Monday 16 July 2018

More worms are needed!

Early last Sunday morning, I was responding to an e-mail and needed a reference to The Blob to save me re-writing one of my well-worn anecdotes. As a by-product to that search I came across a Trib to The Boy, who helped me declutter about 50kg of scientific papers when he was 'resting' between jobs 12 years ago. My offspring have told me quite clearly that they will pour rancid milk on my grave if I leave them a mess of papers to go through after I pop my clogs. Because I love the kids, I thought I'd wade through one of my filing-cabinets to see if I could simplify their post-mortem paperwork.  An hour later, I'd culled a xerox-box full [~10kg] of discards: Win!  I also found a paper that I've been hankering after since I started The Blob. Win! Win!

It's like with trying to Google a remembered article at the intersect between Beirut and cooking oil without getting lost in a storm of recipes from Claudia Roden. Well like my recent triumph about eggs and Sarajevo, throwing out the dross has surfaced some evidence for the hygiene hypothesis: that we are beset with allergies, eczema, asthma, lupus, psoriatic arthritis and other autoimmune diseases because we never meet pathogens as kids. The immune system, having been crafted over millions of years to aggressively fight infection, is incapable of sitting on its thumbs if there is nothing left to fight. I remember the paper "Trichuris suis therapy in Crohn's disease." because it was one of the most interesting which was discussed that year at the Journal Club which I coordinated at St. Vincent's Hospital. But I got some key data wrong which meant my google-hunt and pubmed-search lurched quickly off the tracks on which I was running. Crohn's Disease is no fun: Diarrhea, Fever, Fatigue Abdominal cramps, Bloody stools, Mouth sores, Reduced appetite, Weight loss, Anal [not St Martin's] fistula, Inflammation of skin, eyes joints, liver or bile ducts, Delayed growth or sexual development.

Trichuris trichiura is the human whipworm a nematode about 50cm long which inhabits the large intestine of about 1 billion people. Not you and me, because we aren't poor and black and living in the tropics without proper sanitary facilities. The adult whipworms, with their heads embedded in the gut epitheium have their arse end hanging out into the lumen of the gut into which the females shed 5,000 fertilised eggs a day. Some of which get into the food supply or on the shitty fingers of the neighbours. Those dispossessed people in the tropical and sub-tropical Third World are notable, not only for their load of intestinal worms but also for the comparative absence of the Diseases of the West: asthma, IBS, MS, etceterzema. It didn't take long for someone to put these two observations together to suggest a causal relationship between them..

The paper which surfaced in my filing 'system' is a nifty advance on the hygiene hypothesis into a testable experiment. No Ethics Board is going to countenance deliberately infecting sick people with a known and debilitating human pathogen. Therefore the team from U Iowa Medical School deliberately infected patients living with the Crohn's Disease [see IBD link above] with 8 x 2400 eggs from Trichuris suis the pig whipworm. It has long been known that whipworms are quite species-specific and T. suis just can't get established in the human gut or vice versa. Part of the reason for that is because the human immune system gives it a damned good alien drubbing and stops the eggs from hatching or, if they hatch, from getting a toe-hold in the wall of the human gut. The immune response is necessarily systemic: anti T. suis agents are released into the blood-stream and find their way to the gut. OR the ongoing immune response to Crohn's is diverted to combat the whipworm eggs and leave the intestinal epithelium alone.

Excited as I was back in 2005 when the paper came out, I'm a bit more skeptical now.
  • It's an open label trial (everyone knows the treatment that is being administered).
  • There are no controls - where, say, half the participants get a teaspoon of baker's yeast instead of the eggs
  • The sample is small - only 29 participants with an initial CDAI (Crohn's Disease Activity Index) greater than 220. Hey, you can calculate your own: +20 for anal fistula, +2 for each extra loose stool. The cut off between 'normal' and Crohn's is CDAI= 150; so >220 is definitely clinical Crohn's
  • It is still being cited in the Wikipedia entry 13 years on
Nevertheless, after 24 weeks of getting a dose o' whipworm every 3 week 23/29 patients reported a significant reduction in their CDAI and 21/23 were effectively cured.  It might be a life-time commitment because the study doesn't claim that the treatment has reset the inflammatory clock but that it a small price to pay for such a dramatic reduction in symptoms. Then again, it could be that, without a reset of the clock, eventually the immune system will get used to the whipworm eggs and return its attention to hacking blood out of the bowel.

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