title: Emerged HA and NA mutants of the pandemic influenza H1N1 viruses with increasing epidemiological significance in Taipei and Kaohsiung, Taiwan, 2009-10.
abstract: The 2009 influenza pandemic provided an opportunity to observe dynamic changes of the hemagglutinin (HA) and neuraminidase (NA) of pH1N1 strains that spread in two metropolitan areas--Taipei and Kaohsiung. We observed cumulative increases of amino acid substitutions of both HA and NA that were higher in the post-peak than in the pre-peak period of the epidemic. About 14.94% and 3.44% of 174 isolates had one and two amino acids changes, respective, in the four antigenic sites. One unique adaptive mutation of HA2 (E374K) was first detected three weeks before the epidemic peak. This mutation evolved through the epidemic, and finally emerged as the major circulated strain, with significantly higher frequency in the post-peak period than in the pre-peak (64.65% vs 9.28%, p<0.0001). E374K persisted until ten months post-nationwide vaccination without further antigenic changes (e.g. prior to the highest selective pressure). In public health measures, the epidemic peaked at seven weeks after oseltamivir treatment was initiated. The emerging E374K mutants spread before the first peak of school class suspension, extended their survival in high-density population areas before vaccination, dominated in the second wave of class suspension, and were fixed as herd immunity developed. The tempo-spatial spreading of E374K mutants was more concentrated during the post-peak (p = 0.000004) in seven districts with higher spatial clusters (p<0.001). This is the first study examining viral changes during the naïve phase of a pandemic of influenza through integrated virological/serological/clinical surveillance, tempo-spatial analysis, and intervention policies. The vaccination increased the percentage of E374K mutants (22.86% vs 72.34%, p<0.001) and significantly elevated the frequency of mutations in Sa antigenic site (2.36% vs 23.40%, p<0.001). Future pre-vaccination public health efforts should monitor amino acids of HA and NA of pandemic influenza viruses isolated at exponential and peak phases in areas with high cluster cases.
authors.affiliation: Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan, Republic of China.
authors.forename: Chuan-Liang
authors.initials: CL
authors.lastname: Kao
authors.forename: Ta-Chien
authors.initials: TC
authors.lastname: Chan
authors.forename: Chu-Han
authors.initials: CH
authors.lastname: Tsai
authors.forename: Kuan-Ying
authors.initials: KY
authors.lastname: Chu
authors.forename: Shu-Fang
authors.initials: SF
authors.lastname: Chuang
authors.forename: Chang-Chun
authors.initials: CC
authors.lastname: Lee
authors.forename: Zheng-Rong Tiger
authors.initials: ZR
authors.lastname: Li
authors.forename: Ko-Wen
authors.initials: KW
authors.lastname: Wu
authors.forename: Luan-Yin
authors.initials: LY
authors.lastname: Chang
authors.forename: Yea-Huei
authors.initials: YH
authors.lastname: Shen
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Huang
authors.forename: Ping-Ing
authors.initials: PI
authors.lastname: Lee
authors.forename: Chinglai
authors.initials: C
authors.lastname: Yang
authors.forename: Richard
authors.initials: R
authors.lastname: Compans
authors.forename: Barry T
authors.initials: BT
authors.lastname: Rouse
authors.forename: Chwan-Chuen
authors.initials: CC
authors.lastname: King
mesh_terms: D006388:Hemagglutinins / Q000235:genetics*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics* / Q000472:pathogenicity*; D007251:Influenza, Human / Q000453:epidemiology* / Q000821:virology*; D009154:Mutation; D009439:Neuraminidase / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D013624:Taiwan / Q000453:epidemiology
chemical_list: D006388:Hemagglutinins; D009439:Neuraminidase