Small Cluster of Oseltamivir-Resistant Influenza Identified

By Marilynn Larkin

June 24, 2021

NEW YORK (Reuters Health) - Four cases of oseltamivir-resistant influenza A(H1N1)pdm09 infection were identified among individuals living in a border detention center in Texas, highlighting the need to monitor both drug resistance and antigenic drift in circulating viruses, researchers say.

"It is not easy to predict when and if drug-resistant viruses could outcompete drug-sensitive viruses and spread globally," Dr. Larisa Gubareva of the US Centers for Disease Control and Prevention told Reuters Health by email. "For example, rapid global spread of oseltamivir-resistant influenza A viruses was observed during the 2008-2009 season."

"Our concern is that A(H1N1)pdm09 viruses, which are most prone to become resistant to oseltamivir, have evolved and are now antigenically different from previously circulating viruses," she said. "If such viruses become drug-resistant, like the cluster of viruses detailed in this paper, they could overcome pre-existing immune responses and may transmit more efficiently among humans."

"Notably," she added, "for the upcoming 2021-2022 Northern Hemisphere influenza season, the World Health Organization updated the recommendation for the A(H1N1)pdm09 vaccine strain component, and this matches the antigenically drifted viruses we described."

As reported in Emerging Infectious Diseases, during the 2019-2020 influenza season, the pH1N1 subtype predominated in the U.S. Later in the season, fewer influenza samples were identified, likely because of COVID-19 pandemic mitigation strategies.

Of the 951 pH1N1 isolates collected, four (0.4%) had the NA-H275Y marker.

Additional surveillance, conducted on 282 viruses from 18 states collected from November 2019-March 2020, yielded another six (2.1%) NA-H275Y viruses, for a total of 10 (0.8%). Of these, four (7.7%) were detected among 52 viruses from Texas.

Further investigation revealed that the four isolates were collected from the same location, a border detention center in Webb County, Texas, on the same day (January 24, 2020).

An influenza outbreak occurred at the center in January 2020, resulting in eight cases. All patients showed similar symptoms, and oseltamivir was prescribed on the same day.

Only four nasopharyngeal specimens, collected from men ages 25-59, were available for analysis. Real-time reverse transcription PCR of the samples determined the cycle threshold (ct) values as 16.7-25.9, indicating relatively high viral loads. Next-generation sequencing analysis showed that the viruses had the oseltamivir resistance-conferring mutation, NA-H275Y.

Testing of 36 additional pH1N1-positive respiratory specimens collected in Webb County during the full flu season (November 2019-March 2020) showed ct values of 21.1-37.5; however, pyrosequencing analysis concluded that there were no additional specimens with the NA-H275Y mutation.

Dr. Gubareva said, "At this time, we have not detected widespread circulation of drug-resistant influenza viruses. However, the 2020-2021 influenza season had an unusually low circulation of influenza viruses in the U.S. and globally, so there were very few influenza positive specimens available for analysis. It is possible that low-level undetected circulation of drug-resistant influenza viruses occurred."

"Clinicians can stay up-to-date with current virologic reports, such as CDC's weekly FluView report," she added, (, and should be aware that the antiviral baloxavir marboxil is effective against influenza A and B viruses, including oseltamivir-resistant viruses.

"Most importantly," she said, "clinicians should encourage their patients to get flu vaccine this upcoming fall." The updated vaccine may also prevent the spread of the drug-resistant viruses reported in the paper, she said.

Dr. Daniel Kuritzkes, Chief, Division of Infectious Diseases at Brigham and Women's Hospital in Boston, commented in an email to Reuters Health, "Whereas a cluster of just four cases that remained contained within the detention facility is not cause for alarm, it does highlight the potential for influenza to develop resistance to our most commonly used drug and, when coupled to shifts in influenza subtype, to escape from vaccine-induced immunity, setting up the potential for broader epidemic spread."

"Given the global economy and worldwide travel seen in typical years," he said, "these cases certainly should be viewed as a potential global issue, not just confined to the U.S."

"Not only is it our obligation to ensure the health of those in U.S. custody, it is also in our best interest in order to prevent outbreaks within detention centers that have a high likelihood of infecting staff at the facility and spilling out into the community at large," he said.

"Proper infection control and quarantine procedures need to be in place not just for COVID-19, but for influenza as well," he noted. "As we relax restrictions surrounding COVID-19, we can expect an increase in cases of these other respiratory viruses."

SOURCE: Emerging Infectious Diseases, online June 16, 2021.