Monday, 10 March 2014

Clostridium damned difficult

Clostridium difficile was being written up again last week in Nature.  It's an awkward sort of a microbe: difficult to diagnose, difficult to culture in the lab, and a serious killer to boot.  Ordinary folk don't even know how to pronounce the specific name:  a ploddy diffiseel ? a pedantically sounded final e diffisil√© ? a florid italinate diffeechilley?  Most of us, including wikipedia, give up and call it C-diff.  It's interesting because it is somewhat opposite to Marshall and Warren's H.pylori, which can be cleared up pretty damned quick with a short course of antibiotics.  Gonorrhoea used to be similarly amenable to treatment until we squandered our augmentin on pigs and as growth promoters in chicken.

C-diff on the other hand usually springs up to kill after a short course of antibiotics has shifted the balance of power in the gut to allow this minor (<2%) player in our intestinal flora to foment its revolutionary take-over.  C-diff is indicated by a watery diarrhoea with a distinctive odour, fever, and a recent course in antibiotics. It is a classic iatrogenic (doctor induced) nosocomial (hospital acquired) infection, far more common in places for healthcare than in the outside world and often induced by medications which suppress acid production in the stomach (hello Tagamet). It makes you think that having a gastric pH not far off that of car-battery acid might not be primarily about digesting food but rather for digesting pathogens before they get access to the goodies further down the tube.  And once you've got C-diff in spades, it's really hard to shake off because it is resistant to so many of the antibiotics - that's presumably why it is triggered by a course of these drugs administered for something else.

In teaching Food and Fermentation Microbiology this last year (great fun!!), I've tried to encourage the students to use their noses, which can be pretty accurate diagnosticians.  You know how domestic trash has a really distinctive smell which is different from toilets which is different from pig-slurry. After 5 days without a fridge during the last power-cut, my sour-dough starter developed a worrying smell of acetone with overtones of esters (pineapple, pear-drops, hint of jasmine to a better nose than mine).  It was still full of oomph for raising bread but the product was very sour.  So I'm still dithering about throwing it out and getting fresh start from a neighbour.  Needless to say (the young of today - harrrumph) the students refused to engage and skittered about the room squeaking girlishly holding their noses - some literally.  I'm sorry to use "girlishly" but you know what I mean and the boys were worse than the women.

But as with so much in our scientific world there is a three-letter acronym (TLA) in the wings which is showing great promise for forcing Cthulhu-diff back into the cellar and shutting the trap-door on it: not to wipe it out entirely but to allow the other denizens of the dark to keep it under control.  FMT is faecal microbiota transplantion and it works on the old principal "Eat shit, a trillion horse flies can't be wrong".  Of course, science tries to make it more sciencey than that and to make it more uniform and reliable but the idea is to deliver an aliquot of microbes from a healthy gut into the intestine which is infested with C-diff: by nasal tube or from the other end by enema or colonoscope.  This is rather humbling: the intestinal flora is comprised of about 200 trillion cells from maybe 10,000 different species, and we have less idea about how they function and interact than we do about the animals than cavort and copulate and kill on the plains of the Serengeti.  Despite not knowing how it works, we now cannot deny that work it does. A year ago the first randomised controlled trial of this therapy was wrapped up early because those receiving FMT were twice as likely to have their symptoms resolved and it was deemed unethical to continue giving the crappy no-crap option when the crap option was clearly better.

The FDA is now scrabbling to get its regulatory act together to allow this therapy before C-diff kills its annual quota of 14,000 US citizens and a pro-rata equivalent of Europeans.  BUT we don't want to repeat the errors of the Blood Transfusion Board which developed and delivered a new therapy for hemophilia which, because it was badly thought through, contrived to infect 300 misfortunate bleeders with HIV.  So regulation is probably a Good Thing if only because it might "reduce the demand for risky at-home procedures" (!?).  Also because we know so little about how the human intestinal flora works, we want to be careful that we don't leap from the C-diff frying pan into the, as yet unknown/unnamed, C-death fire.  The whole story is freely available at Nature.

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