The influenza virus undergoes continual evolutionary change. The swapping of whole genes between strains of influenza, reassortment, is known to be the mechanism that produced the 1957 and 1968 influenza pandemics, and therefore considered the main mechanism of producing our pandemic strains.
Scientists, along with the “Flu Obsessed”, have been concerned that H5N1, currently a wholly avian influenza virus, would reassort with a human influenza virus. H1N1 and H3N2 being the two current human type A Influenza viruses in circulation. In order to accomplish this sleight of hand on the genetic level a single virion (a single virus) from each different strain of virus, one from H5N1 and one from a currently circulating strain would have to infect the exact same human cell at the same time.
Now, without getting into a whole bunch of mind numbing scientific minutia there are tremendous hurdles that the second virus would have to overcome in order to infect a cell already co-opted by another virus. For those curious, the mechanisms of those hurdles at work are cell apoptosis and cell superinfection; high points relevant to influenza can be found at the links.
For those satisfied with the broad-brush strokes nature has it set up so that it is almost impossible for more than one influenza virion to gain entry into a cell, and apoptosis (the death of the invaded cell) occurs within hours of influenza entering a cell, variable, but 4 – 6 hours is probably the operative range. Combined they form rather strong prima facie evidence that a single cell being infected by two different influenza strains is generally an extremely rare and difficult happenstance.
Yesterday CIDRAP’s Maryn McKenna reported on a bombshell that was dropped at the International Conference on Emerging Infectious Diseases by Indonesia’s Vivi Setiawaty of Biomedical and Pharmaceutical Research and Development about a 16 year old Indonesian girl who is reported to have been infected by H5N1 and H3N2 at the same time, known as a co-infection.
A snip from Ms. McKenna’s report offering an excellent glimpse into the confusing issues presented by this paper:
Throat and nasal-swab samples that were taken on the 6th day of her symptoms tested positive by reverse-transcriptase polymerase chain reaction (RT-PCR) for both avian influenza H5N1 and the seasonal flu strain H3N2 at the Indonesian National Institute of Health Research and Development. Serology test results were less clear. Antibody titers from serum samples taken the 6th day provided a weak indication of H5N1 infection (titer of 1:10) but were negative for H3N2; convalescent sera, on the other hand, gave a strong indication of H3N2 infection (titer of 1:640) but were negative for H5N1.
RT-PCR testing, the first test performed, and the one that came back positive for both H5N1 and H3N2, is the most prone to false results, and officially treated as presumptive pending further testing. Blood was drawn the same day (6th day of illness) and it came back showing a weak titer response for H5N1 but none at all for H3N2. Blood tests that early in an infection are notorious for giving “false negatives” as the body generally hasn’t had enough time to produce antibodies that would be freely circulating in the blood. This is true for human influenza infection, and as far as I am aware, at least generally true for an H5N1 infection.
The later blood test, referred to as “convalescent sera” (blood taken later or after recovery) was strongly positive for H3N2, and would be what one would expect to see after an infection since the body has had time to produce the freely circulating antibodies. This same test came back negative for H5N1. Blood tests several weeks after an infection are considered definitive when proving infection or non-infection, with the caveat that the tests were performed correctly of course. Lastly, it is worth noting that H5N1 has historically produced a strong- to- excessively strong human immune response, so a lack of climbing antibody titers would seem unlikely in the extreme for an infection in a sixteen year old.
We have two choices when deciding what to believe. We can believe the most prone to error test shows the correct results and believe that the most definitive test was done incorrectly producing a “false negative”. Or we can believe that the test results as this report states are what they are but the interpretation of them may need further review. Since no independent verification from a WHO reference laboratory was conducted we may never know for sure, but I choose to class this as a “maybe, but highly unlikely” case of a co-infection of H5N1 and H3N2 until I have more information.
I would be remiss if I didn’t say that being ill with two different strains of influenza at the same time is probably not impossible, and may not even be that terribly unusual when multi-strains are co-circulating in the population. However, I am trying to say that those two strains would not likely infect the same human cell within such a short time span, something evolution has mechanisms in place to guard against.
Added to the time and biological improbability is that now, to the best of our knowledge, avian influenza and human influenza do not infect the same types of human cells.
Since it is that, the two strains meeting up in the same cell(s) and exchanging genetic material, which makes this case such a potential bombshell I felt it important to list out all of the issues as I understand them that would argue against it, both in general and with this case specifically.
Who knows, perhaps next week more information will be available and I will revise my opinion and assessments. I would be the last person to say I have the answer to this puzzle, but I do have an insatiable appetite – an appetite not likely to be satisfied any time soon – to understand the myriad pieces spread out on the table before us.