Experts cautiously optimistic on future impact of H1N1

Sep 28, 2010 (CIDRAP News) – With most Americans already possessing some degree of immunity to the 2009 H1N1 virus, the history of pandemics suggests that it's not very likely to make a big comeback anytime soon, according to three experts at the US National Institute of Allergy and Infectious Diseases (NIAID).

Writing in the online journal mBio, the experts—David M. Morens, Jeffrey K. Taubenberger, and NIAID Director Anthony S. Fauci—estimate that about 59% of Americans already have immunity to the virus, which reduces the risk of an "explosive" resurgence. While cautioning that flu remains unpredictable and poorly understood, they say the virus could even disappear.

"Past history and current understanding suggest cautious optimism that pH1N1 will eventually adapt to stable circulation via genetic changes resulting in continuing moderate or low mortality rates or possibly even disappear entirely," they write in a perspective article released today.

In addition, they say that the population segment that is still vulnerable to the virus is mostly people younger than 50. Those older than 50 should remain "substantially protected" if they get their annual flu shot, which this year includes the former pandemic virus.

The immune majority
Serologic data from the United States and elsewhere suggest that about 19% of the US population, mostly people over 55, had some protection against the novel H1N1 virus even before it was detected last year, the article says. With the addition of about 62 million people without previous immunity who were vaccinated and another 61 million who were infected during the pandemic, roughly 59% of the US population is now protected, the authors estimate.

Certain other factors, such as possible protection provided by the 1976 "swine flu" vaccine, may push that percentage even higher, they add, commenting, "Clearly, a large percentage of the U.S. population must already be immune to pH1N1, reducing opportunities for explosive pandemic spread in the future."

Given this high level of population immunity, the authors look to history to assess what mutations or mechanisms might enable the virus to continue circulating. They write that the previous four pandemics—those of 1889, 1918, 1957, and 1968—suggest several possibilities.

The record of the 1889 and 1918 pandemics shows that new waves of cases are possible in completely naïve or partially immune populations after the initial wave of a pandemic. But current population immunity to pH1N1 probably already exceeds the levels achieved in the first year of past pandemics, and records from the past six pandemics indicate that there was only one "explosive recurrence," if any, the article says.

Other possible survival mechanisms explored by the authors include antigenic shift (a major change in the virus's hemagglutinin protein); viral evolution by "intrasubtypic reassortment" (ISR), leading to a minor shift in the hemagglutinin; and antigenic drift, or gradual evolution that enables the virus to avoid extinction.

Many mysteries
History leaves many uncertainties about the potential impacts of all of these, but there are reasons to think that an ISR or even an antigenic shift to an H2 or H3 type of hemagglutinin would not have a severe impact, the authors write.

They say that the possibility of successful antigenic drift remains especially unpredictable. For example, no one knows how and why seasonal H1N1 viruses, which had disappeared with the H2N2 pandemic in 1957, reemerged in a partly immune population 1977 and have continued to circulate since then.

"In summary, history suggests that pH1N1 likely faces extinction unless it mutates, either by mechanisms (such as antigenic shift or ISR) that have never been documented to occur in early pandemic years or by successful antigenic drift, whether slow (as with seasonal H1N1) or aggressive (as with H3N2)," the article says. It adds that aside from population immunity, the factors driving pH1N1 evolution are poorly understood.

While finding reasons for cautious optimism, the authors advise, "Other postpandemic viruses have continued to cause various rates of excess mortality among younger persons for years after pandemic appearance." Therefore, everyone from the age of 6 months up to about 50 years will be "aggressively targeted" for vaccination this fall, they conclude. (The Centers for Disease Control and Prevention now recommends flu vaccination for essentially everyone older than 6 months.)

Morens DM, Taubenberger JK, Fauci AS. The 2009 H1N1 pandemic influenza virus: What next? mBio 2010 Sep/Oct;1(4) [Abstract]

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