In 1979, an avian influenza virus of the H1N1 subtype began to circulate in European swine herds, rapidly replacing classical swine H1N1 viruses. Spill-back transmissions to turkeys were recorded occasionally, but they might have been underreported due to the asymptomatic nature of the infection and the lack of specific surveillance. In our study, we evaluated the infectivity and transmissibility in turkeys of seven strains of H1N1 avian-like swine viruses isolated from 1979 to 2006, and compared them with their closest progenitor A/duck/Bavaria/1/77 (H1N1), to establish whether the adaptation to pigs has gradually decreased their fitness in turkeys. Our data indicate that the circulation of European H1N1 in pigs might have impaired the possibility of infecting turkeys. Nevertheless, the two swine-origin strains, which showed the ability to replicate and transmit in turkeys, possess typical swine-like genetic traits, not different from the rest of the tested isolates, suggesting replication of avian-like swine H1N1 viruses in turkeys as a strain-dependent polygenic feature. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Epidemiological and Evolutionary Inference of the Transmission Network of the 2014 Highly Pathogenic Avian Influenza H5N2 Outbreak in British Columbia, Canada

    PubMed Central

    Xu, Wanhong; Berhane, Yohannes; Dubé, Caroline; Liang, Binhua; Pasick, John; VanDomselaar, Gary; Alexandersen, Soren

    2016-01-01

    The first North American outbreak of highly pathogenic avian influenza (HPAI) involving a virus of Eurasian A/goose/Guangdong/1/1996 (H5N1) lineage began in the Fraser Valley of British Columbia, Canada in late Novembe