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Global Expansion of H5N1 Raises Pandemic Concerns
Recombinomics Commentary 22:26
May 22, 2008

Today’s report on more H5N1 confirmed whooper swans in Japan increases the likelihood of a significant global expansion of H5N1.  These outbreaks of the Fujian strain in Japan are associated with record levels of H5N1 in South Korea, setting the stage for an expansion of H5N1 into new areas.  H5N1 has not been previously confirmed in these northern areas of Japan or southeastern Russia.  Movement into new areas parallels development almost exactly three years ago at Qinghai Lake, when H5N1 caused a massive wild bird outbreak leading to a dramatic global expansion of the Qinghai strain, which moved clade 2.2 into 50 countries west of China where H5N1 had not been previously reported.

In the current expansion, the Fujian strain (clade.2.3) is moving into new areas.  However, the monitoring of this movement is punctuated with false negatives.  One of the birds reported today died last month, but initially tested negative on the rapid test.  This result mimics the data for the soldier in South Korea who tested positive in 2 or 3 lab tests, bit was declared negative because the N1 test was negative.  The case was relatively mild, which raises concerns of more efficient transmission and undetected case.

The soldier in South Korea has parallels with the announcement of the first confirmed H5N1 case in Bangladesh.  Although the child was infected in a Dhaka slum in January, he was not confirmed positive because in January he tested negative for H5, but has since tested positive in the testing by the CDC in Atlanta.  Like the case in South Korea, or multiple mild cases in Egypt a year ago, such cases are easily missed in testing, if the testing is done at all.  Such cases are more likely to spread H5N1 to others because they are more mobile because they are not as sick, and contacts are also not likely to be tested.

The infection in a slum in Dhaka, with no contact with domestic poultry raises transmission concerns.  Dhaka had reported dead crows, which were confirmed H5N1 positive in multiple cities in Bangladesh.  There were similar reports of dying wild birds in major cities in India, including Calcutta.  In India, testing was minimal.  Villagers who ate H5N1 infected birds and developed symptoms were watched, but not tested.  The number of mild cases in India and Bangladesh was undoubtedly significantly higher than the one reported case.

Although mild H5N1 is a decided plus for patients who recover, the passage of H5N1 through mammalian hosts leads to adaptation, which is the greatest concern for H5N1.  Moreover, since H5N1 can readily recombine with more aggressive strains of H5N1, the milder versions can acquire the ability to transmit efficiently, and the re-acquire virulence properties.  These types of changes can be seen at the genetic level by characterizing acquire polymorphisms.  In Israel, the H5N1 PB2 gene has acquired a number of human polymorphisms.  Similarly, the H1N1 that is Tamiflu (oseltamivir) resistant has acquired a polymorphism, H274Y, which is found in H5N1.  As noted, Florida isolates have acquired an additional NA polymorphism that is almost exclusively found in H5N1.

These cross species polymorphisms exchanges suggest that the prevalence of H5N1 in human hosts is far more common than is reflected in official WHO cases.  Surveillance programs in humans and wild birds remains poor, so much of the H5N1 activity involves silent changes.

However, the movement of the Fujian strain into long range migratory birds is clear, and this strain will be co-circulating with the Qinghai strain, leading to more exchanges of genetic information and infections of more birds which are eaten by more mammals.  Surveillance of mammals is even poorer than surveillance of wild birds and humans, lead to more silent spread of H5N1.

The geographic spread of H5N1 has become increasingly obvious, and the latest data from Japan, South Korea, and southeastern Russia signal a new advance into new regions such as northeastern Asia and North America.

This global expansion should become increasingly clear in the upcoming months.

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