Influenza B viruses with partial resistance to neuraminidase inhibitors have emerged during routine antiviral therapy and appear to be transmitted from person to person within communities as well as within families.
That finding emerged from a Japanese study.
So far, the rate of emergence of resistant influenza B viruses appears to be “low but appreciable” at 1.4%, and the mutant viruses appear to be as virulent as wild-type viruses, Dr. Shuji Hatakeyama and associates wrote.
In an editorial comment accompanying this report, Dr. Anne Moscona and Dr. Jennifer McKimm-Breschkin said that until now, the medical community has been somewhat complacent about resistant influenza B because little resistance has been documented, and the few resistant strains that have emerged in animal and in vitro studies appeared to have compromised infectivity and transmissibility. “This has led to the belief that significant transmission is unlikely to occur among humans,” they wrote.
Now the findings of Dr. Hatakeyama and associates make it “strikingly clear” that resistant strains are already circulating among humans and that they induce infection with the same duration of symptoms, level of viral shedding, and clinical outcome as nonresistant strains.
This means “it is no longer possible to be confident that resistant strains will have little effect on epidemic or pandemic influenza,” the editorialists said.
Dr. Hatakeyama of the University of Tokyo and associates tracked patterns of resistance and transmission during an influenza B outbreak in the winter of 2004–2005 that caused a widespread epidemic in Japan, the country with the highest use in the world of neuraminidase inhibitors such as zanamivir and oseltamivir.
Pharyngeal or nasal swabs were obtained before and after antiviral therapy from one sample of 74 infected children and from another sample of 356 children (median age 5 years) and 66 adults (median age 34 years) with influenza B.
Seven subjects (1.7%) had strains with partial resistance to zanamivir, oseltamivir, or both, even though they had never been treated with antivirals. There was evidence that identical strains had been transmitted among family members as well as among members of the same community (JAMA 2007;297:1435–42).
There were no differences in symptoms, clinical course, or viral shedding between subjects with resistant strains of the virus and those with wild-type virus, which indicated that these mutant viruses “do not lose virulence even though they have evolved to a status that is less sensitive to the drug,” they noted.
In their editorial comment, Dr. Moscona of Weill Medical College of Cornell University, New York, and Dr. McKimm-Breschkin of Molecular and Health Technologies, Parkville, Australia, said, “Contrary to what had been hoped until now, some resistant variants are vigorous pathogens.
“The presence of low-level resistance sets the stage for selective pressure for development of high-level resistance,” they noted (JAMA 2007;297:1492–3).