Person 1: “So, how effective is the seasonal flu shot?”

Person 2: “I heard about 1%. If you get the flu shot, you’ll have a 1% difference in if you get the flu.”

Person 3: “That’s crazy. I don’t know where you are getting your data from. It can’t be 1%, but I admit I don’t know what the actual answer is, but it can’t be that.”

Persons 4 through 6: “Well, if YOU don’t know, and HE says 1%, I’m going with the 1%. Too much trouble to get a flu shot anyway.”

Person 3: “Wait, wait! That’s crazy! That makes no sense!” as persons 1, 2, 4, 5 and 6 are filing out of the break room to go back to work. “You can’t leave thinking that 1% is correct! It can’t be correct!!!”

Person 5: [Over her shoulder on the way out the door.] “Hey, why don’t you go ask your husband. He’s a Scienceblogger, right?”

Another answer is found by checking with the CDC web site. They say that in persons under 65 who are otherwise not at risk, the flu vaccine reduces the chance of getting influenza by about 70 to 90%

But, if you go to one of the authoritative science blog sites like Effect Measure, you get a somewhat different story:

CDC wants us to get vaccinated for flu every year. … They want us to get vaccinated because they think the vaccine works … citing figures that the vaccine is 58% effective or 91% or effective or some other number, depending on what group is being talked about … This post is not about contradicting CDC, since I mostly agree that flu vaccination programs are sound public health. It is about clarifying some things that are glossed over when CDC talks … bla bla bla bla bla

and so on and so forth and I’m pretty sure I know less than when I started after reading that post. (… in a good way … it is an excellent post.)

It turns out that the issue is quite complicated, but I think I can explain it. But you have to be ready to change how you think about a couple of things.

First, you have to understand that at some level, a vaccine only works on people who get the flu. The vaccine does not shield you like a force field on Star Trek so the virus does not get at you. No. The virus gets at you, gets in you, and is inside your body …. so in a sense, you’ve “got” the flu, and then your immune system fights it off hopefully before you become symptomatic. Or maybe it fights it off enough that you get sick but not too sick. Or maybe it fights it off enough that you end up not spreading it to someone else. The vaccine sets things up so that your immune system is prepared to do this much more effectively than if you had not had the vaccine. (Oh, and by the way, does that person who did not get the flu from you, because you had the vaccine and thus did not pass it on, count when counting percentage of effectiveness of the vaccine?)

So you can see that it is fairly complicated. How to count the flu as an infection or the vaccine as an anti-flu agent is a matter of infection, symptom, virulence, reinfection, and so on.

There is another level of complication: There is not one flu. The so called “seasonal flu” is, in a given year, several different strains of influenza virus. The so called “flu vaccine” is a mixture of vaccines for each of several strains that are believed to be the most likely to circulate. Some of these vaccines may actually give cross immunity to other strains, or they may not. Generally not much, it would seem. Usually, the strains that are addressed by the vaccine are the very ones that are circulating, but some years, a strain or two circulates above minimal levels that was not included in the mix. A very high number for infection rates for a non-vaccine strain might be 20 or 30%, but that is rare.

Here’s the question one really wants to know the answer to: Imagine two alternative universes. In one there is seasonal flu but no vaccine, in the other there is a vaccine. Within both of those universes we pick out a large number of people matched up in both … the dopplegangers if you will … and vaccinate all of them in the second universe. Then we ask, Of these paired-up people, how many got the flu in the first, no-vaccine universe, vs. how many got the flu in the second, vaccine-capable universe?

If we picked 10,000 people to vaccinate, and in the non-vaccine universe, 1,000 of them got the flu badly enough to be as sick as a dog or worse (like, they died) and in the vaccine-capable universe, of the 1,000 dopplegangers only 200 got the flu to this level, we could say that the flu vaccine is 80% effective. I’m pretty comfortable saying that this 80% is a useful, meaningful number.

But the reality is more complex. In truth, the vaccine might be 100% effective for one strain, 50% for another, and there might be a rare strain circulating that is not addressed in the vaccine, but the prevalence of each strain vs. differential effectiveness resulted in the observed apparent overall effectiveness of the strategy of vaccination of 80%. In truth, 78 of those people who did not get the flu didn’t get it not because the vaccine worked but because they were never exposed to the flu in the vaccine capable universe because the person who was going to give them the flu did not get it themselves. In truth of those 800 people who “didn’t get” the flu, 123 of them did get it, and did get sick, but not too sick and they didn’t think it was the flu even though it was. In truth, 18 people in the first universe were counted as having the flu but it was a false positive. And so on.

In conclusion, no, it is not 1%. It is closer to 70 to 90% just like the CDC says, on average, for people not otherwise at risk who are under 65.

If you don’t get vaccinated because you think vaccines are dangerous or you think you can avoid the flu by taking vitamins then you are a moron. If you do’t get vaccinated because you think the flu vaccine is only 1% effective then you are … an entirely different kind of moron. Either way, get a shot and don’t be a moron. The person you give the flu to because you didn’t get the shot may be one of those that dies. Wouldn’t that be smart. Not.

Less traditional and less reliable sources have suggested that there are a large number of cases of type A flu (not necessarily the swine flue) in Queens New York, perhaps something like 100, and two cases in Kansas. If these are real, they will probably be reported by WHO and CDC over the next 24 hours.

In Mexico, there are three separate situations being reported. According to WHO:

In the Federal District of Mexico, surveillance began picking up cases of ILI starting 18 March. The number of cases has risen steadily through April and as of 23 April there are now more than 854 cases of pneumonia from the capital. Of those, 59 have died. In San Luis Potosi, in central Mexico, 24 cases of ILI, with three deaths, have been reported. And from Mexicali, near the border with the United States, four cases of ILI, with no deaths, have been reported.

Of the Mexican cases, 18 have been laboratory confirmed in Canada as Swine Influenza A/H1N1, while 12 of those are genetically identical to the Swine Influenza A/H1N1 viruses from California.

Swine flu us common, not surprisingly, in pigs and passes to humans fairly often. There is a low level background of swine farmers getting the swine flu … and getting sick enough to notice it (many more may get infected but don’t become ill or mistake it for a cold). Rarely, swine flu shows up in a form that can pass between humans.

Flu evolves (if that is the correct term) by exchanging large sections of genome back and forth during its life (if that is the correct term) cycle. A flue can be constructed of bits of avian, bits of swine, and bits of human flu, for instance. A combination of swine and human flu may have the property of transmission between humans and some added virulence (because the swine part is new to the immune system). This particular flu seems to be a combination of swine and human as well as avian components.

One alarming feature of this flu, if confirmed, is that it seems to be worse in healthy prime age individuals. Now, don’t get too worried about this yet, but this could be a problem. This was the case with the 1918 flu, which infected half of the human population and killed millions. The so called “Spanish Flu” was a combo of human and avian genetic components. It killed by causing an overreaction in the immune system. The healthier you are, the better your immune system. The better your immune system, the more likely that flu would kill you.

So you can see why health officials are worried about this flu. You don’t have to worry yet, though. This could still fizzle out. Just keep an eye on things.

Or, panic.

If you read the better done public-oriented literature of this period, you will learn that the nature, cause or origin, and pattern of the 1918 epidemic has been very mysterious. The same level of mystery (but with only a few victims) arose in connection with the Swine Flu threat of the 1970s (see expecially Garret’s book for how this event links to current attitudes as well as public policy regarding vaccines).

This brings us to some time last year or so, when key papers were published (and I presume presented at conferences) regarding what may ultimately be seen as the most important single step in the history of understanding the way the flu vaccine works, and thus, how to combat it. (See this to explore one of those key moments in research history.)

The new knowledge is essentially an improved evolutionarily and developmental understanding of how influenza virus strains change over time. To put it very simply, these viruses are made of chunks that come apart in the host and then recombine. If there are multiple ‘strains’ (think species, more or less) of influenza in an individual, these genetic chinks, each representing a huge percentage of the influenza genome, can and do re-combine to form entirely new strains.

That is in a sense macro-evolution of a pathogen in situ, in the host. What is an immune system to do!?!!?!?? Not much, really. This can be very fatal.

It is now understood that these epidemic or pandemic influenza outbreaks arise from these recombination events. If you now look back at the quirky data, the odd logic influenza seemed to be patterned by, the epidemiological dead ends that seemed to confound everyone through the lens of knowledge of these genetic chunks, called “reassortants,” things suddenly become much much clearer.

A paper has just come out in PNAS reporting research using a primate model to explore immune response and associated pathology under the influence of a recombinant influenza virus, and this research is a direct outcome of this new way of looking at the flu. I offer it here without comment largely because you can get the article yourself, since this one is an OpenAccess piece from the normally not OpenAccess PNAS. Here.

The Abstract from the paper:

The mechanisms responsible for the virulence of the highly pathogenic avian influenza (HPAI) and of the 1918 pandemic influenza virus in humans remain poorly understood. To identify crucial components of the early host response during these infections by using both conventional and functional genomics tools, we studied 34 cynomolgus macaques (Macaca fascicularis) to compare a 2004 human H5N1 Vietnam isolate with 2 reassortant viruses possessing the 1918 hemagglutinin (HA) and neuraminidase (NA) surface proteins, known conveyors of virulence. One of the reassortants also contained the 1918 nonstructural (NS1) protein, an inhibitor of the host interferon response. Among these viruses, HPAI H5N1 was the most virulent. Within 24 h, the H5N1 virus produced severe bronchiolar and alveolar lesions. Notably, the H5N1 virus targeted type II pneumocytes throughout the 7-day infection, and induced the most dramatic and sustained expression of type I interferons and inflammatory and innate immune genes, as measured by genomic and protein assays. The H5N1 infection also resulted in prolonged margination of circulating T lymphocytes and notable apoptosis of activated dendritic cells in the lungs and draining lymph nodes early during infection. While both 1918 reassortant viruses also were highly pathogenic, the H5N1 virus was exceptional for the extent of tissue damage, cytokinemia, and interference with immune regulatory mechanisms, which may help explain the extreme virulence of HPAI viruses in humans.

C. R. Baskin, H. Bielefeldt-Ohmann, T. M. Tumpey, P. J. Sabourin, J. P. Long, A. Garcia-Sastre, A.-E. Tolnay, R. Albrecht, J. A. Pyles, P. H. Olson, L. D. Aicher, E. R. Rosenzweig, K. Murali-Krishna, E. A. Clark, M. S. Kotur, J. L. Fornek, S. Proll, R. E. Palermo, Carol. L. Sabourin, M. G. Katze (2009). Early and sustained innate immune response defines pathology and death in nonhuman primates infected by highly pathogenic influenza virus Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.0813234106