Flu viruses with novel mutations inhibiting oseltamivir detected globally
Click Here to Manage Email Alerts
Key takeaways:
- Since May 2023, a combination of neuraminidase mutations has been detected in influenza A(H1N1)pdm09 viruses.
- The mutated viruses have a 13-fold reduced susceptibility to oseltamivir.
A novel combination of neuraminidase mutations detected in influenza A(H1N1)pdm09 viruses on several continents has left these viruses less susceptible to treatment with oseltamivir, researchers found.
“Some mutations in the genes of influenza viruses can reduce the effectiveness of available antiviral medications. Therefore, scientists continuously monitor circulating influenza viruses for such mutations,” Larisa V. Gubareva, MD, PhD, team lead of the Influenza Division at the CDC’s National Center for Immunization and Respiratory Diseases, told Healio.
“During routine monitoring of influenza viruses, CDC laboratory observed a previously unseen combination of two mutations in the neuraminidase of a seasonal virus named A(H1N1)pdm09 collected in the United States in October 2023,” she said.
According to Gubareva, how this combination of mutations affects an antiviral’s ability to inhibit the neuraminidase was not known. She said, though, laboratory testing showed that the virus was found to be about 13 times less sensitive to oseltamivir than viruses without this combination of mutations.
“Upon further analysis of genetic sequences of viruses submitted to CDC by U.S. state public health laboratories and other international laboratories, we detected 16 additional A(H1N1)pdm09 viruses with this combination of mutations,” Gubareva said, noting that these viruses were collected from four other countries/territories, including Bangladesh, Hong Kong, Maldives, and Niger, between August and November of 2023.
“This study was extended to determine how broadly viruses with these mutations were circulating worldwide, as well as how such viruses emerged,” she said.
Between May 2023 and February 2024, the researchers analyzed 2,039 pH1N1 viruses from the U.S. (n = 1,274) and 38 other countries (n = 765), of which four had the H275Y substitution, indicating low frequency of oseltamivir resistance. Additionally, neuraminidase substitution of I223V was revealed in 18 and S247N in 15, indicating “mildly elevated” oseltamivir resistance. The researchers also detected 17 viruses carrying both I223V and S247N substitutions.
Among these, viruses with single mutations exhibited normal inhibition by oseltamivir, whereas the six viruses with both I223V and S247N mutations displayed 13- to 16-fold less sensitive to oseltamivir and normal inhibition (less than fourfold) for other neuraminidase inhibitors. The researchers noted, though, that both single and dual mutants remained susceptible to the polymerase cap-dependent endonuclease inhibitor baloxavir.
Looking specifically at viruses with dual mutations, the researchers determined that the first dual mutant was collected from Canada in May 2023 and the latest were collected from France, the Netherlands, Spain and the United Kingdom between January and February 2024.
The Netherlands had the most cases of viruses with dual mutants (n = 30), followed by France (n = 24), Bangladesh (n = 11), Oman (n = 9) and the United Kingdom (n = 9). Additional cases were found in Hong Kong (n = 4), Niger (n = 3), Australia (n = 2), Spain (n = 2), and the U.S. (n = 2), with single cases also being detected in Canada, Ethiopia, Maldives, Norway and Sweden.
“This report conveys our concerns about a multicountry detection of influenza A(H1N1)pdm09 viruses with a previously unseen combination of mutations that were naturally acquired,” Gubareva said. “In a laboratory test, these viruses were found to be about 13 times less sensitive to oseltamivir than those without this combination of mutations. However, mutated viruses retained sensitivity to other available anti-influenza medications, including the newer antiviral, baloxavir marboxil.”
Gubareva added that there are no immediate implications with regard to clinical care decisions at this time, although it is currently unknown how widely these mutated viruses will circulate in the upcoming season.
“Influenza vaccination is available and should offer protection from infections caused by viruses with and without these mutations,” she concluded.
Collapse
Patel MC, et al. Emerg Infect Dis. 2024;doi:10.3201/eid3007.240480.
Read more about
Click Here to Manage Email Alerts