Effect Measure

We seem to be doing a lot of vaccination stuff here lately. It’s an obvious public health topic, one that’s in the news and (in some quarters) considered controversial. I’m a strong proponent of vaccination where it makes sense (which is in most of the instances where it is used) but that doesn’t mean I think it is problem free. For a public health scientist the problems are not only interesting but of practical import. Yesterday’s post about fainting during vaccinations produced an unexpected comment thread from people who have at one time or another fainted during a vaccination or medical procedure, for example. The rare adverse event, even if it is one in a million or ten million, can affect public confidence in a whole vaccination program since when you are giving tens of millions of doses, even rare events are bound to occur, even though the net benefit to the public is very large compared to the tiny risk. But one issue that has been hidden, probably because many of our most effective and important vaccines are relatively recent, is our ignorance about how long they are effective. This arose recently in a multi-state mumps outbreak where it turns out most of the indigenous cases were among those previously vaccinated against the disease. Apparently the vaccine’s effect had waned. This has raised some interesting questions.

When a disease circulates in a community, adults who were immune as a result of childhood infection receive continual “booster infections” that keep their immunity current and “topped off.” When a substantial portion of the population is vaccinated with a effective vaccine, however, the virus no longer circulates in the community and the booster effect doesn’t occur. If there is a natural waning of immune protection in the absence of new exposure to the virus we could produce an aging population with little or no protection to some important childhood diseases. If the world’s population were as well covered by vaccines as in the US, this wouldn’t be as much of a problem because the virus wouldn’t be circulating anywhere. But that’s not the case and the mumps outbreak started from unvaccinated cases that acquired natural infection outside the US and were then able to infect US cases whose vaccine-acquired immune protection had decayed.

The remedy for this might be to give booster shots to adults at an appropriate interval — if we knew what an appropriate interval was:

“I don’t think we know much at all,” acknowledges Dr. Samuel Katz, co-inventor of the measles vaccine and a pediatric infectious disease expert at Duke University in Durham, N.C.
Figuring out answers about the durability of immunity – naturally and vaccine-acquired – in a time without natural boosting won’t be easy.

[snip]

Dr. Michael Osterholm says scientists should be doing long-term immunity studies – following groups of people for decades – in the way cancer researchers track groups of people to try to discern what causes cancer.

“That would help us understand at what point does the level of protection drop for a population. Not any one individual. But a population norm where you would now recommend that a booster shot should occur as a standard of medical practice,” suggests Osterholm, director of the Center for Infectious Diseases Research and Policy at the University of Minnesota. (Helen Branswell, Canadian Press)

There are a bunch of difficult questions here. Is there a way to know, say by measuring a particular antibody level, when a person’s immunity has sunk to a level it is no longer protective? This is a scientific question that goes beyond childhood vaccines. For example, in testing proposed vaccines against influenza A/H5N1 (aka bird flu) we don’t know if they protect people because (fortunately) we haven’t had an outbreak of transmissible bird flu. As a fall back we measure the level of neutralizing antibodies in the blood of vaccinated subjects and, based on previous experience with other kinds of flu, guess at a protective level. It may be a pretty good guess, but it’s still a guess. We have similar problems in following the immune status of previously people vaccinated against other diseases long ago. Like mumps.

This is very tough science and just one of many urgent public health research questions that affect all of us. What’s the Bush administration response?

Cut the NIH budget.

Comments

  1. #1 albatross
    May 8, 2008

    So, the fact that a lot of older people who had been vaccinated got mumps tells us that the vaccine is probably losing effectiveness under these conditions. Can we infer anything more than that?

    This isn’t my field, so I’m probably either saying something obvious or silly, but it seems like someone might be able to learn a fair amount about how the effectiveness of the vaccine falls off just by trying to analyze the available data. I think the main requirement is to get a class of people we can count, all of whom had some similar level of exposure, and some of whom are known to have gotten infected. (The choice of classes of people based on existing known infection is a kind of data snooping, but if there aren’t too many possible classes, it’s not too bad.) The obvious class to propose, if the set of infected people is large enough, is the full-time custodial parents of children who got mumps and were also vaccinated.

    The goal here is to get a set of K exposed vaccinated parents, of whom R got mumps, as a kind of quick estimate of the fraction of vaccinated people who lost their immunity. If those numbers were big enough, we could use that dataset to do more complicated statistics.

    Writing this, I expect there are dozens of problems with doing this analysis, or it would already be being done. But it’s just a thought. (Besides, it’s hard to make too much of a fool of yourself outside your own field….)

  2. #2 revere
    May 8, 2008

    albatross: You absolutely have the right idea. That is the way epidemiologists think. Since I’m an epidemiologist I also know that practically speaking there are a lot of non-obvious difficulties here. For example, the new cases are themselves adults so they don’t have a uniform set of caregivers, assuming you could find enough of them to study. The CDC study was an attempt to tease out the effect of prior vaccination among cases, so we know protection doesn’t last as long as we thought (or hoped) but specifying this further will require a lot more data over a longer time period, something we all hope we won’t have. Still, finding the right “natural experiment” and then observing it is what epidemiologists do. Maybe you need to think about a second career.

  3. #3 C. Corax
    May 9, 2008

    There’s been a hue and cry in the dog community from folks who swear that regular vaccination boosters are killing dogs. At least some vets have responded by testing antibody levels in dogs to determine whether they actually need booster shots.

    Are you saying that it’s all hokum, that there is no antibody test for continued immunity? Or are dogs just that different from humans that what works for them won’t necessarily work for us?

  4. #4 revere
    May 9, 2008

    CC: If we know from actual data what levels of what antibody (remember that there can be many “different” antibodies raised to a particular agent) were protective most of the time than we could use a blood test. For H5N1 we are guessing, based on levels of neutralizing antibody (i.e., a particular testing protocol). I don’t know about veterinary vaccines. Because you can do experimental challenge tests with animals you can’t do with people and because of the economic factor providing an incentive we may know more about this than we do for humans.

  5. #5 ry
    May 10, 2008

    Revere:

    I’ve never understood why this type of followup has never been done routinely on every vac. Who decided it shouldn’t be done? How can doctors or scientists keep advising vaccine updates when they have no idea how long they’re effective? This lack of an adequate answer is directly related to why vaccine rates are dropping, it’s the elephant in the room that isn’t addressed. People want info not I don’t know.

    Could there be a correlation on effectiveness of initial vaccines that’s directly related on how vaccines are handled in an office? For example: A vial that’s supposed to stay refrigerated but sits out all day for multiple uses in ED’s and offices or maybe inadvertenly frozen because temperatures in frig aren’t monitored? Also, vaccines given too soon or too long (before and after) CDC recommended spread during the monthly intervals? Would this effect outcome?

    The last time I questioned a vaccination suggestion the MD was instantly defensive, almost to the point of blow up. I don’t take medications without asking questions and I’m not taking a vaccine without asking either. This whole area needs a serious M&M conference.

  6. #6 anon
    May 13, 2008

    you needn’t test it on H5N1. Seasonal flu is quite similar,
    immunogenetically.
    And you needn’t take humans, try ferrets,swine,birds,mice
    and only occasionally compare with humans to check
    how well it can be compared.
    Also check with data from immunity gained by real
    outbreaks : protection of older people in 1968,1977 pandemics etc.