There is germaphobia, the fear of germs. Or Germans.  One of the two. Oddly, I do not fear most germs, despite my daily reminders as to how destructive these wee beasties can be.   I recognize their limits and my immunologic strengths and know I have more to fear from cars or unsaturated fats than E. coli or influenza.

There is also a fear of vaccines, the too many too soon that is said to be at the heart, or maybe the left atrial appendage, of one of the imaginary problems with vaccines.  There are, by my counting, 5 live attenuated viruses and 21 different antigens in the vaccine schedule by age 6, for a total of 26 or twice thirteen.  Some fear those antigens and viruses, making it a  triskaidekaphobia times two (1).

From my perspective the paltry quantity of antigens children receive with the vaccine schedule are, when compared to the enormity of antigens in the environment, a rounding error.  We are awash in bacteria, fungi, viruses and an enormous number of environmental organisms.  I think of each of us like Pig-Pen, but instead of dirt, we are in a cloud of micro-organisms.

Our immune systems, contrary to the opinions of the unimaginative who direct scorn and derision at Dr. Offit, can cope.  As discussed, we have a ability to stave off the phenomenal number of organisms that would just as soon use us as the ultimate supersized meal.  Of course, it is not all the immune system that keeps the wee beasties away.  Being warmer than ambient temperature helps.  Understanding disease epidemiology, hygiene and the prn malum q 24 h also keeps the doctor away.Hygiene is an interesting two edged sword, and the rule in medicine is that no good deed goes unpunished. We are cleaner, at least in the urban industrialized wWest, than  most people through most of history.  Exposure to a large assortment of environmental filth and germs, with the exception of my 13 year old’s bedroom, is rare.  Cleanliness has helped to decrease the spread of contagion both in the community and in the hospital, at least for those who believe in good hand hygiene (2) and sterile technique.

However, lack of exposure to the background microbiology has had a potentially interesting downside.  Several epidemiologic studies have demonstrated an association between, to put it crudely, increased cleanliness and an increase in asthma and atopy (3).   The NEJM had a recent article with a similar result,  Exposure to Environmental Microorganisms and Childhood Asthma. From my perspective, this link between cleanliness and allergic disease  is interesting, but not what I want to focus on.  An interesting suggestion of this study is that, while you cannot boost the immune system, evidently the immune system needs a good microbial work out as it develops to ensure proper functioning as an adult.  Not only is the infants immune system able to process and react to a mind boggling number of antigens, apparently it needs to be exposed to these antigens in childhood for optimal function.  The motto ‘Use it or lose it’ applies to B cells as well as biceps.

In the NEJM study they surveyed the bedding and dust for microorganisms in the environment of children who live on farms and those that live in an urban environment.  They did both microbiology counts and molecular methods to evaluate the number of organisms in the environment.

Kids on farms live in a haze of bacteria and fungi at levels far higher than their urban counterparts and to their benefit. Organisms isolated included

“Listeria monocytogenes, Bacillus licheniformis and other bacillus species, corynebacterium species, methylobacterium species, xanthomonas species, enterobacter species, pantoea species, and others. …Staphylococcus sciuri and other staphylococcus species, salinicoccus species, macrococcus species, bacillus species, jeotgalicocus species, and others. …eurotium and penicillium species”

I no longer feel  as bad about the time my son was playing in the dirt, flipped a rock over and, before I could react, ate the slug he found underneath.  He was just exercising his young immune system. The NEJM study only evaluated the microbiology of the inside environment; there was no measurement of the larger outside environmental community.  I would imagine the number of organisms outside the home dwarfed what they could find inside.

As the accompanying editorial notes

“… that newborns begin to be colonized by microbes at birth, coincident with a period of rapid development of the immune system and lungs. These symbiotic organisms can be beneficial (e.g., gut bacteria that synthesize vitamin K) or pathogenic, or they may have no effect on the host (commensals). The authors propose that microbes found on farms adeptly stimulate innate immune receptors in early life and thereby favor the generation of regulatory T cells that promote immunologic tolerance.”

and the results are limited by

” microbial diagnostics provid(ing) only a low-resolution picture of microbial identity and diversity.”

There are far more wee beasties in and on us that we can currently identify. Farms, I would wager, are filled with far fewer bacteria than the environment in which pre-industrialized humans evolved.  Too many too soon runs counter, as does much of what is understood by antivaxers, to reality. When you are young, you can’t get enough.  The early immune system is the Johnny Rocco of the body (4).

The world is a crowded place at the level of the microorganism and we have evolved to respond to that crowding from birth.  Not just respond, but we need to be exposed to these antigens.

“Nothing is unnatural – just untried.” ~Rita Mae Brown

It may be argued that vaccines are not natural, whatever natural is.  I am the result of natural selection, so is not everything I do natural?  Infection with a needle is not how bacteria, fungi and virus get into the body.  I suppose this is a group of people who never had a percutaneous injury with a splinter or a cut from a thorn or a child who did not skin their knee on the dirt.  Percutaneous inoculation is a common way to be exposed to environmental antigens, just not as safe a way when sterile technique is avoided.

One would wonder if vaccines, in our ever so clean modern environment, could not only protect against the plagues of the past, but be a surrogate for our former environmental exposure to microbial squalor?

“adolescents having been vaccinated (n = 694) had a significant lower risk to suffer from asthma or atopic diseases than non-vaccinated adolescents did (n = 24) [odds ratio (OR) = 0.30; 95% CI: 0.10, 0.92]. The relationship did not depend on the disease against which the vaccine was used as prophylaxis, the observance of the vaccination schedule or the number of inoculations. A higher protection was observed in the case of live attenuated vaccines (oral poliomyelitis and bacilli Camille-Guerin; OR = 0.26; 95% CI: 0.08, 0.83). These results, in agreement with previous ecological data, support the hypothesis that early vaccines could promote Th1 proliferation in response to the infectious agent contained in it, which inhibits the enhancement of atopic manifestations. Further studies are needed to confirm the phenomenon.”

None of the above is  rock solid information when applied to vaccines, but an intriguing curiosity and, perhaps, hints about into disease etiology, but interesting when considering the potential responses of children to vaccines.  Too many too soon?  Doubt it.  Just enough, just in time?  Maybe.  Consider that receipt of MMR on schedule has been associated with decrease in autism.  I, of course, do not know what causes autism.  I had thought that the MMR results could be explained by lack of protection to neurotropic virus in the unvaccinated, but now I wonder.  There are articles on autoimmunty as a factor in autism, way beyond my current knowledge base . I will defer to others on the validity of these studies, I note them with interest but no deep understanding.

I think all human disease has, at its core, an association with infections. Most of the microbial studies on autism have concerned the use of antibiotics to treat the disease.  Autism rates have increased along with the expanded vaccine schedule, increasing cleanliness, global warming and the decline in pirates. The Amish do not get autism and they don’t live in a (relatively) sterile urban environments, and use a horse and buggy for transportation.    There must be a association in there somewhere that is actually causal. I know, probably not, but play along at home.

Let us  speculate: It would be ironic if  someday it was determined that part of the etiology of autism is, like asthma,  partly due to our microbial free environment and subsequent immune dysregulation and that vaccines, by supplying a surrogate immune stimulation, are protective.  Those who fought vaccines as a cause of autism turn out to be partly responsible for autism’s spread.  Truly worthy of  Medical Hypothesis, I admit, but it is amusing to speculate.  Someday science will sort it out.

It is fun to think about possible ramifications of the current literature.  I would certainly not use the speculation as a basis for my practice or to develop a therapeutic or preventative intervention with an exclamation mark. Hmm.  Or should I? I need to patent  a neonatal and infant probiotic  autism prevention supplement (NIPAPS!) containing the correct proportion of live and killed naturally occurring environmental bacteria and fungi.   There is a fortune to be made if I can just get rid of my ethics and morals.

Rationalization.

(1)  Not certain what ancient Greek for ’26′ would be.

(2)  Stay away from the Atlanta VA ICU. http://www.medscape.com/viewarticle/737884

(3)  Sorry.  Just epidemiology.  No gold standard, randomized, placebo controlled, blind trials utilizing the hypothetical/deductive technique, so ignore everything that follows. I am a snot.

(4) Johnny Rocco: Well, I want uh …
Frank McCloud: He wants more antigens, don’t you, Rocco?
Johnny Rocco: Yeah. That’s it. More. That’s right! I want more antigens!
James Temple: Will you ever get enough?
Frank McCloud: Will you, Rocco?
Johnny Rocco: Well, I never have. No, I guess I won’t.
~ Key Largo