studies

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Dosing

I was thinking about worm dose and efficacy. (Brace yourself; this is
long and convoluted.) If one were to be dosed once with 10 larvae,
then accounting for attrition, there would be perhaps 7 left in the
gut. (And this number may be a high estimate.) Assuming a 50% gender
split, there would be 3 or 4 males. (And there could be 2, 1.) This
Cornell transcript claims the males die off after copulation.
(http://www.cumc.columbia.edu/dept/ps/2007/para/old/transcript_02_pd02.pdf)
Even if they don’t, this paper claims the lifespan, though averaging
3-5 years, is really much shorter than that.
(http://www.jimmunol.org/cgi/content/full/173/4/2699) Would 3 or 4
worms be enough to maintain a steady immunological state? How many
months/years would they live and would there be an average drop off
around the same time? (meaning; do they all die at once?) As
Nottingham is only studying their Crohn’s patients for 6 months, they
will not collect this data, which is unfortunate. (length of
efficacy, worm lifespan, wormcount after x number of months/years,
timing of necessary reinfection, etc.) So we’re on our own…

This study says that adding a population of 50 in two healthy people
who hosted existing hookworms resulted in some old worms dying and new
ones replacing them, with no netted increase in number.
(http://www.ncbi.nlm.nih.gov/pubmed/17035088) So for these two
people, adding worms at a high, one time dose, didn’t result in a
greater population. What the paper doesn’t address is age of the
worm. How many new worms replaced the old? Would one end up with a
mixed age population? That should extend efficacy, assuming the new
ones live longer than the first cohorts. (Some worms would be old
crones…surrounded by fresh whippersnappers.)

It seems like the only choice to maintain a healthy, thriving
population is to redose periodically, with a small enough number not
to illicit enough of an allergic response to expel the new or old
population. What is the number before adding becomes displacing? If
one started with 10, was left with 5, added 15, they merely displaced,
then one is left with 5 again. Would adding 2 be more effective?

And then I wonder how much of the acquisition of new larvae is part of
the immunological puzzle. If there is an additional, temporary
benefit from each subsequent infection, ( the bounce, or the “hookworm
high”) then perhaps maintaining both the immunological and
psychological health of the human and an effective worm burden is
based on the constant periodic addition of small numbers of worms.

Which means the patients who get one dose only are incomparable to the
ones who get 3 doses, who are incomparable to Jasper, for example,
who’s had multiple tiny doses. Perhaps his efficacy would have
waned if a small, steady population wasn’t supplied?

If there is a psychological component to small reinfections, along
with a temporary immunological benefit, perhaps man evolved to have
this periodically. Sort of a natural antidepressant to go with the
immune regulation. This study finds antidepressant qualities in the
soil bacteria itself
(http://www.medicalnewstoday.com/articles/66840.php), showing even
greater depth to the whole hygiene hypothesis. Depression as a
consequence of our sterility. We may need not only the worms, but the
soil they came from.

Which means trying to recreate the natural state by supplying one
aspect of it; the worms, in an unnatural dose (one time, a great
number) and removing everything else may not work. What is the
natural number and frequency of infection in the wild for a healthy
adult anyway?

This really argues against a one time inoculation, at least based on
the theory that the worms’ benefit will last as long as they are
alive. Yet it also argues against multiple inoculation therapy, as
that might cause one to end up with the same amount as one began with,
or less. It seems the only way to recreate the natural state is to
add 1 or 2 worms at a time.

There are no answers to any of these questions yet…Will we die
before we learn how to properly live?

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http://www.cumc.columbia.edu/dept/ps/2007/para/old/transcript_02_pd02.pdf

A little more information about hookworms and the hookworm eradication
project…

Is this true about the males? That they detach after mating; I wonder
how the life cycle would continue then.

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Two patents on helminthic therapy:

http://www.wipo.int/pctdb/en/wo.jsp?IA=WO2006%2F014907&WO=2006%2F014907&DISPLAY=\
STATUS

http://www.freepatentsonline.com/EP1749534.html

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Worm proteins injected intraperitoneally (shot in the abdomen) ameliorate colitis in mice.

http://www3.interscience.wiley.com/journal/121530207/abstract?CRETRY=1&SRETRY=0

“Conclusions: Treatment with proteins of S. mansoni and A. caninum ameliorated TNBS-induced colitis in mice. S. mansoni proteins increased mRNA expression of regulatory cytokines while suppressing expression of proinflammatory cytokines. Therefore, we suggest a therapeutic potential for helminth proteins in the treatment of IBD.”

This is probably the way helminth therapy will go. A shot every 2 weeks in the abdomen. No icky worms to think about. All sterile and in a nice box in the fridge. No worries about worm death…I wonder if it will hurt as much as Humira…

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One of the things those with Crohn’s disease ponder is the relationship between MAP (mycobacteria subspecies avian paratuberculosis) and helminths. MAP is one of the infections that some people think causes or contributes to Crohn’s, as it is abundant in our milk supply, survives pasturization and is very similar to Johne’s disease, which is basically Crohn’s in cattle.

The depressing thing about MAP, is like most mycobacteria, it is exceptionally hard to kill. Triple antibiotic therapy, usually for a course of many years, is required, and it is similar in leprosy in that one may never eliminate the infection, as it is even slower growing.

So how would helminths alter an existing infection? I was just reading Weinstock’s and Elliott’s patent on all use of helminths for all autoimmune diseases, and it mentions in the mouse model, that those mice infected with an existing mycobacterial infection, given helminths, have altered response to that infection:

“The immune response to helminthic parasites promotes Th2 responses to unrelated antigens. Infestation with helminthic parasites, which all induce Th2-type inflammation, can modulate the Th1 immune response to unrelated concomitant parasitic,
bacterial and viral infections (Kullberg et al., 1992, J. Immunol. 148:3264).

Animal experimentation supports this contention. Mice infected with Mycobacterium avium develop chronic Th1-type granulomatous inflammation in the lungs and liver. Splenocytes and granuloma cells from these infected animals normally produce
IgG2a and IFN-γ, and no IL-4 or IL-5. However, mice infected with S. mansoni after the establishment of Mycobacterium avium infection form mycobacterial granulomas containing eosinophils. Also, splenocytes and granuloma cells from co-infected
mice secrete more IgG1 and much less IgG2a. The cytokines released from these cells both constitutively or after mycobacterial antigen stimulation include IL-4 and IL-5, and much less than normal quantities of IFN-γ.

Th1 responses promote IgG2a production, whereas Th2 reactions enhance IgG1 and IgE. FIG. 3 shows that mice infected with M. avium have high serum IgG2a levels. Yet, co-infected animals have normal serum IgG2a concentrations, but increased IgG1
and IgE levels.

These data taken together show that a Th2 response to a helminthic infection can down-modulate the ongoing host response to even a strong Th1-inducing organism like M. avium.”

For those of us possibly infected with MAP, helminth infection should down-modulate the immune response. At least according to this patent.

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