Seasonal flu vaccine mismatch

We've discussed this already, but now CIDRAP News also has a story (which they got from AP) that this year's flu vaccine is not perfectly matched to the all the circulating viruses (of course we had it first, but hey, who's keeping track?). The data that are used to prepare vaccines for the next flu season come from predictions based on what is seen during the current season as determined by a global surveillance network (the same network at issue in the refusal of Indonesia to share H5N1 isolates, although this mismatch has nothing to do with the Indonesian situation). The circulating strains change every so often and the vaccine makers have been pretty good at guessing the next year's strain but every once in a while they miss:

As seasonal influenza makes its annual march across the country, surveillance data from the US Centers for Disease Control and Prevention (CDC) reveals that 23% of the viruses that have been identified belong to a strain that is not included in this season's vaccine.

CDC Director Dr Julie Gerberding said the influenza A H3N2/Brisbane-like strain emerged at the end of Australia's influenza season, too late for inclusion in US flu vaccines, according to a Feb 2 report from the Associated Press (AP).

According to the CDC's most recent weekly flu report (for Jan 20 through 26), US laboratories have characterized 197 flu viruses so far this season. Forty-six (23%) were A/Brisbane/10/2007-like, which the CDC says is a recent antigenic variant that evolved from an A/Wisconsin/67/2005-like strain, a component of this year's seasonal flu vaccine.

The Brisbane-like viruses made up 87% of the 53 type A H3N2 isolates collected so far, according to the CDC. Of the other isolates, 101 were type A H1N1 viruses and 43 were type B viruses. (CIDRAP News)

So far it is the other circulating influenza/A, H1N1, that predominates (three quarters of the isolates). The flu vaccine is well matched to this strain so will likely afford protection against the majority of flu virus that is around (although things often change as the season progresses and we are just starting to see marked upswings in flu activity). It is also the H1N1 subtype that is showing increasing resistance to Tamiflu, not the H3N2 where the mismatch occurs.

Bottom line: you are better off getting the vaccine on two counts. It protects against most of the flu around, so you won't get it. And if you do, the only oral antiviral now recommended may or may not work. So far H3N2 is not showing much Tamiflu resistance, so if you get vaccinated but come down with the mismatched flu you can still be treated.

I know from years of Comment Threads here that some people don't think either the flu shot or antivirals are worth anything.

You're welcome to a scientifically tested a chicken soup recipe.

If data are what you are hungry for, you can find the latest CDC surveillance report here.

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Why don't we once and for all just prove that influenza vaccine works or it doesn't work...we certainly have the expertise to do so.

In my opinion, we have a lot of 'faith' based medicines today and infrequently, as a result, they do more harm then good...

...and I understand that many well-educated healthcare workers don't have the faith when it comes to influenza vaccines.

It has been very apparent on the front lines this year. Anecdotally, we're seeing much more flu than usual, with several documented cases each week in vaccinated individuals. Sucks.

"And if you do, the only oral antiviral now recommended may or may not work."

revere,

sure Relenza may be inhaled, but you are allowed to mention it. Zanamivir was the first NA inhibitor, it was designed primarily to be effective and avoid viable resistance.... unlike Tamiflu which has the advantage of being orally administered, but then so are M&M's.

I'm not so sure that seasonal influenza's and particularly H5N1 (and probably H)7... aren't feeding on antivirals to their evolutionary advantage.

Evolutionary pressures on influenza certainly has increased and is ever increasing.

Injecting antivirals indescriminately into the most active flu zones is in the longterm, counterproductive in my opinion, although it may delay things in the short-term.

Chicken soup - that sure is ironic, when you take into the account H5N1 :D

By Helblindi (not verified) on 08 Feb 2008 #permalink

Does anyone really get a Rx for Tamiflu or Relenza? About ten years ago, my husband was in the early stage of flu. I forget the crisis at the time, but we were trying very hard to keep him from falling ill. I had him call the Dr.'s office to see if he could get Amantadine. There was much hemming and hawing. He got a small number of pills, as I recall.

Granted, that was nearly a lifetime ago in medical terms, but how many main-stream docs prescribe Tamiflu or Relenza as a matter of course? How many "more conservative" docs do? When do you call for the Rx? When your spouse is sick, so you won't fall ill? When the kids have a fever?

For most all of us, influenza is a short-term misery with no lasting after-effects. Do docs hesitate to prescribe when there is no great risk if the patient gets the flu?

I've been figuring that we'd just groan and bear it if we were visited by H3N2 at our house. (Maybe our son's swim coach would prefer that we call the doc if our boy is threatened with flu just before Sectionals and State finals!) I didn't really imagine that getting a Rx for garden-variety influenza would be an option.

(Our doc is in his early 50s, and also a professor in Family Medicine, so I have considered him to be fairly up-to-date with treatment protocol. He's also conservative when it comes to prescribing the latest new wonder drug.)

By wenchacha (not verified) on 08 Feb 2008 #permalink

Tom: I think we have discussed this before. Doing a RCT for influenza vaccine is not a snap. Since there is substantial evidence it works, you can't just give a placebo for it. It is also not "all or none". It may work for some groups (say under 65) and not as well as others. You tend to simply things that aren't so simple.

wenchacha: There is considerable regional and national variation in the use of Tamiflu for influenza. In the US it is complicated by a lack of universal health care and whether the drug is on an insurance company's formulary.

miso: Yes, Relenza. It can cause bronchospasm in some and isn't recommended for children. The current strains of H1N1 resistant to Tamiflu are not resistant to Relenza. So if you can find Relenza and you can take it and your infection isn't systemic, it will work as well as Tamiflu on a sensitive strain.

I have another idea, why the vaccine may work so poorly :
if prevents us from getting immunity from asymptomatic infections

as I remember, Relelenza doesn't work so well
on most strains, reduced efficiency as compared with
Tamiflu.

We missed early flu immunization when we would normally have scheduled it late last year. Various sources of external chaos pushed it to the back of the queue.

Now that we are looking to catch up, the organization from which we have obtained seasonal flu shots for the past several years informs us that they have concluded their field clinic program for this season, and have no more vaccine available.

We have the time, mobility and money to reroute to another provider should we deem it necessary. I wonder how many people in the population at highest risk for flu, the impoverished elderly, are going to end up going without.

--

Maybe I'll try the soup. Coughed so hard with flu I've hurt my back. Appointment with neurosurgeon in 2 weeks.....

Revere.

First of all, we know that all laboratory results for vaccine efficacy in laboratory animals is 'cooked'...maybe unintentionally but 'cooked' just the same.

They produce a vaccine to a specific virus and then 'freeze-frame' the virus...and in the case where natural evolution of the virus in the field is eliminated...the vaccine works...

...which of course doesn't mean much when dealing with a virus that has 'harnessed' its inherent genetic instability so unbelievably well.

Secondly, the type of screening and survelliance studies they have used don't mean anything because they are too subjective...leaving it to subjective diagnosis of influenza which doesn't work because most influenza's are actually food poisonings.

Thirdly, as I'm sure you know, influenza outbreaks occur sporadically and vary naturally in different locations...so because one city vaccinates and another doesn't and the one that vaccinates doesn't get influenza...also means absolutely nothing.

So...like antivirals...we are left in a situation where all the avaliable funding is being spent on treatments-preventatives that work in the lab but not in the field.

So the question is...can we do a double-blind 'quality' study without the ethical pitfalls of giving unknowing human experimental subjects placebos.

...and I believe the answer is clearly yes.

This could be done by utilizing the personal choices of subjects...and this could be done with healthcare workers because they are naturally divided on these specific issues.

So we make sure sampling is balanced for age, race, income distribution, lifestyle and geography...

...and then we measure over a large sample size to determine whether the seasonal influenza works or not...and we don't take into account such things as vaccine mismatches because if we have mismatches every second year then the vaccine doesn't work anyway.

Since it is the personal choice of the subject then we don't have the inherent ethical problem of a double-blind study.

However, we must have acute and convalescent blood samples as the basis of a definitive diagnosis...

...we do this by paying the subjects for their time...such that they will allow the required blood sampling...

...and since we may very well be wasting several billion dollars on vaccines at the moment, the opportunity cost of a few tens of millions of dollars to pay people for their time and suffering is minscule in my opinion.

We should remember that pandemic influenza is a whole different animal from seasonal influenza...and if seasonal vaccine doesn't work well then we can forget it in a pandemic.

I happen to believe that seasonal influenza vaccine works on 5% of those vaccinated...and since partial immunity allows enhanced circulation of viruses...then a poor vaccine could be actually helping viral evolution...and the same goes for a partially effective antivirals.

However...we do know that secondary bacterial pneumonia vaccines work...and that anitibiotics work...and that electrolytes work...and some of us know that prednisolone works especially for the toxemia of those secondary bacterial pneumonias that may be the bigger killer in a pandemic /:0)...and we know that public health infrastructure will collapse and be unable to help young parents cope with their childrens suffering...

and we know, beyond a shadow of any doubt, that vaccine requiring live birds and eggs with a virus that likes to kill both live birds and eggs...is never going to see the light of day...because in a pandemic, the humans become reverse vectors infecting the chickens and eggs that are supposed to be harvested to make the vaccine...six months later.

...so we need completely new vaccine technologies with completely unique immunological targeting...and also vaccines that do not require live chickens or eggs that can be produced in three weeks rather than three months.

I would rather put the monies into infrastructure and secondary support and medication kits for every person who requires ready to go proactively...as in now.

Authorities seem to have forgotten the immensity of the threat potential from H5N1...whether we think it is going be achieve pandemic potential is a different matter...we must prepare for the worst...but I know in the most case, I am preaching to the converted...and therefore apologize proactively as well.

Thanks.

Revere-Are you saying that due to age, ethnicity maybe, etc. that the annual vax might not work in them at all? Right now I understand it to bring you back about a day earlier.

If thats the case, how does that work its way into the possibilities of a molecular vax for us and H5N1?

And with this in mind for both types of vax, if you come back that day earlier are you shedding virus then too. I mean if a normal flu takes about 10 days to get you well enough to think about heading back, you come in honking and coughing and spraying that shit everywhere. Are you still infectious at the time your temp goes back down?

By M. Randolph Kruger (not verified) on 08 Feb 2008 #permalink

Randy: You are mixing up the antivirals (to treat disease) and the vaccine (to prevent it). The issue (which we've posted on here several times) is whether the vaccine works as well in the older age group because the immune system doesn't respond as vigorously. The observational studies on seasonal vaccine say it is highly effective but the randomized trials raise doubts about the older age group.

I have a pulmonologist with whom I can communicate by email, which is very cool. With me being high risk, and with everybody I know griping about what a bitch this flu that's going around is, he quickly agreed to writing me for Tamiflu. I pointed out that symptom onset might be a little too long to wait to begin the process: get script, drop off at pharmacy, wait till they recieve it (no, they don't have it in stock), do the prior authorization dance with the provider for a non-formulary drug. By halfway through my first day with flu, details like that might be a bit much for me to handle. I have a small supply of amantadine I've been sitting on for several years (shelf life is pretty good, especially in a cool, dark place like the one I've been keeping it in). Too bad the stuff is probably useless, especially against the poorly-matched H3N2 strains. I was hoping resistance to the amantadanes might have dropped off some since the CDC advisory in, what, 2005? Unfortunately, resistance to antivirals appears to be like the price of coffee: once it goes up, it tends to stay up.

Racter: It's not clear amantadine resistance is related to amantadine use. It might be just linked to something that is useful for circualting strains. So it could revert to sensitivity, too. There are also groups interested in making M2 inhibitors that aren't resistance provoking. So things could change.

it is commonly assumed in the papers, that Amantadine resistance is related to Amantadine use.
It would be a strange coincidence, else.

Revere-No I didnt mix it up, but you did answer the question though and that was whether there would be any response in older people but not ethnicity.

This is Canadian FluWatch and I am assuming like all good Canucks they tipped on down and got their flu shots this year because it was UHC and "free" technically.

Their graphics would indicate that its not working out so well for them and the age groupings are in line with the CDC graphics and pretty much mirror each other. Thus this gives rise to the Tom DVM series of posts about vaccinations. No, I would never tell anyone NOT to get the flu shot. Just the opposite but again by the same token it calls the process into question. Do we by vaccinations run the risk of creating a super bug because it simply isnt able to knock it down hard enough?

http://www.phac-aspc.gc.ca/fluwatch/07-08/w04_08/index-eng.php#1

Dont bother with the CDC site, its basically the same image for January. From what I understand there is 60% of the people that will not take the shot for whatever reasons each year. That includes the medical community. 6 out of every 10 dont.

By M. Randolph Kruger (not verified) on 08 Feb 2008 #permalink

I guess I always just assumed that increased use of amantadanes was the selective presssure driving resistance, and that the resistance comes at a fairly high price for the virus. Therefore, I expected to see resistance fade with a decline in use, and when I didn't, I was a little confused. After all, M2 is highly conserved in the viral genome and all that, right? When I saw in the January 25 MMWR report results of a survey indicating that significant numbers of providers have been prescribing amantadanes despite the CDC's recommendation, I figured that explained it.

Randy, try the CDC site again. They were rather late updating today for some reason.

USA is not so important. Other countries still
use Amantadine. Resistance has a bit declined last season,
95%-->90% or such

Anon-90% where?

By M. Randolph Kruger (not verified) on 08 Feb 2008 #permalink

percent of Amantadine resistant human sequences
in Genbank 1993-2007:
H3N2:00,03,00,00,00,02,05,00,00,01,02,02,32,94,90
H1N1:--,--,04,03,--,--,--,04,03,--,04,--,08,14,00
H5N1:--,--,--,--,13,--,--,00,30,19,46,69,37,33,36