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H5N1Wild Bird Flu in Humans in China

Recombinomics Commentary

November 16, 2005

The Chinese Health Ministry said Wednesday evening that bird flu had been confirmed in a 9-year-old boy and his 12-year-old sister in central China's Hunan Province and a 36-year-old woman in Anhui Province in east-central China. The boy has recovered and was released from hospital last weekend while the girl and woman died.

In confirming all three cases as infections with the H5N1 bird flu virus, the Chinese authorities went even farther than the WHO was willing to go.

The above comments mark a milestone for H5N1 infections in humans in China.  Although human cases have been suspected for some time, this is the first admission by China of human cases.  Moreover, the rising titer in the 9 year-old boy meet the WHO criteria for a confirmed case, so if the lab results are confirmed by an outside lab, China will be added to the short list of countries with confirmed H5N1 infections in humans.

Today's announcement is a logical result from the H5N1 wild bird flu outbreak that began in May at the Qinghai Lake Nature Reserve.  Initially 178 bar headed geese were found dead and although bird flu was initially denied, China filed an OIE report on May 21 indicating 519 wild birds had died, including bar headed geese and 4 additional species of migratory waterfowl.  These results were unusual because waterfowl are generally resistant to H5N1 infections and the finding of H5N1 in such long range migratory birds indicated H5N1 was ready to significantly expands its geographical reach.

Isolates from Qinghai Lake were sequenced and HPAI H5N1 was confirmed.  Although the sequences were distinct from prior H5N1 sequences, there were common genetic features seen in earlier HPAI H5N1 sequences from Asia including an HA cleavage site containing the multi-basic sequence RRRKKR as well as an N1 with a 20 amino acid deletion.

The sequences were clearly recombinant in nature with polymorphisms from Asia and Europe, but the PB2 gene had the E627K polymorphism, which had previously been associated with virulence in mice.  However, the polymorphism had never been previously found in H5N1 from birds.  It was present in all human isolates of H1, H2, and H3 sero-types, but had only been found in H5N1 isolates from mammals, including human isolates from outbreaks in 1997 and 2004.  E627K in the human cases were associated with poor outcomes.

Third party reports from boxun indicated that there were human fatalities associated with the outbreak at Qinghai Lake.  Although China denied such infections, and inspection visit by WHO identified only two patients who had been tested.

H5N1 at Qinghai Lake did not die out because in June there were infections on farms in Xinjiang province, which was followed by major outbreaks in Russia, Kazakhstan, and Mongolia.  However, these outbreaks were not associated with human cases, even though the isolates were closely related t the Qinghai isolates.

H5N1 was expected to migrate into Europe as the temperatures in Siberia and Mongolia dropped and H5N1 has been confirmed in Turkey, Romania, and Croatia.  However, these countries also did not report human cases.

H5N1 outbreaks were also reported in eastern China and the reports radiated out from Mongolia with outbreaks in Inner Mongolia, Anhui, and Hunan.  The Hunan outbreak was associated with the two siblings mentioned above.  Recently, the case in Anhui was also announced.  There are also human cases under investigation in Liaoning and Hunan.

All of these outbreaks, including four outbreaks in Liaoning, are linked to migratory birds, expanding the number of H5N1 strains linked to human disease.  These cases raise the possibility of widespread transmission of H5N1 and China has responded with vigorous vaccine strategies involving three different vaccines in Liaoning as well as universal vaccination of all poultry in China.

Boxun has come out with a new report that describes significant numbers of infections and fatalities in humans.  The provinces with the highest numbers of human fatalities are the same provinces reporting H5N1 outbreaks.  These largest numbers are in Qinghai (143 deaths), Liaoning (69 deaths), Inner Mongolia (28 deaths), Hubei (25 deaths), Xinjiang (18 deaths), Hunan (8 deaths), Xichang (7 deaths).  In all of these provinces there are reports of human to human transmission.

Although these reports have not been confirmed, the do correlate with the reported H5N1 outbreaks and would be expected to elicit the aggressive measures being implemented in China.

Independent confirmation of this reported serious situation would be useful.


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