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Flu Pandemic Monitoring in Taiwan

Recombinomics Commentary
December 31, 2004

>>"Once a suspected case is identified, we will analyze the swab and blood samples. If the results confirm an H5 or H7 strain of the flu, we will treat patients with antiviral drugs," said Yan Jer-jea, director of the center's immunization division.

The center has over 2.27 million antiviral tablets stockpiled, which can treat about 227,000 people.<<

The CDC in Taiwan is publicizing plans to respond to avian flu cases targeting patients who are infected with avian viruses known to infect humans (H5 and H7).  However, such plans would miss the H1N1 isolates with WSN/33 genes such as those observed in swine on farms in Korea.  Although these sequences became public a month ago, there still has been no announcement or alerts for unusually severe H1N1 cases.  The hemagglutinin of the WSN/33 swine sequences have 60 amino acid differences with the H1N1 virus used in current flu vaccines, A/New Caledonia/20/99.   There are also 45 amino acid differences in the neuraminidase, excluding the 16 amino acid deletion.  Thus, most people born after 1933 would have limited immunity to either of the H1N1 Korean swine isolates, A/swine/Korea/S10/2004(H1N1) and A/swine/Korea/S175/2004(H1N1).

Like the Health and Human Services in the in the United States, CDC in Taiwan has been stockpiling antiviral agents.  However, there are only 3 antiviral drugs approved for chemoprophylaxis of Influenza A in the United States. Two of these drugs, amantadine and rimantadine are M2 ion channel blockers, but like WSN/33, H1N1 swine isolates have a mutation at position 31 of M2 and are resistant to the anti-viral activity of ion-channel blockers.  The H5N1 isolates from fatal cases in Vietnam and Thailand also have mutations at position 31 and 27, and these viruses are also resistant to the drugs targeting M2..

The other anti-viral drug is oseltamivar (Tamiflu) The related drug, zanamivar (Relenza), is approved for a smaller subset of patients and is administer via inhalation with a breath activated plastic device.  These drugs target neuraminidase, but both H5N1 and WSN/33 related swine H1N1 isolates have deletions in the neuraminidase gene product (20 and 16 amino acids respectively) and Tamiflu activity against N1 subtypes is markedly lower than N2 subtypes.  Tamiflu was used at elevated doses in Thailand in an attempt to save tigers infected with H5N1 and the effort was largely unsuccessful.

Thus, although anti-virals are being stockpiled at the Strategic National Stockpile in the US as well as other agencies such as the CDC in Taiwan, the effectiveness of such drugs in significantly stemming a pandemic associated with the H1N1 or H5N1 viruses described above is largely unproven.

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