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Volume 13, Number 9—September 2007

Reduced Sensitivity of Influenza A (H5N1) to Oseltamivir

Jennifer L. McKimm-Breschkin*Comments to Author , Paul W. Selleck†, Tri Bhakti Usman‡, and Michael A. Johnson†
Author affiliations: *CSIRO Molecular and Health Technologies, Parkville, Victoria, Australia; †CSIRO Livestock Industries, Geelong, Victoria, Australia; ‡Disease Investigation Centre Region IV, Yogyakarta, Indonesia;

Main Article

Table 1

Mean IC50s of NA sensitivities in MUNANA*-based enzyme inhibition assay for influenza (H5N1) isolates from each region compared with a human influenza (H1N1) control and known resistant H274Y isolate†

Isolate Zanamivir,‡§ 
mean IC50, nmol/L Oseltamivir,‡§ 
mean IC50, nmol/L 4-Amino-Neu5Ac2en,‡§ 
mean IC50, μmol/L
Subtype H1N1
A/Mississippi/3/2001 [2]¶ wt 1.18 (0.24) 2.16 (0.31) 1.12†
A/Mississippi/3/2001 H274Y [4]¶ 1.41(0.26) 475.1 (344) 1.31†
Clade 1 subtype H5N1 2004
Malaysia 2004 [2] 1.21 (0.13) 0.47 (0.07) 2.82 (0.77)
Vietnam 2004 [8] 1.40 (0.44) 0.55 (0.26) 2.47 (0.42)
Cambodia 2004 [6] 1.96 (0.56) 0.41 (0.24) 2.59 (0.15)
Clade 1 subtype H5N1 2005
Cambodia 2005 [4] 1.53 (0.4) 2.88 (0.58) 2.56 (0.53)
Clade 2 subtype H5N1
Indonesia 2005 [6] 1.42 (0.63) 11.45 (4.32) 2.00 (0.77)

*Sigma, Saint Louis, MO, USA.
†IC50, drug concentration for 50% inhibition of enzyme activity; NA, neuraminidase; wt, wild type.
‡Drugs provided by GlaxoSmithKline (Stevenage, Hertfordshire, UK).
§Nos. in brackets indicate the nos. of isolates tested against zanamivir and oseltamivir in the same assay. Nineteen influenza (H5N1) isolates were retested in an independent assay against oseltamivir and 4-amino-Neu5Ac2en. Means for oseltamivir are the results of the 2 independent experiments. IC50s for each isolate were calculated by using the Sigmaplot nonlinear curve-fitting function (Systat Software Inc., London, UK). Values in parentheses are standard deviations for the means of the individual IC50s for the isolates in each group.
¶Several plaques were tested from the A/Mississippi/3/2001 against zanamivir and oseltamivir, but only 1 plaque of each was tested against 4-amino-Neu5Ac2en.

Main Article

1Isolates tested were the following: A/Mississippi/3/2001 wt, A/Mississippi/3/2001 H274Y; A/quail/Kelantan/6309/2004, A/chicken/Kelantan/5858/2004, A/quail/Vietnam/007B/2004, A/duck/Vietnam/007A/2004, A/chicken/Vietnam/0024/2004, A/chicken/Vietnam/0023/2004 A/chicken/Vietnam/0018/2004, A/chicken/Vietnam/0015/2004, A/chicken/Vietnam/0010/2004, A/chicken/Vietnam/008/2004; A/chicken/Cambodia/Siem Reap/77B/2004, A/chicken/Cambodia/Siem Reap/76/2004, A/chicken/Cambodia/Takeo/45/2004, A/chicken/Cambodia/Kandal/23/2004, A/chicken/Cambodia/Pong Peay/1B/2004, A/chicken/Cambodia/Pong Peay/1A/2004, A/goose/Cambodia/Kandal/2005, A/chicken/Cambodia/Kandal/3/2005, A/chicken/Cambodia/Kandal/2/2005, A/chicken/Cambodia/Kandal/1/2005, A/chicken/Indonesia/Wates/130/2005, A/chicken/Indonesia/Wates/126/2005, A/chicken/Indonesia/Wates/83/2005, A/chicken/Indonesia/Wates/80/2005, A/chicken/Indonesia/Wates/77/2005, A/chicken/Indonesia/Wates/1/2005.

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