Qinghai H5N1 Migration in Europe the Middle East and Africa
Recombinomics Commentary
April 20, 2007
The broad dispersal of these isolates throughout these countries during a relatively short period, coupled with weak biosecurity standards in place in most rural areas, implicates human-related movement of live poultry and poultry commodities as the source of introduction of influenza (H5N1) into some of these countries.
The virus' presence in wild birds leaves open the alternative possibility that migratory birds may have been the primary source, with secondary spread possibly caused by human-related activities.
According to the researchers, the broad dispersal of the disease also suggests that human movement, and not the migration of wild birds, is primarily responsible for the rapid spread of 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."
The above comments in the paper, "Genome Analysis Linking Recent European and African Influenza (H5N1) Viruses", represent an unfortunate representation of the expanded geographical reach of the Qinghai (Clade 2.2) strain of H5N1 and associated evolution. The paper provides sequence analysis of samples collected in early 2006, which confirm that all of the H5N1 isolates in Europe, the Middle East, and Africa were the Qinghai strain, and there are regional differences. However, that conclusion, along with the fact that the vast majority of the spread is due to migratory birds, has been quite clear since 2005. The above paper focuses comments on trade as a source of spread to "some of these countries", but provides no evidence for such a statement, and follows with the false statement in media reports, claiming that "migratory pathways of wild birds don't correspond with movement of the genomes that we sequenced".
The correspondence of the H5N1 spread with migratory bird pathways has been known since the summer of 2005 (see dynamic map), and such pathways predicted the movement of the Qinghai strain of H5N1 from southern Siberia / northern Mongolia into Europe, the Middle East, and Africa. The sequences in the paper provide further confirmation that the primary mover of the Qinghai strain of H5N1 is migratory birds.
The strain was first reported at the Qinghai Lake nature reserve in May, 2005. Initially, all positives were from dead bar-headed geese. The subsequent OIE report described infections in five species of waterfowl and the number of dead birds continued to rise through the month of May. Most of the dead birds however, were bar headed geese that can fly 1000 miles in a 24 hour period, providing a mechanism for transporting H5N1 over long distances. The Qinghai Lake nature reserve was populated by over 100 species of waterfowl and is at the intersection of multiple flyways. Many of the species at Qinghai Lake in the spring, spend the summer in southern Siberia and northern Mongolia.
Thus, when H5N1 was reported at another nature reserve, Chany Lake in Novosibirsk, and sequence analysis showed that the H5N1 in Russia was the Qinghai strain, there was little doubt that long range migratory birds were spreading H5N1 over long distances. The reports of Qinghai H5N1 in and around Chany Lake were quickly followed by reports of H5N1 in adjacent Kazakhstan, as well as Erhel Lake in Mongolia. None of these countries had previously reported highly pathogenic H5N1, and all three reported Qinghai outbreaks in the summer of 2005.
The reports of widespread infections in the summer of 2005 in Mongolia and Russia led to prediction that H5N1 would spread to Europe, the Middle East, and Africa in the fall of 2005 and winter of 2006. This prediction was confirmed by the detection of H5N1 in the Volga Delta in Russia, and the Danube Delta in Romania. These areas had not previously reported H5N1, and again the H5N1 was the Qinghai strain, which was being detected in dead waterfowl (primarily mute swans). These confirmations in the fall of 2005 provided additional evidence for the movement of Qinghai H5N1 from one nature reserve to another, faithfully following known migratory bird flyways.
H5N1 was also reported in western Turkey in the fall of 2005, but most countries denied H5N1 infections in wild birds or poultry. The failure to detect H5N1 in wild birds was due in part to the low sensitivity of the testing, as well as the low levels of H5N1 in live birds. Although Russia had detected H5N1 in hunter killed birds in regions that were heavily infected with H5N1, none of the European countries had detected H5N1 in wild birds. Egypt subsequently identified H5N1 in a healthy teal in the Nile Delta in a sample that was collected in December, 2005, but initial testing was negative.
Thus, false negatives in Europe, the Middle East, and Africa led to the false conclusion that H5N1 migration into the region was limited. However, the deaths of several patients in eastern Turkey due to Qinghai H5N1 infections clearly demonstrated that H5N1 was in the region, and subsequent testing demonstrated that H5N1 was widespread in wild birds and poultry in Turkey. Although neighboring countries continued to deny H5N1 presence, culling of poultry began in January, 2006. In February 2006, H5N1 detection exploded, and was reported for the first time in over 40 countries in Europe, the Middle East, and Africa. All of these infections were due to the Qinghai strain. A presentation in Italy in the spring of 2006 indicated that over 700 H5N1 positives were detected in Europe, and phylogenetic analysis of approximately 80 of the isolates showed that they were all the Qinghai strain.
There was little evidence to support significant movement by trade. Although poor biosecurity can lead to local spread, the evidence against long distance spread of Qinghai H5N1 by trade is also overwhelming. The "Asian" strain of H5N1 was first reported in China in 1996 and subsequent isolates from China and Hong Kong between 1996 and 2003 indicates H5N1 infections were a continuous problem. In 2003/2004 H5N1 exploded out of China and was reported in countries to the east and south east of China, but no country to the west reported H5N1.
However, after detection of the Qinghai strain in migratory birds in May, 2005, H5N1 rapidly spread into Europe, the Middle East, and Africa, and the spread followed migratory bird pathways. Recent reports of H5N1 in feces collected from live markets in southern China between mid-2005 and mid-2006 only found one Qinghai strain. The vast majority of the 4141 reported isolates in China were the Fujian strain (clade 2.3). Moreover, the H5N1 detected in quarantine in England in late 2005 was also the Fujian strain, but the Fujian strain has never been reported in wild birds or domestic poultry in Europe, the Middle East, or Africa, further discounting the role of trade or exotic birds in the spread of Qinghai H5N1 into regions west of China.
In addition, the sequences of H5N1 in the 2006/2007 season from birds or humans in Egypt supports multiple introductions of H5N1 and the continued evolution of H5N1 by recombination. The recent simultaneous acquisition of a polymorphism previously detected in a large subset of wild bird isolates in Germany provides compelling evidence for widespread infections by a common source. The polymorphism, NA G743A, was detected in six isolates in Egypt, representing three distinct subclades, and the polymorphism was also found in Moscow, in an additional Qinghai subclade.
This simultaneous appearance on multiple Qinghai genetic backgrounds in diverse locations is most easily explained by recombination between migratory birds and local H5N1 populations. The German isolates had a number of regional markers for Germany, but lacked markers from Egypt or Russia (which were closely related to 2006 isolates from Azerbaijan). The 2007 isolates were collected over a short time frame in the winter of 2007, and the new acquisitions were on very distinct genetic backgrounds.
The evolution of H5N1 is driven by migratory birds and recombination. This mechanism produces multiple subclades in Europe, the Middle East, and Africa. The above comments, which fail to understand this most basic mechanism of H5N1 evolution, are cause for concern.
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