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Nine Workers With H5N1 Antibodies in South Korea
September 15, 2006
Recombinomics Commentary

Five more South Koreans were infected with the H5N1 bird flu virus about three years ago but none of them developed any serious illnesses, officials said on Friday after recently completed testing on old samples.

South Korea, which did not have comprehensive testing at the time, sent samples of 318 poultry industry workers taken during an outbreak in late 2003 and early 2004 to the U.S. Centers for Disease Control and Prevention in 2005 for further examination.

Of those workers, four South Koreans were infected, the CDC has said. The government said in February the four did not develop major illnesses.

The results prompted South Korean health officials to send samples to the CDC from another 2,109 people and of these, five were also infected, the health agency said on Friday.

"The five did not develop major illnesses and have no strain to transmit bird flu," the Korea Centre for Disease Control and Prevention said in a statement.

The above comments on nine South Koreans who developed H5N1 bird flu antibodies suggests that mild H5N1 infections are more common than rfepresented by  the number of confirmed cases listed by the WHO.  The H5N1 from South Korea in late 2003 was similar to the H5N1 isolated in Japan in early 2004.  Japan also reported H5N1 antibodies in farm workers who cleaned up H5N1 contaminated farms.  Like the South Korean cases, these patients had mild or no flu symptoms and the antibodies were detected retrospectively.

Although the reported 2003/2004 infections did not lead to serious disease, sequences from the isolates from Korea and Japan were found in the Qinghai strain of H5N1 which was initially identified in May, 2005 in dead bar-headed geese at Qinghai Lake.

This strain subsequently was detected in Russia, Mongolia, and Kazakhstan in the summer of 2005 followed by detection in Europe, the Middle East, and Africa.  None of these countries had reported HPAI H5N1 infections prior to the Qinghai outbreak.

The role of the Qinghai strain in mild infections remains confusing, largely due to a lack of transparency in Turkey, Weybridge, and the WHO.  The first confirmed H5N1 cases were reported in late 2005 / early 2006 in Turkey.  Media comments initially described bird flu symptoms in two large families in eastern Turkey.  At the time H5N1 had been confirmed in birds in western Turkey in October, 2005, but outbreaks in eastern Turkey were denied.  Subsequent OIE reports indicated that H5N1 in birds was widespread throughout Turkey in weeks or months before the human cases were reported.  Initial WHO updates failed to note that the confirmed H5N1 in the two families were in patients who were cousins and had had contact prior to symptoms, strongly suggesting that these cases were largely due to human-to-human transmission, followed by cluster-to-cluster transmission.  A change in the receptor binding domain of the index case was also noted.

Twenty-one cases were H5N1 positive and described in WHO updates, although disease onset dates and relationships between clusters were withheld.  Almost all of the cases were from clusters of two or more family members.  Included were mild cases such as two brothers who played with gloves used by their father to carry an H5N1 wild birds, or two other brothers who played catch with an H5N1 infected dead bird.  These patients were tested because of exposure, even though they had mild or no symptoms.

The twenty-one H5N1 positive samples were sent to Weybridge for confirmation, but only 12 samples were confirmed.  However, since most of these samples were from clusters, the likelihood of false positives was low.  Sample degradation after collection and/or shipment is a likely cause for false negatives.  The 12 positives were not described, other than an acknowledgement that the four fatal cases were H5N1 positive.  The sequences of H5N1 from the index case A/Turkey/12/2006 or his sister, A/Turkey/15/2006 have been made public as have sequences from two survivors.  However, even the age and gender of the two surviving patients has been withheld.  Similarly, none of the sequences from the bird isolates in 2006 have been released, so the involvement of H5N1 in mild cases remains unclear.

Similarly, many patients with symptoms and members of clusters that were H5N1 confirmed remain of the WHO list of confirmed cases.  Since these patients survived, confirmation can be achieved by simply collecting and testing another serum samples.  Samples collected in 2004 from survivors of 1918 pandemic flu had high titer neutralizing antibodies more than 80- years after exposure.  Thus, detecting antibodies months or years after exposure is relatively straightforward.  WHO had indicated in January that they would collect 10,000 serum samples from patients or contacts in Turkey.  The status of these collections has not been made public.

Thus, the ease of transmission of Qinghai H5N1 in patients in Turkey remains uncertain. 

As the number of mild or asymptomatic H5N1 infections in patients increase, the poor surveillance and follow-up of patients and contacts in H5N1 clusters remain a cause for concern.

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