Tuesday, October 29, 2019

Disulfirm/Antabuse

Its true: Antabuse/disulfiram is the most exciting new therapy for Lyme since daptomycin.

We are getting a lot more experience with disulfiram/Antabuse.  In some cases, it seems to be very effective.  I don’t think it is clear which microbes it is active against. It is an old drug repurposed as an antibiotic.  Its antimicrobial spectrum may remain unknown for the foreseeable future (there is no money researching it).  One thing worse than dreaded MRSA is VRSA – vancomycin resistant Staph aureus.  In vitro it was shown that the addition of disulfiram to vancomycin conferred the ability to kill this dreaded superbug. This should be catching some eyes, even outside the Lyme world.

Disulfiram clearly has potent antibiotic effects. It also has side effects. Twenty five percent of users have some rise in liver function tests –markers of liver inflammation. The rise is usually modest, and therapy can continue if AST/ALT numbers don’t exceed 2-3 twice the normal limit, with close monitoring. Three times makes me nervous. My comfort zone limits closer to 2.  Waiting for numbers to normalize and restarting with a lower dose may work. Severe liver disease may occur 1-2% of the time, not a trivial number.

ONLY YOUR DOCTOR CAN MAKE CLINICAL DECISIONS REGARDING ANTABUSE AND LIVER TEST.  THIS IS WRITTEN FOR GENERAL INFORMATIONAL PURPOSES ONLY; FULMINANT LIVER DISEASE CAN BE FATAL.

You should never treat yourself. The man who has himself as his doctor has a fool for a patient.

Side effects may include, dizziness, brain fog, fatigue, GI intolerance and others – in my patients. Many patients have had to discontinue because of side effects. Monotherapy may be fine. It runs counter to my experience, so I tend to prescribe it with doxycycline.

A word for the wise. We don't really know how safe the drug is.  Sometimes problems only become known when an occasional drug becomes one in common use. We have seen it over and over, for example, fenfluramine off fen-fen fame caused unexpected heart and lung disease and Vioxx the great new anti-inflammatory caused heart disease. Drug companies who have studied drugs extensively and had FDA approval call this "post-marketing" side effects.

Yes, Antabuse is an old drug used by hundreds of recovering alcoholics. When this old drug, largely disregarded from decades, it is suddenly used by thousands of lyme sufferers it many ways acquires characteristics of a new drug. In this case one that has not been tested. Quality control of generics is increasingly becoming an issue, e.g. Zantac.

I am prescribing the drug, just not throwing caution to the wind.

There is the issue of dose.  For alcoholics the loading dose is 500 mg and maintenance dose is 125-250 mg. This suggests that lower doses have efficacy.

There is some confusion about Lyme Herxheimer reactions.  From experience, Lyme, Babesia and Bartonella have separate and distinct Herxheimer responses.  Herxheimer reactions occur when mass killing of chronic, entrenched infection leads to an over-reaching immune response, a cytokine storm. The average, non-Lyme doctor, is unaware of the phenomenon treating mostly acute infections. These same doctors no doubt encounter a fair number of Herxheimer reactions which are misdiagnosed, e.g. drug allergy. Some patients have an “allergy” to every antibiotic. No, they don’t. Other patients say, “every time I take an antibiotic it hits me hard.”

Babesia and Bartonella Herxheimer reactions are very vexing, chronic and sometimes difficult to manage. They are qualitatively different from Lyme Herx reactions.

Lyme “Herxes” tend to be easier and follow a specific pattern.  An antibiotic is introduced, with days severe symptoms ensue, like fatigue (inability to get out of bed fatigue) low grade fevers, brain fog, achiness etc. After a period of days, weeks, usually no more than 3 weeks, symptoms begin to improve and go away and the patient improves. The Herxheimer reaction (Lyme only) should not return in cycles. Such cycles, apparent recurring Herxes, may be the result of normal ups and downs of the disease or due to killing something else other than Lyme. If we add one or more drugs, which gain access to a previously off-limits group of bacteria (round forms, biofilms etc.) a Herx may return, maybe even a more difficult Herx.

Dr. Zhang has dichotomized Lyme bacteria for us: active forms (free spirochetes) and stationary/persister forms (round bodies, biofilms).

After a reasonable amount of treatment with antibiotics targeting both populations, e.g. doxycycline, rifampin and Flagyl we would like to think there are few Lyme bacteria left. We are incorrect.

Add in disulfiram and an intense Herxheimer reaction may ensue (in some cases, not all).  Patient tolerance to  varying doses of the drug is all over the map.  Some handle 500 mg out of the gate, others struggle with 125 every other day.

It makes sense to start with a low dose and gradually increase over time.  I am more aggressive apparently than many others.  Most patients can increase from 250 mg daily ramped to 500 mg over a week or two. For sensitive patients much lower doses and more gradual ramping is required.

I have seen patients on the border of needing IV antibiotics  get better with Disulfiram.

It doesn’t always work. There is still no one drug that works for every patient.  And symptoms still relapse quickly with discontinuation after a few months.  Some patients are still going to need IV antibiotics, (Rocephin, daptomycin, doxycycline) if possible.

In my experience disulfiram doesn't appear to kill Babesia. My experience. Babesia is an opportunistic infection riding on Lyme’s coat tail.  Lyme has inherent immune suppressing properties. If Lyme is largely gone, Babesia symptoms may abate as well. In a normal host the body's immune system can eradicate Babesia, or reduce it to a mild parasite causing no symptoms. Just a thought.

So far, we only know that Antabuse kills Lyme spirochetes and Staphylococcus. Hopefully research will be funded so we can learn more about the drug. We really don't know what it does or doesn't kill.

Bottom line: Go for it! Monitor labs, watch for side effects (no alcohol including herbal tinctures): disulfiram –is  not an overnight miracle cure -- but it is quickly rising to the top of the list of  go-to Lyme drugs.  

Monday, October 14, 2019

Unecessary suffering and beating a dead horse

My new 40 year old patient is besides herself.  She has struggled with a tickborne illness for 5 years.  She has managed to keep her job, but barely. She cries uncontrollably.  She is very irritable and angry. She complains of anxiety and panic attacks.  Mostly, she is depressed. She admits to night sweats.  She denies air hunger.  Ongoing symptoms include exhaustion, chills, poor sleep, tinnitus, painful lymph nodes, abdominal pain and nausea, GERD, irregular menses, joint pain, headache, dizziness and vertigo and feeling off balance, dysesthesias and crawling sensations, panic attacks, suicidal ideation (no plan or intent), brain fog, trouble with with focus and concentration and thinking clearly. She has had a lot of unexplained abdominal pain over the years.

She has seen 2 "Lyme"  doctors off and on over the last 5 years. She has also seen many "regular" doctors.  The first Lyme doctor diagnosed Bartonella and treated her extensively with minocycline, azithromycin and rifampin.She didn't get better.   A second Lyme doctor confirmed the diagnosis of Bartonella.  Laboratory tests were negative but the physician was certain on clinical grounds the diagnosis was correct.   After all, what else causes severe GI symptoms and abdominal pain?  Anxiety and irritability are typical symptoms, almost diagnostic - she heard somewhere.

The "regular" doctors diagnosed depression, fibromyalgia, chronic fatigue syndrome and hypochondriasis.

One Lyme doctor treated her with ivermectin for one year.   She states she thinks she had a Herxheimer reaction but does not know why this drug was prescribed. The treatment did not help.

The same doctor prescribed Biaxin and rifampin.  The dose of rifampin was increased to 1200 mg daily.  After 9 months of this therapy she has gotten worse.  The doctor told her she has not been treated long enough. She decided she has waited long enough.  She thinks she had Herxheimer reactions but never got better.

She has never been treated for Babesia or even Lyme. A course of doxycycline with other Lyme drugs was never prescribed -- or anti-Babesia therapy.

A LymeWestern Blot was equivocal by MDL standards, IgG only.
Serologial tests demonstrated a low positier titer for Rickettsia species.
All other serological tests, inclusive of  Bartonella and Babesia were negative.
CRP was elevateed at 10.

I am able to offer another test in my CLIA certified blood parasitology lab.

Her an image taken from her Giemsa smear:



If a patient doesn't respond to a therapy the clinician is obligated to go back to the blackboard and take another look.

The slide shows marked infection with the malaria-like red blood cell parasite: Babesia. Few things are black and white in Lyme's orbit. This is an exception.

This CDC endorsed standard malaria/Babesia smear is a gold standard.    Many tests circulating in the Lyme-osphere are questionable.

Even without this piece of dramatic evidence, the patient should have been treated for Lyme, e.g. Doxycycline/Ceftin (Tindamax, Flagyl, disulfiram and others) and also treated for Babesia.

This poor long-suffering patient went  5 years, with night sweats and profuse tearfulness (depression) and Babesia was never considered or treated.

Hundreds of things can cause abdominal pain other than Bartonella, etc, etc. The symptoms of Lyme and common coinfections overlap. No one symptom should be attributed to  a particular tickborne pathogen.

Babesia treatment includes Zithromax and high doses of Mepron plus Coartem plus Krintafel. It is important to completely knock out Babesia when first encountered.  Otherwise, the parasites relapse and return mean and drug resistant.  *Please don't use Malarone because Mepron, the yellow paint is hard to stomach. Two malarone twice daily provides a daily Atovaquone dose of 1000 mg.  Two tsp of Mepron twice daily provides 3000 mgs of atovaquone, three times the dose. This dose falls within FDA approved, manufacturer guidelines. This high initial dose must be used to avoid drug resistance and years of misery. If its virgin Babesia you have one change to hit it hard and fast. Don't miss.

I am optimistic. We will get her better and sooner rather than later.

Tuesday, September 3, 2019

Lyme germ warfare?


Complex subjects, like the provenance of Lyme, are oversimplified into a soundbite and the truth is lost in the noise. The Washington Post does us a disservice.

Sam Telford, in the Washington Post told us that Lyme is not an escaped military bioweapon. The headline is  an implicit smirk at the alternative Lyme community said to be steeped in unfounded conspiracy theories. Ant-science. Fits right into the IDSA narrative.

Dr. Telford is a smart guy, a professor of Biowarfare at Tufts University, who has researched the topic for decades. Largely, he is telling the truth. Largely.

Let's listen to his truth. It speaks volumes.

Lyme is an old disease, even ancient.   Lyme was found in the 5300-year-old ice man dug up from the permafrost in the Alps – previously published in National Geographic.  Lyme infected ticks were found from 1945 and 1896 in the northeast US. Facts.

Ticks (Lyme carrying ticks) were studied during the cold war as a means of transmitting germ warfare.  Fact.

Deadly agents, including Tularemia and Q fever – transmitted by the same Ixodes ticks were studied (and continue to be an area of research -- other source).

The double helix of DNA was discovered in 1953.  Scientists during the cold war (1950s - 1980ish) lacked technology to modify germs and make them more deadly. Now it can be done.

Germ warfare research was done at Fort Dietrich and Plum Island. Modern Biocontainment procedures were unknown. (Animals and Ixodes ticks were allowed to roam free on the Island, with the belief they could not leave the island -- other sources). It was unknown that seabirds could ferry ticks to the mainland.

Lyme and the coming epidemic was something military researches could not have imagined.  The Lyme Bacteria was not discovered until 1981.

The Lyme epidemic cannot be entirely sourced to Plum Island since the epidemic broke out in the Midwest and West Coast at around the same time as Lyme Connecticut. The author does not say that Plum Island didn't contribute to the epidemic. 

Willie Burgdorfer participated in tickborne biowarfare research for the US Department of Defense.

Dr. Telford says a few dumb and obviously incorrect things: Willie was just joking with the interviewer about his role in germ warfare research.  Plum Island was repurposed for agriculture research in 1954 -- during the height of the cold war. (not a cover story).
And -- the US stopped bioweapon research in 1969 because Nixon said so. 

These are the clearly established facts.

In summary:  Our government was involved in germ warfare research for years. Some of the research involved ticks and tickborne disease (Q fever, Tularemia). Willie Burgdorfer, whose names is attached to the Lyme agent, B. burgdorferi worked for the government and  some of this research was with the same ticks that transmit Lyme disease. Biocontainment procedures were unknown and government scientist did not know the ticks and the unknown pathogen (Lyme) could easily jump across the Long Island Sound to Lyme Connecticut. 

It is easy to conjecture the Government unwittingly helped spread the epidemic of Lyme disease to New England as an unexpected consequence of secret germ warfare research. And, it is widely known the Government has a habit of not admitting wrong doing and covering its tracks. 

When we say Lyme was not an escaped bioweapon the statement is both true and false. There was no conspiracy to infect Americans with a horrible disease. But is seems likely that an unexpected consequence of tickborne disease bioweapon research on Plum Island was the spread of some Lyme infected ticks to the mainland. 

The law of unintended consequences applies and there is much we will never know.

Congress can investigate and it will be a waste of time.

Thursday, July 18, 2019

Novel drugs for Lyme


The dry spell is over. We have some promising new therapies.

Investigators have been used a method to screen large numbers of drugs which might treat Lyme. Dr. Lewis has apparently found that disulfiram, Antabuse, used to treat alcoholics and makes them vomit if they drink alcohol seems to kill Lyme. Apparently, he has discussed his findings at lectures. Practicing doctors don’t get the low down until findings are published in a journal. A recent case report of 3 patients showed efficacy of the drug.  Antabuse is something I have used throughout a 37-year career in medicine. It is generally safe, but liver tests need to be monitored. Repurposing the drug empirically seems quite reasonable. Dr. Fallon, Columbia University, is doing a clinical study. 

The fact that Antabuse is not an antibiotic is exciting.

The combination of Rocephin, doxycycline and daptomycin may be effective in humans. A clinical question is how long do the drugs need to be given?  Will we see durable benefits in 30 days, 60 days etc.?  Can an intensive IV therapy circumvent months, even years of other complex and perhaps less effective therapies? Let’s find out.

Controlled clinical trials are important. Placebos are incredibly effective. Personal interactions influence outcomes as do other confounding variables.  Studying a complex disease like Lyme is challenging; coinfections are not accounted for and a million other variables are not and perhaps cannot be taken into account.. Study results must be interpreted with care, nuance and ample discussion. The limitations of the study must be addressed. And I hope investigators will not be strong armed by politically motivated institutions to parse words when stating conclusions.  These few words have been misinterpreted, willfully with far reaching ramifications. The IDSA drew incorrect and absurd conclusions from Fallon's last Lyme study. And here we go with another set of IDSA recommendations.

Tafenoquine in the form of Krintafel is being used for treatment resistant Babesia. Looks good so far.

Friday, June 28, 2019

Bartonella persisters and daptomycin: two for the price of one?


While Lyme persistence I denied for political reasons the persistence of other human zoonotic pathogens is recognized. 

I have seen two cases of brucellosis recently and Brucella is recognized as a persistent bacterium, perhaps impossible to eradicate, at least with currently used and/or recommended therapy.

B. abortus is one of several well-known human pathogens of the genus, the one which may be acquired via tick bites.

Brucellosis can be acquired by consumption of uncooked meat and raw milk. I don’t understand the fad of drinking unpasteurized milk, a potentially deadly fad.

Brucellosis may cause numerous untoward clinical syndromes many of which similar to those seen with chronic Lyme.

Bartonella, especially B. henselae is a well known tickborne pathogen also known to exhibit persistence. The bacteria, a fastidious (difficult to culture) gram negative rod is an obligate (facultative) intracellular gram-negative bacteria associated with well described clinical syndromes, discussed elsewhere. Spotty medical literature supports the notion that Bartonella infection is clinically persistent.

Biologically, Bartonella are the only bacteria which may reside in red blood cells. The only other RBC pathogens are malaria and babesia species. Specific biological features, a protected niche and the discovery of stationary forms provide an ample narrative of fact and biological plausibility for persistence. 

The primary home for these bacteria is not RBCs but the endothelial cells that line blood vessels. This is why bartonellosis causes well known vasculitis syndromes. 

Zhang, a prolific publisher, should now be a star at JHH published about Bartonella persisters in antibiotics April. Again, daptomycin is the star.   Daptomycin has the best activity against stationary (persister) forms. Only aminoglycosides, e.g gentamycin are competitive.  In my experience, gentamycin may eradicate clinical infection, but not consistently. Complex multidrug regimens are frequently recommended for Bartonellosis, perhaps this is unnecessary.

This study added to others vis-à-vis Lyme raises the clinical (preclinical) question. Should patients with chronic illness caused by Lyme and Bartonella be treated with combination IV therapy, Rocephin, Doxycycline and Daptomycin earlier rather than later in the course of treatment?

From an Evidenced Based Medicine approach this is anathema,  such therapies can only be recommended after randomized clinical trials, peer reviewed and published.

Such studies are perhaps decades away.  Currently the political divide make diagnosis of Lyme nearly impossible, let alone coinfections.

The preclinical approach allows for empiric use of the therapy without waiting for IDSA approval, which may or may not ever come.

This concept of applying preclinical data (translational medicine) is well developed and well used in the field of oncology. Of course, cancer is considered a serious disease (and Lyme isn’t?).

Those of us in the alternative universe of Lyme disease are accustomed to very long-term antibiotics, including IV ones.  In this world, the use of these 3 IV drugs sounds reasonable. In the other world we are no strangers to cocktail therapy and IV therapy.  In the IDSA/CDC world of doxy for 3 weeks even discussion of this idea is heresy or treasonous, if such things apply in medicine (apparently, they do).

Treating chronic Lyme through the other world approach is very complicated, lengthy and expensive. This sort of preclinical information should be considered in lengthy, informed consent discussions with patients.  

Monday, June 24, 2019

Lyme arthritis, peptidoglycans and political correctness




Medical science and other branches of science are biased and political.  A researcher, an investigator(s) has to walk on eggshells when their findings bump up against beliefs of mainstream beliefs espoused by the experts. They have to fall in line with political correctness if they hope to see their research published, and if they want to keep their jobs as academic researchers. .  

The research findings published in the PNAS, Proceedings of the National Academy of Science this month entitled Borrelia burgdorferi peptidoglycan is a persistent antigen in patients with Lyme arthritis appears to be excellent science.

The research moves the ball forward in our understanding of chronic inflammation associated with Lyme disease. Political correctness and conformity with mainstream thinking corrupts the paper from the start seriously damaging the credibility of the authors.  Immediately the terms postinfectious Lyme arthritis and posttreatment Lyme disease are used and they poison the broth.

The preponderance of scientific evidence, overwhelming and mounting evidence supports the understanding that Lyme bacteria persist in the face of the standard antibiotic therapies discussed.

The finding that peptidoglycan (PPG), the crosslinking molecules which comprise cell walls in gram-negative and gram-positive bacteria are a major determinant of persistent Lyme arthritis is new information that moves the ball forward.

Borrelia spirochetes have a double outer membrane and lack PG cell walls. However, PG molecules are present internally, inside the outer membrane (cell envelope) providing support to the spirochetes.

The fragments of PG are call muropeptides.

We learn Bb, Lyme processes a unique PG structure. And we learn these fragments are highly immunogenic – incite an excessive immune response or cytokine response likely responsible for clinical manifestations of Lyme arthritis.

Perhaps the peptide fragments do cause an autoimmune response. Although the theory is discussed at length this is not what the research shows. Lyme related joint inflammation is directly caused by unique Lyme PGs.  


A variety of experiments, controlled experiments using a variety of bacteria with different PGs, a variety of clinical diagnoses, mice, humans, joint fluid and serum support the findings. The findings are based on a great deal of animal and human research.

Antibodies were developed against Lyme specific PGs. These antibodies could be the basis for a new, more accurate diagnostic test.

From recent research we know that Lyme biofilms and planktonic round forms cause more inflammation than spirochete forms. We know these are the most antibiotic tolerant forms or resistant forms.

The article at length discusses issues related to diminished bacterial recycling of PGs compared with gram negative bacteria.

Two theories are proffered as to how Lyme PG persists after “curative therapy” with a short course of doxycycline or Rocephin. The authors suggest that these mechanisms account for the persistence of symptoms lasting weeks or months.

But Lyme arthritis lasts for years. Biofilm forms are impervious to standard antibiotic therapies.

Somehow the authors suggest that immune suppressive therapy should be considered rather than additional antibiotics.

We have heard catchy phrases like “persistence of evidence or evidence of persistence." The issue has prevsiously be settled.

Good science can easily self-destruct with the unforced errors all for the sake of political correctness.

To bad.

Thursday, June 6, 2019

Lyme, Alzheimer's, Enbrel -- new potential treatment

I have learned that most people want a simple sound bite answer or conclusion. The edges of medicine always operate in the grey and nuanced.

It has long been dogma in Lyme circles that immune suppressing drugs, e.g. Enbrel are very dangerous and should not be used.  The same is true with prednisone.

I have patients who get the occasional injection by their rheumatologist; joint pain gets better and they are no worse for the wear.

The drug is used for psoriasis amongst other many other conditions. The drug has serious side effects: its use should not be taken lightly.

A study suppressed by Pfizer, brought to light be the Washington Post, was based on insurance company data considering outcomes of  hundreds of thousands of patients and found those taking Enbrel had a 64% decrease in the incidence of Alzheimer's disease. 

Enbrel impairs the function of TNF alpha, a master cytokine responsible for trafficking immune cells.

Pfizer did not make the disclosure because: a generic version will be  available.  A shiny new, me-too drug promoted heavily by pharm reps costing obscene amounts of money will take its place. Doctors will be given shiny data, along with lunch, proving equivalency? with the old drug.

The myth that generics are poor (dangerous) and lack quality control may be resurrected.

Watch out for first year generic prices: cute trick. For the first year a single company is given a monopoly and only required to reduce the price by 20%.  "See, the generic is almost as cheap as the brand," the rep will inform a doctor. This is a bad pro big-pharma rule passed by Congress decades ago I'm sure) by the way. Cheap is a relative term.

The pharmaceutical giant, Pizer has excuses, reasons why it withheld the data, for example, they  claimed the data is wrong because of biological plausibility: the molecule is too large to cross the blood brain barrier.

Really? I care if the molecule gets into the brain; maybe it's an advantage.  The brain has its own immune system which needs to be tweaked lightly. Ask anyone who has had a brain Herxheimer reaction knows. The Cytokine storm which may make you crazy results from peripheral cytokine reactions/overproduction primarily.  And there is no data the molecule cannot get into the brain. Cytokines get in the brain.

Alzheimer's is in part motivated by inflammation. Other major factors are: production of amyloid beta protein (AB) (plaques and tangles), genetic factors and multiple external factors.

It is thought that AB protein is a naturally occurring antibiotic which responds to inflammation. Discussed elsewhere. Lyme resides in the brain along with many  bacteria, viruses, protozoans. It is true that spirochetes have been reported to aid in the transportation of AB into the brain.  Infection (or colonization) may be omnipresent and therefore not the whole story -- or the most critical piece.

The vast majority of my patients present with cognitive complaints. Many or most Lyme patients, at one time or another fit the criteria for a disorder call MCI, minimal cognitive impairment. The mainstream medical community considers this a pre-Alzheimer's condition, often.

What's a Lyme patient to do?

First off, if symptoms completely resolve with usual therapy do nothing.

If you are a patient who has had very aggressive therapy, e.g. months of IV antibiotics and cognitive symptoms persist, look up MCI and consider the following:

Get an AB PET. The tests measures metabolic activity in the brain and the presence of early AB protein deposition. IF the test is positive you are at very high risk for developing Alzheimer's.

Prednisone and Enbrel have largely been dangerous seen as because patients are misdiagnosed and not also treated for Lyme. Enbrel is likely tolerably safe, in many cases, considering benefit to risk ratio.

A lot of money has been spent searching for an Alzheimer's cure. To no avail. Nothing very promising in the literature.

I for one am very angry with Pfizer. I suppose it is typical behavior in the industry. We still need big pharma. Don't throw out the baby with bathwater. Hold them accountable. But, do not  conclude big pharma is corrupt therefore all drugs developed through the system are fruit of a poisoned tree and are therefore inherently untrustworthy and dangerous -- in addition to being immorally overpriced.

It's a bad syllogism. Drug companies are a very necessary evil.

Getting back to Enbrel Is this a silver bullet?.  More comment, biostatistics and analysis are required as well as prospective RCT medical studies. Since the drug will be generic soon big pharma will not finance the research. Fortunately, Alzheimer's, a burgeoning epidemic as our population ages, is well funded through private sources.

Ideal prospective studies, which will likely be done make observations moving forward starting with a baseline current population. The process is slow.

Retrospective, population studies, primarily manipulation of data already there will not take long. These studies are never as good as prospective studies but perhaps good enough.

If you want my  bottom line: don't run out and get Enbrel-- YET.

I am not endorsing the use of the drug for any medical condition, including Alzheimer's,
This site is for informational purposes only.  Medical care can only be delivered by a certified medical practioner who properly evaluates your particular issues. Please don't diagnose or treat yourself. 





Monday, May 20, 2019

Posttreatment Lyme disease case


A 52-year-old female was seen in my office several months ago.  She has a history of tick bite and bull’s-eye rash treated with recommend "standard" doxycycline for 3 weeks and she felt well -- until she didn't.  Symptoms appeared gradually.  Eighteen months later18 months later she complained of: incapacitating fatigue, poor sleep, diffuse pain, weakness, numbness and tingling, headaches, cognitive impairments–trouble remembering words, impaired focus and attention and memory loss, to the point of disability. She was hanging onto her job by a thread.

She also experienced severe night sweats but had chalked it up to menopause. The  sweats however,  were new and drenching, occurred several days weekly and  were qualitatively different from previous night sweats -- primarily hot flashes. 

With further question she stated she had been experiencing gasping mid-sentence and thought  she had developed a tic. 

Lab testing was positive for Lyme (CDC, IgM and IgG) and Anaplasma.

Lyme was initially treated with a triple regimen, doxycycline, rifampin and Tindamax. Also covers Anaplasma. 

Within 4 months she reported getting her life back and regaining a high level of function. Babesia symptoms, well described above (night sweats, air hinger) persisted.

The treatment was changed.  Rifampin was discontinued.  Doxycycline, Zithromax and Mepron were prescribed. 

Notes:  Typical  posttreatment Lyme disease, relatively early presentation (in my practice). The role of coinfection has been ignored in clinical studies.  Lyme as sole infection, absent coinfection is rare. Coinfections may be difficult to diagnose because of poor diagnostic testing.
Human trials have used only doxycycline and Rocephin. In mice, triple IV therapy: daptomycin, doxycycline and Rocephin (ceftriaxone) was shown to eradicate Lyme spirochetes.  

Medical literature suggests that about 20% of early patients treated by CDC standards will have chronic symptoms.
Many reasons have been suggested, Including:

Tick inoculates human host with antibiotic resistant biofilms.
Coinfections.
Strain specific virulence factors.
Host specific immune responses. 
Host already infected but asymptomatic.

Standard therapy ineffective -- high failure rate unacceptable, leads to chronic illness and/or serious sequalae.

Clinical approaches may include: 

More aggressive cocktail therapy early
Careful monitoring of patient for persistent symptoms and symptoms suggesting coinfection and early treatment
Not telling patients: don't worry, symptoms will clear.

Tuesday, May 7, 2019

PANDAS/PANS and Lyme, clinical notes


PANDAS and Lyme.

Based on my beliefs and clinical experience.

Mainstream medicine currently does not recognize PANS, the notion that other infectious organisms can induce the same disorder or exacerbate the disorder.
PANDAS stands for: Pediatric autoimmune syndrome associated with streptococcal infection. 

PANS stand for Pediatric autoimmune neuropsychiatric syndrome.

I would suggest the proper acronym is ANS.  The disease is not limited to children and occurs in adults.  

Mainstream view: Strep only.  Autoimmune, not related to persistent infection.
Alternate view:  Multiple microbes may be involved including tickborne pathogens: Lyme and Bartonella. Maybe others. 

When confronted with something new it is only natural that doctors compare the disorder to other similar ones, well described and put place the new illness into a similar, pre-made boxe..  Streptococcus is well known to be associated with a variety of syndromes which may be averted with early treatment. The syndromes in question are autoimmune and post-infection – as  every medical student knows and include rheumatic fever and glomerulonephritis. 

Rheumatic fever (RF) can weaken heart valves, cause arthritis and lead to a movement disorder. RF is rarely seen these days. 

PANDAS was put in the box of RF. Lyme, not even considered, would likely be put in the same box if so discovered. 

Most practitioners see PANDAS, PANS as a subset of autoimmune encephalitis. Therefore, the RF analogy is incorrect.  PANDAS/PANS is something else.
Novel autoantibodies have been discovered, i.e. Moleculera Cunningham panel.
PANDAS/PANS (PP) responds to IVIG. IVIG  has not benefited acute RF in clinical trials. 

Immune modulation with drugs for autoimmune encephalitis including rituximab has helped some patients with PP (with other therapies). 

PP is associated with sudden neuropsychiatric symptoms which appear overnight.
Typical symptoms include:  change in behavior/personality, OCD, tics, Tourette’s, anxiety, ODD and others. 

The disorders are not limited to children. There exists a population of adults, long treated with psychiatric drugs, ineffectively, who have persistent PP symptoms which may respond to PP therapy to be described. 

Primary therapies include: IVIG and antibiotics. 

In patients with chronic Strep pharyngitis/tonsillitis tonsillectomy may be of benefit.
The duration of antibiotic therapy and of IVIG is best left open. Every patient is different. 

If Step is the only concern drugs like amoxicillin or Zithromax may be adequate.
IVIG. Two issues to discuss. 

One theory is that treatment need be given only once every 6 months the other is it must be given every 3-4 weeks.

Dose: Getting approved for IVIG is difficult. Getting IVIG approved for the optimal dose is more difficult. 

There are 2 general sets of illness and 2 dosing sets. 

Neurological disorders are treated with high dose IVIG (1.5- 2 gm/kg) and immune deficit disorders low dose IVIG (0.4-1 gm/ kg)

PP patients are usually only approved for low dose therapy. 

(I am not saying the patients who truly have an immune deficit will not benefit from low dose therapy, rather I am say PP patients will receive an inadequate dose). 

There is a theory that low dose IVIG can actually make PP worse. I think this may apply when the therapy is given subcutaneously once weekly, not IV. Patients should receive IV therapy. The starting dose is generally around 0.6 gm/kg and the dose may be titrated upward based on clinical effectiveness. Published data with other forms of autoimmune encephalitis suggest doses as low as 0.4 gm/kg have been helpful.

Patients with Lyme, more often than not, also are infected with Bartonella and Babesiosis. 

Therapy should start with doxycycline because it covers a wide array of other coinfections and possible contributors, such as Mycoplasma. 
Bartonella therapy is generally inclusive of Rifampin/rifamycins and possibly Dapsone. 

I think Dapsone may not be a great Lyme drug but rather have great activity against Bartonella. 

As discussed elsewhere, antimicrobial choices may need to be shifted to cover the complete array of coinfections, including Babesia. 

Antimicrobial therapy, in the presence of tickborne pathogens may need to be low and slow because of the risk psychiatric Herxheimer reactions and worsening of autoimmune neuropsychiatric symptoms.

If Step is primary a higher dose needs to be used. Something like Keflex might be a consideration since it kills only Strep and no tickborne pathogen that I am aware of. This is the idea that targeted therapy may reduce psychiatric Herxheimer effects.

I reiterate: I think medicine is a weak science.  In PubMed there are hundreds of thousands of references to hypertension and yet recommended therapies seem to change every year or two. 

Medical studies, by necessity are internally valid. Yes, there are biases from the get-go. Aside from that: inclusion criteria are narrow (symptoms and lab tests), therapies are limited, e.g. one antibiotic and endpoints are narrow – e.g. one symptom is evaluated, such as improvement in cognition. To date, study groups have not used consensus methods (each group have evaluated the symptom with a different set of tools).
Studies frequently lack external validity or real-world application.  Minimal results are expanded, generalized -- to fill an ethos of preexistent belief about the inherent nature of the disease and its appropriate treatment. 

Evidence Based Medicine as a construct only looks at clinical studies, frequently deficient, and excludes basic science research and “biological plausibility.”
PP remains “controversial” and contested much as does Lyme writ large. What else would you expect?


Not to be used to diagnosed or treat any patient or particular illness. My clinical impression are presented strictly for general informational purposes.




Friday, April 26, 2019

Zhang's mice. And, where have all he patients gone? The cure!


Lyme cured! Or is it. Dr. Zhang and (Jie Feng) are heroes in the Lyme story and their work will be of great import in the history of medicine.

Dr. Zhang and colleagues have been very busy building the case for chronic Lyme disease or persistent Lyme disease. Their publication March 28, 2018 support previous in-vitro (test tube) studies in a mouse, called a “murine model.” He has previously demonstrated that Borrelia burgdorferi strains, bacteria responsible for Lyme disease subdivide into different morphological forms. The means the same bacteria, with the same DNA, can alter their appearance and function dramatically. We associate a thin spiral, elongated form with Lyme, a spirochete. But the long thin forms of Lyme can change shape and appear round. Alternatively, the spirochetes can aggregate in a community protected by strong mucopolysaccharide substance, a microcolony or biofilm.

Three forms:  spirochetes, round forms and microcolonies (biofilm colonies).

The bacteria can be free floating in the blood referred to as planktonic forms. The term contrasts bacteria safely guarded in the biofilm (microcolony) form. I have always thought of planktonic bacteria as free swimmers. They are demonstrated to be primarily round form and non-motile in the studies.

Test tube finding (in-vitro) support the mouse study.

The different forms, morphologies Lyme takes on are best killed by different antibiotics. Only a specific combination of three antibiotics eradicates Lyme spirochetes in mice infected with microcolonies.

Posttreatment Lyme or persistent/recurrent symptoms may occur in 20% of patients treated by standard protocols, generally with doxycycline. (This is from the CDC). A study from 2015 indicates that 36-63% of patients may have persistent symptoms.

The term PTLDS, posttreatment Lyme disease syndrome is popular but not helpful.  I believe its use is primarily political, used in deference to the powers that be.

PTLDS ostensibly describes a group of patients with early diagnosis and treatment who nonetheless develop chronic symptoms.

The authors brilliantly point out that there exists a large population that never receive early diagnosis or treatment which he refers to as type 2 patients.  In my experience most patients are type 2.

Experimentally, spirochetes were divided into the three forms through laboratory procedures. 

Mice were inoculated with either spirochete or persister forms.

Pathologists examined tissues for inflammation. The  greatest was observed in mice infected with persister forms, especially biofilm forms.

Mice infected only with spirochetes could be cured with doxycycline and other antibiotics.

Mice infected with stationary forms were only cured with the specific combinations of: Daptomycin, Ceftriaxone and doxycycline. Negative cultures were obtained from  ear biopsy and bladder tissues.

The authors suggest that different forms of Lyme are delivered through the tick bite. Biofilm colonies may be introduced in tick saliva and then seed other tissues.

This is contrary to what I know about the bacteria.  Lyme bacteria are highly motile, extracellular and possess ligands which facilitate adhesion to the matrix between cells. The bacteria are polytropic or pantropic and quickly infect many tissues and organs. There is no known mechanism by which biofilms can directly seed other tissues. The standard model is that organisms within a biofilm communicate by molecular signaling, quorum sensing-- and that individual, planktonic spirochetes are released under the right conditions to seed new tissues and create new biofilm colonies.  The spirochetes may be protected by special compartments in the body, for example they readily cross the blood brain barrier and live in the brain, an immune privileged area. Biofilms have been demonstrated in the brain. I think only individual spirochetes with their lipophilic outer membrane can get through the blood brain barrier.

There is ample evidence that spirochete rapidly convert to round forms when attacked by antibiotics. In-vitro colonies of spirochetes morph into other forms, persister forms, the 5% doxycycline does not kill.

If biofilm colonies are truly injected into skin by ticks at the outset, standard therapy, doxycycline and others is doomed to fail.  Very plausible. Frightening. 

The currently recommended therapy for early, stage 1 Lyme disease is a failure. It might be argued that other regimens should not be experimented with. These new therapies have no scientific basis. But there is compelling scientific evidence that standard therapy is a failure.  

Oral therapies with combinations that showed some promise invitro might have a better chance, for example, doxycycline, rifampin and artemisinin.

The curative therapy described is problematic. Ceftriaxone and doxycycline are standard, generic fare but not daptomycin. Daptomycin is a relatively new, powerful antibiotic currently held in reserve for multi-resistant bacteria such as MRSA.  It’s non-generic cost of $400.00 per dose/day-- not covered by insurance may be prohibitive. A thirty-day course costs $12,000. Generic available, $150.00 per dose. Cost lowered to about $4000.00 monthly.

Experimental treatment based on scientific plausibility and clinical experience for late stage Lyme has helped many, many patients.

The paradigm that Lyme disease present with: an observed tick bite, a bull’s eye rash, Bell’s palsy, a swollen knee, meningitis, heart block and other well described acute manifestation is wrong.

Ticks go unseen, rashes are the exception not the rule and most patients present with -- fatigue, pain, neurological symptoms and cognitive dysfunction – the bones of Lyme disease. The meat is filled with symptoms referable to nearly every organ system. Most patients go misdiagnosed for months, years or decades. This is the tragedy of the Lyme epidemic.

Patients are belittled, diagnosed with chronic fatigue syndrome, fibromyalgia, depression and/or the aches of pains of daily living.

Doctors who take chronic Lyme seriously are ridiculed by peers and medical licenses are censured.

There is math problem

Of 300,00 type 1 Lyme cases yearly in the U.S. 60,000 become chronically ill.  The number is at least doubled when you add in type 2 cases.

This means there must be hundreds of thousands of patients, more likely  not millions of patients suffering with chronic Lyme disease.

Despite this patient are nearly universally told it’s not Lyme, can’t be Lyme, no known disease acts like that, etc.

This leaves a simple question: Where are all the missing patients?

Einstein warned scientist lack imagination. Everything doctors do today with be laughable to future counterparts. Phages which kill only specific bacteria or other technologies will surely make antibiotics obsolete in the not too distant future.

Tuesday, April 23, 2019

Antibiotics and Germs


Its still complicated but I am trying to explain some basic concepts for the lay person.

Antibiotics only kill germs called bacteria.  Germ is not a medical term but a colloquial substitute for pathogen, a microorganism of one sort or another that causes human illness.

Disease causing germs are representatives of various families in the animal kingdom of microbes, including:  bacteria, viruses, fungi, yeast, protozoans and worms .

With few exceptions, antibiotics kill only bacteria so that is what we will discuss.

Bacteria are one cells prokaryotic microbes, so named because they lack an organized nucleus.

Please keep in mind that the vast, vast majority of bacteria are friendly or harmless, including the 2-6 pounds of normal “flora” we carry around, necessary for immune functions and detoxification.

Bacteria present as a menagerie of forms and shapes: comma, spiral (spirochete), cocci (round), rod (elongated), chains, grape-like groupings, filamentous etc.

THE SHAPE OF A  BACTERIA DOES NOT DETERMINE WHETHER IT IS A PATHOGEN, A GERM.  ONE SPIROCHETE MAY BE NORMAL FLORA, HARMLESS, AND ANOTHER MAY BE LYME.

Families of antibiotics may contain similar members. Members of the same family may perform different.

In general, specific antibiotics target bacterial germs which possess certain characteristics.

For example, an antibiotic may target bacteria with cell walls constructed  somewhat differently --  gram negative or gram positive. Antibiotics may target gram positive bacteria, gram negative or others such as intracellular bacteria etc.

Intracellular bacteria may only survive in host cells: some have no cell wall e.g. mycoplasma.

Bacteria (think Lyme) may lack a cell wall but rather have a double outer membrane.

Antibiotic classes include penicillins and cephalosporins which are considered cousins because both share a  ring structure (beta lactam). The drugs are divided into generations. First generation, second and third.

With progressive generation more types of bacteria are killed (broad spectrum versus narrow spectrum.  


Antibiotic classes include tetracycline, macrolide, sulfa, rifamycin, quinolone, antiparasitic, e.g. (Flagyl (nitroimidazole) etc.

We use principals of pharmacology to decide which antibiotic(s) to use for a particular infection.  Deciding factors may include the severity and location of the infection.

We consider MIC, minimal inhibitory concentration and MBC, minimal bactericidal concentration.  This means the amount of antibiotic to inhibit growth or to kill the bacteria.

We must consider the risk of side effects and complications, like C. diff colitis.

We have to make sure the antibiotic can get to the source of trouble, for example the brain, with ability to transverse the special BBB) blood brain barrier.

There are a lot of very complex factors that influence antibiotic decision making.

Treating chronic Lyme disease is a vary complex process.  As  with a patient I saw this afternoon, Lyme  triggered a cascade of problems, including: dysautonomia (POTS), MCAS, mast cell activation syndrome. 

She also suffers with a very stubborn case of babesiosis.


There are a lot of balls in the air to juggle.

 A recent live Facebook event was successful.
I hope we will soon cut through some of the confusion.

I will be scheduling another live Facebook presentation: Treating Lyme with Q&A in the near future. My Facebook coordinator Brittany Goff will be setting this up.

Tuesday, April 9, 2019

Lyme, evidenced based medicine, Fallon and the Institute of Medicine


I recently gave a talk about Lyme and EMB, evidenced medicine.  I had no idea that Brittany, who runs my Facebook page, live-streamed and posted the talk on Facebook.

The Institute of Medicine holds a lot of sway in the medical community.  Something called “patient centered medicine” is said to be enshrined.  There are many facets to patient centered care -- the one of interest to me here is that patient preferences are given credence.  In fact, the IOM states not to consider patient preferences is morally wrong, a violation of patient rights.  Vocal critics say this ignores EBM, evidence-based medicine. Not true. EBM is part of the consideration, not the only consideration.

Evidenced based medicine doesn’t require consideration of scientific plausibility.  If the results of a study contradict accepted science or reality, then it is likely the study if flawed. 

This is about where we are with Lyme disease, I think.

All clinical trials are flawed and biased in many ways. The interpretation of results is frequently fraught. Text books of statistics  are full of complex mathematical equations and show innumerable ways of crunching the same data and numbers.   If an investigator does not like the conclusions, other statistical models can be tried until he finds the one meets the objective: support preexistent beliefs.  It is like trying on new shoes. This is particularly true when subjective questionnaires are used for endpoint analysis.

To avoid bias: Methods of statistical analysis is a variable which must be controlled, delineated before the start of the trial and strictly adhered to.  Appropriate clinical questions need be determined  at the outset. 

For medical studies THE statistical question is: did the treatment benefit the treated cohort in a manner that cannot be explained by chance alone?  Or with 95% certainty.

In the Fallon study:  Did treated patients have cognitive improvements 12 weeks after therapy compared to the group given placebo, by statistical analysis?  In the treatment group were improvements in fatigue durable after 24 weeks? The answer in each case is yes.  As Dr. Fallon later states, the study shows efficacy: the treatment works.

Those who claim the study was negative are looking at the wrong question.

The study showed:  IV Rocephin 10 weeks caused cognitive improvements at 12 weeks which later, without further treatment reversed, whereas--improvements of physical symptoms like pain, fatigue and function were maintained at 24 weeks.  

The study conclusion stated the treatment was not effective for PTLDS.

This never sat right with me.  The conclusion is not reflective of what the study shows.  Do University internal politics had something to do with crafting the wording. This process is certainly not transparent.

The terms efficacy and effectiveness sound the same but are different.  Efficacy is the demonstration of A positive clinical response to treatment.   Effectiveness refers to successful clinical use of a treatment as a whole.

The second standard had the same chance of being proved as threading a camel through the eye of a needle.  The first standard shows proof of concept and that is huge. The conclusion does not reflect the paradigm shattering enormity of the study.

The favored null hypothesis of mainstream medicine in 2007 (and now?) was:  Persistent symptoms after Lyme treatment is a post treatment Lyme syndrome, an autoimmune affect, all the (clinically significant) spirochetes (Borrelia burgdorferi) have been eliminated.  

Fallon’s study proves the alternative hypothesis: Post treatment symptoms are associated with persistent infection and respond to additional antibiotics.

The IDSA makes the classic type I mistake of failing to discard the incorrect null hypothesis.

EBM -- IDSA guidelines were written on the basis of a glaring mistake of logic and statistics.

Biological plausibility, although not a necessary consideration here, was not looked at.  The fact that Lyme had not been eradicated in animal models then (and now) suggested that persistence of Lyme in human cases is highly likely.  The results should not have been surprising. 

In the IOM approach, EBM is decided by a closed panel, opinion driven, and at best provides narrow endpoints lacking generalization. The two other key elements of patient oriented medicine are medical judgement and experience – the art of medicine and patient preferences.

The IOM argues that clinical experience is necessary to fill in gaps or gaping holes left with only the EBM approach.  The IOM brilliantly exposes the inherent weakness of EBM.  Within this framework doctors are healers in the traditional sense and allowed to figure out the puzzle each patient is. This is critical when the disease is extremely complex and multisystem.  

My next talk will be about treating Lyme.  I want to get into some specifics.  I hope to tease out the roles of science, EBM, clinical experience, patient preferences, and the principal of first do no harm.

.

Tuesday, March 26, 2019

Lyme and the plague


A perfect storm.  It was a perfect storm which led to the spread of the bubonic plague endemic which hit Europe in waves over more than 5 centuries.  The plague is a vector borne zoonotic disease and, in this way, similar to Lyme disease. The reservoir for the disease is rats who travelled in the bowels of trading ships making new homes in heavily populated port cities and other population centers. The vector was not a tick but rather an unsuspected rat flea which carried the deadly bacteria, Y. pestis.  The infection led to gruesome deaths killing half the population of Europe and decimating much of Asia, killing a third of the global population. Plague doctors suspected the disease was carried by a miasma, bad air, perhaps carried by birds. They donned scary beaked costumes and bled patients to rectify an imbalance of the 4 bodily humours. Some of their patients lived; the mortality rate was somewhere between 40-90%. When patients recovered, they claimed success. It was a perfect storm because populations became increasingly concentrated in cities like London, trade was active amongst Europe and Asia and the rat hitchhikers found wonderful new homes with food and shelter and because at the height of the plague, around 1360, the germ theory of disease would not be discovered for another 500 years. 
Today, Lyme, and some consider a silent plague has much in common with the black death.  Lyme disables rather kill and the subtle manifestations, or not so subtle if you look carefully, go unseen by the Medical community, writ large.  In this case birds really do transmit the disease increasing tick habitat over years and decades.  Rather than staying close in cities where one can walk everywhere, the car led to populations spreading out, suburbs abutting wooded areas and habitat for animals including Lyme requisite mice and deer.  Deer became increasingly plentiful. Predators, like mountain lions were scarce.   Mice thrive because potential predators: fox, raptors, owls and others moved away as well.  Deer, mice and ticks increased dramatically in number.  Over time, tickborne pathogens flourished and more and more ticks became infected, now most ticks (deer ticks and lone star ticks), with Lyme and other nasties. 
Betty was reading a book, enjoying a glorious late spring day, lounging in her chair next to the garden she planted in her back yard, a yard shared with so many beautiful white tail deer. Her husband Bob, sweating in the sun, smiled at her, enjoying the task of clearing brush in the wild back of the property. 
Betty developed fatigue, malaise, diffuse muscle pains, night sweats, brain fog, depression and irritability.  She visited her GP who even did a Lyme test (just to be thorough) and diagnosed depression, sending her off with a bottle of Prozac. 
Bob developed strange rashes, headaches and numbness and tingling in his feet.  His doctor suspected neuropathy and this was confirmed by an EMG.  His blood sugar has been borderline and his father has diabetes. He was sent home with a diagnosis of diabetic neuropathy and a bottle of Neurontin, gabapentin. 
The idea was developed by Pasteur in the 1850s and further worked out by Koch in the 1860s-1870s. The germ theory was born. Poor Semmelweis, an Austrian obstetrician in the 1840s went mad asking only that colleagues wash their hands, to prevent so many childbed fevers and deaths of newborns and their mothers, but no one listened. 
Penicillin, the wonder drug of the 20th century was discovered in 1929 and mass produced in the middle of the second world war. 
Medical knowledge and science have exploded exponentially. The entire human genome has been sequenced.  HIV/AIDS has been conquered.  People no longer die from small pox, syphilis, tuberculosis or the plague.
So why I ask, do the modern-day doctors caring for these two souls afflicted with disabling if not deadly illness, treat them with the same level of knowledge, expertise and self-confidence as bird costumed plague doctors of 1360 bleeding patients to correct bodily humours?  Of course, we know.  But nothing can justify the horrific sentence of misery imposed on these unknowing and trusting patients.  Before long, Betty will have lost her mind, become confused and suicidal and admitted to a psychiatric hospital for electroconvulsive shock therapy.  Bob will have become progressively weaker confined to a wheelchair with the diagnosis of autoimmune CIDP, crying every night, trying to comprehend what has happened to his beautiful, wonderful wife.  

It feels like Semmelweis all over again. 

Note: case presentations fictional. 

Tuesday, February 19, 2019

Babesia confusion


Babesia is a protozoan, a higher life form than bacteria. Both are single cell organisms.  The primary difference is protozoa have an organized nucleus containing DNA. It is a member of the phylum Apicomplexa.  This is a relatively small group of organisms. Its closest relative is Malaria; only Babesia and Malaria (Plasmodium spp.) are intraerythrocytic, meaning live inside red blood cells. Because of this, many therapies against malaria are also effective against Babesia.  Mainstream medicine offers two therapies only: quinine/clindamycin and Zithromax/Mepron (atovaquone). These approaches frequently fail and additional approaches are required. 
Historically, Babesia was first described in the 1950s as a cattle disease.  The first human cases, B. microti were described around Nantucket Island in the 1960s.  Many physicians have stubbornly, erroneously clung to the belief that human babesiosis on the east coast, is virtually always caused by B. microti.  Although B. duncani was first described on the West Coast, it currently accounts for the majority of speciated cases diagnosed on the East Coast as well.  More often than not the diagnosis is made without speciation. (the species of Babesia causing the illness is not identified).  There are more than 100 species of Babesia known.  Other species, MO1, CA1 are recognized human pathogens in the US.  B. divergens, a bovine species, is known to have jumped species, cow to human.
Most Lyme doctors make the diagnosis empirically, based on symptoms.  Underused diagnostic tools include Giemsa stains and FISH tests.  Many Babesia symptoms are nonspecific.  In my practice I especially pay attention to a triad:  night sweats +/- feeling feverish, air hunger and change in emotional state – especially random bouts of tearfulness. 
For many patients the two “standard” therapies, as stated above, proves ineffective or only partially effective.  Other therapies may be effective and medically necessary.  Therapies must be science based and rational. The term evidence based refers to mainstream treatment vetted through a peer reviewed process and frequently, not always FDA approved.  Second tier drugs and therapies are used when “evidence based” treatments have failed.  Science based approaches require biological plausibility, e.g. med works well against malaria and/or their use is supported by body of empirical evidence, e.g. traditional herb has been used for a century to treat malaria.  Doctors prescribing these therapies need to be knowledgeable about the disease.  
One approach/theory must be debunked.  This is the idea that 4 months of treatment is all that is required.  The basis for this thinking is that red blood cells only live 120 days. Therefore, after 4 months every infected red blood cell will have been replaced. It may sound plausible, but the reasoning is not sound. Every red blood cell (RBC) has a different birthday and at a different point in its lifecycle.  Cells are destroyed and made every day.  Infected senescent cells may transfer merozoites (infecting stage of parasite) to new born cells on any given day.  There is no specific duration that will always be effective. A short course of therapy, e.g. 3 weeks of quinine/clindamycin could at times achieve compete remission. 
Antimalaria drugs make work well but not all antiprotozoal drugs kill Babesia. This seems to be a common misconception.  Some drugs used to treat toxoplasmosis (like Mepron) may be effective against Babesia.  Drugs active against, Giardia, Amoeba, Leishmaniasis and other protozoans will likely not be effective.  Flagyl is a broad-spectrum drug with activity against Giardia and Amoeba. It is also an effective anti-Lyme drug. It has no activity against Babesia. 
Anti-worm drugs, such as ivermectin, is active against microfilaria, and has no antibabesia properties.  If the drug provides relief of symptoms it is doing something else.
Unless you are a scientist -- reading about complex cellular biology, biochemistry, etc. is likely only to confuse. A patient copied and pasted something from the internet which claims that Babesia infection suppresses the production of nitric oxide.  The truth is that Babesia infection activates macrophages and stimulates the production of nitric oxide (NO).  Nitric oxide is an extremely complex signaling molecule and an entire science journal is dedicated to this one compound. Reading about cytokines and metabolic pathways, killer T cells, Th1, Th2 etc. and trying to apply it to your illness is an example of how a little knowledge can be dangerous.
The Mepron/ Zithromax combinations is the most widely used initial approach.  The higher dose, Zithromax 500-600 mg and Mepron 2 tsp twice daily is more likely to be effective.  Medication doses are within FDA recommended levels.  This is generally the best place to start. 
Quinine/clindamycin is too toxic for most to tolerate but is very effective. 
Malarone has been used in lieu of Mepron but the dose of the active ingredient, atovaquone is quite low. 
The traditional herb artemisinin has a long track record and is a very helpful adjunct to treatment.  Combining active artemisinin with the whole plant (artemisia) may enhance adsorption and bioavailability.
The FDA approved Coartem contains artemether, a more active derivative of artemisinin and is very effective. 
Liposomal artemisinin available through a compounding pharmacy is a potent alternative. 
Artesunate is another artemisinin derivate, available in other countries; it may also be highly active.  An oral version of the agent is also available through TCM (Traditional Chinese Medicine) sources. 
There are many traditional herbs, this is a partial list.   Cryptolepis can be very effective at times, sold as a single agent through a compounding pharmacy.  
Herbal combination therapy, described by Buhner: cryptolepis, sida acuta and alchornea may be an effective option. 
Daraprim (with leucovorin) folic acid antagonist, a drug typically used to treat toxoplasmosis and has some anti-Babesia properties.  It may be helpful adjunctively. 
Larium, related to quinine (with doxycycline) is very effective but its use has been limited because the side effect depression. 
Antibiotics, generally not effective as single agents.  IV clindamycin can be effective in stubborn cases. 
Bactrim touted to have anti-babesia properties is typically ineffective. 
Other, novel approaches have been used in patients with very resistant disease.  For example, the anticoagulant heparin coats merozoites and inhibits RBC penetration. (works in mice, some human data).


Babesia can be associated with numerous symptoms: fever, feeling flulike, malaise, fatigue, chills, sweats, headache, air hunger, cough, joint pain, muscle pain, cough, abdominal pain, nausea, depression, changes in emotional state and many others.

Clinically, Babesia is usually seen as a coinfection with Lyme and other tickborne pathogens and symptoms may be more confused.  Babesia is the second most common tickborne infection after Lyme. Long term remission is attainable in the vast majority of patients, time frame unpredictable.

Wednesday, February 13, 2019

Lyme ADD

Attention deficit disorder, ADD/ADHD brains operate in much the same way.  For purposes of this piece I will only discuss ADD. ADD is common, perhaps much more than appreciated. It may affect 20% of the general population. Symptoms vary tremendously in degree  and severity from one person to the next. 

ADD is closely associated with “executive function” disorder. Brain housekeeping functions controlled by the frontal lobe are askew.  Patients have problems with focus, attention and staying on task.  Minds wander. Patients are impatient and interrupt. They don’t follow conversations; their minds are elsewhere. Their memories are full of holes. They lose their keys, wallets and misplace important papers. They forget where they parked their car at the mall. Routine tasks don’t get done, like washing dishes or filing tax forms. If something interests the ADD brain the person may hyper-focus: play a video game for hours on end, stay up all night reading a book despite predictable exhaustion the next day.  It is not all bad. People with ADD can be extremely creative, interpret the world in unique ways.  For example, only an ADD Einstein could imagine what it is like to travel next to a beam of light and discover relativity.  The same Einstein never learned to drive a car, he lacked the required focus. (Einstein’s brain was unique in other ways as well). ADD people are risk takers, which may be good or bad. They have other unique personality traits/quirks. 
These are the symptoms I hear every day from Lyme patients. They have ADD. Adult ADD. Or do they?
Adult ADD is a misnomer.  ADD is a genetic brain glitch. You are born with it. Symptoms should be present in elementary school or before.  Preexisting ADD may be discovered at any age.  Once it was believed that ADD, a pediatric disorder resolved over time. Perhaps the hyperactivity component resolves in many cases; the important frontal lobe executive dysfunction does not. 
The important question for a Lyme patients is: were you like that before?  If the answer is: no, I was precise, organized and orderly. Then the diagnosis is not ADD.  It is Lyme masquerading as ADD, or “Lyme ADD.”  Findings on functional brain scans, like SPECT may be similar to those seen with ADD.  Patients with preexisting ADD are afflicted the most. They experience ADD on steroids. 
Of course, Lyme, Lyme brain, Lyme encephalopathy, neuroborreliosis (synonyms) are treated with antibiotics etc.  But “Lyme ADD” patients can also be effectively treated, if only temporarily with classic ADD drugs and experience much improvement. 
Stimulants tend to be the most effective agents and may be multipurpose since most patients are suffering with severe fatigue as well.  Drugs like Nuvigil work only for wakefulness, not for ADD.  The principal drugs are Ritalin and Adderall and there are multiple variants. 
Proper dosing, side effect are other clinical details are outside the scope of this discussion. 

Appropriate treatment may drastically improve quality of life for many suffering with "Lyme brain."

Thursday, February 7, 2019

Lyme and Hashimoto's.


It has been reported by “Lyme doctors” that Lyme infection is associated with endocrinopathies (disorders of the endocrine system). The most frequent is thyroid disease, generally autoimmune hypothyroidism AKA Hashimoto’s disease.  When looking at Lyme associated endocrine disorders, we need to take them one at a time.  A patient I saw today gained 70 pounds and was first diagnosed with hypothyroidism prior to Lyme. Thyroid supplementation helped him loose the weight. Thyroid disease, particularly autoimmune Hashimoto’s disease is very common. Lyme is very common. But do Lyme patients have hypothyroidism more frequently than would be expected on the basis of chance? Is there is a causal relationship? Hypothyroidism is almost entirely autoimmune. Anti-TPO and other anti-thyroid autoantibodies are invariably present. First off, we know that Hashimoto’s is a familiar disorder, e.g. mom and 2 daughters all suffer with it.  It has been well established that there is genetic predisposition, i.e. HLA DR3, DR5 mutations. 
Autoimmune disease likely is caused by several different mechanisms, one is called molecular mimicry. It has been reported that Bb shares certain amino acid sequences with thyroid proteins.  Antibodies directed against Lyme, in genetically predisposed individuals, may precipitate the productions of self-directed antibodies.  In other words, Lyme antibodies accidentally trigger anti-thyroid antibodies in some cases. 
It appears there may be a causal relationship.  I don’t think there is anything published confirming this suspicion. 
Most endocrine disorders are not autoimmune, including: hypothalamic, pituitary, adrenal disorders, sex hormones and (? POTS -- angiotensin 1 receptor).  If relationships exist, other factors are in play. 
All of my Lyme patients, who invariably complain of fatigue, have their thyroid functions checked.  Most doctors just screen with TSH.  T3 and T4 may be helpful but anti-thyroid antibodies are essential.  If these antibodies are present the patient will need thyroid supplementation sooner or later. If they have exhaustion – sooner, irrespective of the other numbers (except with hyperthyroidism or Grave’s disease).

Thursday, January 31, 2019

Lyme disease and Sherlock Holmes: facts precede theory


Lyme patients, suffering with chronic fatigue, chronic pain, cognitive difficulties seek medical care through “the system.” Where else would you go?  
More often than not, the doctors, the healers? dismiss patient symptoms and concerns, the tears and misery,  not looking up from the omnipresent computer screen saying it’s all in their head, without emotion, without a single iota of compassion or empathy.  
Patients seek validation, but it is not to be found as the physician scribbles a referral for a psych eval as he calls "nurse" and moves to the next exam room. 
The healer is gone, replace by an evidenced-based robotic technician.
A 30-year-old former military officer complains of: severe fatigue, generalized pain, weakness, brain fog, “strange symptoms,” and bouts of presyncope (almost passing out) leading to ER visits was told by one doctor he suffers with a psychosomatic disorder. He lives in a wooded area; favorite activities including running through the woods with his 3 dogs (none treated for ticks), hiking, camping and running. He trained in Quantico VA, crawling through tall grasses and wooded areas 7 years ago.  Doctor after doctor after doctor found nothing wrong, and all reassured him that he did not have Lyme -- because the standard test was negative. 
A 62-year-old female has been diagnosed with longstanding, severe fibromyalgia. She is plagued by allodynia (touching skin excruciating) and she exhibits diffuse, paired tender spots: neck, trapezius, interscapular, paraspinal, SI, chest wall, anterior shoulders, above elbows and knees, anserine bursa area, ankles, heels, shins and other. There is no evidence of joint inflammation, swelling, warmth or redness. (Classic findings of fibromyalgia). Her rheumatologist diagnosed post-Lyme arthritis and wants to prescribe Zeljanz. The patient didn’t even know the drug is an immune suppressing biological until I told her.  In this case a rural rheumatologist accepted a non-CDC interpretation of a Lyme test.  
Sherlock Holmes was a very smart guy (physician author, Arthur Conan Doyle). Paraphrased, he said:  you must collect all the data before formulating a theory; if you start with theory you will twist the facts, to comport with your theory. The theory (therefore conclusions) will be severely biased. Roughly what he said. 
If you start with theory, the foregone conclusion really that Lyme is rare, presents classically doesn’t persist etc. (IDSA theory), you dismiss, distort or spin the facts, crucial facts -- like crawling through grass and woods surrounding Quantico VA, camping, hiking and hunting. If you start with an open mind, collect the facts and process them, a different theory clearly emerges: patient one is suffering with manifestations of Lyme. 
The theories or hypotheses must fit the facts. Doctors must start with a reasonable fund of knowledge. I think patient 2 was diagnosed with posttreatment Lyme disease syndrome.  OK. Maybe.  However, the diagnosis of post-Lyme arthritis and the recommendation of Zeljanz can only come from a place of creative ignorance.  Perhaps attractive drug reps are leaving samples. The dangerous drug goes for more than 2000.00 dollars a month. 
Lyme disease complex -- our understanding of the disease nascent, a work in progress. Different practitioners are finding different ways of understanding the disease guided by differing philosophies, belief systems and so on.  A work in progress. 
Chronic Lyme disease is what I have been chasing all these years. 

How do I define chronic Lyme disease:
Lyme disease is a chronic, complex, (usually) multisystem disorder characterized by an intense inflammatory response causing a wide spectrum of symptoms and syndromes, associated with persistence of the causative microorganisms (Borrelia species), frequently in conjunction with other opportunistic microbes (co-infections) which also tend to persist.  Something like that. 
How do we define posttreatment Lyme disease syndrome?
Perhaps we need to return to the wisdom of the late 19th century detective.  It has the same definition. It is really the same thing except the afflicted patient has treated with a formulaic course of antibiotics which proved ineffective.  Bending over backwards, to compromise with the Lyme deniers may admittedly be destined to fail.  Is it a workable bridge or a bridge to nowhere?  The designation of PTLDS may have a dark side if used as a justification for prescription of dangerous biologicals. The facts are the facts.  Facts must precede theory. Evidenced based guidelines (IDSA) start with entrenched theories; facts are twisted to the breaking point in support of deeply flawed beliefs which are severely biased – at the very least.  It is elementary my dear…