NEW YORK (Reuters Health) - In young children with influenza, viral mutants resistant to oseltamivir (Tamiflu; Roche) arise in about 20% of those treated with the neuraminidase inhibitor, Japanese researchers report in the August 28th issue of The Lancet.
Dr. Yoshihiro Kawaoka of the University of Tokyo and colleagues point out that it is difficult to generate viruses resistant to neuraminidase inhibitors in cell culture. Moreover, the frequency of oseltamivir resistance in controlled clinical trials has been low. That has led to the impression that such resistance does not pose a serious threat.
However, the investigators isolated virus with a neuraminidase mutation in samples from 9 of 50 infected children, aged 2 months to 15.8 years. Furthermore, children with resistant variants had more protracted virus shedding.
Drug-resistant mutants were detected beginning on day 4 and persisted on each succeeding day of testing through day 7. None were isolated from the patients aged 7 years or more.
The investigators suggest that their cohort of young patients, presumably experiencing their first or second influenza infection, may be somewhat more comparable than are adults in general to a population experiencing pandemic influenza.
They add that resistant strains may retain their pathogenicity, “emphasizing the need to continue monitoring for the emergence and spread of these mutant viruses.”
“A higher prevalence of resistant viruses,” the researchers conclude, “should be expected during pandemic control efforts using neuraminidase inhibitors than during interpandemic episodes.”
This report is “a timely wake-up call,” Dr. Anne Moscona of Mount Sinai School of Medicine in New York observes in an accompanying editorial. This is particularly so, given the highly pathogenic avian flu viruses that have become endemic in Asia.
Because avian viruses that caused outbreaks in the past are sensitive to 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 oseltamivir-resistant virus will be transmitted in humans.
Tamiflu, which was used earlier this year to help protect Asian workers culling chickens infected with bird flu, was Roche’s 12th-biggest drug last year with 431 million Swiss francs ($338.3 million) in sales. ($1=1.274 Swiss Franc).
Source: Lancet 2004;364:733-734,759-765. [ Google search on this article ]
MeSH Headings:Biological Phenomena: Biological Phenomena, Cell Phenomena, and Immunity: Biological Sciences: Biology: Drug Resistance, Microbial: Genetics: Genetics, Microbial: Microbiologic Phenomena: Pharmacogenetics: Virus Shedding: Viral Physiology: Biological SciencesCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
