Seroconversion after measles or MMR vaccine

or: Dr. Bob strikes again

Dr. Bob Sears has a great sense of humour. He likes to drop a completely batty or offensive post, only to backpedal with a “just kidding” in response to expert critiques of his book. A recent gem on his blog on the upcoming H1N1 vaccines (which is astonishingly content free):

Just how bad is the H1N1 flu? Our experience so far indicates that it is a little worse than the regular flu, but it is not the rampaging epidemic that will sweep through the country and kill everybody. So why is the government so worried? It’s because the evil drug companies are paying them to act worried and create hype over the H1N1 flu so that the drug companies can make billions of dollars selling a vaccine that everyone will be scrambling for. The companies can then hand some of that money back to the government officials who helped them out.

Followed by an immediate

I jest.

In my opinion, he is not jesting, but rather “probing” his audience to see just how far out towards the fringe he will find most customers for his “alternative” schedule and books. This is all reasonably subtle, although Dr. Bob probably underestimates (or does he) how thoroughly his posts are read.

A couple of days ago, Dr. Bob struck again, although I am afraid, this one might turn into an explicit “recommendation” in the revision of “The Vaccine Book”:

Dr. Bob Answers by Dr. Bob - posted on 8/4/2009

I just found out some interesting info. I'd known this already, but hadn't realized it's [sic] implications.
ONE dose of the MMR vaccine creates immunity in 97% of kids. I had thought that the reason for the booser [sic] was that because this wears off, so another dose is needed. At an AAP lecture last month, this topic came up.
It turns out the second dose isn't a booster at all. A booster means that immunity wears off and needs to be re-boosted. The second MMR isn't given because imunity [sic] wears off (although eventually it does in adulthood). It's given to try to induce immunity in the 3% of children who don't respond to the first MMR shot. Doctors were also suggesting that it would make more sense to give two MMR doses during toddlerhood, so these 3% don't go through young childhood without protection.

So, this means that technically 97% of kids don't need that second MMR. It would make more sense to check titers on all kids, then only give the second dose to those who need it. some of the peds in my area actually do just that (they aren't anti-vaccine at all).

So, I'm thinking that this might be a good general policy for everybody. So, I'm considering not recommending a second dose, unless titers show it is needed. I will likely make this an official change in my alternative schedule. I just have to put a little more thought into this before I make this official.

However, the government doesn't recommend this because the healthcare costs of coordinating this type of thing for everybody would be very high - it's much cheaper just to give everyone a second dose, since the vaccine is harmless (?)

I (or YOU) may have just opened a can of worms.

(from this post - typos are his)

This is Dr Bob at his best, which unfortunately is not very good. Since his measles/MMR vaccine recommendations have major public health implications, let me summarize what we know (from the biomedical literature).

A good place to start are the vaccine package inserts. Here is the one for Attenuvax, the monovalent measles vaccine, usually produced by Merck, but on backorder at the moment (presumably until 2011) and the only monovalent measles vaccine licensed in the US. I am assuming this is where the “97%” that Bob quotes comes from. The package insert states that “97% or more” seroconvert, but “1 to 5% remain unprotected”. Seroconversion means that vaccinees who had no antibodies to the specific vaccine/disease show specific antibodies after disease or vaccination (the blood serum "converts" from negative to positive).

There is some (not much under that brand name) literature:

A small study looked at seroconversion depending on age. They vaccinated 15 15-months olds with Attenuvax, all 15 seroconverted (i.e. 100%). Then they vaccinated 6-months olds, 74% of 19 6-months olds vaccinated seroconverted, but had a lower titer than the older children. Significantly, upon boosting, all infants seroconverted and developed a higher titer. This is further confirmed by Erdmann and colleagues who find that titers can increase after revaccination or measles infection after one measles shot.
While these are small studies, they illustrate the principle that titers after one shot can be low and poor responders will be boosted by the second measles shot. This boosting effect of the second measles containing vaccine has also been observed in a very systematic MMR study from Sweden.

To dissect the 97%/100%-1 to 5% number in the package insert further, we can look at this larger study of over 600 children: Watson et al find that 5.4% of children at school entry who were initially vaccinated with monovalent measles vaccine at 15 to 17 months are non immune. This is the most realistic study I can find. The authors do not see an influence of age on seroconversion, so based on this available literature, we can assume that between 94 and 95% of children would seroconvert after vaccination with monovalent measles vaccine and remain immune until school entry.

The other possible vaccine, we can use to immunize against measles, is the MMR. The MMRii package insert states that seroconversion for measles is 95%. This is consistent with the majority of the available biomedical literature (see for example here and here). A huge number of studies using different measles containing vaccines consistently show a better immune response to the measles component in children older than a year (12, 15, or 18 months) vs infants (6 or 9 months). Dr. Bob consistently implies that the MMR vaccine given at age 4 would lead to sufficient seroconversion in most children (maybe extrapolating from the better responses in toddlers vs infants), however, the only paper systematically comparing the effect of age on seroconversion beyond the age of two finds that younger children respond better than the school age vaccinees.

Taken together, clinical data from Attenuvax and MMRii indicate a realistic rate of seroconversion of about 95% which would mean that up to 200’000 children per year/birth cohort in the US remain susceptible to measles after their first MMR/monovalent measles vaccine.

When devising a general vaccine recommendation, one cannot ignore the mumps and rubella components of the MMR. While the initial rubella seroconversion is consistently reported as excellent and near 100%, secondary vaccine failure occurs and leads to susceptibility during pregnancy. Currently, up to 9% of women in the US are found to be susceptible to rubella, having received a booster is highly predictable of protection at reproductive age. Even more dramatically, initial seroconversion to mumps can be variable (rates as low as 75% are reported in the literature, although values around 90% are more typical) and mumps immunity wanes with time, therefore putting a child who is not boosted at a significant risk (see for example here and here ).

So how practical is Dr Bob’s suggestion of one MMR at age 4 and a subsequent titer check and revaccination for the non immune as a “general recommendation”?

1. Children would go entirely unprotected for the first 4 years of their lives, leaving them vulnerable at an age when measles have a particularly high risk of complications, including SSPE.
2. After MMR vaccination at age 4, ALL children would need to have their titers tested. This involves a (sometimes very painful and traumatic) blood draw and titer tests for measles, mumps and rubella. Presumably, insurances will not pay for this (which doesn’t bother a doctor in private practise, like Dr Bob, but may lead to reduced compliance in the general public).
3. 5% of all children tested will not be immune against measles – more will have a low titer, up to 20% will not be immune against mumps, 1% or so will not be immune against rubella. Therefore, up to 20% of all children (or more, if you include the ones with low titer) would benefit from the second MMR.
4. All women would have to be re-screened before trying to conceive to see whether they are still immune to rubella.

I cannot give out medical advice, I am not an MD. However, given all available data, the strategy suggested by Dr Bob Sears seems to present a significant threat to public (and individual) health due to the long period he intends to leave children unprotected. His strategy is unnecessarily costly and complicated which may lead to a decrease in compliance and further increase in the number of susceptible children, then in a school setting where measles and mumps spread particularly well. In the long run, children who tested “immune” against measles, mumps and rubella and did not get the second MMR might lose measles, mumps and rubella immunity, contributing to outbreaks in high schools and colleges/universities. Women may lose rubella immunity, leading to a re-emergence of congenital rubella syndrome.

A general vaccination schedule comprising 2x MMR, the first one at age 1 (12 to 15 months) and the second one between 4 and school entry is safer (immunity earlier, better long term immunity for every child), cheaper (no titer tests) and easier to follow (fewer doctors’ visits). Unless, of course, one considers the second MMR as some unmeasurable danger that is best avoided, which brings us back to Dr. Bob’s MMR recommendations and his true beliefs. Does he really believe the second MMR would be so traumatic that it is worth avoiding it at the above mentioned expenses (both medical and financial), or is this “new” recommendation a plot to keep the “brave Maverick doctor" label when all science points to no connection between MMR and neurodevelopmental disorders? Certainly, Dr. Bob is more brazen about his choice of professional alliances of late, moving further and further away from a position that would be acceptable for any "majority".

edited within first hour of posting to fix links and typo