lyme disease problems?

I am working on a javascript program to help neurolymies process information they find on the internet (convert paragraphs into sentences).  This has a somewhat lower priority than trying to repair the catastrophic engine failure my car has experienced, but I may work on it during breaks.

Summary

On 10/14/2009 during a hiking trip through the West Point area of NY state, I removed a tick from my body (probably within 24 hours of being bit) that had a bright red circle around it (see picture).   It was one of about 200 ticks that I removed during an intense 5 day portion of a longer hike, and the only one that I know of that had a circle around it.  The circle cleared after 2 days with no associated fever  The only possibly relevant symptom that I noted at the time, was a reduction in my stamina level for the rest of the hiking trip (another 2 weeks of easy hiking with a 70 pound pack).   Because of the rapidity of both circle appearance and clearance, I believe that I was exposed to a pretty high dose of lyme, and there are 2 possibilities:

1)      Someone slipped me some doxy within 1 day of exposure.  I had run out of both food and water, and was simply surviving off of about 400 calories worth of food handed out on the trail, and drinking lake water.  The doxy would have also worked against giardia (http://aac.asm.org/cgi/reprint/33/12/2144.pdf). 

2)      I was already vaccinated against lyme via a benevolent tick carrying an antigen but not the whole organism, and my body was primed to clear it.  I consider this less likely, as my dog proceeded to get sick, but still possible because I do a lot of work with animals, and I’m guessing that these benevolent vaccines are around. ( Edited: 4/10: I’m  going to rule this possiblity out, on the basis of the titer and Western blot results.)

My dog (34 lb), who was with me on the trip, tested positive for both lyme and anaplasmosis on 11/10/2009.  He was anorexic and lethargic.  His platelet count was 25K – he would have been boosted if it had dropped lower.   He was treated with a 6 week course of doxy (100 mg/2X a day), and recovered, although I believe that he is still not 100% (he kind of just wants to hang out).

About the same time that my dog was being treated with doxy, I noticed that I was having problems reading a map.  Straight lines were wavy, light was being scattered, it was harder for me to see in low light, and there was blurriness (that was correctable with $1 glasses from the dollar store).

On 1/20/2010, I saw a retinal disease specialist who took pictures of my eyes, and documented bilateral optic neuritis, and uveitis (inflammation) secondary to a hemorrhage in the right eye.  This was treated with steroid eye drops for 4 days, and the vision problems resolved.  I was also tested for TB, herpes, HIV, syphilis, and lyme.  The only abnormal findings were 2 indeterminate bands on the lyme Western blots (the p41 band on the IgG Western and the p66 band on the IgM Western).  Both IgG and IgM lyme titers were negative.  The p41 band (flagellin (http://jmm.sgmjournals.org/cgi/reprint/36/3/209.pdf) is the first band to appear according to Burrascano. (http://www.ilads.org/lyme_disease/B_guidelines_12_17_08.pdf).  It is of note that it is not present in the IgM Western, and therefore indicating a possibly non-flagellar form of the disease or a coinfection.

The way a western blot works is that the lyme proteins are first run out on a gel.  The gel is then soaked in the human antibody portion of the blood of the individual suspected of having lyme disease.  These antibodies will find and bind to the band in the gel that is specific to the antibody.   The gel is washed so that all non binding antibodies go away.  Then the gel is soaked in antibodies that recognize human antibodies. 

So what does an indeterminate band mean.  It means that there was a little human antibody from a past (not recent) reaction in my blood bound to the flagellin band (p41).  Little antibody bound could mean a few things:

1)      Because of the recentness of the exposure, little antibody is present.

2)      Because all the lyme is sequestered in a certain cell type, little antibody is present, and what is present is completely bound to whatever cell type the lyme is in.

3)      Another antibody to a different bacterium that also has flagellin, but a slightly different sequence, is being produced.  This antibody has a lower affinity for the B. burgdorferi flagellin, but a high affinity for the flagellin of the organism that I am infected with.

4)   Trivial explanation.  All signals have noise.  Reading a band is finding signal (a peak) in a certain place against a background of noise.  So, the height of the peak becomes significant.  The gel was run twice in my case.  So one would look at the probability of having 2 events "gels" occur at x standard deviations from the noise in 2 trials.  Statistically, quantifiable odds.

If we knew the organism, and ran that on a gel, it would light up like a Christmas tree on a gel.

So, how to proceed?  Well, the smart way low-cost way, would be to have a panel of organisms with known cross-reactivities to antibodies.  But antibodies are different in different people.  The antibody that I make to a lyme protein, may not be the same antibody that some other person makes. 

So, the most definitive way to proceed, is to run the gel again, cut out the band that has the faint reactivity, and run this through a mass-spectrometry sequencing reaction.   Once the idiotype is known, you then clone the antibody, couple it to a column, and then run a sample of your own blood through the column to see what it pulls off.  Since we know it has flagellin, we can assume it is bacterial, and culture the blood to enhance the signal (since lyme is spread through the blood (with tick bites), PCR of blood should detect it, and it should be possible to culture it).  If nothing comes up, we could try lots of known organisms to see what binds, and finally, if that is negative, collect lots of ticks from the West Point area, sort them, grind them up, and run those over the column.  (Of course, as with many parasites, the organism may not present in the tick host, the same way that it does in the mammalian host.)

Once we have something that binds, and then can be eluted off.  We can sequence it, and check the sequence.  From a clinical point of view, culturing the blood should allow antibiotic sensitivity to be determined.

Distinguishing between 1) and 3) can be accomplished by titering the antibody on the Western, and enhancing the binding conditions of the Western (longer reaction time, lower wash time, more favorable binding conditions (temperature, salt, detergent).  The point is to distinguish a low amount of antibody with an association constant of 10^9 M-1 from a higher amount of antibody with an association constant of 10^3 M-1, and to pull up associated bands if present.  A 3-D grid screen, for temperature on one axis and concentration (log scale) or pH, would allow 9 to 25 conditions to be screened to try to improve the signal on the gel.  This could be done in a calculated way for the known antigen using for example a titration calorimeter to determine the enthalpy and heat capacity of the reaction (lets you know which way the affinity will vary with temperature) (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2581910/ ).

I am hypothesizing that antibiotic cleared most of the lyme initially, but that some is present in my body in either the cell-wall deficient form, or in a cyst-like form.  Lyme disease like many tick-borne diseases is apparently associated with lowering of the platelet count, and this might be responsible for the hemorrhage in my eye.  Although I am a type 1 insulin-dependent diabetic for 40 years with severe background diabetic retinopathy, the timing of the hemorrhage is notable.  It is possible that a small hemorrhage from diabetes probably constantly present, allowed lyme or an  associated coinfection to leak into the eye.  This may have then lowered the platelet concentration locally, producing a more significant hemorrhage, leading to more agent in the eye.  The existence of inflammation in spite of the immune privilege usually associated with the eye is of note (http://www.karger.com/gazette/64/streilein/art_2_0.htm).  High blood sugar is likely to exacerbate the lyme disease if present since bacteria thrive off of sugar.

Finally, I note 2 additional possible flare-ups since the tick bite.  About 1/1/2010, a short, not too horrible bout with flu-like symptoms (I am very rarely sick).  More recently, about 3/20/2010, a painful hip problem with no explanation that resolved for 24 hours with 1000 mg of aspirin and that I treated by tapering the dose of aspirin for 5 days until it disappeared.  This hip pain (3 on a pain scale of 1-10) kept me from being able to sleep as it intensified when I lay down or sit down.  It almost disappeared with exercise.  It started in the lumbar region (probably L1-L3), and extended to the outside of the hip over the iguinal ligament, and then down to the lesser trochanter, radiating medially, anteriorly, and distally from the hip.  Applying pressure at the iguinal ligament or in the lumbar region of the spine alleviated the pain.  This problem that resolved with no apparent consequences, occurred about 4 months after I subluxated this hip in an injury (ranked a 10 on a pain scale of 1-10) that completely healed in about 2 months with my applying hand pressure to the hip as I walked (after repositioning the hip), and being very careful how I walked (slowly, heel-to-toe, no outward movement). 

So, I think to summarize:

1)      Highly probable lyme exposure with sequelae from the spirochetes evolving from cysts or cell wall deficient strain (http://www.lymebook.com/top10forms).

2)      Wait for probable flare up to retest and improve band analysis.

3)      Platelet count.

4)      Culture blood (also PCR test).

5)      Rule out coinfections (consider MS rule out unnecessary although this may develop in a few years).

6)  Check with military to see if others with tick bites have eye symptoms and back symptoms since they are out in these woods quite a bit.

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