Sunday, November 6, 2011

Lyme: the tissue pathogen

It has long perplexed me why Borrelia bacteria appear to be so abundant in the blood of other mammals but so sparse in human blood. An Ixodes tick, generally the poppy seed size nymph form has a blood meal, typically from a mouse, becoming infected with Lyme along with an assorted host of other co-infecting germs. Even though the tick takes many such meals - (how much blood can the tick eat)? - it would appear that spirochetes must exist in fairly high numbers in circulating blood in these other mammalian hosts.

In humans the paradigm/narrative states: the spirochetes stick to the extracellular matrix, become intracellular, convert to cyst forms, avoid immune defenses and antibiotics by avoiding blood and body fluids and finds safe harbor within biofilm communities.

"It is a tissue bacteria, not one to be found in the blood."

Now thinking about these statements they do seem wrong. Textbooks have instructed me the bacteria is spread via the blood stream. I conveniently discarded this explanation along other textbook things Lyme. But - Lyme bacteria cannot spread to many disparate tissues including the central nervous system unless carried by circulating blood. Of course I knew this. Right.

We have looked for the bacteria in blood of infected humans by PCR testing, a direct assay for detection of Lyme DNA. This is what has mislead me. The results have been almost always negative. Getting a positive PCR for Lyme has been like hitting the jackpot.

With improved culture techniques Lyme bacteria have now successfully been cultured from human blood consistently.

Culture is the absolute gold standard for proving the presence of the bacteria and chronic Lyme disease (not post Lyme syndrome).

Why the negative PCRs?. PCR technology uses primer pieces of DNA which target sub-regions of the organism's complete genome. These reactions are amplified and read by a machine. The primers target specific regions of DNA known to be conserved within different strains of the organism.

Sample size may be an issue. The PCR machine may be sampling a small amount of DNA taken from a small sample of blood. PCR testing may not be sensitive enough to detect the most minute traces of DNA. There are also various technical glitches which may occur with the technology.

With culture techniques a larger amount of blood/DNA may be tested. Perhaps this is why culturing has been more successful.

Bottom line: new staining and culturing techniques may be shattering another part of the paradigm. Lyme is not just a tissue pathogen in humans but can usually be found in blood if you just know how to look for it.

8 comments:

Patriot Kate said...

Hello! I hope you are doing well. I've been praying for you every day. I got 14 months of infusions because the insurance company "made a mistake"! LOL They said they did not know I had lyme. They kept authorizing it every month. Made some interesting observations during treatment. The infusions along with some other treatment saved my life. I was amazed to be accepted as a patient by my new doc. I've been off antibiotics since last January 1st. Thank you for never giving up on me. I was just too sick to make the trip anymore. So much has happened, hope to catch up with you one day. It's so great to feel so well every day! With Best Wishes from a loyal ex-patient. Miss you lots!

la quinta kid said...

Hi Doc. I'm wondering if you have had a chance to test the new Advance Labs culture test I think you are referring to in this post.

Will this test be accepted by insurance companies to approve prolonged antibiotic therapy?

Camp Other said...

Given Barthold's research showing that spirochetes evade the immune system when in lymph nodes, I would think travel through the lymph system could also be a possibility. What about taking a biopsy from lymph nodes to find Bb?

How do you know the spirochetes spend that much time intracellularly? Far as I know, there are in vitro studies which show this, but not so much in terms of in vivo studies. Also, Janet Weis did NO studies in the 90s which provided evidence that they weren't intracellular for that long a period of time.

I keep thinking that a big reason testing is an issue is that not all strains produce the same Osps or IRs. For example, there's no VlsE output for N40... if someone gets a C6 ELISA, how does that work out for them if they're infected by N40? They must show positive for other regions/Osps.

Liz Schmitz said...
This comment has been removed by the author.
Liz Schmitz said...

Maybe we've been looking for the wrong forms and that's why we don't readily see Bb in the blood. In this study, researchers at Chapel Hill in NC found that "tick transmission converts a homogeneous spirochete population into a heterogeneous population that is poised to infect the mammalian host."

(http://www.pnas.org/content/98/2/670.full )

In other words, the borrelia changed to adapt to (and invade) the host. By looking for only motile spirochete forms, perhaps we're missing the boat. By the way, in a paper published years ago, Lida Mattman et al. reported a method, step-by-step, she and other researchers used to easily grow Bb in the blood.
Liz Schmitz, Georgia Lyme Disease Association

Jessica said...

So, I'm a new lyme patient and brand new to this blog, which I've been reading, and has been so helpful and specific. I have been struggling to get a diagnosis for my problems for quite some time. Had a full workup at top medical center for everything. I suspected lyme, and got the EM-rash 18 months ago, before these symptoms started, but had a negative Elisa. I ordered IGenex tests and was reported positive on 5 different bands, and overall positive. My conventional doctors reordered Western Blot from Mayo and I was negative. No bands reported. They said they had no other explanation for my myriad of symptoms, but would not treat based on Igenex tests, and to take an anti-depressant and "wait and see" if something more serious develops, like meningitis. I thought that was a stupid idea. I am not depressed, have never been depressed, so I was pretty angry with this advice.

I ordered a CD57 NK count, which was 29. I explained this to them and why it might be a good indicator for infection, and they had never heard of it, despite being ID doctors, and would still not help me. I just flew to Virginia to get started with a lyme specialist. They were quick to diagnose, and I'm getting started on Omnicef and later, Zithromax, which they said is to target lyme, but also suspected Bartonella (I had severe anxiety/panic onset with no trigger and no clinical history of even modest anxiety).

I am commenting on this post because the day before I flew to Virginia to start antibiotics, I sent in a culture kit to Advanced Lab Services. I'm really curious to see if they successfully culture my case. Since I was completely denied treatment at my home top medical center, I wanted the culture done so I could send in my flourescent stained spirochete picture to the treating neurologist who told me to take an anti-depressant. A little immature? Yes. But after what I've been through, I will feel a little bit vindicated.

I'll report back and let you know whether they can successfully culture my case. Since I was negative on the mayo tests, I hope a positive culture will lend more support for labs like Igenex, without which I would be wandering around miserable without any diagnosis.

Sta12s said...

Interesting thesis on neuroborreliosis:

http://www.diva-portal.org/smash/record.jsf?searchId=1&pid=diva2:444748

Jessica said...

I wanted to report back to you, Lyme MD, that I was found positive on culture from Advanced Lab Services and reported to the CDC. This was despite a completely negative ELISA and negative Western Blot from Mayo Clinic. I had a positive test from Igenex, a CD 57 count of 29, but neither piece of evidence was strong enough for my doctors to be willing to treat me for lyme disease. I am now taking combo oral zithromax and omnicef and am getting much better. Wanted to update you on the results of my culture. I'm wondering if I should re-order the WB from Mayo now that I've been in a month of therapy? Do many seronegative patients convert after a period of antibiotic therapy? I think my circulating antibodies were do low due the antigen binding in the tissue and they might be higher now that I have killed off some of the bacteria. Thoughts?