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H5N1 False Negative Soldier in South Korea Causes Concern

Recombinomics Commentary 13:21
May 10, 2008

A South Korean soldier tested for bird flu did not contract the deadly virus and will be released from hospital, according to a statement obtained on Friday.

"The soldier, who was quarantined after showing symptoms of bird flu, has tested negative. We have determined his condition was caused by bacterial pneumonia," the Korea Centre for Disease Control and Prevention said in a news release.

Inspectors at the center said yesterday that even though initial examinations detected a small amount of the H5 virus in the patient’s body, including the HA gene that indicates the presence of the virus, they could not find any indicators of the highly contagious H5N1 strain — the HA and NA genes — after more detailed tests. H5N1 is one of four strains of the virus that affects humans.

°We think that the H5 virus in the patient’s body was unstable, said Lee Joo-yeon, an inspector at the center. °It was too weak to prompt the symptoms of bird flu. Also, he did not have the N1 strain of the virus."

Inspectors participating in the tests said that human cases of avian influenza are confirmed when the H5 virus, including the HA gene, and the N1 strain, including the NA gene, are all detected, under the guidelines of the World Health Organization.

The above comments on the H5 confirmed soldier in South Korea raise serious transparency issues.  The detection of H5 in a soldier culling H5N1 infected poultry leaves little doubt that the solder was infected with H5N1.  The WHO guideline for confirming H5N1 infections do not require the isolation of the virus.  Two labs independently confirming H5 is a confirmed cases.  Many H5N1 confirmed cases have failed to yield an isolated virus.  Since the soldier was under oseltamivir (Tamiflu) chemoprophylaxis and was quickly treated with an increased dose, the failure to isolate virus is not a surprise.  Most of the H5N1 isolates from patients are from fatal cases and from samples collected near the time of death when the viral load is high.

There are many examples of false negatives in H5N1 cases.  These examples are most obvious when the H5N1 infection involves clusters.  In Turkey, the first confirmed cases were among four siblings who presented with symptoms.  Although three of the four were unconscious, like the soldier above, they all initially tested negative for H5N1.  The three siblings that were unconscious died, and were confirmed with samples collected from their lungs.  However, virus was only isolated from 2 of the 3.  Moreover, the fourth sibling was never confirmed.  However, the lack of confirmation was not unusual.  Turkey lab confirmed 21 cases.  However, only 12 of 21 were confirmed by the WHO reference lab, and WHO acknowledged that samples had degraded.  Moreover, of the 12 confirmed cases, only four yielded H5N1 virus.

Similar results were obtained for the outbreak in Pakistan.  Local lab testing yielded 10 H5 positives, but on site testing by a WHO reference lab only confirmed one case.  However, since the initial positives included four brothers who developed pneumonia, it was clear that many or all cases lab confirmed on Pakistan were true positives.  Eventually two of the brothers were confirmed because of H5N1 antibodies.  However, antibody test are optimal when convalescent serum samples collected 3-4 weeks post symptoms are used.  Clearly such tests have not been conducted on the soldier above since symptoms began on April 20, yet South Korea has falsely declared the patient negative.

Thus, South Korea is defining new requirements for H5N1 confirmation, which raises serious transparency issues regarding lab confirmation of H5N1 in patients and poultry in Korea.

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