A comprehensive surveillance of adamantane resistance among human influenza A virus isolated from mainland China between 1956 and 2009.
BACKGROUND
Adamantane-derived drugs have been used for treatment and prophylaxis of influenza A virus infection for many years worldwide. Rapid surveillance of antiviral drug resistance is important for appropriate clinical guideline development. Here, we retrospectively assessed adamantane resistance among different influenza A subtypes (H1N1, H3N2 and H5N1) over 53 years (1956-2009) in mainland China.


METHODS
A total of 1,451 viruses, including 773 H3N2 viruses, 647 H1N1 viruses and 31 human H5N1 viruses, were analysed by matrix gene sequencing and assayed for drug resistance.


RESULTS
Our results show that the prevalence of adamantane-resistant H3N2 viruses was low between 1956 and 2002, but substantially increased in 2003 to the extent that since 2006 all H3N2 viruses have been drug resistant. The percentage of adamantane-resistant H1N1 viruses also increased from 50.0% in 2004 to 98.7% in 2007; however, this decreased to 46.7% in 2009. Only three adamantane-resistant H5N1 viruses have been detected since 2003, when the first case of human H5N1 virus infection was detected in mainland China. Phylogenetic analysis demonstrated that the increase of adamantane-resistant isolates was caused by point mutations or intrasubtype reassortment instead of intersubtype reassortment.


CONCLUSIONS
Because of the high percentage of adamantane-resistant H3N2 and H1N1 viruses in mainland China, the use of amantadine and rimantadine drugs for prophylaxis and treatment of current seasonal influenza A infection is not recommended.
Lan
Yu
Y
Chinese National Influenza Center, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China.
Zhang
Ye
Y
Dong
Libo
L
Wang
Dayan
D
Huang
Weijuan
W
Xin
Li
L
Yang
Limei
L
Zhao
Xiang
X
Li
Zi
Z
Wang
Wei
W
Li
Xiyan
X
Xu
Cuilin
C
Yang
Lei
L
Guo
Junfeng
J
Wang
Min
M
Peng
Yousong
Y
Gao
Yan
Y
Guo
Yuanji
Y
Wen
Leying
L
Jiang
Taijiao
T
Shu
Yuelong
Y
D000218:Adamantane / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000494:pharmacology; D002681:China; D024882:Drug Resistance, Viral; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000235:genetics; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects* / Q000235:genetics; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects* / Q000235:genetics; D010802:Phylogeny; D012367:RNA, Viral / Q000235:genetics; D012299:Rimantadine / Q000627:therapeutic use; D018571:Sentinel Surveillance; D020539:Sequence Analysis, Protein; D017423:Sequence Analysis, RNA; D014763:Viral Matrix Proteins / Q000235:genetics
D000998:Antiviral Agents; D012367:RNA, Viral; D014763:Viral Matrix Proteins; D012299:Rimantadine; D000218:Adamantane