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Monitoring Migration of H5N1 Bird Flu In Asia and Europe

Recombinomics Commentary

August 12, 2005

Is it possible that a particular species  of migratory bird travels this north-west route in the spring/summer and could be spreading the virus? We would be interested to know if there are (local?) experts with knowledge about specific Asian avian migratory routes who might be able to help pinpoint one or more avian species that could be spreading the virus.  This would be interesting to know and would contribute to our understanding -- and perhaps to our ability to control -- these avian influenza outbreaks.

The above comments at Promed reinforce the need for an aggressive monitoring system and the outbreaks of H5N1 at Qinghai Lake in Qinghai, China and Chany Lake in Novosibirsk, Russia highlight the need and show that such a broadening of the H5N1 database is very doable and important.

The migration from Qinghai Lake to Chany Lake was predicted both by prior observations as well as sequence data.  H5 has been isolated previously at Chany Lake in the past.  The low pathogenic virus was clearly related to H5 isolates from Europe, but also had polymorphism from Asia clearly showing that such isolates were recombinants.

The sequences from Qinghai Lake reinforced those observations.  One constellation of polymorphisms in PB2 was particularly telling.  The 3 changes were found in an H3N2 isolate from a child in Hong Kong in 1999 and it matched swine sequences from Europe , which includes several mammalian serotypes (H1N1, H1N2, H3N2).  Those polymorphisms were in a gene that had many Asian polymorphisms, providing additional evidence of the acquisition of mammalian polymorphisms via recombination.

Sequencing of Novosibirsk isolates clearly showed that they originated at Qinghai Lake.  The NA sequences was virtually identical, the HA multibasic cleavage site matched, and a virulence sequence matched.  The virulence sequence was almost certainly the PB2 polymorphism, E627K.  This polymorphism is particularly revealing because the Qinghai isolates marked the first reported isolation of H5N1 with that polymorphism in a bird.  The polymorphisms has been found in all human isolates (serotypes H1N1, H1N2, H2N2, H3N2), but all H5N1 isolates with the polymorphisms were from mammals (passage through mouse brain, tigers in Thailand, or humans from Hong Kong in 1997 or Vietnam and Thailand in 2004).  The H5N1 isolates from mammals was associated with a poor outcome and the change was associated with increased virulence in mice.  The Qinghai isolates were also virulent in chickens.  Experimentally infected chickens dies within 20 hours.

Because the H5N1 in Qinhai Lake and Novosibirsk is so virulent, its path is easily marked by deaths in domestic poultry and other migrating birds.  As see in the map tracking reported deaths, the H5N1 was first reported at Qinghai Lake in May.  In June there were outbreaks to the northwest, in Tacheng and Urumqi in Xinjiang.  In July there were outbreaks in villages to the east, west, and south of Chany lake in Novisibirsk.  In August, as birds began to migrate to warmer climates there were outbreaks to the east and west along Russia's southern birder with Kazakhstan.

In recent days, the migration has been extended to the eastern base of the Ural mountains in Kurgan, to the southwest in Kazakhstan, to the southeast in Altay Kray in Russia and several locations in Mongolia.  In addition, migration south from Qinghai Lake caused an outbreak in Tibet.

The number of reported outbreaks suggests the H5N1 was amplified at Chany Lake.  Full sequences will define additional recombination.  The number of species at Qinghai Lake and Chany Lake are large, so the efficient transmission of H5N1 to a number of migratory birds will cause more infections as these birds fly to warmer climates for the fall and winter.  The reported collection of samples at Qinghai Lake was small. The large numbers of infected water fowl at Chany Lake offers an opportunity to significantly enhance the database on H5N1 in migratory birds.  Unfortunately, the upcoming weeks will offer many additional opportunities in Asia and Europe.

The OIE report from Novosibirsk demonstrated several different combinations of virus and antibodies.  Some birds had antibody and no detected H5N1 indicating they had survived a prior infection and could therefore transmit H5N1.  Others were alive and had antibody and virus, indicating they were active transmitters.  A third group had antibody and virus, but had died.  Migratory birds in this category could transmit H5N1 via contact with other birds in the flock or at the nature reserve.

The virulent H5N1 at Chany lake and Qingahi Lake are easily isolated.  Harbin in China has submitted OIE reports from Qinghai Lake, Xinjiang, and Tibet.  In each case H5N1 was tested in a pathological test on chickens and in each instance the H5N1 was highly pathogenic (HPAI).  Sixteen sets of sequences from twelve birds have already been published for Qinghai Lake.  Early reports indicated at least nine independent isolates were obtained at Novosibirsk and initial reports on the sequences indicate that the isolates are closely related to the Qinghai isolates.

The HPAI H5N1 should be easy to track and more samples from healthy birds will help determine which birds transport H5N1.  However, the mounting dead bodies on the ground, should easily define the migratory routes, which will likely cover most of Asia, Europe, and beyond.


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