Coinfection With Seasonal and Pandemic H1N1: A Dangerous Combo

Fran Lowry

September 15, 2010

September 15, 2010 — Coinfection with seasonal influenza A (H1N1) and pandemic (H1N1) 2009 could result in the emergence of a harmful new strain of the virus that could be resistant to treatment, according to a new study published online today and scheduled to appear in the October 2010 issue of Emerging Infectious Diseases.

"The potential for reassortment of cocirculating seasonal influenza A viruses with pandemic (H1N1) 2009 virus within New Zealand generated considerable interest during the recent 2009 Southern Hemisphere influenza season," write Matthew Peacy, PhD, from the Institute of Environmental Science and Research, Upper Hutt, New Zealand, and colleagues. "Of particular concern is the potential reassortment of neuraminidase gene segments leading to an oseltamivir-resistant pandemic strain."

Changes in the genome could alter the transmissibility, antigenicity, antiviral drug resistance, or virulence of the virus. Reassortment can occur when 2 viruses coinfect the same cell, and pandemic H1N1 is itself a reassortant virus containing gene segments of avian, human, and swine influenza, the authors write.

They tested viral cultures of pandemic H1N1 virus for oseltamivir resistance and found evidence of coinfections of resistant seasonal H1N1 and susceptible pandemic H1N1 influenza.

After discovering coinfection in viral culture, they then screened 1044 samples that were positive for pandemic flu for the presence of seasonal flu and identified 11 coinfections. Two additional samples showed coinfections, but these could not be confirmed.

"Although influenza co-infections are rare, we have shown that they occurred during the first stage of a pandemic when seasonal strains cocirculated. This cocirculation poses a risk for further reassortment for the pandemic strain, which could result in a new pandemic strain," Dr. Peacy and colleagues write. "Of particular concern is the potential generation of an oseltamivir-resistant pandemic strain."

They add that the genesis of a harmful influenza reassortant "warrants further investigation in animal models or in vitro systems. Further analysis of natural co-infections may help elucidate a role for the human host in influenza reassortment."

Meanwhile, the emergence of oseltamivir-resistant pandemic flu in just 48 hours has been reported, also published online today and in the October 2010 issue of Emerging Infectious Diseases.

According to a case report by Masafumi Inoue from the Agency for Science, Research and Technology, Singapore, and colleagues, oseltamivir-resistant pandemic virus developed in an infected woman just 48 hours after treatment with oseltamivir.

In this case, H275Y, the principal mutation associated with oseltamivir resistance in influenza A N1 viruses, was detected in a pandemic virus isolated from the 28-year-old woman on the sixth day of her illness, within 2 days of exposure to oseltamivir.

Although drug-resistant strains of pandemic flu virus have been reported, these cases have been in immunocompromised patients and have taken 11 to 23 days and, more recently, 4 to 14 days of treatment with oseltamivir to develop.

Clinicians should consider resistance when patients do not respond to oseltamivir for pandemic (H1N1) 2009 "because H275Y can emerge literally overnight, as the case reported here reminds us," Inoue and colleagues conclude.

The study by Peacey et al was supported, in part, by the New Zealand Influenza sentinel surveillance system, which is funded by the New Zealand Ministry of Health. The case report by Inoue et al was funded by Tan Tock Seng Hospital, the Ministry of Health, and the Agency for Science, Technology and Research, Singapore.

Emerg Infect Dis. Published online September 15, 2010.

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