Bird Flu Remains A Global Threat

Oxford Analytica 02.07.07, 6:00 AM ET

Authorities in the United Kingdom on Feb. 5 completed a cull of turkeys on a commercial poultry farm, following confirmation that H5N1 avian influenza had entered the flock. Recent research on the "rescued" 1918 strain of human influenza has revealed how it and H5N1 kill by irreparably damaging the lungs, and what parts of the virus structure are required to make it highly transmissible.

The threat remains of a human pandemic arising from avian influenza:

—It has killed over half of those humans who have become infected by it, but so far, there has been no pandemic because it cannot spread easily between humans.

—Yet prevalence of the disease in cats shows that the virus is adapting to mammalian hosts, giving it increased opportunities to mutate.

A new variant of H5N1 avian influenza, the "Fujian-like" strain, has emerged in China:

—In the past year, its prevalence has increased from 3% to 95% of avian influenza detected in the country.

—Infected but apparently healthy birds are increasingly appearing in markets.

—This has created evolutionary pressure for the emergence of an H5N1 variant that the antibodies the vaccine induces do not recognize.

The Fujian-like strain has spread to Malaysia, Laos and Thailand, and it could start another wave of infection. The human anti-H5N1 vaccine that pharmaceutical companies are developing will not protect against the new strain should this develop human pandemic capabilities.

The H5N1 strain arose in southern China. Margaret Chan, the new head of the World Health Organization, is the first Chinese citizen to lead a United Nations agency. She hopes her origins will help her deal with the Chinese authorities, whom the WHO criticized for lack of transparency over their handling of bird flu.

Ever since the H5N1 bird flu spread from China in 2005, it has been debated whether this was due to wild migratory birds or commercial trade in domesticated birds. Some preliminary conclusions can be drawn:

—Recent research that has identified exact strains found worldwide has shown that both routes were involved.

—Most of East Asia except Japan got H5N1 through poultry, while migrating wild birds took it from China to Russia, Europe, the Near East, Africa and Japan.

—Data suggest that the disease will probably reach the Americas through poultry transportation, though wild birds will spread it.

A recent report from Indonesia stated that, in locations where poultry have been infected with H5N1, cats were found to be carrying antibodies. H5N1 already had been seen in domestic pigs and cats, but this study points to a much higher rate of infection and survival than has been found in apparently healthy poultry. It suggests that, as the disease continues to spread, it will find more opportunities to adapt to living in mammals.

The 1918 human influenza pandemic killed an estimated 50 million people worldwide. Infectious human influenza virus particles of this strain were recently recreated in the laboratory to enable research on why it is highly lethal and infectious. Such understanding is important, since the 1918 strain has many properties in common with H5N1.

A report has been published in Nature on the effects of the 1918 virus on macaque monkeys:

—It confirms clinical reports from 1918 that the disease kills by causing severe and irreparable damage to the lungs.

—By employing modern techniques to analyze gene expression responses in infected lung cells, researchers were able to confirm that infection caused "disregulation" of the normal anti-viral response.

This is the same response observed in recent human victims of H5N1, and accounts for the high mortality rate. Drugs that target "overzealous" immune response are being investigated as potential anti-viral agents against pandemic avian flu.

Experiments—recently published in Science—also have been undertaken with ferrets to discover what causes the high infectivity of the 1918 flu virus:

—These have shown that mutation of only one or two amino acids within the 1918 viral proteins is sufficient to block infectivity.

—Reciprocally, this indicates that only one or two mutations may change H5N1.

The WHO has welcomed these findings as having predictive power in identifying potentially pandemic mutant strains from among wild bird flu isolates.

Sophisticated research is revealing global vulnerability to avian influenza and the need at an international level to protect against a pandemic, the effects of which will be global in reach.

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Oxford Analytica is an independent strategic-consulting firm drawing on a network of more than 1,000 scholar experts at Oxford and other leading universities and research institutions around the world. For more information, please visit www.oxan.com.

http://www.forbes.com/2007/02/06/avian-bird-influenza-biz-cx_0207oxford_print.html