Incidence of adamantane resistance among influenza A (H3N2) viruses isolated worldwide from 1994 to 2005: a cause for concern

Incidence of adamantane resistance among influenza A (H3N2) viruses isolated worldwide from 1994 to 2005: a cause for concern
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DOI:
10.1016/s0140-6736(05)67338-2
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发表时间:
2005-10-01
期刊:
影响因子:
168.9
通讯作者:
Klimov, AI
Klimov, AI
中科院分区:
医学1区
文献类型:
--
作者:
Bright, RA;Medina, MJ;Klimov, AI

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背景多年来,金刚烷一直被用于治疗甲型流感病毒感染。研究表明,在流行的流感病毒中,这些药物的抗药性发生率很低;然而,它们的使用在世界范围内正在上升,据报道,从亚洲家禽和人类中分离出的甲型H5N1流感病毒具有抗药性。方法我们分析了1994年10月1日至2005年3月31日期间从世界各地获得的流感现场分离株的数据,并将其提交给美国疾病控制和预防中心的世卫组织流感合作中心。我们使用焦磷酸测序、验证性序列分析和表型试验来检测流通中的甲型H3N1流感病毒(n=6524)、甲型H1N1流感病毒(n=589)和甲型H1N1流感病毒(n=83)的耐药性。在监测的十年中,耐药率显著上升,从1994-1995年的0.4%上升到2003-2004年的12.3%。耐药病毒比例的增加主要是从亚洲获得的,自2003年以来分离的耐药病毒中有61%来自亚洲人。我们的数据引起了人们对金刚烷的适当使用的担忧,并提请人们注意跟踪耐药甲型流感病毒的出现和传播的重要性。
Background Adamantanes have been used to treat influenza A virus infections for many years. Studies have shown a low incidence of resistance to these drugs among circulating influenza viruses; however, their use is rising worldwide and drug resistance has been reported among influenza A (H5N1) viruses isolated from poultry and human beings in Asia. We sought to assess adamantane resistance among influenza A viruses isolated during the past decade from countries participating in WHO's global influenza surveillance network.Methods We analysed data for influenza field isolates that were obtained worldwide and submitted to the WHO Collaborating Center for Influenza at the US Centers for Disease Control and Prevention between Oct 1, 1994, and Mar 31, 2005. We used pyrosequencing, confirmatory sequence analysis, and phenotypic testing to detect drug resistance among circulating influenza A H3N2 (n=6524), H1N1 (n=589), and H1N2 (n=83) viruses.Findings More than 7000 influenza A field isolates were screened for specific aminoacid substitutions in the M2 gene known to confer drug resistance. During the decade of surveillance a significant increase in drug resistance was noted, from 0.4% in 1994-1995 to 12.3% in 2003-2004. This increase in the proportion of resistant viruses was weighted heavily by those obtained from Asia with 61% of resistant viruses isolated since 2003 being from people in Asia.Interpretation Our data raise concerns about the appropriate use of adamantanes and draw attention to the importance of tracking the emergence and spread of drug-resistant influenza A viruses.