Perspective: Pandemic Influenza Viruses — Hoping for the Road Not Taken [H7N9]

New England Journal of Medicine
June 20, 2013  Vol. 368 No. 25

Pandemic Influenza Viruses — Hoping for the Road Not Taken
David M. Morens, M.D., Jeffery K. Taubenberger, M.D., Ph.D., and Anthony S. Fauci, M.D.
N Engl J Med 2013; 368:2345-2348 June 20, 2013 DOI: 10.1056/NEJMp1307009

Excerpt [Closing paragraphs]
…Finally, there is remarkable clinical–epidemiologic similarity between H7N9 and H5N1, with the important distinction that since H5N1 is a highly pathogenic avian virus that kills domestic poultry, its movement is more visible than that of H7N9, whose low pathogenicity keeps it hidden until a rare human is infected. In most other respects, H5N1 and H7N9 are alike: many humans have been exposed to both without clinically apparent or immunologically detectable evidence of infection; disease in sporadic human cases has been far more severe than in cases caused by any human-adapted influenza A virus ever encountered (59% and 28% case fatality reported for H5N1 and H7N9, respectively, as of the end of May); the clinical presentation includes bilateral pneumonia progressing to acute respiratory distress syndrome and multiorgan failure; there has been little or no evidence of person-to-person transmission; and rare case clusters (tenuously identified so far in the case of H7N9) suggest common source exposures in genetically related persons.

As with H5N1,3,4 in H7N9 these epidemiologic features may be signatures of a fundamentally poorly adaptable avian virus that nevertheless productively infects those rare humans with unidentified genetic susceptibilities, who are “found” by widespread poultry epizootics that expose large human populations. Conceivably, questions raised by H5N1 and H7N9 will be faced repeatedly as large-scale domestic poultry raising and transport, coupled with exploding human populations, create opportunities for any avian virus that encounters domestic poultry to expose large numbers of humans.

Like every human influenza pandemic and major outbreak in more than a century,    H7N9 has left us surprised and puzzled. It is only slightly reassuring that since 1918, we have never seen an influenza pandemic emerge through direct viral mutations alone. But every pandemic emergence seems to be a law unto itself, and we cannot know whether or under what circumstances the highly unusual H7N9 virus might be able to become pandemic. Influenza viruses’ unpredictability renders     H7N9 pandemic preparedness essential. Indeed, preparation has already begun, with the goals of developing sensitive and specific diagnostics; determining drug sensitivity; establishing seed viruses, pilot lots, and potency assays for vaccine development; and setting up clinical trials to test appropriate vaccine doses for various demographic groups (children, adults, the elderly).

H7N9’s journey has just begun. We can only hope that the road to a pandemic is the road not taken.

The H7N9 Influenza Virus in China — Changes since SARS
Yu Wang, M.D., Ph.D.
N Engl J Med 2013; 368:2348-2349June 20, 2013 DOI: 10.1056/NEJMp1305311
Ten years after the emergence in China of the severe acute respiratory syndrome, an avian influenza A (H7N9) virus has emerged there, causing substantial disease. But China is now better prepared to address emerging infectious diseases and potential pandemics.