The writing committee consisted of the following: John H. Beigel, M.D., National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.; Jeremy Farrar, D.Phil., Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam; Aye Maung Han, M.B., B.S., Department of Child Health, Institute of Medicine, Yangon, Myanmar; Frederick G. Hayden, M.D. (rapporteur), University of Virginia, Charlottesville; Randy Hyer, M.D., World Health Organization, Geneva; Menno D. de Jong, M.D., Ph.D., Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam; Sorasak Lochindarat, M.D., Queen Sirikit National Institute of Child Health, Bangkok, Thailand; Nguyen Thi Kim Tien, M.D., Ph.D., Pasteur Institute, Ho Chi Minh City, Vietnam; Nguyen Tran Hien, M.D., Ph.D., National Institute of Hygiene and Epidemiology, Hanoi; Tran Tinh Hien, M.D., Ph.D., Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam; Angus Nicoll, M.Sc., Health Protection Agency, London; Sok Touch, M.D., Ministry of Health, Phnom Penh, Cambodia; and Kwok-Yung Yuen, M.D., University of Hong Kong, Hong Kong SAR, China. Address reprint requests to Dr. Hayden at the Department of Internal Medicine, P.O. Box 800473, University of Virginia Health Sciences Center, Charlottesville, VA 22908, or at fgh@virginia.edu.

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Avian influenza A (H5N1) infection in humans

Pandemic influenza virus has its origins in avian influenza viruses. The highly pathogenic avian influenza virus subtype H5N1 is already panzootic in poultry, with attendant economic consequences. It continues to cross species barriers to infect humans and other mammals, often with fatal outcomes. Therefore, H5N1 virus has rightly received attention as a potential pandemic threat. However, it is noted that the pandemics of 1957 and 1968 did not arise from highly pathogenic influenza viruses, and the next pandemic may well arise from a low-pathogenicity virus. The rationale for particular concern about an H5N1 pandemic is not its inevitability but its potential severity. An H5N1 pandemic is an event of low probability but one of high human health impact and poses a predicament for public health. Here, we review the ecology and evolution of highly pathogenic avian influenza H5N1 viruses, assess the pandemic risk, and address aspects of human H5N1 disease in relation to its epidemiology, clinical presentation, pathogenesis, diagnosis, and management.

http://www.hkupasteur.hku.hk/publications/pdf/Peiris_et_al_2007.pdf

Avian Influenza Virus (H5N1): a Threat to Human Health

Recent outbreaks of highly pathogenic avian influenza A virus infections (H5 and H7 subtypes) in poultry and in humans (through direct contact with infected birds) have had important economic repercussions and have raised concerns that a new influenza pandemic will occur in the near future. The eradication of pathogenic avian influenza viruses seems to be the most effective way to prevent influenza pandemics, although this strategy has not proven successful so far. Here, we review the molecular factors that contribute to the emergence of pandemic strains.

Influenza: lessons from past pandemics, warnings from current incidents

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(07)61297-5.pdf

Antigen sparing and cross-reactive immunity with an adjuvanted rH5N1 prototype pandemic influenza vaccine: a randomised controlled trial.

The spread of highly pathogenic avian influenza H5N1 viruses across Asia in 2003 and 2004 devastated domestic poultry populations and resulted in the largest and most lethal H5N1 virus outbreak in humans to date. To better understand the potential of H5N1 viruses isolated during this epizootic event to cause disease in mammals, we used the mouse and ferret models to evaluate the relative virulence of selected 2003 and 2004 H5N1 viruses representing multiple genetic and geographical groups and compared them to earlier H5N1 strains isolated from humans. Four of five human isolates tested were highly lethal for both mice and ferrets and exhibited a substantially greater level of virulence in ferrets than other H5N1 viruses isolated from humans since 1997. One human isolate and all four avian isolates tested were found to be of low virulence in either animal. The highly virulent viruses replicated to high titers in the mouse and ferret respiratory tracts and spread to multiple organs, including the brain. Rapid disease progression and high lethality rates in ferrets distinguished the highly virulent 2004 H5N1 viruses from the 1997 H5N1 viruses. A pair of viruses isolated from the same patient differed by eight amino acids, including a Lys/Glu disparity at 627 of PB2, previously identified as an H5N1 virulence factor in mice. The virus possessing Glu at 627 of PB2 exhibited only a modest decrease in virulence in mice and was highly virulent in ferrets, indicating that for this virus pair, the K627E PB2 difference did not have a prevailing effect on virulence in mice or ferrets. Our results demonstrate the general equivalence of mouse and ferret models for assessment of the virulence of 2003 and 2004 H5N1 viruses. However, the apparent enhancement of virulence of these viruses in humans in 2004 was better reflected in the ferret.

Avian Influenza (H5N1) Viruses Isolated from Humans in Asia in 2004 Exhibit Increased Virulence in Mammals

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(04)15892-3.pdf

JH Knight

Papers

Responsiveness to a pandemic alert: use of reverse genetics for rapid development of influenza vaccines.