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H5N8 Wild Birds Are Not Victims
Recombinomics Commentary
November 29, 2014 19:45

An alternative hypothesis, of course, is that it has reached Europe as part of the trade with poultry and products. After all, the chicken is the most common migratory bird on the planet, although it doesn’t fly on its own wings.

The ‘chicken vs. duck’ argument is an inflamed old discussion, where different people tend to have polarized positions. In my opinion, a middle stance is more appropriate. Likely, both wild birds and poultry can affect geographic spread of highly pathogenic viruses, but the circumstances may act differently from case to case.
The biggest problem at present is our lack of data. A few days ago, the H5N8 virus was identified in a Teal shot as part of active surveillance in Germany. Depending on your preferences, this finding in a healthy duck (that’s at least what the reports say) could either be a ‘game changer’, providing evidence for a link to wild birds, or a spillover event from poultry to wild birds.

The above comments on the H5N8 outbreaks in Europe suggest that there is still a debate on the mode of transmission of highly pathogenic avian influenza (HPAI) H5 in Asia to Europe.  However, this debate was settle in the summer of 2005 when H5N1 (Qinghai strain, clade 2.2) was identified in wild birds in Russia and Mongolia.  The long range transmission of (HPAI) was further supported by the dramatic H5N1 global expansion to Europe, the Middle East, northern and western Africa, and south Asia in 2005/2006.  The export from Asia to Europe was repeated the following year for the Uvs lake version of clade 2.2, which was followed by the export from Asia to Europe of the wild bird Fujian strain (clade 2.3.2) in 2010, and most recently by the Asia to Europe export of H5N8 (clade 2.3.4) in the fall of 2014.

In early 2005 there was still debate on the direction of transmission of H5N1 between poultry and wild waterfowl.  Various conservation groups maintained that HPAI in wild birds was due to transmission from poultry to wild birds (wild birds as victims) and that the “natural” H5 in wild birds was low path (wild birds with H5 had mild infections or were asymptomatic and the H5 in wild birds did not have the poly-basic cleavage site found in HPAI).  The low path H5 also gave waterfowl some immunity to HPAI, which was generally more pathogenic in terrestrial birds (like chickens and turkeys).

However, in the spring of 2005 China reported a massive wild bird die-off at Qinghai Lake in central China.  Although China initially denied the presence of H5N1 based on the presentation of the dead long range migratory birds (dominated by bar-headed geese), H5N1 was quickly lab confirmed.

Two research groups (on from the national labs in China and the other from Hong Kong) published back to back papers in Nature and Science.  Both groups agreed that the sequence data supported a novel sub-clade (2.2 – also known as the Qinghai strain) which was easily distinguished from clade 2 in Indonesia (2.1) or China (2.3) or Clade 1 in southeast Asia.  The new sub-clade raised serious concerns because the PB2 had E627K, which was largely limited to human seasonal flu, but had been reported in a subset of H5N1 cases in Hong Kong in 1997, as well as human cases in southeast Asia on 2004 or other mammals, such as dogs and tigers.  Research on E627K showed that it produced optimal polymerase activity at 33 C in marked contrast to E627, which was “avian” and produced optimal polymerase activity at 41C, close to the body temperature of birds.  E627K was also linked to increase virulence in mice, including neurological tropism (found in mouse brains).

In addition to the presence of E627K, clade 2.2 raised additional concerns because it was in long range migratory birds.  Although H5N1 was linked to a massive die-off of bar headed geese, both groups found H5N1 in multiple waterfowl species at the lake.  However, the group from China noted similarities with H5N1 found previously in South Korea and Japan, while the group from Hong Kong noted similarities with a Shantou guinea fowl.  Thus, the initial data from Qinhai lake in the spring of 2005 did not resolve the direction of the transmission (wild bird to poultry or poultry to wild birds).

However, shortly after the outbreak at Qinghai Lake, China reported the deaths of ducks at a farm in northwest China, raising the strong possibility that H5N1 was migrating toward summer nesting at Chaney Lake in Novosibursk, Russia and were infecting poultry en route.
Prior to 2005 the Asian versions of H5 HPAI had not been reported west of China (other than two clade 1 Crested Hawk-Eagles  being smuggle to Belgium from Thailand - which were confiscated on the plane and never reported outside of southeast Asia).  However, in the summer of 2005 Russia reported Qinghai H5N1 in waterfowl on farms as well as a healthy wild bird bird (crested grebe).  The OIE reports noted that the initial cases were waterfowl that shared ponds with wild birds, and sequence data confirmed clade 2.2 in the domestic birds as well as the wild birds, including the asymptomatic grebe.  Since HPAI H5N1 had never previously been reported in Russia (or neighboring Kazakhatan), the reports of HPAI H5N1 in the summer of 2005 strongly suggested that the H5N1 was being transported by long range migratory birds and had led to domestic poultry outbreaks in Russia and Kazakhstan, largely eliminating the two main arguments of conservation groups (“wild birds as victims” and “dead birds don’t fly”), since Chany Lake in Russia was about 1500 miles from Qinghai Lake (as wild birds fly).

However, conservation groups were undeterred by the Russian data, so when deaths of wild birds at Erkhel Lake in Mongolia was reported a few weeks later, a group aiding in the investigation predicted that the cause of death would not be H5N1 because the outbreak wasn’t as severe as the outbreak at Qinghai Lake in the spring was maintain even after initial data showed that the dead wild birds were H5 confirmed.

When H5N1 was confirmed, the group in Mongolia still predicted the wild birds wouldn’t spread H5N1 because cloacal swabs of the live birds were negative for H5.  However, it was well known that Qinghai H5N1 had E627K which favored growth at lower temperatures and subsequent studies confirmed much higher levels of clade 2,2 in upper respiratory samples compared to cloacal swabs which had low or undetectable levels.  After these studies were published the conservation groups collected 100’s of thousands of feces to generate false negatives and claim that wild birds could transmit H5N1.

However, the Ekhel Lake data was conclusive. There was little domestic poultry in Mongolia and H5N1 has never been previously reported.  The Lake was 1000 miles from Cheny Lake in Russia and 900 miles from Qinghai Lake China.  The lower number of deaths suggested that some species were relatively immune from clade 2.2, which was also supported by the detection of clade 2.2 in an asymptomatic crested grebe in Russia or a teal in Egypt, A/teal/Egypt/14051-NAMRU3/2005.

The detection of clade 2.2 in Russia, Mongolia, and Kazakhstan in the summer of 2005 predicted that clade 2.2 would use long range migratory birds to spread H5N1 to Europe, the Middle East, and Africa in late 2005 or early 2006.

In the early fall media reports cited H5N1 bird deaths in the Volga delta, which was followed by H5N1 deaths of waterfowl in the Danube Delta in Romania.  Initial cases involved swans, which were large and easily noted, but early reports indicated that swans had been dying for weeks prior to the first confirmed cases.  In 2005 more examples were reported by Ukraine on the Crimean peninsula as well as western Turkey.  Other countries in the area denied H5N1 linkage to massive wild bird die-offs, but reports of H5N1 dramatically increased in early 2006 after Turkey confirmed the deaths of three children in a family from eastern Turkey.
In November, 2005, Recombinomics predicted clade 2.2 human cases based on donor H9N2 sequences in the Middle East.  Recombination between H9 and H5 from clade 2.2 could produce S227N, which had been previously cited as producing increased avidity for mammalian gal 2,6 receptors found in the upper respiratory tract of humans.  S227N was confirmed in the first reported clade 2.2 human case, which was from the index case of the Turkey cluster.

The cases in Turkey were followed by human clade 2.2 cases in Azerbaijan, Iraq, Egypt, and Nigeria in 2006/2007.  Clade 2.2 was widely reported in wild birds as well as poultry throughout Europe, the Middle East. North eastern Africa, west Africa, and south Asia.  All of the H5N1 in these countries was reported for the first time in 2005 or 2006 and all sequences in wild birds, humans, and poultry were the Qinghai strain.
Although these data clear showed that the H5N1 long range transmission was by wild birds, subsequent outbreaks in Europe followed a similar pattern.  In the summer of 2006 a slightly different version of clade 2.2 was reported at Uvs Lake in Mongolia, with spillage to adjacent areas in Russia.  This Uvs lake strain subsequently appeared in Europe in 2007, in many of the same areas as the current H5N8 outbreak.

Similarly, in 2010 the wild bird version of the Fujian strain (clade 2.3.2) appeared in Europe (Bulgaria) which had been predicted by poultry outbreaks in South Korea and south-eastern Russia and wild bird outbreaks in Japan in 2008, followed by the detection of this sub-clade in Mongolia.

In early 2014 outbreaks of H5N8 were reported in China, South Korea, and Russia.  The H5 was the Fujian clade 2.3.4, which had been reported in H5N1 human cases in China in 2006.  This sub-clade was reported in November in Germany, the Netherlands, and England A/turkey/Germany-MV/R2472/2014, A/Ch/Netherlands/14015526, A/duck/England/36254/14) on poultry farms, as well as an asymptomatic wild teal in Germany.  The sequences from all three countries were virtually identical with each other and November sequences from wild duck feces in Chiba, Japan (A/duck/Chiba/26-372-48/2014 and A/duck/Chiba/26-372-61/2014).  November wild bird collections in Shamane, Totorri, and Kagoshima (see map), provide additional confirmation of wild bird export of HPAI H5 from Asia to Europe.

Thus, the geographic, temporal, and sequence data settle the issue of long range H5 HPAI transmission by wild birds and subsequent spread in 2006, 2007, 2010, and 2014 show that this type of spread is common, no additional studies required.

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