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catsittingstillI have been thinking about the flu, of late.
It's on my mind because I keep hearing on the local news that this or that school district is closing all the schools for a day or two because of illness, which is not usual. It's personal because Kip and I have been sick twice (each) in February, which is not usual either. So I went and looked it up in the Microbiology book I got when I thought I was going to be teaching a Micro class, and checked out the news about the most recent flu season online.
It's on my mind because I keep hearing on the local news that this or that school district is closing all the schools for a day or two because of illness, which is not usual. It's personal because Kip and I have been sick twice (each) in February, which is not usual either. So I went and looked it up in the Microbiology book I got when I thought I was going to be teaching a Micro class, and checked out the news about the most recent flu season online.
Influenza anatomy.
The flu (influenza) virus is an RNA virus, which means its genes are "written" in RNA instead of DNA, which is used for the genes of everything that isn't a virus (plus some viruses). Unusually for a virus, its genome consists of eight separate pieces rather than one. These pieces of RNA are surrounded by a protein coat of one of three different types, A, B, and C. Type A influenzas infect a lot of species, type B influenzas appear to infect only humans and are less serious, and the rare type C influenzas infect humans and pigs.
The protein coat is surrounded by a lipid membrane (which the virus particle, or "virion," stole from the outside of the last cell it infected). The membrane has virus protein "spikes" imbedded in it. Most of these spikes are hemagglutinin, which binds to polysaccharides (molecules made of many sugars stuck together) normally present on the outer membrane of the cells the virus infects. However, when the newly reproduced virus buds off the infected cell, hemagglutinin would tend to make it stick to that cell, preventing it from dispersing to infect other cells. Neuraminidase, which is about 1/6th of the spikes, cuts the polysaccharides so that the virus can get loose.
There are 15 or 16 types of hemagglutinin and 9 types of neuraminidase, and it is common to tell flu viruses apart by them. They're conveniently (if unimaginatively) designated by numbers, so if someone talks about H5N1 flu, (like bird flu, for instance) they mean an influenza virus with hemagglutinin type 5 and neuraminidase type 1.
Mutants—they're all mutants!
The flu virus genes start out as RNA. To hijack the infected cell, they need to be DNA, because the cell's enzymes are all set up to work with DNA as their starting material. Influenza virions include some copies of a protein called reverse transcriptase that "reads" RNA and "writes" a corresponding strand of DNA for the cell's enzymes to work with. But reverse transcriptase makes a lot more mistakes than the enzymes that make DNA copies of DNA, so flu mutates fast. Usually these mutations make slight changes in the genes, which result in just a single amino acid difference in the proteins they code for. When these small mutations fall in the genes for hemagglutinin or neuraminidase, they change the outside of the virion, so that antibodies to the previous version don't work as well. This is called "antigenic drift" and helps explain why the flu is one of those diseases you can get over and over. Some of these small mutations, of course, occur at just the wrong place in the proteins they hit, destroying their function. These mutants just can't reproduce, so we never see them. And some of the small mutations (slightly under a third) do nothing at all—they change the DNA to something that still reads for the same amino acid; the resulting protein is unchanged.
Sometimes, however, the H and/or N proteins will change drastically. This is called "antigenic shift" and is one reason for the occasional flu pandemics that sweep whole continents or even the world. The most famous one was in 1918, in which the virus, normally confined to the nose and throat, was able to invade the lungs and cause pneumonia, leading to a phenomenally high death rate. The fact that flu RNA comes in 8 parts, and that one creature can be infected by more than one kind of flu at once, makes it relatively common for the flu genome to "reassort"—for pieces of more than one flu virus genome to come together to make a new flu virus. This is apparently most likely to happen with type A influenza, which can infect a number of species, and it is one reason for the concern about flus from poultry and pigs—they have their own influenzas, and can also be infected by human influenza, so they are suspected of being "recombination reservoirs." Hence the concern about bird flu.
So what's up with this flu season?
It all comes down to how the flu vaccine is made.
Viruses aren't exactly "alive" as we usually use the term. They are pretty much static outside a cell—they have to hijack a living cell's proteins to reproduce themselves. So they can't be grown in broth or on Petri dishes. The flu virus can be grown in embryonated eggs (eggs that have been fertilized and would hatch out into chicks if the flu didn't kill them), but this takes a lot of time. There are also a lot of possible types of flu—remember those A, B and C protein coats and those 15-16 types of H and 9 types of N spikes? So what happens is that in February of last year, microbiologists gathered as many samples as possible of the strains of influenza that were active around the world, typed them, and made their best guess as to which three types were going to be the biggest problem this year. Usually they pick two A strains (more serious and tend to spread more widely—this years were H1N1 and H3N2) and one B strain (tend to be more geographically limited and to cause less serious illness), but not a C strain, because those are so rare. Then those three strains were grown in chicken eggs and purified and treated over the spring and summer to make the flu vaccines that were available last fall.
They missed one. It's not very surprising—this trick is like trying to guess in February what the weather will be like next February, and frankly it's amazing they usually do as well as they do. For16 of the last 19 flu seasons the vaccines were well matched to the strains causing the most cases. The many strains of flu going around at any one time plus the joys of antigenic drift mean that during these good years, the vaccine for the year was 70-90% effective. But this year there's a strain out there that's causing about a third of the flu cases that wasn't in the vaccine. It's called the Brisbane/10 flu, and was first spotted in Australia (flu strains are often named after the location where they were first identified) late last February—late enough that it couldn't have been included in this year's vaccine even if it had seemed significant at the time, which it didn't. It is an H3N2 strain, and normally the vaccine would have protected against it, but the H3N2 strain used for the vaccine, called Wisconsin, is different enough from Brisbane/10 that it isn't providing good protection. In addition the type B strain chosen wasn't a good match for the most common type B influenza going around either. The vaccine probably still provides some protection, and may reduce the severity of flu even if it doesn't prevent infection, but it's not doing its usual job.
The frequency of the flu this year probably has to do not only with the vaccine not working very well, but with an increase in infections in unvaccinated people too--the changes in the type AH3N2 and the type B virus mean that leftover resistance from having had the flu last year or the year before presumably won't work as well either.
So, when I was staggering from the bed to the couch, aching and shivering, that was probably the flu. It might have been the Brisbane flu—I got it from Kip, and while I didn't have my flu shot, he did have his. It might have been the major type B flu going around—it was rotten, but the really bad part was only a day or so, and type A sounds like it would be more severe than that. It might have been some other, rarer type of flu that the vaccine didn't cover. It might even be the start of a pandemic (more than 10% of the population infected). But on the bright side, it won't be anything like 1918. If this year's flu had a 20-50% death rate, we'd know about it by now.
References:
2007 Tortora G. J., Funke B. R., and Case C.L. Microbiology: An Introduction 9th edition Pearson Education Inc. pp 731-733
Nearguard, L. Feds Meet on for Next Year's Flu Vaccine, Associated Press via Google: http://ap.google.com/article/ALeqM5hlYJygNjxyRxe3HonbKP6u2tONlgD8UULL8G0
Wikipedia article Influenza, http://en.wikipedia.org/wiki/Influenza, accessed 20 Feb 2008
The flu (influenza) virus is an RNA virus, which means its genes are "written" in RNA instead of DNA, which is used for the genes of everything that isn't a virus (plus some viruses). Unusually for a virus, its genome consists of eight separate pieces rather than one. These pieces of RNA are surrounded by a protein coat of one of three different types, A, B, and C. Type A influenzas infect a lot of species, type B influenzas appear to infect only humans and are less serious, and the rare type C influenzas infect humans and pigs.
The protein coat is surrounded by a lipid membrane (which the virus particle, or "virion," stole from the outside of the last cell it infected). The membrane has virus protein "spikes" imbedded in it. Most of these spikes are hemagglutinin, which binds to polysaccharides (molecules made of many sugars stuck together) normally present on the outer membrane of the cells the virus infects. However, when the newly reproduced virus buds off the infected cell, hemagglutinin would tend to make it stick to that cell, preventing it from dispersing to infect other cells. Neuraminidase, which is about 1/6th of the spikes, cuts the polysaccharides so that the virus can get loose.
There are 15 or 16 types of hemagglutinin and 9 types of neuraminidase, and it is common to tell flu viruses apart by them. They're conveniently (if unimaginatively) designated by numbers, so if someone talks about H5N1 flu, (like bird flu, for instance) they mean an influenza virus with hemagglutinin type 5 and neuraminidase type 1.
Mutants—they're all mutants!
The flu virus genes start out as RNA. To hijack the infected cell, they need to be DNA, because the cell's enzymes are all set up to work with DNA as their starting material. Influenza virions include some copies of a protein called reverse transcriptase that "reads" RNA and "writes" a corresponding strand of DNA for the cell's enzymes to work with. But reverse transcriptase makes a lot more mistakes than the enzymes that make DNA copies of DNA, so flu mutates fast. Usually these mutations make slight changes in the genes, which result in just a single amino acid difference in the proteins they code for. When these small mutations fall in the genes for hemagglutinin or neuraminidase, they change the outside of the virion, so that antibodies to the previous version don't work as well. This is called "antigenic drift" and helps explain why the flu is one of those diseases you can get over and over. Some of these small mutations, of course, occur at just the wrong place in the proteins they hit, destroying their function. These mutants just can't reproduce, so we never see them. And some of the small mutations (slightly under a third) do nothing at all—they change the DNA to something that still reads for the same amino acid; the resulting protein is unchanged.
Sometimes, however, the H and/or N proteins will change drastically. This is called "antigenic shift" and is one reason for the occasional flu pandemics that sweep whole continents or even the world. The most famous one was in 1918, in which the virus, normally confined to the nose and throat, was able to invade the lungs and cause pneumonia, leading to a phenomenally high death rate. The fact that flu RNA comes in 8 parts, and that one creature can be infected by more than one kind of flu at once, makes it relatively common for the flu genome to "reassort"—for pieces of more than one flu virus genome to come together to make a new flu virus. This is apparently most likely to happen with type A influenza, which can infect a number of species, and it is one reason for the concern about flus from poultry and pigs—they have their own influenzas, and can also be infected by human influenza, so they are suspected of being "recombination reservoirs." Hence the concern about bird flu.
So what's up with this flu season?
It all comes down to how the flu vaccine is made.
Viruses aren't exactly "alive" as we usually use the term. They are pretty much static outside a cell—they have to hijack a living cell's proteins to reproduce themselves. So they can't be grown in broth or on Petri dishes. The flu virus can be grown in embryonated eggs (eggs that have been fertilized and would hatch out into chicks if the flu didn't kill them), but this takes a lot of time. There are also a lot of possible types of flu—remember those A, B and C protein coats and those 15-16 types of H and 9 types of N spikes? So what happens is that in February of last year, microbiologists gathered as many samples as possible of the strains of influenza that were active around the world, typed them, and made their best guess as to which three types were going to be the biggest problem this year. Usually they pick two A strains (more serious and tend to spread more widely—this years were H1N1 and H3N2) and one B strain (tend to be more geographically limited and to cause less serious illness), but not a C strain, because those are so rare. Then those three strains were grown in chicken eggs and purified and treated over the spring and summer to make the flu vaccines that were available last fall.
They missed one. It's not very surprising—this trick is like trying to guess in February what the weather will be like next February, and frankly it's amazing they usually do as well as they do. For16 of the last 19 flu seasons the vaccines were well matched to the strains causing the most cases. The many strains of flu going around at any one time plus the joys of antigenic drift mean that during these good years, the vaccine for the year was 70-90% effective. But this year there's a strain out there that's causing about a third of the flu cases that wasn't in the vaccine. It's called the Brisbane/10 flu, and was first spotted in Australia (flu strains are often named after the location where they were first identified) late last February—late enough that it couldn't have been included in this year's vaccine even if it had seemed significant at the time, which it didn't. It is an H3N2 strain, and normally the vaccine would have protected against it, but the H3N2 strain used for the vaccine, called Wisconsin, is different enough from Brisbane/10 that it isn't providing good protection. In addition the type B strain chosen wasn't a good match for the most common type B influenza going around either. The vaccine probably still provides some protection, and may reduce the severity of flu even if it doesn't prevent infection, but it's not doing its usual job.
The frequency of the flu this year probably has to do not only with the vaccine not working very well, but with an increase in infections in unvaccinated people too--the changes in the type AH3N2 and the type B virus mean that leftover resistance from having had the flu last year or the year before presumably won't work as well either.
So, when I was staggering from the bed to the couch, aching and shivering, that was probably the flu. It might have been the Brisbane flu—I got it from Kip, and while I didn't have my flu shot, he did have his. It might have been the major type B flu going around—it was rotten, but the really bad part was only a day or so, and type A sounds like it would be more severe than that. It might have been some other, rarer type of flu that the vaccine didn't cover. It might even be the start of a pandemic (more than 10% of the population infected). But on the bright side, it won't be anything like 1918. If this year's flu had a 20-50% death rate, we'd know about it by now.
References:
2007 Tortora G. J., Funke B. R., and Case C.L. Microbiology: An Introduction 9th edition Pearson Education Inc. pp 731-733
Nearguard, L. Feds Meet on for Next Year's Flu Vaccine, Associated Press via Google: http://ap.google.com/article/ALeqM5hlYJygNjxyRxe3HonbKP6u2tONlgD8UULL8G0
Wikipedia article Influenza, http://en.wikipedia.org/wiki/Influenza, accessed 20 Feb 2008
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no subject
Date: 2008-02-21 09:38 pm (UTC)I wonder if anyone's ever done a study of flu transmission and science fiction conventions?
Oh, and the point that I kind of misplaced was - this was a fascinating post, thanks for posting it.
no subject
Date: 2008-02-21 10:54 pm (UTC)no subject
Date: 2008-02-21 09:41 pm (UTC)no subject
Date: 2008-02-21 10:55 pm (UTC)no subject
Date: 2008-02-21 10:42 pm (UTC)Very interesting update. I never knew how they chose which strains to grow before.
no subject
Date: 2008-02-21 10:56 pm (UTC)I'm glad you liked the post. I learned quite a bit writing it.
no subject
Date: 2008-02-21 11:24 pm (UTC)Should we worry about the mercury compound in most flu vaccines? How does the amount of mercury in a flu vaccine compare with the amount in a serving of swordfish?
no subject
Date: 2008-02-22 01:15 am (UTC)I am not a doctor, but I'd say don't worry about it unless you happen to know you're (or the person receiving the vaccination is) allergic to mercury, in which case, talk to your doctor.
There are unsubstantiated rumors connecting, if I remember right, thimerosal and autism, but I think this is more correlation (autism is a changed behavior set that tends to become visible to parents right around the same developmental stage as vaccines are given anyway, so vaccines get the blame even though they don't deserve it), than causation. As far as I know there is no scientific evidence of a connection.
no subject
Date: 2008-02-22 02:16 am (UTC)no subject
Date: 2008-02-22 02:30 pm (UTC)no subject
Date: 2008-02-22 02:36 am (UTC)(Source: http://www.vaccinesafety.edu/thi-table.htm)
For comparison: The EPA limit for mercury in drinking water is 2 ppb, or 0.48 mcg of mercury in an 8 oz glass of water. The FDA limit for mercury in seafood is 1 ppm of methylmercury, or 85.2 mcg of methylmercury (79.3 mcg of elemental mercury) in a 3 oz serving of fish.
(Source: http://www.atsdr.cdc.gov/tfacts46.html#bookmark10)
no subject
Date: 2008-02-22 02:30 pm (UTC)no subject
Date: 2008-02-22 12:21 am (UTC)Thanks for the research!
no subject
Date: 2008-02-22 01:17 am (UTC)But I hope you don't get it too.
no subject
Date: 2008-02-22 12:34 am (UTC)A new strain of AH3N2
It comes from Brisbane,
A terrible pain,
I hope she won’t pass it to you.
no subject
Date: 2008-02-22 01:17 am (UTC):-)
no subject
Date: 2008-02-22 01:41 am (UTC)(I find this is one of the great things about blogs. It occurs to other people to go find out things that it might not occur to you to go look for but that it turns out you're glad to know.)
no subject
Date: 2008-02-22 02:31 pm (UTC)no subject
Date: 2008-02-22 09:08 am (UTC)no subject
Date: 2008-02-22 02:32 pm (UTC)no subject
Date: 2008-02-22 04:50 pm (UTC)no subject
Date: 2008-02-22 05:58 pm (UTC)no subject
Date: 2008-02-22 06:58 pm (UTC)