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Evolving Catastrophic H5N1 Bird Flu Pandemic in 2005

Recombinomics Commentary

July 17, 2005

The latest boxun report describes 10 strains of H5N1 circulating in China.  Eight of the ten have some evidence for human infections, but there is no direct independent confirmation of the data.  The data suggest that the 2005 pandemic is well underway and a wide range of catastrophic events will continue to make news.  The report also suggests H5N1 in China is diverse and evolving, expanding a trend that will likely culminate in an event that may make the 1918 flu pandemic look tame.

Although the specifics of the report are not directly confirmed by third parties, the actions of China and the sequences of the H5N1 emerging from China, strongly support the descriptions of the strains in the boxun reports.

China's statements and actions support many of the details in the boxun story.  When H5N1 exploded throughout Asia, and affected countries adjacent to China, the role of China as a breeding grounds for H5N1 was suspected.  There had been many reports of H5N1 in Hong Kong and most of the poultry in Hong Kong's live markets comes from China.  The H5N1 deaths of members of a Hong Kong family that had visited Fujian province in 2003 were a signal that China had H5N1 that could infect humans.

In 2004, when H5N1 infections were being reported throughout Asia, China also admitted to having H5N1 outbreaks in poultry.  Only Vietnam and Thailand reported human cases, although most of the H5N1 detected in 2004 was the Z genotype, and more closely related to other Z genotype isolates than the 2003 isolates from the family that had visited Fujian province.

In 2005 the reported outbreaks had taken on a somewhat different distribution, but evidence began to mount suggesting that the differences were more related to reporting than actual changes.  Human cases were limited to Vietnam and Cambodia, but recent sequence data on 2005 isolates demonstrates considerable genetic diversity, yet there were human cases in the north and south.  In the north there were two versions of H5N1 that lacked an ARG residue in the HA cleavage site.  This missing ARG had been seen earlier in isolates from China.  In the Manila report some additional information was presented.  The isolates in Vietnam were segregating into two groups.  Northern Vietnam isolates resembled 2005 isolates from Thailand, while southern Vietnam isolates were more like isolates from Cambodia. 

In 2005 Cambodia reported human H5N1 cases, but Thailand did not.  The lack of human cases in Thailand was suspect because of numerous H5N1 outbreaks in birds in 2005, as well as human and wild cat outbreaks in 2004 in Thailand.  Similarly, the lack of human cases in Indonesia became suspect when H5N1 antibodies were found in a poultry worker and H5N1 virus was found in swine.  Now there appears to be human-to-human transmission of fatal H5N1 in Indonesia.

The 2005 sequences in Indonesia and Vietnam have similarities with 2004 Yunnan H5N1 sequences.  Although China has not reported any H5N1 outbreaks in 2005 prior to the May outbreak in Qinghai, the Nature paper described 2005 H5N1 isolates from four provinces in China, Fujian, Hunan, Yunnan. And Guangdong.  The 2005 isolates from Hunan, Yunnan, and Guangdong (Shantou), were similar to isolates from 2003 or 2004.

Thus, as the number of diverse H5N1 isolates from people in northern and southern Vietnam as well as Cambodia and Indonesia increase, the likelihood of human cases in China also increases, yet China has never reported a human H5N1 case.

The boxun report describes eight strains of H5N1 than have been linked to human cases.  The strain of greatest virulence, RK7, appears to be the same as the eight isolates described in Nature and Science.  It is quite lethal in experimental chickens and mice and boxun report indicating it is lethal in humans.  Supporting the human lethality is the present of the PB2 polymorphism E627K, which is associated with H5N1 virulence in mammals. 

E627K is found in all human isolates, but the only H5N1 isolates with the change are from mammals that had a poor outcome.  Prior to Qinghai Lake, all bird H5N1 isolates had the E at position 627.  Thus, finding E627K in all 8 Qinghai isolates is unprecedented, as is the large number of dead migratory birds with H5N1.

The boxun reports are indirectly supported by the Nature and Science reports, as well as sequences in human cases in countries adjacent to China.  There is much more reason to doubt statements by China on the lack of human infections in China or statement by WHO on the lack of mild H5N1 cases in northern Vietnam. 

The data in the boxun report is considerably more believable and the data suggests a catastrophic pandemic will expand, as birds migrate away from Qinghi Lake and summer nesting sites and return to Europe, India, and southeast Asia to spread a variety of new and old H5N1 strains capable of causing lethal infections in humans and a variety of other species.

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