Blt19 14 Jan 09 A Prof Raymond Lin Respiratory Tract Infections


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Blt19 14 Jan 09 A Prof Raymond Lin Respiratory Tract Infections

  1. 1. Antiviral resistance of influenza viruses in Singapore 3rd Meeting of National Influenza Centres in the Western Pacific and South-East Asia Regions May 5-8, 2009
  2. 2. Background <ul><li>We started HA and NA fragment sequencing from Sept 2007 to fulfill the objectives of influenza surveillance </li></ul><ul><li>At the mean time, we looked at particular mutations related to virulence and antiviral resistance in order to </li></ul><ul><li>Collect information to assist in making recommendations for antiviral usage </li></ul><ul><li>Provide scientific evidence for pandemic plan </li></ul>
  3. 3. Methods <ul><li>Conventional Sequencing (HA and M) </li></ul><ul><li>Pyrosequencing (HA and M, April 2009) </li></ul>
  4. 4. Markers of admantanes resistance <ul><li>Adamantanes (amantadine and rimantadine) </li></ul><ul><ul><li>Block the ion channel formed by M2 protein, stop infection by preventing release of viral RNA </li></ul></ul>* Alone or combined (e.g V27A and S31N); * Confers cross-resistance to amantadine and rimantadine E G 34 N S 31  V or T A 30 A V 27 F L 26 Mutant Wild type Position
  5. 5. Results of S31N in 2008 32 1 No. of Mutant 100% 32 H3N2 17% 6 H1N1 % of Mutant No. tested Subtype
  6. 6. Markers of neuraminidase inhibitors <ul><li>NA 274 (actually position 275 in N1) </li></ul><ul><ul><li>His (H) is susceptible </li></ul></ul><ul><ul><li>Tyr (Y) is resistant </li></ul></ul><ul><ul><li>Actually at position 255 of H5N1 genotype Z NA with 20 AA deletion </li></ul></ul><ul><li>NA 294 (actually position 295 in N1) </li></ul><ul><ul><li>Asn (N) is susceptible </li></ul></ul><ul><ul><li>Ser (S) is partially resistant </li></ul></ul><ul><ul><li>Actually at position 275 of H5N1 genotype Z NA with 20 AA deletion </li></ul></ul><ul><li>Others including: </li></ul><ul><ul><li>N2 E119V and R292K </li></ul></ul><ul><ul><li>B: D198E or N, R152K, R371K and I222T </li></ul></ul><ul><ul><li>…… .. </li></ul></ul>
  7. 7. Results of H275Y in H1N1 2008 2009
  8. 8. NAI results from WHO CC Results from WHO CC Melbourne
  9. 9. Future plan <ul><li>Pyrosequencing (collaboration with Singapore Polytechnic) </li></ul><ul><li>M segment </li></ul><ul><li>HA segment </li></ul><ul><li>Neuraminidase inhibition assay (NAI assay) </li></ul><ul><li>Oseltmivir was in place already </li></ul><ul><li>Will request pure zanamivir from GSK (MTA) </li></ul><ul><li>Workshop in Melbourne </li></ul>
  10. 10. Acknowledgements <ul><li>Influenza surveillance team, NPHL, Singapore </li></ul><ul><li>Virology Laboratory, Singapore General Hospital </li></ul><ul><li>Ministry of Health, Singapore </li></ul><ul><li>Melbourne WHO CCs </li></ul><ul><li>Singapore Polytechnic </li></ul>