Oseltamivir resistance mutation N294S in human influenza A(H5N1) virus in Egypt.
In December 2006, three human specimens were received that were suspected positive for influenza A(H5N1). The specimens were tested using real time PCR. And the presence of A(H5N1) virus was confirmed in 2 patients (16F and 26M), The NA sequence from A(H5N1) positive specimens collected before and after antiviral therapy revealed a mutation (N294S) (N295S according to N1 numbering), previously associated with resistance to oseltamivir. When tested with NA inhibition assays, the two N294S viruses from Egypt exhibited from 57 to 138-fold reduction in susceptibility to oseltamivir, depending on the assay. To our knowledge, this is the first time oseltamivir resistance has been detected in A(H5N1) infecting a human prior to treatment.
Earhart
Kenneth C
KC
U.S. Naval Medical Research Unit No. 3 (NAMRU-3), Cairo, Egypt. kenneth.earhart@med.navy.mil
Elsayed
Nasr M
NM
Saad
Magdi D
MD
Gubareva
Larisa V
LV
Nayel
Ahmed
A
Deyde
Varough M
VM
Abdelsattar
Ali
A
Abdelghani
Ahmad S
AS
Boynton
Bruce R
BR
Mansour
Moustafa M
MM
Essmat
Hala M
HM
Klimov
Alexander
A
Shuck-Lee
Deidra
D
Monteville
M R
MR
Tjaden
Jeffrey A
JA
D000293:Adolescent; D000998:Antiviral Agents / Q000494:pharmacology*; D001483:Base Sequence; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics*; D004534:Egypt; D005260:Female; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D007251:Influenza, Human / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D020128:Inhibitory Concentration 50; D008297:Male; D008826:Microbial Sensitivity Tests; D009154:Mutation / Q000235:genetics; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D053139:Oseltamivir / Q000494:pharmacology*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012367:RNA, Viral; D055815:Young Adult
D000998:Antiviral Agents; D012367:RNA, Viral; D053139:Oseltamivir; D009439:Neuraminidase