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Second Bird Flu Patient in Turkey Dies
Recombinomics Commentary
January 5, 2006
Fatma Kocyigit, 15, died in a hospital in the eastern city of Van, four days after the death of her 14-year-old brother, Mehmet Ali, Anatolia said. Their 11-year-old sister, Hulya, who is also suspected of having bird flu, was in serious condition on Thursday morning, according to doctors.
About 10 other patients with similar symptoms were being treated at the hospital.
The Kocyigit children helped to raise poultry on a small farm in the eastern town of Dogubeyazit, close to Iranian border, and were in close contact with sick birds.
Akdag contradicted a ministry statement earlier this week that said the boy''s death at a hospital in southeastern Van province on Sunday was not caused by bird flu. Akdag said authorities repeated the test in two separate laboratories following an autopsy on the boy.
The above comments raise additional concerns about increased efficiency of human-to-human transmission of H5N1. Although the number of cases positive for H5 has been limited thus far, the limitation appears to be related to samples collection. Both fatal cases initially tested negative for influenza, but those tests used nasal swabs. However, since the patients had already developed pneumonia, the H5N1 had already moved to the lungs, which is why the subsequent tests on lung samples were positive.
The clinical picture is more diagnostic than the early lab tests, and the clinical picture suggests all of those hospitalized with high fever, pneumonia, and bleeding gums have H5N1 infections. The number of patients fitting those conditions may already be as high as 15.
Some reports indicate that those hospitalized are from two families. However, even if only two families are involved, they would represent the two largest familial H5N1 clusters reported to date. The highest previous cluster was a family of five from Haiphong in northern Vietnam in march of 2005. However, all five of those family members recovered.
In the current outbreak, two siblings have died and a third is in critical condition. The other patients are in serious condition and should be on ventilators. However, the surge of patients has already created a shortage of ventilators.
The advanced condition of the hospitalized patients raises concerns that additional cases will be discovered as milder cases progress. Four provinces in Turkey had recent reports of poultry deaths and H5 had already been confirmed in one adjacent province. The high concentration of cases already in the hospital suggests more outbreaks in Turkey are likely.
The more efficient transmission of H5N1 to humans could be driven by the S227N polymorphism which was identified on two H5N1 from Hong Kong patients who had visited Fujian Province in 2003. Generation of that polymorphism via recombination between the H5N1 in wild birds and H9N2 endemic to the Middle East is a cause for concern. Dual infections by H5N1 and H9N2 in the past have generated reassortants and recombinants in Asia, so similar shuffling of genetic information in the Middle East would not be unexpected.
The two fatalities mentioned above represent the first two confirmed H5N1 fatalities outside of eastern Asia. They are also the first human H5N1 infections closely linked to migratory birds transmitting the H5N1 clade first identified at Qinghai Lake. However, sequences from 2005 human cases in China and Indonesia have not been made public, so those transmissions may also involved similar sequences, although media reports suggest the human sequences are more closely related to the local H5N1 described previously in poultry. However, the published sequences of the H5N1 wild bird sequences also reveal acquisition of a number of polymorphisms via recombination, suggesting the wild bird sequences can play a more subtle role in the evolution of H5N1 sequences.
Recent OIE reports from the Ukraine describe two HPAI HA cleavage sites, demonstrating the continuing evolution of H5N1 in the area. The cases in Turkey raise the number a H5N1 strains capable of causing fatal infections in humans and highlight the need for a much more aggressive and varied pandemic vaccine approach. The genetic drift between the wild bird sequences and those from Vietnam in 2004 suggests that the current pandemic vaccine in clinical trials will have limited use against the H5N1 in Turkey.
However, it is likely that the H5N1 in Turkey will be sensitive to the amantadanes, although media reports suggest such anti-virals have not been used in the Turkish cases. Media reports indicate the human H5N1 cases in Indonesia and China have been amantadine sensitive, and amantadine was successfully used in the treatment of the confirmed case in Hunan.
H5N1 has been isolated from many if not all of the outbreaks in China, and the comments above suggest that H5N1 will be isolated from autopsy samples in the current outbreak in Turkey. Moreover, isolation of H5N1 from the poultry in Turkey should be relatively straight forward.
Russia is to be commended for the rapid deposit of complete H5N1 from recent outbreaks in the Volga Delta, Tula, and Kurgan as well as sequence data from earlier outbreaks in Novosibirsk.
Sequences from recent cases in China, Indonesia, and Turkey would be useful.
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