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Circulation of H5N1 and H7N3 in England
Recombinomics Commentary
February 5, 2007

Fears were raised last year, after a swan with H5N1 was found in Fife, that the disease could have reached the wild bird population, but these faded after it was found to have migrated across the North Sea during cold weather.

This year ornithologists say there has not been the same movements of wild birds, because of the warmer winter, so it is possible that the strain arrived in the autumn.
Some waterfowl, particularly geese, gulls and ducks such as pochard, are known to be "virus time bombs" because they cancarry the disease without it being apparent.

David Catlow, the president of the British Veterinary Association, said: "There are two lines of inquiry – one that it comes from Hungary, the other that it is in wild birds.

"We do think there is a low level of H5N1 in the wild bird population in Europe. We have put all the controls in place to stop direct transmission but we can't stop a bird population moving around.

"This [the Norfolk outbreak] is the Asiatic strain that has affected Turkey and Hungary, not a new mutation or different strain of H5N1.

"That is why Defra has widened the buffer zone and will be taking surveillance of the wild bird population."

The above comments describe the H5N1 detected in England last year and this year and acknowledge that H5N1 is in wild birds in Europe.  These comments are supported by confirmed H5N1 cases throughout Europe last year, and a limited number of confirmations this year.  Most of the confirmations in Europe were in January / February of 2006.  These confirmations extended through the Middle East and into Africa, including Egypt.  All of the high path H5N1 isolates were the Qinghai strain (Clade 2.2).

Recently, H5N1 was confirmed in Hungary and Krasnodar.  However, last year H5N1 was widespread in countries between the two recent outbreaks, including Ukraine and Romania.  Similarly, last year H5N1 was in countries between Hungary and England.

Sequence analysis identifies a series of regional markers that sub-divides the Qinghai strain further.  A series of markers links recent human cases in Egypt to locations upstream, including Germany and Italy, as well as downstream, including Djibouti in eastern Africa, and Nigeria in western Africa.  These markers reflect recombination with local avian influenza and allow origins to be traced.

Recent isolates in Egypt have linkages that extend back to the H7N3 outbreak in England last year.  The change in M230I, which is adjacent to the receptor binding domain, highlights recombination between H5N1 and H7N3.  In Egypt, M230I is found in two forms.  In the human cases, including the Gharbiya cluster, the coding for M230I matches H5N1 in Asia.  The Gharbiya cluster has additional changes HA V223I and NA M29I which are found in H5N1 in geese in Shantou.  However, the M230I in most of the recent bird isolates in Egypt have M230I that matches the H7N3 found in England last year, which is the same region as the H5N1 this year.

This co-circulation of H5N1 and H7N3 in wild birds in the same region is cause for concern.  Transmission of H7 to humans is more efficient than H5N1.  Human cases were linked to H7N3 in England, H7N3 in Canada, and H7N7 in the Netherlands.  All of these outbreaks had M230I.  Now this same version of M230I is reported in the Qinghai version of H5N1 for the first time in the recent isolates in Egypt.

This M230I receptor binding domain change is in addition to other changes in human cases in Egypt (V223I, S227N), Turkey (S227N), Iraq (N186S, Q196R), Azerbaijan (N186K).  The above changes are in Qinghai isolates, which also have PB2 E627K, raising concerns of increased efficiency of human transmission.

The finding of H5N1 in the same region as H7N3, as well as M230I in H5N1 in Egypt with H7N3 coding raises concern over additional recombination resulting in new combinations of receptor binding domain changes and increased efficiency of transmission of H5N1 in humans.

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