After H1N1, Researchers Warn of a Potential New Superbug

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Made Nagi / EPA / Corbis

Indonesian health officials destroy fowl suspected of carrying the avian flu virus in a neighborhood in Badung, Indonesia

When the 2009 H1N1 flu virus emerged last April, it triggered the first new pandemic in more than 40 years, producing endless headlines and panic. But, now, some 10 months into the pandemic, the public's fear has subsided. H1N1 turned out to be relatively weak, and action by global and national health officials has helped blunt the damage caused by the virus; by mid-February, more than 16,000 people worldwide had died from the new flu, according to the World Health Organization (WHO), but that figure is in line with mortality in a normal flu year.

On Tuesday the WHO will convene a special panel that could begin the process of declaring an official end to the pandemic. "We hope that the worst is behind us and the overall trend will be going down," said Dr. Keiji Fukuda, the WHO's special adviser to the director-general for pandemic influenza, in a Feb. 18 press conference.

But the close of the H1N1 pandemic does not eliminate the long-term threat from influenza. Another pandemic could arise at any time, and a new paper published in the Feb. 22 Proceedings of the National Academy of Sciences (PNAS) demonstrates that it could even come from an existing flu virus that many of us have forgotten about: the H5N1 bird flu, which has infected 478 people in 15 countries since 2003, with 286 deaths — a fatality rate higher than 50%.

A team of scientists from the U.S., Indonesia and Japan, led by virologist Yoshihiro Kawaoka at the University of Wisconsin — Madison, combined a strain of the deadly H5N1 avian virus with strains of H3N2 human seasonal flu, creating 254 new, mutated viruses. By injecting them in lab mice, researchers found that some of the hybrid viruses were both deadly (like bird flu) and transmissible (like seasonal human flu) — the kind of genetically mutated superflu viruses that experts have been warning about for decades.

The reason H5N1, which first cropped up in humans in 1997, has never given rise to a pandemic is that the virus does not appear to spread easily among people. It has been transmitted between humans only in rare cases, usually among family members in close conditions. But the fear has long been that if bird flu genetically mixed with human flu — in a process called reassortment, in which two flu viruses swap genes in an infected cell — it could create a new strain that is both deadly and transmissible, as illustrated by the new PNAS study. That's how many past pandemic viruses, including 2009 H1N1, were created, leading to new strains to which humans have no natural immunity.

In 2008 scientists from the Centers for Disease Control and Prevention generated artificially combined H5N1 and H3N2 viruses in a lab, but the resulting hybrids were all less deadly than the original bird flu strain. That led to hopes that the H5N1 virus simply lacked the ability to be a true pandemic killer and that to become more transmissible, it would necessarily have to become less dangerous.

But the PNAS study undermines that hope. The key difference in this study was the presence of a single gene from the H3N2 human virus: the PB2 protein, which gave the hybrid viruses the ability to spread easily among the lab mice. Scientists think the protein may allow hybrid viruses to grow more efficiently in the lower temperatures of the upper respiratory tract, from which the virus can more easily spread to others. (The H5N1 virus tends to infect the lower respiratory tract in humans, where it can't easily get out and spread.)

Nevertheless, in the real world, H5N1 has not yet mutated into a more contagious form, despite having had plenty of chances to mix with human flu viruses. That could mean bird flu will remain a dead end, infecting the occasional unlucky person but never turning into a full-blown pandemic. But the PNAS study suggests that the potential exists, and it gives health officials a surveillance target in the form of the PB2 protein in each human H5N1 infection. Global health experts must always be ready: while the 2009 H1N1 pandemic may be winding down, the next flu war has already been brewing.