Thursday, June 2, 2016

The Lyme brain and nootropics

Cognitive impairment is one of the most disabling symptoms seen in patients with Lyme disease.  The symptoms can be quite subjective. The symptoms can be very disconcerting and at times disabling. The complaint is almost universally overlooked by general physicians and neurologist. After all, there is no evidence of dementia.  Many patients will pass neurocognitive testing, rarely offered and quite expensive. SPECT scans, infrequently performed, may or may not be abnormal and when abnormal brushed off as nonspecific. But as a patient recently shared with me, before Lyme she performed great at a high level job requiring timely completion of complex intellectual tasks; she can still get the job done but it takes 3 times as long. On this basis it is no longer financially viable for her to continue the consulting work and she is applying for disability. Doctors tell their patients: its normal to be a little slower after 50, it is natural for math skills to slip a bit.  Increased difficulty with word retrieval is par for the course with middle age.  Maybe to some extent this is true, but Lyme patients experience something qualitatively – and quantitatively different.  Mainstream medicine with its black and white world view is deaf and blind to the complaints of Lyme sufferers who may: get lost, confused, space out and put their cell phones in the fridge. If it is not Alzheimer’s disease, frontotemporal dementia, Lewy body disease, a brain tumor, a subdural hematoma, hydrocephalus, a prion disease or a few other conditions patient are told there is nothing to worry about. We know differently.  Of course the same Lyme patients complaining of brain fog also complain of fatigue. Frequently the two are intimately connected and it is hard to separate cognitive issues related to fatigue from those that exist independently. The question then is: what, if anything can be done? 
Clearly if we are dealing with germs in the brain we need to use antimicrobial agents which are powerful, able to penetrate into the brain and able to target the specific organisms of concern.  Typically, the focus is on spirochetes, pleomorphic variants, blood parasites, bacteria in blood vessels, biofilms and perhaps other organisms, like worms.

What else?  How do we make the brain work better?

Drugs that make the brain work better are called nootropics. The best known are stimulants.  Drugs like Provigil help with wakefulness. Clearly treating fatigue may help. Drugs like Ritalin, Adderall help with focus, attention and task performance. These drugs impact the neurotransmitter dopamine and are particularly active in the frontal lobe, executive function area of the brain.

Drugs like Namenda, commonly used in Alzheimer’s disease, negate excessive activity of the neurotransmitter glutamic acid caused by brain inflammation and related neurotoxins. Patients on this drug frequently find they are able to think more clearly.
Cholinergic drugs promote the activity of acetylcholine, a neurotransmitter involved with memory and other cognitive functions.  Rather than a prescription drug, I have found the supplement Procera (or similar) to positively impact cognition.

Do bile acid binders, cholestyramine and Welchol help?  In some patients the answer seems to be yes. I am not sure why.  Toxins?  I don’t think so. The prototypic neurotoxin, QUIN does not cross the blood brain barrier well, hence the use of drugs like Namenda. However, bile acids and cholesterol, both of which are lowered with bile acid sequestrants have signaling effects in the brain.

Glutathione may help, but only IV.  It may reduce the burden of free radicles, reactive species causing oxidative stress, negatively impacting function of neurons. In addition, mitochondrial dysfunction is directly connected to oxidative stress. Alleviated the latter promotes function of the former. Mitochondria in brain cells are essential for the production of energy.
Ketone bodies?  Some patients experience incredible improvements on an Atkins like diet. A ketogenic diet changes the brains fuel from primarily to glucose to primarily ketone bodies. This may result in neuroprotection, decreased brain inflammation, decreased oxidative stress and better mitochondria function.  Perhaps ketone supplements help as well.

Hyperbaric oxygen therapy.  For practical reasons most patients only have access to home units with offer a low pressure. A new unit can be purchased for as little as 5500 dollars. Patients who do the best spend 2 hours or more per day in the chamber. The treatment reduces oxidative stress, promotes glutathione and has been specifically shown to improve neuroplasticity with reversal of abnormal SPECT scan patterns.

Food for thought

( Nothing here should be construed as specific medical advice)

Friday, April 15, 2016

Babesiosis: species unknown.

This image is a copy (colors modified) of a Giemsa blood smear obtained from the blood of a 40 year old female 3 years of persisting low grade fever despite appropriate antimicrobial therapy.

Parasites seen within red blood cells assume a variety of shapes and configurations

Human Babesiosis, infection with B. microti was reported first in the 1960s. B. microti is still around, but most cases of human babesiosis are caused by another parasite(s) Three other species of Babesia are recognized by the CDC as known causes of human babesiosis in the US: B. microti, WA1 (B. duncani), MO1 and CA1. These parasites are nastier and are much more common (at least WA1). One study in 2011 found that 2% of the general population tests positive for B. duncani. Over 100 species of Babesia are known, many of which are known to cause animal disease only. Deer ticks and lone star ticks carrier many unknown Babesia species. In Europe B. divergens is a recognized cause of human babesiosis and considered more severe than human disease with B. microti.  This bovine parasite made the jump from cattle to humans proving the notion that such shifts occur in nature.

Babesia are malaria-like. They are pleopmorphic one cell protozoans, eurcaryotes (defined nucleus) which parasitize host red blood cells. The parasites have a complex life cycle. Sexual reproduction occurs in ticks (genetic material exchanged) and only asexual reproduction occurs in the host.  As with malaria, both genuses (Plasmodium vs Babesia)  have the habit of rapidly becoming drug resistant. Malaria is widely recognized and considered one the most serious public health threats globally. Malaria  infects 1/3 of the world's population, frequently announces it presence with acute high fevers and shaking chills and kills more than 600,000 yearly. Babesia is less lethal and more subtle. The incidence of infection and with which species is unknown and the subject remains uninvestigated. Guilt by association.  Babesia shares a common fate with its accompanying Lyme: dismissed and ignored by mainstream medicine. Babesia symptoms are nonspecific -- but not really. Remarkably, the symptoms of night sweats, sometimes fevers, air hunger, depression with weepiness (and others) are dependably seen. Babesia should be suspected with persisting low grade fevers. Most patients are diagnosed clinically because laboratory testing is unreliable, unavailable and expensive. Nonetheless, my policy is to test -- even in the absence of typical symptoms. Results are sometimes surprising.  For example, I recently found parasites in the blood cells of a man suffering with early onset dementia and all other tests were negative or ambiguous.

Antibody testing for B. microti is widely available. Unfortunately this is the rarer and milder version of the parasite. Testing for WA1 antibodies had suddenly become much more difficult. IFA (immunoflorescent antibody) testing has been more popular than the classic ELISA test. Similar information is obtained. Positive reactions are tagged with molecules that literally glow in the dark when viewed under a special microscope. The FISH (florescent in-situ hybridization) test offered by IgeneX is another option. Here the genetic structure of the parasites are tagged making the whole parasites glow in the dark. The test may not work for organisms of unknown genetic makeup. PCR tests pull out the parasites with a probe of primer DNA which binds the parasites and makes many copies. PCR also only works when the genetic structure of the parasites are known ahead of time.

I think the first line test is a blood smear. You don't have to know the species or DNA ahead of time. This does require a CLIA certified blood parasitology lab. The limiting factor is that the samples need to be prepared immediately otherwise parasites rapidly degrade and become more difficult to find.

My 40 year old patient has suffered with chronic fatigue syndrome and disabling chronic pain. Prominent symptoms include depression, headaches, joint/muscle pain and cognitive impairment. Her quality of life has been very poor. Symptoms have tenacious in the face of aggressive treatment. Standard antibody tests for B. microti and B. duncani have been negative. Two prior blood smears, a year apart were negative. Recently we found the above result. An active area of red blood cell parasites is clearly seen. Without PCR the result cannot be speciated. But since she suffers with tickborne illness and she has not travelled outside the US it is a pretty good bet she has babesiosis. Armed with this new finding, I ramped up the doses of anti-Babesia therapy beyond standard doses and combined several drugs in cocktail fashion. Finally, after years, the fevers are gone.

A vexing problem is that Babesia species, knowns and unknowns, have become increasingly difficult to treat because of widespread drug resistance. Creative, complex drug cocktails are increasingly becoming necessary to treat this frequently virulent and persistent pathogen.

Western Blot are frequently equivocal.

The results shown above are quite clear.

I am consistently able to find evidence of Babesia-like parasites in about 25% of my patients. In patients with soaking night the incidence is much greater. (I can only tests patients seen in my practice).

I suspect most of the unknowns are WA1. I have found that patients may seroconvert after treatment.

Tuesday, March 15, 2016

Babesia talk, all are welcome, space limited







I will cover clinical features, diagnosis and treatment. I will be showing some slides of blood smears and discus the use of blood parasitology in making the diagnosis.

Unfortunately, one of the best tools for diagnosing babesiosis has suddenly been pulled from both LabCorp and Quest. The WA1 or B. duncani antibody test.  The B. microti test which is still offered although not as helpful. The vast majority of positive results, for years, have been B. duncani, the much more prevalent species. In 2011 a study found B. duncani in 2% of the general population and B. microti in 0.4% of the US population. B. duncani has a wide geographic presence, consistently seen along side Lyme in every locale. At this point I am only able to send this test to IgeneX for this valuable test.  It is available through a few other reference labs at a higher cost.

The withdrawal of the "WA1" test was  sudden and unexpected and without explanation. This is a real set back.

Thursday, March 3, 2016

Western Blots in perspective

Doctor, can you help me understand my Lyme test, Western Blot?
Many patients spend a lot of time on the internet in efforts to understand the significance of mysterious numbered bands. What does it all mean?

As a starting point: lower your expectations. Lyme Western Blots, like all Lyme tests, lack accuracy and should be taken with a grain of salt.

A Western Blot is a second test, (IDSA/CDC)  a confirmatory test, used to confirm positive results from the initial test an ELISA - according to the IDSA/CDC. The CDC requires the second test because they believe the ELISA is inaccurate, leading to too many false positives, whereas, those in the ILADS camp believe the opposite. On the other side it if felt the ELISA test in nearly completely worthless because of false negative: it misses the majority of cases. Therefore the ELISA is skipped and the Western Blot is ordered directly. In addition, the Western Blot, although more helpful, is still inaccurate in many cases.
The two views are so divergent that mutual understanding and compromise, for the present time, is impossible.
For purposes of this discussion, all of these tests attempt to measure an immune response mounted by a patient who has been exposed to Lyme, or Borrelia burgdorferi. These tests look for antibodies made by an infected person's immune system. These antibodies are tiny proteins, also called immunoglobulins.
These discrepancies are rooted in the early days of the disease. The Lyme bacteria first described in 1982. Soon thereafter scientist went to work developing new diagnostic tests.  Lyme, viewed as a new and emerging disease was thought to be rare and geographically confined. This assumption may have lead to problems with test development from the outset.
The Lyme tests observe reactions between antibodies (from found in patient's blood) and antigens  derived from the Lyme spirochete. This sounds straightforward but it isn't. When a Lyme patient's blood is combined with chopped up pieces of Lyme, an antigen--antibody reactions occur which may be seen as clumping. Many antibodies, ( and there are many thousands), unrelated to Lyme, may still adhere to antigen in the laboratory. This is the nonspecific reactivity or background noise that always occurs with such tests. Scientist are charged with the task of removing the nonspecific clumping, leaving behind the true Lyme-antibody clumping. Not so easy. This call is something of an educated guess. The decision as where to set the bar is made by a committee of experts. To do a good job the experts have to know who has the disease. The experts need control sample taken from truly non-infected persons. If the disease is rampant and difficult to diagnosis and if many control samples are from non-symptomatic persons infected with Lyme the test will perform poorly - or not at all.

The scientist working on the tests found that many supposed negative control groups reacted strongly to the ELISA. This was unexpected and surprising. It was assumed that there was something unique about Lyme antigens leading them to elicit such a high degree of nonspecific, therefore falsely positive, ELISA reactivity. The notion that the high degree of reactivity might be due to a high incidence of infection in the community was not considered. Scratching their collective beards, the test developing scientist decided a second level of testing was needed to confirm the diagnosis. The Western Blot.

The Western Blot is used clinically for only one other infection I am aware of: HIV. This should raise a red flag.

A Western Blot is more sophisticated. Homogenized Lyme bacteria can be placed on a special strips and passed through an electric current. This process separates out the Lyme antigens based by their respective weights. The heaviest proteins (antigens) migrate to the bottom of the strip, the lightest stay on the top. When these strips are incubated with patient serum, lines form on the strip, representing individual antigen-antibody reactions called bands. From the start there was confusion about the correct use of this second tier test.

In the early 1990s it was clear to Lyme researchers that Lyme testing was disaster. Labs used different techniques and got very different results. A conference was set up in Dearborn Michigan in 1994. Researchers, lab directors and the CDC showed up. The goal was to come up with a standard metric so that labs everywhere would be reading from the same sheet of music when discussing Lyme test results. Lyme Western Blots are divided two tests. Two distinct classes of immunoglobulins (antibodies) are produced by our immune system in response to infection: IgM and IgG.  Western Blot criteria for these two classes of antibodies were discussed at the meeting. One group (Dressler) presented an IgM criteria of 2/8 bands for a positive result.  A second group, (Krupp) suggested a criteria of 2/4. Quite different. Each lab had used a different strain. N40 and B31 respectively. The researchers threw out the N40 test because of poor 39 band reactivity. It was agreed to use the 2/4 criteria. One of the 4 bands (37) was discarded at the last moment so the adopted criteria became the well known 2/3.  Strangely, IgG criteria for positivity, the well known 5/10, came from Dressler's research. In other words, one strain was used for IgM criteria and another for IgG criteria. Certain key bands were intentionally overlooked because of impact on the long discarded Lyme vaccine.

The researchers had one agenda, the CDC another. The researchers sought a uniform, consistent standard so they could reasonably communicate with each other. The CDC wanted a surveillance standard: a test that they could use to track the disease in different locations over time.
The conference never pretended to be in the business of finding an accurate diagnostic test for Lyme: rather a standard for research purposes only. The test that resulted from this meeting can be fairly called a CDC surveillance test. This test continues to be used erroneously for purposes of diagnosis. To makes matters worse, many clinicians believe the test can be used to reliably diagnose the disease. 

The Lyme bacteria possess numerous surface structures against which antibodies can be made. Bands show up if a particular antibody directed against a particular antigen is present in the serum in adequate numbers.

Multiple labs use different bands and different numbers of bands. Here I will get a total by adding IgM and IgG results together.

CDC tests looks at 13 total bands
IgeneX test looks at 28 total bands
Stony Brook test looks at 52 different bands.

In theory IgM bands precede IgG bands. IgM bands are associated with new infection. IgG bands are associated with older infection. Not always.  An effort to apply this principal to Lyme bands has led to endless confusion. In the case of Lyme the rule does not apply.  Lyme infection leads to strange antibody responses. IgM and IgG are jumbled up. The presence of one or the other or both usually has no special meaning.

As alluded to, some antibody responses are nonspecific (background responses) and some are very specific. Some are somewhat specific. For example the 41 band represents a spirochete infection but is not highly specific for Lyme. Some highly specific bands include: 23-25, 31, 34. 37, 39, 66, 83-93. Whether or not bands are reported positive or not varies from lab to lab. Some labs use computers and measures pixels. With this configuration a band is reported positive if it has at least 60% the pixels of control strip. Other labs do the eyeball test. An IND from IgeneX means a reaction, less than the positive cut off point was present. The word indeterminate from Stony Brook means something completely different. It means that at least one of the CDC bands is present.

These test results may or may not be helpful. Western blot results are a lot more helpful when clearly positive. Each clinician may interpret results differently because there is no standard, widely accepted criteria. Based on the state of the art and limitations of the test it should stay that way for now.

The diagnosis of Lyme is clinical. The Western Blot is a tool which may or may not be helpful.

Wednesday, February 10, 2016

Borreliosis, new and emerging species

A 38-year-old male sought my attention this week because of strange neurological symptoms in the aftermath of a tick bite. He lives in a small town around Richmond VA.  He has had a lot of tick bites over a period of years, ticks of various sizes. He and his family love to hike, camp and generally spend a lot of time in wooded area. In the early Spring of 2015 he found a tick on his calf which he removed. Within days, he developed a red expanding rash on his upper thigh. The rash encompassed the entire anterior portion of the upper thigh. He never developed a bull’s eye rash. The rash was consistently red. The lymph nodes in the groin become swollen and slightly tender. Within days of the tick bite, he developed an array of symptoms: fast heartbeat, anxiety, headache, tingling sensations, poor concentration and others. He went to the ER at the local hospital. He was diagnosed with panic attack and cellulitis (infection of tissues under the skin). Lyme disease was dismissed as a possible explanation. Nonetheless, he was prescribed a week of doxycycline for the cellulitis. He did not improve. He experienced progressive symptoms: neck pain, back pain, muscle twitches, strange vibrations, electrical shooting pains, tingling sensations, zapping sensations. He had a strange feeling of heaviness. He eyes become very sensitive to light. He developed tinnitus (ringing) in both ears and he became very sensitive to loud sounds. He noticed poor endurance and fatigue. It became hard to fall asleep. His cognition felt foggy. Memory was not as good. He had episodes of spacing out and concentration and focus has been a problem.

He went to his family doctor after a couple of months of misery. He was quickly evaluated. A few blood tests were done. The patient was invited back to the doctor’s office after several days and told he had a post-viral syndrome because EBV (Epstein Barr Virus) titers were high. Lyme antibodies were negative. The doctor recommended he wait it out. Things would improve. They didn’t.

In July 2015 he talked his doctor into ordering a whole set of tickborne disease tests at IgeneX. He was told the results were negative. He found a local holistic doctor who prescribed a month of 2 antibiotics and natural therapies. He felt worse. Two doctors now had reviewed the IgeneX reports and read them as negative.

It is only now that he seeks my help.

At this point the reader might be thinking the Western Blot results were somehow positive. This would be incorrect. Two doctors had not looked very carefully at the report. The PCR test for Lyme DNA was positive. IgeneX notes that the test is not specific for Borrelia burdorferi but may also pick other forms of Lyme, including B. andersonii, a contender for STARI.

News Flash. As I have been saying, there are other, mostly unknown species of Lyme. Just this week it was announced: new Lyme organisms discovered by researchers at the Mayo Clinic, modestly named, B. mayonii.

I believe this patient is infected with a variant Lyme strain. Therefore, the minimal reactivity on the Western Blot test would be expected.  The positive PCR was a stroke of luck. Likely vector: lone star tick;  likely pathogen alternative form of borrelia, not B burdorferi.

The diagnosis for this patient could be called Lyme disease. Borreliosis is a better term as it announces the fact that essentially the same illness can be caused by other Borrelia species.

By the way: Check out Fitzpatrick’s color atlas of dermatology. All of the images of EM rash are red patches, just like the patient had. None are bull’s eye.

Thursday, January 21, 2016

Not your father's Lyme disease

Lone star ticks, (Amblyoma americanum). are taking over. They now comprise more than 80% of the small black legged, hard bodied ticks found in the D.C metro area and elsewhere. These guys are very aggressive. They may be hard to distinguish from their deer tick (Ixodes scapularis) colleagues. Adult females are easy to spot: white spot on top. The shape and coloration is somewhat different. Take a careful look with a magnifying glass and compare to pix on google images. The CDC party line is: Lone stars do not transmit Lyme; they transmit STARI which is a mild disease and easy to treat. The CDC website states it is unknown wich bacteria causes the syndrome. The CDC website says Borrelia lonstari was a suspect but “further research” showed this not to be the case. This “definitive” research is the product of a small study published by Gary Wormser (name familiar) in 2005. Thirty EM rashes were examined for B. burdorferi (classic Lyme) and B. lonestari. Wormser did not find the genetic signature of B. burgdorferi or B. lonstari (or any Borrelia species) Therefore, the case is closed. Incidentally, all cases were from the Cape Girardeau are of Missouri (along the Mississippi river). I leave it to the reader to make sense of this research.  It is said that an inhibitor in lone star tick saliva makes them an inhospitable host for B. burdorferi. Perhaps. Nonethess, multiple studies have shown that B. burdorferi can be found in lone stars.  A patient in my practice with PCR (blood) proven B. lonestari was amongst the sickest patients I have seen. The only lab that I know of that does this test is Clongen. What about Western Blots? This patient was negative except for band 41 at two reference labs.
The Western Blot (as we currently know it) may soon be obsolete as the mix of Borrelia pathogens changes. Clongen found many Babesia organisms in these ticks, species unknown. Laboratory testing for unknown species of Babesia is impossible, except for fresh, properly stained blood smears. Bartonella is already a complete mystery: I say no more here.

Diverse ticks (Ixodes species) around the globe are known to transmit Borrelia species causing a Lyme-like illness, referred to as Borrelia burgdorferi sensu lato. Rapid changes are occurring in the US. The spirochetes live in an expanded reservoir, beyond white footed mice; the species are different; the strains are different and of course the vectors are different.

The coinfections are different and may be complete unknowns.

Here are a few clues: Ehrichia antibodies equal lone star tick. Only Anaplasma in deer ticks. RMSF antibodies show up a lot. I am not sure what this means. Cross reacting Rickettsia sp?  RMSF occurs only in lone stars not deer ticks. Meat allergies (anti-gal) only from lone stars: can be devastating.

The Lyme disease and associated tickborne pathogens paradigm is changing dramatically and very quickly. Be cognizant as we move forward.

Wednesday, January 6, 2016

A 70 year old man with a decade of night sweats, neuropathy and elevated muscle enzymes

A 70-year-old male believes he has had Lyme disease for over 10 years, first diagnosed 3 years ago.
He recalls a tick bite 10 years ago which led to chronic symptoms, mild enough to be ignored.

Four years ago he was admitted to a hospital with acute neurological manifestations. Primarily he complained of poor balance and difficulty walking.

An EMG was positive for neuropathy. A brain PET (nuclear scan) showed diffuse but non-diagnostic abnormalities.

Despite this scan he remained cognitively sharp and still teaches high level math.
The diagnosis of Lyme was made 3years ago. Prior therapy with Omnicef, Zithromax and Mepron had been unhelpful.

He has numerous concomitant chronic disorders any of which may cause neuropathy: well controlled type 2 diabetes, pernicious anemia, hypothyroidism and MUGUS.
Features of his illness include: daily night sweats for over 10 years after the tick bite and persistently elevated muscle enzymes (CPK), unexplained.   

He had been already treated for more than 2 years: I have been treating him for only 3 months.

He improved fairly quickly with a doxycycline based cocktail.  Then Rifampin was added.
He reports that this is the first time he has not had night sweats in 10 years. Muscle enzymes normalized, first time in 4 years, and, neuropathy symptoms have improved and he is walking better.

This response was far beyond my most optimistic expectations.

Neuropathy: from the perspective of neurologists (in general) his neuropathy would most likely be due to diabetes. All of his “mainstream” illnesses are associated with neuropathy. Never count Lyme out – or perhaps Bartonella in this case. It takes a long time for neuropathy to improve. Symptomatic relief may have more to do with Benfotiamine, a product related to vitamin B1 I suggested he try.

Night sweats: His lab workup for Babesia was negative (including freshly stained blood smear). He had none of the other symptoms which are classically associated with Babesia infection, including air hunger and depression. Rifampin does improve eradication of Lyme persisters when added to other antibiotics but I think the response to Rifampin leads us to Bartonella. There are a host of new and emerging species of Bartonella seen association with tickborne illness.

Muscle enzymes: It is well documented that Lyme can directly infect muscle tissue and elevate muscle enzymes. Bartonella? Bartonella infection causes vasculitis. The bacteria reside within he endothelial cells which line blood vessels. The strange rashes that accompany the infection are a manifestation of inflamed blood vessels. Other causes of vasculitis (medical literature) may cause low grade fevers, night sweats and muscle abnormalities.
PET and SPECT scans may have limited value and be nonspecific. Results should be interpreted in this vane. Cerebral vasculitis may be a consideration.

No response: to Omnicef, Zithromax and Mepron. Additional clues that Lyme and Babesia may not be the most important players. Always start with doxycycline unless there is a compelling reason for not doing so. Doxy is a necessary component of the 3 drug regiment which killed Lyme in Dr. Zhang’s test tubes. It is perhaps the best anti-spirochete Lyme drug. Doxy treats numerous coinfections and doxy is very handy when 3 drug “cocktails” are concocted for Lyme patients. This patient had already experienced considerable relief from a doxy based cocktail before Rifampin was added.

Lyme is ever confusing and at times surprising. For me it is important to attempt to work out the mechanisms (pathophysiology) of symptoms in each patient which provides a basis for treatment going forward.

Are my hypotheses correct? It provides me with a narrative. Of course I am only making educated guesses.  Research one way or the other which could help us understand what is going on with this patient is not in the pre-contemplative stage. Nowhere near it.
Lyme is a tragic disease.

The CDC admits there are at least 300,000 new cases a year. There are a lot more. Most cases are missed or misdiagnosed.
The manifestation of this chameleon diseases are protean.

The disease threatens the premises which hold together the gestalt understanding of human disease. An acceptance of these mind bending notions would require serious revisions of uncountable chapters in medical textbooks.
In a sense this may be what the paradigm war is about. It is not about whether Lyme persists or how long patients should be treated etc. It is about a fundamental rethinking of disease with a new found appreciation of the contribution of microorganisms.

This notion both daunting and scary.

Come, gather round people wherever you roam
And admit that the waters around you have grown
And accept it that soon you'll be drenched to the bone
If your time to you is worth saving
Then you'd better start swimming or you'll sink like a stone
For the times, they are a changing

Bob Dylan