2008 年南非出现对神经氨酸酶抑制剂敏感的甲型 H1N1 流感病毒耐药表型的取代，以及 2009-2013 年期间对神经氨酸酶抑制剂敏感的甲型和乙型流感病毒的流行。
Replacement of neuraminidase inhibitor-susceptible influenza A(H1N1) with resistant phenotype in 2008 and circulation of susceptible influenza A and B viruses during 2009-2013, South Africa.
机构信息
Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.
Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia.
出版信息
Influenza Other Respir Viruses. 2019 Jan;13(1):54-63. doi: 10.1111/irv.12611. Epub 2018 Oct 31.
BACKGROUND
Data on the susceptibility of influenza viruses from South Africa to neuraminidase inhibitors (NAIs) are scarce, and no extensive analysis was done.
OBJECTIVES
We aimed to determine oseltamivir and zanamivir susceptibility of influenza A and B virus neuraminidases (NAs), 2007-2013, South Africa.
PATIENTS/METHODS: We enrolled participants through national influenza-like illness surveillance, 2007-2013. Influenza diagnosis was by virus isolation and quantitative polymerase chain reaction (qPCR). Drug susceptibility was determined by chemiluminescence-based NA-STAR/NA-XTD assay. Sanger sequencing was used to determine molecular markers of NAI resistance.
RESULTS
Forty percent (6341/15 985) of participants were positive for influenza viruses using virus isolation (2007-2009) and qPCR (2009-2013) methods. A total of 1236/6341 (19.5%) virus isolates were generated of which 307/1236 (25%) were tested for drug susceptibility. During 2007-2008, the median 50% inhibitory concentration (IC ) of oseltamivir for seasonal influenza A(H1N1) increased from of 0.08 nmol/L (range 0.01-3.60) in 2007 to 73 nmol/L (range 1.56-305 nmol/L) in 2008. Influenza A isolates from 2009 to 2013 were susceptible to oseltamivir [A(H3N2) median IC = 0.05 nmol/L (range 0.01-0.08); A(H1N1)pdm09 = 0.11 nmol/L (range 0.01-0.78)] and zanamivir [A(H3N2) median IC = 0.56 nmol/L (range 0.47-0.66); A(H1N1)pdm09 = 0.35 nmol/L (range 0.27-0.533)]. Influenza B viruses were susceptible to both NAIs. NAI resistance-associated substitutions H275Y, E119V, and R150K (N1 numbering) were not detected in influenza A viruses that circulated in 2009-2013.
CONCLUSIONS
We confirm replacement of NAI susceptible by resistant phenotype influenza A(H1N1) in 2008. Influenza A and B viruses (2009-2013) remained susceptible to NAIs; therefore, these drugs are useful for treating influenza-infected patients.
背景
关于南非流感病毒对神经氨酸酶抑制剂（NAIs）的敏感性的数据很少，且尚未进行广泛分析。
目的
我们旨在确定 2007-2013 年南非甲型和乙型流感病毒神经氨酸酶（NA）对奥司他韦和扎那米韦的敏感性。
患者/方法：我们通过全国流感样疾病监测，于 2007-2013 年期间招募参与者。流感诊断采用病毒分离和实时定量聚合酶链反应（qPCR）。药物敏感性通过基于化学发光的 NA-STAR/NA-XTD 测定法确定。桑格测序用于确定 NAI 耐药性的分子标记。
结果
使用病毒分离法（2007-2009 年）和 qPCR（2009-2013 年）方法，40%（6341/15985）的参与者的流感病毒呈阳性。共产生了 1236/6341（19.5%）病毒分离株，其中 307/1236（25%）进行了药物敏感性测试。2007-2008 年期间，季节性甲型流感 A（H1N1）病毒对奥司他韦的 50%抑制浓度（IC ）中位数从 2007 年的 0.08 nmol/L（范围 0.01-3.60）增加到 2008 年的 73 nmol/L（范围 1.56-305 nmol/L）。2009-2013 年的甲型流感病毒对奥司他韦敏感[甲型流感 A（H3N2）的中位 IC 为 0.05 nmol/L（范围 0.01-0.08）；甲型流感 A（H1N1）pdm09 为 0.11 nmol/L（范围 0.01-0.78）]和扎那米韦[甲型流感 A（H3N2）的中位 IC 为 0.56 nmol/L（范围 0.47-0.66）；甲型流感 A（H1N1）pdm09 为 0.35 nmol/L（范围 0.27-0.533）]。乙型流感病毒对两种 NAI 均敏感。2009-2013 年流行的甲型流感病毒中未检测到与 NAI 耐药性相关的取代 H275Y、E119V 和 R150K（N1 编号）。
结论
我们证实了 2008 年 NAI 敏感表型流感 A（H1N1）的替代。2009-2013 年期间，甲型和乙型流感病毒仍对 NAI 敏感；因此，这些药物可用于治疗流感感染患者。
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