From: odp@ldgo.columbia.edu (carl brenner)
Newsgroups: sci.med
Subject: Re: Yet another Lyme question
Date: 28 Sep 92 18:28:52 GMT
Organization: Lamont-Doherty Geological Observatory

In article <1882@hsdndev.UUCP>, rind@binoc.bih.harvard.edu (David Rind) writes:
> In article <1992Sep27.172718.11900@lamont.ldgo.columbia.edu>
>  odp@ldgo.columbia.edu (carl brenner) writes:
> >In article <1877@hsdndev.UUCP>, rind@binoc.bih.harvard.edu (David Rind) writes
> >> >> Neither of these papers discusses relapse rates.  
> >	This thread got started when someone else (not me) said something
> >about a 50% failure rate.
> 
> Again, a failure to prevent late sequellae is not the same as a relpase.
> The paper in question did discuss failures of this sort (though nowhere
> near 50%).   The distinction matters.

	Yes, it sure does. This is the $64,000 question in Lyme research.
One side says "relapse" and the other says "sequela." Neither can prove
their case conclusively, though the growing number of papers and abstracts
on culture-confirmed treatment failures, and the emerging data on
intracellular localization of the spirochete, have led me to go from
the latter group to the former.

> In dealing with
> an infectious disease, in the absence of empiric evidence one way
> or the other, seeing *relapses* would be strong evidence that longer
> courses of treatment are needed.  This is not true for late sequellae
> which may or may not be altered by longer therapy -- only a trial
> of different courses of antibiotics could answer that question.

	I urge you to apply to NIH for a grant to do just such a study.
(Though, I think we'll end up measuring efficacy rather than actual persistence
of infection. As I mentioned earlier, there are a few studies showing
that the spirochete has survived long term, high-dosage therapy in some
people. In any case, the study you propose would certainly be valuable
just to determine whether treatment is worth it even in cases like this.)
	Studies have been done along these lines by several clinicians, but
they're by definition pretty empirical, because you can't really measure
persistence of infection. Most academic researchers dismiss such studies
as anecdotal, and they are. But I think they should be aired in any case.

> >	The control group never had Lyme.
> 
> This was what I was concerned about in the experimental design.
> PCR is so inordinately sensitive, that any contamination of the
> CSF (perhaps by blood as the needle went through skin) might
> cause a positive PCR result.  The study might be more convincing
> if the controls were people with Lyme who clinically did not seem
> to have had CNS dissemination.  Otherwise, how do you know that the
> DNA being detected is really coming from the CSF?

	Gee, contamination like that sounds pretty contrived to me, but I 
guess it's theoretically possible. Also, I'm not convinced that your proposed 
control group in fact exists; by the time folks get sick, the organism may very
well be in the CSF. 
	If we do this study, and the controls are positive also, it could
be interpreted as either evidence of early invasion without symptoms *or*
contamination along the lines you've suggested (which assumes dissemination
in blood without CNS penetration). If the controls are negative, then we've
learned something.
	Afterthought: you know anything about Treponema? Do syphilis
spirochetes hang out in CSF during "dormant" periods?

	If you're interested in these questions about persistence of
infection, you might want to give Paul Duray a call. He's a pathologist
at Brigham and Women's, and has done autopsies on Lyme patients. I believe
he's stained spirochetes from the tissues of dead Lyme patients who were
on extended antibiotic therapy before dying.


> -- 
> David Rind
> rind@binoc.bih.harvard.edu

 Carl Brenner
Xref: sparky sci.med:18634 talk.politics.misc:49873 alt.activism:17227