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Sifting through confounding variables and historical conundrums, some of the nation's top virologists recently reached a sobering but somewhat equivocal conclusion, "H7N9 might arguably be more likely than other avian viruses to become human adapted."(1)
If so, the next global flu pandemic may be emerging in China, but the test-tube-half-full view includes this fact, "In 94 years of virologic surveillance, we have never seen a poultry-adapted influenza virus cause widespread human transmission."
Little wonder by the article's conclusion, they were frankly lamenting the challenge of pandemic prediction.
"Looked at from the combined points of view of epidemiology, epizootiology, and virology, there may be no more complex infectious disease problem than that posed by influenza," the authors state. "Regardless of whether the current H7N9 outbreak dies out or proceeds to pandemic spread, we have a unique opportunity to learn more of influenza’s many secrets and thereby enhance our ability to prevent and control an important disease that seems destined to appear again and again, in multiple guises, far into the foreseeable future."
The report by researchers at the National Institute of Allergy and Infectious Diseases -- part of the National Institutes of Health -- evaluated past outbreaks of H7 subtype influenza viruses among mammals and birds and compared H7 viruses with other avian influenza viruses and strains.
Unlike the H5N1 virus -- the avian "bird flu" strain so pathogenic in poultry it was dubbed "chicken ebola" -- the H7N9 virus "spreads silently in poultry," the authors note. Nevertheless, the two avian viruses share a number of epidemiological features. For example, both viruses have produced a characteristic clinical picture in humans that includes bilateral pneumonia, acute respiratory distress syndrome, and multiorgan failure. Other similarities include:
Human cases have been rare but unusually severe and often fatal.
Large numbers of humans have apparently been exposed to both viruses without immunologically detectable or clinically apparent infection.
Person-to-person transmission has rarely if ever occurred; and although uncommon, case clusters seem to indicate common source exposures in persons who are genetically related.
The lost Equine line
As appears to be the case for H5N1, H7N9 may be exhibiting features of a poorly adapted avian influenza virus that is now and may remain unable to infect humans easily but which is at the same time capable of causing severe disease in rare persons with as-yet-uncharacterized genetic susceptibilities, they observed. However, an H7 strain previously made the jump to horses, though causing only uncommon and mild infections in humans.
"The origins of this virus lineage are incompletely understood, making it difficult to predict the length of time it had been adapted to horses, but it was generally believed at the time of its initial isolation in 1956 to have circulated for decades beforehand," the researcher state. "Equine influenza-like epizootics had been exceedingly common for centuries but began to disappear as horses were replaced by automobiles and farm machinery, around the time of World War I. Since the 1970s, the equine H7N7 virus has become extinct or at least virtually undetectable by surveillance. Nevertheless, the ability of an H7 virus to adapt stably to a mammal over several decades raises the possibility that another H7 virus, such as H7N9, may adapt to a mammal in an analogous manner or even to humans."
H7 viruses have also repeatedly infected humans, sometimes causing atypical clinical features, such as conjunctivitis.
"It is concerning that the recent H7N9 virus contains an internal gene cassette from an H9N2 virus, representing a lineage that has caused widespread human infection, although there is no evidence that the specific subtype strains of internal genes of the Chinese H7N9 virus have themselves infected humans as components of an H9N2 virus. Nevertheless, given the ubiquity of H9N2 viruses and their capacity to evolve dynamically and to infect and move rapidly between numerous avian and mammalian hosts, H7N9 might arguably be more likely than other avian viruses to become human adapted." the authors noted.
1. Morens DM, Taubenberger JK, Fauci AS. H7N9 avian influenza A virus and the perpetual challenge of potential human pandemicity. mBio 2013 Jul 9;4(4):[Full text]