Monday, May 25, 2009

New York Times' McNeil: Older Americans may be immune to Swine H1N1 flu


Posted on Thursday, May 21, 2009 at 09:40AM by Registered CommenterScott McPherson

Well, well, well. It is always nice and gratifying to have a theory confirmed by the mainstream media and the flu experts.

Let me explain: A few weeks ago (April 26th), I blogged that our current swine H1 might be a relative of the same virus that appeared in 1946-47 and 1951. I also proferred that theory to one of the world's top influenza experts via email. Trust me on that: It is literally a matter of public record.

Now comes an article written by the New York Times' Donald McNeil Jr., who is to the U.S. what Helen Branswell is to Canada when it comes to infectious disease newspaper journalism. In it, Mr. McNeil quotes Dr. Daniel Jernigan of the CDC, who states very clearly that informed opinion is coalescing around a theory that pre-1957 H1 successfully conferred immunity to now-older Americans.

The Times article is somewhat incomplete. It insinuates that all H1 was pretty much the same following 1918, just getting more and more diluted. If you look at influenza textbooks of the past twenty years or so, however, what actually happened is that an event of great significance produced much more severe epidemics of H1N1 in 1946-47 and 1951. It has been postulated that swine H1 might have crossed the species barrier in those epidemics, or a random mutation/mutations changed the gene segments just enough to cause some above-average morbidity.

Among influenza circles, debate still rages (that is a relative term, as "rages" for them might be a "harrumph" or a discreet rolling of the eyes) about whether or not 1946-47's epidemic was in actuality a real pandemic. There are considerable arguments on both sides, and I have seen the words "1946-47 pandemic" in print on more than one occasion, in more than one text. What is known is that some seminal event occurred that rendfered the seasonal vaccine for that year completely useless. The link atthe previous sentencewill take you to a study conducted by the living influenza legend Dr. Edwin Kilbourne on that very vaccine failure.

While quite possibly a pandemic, the 1946-47 epidemic produced huge spikes in morbidity, or illness. What it did not do, however, is kill a lot more people statistically. That was reserved for the 1951 epidemic of so-called "Liverpool flu."

The 1951 Liverpool flu epidemic was a terrible killer of people, strangely enough, in the English-speaking world. In the scientific paper 1951 Influenza Epidemic, England and Wales, Canada, and the United States, researcher Ceclie Viboud and others describe the impact that strain of H1 placed on Britain and North America. In some sections of Britain and the US Northeast, the case fatailty rate for 1951's H1 was worse than 1918-19!

We are used to uttering two words when discussing influenza antigenic mutations: Drift and shift. Drift is what happens when a virus makes copies of itself (badly). Shift is what happens when a major reshuffling of influenza genes takes place. Shift is what makes pandemics, or so we have always thought. Antigenic shift occurs when reassortment takes place between dissimilar flu strains. For previous descriptions of drift and shift, reassortment and recombination, just search this blogsite and Google the terms as well.

But what if antigenic shift occurs within the H1N1 subtype itself? Is the resultant virus truly a pandemic candidate? Is this what occurred in 1946-47? Is this what occurred in 1951? Scientists think so. From Science Daily of March 7, 2008:

ScienceDaily (Mar. 7, 2008) — The exchange of genetic material between two closely related strains of the influenza A virus may have caused the 1947 and 1951 human flu epidemics, according to biologists. The findings could help explain why some strains cause major pandemics and others lead to seasonal epidemics.

Until now, it was believed that while reassortment -- when human influenza viruses swap genes with influenza viruses that infect birds -- causes severe pandemics, such as the 'Spanish' flu of 1918, the 'Asian' flu of 1957, and the 'Hong Kong' flu of 1968, while viral mutation leads to regular influenza epidemics. But it has been a mystery why there are sometimes very severe epidemics -- like the ones in 1947 and 1951 -- that look and act like pandemics, even though no human-bird viral reassortment event occurred.

"There was a total vaccine failure in 1947. Researchers initially thought there was a problem in manufacturing the vaccine, but they later realized that the virus had undergone a tremendous evolutionary change," said Martha Nelson, lead author and a graduate student in Penn State's Department of Biology. "We now think that the 1947 virus did not just mutate a lot, but that this unusual virus was made through a reassortment event involving two human viruses.

"So we have found that the bipolar way of looking at influenza evolution is incorrect, and that reassortment can be an important driver of epidemic influenza as well as pandemic influenza," said Nelson, whose team's findings appear in the current issue of PLoS Pathogens. "We have discovered that you can also have reassortment between viruses that are much more similar, that human viruses can reassort with each other and not just with bird viruses. " (bold mine)

Nelson and her colleagues analyzed the evolutionary patterns in the H1N1 strain of the influenza A viruses by looking at 71 whole-genome sequences sampled between 1918 and 2006 and representing 17 different countries on five continents.

Big differences in the shapes of these eight trees signified that reassortment events had occurred.

The swapping of genes between two closely related strains of the influenza A virus through reassortment may also have caused the 1951 epidemic, which looked and acted in many ways like a pandemic as well. Deaths in the United Kingdom and Canada from this epidemic exceeded those from the 1957 and 1968 pandemics.

Currently, there are many types of influenza virus that circulate only in birds, which are natural viral reservoirs.

Though the viruses do not seem to cause severe disease symptoms in birds, so far three of these viral types have infected humans -- H1N1, H2N2, and H3N2.

Understanding how each strain evolves over time is crucial. H3N2 is the dominant strain and evolves much more rapidly than H1N1. So the H1N1 component of each year's flu vaccine has to be updated less often. In comparison, the H3N2 component of the vaccine has been changed four times over the past seven years.

The H1N1 virus is particularly unusual because it disappeared completely in 1957, only to mysteriously re-emerge in humans in 1977 in exactly the same form in which it had left. It is still not certain what happened to the virus during its disappearance. But since it did not evolve at all over these twenty years, "the only plausible explanation is that it was some kind of a lab escape," says Nelson, who is also affiliated with Penn State's Center for Infectious Disease Dynamics (CIDD). (bold mine)

The Penn State researcher says the study shows that the evolution of a virus is not limited to the mutation of single lineage, and that there are multiple strains co-circulating and exchanging genetic material. The H1N1 and H3N2 strains, for instance, are occasionally generating hybrid H1N2 viruses.

"If we really want effective vaccines each year, our surveillance has to be much broader than simply looking at one lineage and its evolution, and trying to figure out how it is going to evolve by mutation," said Nelson. "You have to look at a much bigger picture."

OK. So here's what this says:

We got so wrapped around the axle of looking for Bird Flu under every duck's behind, and we got so lax at a) swabbing suspected flu patients and b) sending "untyped A" samples to the CDC/WHO, that we completely got snookered (a Southern technical term) by swine H1N1. 

It seems reassortment between similar subtypes happens all the time (I have seen several reports confirming that H1N2 combination) that this new hybrid swine/avian/human H1N1 could very well be following a path already traveled by the H1N1 viruses of 1946-47 and 1951. 

Now let me go a bit further: The Science Daily article also says that H1N1 does not change its genetic makeup easily, nor suffer fools gladly. But its resilience cannot be underestimated. Whether it takes its place in the pantheon of pandemic viruses is yet to be known. And indeed if there is immunity to this virus from baby boomers and older prople, we are having the same argument about "pandemic or not to be a pandemic" that people had in 1947 and 1951 -- arguments still underway today. This also explains why the WHO may be very unwilling to declare a Phase 6 pandemic when this may not actually be a pandemic. Recall that a pandemic by definition includes, at its core, a virus with little to no immunity in the general population.

If billions of people are over age 52, then the criteria for a pandemic virus has not been met -- yet. I say "yet" because I want to also talk about another statistic.
And that is that it only took a few years from the 1951 epidemic to the total disappearance of H1N1 in 1957. Recall that influenza plays King of the Mountain. The year 1951 began H1N1's Farewell Tour, although now in retrospect it was one of those Cher/Streisand faux farewell tours, meaning "Farewell until the next big tour's big fat paycheck."

So which influenza strain will knock H1N1 back off the mountain? Will it be H5N1? A return of H2N2? You know, there is a developing consensus that pandemic viruses recycle themselves every three to four generations. When there are no more immune people to get in the way of a massive infection wave ( categorized as a lack of "herd immunity"), then an older virus energizes itself and springs forward.

Nobody knows what will happen with swine H1N1. But once again, if history is to tell us anything, it is that influenza is wildly unpredictable and we need to be prepared for anything. And we need to look closely at 1951 and 1946-47 for more immediate answers. Fortunately, many of those who researched those epidemics/pandemics are still with us. Let's use their talents and mine their recollections and get busy.

More .... 

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