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H5N1 Wild Bird Flu Migration In Russia Kazakhstan Mongolia

Recombinomics Commentary

August 23, 2005

The notification does not provide details on the final identity of the causal agent, aside from its being an Influenza A, H5 virus. From the reported clinical observations it might be assumed that this is not a highly pathogenic strain. However, laboratory confirmation is needed, particularly the neuraminidase identity and results of the prescribed pathogenicity tests.

A subscriber who preferred to remain unnamed has asked us the following: "Dead ducks don't migrate. All reports of H5N1 virus in wild birds so far appear to be from dead ones. Has anyone, anywhere, actually found a healthy wild bird, capable of migrating, which was carrying and shedding Z-genotype highly-pathogenic H5N1?" A valid question -- which we willingly include, inviting responses. - Mod.AS

The above commentary from ProMed is curious.  It was written in response to Russia's 4th OIE report on the H5N1 wild bird flu outbreak that is migrating across southern Russia and racing toward Europe (see August map).  The evidence for transportation and transmission of H5N1 by migratory birds is overwhelming, yet ProMed is asking questions that have been answered many times over.  They are also raising the dead ducks don't migrate argument once again.

The latest OIE report was filed on August 20 and it provided more information on the H5N1 that had spread across at least 6 southern provinces.  Viral isolates or HI tests had shown that the virus in all regions were essentially the same as the H5N1 described in the prior report dated August 9.

In the latest report, the distribution of the outbreak was described.  Instead of passing quickly from farm to farm, the outbreaks were linked to the proximity of the farm to reservoirs frequented by migratory birds.  The interpretation in the commentary suggested that the H5N1 might not be highly pathogenic and therefore might not be H5N1.

However, the prior report went into extraordinary detail to show that if fact H5N1 was responsible for the outbreaks, and the H5N1 was clearly closely related to the H5N1 from Qinghai Lake.  One standard test for pathogenicity is the sequence of the HA cleavage site.  Multibasic amino acids correlate with high pathogenicity, and the sequence of the H5N1 from Asia has more basic amino acids (six in a row preceedoing the cleavage point) than any reported isolate.  This is quite well known and the sequnece first appear in Asia in Guangdong in a goose in 1996.  This sequence is unique to Asia and all isolates with this sequence are H5N1. The sequence in the Chany Lake isolates is PGQERRRKKR/GL as noted in the earlier OIE report which includes the HPAI sequence from Asia.  Since no isolate other than H5N1 has had this sequence, the sequencing of this small region alone would indicate that the virus was highly pathogenic and was H5N1.

However, the earlier report also provided an extensive HA sequence of one of the isolates and it was closely related to the H5N1 isolates from Qinghai Lake. The only additional polymorphisms were shared with H5N1 from South Korean and Japan, and similar associates were noted for the Qinghai lake isolates.  Thus, all of the sequence data on HA pointed toward a close relationship with the 16 isolates from Qinghai Lake, providing overwhelming evidence that the isolates at Chany Lake, as well as the subsequenced isolates from Siberia, all were H5N1.

The earlier report however, did not rely on the extensive data on HA to conclude that the isolates from Chany Lake were H5N1.  They also sequenced a large portion of the NA gene.  The NA gene of H5N1 is also quite distinctive from other serotypes and the H5N1 from Qinghai Lake had the major characteristics and motifs found in H5N1 isolates in Asia.  The prior report included a phylogenetic tree showing that the Chany Lake isolate was identical to three other isolates (DQ100565 A/great black-headed gull/Qinghai/1/2005(H5N1);DQ095663 A/Bar-headed Goose/Qinghai/67/05(H5N1); DQ095654 A/Great Black-headed Gull/Qinghai/2/05(H5N1).

Thus, both the HA and NA data indicated the H5N1 in Novosibirsk and the other Russian provinces was virtually identical to the highly pathogenic H5N1 isolated at Qinhai Lake.

This relationship was not a surprise.  The H5N1 was identified in five migratory bird species at Qinghai Lake (see May map).  The die-off was without precedent and the isolated H5N1 could kill experimental chickens within 20 hours and mice within 3-4 days.  The large number of migratory birds at Qinghai Lake reduced the likelihood that the H5N1 would burn itself out.  Although over 5000 bar headed geese died, the number of dead birds in other species was markedly less, so it seemed likely that some of the birds would fly to Chany Lake, where many species from Qinghai Lake summer.

This possibility was supported when there were outbreaks in Xingiang Province in June (see June map).  The affected birds were ducks and geese, consistent with the die-off of bar-headed geese at Qinghai Lake.  Moreover, the affected farms were under the flight path from Qinghai Lake to Chany Lake, and the OIE reports for the outbreaks indicated the infections were due to migratory birds and the isolated virus was highly pathogenic H5N1.

When birds started dying at Chany Lake in July (see July map), migratory birds were suspected for the source of the outbreaks near Chany Lake and the adjacent region in Kazakhstan.  The reported sequence data supported the suspicions, which was subsequently bolstered by finding in Kazakhstan and Mongolia that outbreaks there involved wild birds and were linked to migratory birds.  In Mongolia, the outbreaks were at the remote Erhel and Khunt Lakes and included among the dead were whooping swans and bar headed geese.

Thus, the data are overwhelming that the same H5N1 in migratory birds at Chany Lake have now extended H5N1's geographical reach to Russia, Kazakhstan, and Mongolia, three countries that have never previously reported H5N1 from Asia.

All of the above make the initial comments by ProMed curious.  The comment about dead ducks migrating is especially striking.  H5N1 transport does not require that the initial infection remain with one bird.  If the H5N1 transmits to other members of the flock, the H5N1 can be transported even if the initial infected bird dies.  Moreover, the infection can move to other species, as has happened at each of the outbreaks at nature reserves, so even if all members of a flock die, the H5N1 can still be transported by other birds.  Questions about dead ducks migrating seem rather odd for a commentary by an International infectious disease organization

In any event, H5N1 is clearly being reported for the first time in three countries and the transportation and transmission is by migratory birds, ProMed curious commentaries not withstanding.


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