Global Spread of Qinghai H5N1 Bird Flu By Migratory Birds
Recombinomics Commentary
May 6, 2006
Trade in animals, both legal and illegal, is a more likely culprit in spreading bird flu than wild migrating birds, some of the world's top wild bird experts said yesterday.
"Wild bird monitoring is important, but the real threat comes from trade in poultry," John Flicker, the National Audubon Society's president, said after a Capitol Hill briefing.
Aklthough the above comments by wildlife conservation groups have been repeated often, the data clearly shows that H5N1 evolution, transport, and transmission is firmly tied to migratory birds.
Some of the initial data came from sequences of H5N1 in Hong Kong in 2002 and 2003. H5N1 isolates contained sequences that represented recombination between the prior prevalent strains in Hong Kong, but the sequences also had novel polymorphisms not previously seen in the local poultry outbreaks. The introduction of the new sequences was most easily explained by import via migratory birds, which were also H5N1 positive and contained the new sequences.
Recently, new data became available when sequences from wild birds in North America were made public. The sequences were from low pathogenic isolates from mallards in the 1970’s. Many of the sequences from those birds are present in contemporary H5N1 isolates.
The two data sets above however require sequence analysis and recombination. The processes are not well understood by many, so the controversy over the role of migratory birds continued until the Qinghai Lake outbreak, which happened almost exactly one year ago.
On May 9, 2005, China reported 178 dead bar-headed geese at Qinghai Lake. Although involvement of H5N1 was initially denied, China filed an OIE report on May 21 which described H5N1 infections in 519 dead waterfowl. Most of the dead birds were bar-headed geese and the die-off of waterfowl from H5N1 was without precedent. Waterfowl are usually resistant to H5N1 infections and prior isolation of H5N1 in bar-headed geese had not been previously reported. Lab studies showed that the H5N1 was particularly lethal to chickens, killing them within 20 hours. Similarly, experimental mice died 3-4 days after infection.
The large number of dead birds at Qinghai Lake raised the possibility that the H5N1 would burn itself out. Some had suggested that “dead birds don’t fly” and the H5N1 would not extend beyond Qinghai Lake. However, a few weeks later there were H5N1 infections reported in Xinjiang province on poultry farms. Ducks were dying, suggesting that the Qinghai strain was responsible. Since many birds migrate from Qinghai Lake in China in the spring to Chany Lake in Russia in the summer, the dead ducks in western China suggested that the Qinghai strain was migrating to Chany Lake in southern Siberia.
This was confirmed in mid-July when dead birds on farms surrounding Chany Lake were tested. These birds also involved ducks and geese and also were H5N1 positive as were birds in adjacent Kazakhstan. Similarly wild birds at the remote Erhel Lake in Mongolia were also dying and were also H5N1 positive.
In early July sequences from H5N1 from the dead birds at Qinghai Lake were published. Although the sequences were easily distinguished from the H5N1 in earlier outbreaks in China and countries to the east and southeast of China, the H5N1 was highly pathogenic and shared many of the features found in the earlier sequences. However, the Qinghai sequence also had genetic information which was shared with isolates from Europe and had a novel polymorphism, PB2 E627K, which had never been previously reported in a bird H5N1 isolate. E627K was in all H1, H2, and H3 human isolates and in H5N1 from mammals such as mice, cats, and humans, but not birds. All 16 Qinghai bird isolates had E627K which was linked to increased polymerase activity at lower temperature and a poor prognosis for infected mammals.
The Qinghai strain provided a convenient marker for the spread of H5N1. It was easily distinguished from early H5N1 and the Asian version of H5N1 had never been reported in countries to the west or north or China. Thus, when H5N1 was reported in Russia, Kazakhstan, and Mongolia, there was little doubt that the infections were due to migratory birds. Sequence analysis of the H5N1 in those countries also confirmed that the H5N1 was the Qinghai strain.
Although H5N1 had been circulating in China since 1996, when it was detected in a goose in Guangdong, it had not been reported in Russia, Kazakhstan, and Mongolia, countries that share a border with China. Instead, H5N1 spread to the east and southeast when countries reported H5N1 in 2004. That spread of H5N1 was also without precedent, yet there were no reports of H5N1 elsewhere in the world.
Finding H5N1 in long range migratory birds at nature reserves in southern Russia and Mongolia raised the strong possibility that H5N1 would dramatically increase in geographical range because long range migratory birds like the bar-headed geese could fly 1000 miles in 24 hours and Chany Lake was at the intersection of several major flyways connecting Russia to the Indian sub continent, Europe, the Middle East, Africa, and North America.
The spread of H5N1 by migratory birds was confirmed again when reports of H5N1 in dead swans in the Volga Delta and Danube Delta began to appear in late summer and early fall. These areas were know for their abundance of wild waterfowl and were in migratory pathways that included Chany Lake. Analysis of the H5N1 in these wild bird reserves also confirmed that the H5N1 was the Qinghai strain. Additional outbreaks were reported in the fall in Turkey, Croatia, and the Ukraine. None of these countries had previously reported H5N1 infections. H5N1 then was reported in many EU countries throughout Europe. Additional reports came from the Middle East and followed by outbreaks in Africa. All of the isolates were the Qinghai strain of H5N1.
The OIE Mission report from Russia identified over two dozen species of wild birds that were H5N1 positives. These birds were shot from the sky by hunters and were asymptomatic. Additional species have been identified in Europe, indicating that H5N1 infections were widespread and in both migratory and resident wild birds.
The spread of H5N1 at the end of 2005 and beginning of 2006 was without precedent. The infections to the north and west of China were accompanies by human cases in Turkey, Iraq, Azerbaijan, Jordan, and Egypt. All reported isolates from these countries have been the Qinghai strain.
Thus, although H5N1 has been circulating in China since 1996 and dramatically spread into adjacent countries in 2003 and 2004, there were no reported cases elsewhere until H5N1 was transported and transmitted by migratory bird.
Although trade and snuggling of H5N1 infected can extend the H5N1 reach such mechanisms failed to increase H5N1 to reportable levels outside of eastern Asia. This migration of the Qinghai strain of H5N1 dramatically changed the reported cases of H5n1 infections, which have now been reported in the Indian sub-continent, Europe, the Middle East and Africa. Reported H5N1 infections in North America are expect this summer or fall. Recent reports of H5N1 in bar headed geese in remote locations in Gangcha and Yushu countries in Qinghai Province indicate a new cycle of H5N1 transmissions has begun.
The main source of H5N1 worldwide expansion is without question, regardless of how many wild bird experts say otherwise.
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