tetano
Editor, Senior Moderator
J Virol. 2015 Dec 9. pii: JVI.01878-15. [Epub ahead of print]
[h=1]Predicting disease severity and viral spread of H5N1 in ferrets in the context of natural exposure routes.[/h] Edenborough KM[SUP]1[/SUP], Lowther S[SUP]2[/SUP], Laurie K[SUP]3[/SUP], Yamada M[SUP]2[/SUP], Long F[SUP]2[/SUP], Bingham J[SUP]2[/SUP], Payne J[SUP]2[/SUP], Harper J[SUP]2[/SUP], Haining J[SUP]2[/SUP], Arkinstall R[SUP]2[/SUP], Gilbertson B[SUP]1[/SUP], Middleton D[SUP]2[/SUP], Brown LE[SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Although avian H5N1 influenza virus is yet to develop the capacity for human-to-human spread, the severity of the rare cases of human infection has warranted intensive follow-up of potentially exposed individuals that may require antiviral prophylaxis. For countries where antiviral drugs are limited, the WHO has developed a risk categorization for different levels of exposure to environmental, poultry or human sources of infection. While these take into account the infection source they do not account for the likely mode of virus entry that the individual may have experienced from that source and how this impacts on disease outcome. Knowledge of the kinetics and spread of virus after natural routes of exposure may further inform risk of infection as well as likely disease severity. Using the ferret model of H5N1 infection we compared the commonly used but artificial inoculation method that saturates the total respiratory tract (TRT) with virus, to upper-respiratory tract (URT) and oral routes of delivery, those likely to be encountered by humans in nature. We show that there was no statistically significant difference in survival rate with the different routes of infection but the disease characteristics were somewhat different. Following URT infection, viral spread to systemic organs was delayed compared to TRT infection and more focal. By both routes, severe disease was associated with early viremia and central nervous system infection. After oral exposure to the virus, mild infections were common suggesting consumption of virus-contaminated liquids may be associated with seroconversion in the absence of severe disease.
[h=4]IMPORTANCE:[/h] Risks for human H5N1 infection include direct contact with infected birds and frequenting contaminated environments. We used H5N1 ferret-infection models to show that breathing in the virus was more likely to produce clinical infection than swallowing contaminated liquid. We also showed that virus can spread from the respiratory tract to the brain, which was associated with end-stage disease, and very early viremia provided a marker for this. With upper respiratory tract exposure, infection of the brain was common but hard to detect, suggesting that human neurological infections might be typically undetected at autopsy. However, viral spread to systemic sites was slower when exposed to virus by this route compared to when virus was additionally delivered to the lungs, providing a better therapeutic window. In addition to exposure history, early parameters of infection such as viremia could help prioritize antiviral treatments for patients most at risk of succumbing to infection.
Copyright ? 2015, American Society for Microbiology. All Rights Reserved.
PMID: 26656692 [PubMed - as supplied by publisher]
[h=1]Predicting disease severity and viral spread of H5N1 in ferrets in the context of natural exposure routes.[/h] Edenborough KM[SUP]1[/SUP], Lowther S[SUP]2[/SUP], Laurie K[SUP]3[/SUP], Yamada M[SUP]2[/SUP], Long F[SUP]2[/SUP], Bingham J[SUP]2[/SUP], Payne J[SUP]2[/SUP], Harper J[SUP]2[/SUP], Haining J[SUP]2[/SUP], Arkinstall R[SUP]2[/SUP], Gilbertson B[SUP]1[/SUP], Middleton D[SUP]2[/SUP], Brown LE[SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Although avian H5N1 influenza virus is yet to develop the capacity for human-to-human spread, the severity of the rare cases of human infection has warranted intensive follow-up of potentially exposed individuals that may require antiviral prophylaxis. For countries where antiviral drugs are limited, the WHO has developed a risk categorization for different levels of exposure to environmental, poultry or human sources of infection. While these take into account the infection source they do not account for the likely mode of virus entry that the individual may have experienced from that source and how this impacts on disease outcome. Knowledge of the kinetics and spread of virus after natural routes of exposure may further inform risk of infection as well as likely disease severity. Using the ferret model of H5N1 infection we compared the commonly used but artificial inoculation method that saturates the total respiratory tract (TRT) with virus, to upper-respiratory tract (URT) and oral routes of delivery, those likely to be encountered by humans in nature. We show that there was no statistically significant difference in survival rate with the different routes of infection but the disease characteristics were somewhat different. Following URT infection, viral spread to systemic organs was delayed compared to TRT infection and more focal. By both routes, severe disease was associated with early viremia and central nervous system infection. After oral exposure to the virus, mild infections were common suggesting consumption of virus-contaminated liquids may be associated with seroconversion in the absence of severe disease.
[h=4]IMPORTANCE:[/h] Risks for human H5N1 infection include direct contact with infected birds and frequenting contaminated environments. We used H5N1 ferret-infection models to show that breathing in the virus was more likely to produce clinical infection than swallowing contaminated liquid. We also showed that virus can spread from the respiratory tract to the brain, which was associated with end-stage disease, and very early viremia provided a marker for this. With upper respiratory tract exposure, infection of the brain was common but hard to detect, suggesting that human neurological infections might be typically undetected at autopsy. However, viral spread to systemic sites was slower when exposed to virus by this route compared to when virus was additionally delivered to the lungs, providing a better therapeutic window. In addition to exposure history, early parameters of infection such as viremia could help prioritize antiviral treatments for patients most at risk of succumbing to infection.
Copyright ? 2015, American Society for Microbiology. All Rights Reserved.
PMID: 26656692 [PubMed - as supplied by publisher]