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Generational Dynamics Web Log for 27-May-07
China confirms that a soldier has contracted bird flu

Web Log - May, 2007

China confirms that a soldier has contracted bird flu

Leaders of China's Central Committee are "highly concerned" about the case, according to the Xinhua report, which also quotes China's Ministry of Health.

The soldier is 19 years old, and is now receiving treatment at an army hospital. He developed symptoms of pneumonia on May 9, and has been hospitalized since May 14.

This story reminds us that, although another flu season has gone by, the danger has not passed.

The deadly H5N1 Bird flu was virtually unknown three years ago, but during the winter of 2005-2006 it spread like wildfire across Asia, into Europe and Africa.

New infestations of H5N1 again spread rapidly this past winter, especially during the Tet and Chinese New Year celebrations.

According to a posting on the controversial Recombonomics web site by researcher Henry J. Niman, analysis of the gene sequences in cases around the world show that mutations are being spread by migrating birds, and then combined with one another. This analysis is especially revealing when examining the mutations that first were discovered at the huge Lake Qinghai nature preserve in western China in 2005:

"The recent H5N1 sequence data out of the Middle East and Western Africa further support a paradigm shift in the understanding of evolution. The recent data strongly indicate that single nucleotide changes, previously thought to be due to random mutations, are really genetic changes acquired by recombination and are not due to de novo mutations resulting from copy errors. The selection of copy errors represents the previous understanding of genetic evolution and drug resistance, but the current data indicates that rapid change is through selection of recombinants.

H5N1 evolution provides a model for rapid evolution in a natural setting. The growing sequence database provides examples of how influenza genes evolve over time, and the recently discovered Qinghai strain (clade 2.2) firmly ties this evolution to migratory birds.

Sequence data provide the initial evidence against the role of de novo random mutations in influenza evolution. Genetic drift allows the virus to escape immune responses. H5N1 is the fastest evolving influenza serotype and has created the greatest concern because of the associated high case fatality rate in infected hosts, which is coupled with rapid change into an expanding geographical reach and a growing host range. Recent sequence data identified clear cut recombination in H5N1 isolates in China, and recent swine sequences identified sequences copied with absolute fidelity for over 25 years. These two observations raised serious questions about the role of random mutations in the rapid changes seen in both seasonal and pandemic influenza genes.

Similarly, polymorphism tracing identified the rapid movement of polymorphism from one genetic background to another, which followed identifiable pathways that coincided with the movement of migratory birds.

The role of migratory birds became increasingly clear after the H5N1 Qinghai outbreak, almost exactly two years ago. On May 9, 2005, 178 dead bar-headed geese were reported at Qinghai Lake in central China. Although H5N1 involvement was initially denied, a novel strain was identified in five species of long range migratory birds. Eventually the number of dead birds at Qinghai Lake exceeded 5000. Most were bar headed geese that could travel 1000 miles in 24 hours. The establishment of H5N1 in such long range migratory birds set the stage for a rapid expansion of the H5N1 global reach.

A few months later, H5N1 was reported for the first time in Russia, Kazakhstan, and Mongolia. When sequence data indicated that all three outbreaks were due to the Qinghai strain of H5N1 in long range migratory birds, it was clear that a dramatic increase in the H5N1 reach had begun.

The regions in Siberia and Mongolia were linked to migratory pathways that would move H5N1 into Europe, the Middle East, and Africa. Within 12 months H5N1 had been reported for the first time in almost 50 countries west of China and all outbreaks involved the Qinghai strain.

This rapid spread created an experiment of nature for the study of influenza evolution in a natural environment. H5N1 had not been reported in any of these countries previously, and the newly reported sequences included newly acquired polymorphisms that were regionally specific. The polymorphisms could be traced to determine the origins of the changes to confirm the role of recombination in the acquisitions. As expected, the vast majority of the newly acquired polymorphisms were already present in the sequence database. Most could be found in other H5N1 isolates, although contributions from low path polymorphism were also seen.

However, the greatest insight came from closely monitoring changes in a large number of isolates from the same region over a limited time frame. This opportunity was presented by the sequences generated by US NAMRU-3 in Egypt. Like most of the countries in Europe, the Middle East, and Africa, Egypt reported its first case of H5N1 in poultry in February, 2006. However subsequent analysis of an isolate from a healthy teal indicated that Qinghai H5N1 was already in the Nile Delta in December, 2005. Egypt also lies under overlapping migratory bird flyways, allowing for multiple introductions and significant genetic mixing via recombination.

After the outbreaks in the winter / spring of 2006, detection of H5N1 decreased. New infections in poultry and humans were reported in the fall of 2006 signaling a new season and a new set of H5N1 sequences. The new sequences were more genetically complex and the newly acquired polymorphisms were frequently found in earlier Qinghai isolates, although the regional markers seen in early 2006 were also present in 2007. The recently released sequences from 2006 H5N1 isolates in Israel and Gaza indicated that the regional markers seen in Egypt extended to Israel and Gaza, as had been seen earlier in a human isolate from Djibouti. The 2006 isolates from Egypt, Djibouti, Israel, and Gaza formed a genetic baseline for H5N1 polymorphisms in the region, so newly acquired polymorphisms in the 2006/2007 season were easily identified. The large number of poultry and human samples collected by NAMRU-3 provided a real time view of the H5N1 evolution.

The newly acquired sequences were readily found in H5N1 isolates in eastern Asia, including changes in the receptor binding domain as well as oseltamivir (Tamiflu) resistance, providing further evidence for acquisitions via recombination. The donor sequences in eastern Asia were on H5N1 isolates, but these isolates were genetically distinct from the recent isolates in Egypt, which had the regional markers from the prior season.

Similarly, as more sequences from Qinghai isolates from other countries were released, it became increasingly easy to find the newly acquired polymorphism in Egypt in other locations, but the polymorphism was being acquired individually. One of the changes in Egypt was M230I which was encoded two different ways. One matched H5N1 in Asia, while the other matched H7N3 in Europe. However, recent sequences showed that the Asia version of M230I was in a Qinghai isolate in a German eagle owl, indicating both versions that appeared in the Nile Delta in Egypt in the 2006/2007 season were in wild birds in northern Europe in the 2005/2006 season. ...

The evolution by acquisitions of single nucleotide changes via recombination represents a paradigm shift creating an evolution revolution."

The bottom line of all this is that, although bird flu hasn't been in the news much lately, the situation is as threatening as ever.

As I always do, I once again remind the reader that it's impossible to predict when a particular mutation will permit easy human-to-human transmission, which would result in a worldwide pandemic. This could happen next week, next month, next year, or thereafter.

Once again, as I always say, you and your family should prepare immediately for a possible pandemic. If human to human transmission became public next week on Monday, then by Tuesday all the shelves in grocery stores would be bare. If you stock up on food now, then you'll be sure to have what you need. Even if you think that you can beat the crowds to the grocery store, you should still stock up in advance. If you get your canned food after the panic begins, then you're depriving somebody else of food. But if you stock up in advance, then the shelves will be restocked, and you won't deprive someone else of food.

I once again strongly urge my readers to prepare for an H5N1 pandemic or for any kind of emergency (think of hurricane Katrina) by stocking up on food and water and currency and batteries for the entire household to live on for 2-3 months. This may cost a thousand dollars per person, but it's not wasted money since you can always eat the food later if no emergency occurs. Get canned or dried food that can last a long time in storage, and get a large container for storing water. Keep in mind that stored water becomes impure with time, so you'll also need some purifying tablets or bleach to kill bacteria in the water when the time comes. Finally, get whatever medicines you'll need to take care of yourself and your family for a long period of time. (27-May-07) Permanent Link
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