These notes are for the second part of an audio broadcast entitled The Vaccine Detectives done by BBC 4 and aired in January, 2011 (to listen, click on "show all programs" and scroll down towards the bottom of the page). To find out more of the background behind these broadcasts, click here. To read my notes for Part 1 of the broadcast, click here. The simple overview is that Peter Aaby, an anthropologist from Denmark, has been working with a medical team in the West African nation of Guinea Bissau trying to lower the incredibly high child mortality rate (children in Guinea Bissau are 20 times more likely to diet before their fifth birthday then children in Europe are). In this endeavor he and his team have compiled evidence that vaccinations- while generally having positive effects- can have long term effects on the immune system of a child that can be devastating in the long run. Up until now, he is essentially the only researcher to look at the long-term effects of vaccines on the individual and the community. His research (and that of others working in his footsteps) has shown that the effects of vaccines on a child's immune system vary greatly between boys and girls, which is potentially relevant to autism.
The health researchers in Guinea Bissau have conducted clinical trials to determine if giving polio vaccine at earlier ages has an effect on mortality. This interests me because we are told here in the US that the reason that it is not possible to do a vaccinated vs unvaccinated study to see if there are any differences in the autism rate in these two populations is that it is entirely unethical to do any study in which some of the children do not receive the full vaccination schedule as it is recommended by the AAP (despite the fact that enough children already do not receive the recommended schedule to make such a study feasible). To support this point, it is claimed that the recommended schedule represents the most evidence-based approach. But like in Guinea Bissau, the schedule is determined first based on assumptions and tested after the fact. These tests do not always support the original assumptions upon which the recommended schedule is based.
A related example is that the WHO has recommended that babies receive a high dose of vitamin A at 6 months of age because it is believed that this will improve overall immunity. Peter Aaby's team was involved in research that found that giving the dose at birth not only didn't result in the expected 30% reduction in mortality, it actually led to a small increase in mortality. Our assumptions about how babies will respond to substances is not always accurate (I also have to wonder about the vitamin A that was given- it was probably synthetic, which is not used by the body the same way as natural vitamin A). Interestingly, what they also found was that this slight 7% increase in mortality was the result of gender difference. While boys seemed to benefit somewhat from the vitamin A dose at birth, it resulted in a 41% increase in mortality in girls. This was totally unexpected and put a halt to WHO plans to introduce vitamin A at birth to all babies in Southeast Asia. Perhaps more study into this effect will add to our understanding of differences in immune function in boys and girls as infants.
Peter Aaby's team has argued that their findings indicate that DTP lowers the ability of the immune system of girls to fend off other infections, and Christine Ben believes that the reason that vitamin A had such a catastrophic effect on girls when given at birth is because it amplified this effect. Her research was published in the International Journal of Epidemiology, but like other researchers who have found potential issues with vaccination or other preventative health measures, she found journals hesitant to publish her works for fear that the public would hear of it and question what they are told- that all vaccines are safe all of the time, for all children, and that the current vaccination products and programs are founded on entirely evidence-based science. When asked why the WHO is so resistant to follow up on his findings that DTP is harming girls, Peter Aaby responds that they are afraid that if it is found that DTP has a negative effect that it would be devastating on the global vaccination program. I personally think this is an artifact. If the current vaccine program was presented the public with transparency, as being the best we are able to do right now but that we are always searching for ways to make it better and safer, I still think there would be widespread support for the program. Because the program is based on trust, I think the thing that threatens it most is any behavior on the part of those who determine and administer it that they are hiding something or limiting research that could lead to greater safety.
Peter Aaby's work has opened up the question of gender in vaccine response. Vaccine studies have normally been done on men only because women are at risk of getting pregnant. Additionally, women's hormonal cycles are known to play a role in immune response and they didn't want this interfering with the findings. Animal studies also use just one gender. Kim Mullhulland, an Australian vaccine expert, says that the politics of vaccine programs and the need for public acceptance have made it hard to have a scientific discussion about aspects such as the non-specific effects that Peter Aaby's team is finding. He blames what he calls "anti-vaccine movements" for necessitating propaganda on the part of government health organizations in order to counter what he calls the propaganda of these organizations. Yes, there are some who do call for an end to vaccination entirely, but this is not a large and powerful group and it is laughable to think that they are determining public health approaches. The larger voices are not anti-vaccine, they are pro vaccine safety. They are groups that do not believe that vaccine safety is as simple as we are told by health authorities and the media. They are groups who want to see vaccination programs be as safe as possible for all children. It is absurd for Mr Mullhulland to suggest that we can't have a public discussion about making vaccines as safe as possible because there are groups who want to see vaccines be as safe as possible. The narrator also points out that this is a dilemma for the pharmaceutical companies (who make billions of dollars on vaccines per year) and large funders of vaccine programs, such as the Bill and Melinda Gates Foundation.
The question arises, that if vaccines and micronutrients such as vitamin A can interact with each other in ways we don't understand, how do we test all of the possible combinations for safety? Paul Fine, a professor at the London School of Hygiene and Tropical Diseases, is one of Peter Aaby's strongest critics and responds to this question that focusing too much attention on these "nonspecific" effects of vaccines could keep children from getting vaccines that they need to keep them alive. If it's true that giving vitamin A at birth led to a 41% increase in mortality in girls, and that the DTP is causing a significant increase in the mortality rate of girls possibly due to it's interaction with other vaccines, then it hardly seems that ignoring these findings is denying children the best outcome.
Additionally, he says "we're talking very soon about, even in developing countries, them receiving ten vaccines, but I would say here, one does need judgment, because it's too easy to say "oh we must first work out all the possible effects of all the possible combinations", but I think that would just lead to paralysis in terms of moving ahead. We can always increase the level of vigilance- no one is saying we want LESS vigilance". While vaccine programs in the developing world are not the same as those in developed countries, this attitude of set up the schedule first and then research (or not) later does seem to be something they share. He says we need vigilance, I am guessing as far as monitoring adverse events goes? I heartily agree with that. I think he does have a point that in developing countries, it may be prudent to balance fast action with research such that help arrives before it is too late. The WHO's reluctance to look further into Peter Aaby's findings does suggest to me that the level of vigilance here is wanting. This is another parallel with developed countries, in which monitoring programs are seriously lacking in vigilance and as such not picking up on potential problems.
Peter Smith, of the WHO's Advisory Committee on Vaccine Safety, says "you have to ask yourself the question, if this was your child, and it was participating in a trial that had been randomized to vaccine or placebo, and it had been very clear that this vaccine is protective against the condition that it was designed to be protective against, would you want your child to have that vaccine or would you want to maintain that child to be unvaccinated against the possibility of a non-specific effect which may be greater than the effect of the vaccine itself? I think those are very difficult public health questions in which it's not straightforward to answer".
The researcher Christine Ben raises an alternate version of the question- once research has shown an intervention to be harmful, does further study into it needlessly place the lives of thousands of children at risk? After her study was published showing such an astoundingly high rate of mortality for girls following a neonatal dose of vitamin A (and another retrospective study confirmed the findings), the WHO has commissioned three large studies to re-test the same hypothesis. While scientifically it is valid to replicate findings, when those findings involved such a high rate of death, is not unethical to attempt to replicate it? She estimates that about 30 girls died as the result of receiving the experimental early does who wouldn't have otherwise. Since the new studies are 15 times larger, does that mean that the lives of 450 girls are at risk in order to confirm or refute the findings? It's hard to see how this is considered ethical when a study in the developed world, of children who are already unvaccinated vs those who are fully vaccinated is considered so unethical as to be unthinkable? It sure looks as though the lives of children in developing nations are given less value.
There is one last similarity between the vaccination programs of the WHO in developing countries and the trials done in around that program, and the vaccination programs of developed countries, which is that of informed consent of parents. It turns out that parents of the children in the new studies are not being told about the outcome in Guinea Bissau that led to these trials. It is not considered relevant to them to now about the potential risk that participating in this trial is conferring on their daughters. Dr Ball of the WHO said "as far as the informed consent process is concerned, the families are given information in a way that they can understand- that is all the information that is relevant to be given to families...is being given to the families". He goes onto say that it is not possible to give the participants in the new trials information about previous trials.
Recently, 36 leading scientists from 12 countries collaborated to put together a research agenda to look deeper into the non-specific effects of vaccines. This agenda includes trials to review the safety of DTP as well as further study into why boys and girls seem to react differently.
