Playing Grandmaster chess with swine flu

A reader asked an offline question that is general enough to post about (NB: I try to respond to as many questions as I can, but I'm traveling and can't keep up, so in most cases I won't be able to respond. I also don't hand out personal medical advice over the internet, something I consider bad practice). CDC says on the basis of clinical trials with the unadjuvanted vaccine used in the US that two shots, 21 days apart, are needed for children under 10. WHO, on the other hand, is telling its member nations that one will suffice. Why the confusion?

We may be comparing apples and oranges. Many countries use adjuvants in their vaccines which promote a quicker and more powerful response. It appears that a single dose is sufficient for children under 10 when there is adjuvant in the vaccine. Canada currently is using adjuvant, as are many other countries, although concerns from parents have forced the Canadians to offer an adjuvant-free option. Helen Branswell has an excellent piece with a Q&A on the controversy that you should read in its entirety, but it is pitched to a Canadian audience, so I've take out some of what I consider the more general points:

Based on GSK's [vaccine maker GlaxoSmithKline] early data, Canadian officials say it's possible kids in Canada will only need one dose, but they want more information before making that decision.

But given that there must be a 21-day interval between the doses, there is still time to figure this out, experts say.

"For me, given the level of activity, the second wave activity already occurring, our goal should be ... get a first dose into kids. Then we can discuss the second dose," said Dr. Danuta Skowronski, a flu expert with the British Columbia Centre for Disease Control.

"We still have time to work out whether that second dose will be necessary."


A spokesperson for the Public Health Agency of Canada noted that parents who want to go [the route of demanding an unadjuvanted vaccine] need to realize kids will need two adult-sized shots of vaccine, given 21 days apart. And the full protection of those shots will only really be in effect two or three weeks after the second shot is given.


"My concern is we are having intense second wave activity now. So for parents to be holding out for an unadjuvanted when we're facing intense activity now, they'll miss the boat in terms of protecting their kids," said Dr. Danuta Skowronski, a flu expert with the British Columbia Centre for Disease Control.

"Better the bird in the hand than two in the bush."

[Dr. Joanne Langley, who is chair of the Canadian National Advisory Committee on Immunization], a pediatrician who specializes in infectious diseases, agrees.

"I think as a pediatrician, knowing these children are vulnerable, knowing that the likelihood of them having a strong and quick immune response ... is so much lower with an unadjuvanted preparation . . . I think the best choice in that circumstance is to go with an adjuvanted preparation."(Helen Branswell, Canadian Press)

So that's point one. Every child is in a race with the virus. My 5 year old grandson lost the race and is now suffering through fever, aches, pains and feeling ill from Tamiflu. He has asthma so Relenza is not an option. A couple of weeks more and he would have gotten some protection into him. But the virus got there first.

Or maybe more than a couple of weeks. In the US there is no option to get adjuvanted vaccine if you want your child to be protected faster. Again from Helen Branswell:

U.S. pandemic planners decided against using adjuvant in their vaccine. And vaccine without adjuvant doesn't induce a terrific immune response in little kids, whose immune systems are still developing and who haven't had as much exposure to flu viruses as older children and adults.

The study results released Monday were based on a trial in 583 children aged six months to nine years of age who were given two doses of H1N1 vaccine without adjuvant at a 21-day interval.

The response to one dose was poor in children six months to 35 months - only 25 per cent reached the protective mark. In children three to nine years, the rate was 55 per cent, still too low by regulatory standards.

But Dr. Anthony Fauci, head of the NIAID, said after the second dose 100 per cent of the younger children and 94 per cent of the older children had antibody levels that suggest they are protected against the virus.

With an adjuvanted vaccine, a half dose gives antibody titers thought to provide protection in a single shot in babies 6 months to a year and a half. This is the highest risk age group in the population. But adjuvanted or not adjuvanted, it is likely that one shot is better than none at all. That seems to be WHO's reason for recommending one dose for children under 10. There's a global shortage of vaccine and their objective is to get some protection to as many children as possible. Yesterday we noted the melancholy data on child death from pneumonia. Well over half of these deaths are vaccine preventable. With an influenza pandemic ramping up in the developing world, WHO is trying to stem the tide of child deaths that inevitably will follow in its wake.

There are lots of agonizing decisions to be made and no sure answers. Influenza virus is a wily adversary. It's like playing timed chess with a grand master without knowing all the moves or the rules. But move within a certain period of time we must. Is the move the right one? We'll find out after the game is over.


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Actually, I was going to ask about JUST this stuff, so a big Thank You for posting this! I also think it's interesting to compare the situation to a game or a race. After all, viruses are jsut that - playing with us.
Many greetings

By Flu-ctuation (not verified) on 03 Nov 2009 #permalink

My husband and I just had this conversation. When I got my preschooler her first dose a week ago in a neighboring county, there were well over 1,000 people in line. We wondered if getting the second dose was the right thing to do when so many people were being turned away.

But then they held a clinic in our county. Only 200 people showed up for 1200 doses, a similar number the second clinic. That means they're sitting on 2,000 unwanted doses. If I could be sure those would go to counties or countries where the vaccine is badly needed, I might follow the WHO's advice. But if they're going to just sit there gathering dust, we might as well use them.

Even if our child doesn't fall in the lucky 55 percent, will the vaccine at least help prevent complications if she does catch the flu?

This is a little bit tongue in cheek (more than a little bit), but there are ways to produce the physiological effects of adjuvants without using chemical adjuvants. âStressâ acts like an adjuvant.

Making a vaccination event more stressful for the child might increase the effectiveness of that vaccination event. Weighing the relative short and long term physiological and psychological effects of a particular vaccination event adds yet another degree of difficulty to the decisions parents must make.

There is recent work that indicates that giving anti-pyretics before a vaccination does reduce the effectiveness of that vaccination.

Revere: I have the same question as "Curious", since I also have a U.S. preschooler who already had her first intranasal swine flu vaccination on 10/12 (obviously not the adjuvanted version). She is due now for her second vaccination (21 days after the first), but I'm having a hard time finding a place to get it since her pediatrician is all out and doesn't know when they will get more. I'm not asking for medical advice, but rather some peace of mind. I'm wondering whether, even if she doesn't have full protection right now, she still has less likelihood of complications if she does get the swine flu, per the question from Curious:

"Even if our child doesn't fall in the lucky 55 percent, will the vaccine at least help prevent complications if she does catch the flu?"

If so, then it seems like WHO's recommendation for children under 10 makes a lot of sense (even with the non-adjuvanted vaccine), because if children under 10 get the swine flu after one vaccine dose perhaps they have less chance of complications.

Curious, chrisg: I am at a scientific conference and sitting at a table with two immunologists, so I put the question to them. The bottom line for both is that "it couldn't hurt" (i.e., your child won't be worse off) but that there are too many unknowns to give a firm answer to the question. It's not clear what the level of protection that CDC determines will protect is based on (it's a correlation with neutralizing antibody, but what the correlation end point is we don't know; the immunologist said it is possible it is the level needed to get a proper response with the booster, but that there may still be some partial protection). Bottom line: we don't know for sure. But it can't hurt.

We lost the race too. My 8 year old child, scheduled to be vaccinated later this week, was diagnosed yesterday. She is a wretched, crumpled, shivering sight, with subconjunctival hemorrhage in both eyes (presumably from the force with which she is vomiting from the illness and/or the tamiflu). I was up most of the night sponging her to bring down her fever, since she couldn't keep down fever medications.No idea how much tamiflu she is actually absorbing.

Very grateful she was seen by her ped, grateful we were able to find compounded tamiflu syrup, but discouraged that she and many thousands like her will contract the virus despite our best efforts to procure the vaccine.

I hope the smallest Revere recovers quickly and uneventfully.

By sophiequus (not verified) on 03 Nov 2009 #permalink

Revere, thanks for the post explaining the difference between the "one vs two" dose recommendation. Could you explain why the US decided not to use vaccine with an adjuvant?

I am certainly no expert, but my understanding (which may be flawed) is that the two-dose protocol is for killed virus, not for the attenuated live virus.

My 9-year old Canadian son ( in Ontario ) received a *half* dose of the adjuvanted GSK vaccine and has an appointment to go back for the other half in 3 weeks. So this does annoy me, sounds like he could have got the full dose of the adjuvanted vaccine and been done with it.
I questioned the nurse about this, since my son is a big, strong kid for his age, but she indicated there was no discretion possible.


I am sorry to hear about your grandchild having the flu. I waited in line with my wife and 15 month old daughter for 5 hours for them to get the vaccine (wife is a NICU nurse). Luckily they got it and my daughter didn't even cry from the needle. Kathleen Sebelus was there too for observation of the event near DC. Now we just have to hope we can get the 2nd shot for our daughter in a month and keep her from getting sick in the mean time.

I searched on here, but didnt see a post on basic flu care (or anything specific to H1N1). I would really appreciate a post on that, even if its just to point us to the site and endorse it.

I'm trying to prepare as best we can by understanding in advance what we should do home care wise and to buy what I need to have on hand. I still don't have a good grasp of this basic care. The do's and the don'ts. I would really appreciate it if you could post on this basic, but fundamental and vital subject.

Thank you.

Thanks for this post. I was having this discussion with some other moms earlier in the week. A few of us have managed to get our child the first shot and we were confused as to whether we needed to get them a second. I will be following up with his pedi next week to see if we can get it.

Many sympathies to all those taking care of sick kiddies. I hope they all make a swift recovery. When my little boy (not quite 2) got his shots, he said 'hurts... hurts' (he moved his arm, mine didn't hurt at all). I told him it hurts a lot less than flu...

I'm a general pediatrician in Canada, looking after inpatients-most of whom have H1N1 at the moment. Just a note that while it's clear the adjuvanted vaccine is superior (and I'm very glad we're using it here in Canada), the recommendation here is still for two doses. We've had some discussion here this week around the recent WHO statement with our infectious disease specialists (including Joanne Langley whom you've quoted above), and they don't feel there's data yet to tell us that one dose is as good as two, even with adjuvanted vaccine. My reading of the WHO statement is, as you say, that one dose is better than none, so the priority should be two get all children at least one dose-that's not to say it means a second wouldn't be better.

By Joanna Holland (not verified) on 04 Nov 2009 #permalink

In the U.S. where the vaccine itself has no adjuvant, would it not be possible to obtain and administer the adjuvant substances at the same vaccination event, and achieve the improved resonse?
If this works "medically", is there a legal problem?

By Searle Crate (not verified) on 05 Nov 2009 #permalink

Searle: No, that wouldn't be a good idea. The adjuvant is in a specific form and is formulated with the vaccine. Adjuvanted vaccines have had clinical trials and we know their characteristics as far as antibody response. If you formulate them differently you don't.

There are lots of rumor about swine flu, most of the people believe what they hear. Vaccination is also a controversy. Thanks for the information..

By göÄüs estetiÄi (not verified) on 19 Nov 2009 #permalink