Dr. Yoshihiro Kawaoka of the University of Tokyo and colleagues point out in an article in this week´s edition of The Lancet that it is difficult to produce viruses that are resistant to this class of drugs in the lab. Also, viral resistance to Tamiflu in clinical trials has been infrequent, which has led to the impression that resistance is not a serious concern.

However, the investigators isolated virus with resistance mutations in samples from 9 of 50 infected children, aged 2 months to 15.8 years. Furthermore, children with resistant variants had more prolonged virus shedding, meaning they remained infectious for a longer period.

No resistant viruses were found in patients over the age of seven. Kawaoka´s team suggests of young patients, presumably experiencing their first or second influenza infection, may differ from adults who have been exposed to multiple infections.

The researchers add that, despite the mutations, the viruses are still able to cause disease, "emphasizing the need to continue monitoring for the emergence and spread of these mutant viruses."

This report is "a timely wake-up call" -- particularly in light of the bird flu viruses that have become endemic in Asia -- Dr. Anne Moscona of Mount Sinai School of Medicine in New York comments in an accompanying editorial.

Because bird flu viruses that caused outbreaks in the past are sensitive to Tamiflu-like drugs (called neuraminidase inhibitors), keeping stockpiles of these drugs has been considered a crucial means of protection in the event of a pandemic.

However, she adds, it is probably "only a matter of time" before Tamiflu-resistant virus will be transmitted in humans.