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Tuesday, July 29, 2014

The Lyme World On Its Head: Rapidly Emerging New Paradigms

The Lyme world is being turned upside down.

A recent study, as many are aware, performed PCR testing on stored sera of 52 patient samples from patients diagnosed with Lyme disease. Four were PCR positive. This underscores the problem with PCR. It has a low yield. If it were feasible to do 5-10 tests on every patient we would probably have a pretty good test. The finding are intriguing. Two of four, 50% were positive for Lyme as we know it, Borrelia burgdorderi. One was positive for B. Miyamotoi and one a "novel" species of Borrelia.  The paradigm is changing. "Lyme disease" more often than not may be caused by species other than the one over which there has been so much fuss:  B. burgdorferi.  This is just where the story begins. A recent survey of a nearby park (Montgomery County, Maryland)  was performed by Clongen (Dr. Kilani). His team collected 45 ticks. Two were dog tick and the rest were lone star ticks. Not one dear tick in the sampling. Why? Lone star ticks are known to be much more aggressive than deer ticks and appear to be taking over the ecological niche. Do these ticks cause Lyme disease? I think we can answer that question.  One quarter of the lone star ticks were infected with  B. lonestari. About 15% had anaplasmosis and one half showed infection with Babesia species. I do not think the Babesia species PCR is all inclusive, so it is possible that even a higher percentage of these more relevant ticks are laden with Babesia.

Fast forward to a patient I recently saw. This patient had a classic bull's eye rash on his foot in April. A doctor prescribed 3 weeks of doxycycline. When he complained of persisting symptoms another three weeks was prescribed. Symptoms continued. He was prescribed a course of Zithromax which provided little further relief. This patient has suffered with fatigue; night sweats; numbness and tingling; severe anxiety; memory problems and cognitive dysfunction; severe joint pain with swelling; palpitations, air hunger and shortness of breath, weight loss of 15 pounds and other symptoms. These symptoms persisted in the face of more than double the IDSA recommended course of therapy. Post treatment Lyme syndrome, right?  He had a Lyme Western blot through Labcorp: 41 IgG band only. He had PCR testing through Clongen: Positive for large numbers of Borrelia lonestari, not Lyme per se and negative for Babesia. 

Have we have a documented case of post-treatment B. lonstari showing persistence of the organism.  Maybe the first. The PCR test was not previously available. So the patient has STARI, Master's disease.

Wait a minute. Doesn't the IDSA/CDC crew say that STARI is no big deal? Oh yeah. They say the same about Lyme don't they.

Let's put this together. Lone star ticks are emerging as the dominant species of tiny hard body ticks which transmit tickborne disease and Lyme or its equivalent. They do not usually carry classic Lyme B. burdorferi, rather they carry a new germ about which we know very little; in half the cases of "old Lyme" transmitted by deer ticks, other species of Borrelia, rather than the expected B. Burdorferi may be the cause.  We have a paradigm which is being turned on its heels. Borrelia burdorferi as the causative agent of Lyme disease may soon be of historical importance.

Even with the conventional B. burdorferi, Lyme testing is known to be inaccurate (at least in Virginia). What now? We are bereft of any tests. I actually think there is some cross reactivity, so the appearance of CDC "nonspecific" bands may take on more importance in the short term. We are left with the idea that the diagnosis is a clinical one. This idea puts a real sour taste in the mouth of IDSAers who continue to promote an inaccurate, and now perhaps obsolete Lyme test as the basis for diagnosis as they discount the idea that the "subjective" (therefore untrustworthy)  history and physical exam can be used to make the diagnosis. When I went to medical school, a long time ago I know, we were taught that if you listened to the patient he would give you the diagnosis in the vast majority of cases.

How about Babesia? I have seen an epidemic on the rise. Babesia species. Which species? 

Back to the patient at hand. He was PCR negative for Babesia species and sero-negative for B. microti and B. duncani.  I did a blood smear and found a few, possible hemato-parasites. Test indeterminate.

The symptoms sounded classic for Babesia. And -- with anti-malaria therapy --  night sweats, air hunger and other symptoms have abated within only 2 weeks.

We don't have a dependable test for these largely unknown species of Babesia; but we have evidence that this tickborne disease may be playing a very major role in the exploding, frequently devastating (still invisible to many) epidemic.

How about resistance?  There is a lot of information about drug resistant versions of Malaria but none forthcoming about Babesia. Clinically we know this is a problem as we step up the ladder from Meporn to Malarone to Coartem and then to even Larium and Quinine with persisting symptoms.

In front of me is an abstract for J Parasitol 2014, Feb 28, Cao et al who state: "The resistance of Babesia parasites to current anti-babesiosis drugs is an issue of major concern." 

Thank you. Someone is taking notice.

None of this should be that surprising. We are dealing with a new and emerging disease. The tick vectors were barely known to exist before the 1970s. Borrelia are a very diverse genus as are Babesia of which more than 100 species are known to exist.

With incredulity I ask the rhetorical question: how can insurance companies, State Medical Boards, the CDC and the IDSA hold up guidelines written 8 years ago as the gold standard which defines the standard of care for the management of Lyme disease and other tickborne illnesses?