Study: Baloxavir-resistant influenza A can spread without virulence loss
An analysis of flu viruses during Japan's 2019 flu season suggests that 2009 H1N1 and H3N2 viruses can rapidly acquire the I38T mutation in the polymerase acidic (PA) protein, which has been linked to reduce susceptibility to baloxavir marboxil, a new antiviral. A team based Japan reported their findings yesterday in Nature Microbiology.
Baloxavir, which targets the flu virus' polymerase complex, is approved for use in Japan, the United States, and Hong Kong. Earlier studies had identified the mutation linked to baloxavir resistance and hinted that such viruses can spread person-to-person and reduce replication fitness. However, the mutation's impact on viral fitness wasn't known.
For the study, the team looked for the mutation before and after patients were treated with baloxavir in Japan. Before treatment, two patients had flu viruses that carried the I38T mutation. One was from a household of a patient who had been treated with baloxavir.
They assessed the impact on virus replication for four influenza A viruses that harbored the mutation, finding that the mutation impacts the replication of 2009 H1N1, though compensatory mutations can develop. However, the mutation in H3N2 viruses didn't seem to affect fitness.
Virulence testing that compared the effect of mutant viruses with wild-type viruses in hamsters, mice, and ferrets found that virulence was similar for both. Transmissibility experiments with ferrets found that transmission is similar for both the mutant and wild-type viruses, suggesting that the mutant versions have the potential to spread.
Researchers concluded that flu viruses circulating in humans can rapidly acquire the baloxavir-resistance mutation without a loss in viral fitness, and that widespread use of the drug could result in influenza A viruses carrying the resistance mutation. "The proper use of this drug and continued close monitoring for the emergence or prevalence of seasonal influenza A virus PA-I38T variants is extremely important," the group wrote.
Nov 25 Nat Microbiol abstract
WHO: Flu levels still low in North America, rising in Middle East
In its latest global flu update, the World Health Organization (WHO) said flu levels are at inter-seasonal levels throughout most of Northern Hemisphere, but activity is rising in the Middle East.
"Respiratory illness indicators started to increase in some countries of the WHO European region, Eastern Asia, and in North America, but influenza detections remain below seasonal thresholds," the WHO said.
Influenza A is still the dominant strain globally, with fairly equal proportions of influenza 2009 H1N1 and H3N2 among the "A" strains, the WHO said. Of the sub-typed influenza A viruses, 47% were influenza H1N1 and 53% H3N2.
In the Middle East, Bahrain, Kuwait, and Saudi Arabia reported increased influenza A activity. Reports of influenza remain low throughout Southern Asia, Central America, and the Caribbean.
Nov 25 WHO update