"Bird Flu" Genome Study Shows New Strains, Western Spread

A team of researchers report the first ever large-scale sequencing of western genomes of the deadly avian influenza virus, H5N1, that confirms not only that the virus has very recently spread west from Asia, but that two of the new western strains have already independently combined, or “reassorted,” to create a new strain.

The arrows represent the movement of the H5N1 virus into the three distinct regions represented in the genome study. The green, pink and yellow arrows depict the three strains of avian flu that have emerged independently in the West. The orange arrows show the likely source of all the avian influenza strains, which is in China. From there it has moved south into Vietnam and west into central Asia and Russia.

Newswise — In a paper in the May issue of Emerging Infectious Diseases, an international team of researchers report the first ever large-scale sequencing of western genomes of the deadly avian influenza virus, H5N1.

Their study of 36 genomes of the virus collected from wild birds in Europe, the Middle East and Africa (EMA), and Vietnam confirms not only that the virus has very recently spread west from Asia, but that two of the new western strains have already independently combined, or “reassorted,” to create a new strain.

Several samples also contained the mutation associated with the form of the “bird flu” that caused several human deaths in 2006. It is the virus’s ability to rapidly mutate into a pathogen that may eventually be passed between humans that concerns health officials about a worldwide pandemic of H5N1 influenza.

The study also produced some evidence that strengthens the case that humans have had an impact on the movement of the flu out of Asia.

“This is the first time anyone’s looked at all of the H5N1 genomes in the west,” said Steven Salzberg, the study’s lead author and director of the University of Maryland Center for Bioinformatics and Computational Biology. “Until now, the studies have been primarily on samples from the Far East. Our study shows that the virus is spreading west, and that there have been three separate introductions of H5N1 in Europe, the Middle East and Africa.”

The study’s researchers, an unusual team of scientists from 11 countries that range from U.S. to Iran, collaborated to share data and sequence H5N1 samples taken from birds in a widely dispersed geographic region that includes Nigeria, Niger, Sudan, Egypt, Afghanistan, Iran, Slovenia, Croatia and Italy.

“We found that the EMA strains of the virus are distinct from the Vietnamese and other Asian strains,” said Salzberg, “and that they have already divided into three separate new strains. One of the new strains has been the cause of several fatal human cases in Egypt and Iraq.”

The research showed that the three new strains, called clades, evolved independently and in different regions from a single genetic source. “Our analysis places this source most recently in either Russia or Quinghai Province in China,” Salzberg said.

The study shows that the new Euro-African lineage, which was the cause of fatal human infections in Egypt and Iraq in 2006, has been introduced at least three times into the EMA region and has split into three distinct, independently evolving lineages. Two of those sublineages have recently reassorted.

The broad dispersal of the different forms of the virus throughout the different countries over a relatively short period of time points to the possibility of human movement, rather than wild birds as the reason for the quick spread of the H5N1.

“The migratory pathways of wild birds don’t correspond with the movement of the genomes that we sequenced,” said Salzberg. “Humans carry chickens between many of the countries in our study, often transporting them across great distances. That and the weak biosecurity standards in most rural areas point to human-related movement of live poultry as the source of the introduction of H5N1 in some countries.”

While the study “dramatically increased the number of genomes that have been sequenced, we have to do more surveys,” Salzberg said. “It’s surprising that we found what we did with such a small sample.”

The senior author of the study was Ilaria Capua of the Istituto Zooprofilattico Sperimentale delle Venezie, Padova, Italy. Other authors included researchers from Egypt, England, Côte d'Ivoire, Vietnam, Nigeria, Iran, Afghanistan, Croatia and Slovenia.

“The research team represents an unprecedented collaboration among authors from many remote laboratories,” said Salzberg. "Collaborations like this one are essential if the scientific community is going to keep track of avian flu, but most influenza researchers continue to work in isolation, and to work with a limited and exclusive set of collaborators.

“We have to recognize that the flu knows no boundaries, and we must not only collaborate widely, but also share our data freely with one another, as we have in this study.”

The flu genomes in this study were all deposited in Genbank, a public database, immediately after sequencing.

The study was funded by the U.S. National Institute of Allergy and Infectious Diseases, U.S. National Library of Medicine, U.S. Army Research Office, the Italian Ministry of Health, the European Commission for the AVIFLU and FLUAID projects, and the World Organization for Animal Health and the Food and Agricultural Organization of the United Nations.

Emerging Infectious Diseases is a journal of the Centers for Disease Control and Prevention.

FDA Approves First H5N1 Vaccine For Human Use

By Sue Mueller
Apr 17, 2007 - 12:38:37 PM

The U.S. Food and Drug Administration today April 17 announced its first approval of a vaccine for human use in the United States against the H5N1 influenza virus, commonly known as avian or bird flu.

The vaccine, manufactured by sanofi pasteur was found to be able to develop adequate immunity against H5N1 in 45 percent of the people receiving two doses of the vaccine.

The vaccine is not intended to fully prevent bird flu infection when an influenza pandemic emerges, which may be caused by a variant that is immune to the vaccine.

Instead, the vaccine is to provide "early limited protection in the months before a vaccine tailored to the pandemic strain of the virus could be developed and produced."

"The threat of an influenza pandemic is, at present, one of the most significant public health issues our nation and world faces," said Andrew C. von Eschenbach, M.D., Commissioner of Food and Drugs.

"The approval of this vaccine is an important step forward in our protection against a pandemic."

The H5N1 virus, one version of the influenza A virus commonly found in birds, is far more severe than seasonal influenza and the infection happens quickly, with pneumonia and multi-organ failure commonly seen.

No human case of H5N1 has been reported in the United States while almost 300 people worldwide have been infected with this virus since 2003 and more than half of them have died.

Experts and the government officials fear that the current H5N1 influenza virus may someday mutate into a strain that can readily spread from person to person, potentially infecting millions of people worldwide and killing tens of hundreds.

"The timing and severity of an influenza pandemic is uncertain, but the danger remains very real," said Jesse L. Goodman, M.D., M.P.H., Director of FDA's Center for Biologics Evaluation and Research.

"We are working closely with other government agencies, global partners and the vaccine industry to facilitate the development, licensure and availability of needed supplies of safe and effective vaccines to protect against the pandemic threat."

The vaccine is made of a human strain and is intended for immunizing people 18 through 64 years of age who could be at increased risk of exposure to the H5N1 influenza virus contained in the vaccine.

To immunize people against H5N1, two injections of the vaccine approximately one month apart are needed.

The H5N1 vaccine will not be sold commercially. For the time being, the manufacturer, sanofi pasteur Inc. makes the vaccine only for the U.S. government for inclusion within the U.S. Strategic National Stockpile for distribution by public health officials if needed.

The FDA approval is based on the results of a clinical study of 103 healthy people who received two shots of 90 micrograms of the vaccine with 28 days apart. Additional 300 healthy people received two doses lower than 90 micrograms per injection and additional 48 received a placebo.

According to the study, 45 percent of individuals receiving the 90 microgram, two-dose regimen developed adequate amounts of antibodies, which are expected to reduce the risk of getting influenza.

The remaining individuals may also have some protection against bird flu and have the potential to help reduce disease severity and influenza related hospitalizations and deaths even if their antibody levels were below the optimal level.

The vaccine was well tolerated and the most common side effects include pain at the injection site, headache, general ill feeling and muscle pain.

More information on this H5N1 influenza vaccine is being collected on safety and effectiveness in other age groups and will be available to FDA in the near future.

A more potent bird flu is being developed by Sanofi Pasteur and other manufacturers with the support of FDA and the U.S. National Institutes of Health and other government agencies.

For now, the FDA approval and availability of this vaccine will enhance national readiness and the nation's ability to protect those at increased risk of exposure to H5N1 influenza virus.

The U.S. Strategic National Stockpile is maintained by the U.S. Centers for Disease Control and Prevention and large quantities of medicine and medical supplies can be delivered to any states within 12 hours.

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