Variants of viruses that cause influenza B were found to have become resistant to two common influenza drugs known as Tamiflu and Relenza, according to a Japanese study published in the April 4 issue of Journal of American Medical Association (JAMA).

Japan is known to most extensively use the noted antiflu drugs to treat seasonal flu including influenza A and B. The expected results suggest that use of Tamiflu and Relenza should be restricted to reduce the risk of mutated influenza viruses and retain the therapeutical effectiveness of these drugs.

Tamiflu is indicated for treating adults, adolescents, and pediatric patients 1year of age and older with the influenza whose symptoms started within the last day or two.  Tamiflu is also used to reduce the chance of getting the influenza in people aged 1 year and older who have a higher chance of getting the influenza because they spend time with someone who has the influenza.

Tamiflu can also reduce the chance of getting the influenza if there is an influenza outbreak in the community. The use of Tamiflu to reduce the chance of getting influenza has been studied up to 42 days in adults and up to 10 days in children.

Relenza is indicated for use to treat uncomplicated illness due to influenza virus in people 7 years and older who have been symptomatic for no more than 2 days.  Relenza is also used preventively, to reduce the chance of getting influenza illness, in people 5 years and older.

Both antiviral drugs Tamiflu, manufactured by Roche and Relenza, manufactured by GlaxoSmithKline, are neuraminidase inhibitors, which have been effective against influenza and are used extensively. Tamiflu-resistant viruses that cause influenza A have been detected and reported early.   But rare evidence has been reported to suggest that influenza B viruses have been mutated to resist these drugs.

Shuji Hatakeyama, M.D., Ph.D., of the University of Tokyo, Japan, and colleagues examined the prevalence and transmissibility of influenza B viruses with reduced sensitivity to neuraminidase inhibitors in Japan where both Tamiflu and Relenza are used more extensively than anywhere else in the world.

The researchers collected influenza B isolates from 74 children before and after Tamiflu therapy and from 348 untreated patients with influenza (including 66 adults) during the winder of 2004 to 2005 when an influenza B virus caused a widespread epidemic in Japan.

They analyzed a total of four hundred twenty-two viruses from untreated patients and 74 samples from patients after Tamiflu treatment.

The researchers identified a mutated viral strain with reduced drug sensitivity in one (1.4 percent) of the 74 children who had received Tamiflu and seven (1.7 percent) of the 422 influenza B viruses isolated from untreated patients were found to have reduced sensitivity to Relenza, Tamiflu or both.

Based on the clinical and viral genetic information on these seven patients, the researchers believed that four were likely infected in a community setting whereas the remaining three were probably infected through contact with siblings shedding the mutant viruses.

According to the researchers, the pathogenicity or virulence of the mutated viruses is not weakened by the mutation that caused the resistance to Tamiflu and or Relenza, in contrary to the common perception of mutated strains.  

"Influenza B mutants with reduced sensitivity to neuraminidase inhibitors are circulating, and these viruses can cause infections with no difference in duration of symptoms, level of viral shedding, or clinical outcome," Anne Moscona, M.D., of Weill Medical College of Cornell University, New York, and Jennifer McKimm-Breschkin, Ph.D., of Molecular and Health Technologies, Parkville, South Victoria, Australia write in an accompanying editorial.

"In light of the recent observation that oseltamivir (Tamiflu) may be less effective against influenza B than against influenza A, an important concern is whether suboptimal dosing for these viruses will lead to increased selection of viruses with high-level resistance."

“Continued surveillance for the emergence or spread of neuraminidase inhibitor–resistant influenza viruses is critically important,” Hatakeyama and colleagues write. “Further evaluation of the biological properties of neuraminidase inhibitor–resistant influenza viruses is needed to fully assess their pathogenicity in humans.”

Experts urge reduced use of Tamiflu to retain its antiviral power over influenza viruses as it is widely recognized as the sole weapon that can be used in the case of next pandemic bird flu, which is expected to have the potential of killing millions of people worldwide.   Tamiflu can shorten the duration and lessen symptoms of influenza, but can’t prevent influenza.

“The emergence of drug-resistant influenza B should draw attention to the importance of continual monitoring of strains over time and to the need for frequent rethinking of policies for use of antiviral drugs,” Moscona and McKimm-Breschkin write.

Seasonal influenza kills 36, 000 people in the United States every year, according to the Centers for Disease Control and Prevention.   The young, the elderly and those who have their immune systems compromised are at high risk of complications resulting from influenza.

Sources:
 

Hatakeyama S et al. "Emergence of Influenza B Viruses With Reduced Sensitivity to Neuraminidase Inhibitors." JAMA. 2007;297:1435-1442.

Anne Moscona and Jennifer McKimm-Breschkin. "News About Influenza B Drug Resistance That Cannot Be Ignored." JAMA. 2007;297:1492-93.