Influenza A H5N1 clade 2.3.4 virus with a different antiviral susceptibility profile replaced clade 1 virus in humans in northern Vietnam.
BACKGROUND
Prior to 2007, highly pathogenic avian influenza (HPAI) H5N1 viruses isolated from poultry and humans in Vietnam were consistently reported to be clade 1 viruses, susceptible to oseltamivir but resistant to amantadine. Here we describe the re-emergence of human HPAI H5N1 virus infections in Vietnam in 2007 and the characteristics of the isolated viruses.


RESULTS
Respiratory specimens from patients suspected to be infected with avian influenza in 2007 were screened by influenza and H5 subtype specific polymerase chain reaction. Isolated H5N1 strains were further characterized by genome sequencing and drug susceptibility testing. Eleven poultry outbreak isolates from 2007 were included in the sequence analysis. Eight patients, all of them from northern Vietnam, were diagnosed with H5N1 in 2007 and five of them died. Phylogenetic analysis of H5N1 viruses isolated from humans and poultry in 2007 showed that clade 2.3.4 H5N1 viruses replaced clade 1 viruses in northern Vietnam. Four human H5N1 strains had eight-fold reduced in-vitro susceptibility to oseltamivir as compared to clade 1 viruses. In two poultry isolates the I117V mutation was found in the neuraminidase gene, which is associated with reduced susceptibility to oseltamivir. No mutations in the M2 gene conferring amantadine resistance were found.


CONCLUSIONS
In 2007, H5N1 clade 2.3.4 viruses replaced clade 1 viruses in northern Vietnam and were susceptible to amantadine but showed reduced susceptibility to oseltamivir. Combination antiviral therapy with oseltamivir and amantadine for human cases in Vietnam is recommended.
National Institute of Hygiene and Epidemiology, Hanoi, Vietnam.
Mai T Q
MT
Le
Heiman F L
HF
Wertheim
Hien D
HD
Nguyen
Walter
W
Taylor
Phuong V M
PV
Hoang
Cuong D
CD
Vuong
Hang L K
HL
Nguyen
Ha H
HH
Nguyen
Thai Q
TQ
Nguyen
Trung V
TV
Nguyen
Trang D
TD
Van
Bich T
BT
Ngoc
Thinh N
TN
Bui
Binh G
BG
Nguyen
Liem T
LT
Nguyen
San T
ST
Luong
Phuc H
PH
Phan
Hung V
HV
Pham
Tung
T
Nguyen
Annette
A
Fox
Cam V
CV
Nguyen
Ha Q
HQ
Do
Martin
M
Crusat
Jeremy
J
Farrar
Hien T
HT
Nguyen
Menno D
MD
de Jong
Peter
P
Horby
D000293:Adolescent; D000328:Adult; D000547:Amantadine / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D004196:Disease Outbreaks; D024882:Drug Resistance, Viral; D005260:Female; D005843:Geography; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000145:classification* / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification* / Q000472:pathogenicity*; D007251:Influenza, Human / Q000175:diagnosis / Q000453:epidemiology / Q000503:physiopathology / Q000821:virology*; D008297:Male; D053139:Oseltamivir / Q000494:pharmacology; D010802:Phylogeny; D012189:Retrospective Studies; D014744:Vietnam / Q000453:epidemiology
D000998:Antiviral Agents; D053139:Oseltamivir; D000547:Amantadine