MAP is something that I am convinced is directly related to the incidence of Crohn's Disease and/or other IBD disorders.
I am however totally unqualified in bacteriology or microbiology of any sort, never having studied biology formally in any way after leaving school. My sources of information tend to be scientific magazines as background (and nowadays Wikipedia), with online science websites, online papers and fora such as these for leads and more detailed in-depth discussion of topics.
My only personal experience with MAP - if indeed it was, and I have no evidence to say it was, other than circumstance - was that of childhood visits to my uncle's croft where both I and my sister drank unpasteurised milk from his cow Daisy, who subsequently became ill with a wasting disease, and was sent to slaughter. A farmer down the road at whose farm she stayed on occasion (Daisy that is, not my sister !) was plagued by severe gut problems and sickly cattle; I don't know about
the cattle but he was diagnosed with IBD, which in those days would have been about
as detailed a diagnosis as could be expected.
To discuss the points raised by Ankylos a little further:
My understanding is that originally studies that looked (visually) for MAP in humans were done by researchers who had done work with other species such as cattle. They were looking for MAP as found in bovine species, and found none. Later however researchers who did not have experience of MAP in cattle found that MAP tran****ed into another, much smaller form in humans (spheroblasts, if I remember correctly) and hid themselves inside a particular type of cell called macrophages. Later studies were able to isolate genetic sequences that could be sought for and presumably thus found in any spheroblasts but not bovine MAP cells, due to the unusually impermeable, waxy cell membrane possessed by the latter but not the former.
I am not conversant with all the different studies, but I know that microscopy studies did find as much as 90% infection rate by MAP in IBD patients once the smaller cells were being searched for. It is always worth noting that many studies in medicine are plagued by poor design, and most particularly, by low numbers of participants, which can skew the smallest of chance variation and make it seem significant; this is one reason that epidemiology is so valuable in this sort of debate. Mark you, 90% is still significant in any book - if replicated.
1) Leprosy, TB and MAP are all genetic relatives; in the case of TB so closely that generic tests for TB in cattle which show "false positives" may in fact be pointing out MAP. (One wonders how much of the long running and vitriolic debate about
TB in the UK, about
badgers causing transmission to cattle, based on these imprecise tests, is based on false premises. It is known there is widespread presence of MAP in wildlife, watertable and soil.) I believe the reason that TB tests are done pre-TNF therapy because latent TB (which can lurk unseen for decades, a la MAP) once no longer actively opposed by the host's immune system, may run riot and cause irreversible damage.
The mechanism by which TNF therapies work is fairly well understood; they aim to reduce or short-circuit the inflammatory process which leads to increased Crohn's Disease activity. If these therapies are preventing or more likely reducing the creation of macrophages which are the habitat of MAP spheroblasts and which MAP needs in order to transform/reproduce/ or create an inflammatory habitat, then this explains why MAP would not increase dramatically in the same way as diseases using other mechanisms might - eg, TB. (This is all presumption, I am not sure how much evidence there is for this argument as I've never studied it in detail.)
2) I cannot remember where I saw this information, it was YouTube but not perhaps Dr Behr, but my belief is that MAP of a different subspecies (clade) has been found in bovine species such as buffalo, as well as ovine species (ie, sheep, goats, etc). This makes it pretty likely that there will be MAP in species endemic to Africa; not to mention, in the wildlife. (It is extremely widespread amongst mammals in the UK, as would be expected of a slow-acting pathogen with a normally small effect on the ability to reproduce successfully.) So there may be as yet unrecognised reservoirs of MAP that are less effective in infectivity and the lower incidence of CD may be a reflection of both this, and differences in diet - having a diet high in processed carbohydrates is hypothesised to have caused the huge rise in Johne's Disease that suddenly occurred in cattle in the latter half of the 20th century. If a diet high in simple starches/sugars does cause changes in gut mucosa or intestinal flora that predispose towards MAP becoming more infective, this would explain a lot - although an individual's genetic makeup is still obviously important, in humans at least.
3) As regards Australian states' incidence of MAP, I know nothing, so cannot add anything other than speculation. The genetic component will in theory limit the number of potential cases to a lower number here, compared to say the UK. My guess is the testing is poor, and MAP is taking advantage of the Westernised diet to cause IBD.
4) This question is the crux of the matter. Again, personally I have little detailed information on the effectiveness of these therapies; I know trials exist and are reputed to have high remission rates, and that is all. I haven't been able to find any data on long term outcomes or numbers in trials (very much a crucial part of any such trial; below a given number it is worthless statistically) but I can certainly hazard some guesses which are dismaying if true.
a big if ) MAP does cause a slow burn infection of the sort that TB was once famous for, and has a similar sort of cellular membrane in non-spheroblast form (another big if), then it would be as difficult to eradicate as TB used to be before the famous triple therapy that finally put all the sanatoria out of business. This is because for any drug regime to be totally effective, it would have to target two different types of cell physiology. The waxy cell membrane that TB has makes it very unusual; lots of substances simply cannot get through, making it hard to detect or kill - stains and antibiotics never used to interact with it, only once its intricacies had been fathomed were weapons found - but the cost is a relatively inefficient metabolism and slow reproduction. This means - yes, you've guessed - it takes a long time to totally wipe out MAP if there is widespread infection by this sort of cell as well as spheroblasts in the macrophages. Even assuming a treatment regime that attacks both, macrophages have a short lifespan, and are constantly being renewed; so any period where drug attack is less than 100% effective will provide a window for escapees to reproduce and find new hiding places. The good news here is that genetic variability is likely to be low due to the slow reproductive rate and the unusual cell membrane. But it is worth remembering that even today, many years after a "cure" for TB was found, there are people with latent TB who had it so deeply entrenched in tubercules, often in the brain, that it could never be eradicated, and they were simply put onto the paperwork as latent carriers; and occasionally they find the TB flaring up. Personally I think a bacteriophage is the best hope if such an infective agent is responsible for Crohns. (
Don't hold your breath, this wouldn't be nearly so profitable as drugs at $10 000 a pop.)
4) I may be delusional, I believe that I control my Crohn's by diet ! But
control is not cure; far from it. In fact I wouldn't even say that it is full control. What I feel is happening is a balance of power between my immune system attacking a pathogen (wouldn't we all love to know how it does that! ) and the pathogen hanging on and occasionally gaining ground. It is noticeable that whenever I take too much exercise - which in excess has been found in athletes to cause a depression of immune system activity - I not only suffer from severe fatigue similar to athletes "burnout", I also have a marked resurgence in CD symptoms which is virtually simultaneous. Going back to the theory regarding high carbohydrate diet, it is also very obvious to me now that I am on a low-sugar diet that one of the worst things I can do for my CD is consume large amounts of sugar, as I once used to do without a second thought.
And every so often, even when I seem to be eating exactly right, and not overdoing things, and being a good boy, I still find my Crohn's flaring up. I can find no earthly reason why, it generally doesn't last long, but it is very demoralising when it happens and a reminder that stalemate is not control, never mind a cure; in fact, the disease is controlling me as much as the other way around.
The nutritional therapy that I was put on, which has twice led to impressive improvements, emphasised the importance of rebalancing the acidity of the stomach to minimise damage by pathogens and improve digestion, and improving intestinal flora and macronutrient intake for the same reasons. As Ankylos says, MAP may be a secondary infection, as may be many other as yet unidentified agents. It might even be that a single plasmid is to blame, and its presence is spread between not only clades but entire species, so that E.coli with a particular snippet of DNA cause the same sort of damage as C. difficile with the same gene. My personal inclination is to use Ockham's Razor and say that MAP has too many handy coincidences involving it to not be at the heart of things - but who knows, maybe it carries an infectious passenger, in the same way that cholera is carried within another bacteria in sea water...
Finally, if I remember correctly, dairy workers have actually been found to have a particularly low
incidence of CD. This is actually one of the things that led researchers to look at cattle; often prior exposure to proteins or partial organisms belonging to a pathogen or its relatives causes partial or enhanced resistance to the disease it causes. (Think cowpox and smallpox.)
I think we need fewer drug tests and more basic microbiology. But hey, what do I know, I'm an unemployed labourer ? !