Wednesday, November 14, 2018

PTLDS vs chronic Lyme disease

There has been a lot of buzz about Posttreatment Lyme disease syndrome, PTLDS.

A number of papers over the past couple of years have described the syndrome, working towards a common understanding. Mostly the papers have been written by experts on the "I believe in chronic Lyme disease" side of the divide.

It is a narrowly defined entity. 
PTLDS applies specifically to a group of patients with a history of well characterized acute Lyme disease who were treated according to standard guidelines but despite treatment went on to develop chronic symptoms.  
Not included are:  patients who never had acute Lyme but developed chronic symptoms over time,  patients who in retrospect had acute Lyme, e.g. “summer flu” but diagnosis was delayed for months or years,  patients with a wide array of atypical, mysterious symptoms and syndromes (arguably the largest group), patients suffering with other tickborne coinfections,  patients misdiagnosed because CDC surveillance criteria were inappropriately used for purposes of clinical diagnosis,  patients misdiagnosed with a variety of illnesses ranging from fibromyalgia to MS, and patients infected with novel species of borreliosis and others. 

I have referred to the group as CLD, chronic Lyme disease. 

Nonetheless, the PTLDS name is important because it is now part of the EBM fabric. 

Patients who meet the criteria may escape the labels of psychosomatic disorder, fibromyalgia and CFS. (And, between you and me, once a concept becomes part of the EBM repertoire its definition tends to loosen quite a bit). Don't tell anyone. 

PTLDS opens a door. 
There have been only 4 NIH sponsored studies examining retreatment of Lyme patients. The meaning of the studies has been hotly debated for nearly 2 decades. The most important study is  last, published 10 years ago (Fallon 2008). In the double blinded randomized controlled study of a narrowly defined set of patients the results were positive.  The treatment group had substantial, measurable improvements. The "long-term" active therapy was 10 weeks of IV Rocephin. Cognitive improvements and constitutional improvements were present at 12 weeks. No further treatment was prescribed. At 24 weeks cognitive improvement was lost -- not durable with the 10 week treatment, but constitutional improvements persisted. 

The study conclusions have been misinterpreted and abused by those on the other side. 
Fallon writes in 2012: 
“Each of the U.S. treatment trials on PTLDS have concluded with the recommendation the course of therapy tested in each specific trial was not recommend…”
There is a difference however between whether a trial is effective and whether or not a treatment is recommended.”
“…treatment was shown to be effective.”

To state the obvious:  antibiotics don't make you smarter or fix brain dysfunction.

The studies shows a proof of concept. 
Science provides the cover for biological plausibility:  no effort to eradicate Lyme bacteria in mice, dogs or primates has proved effective. Persistence is demonstrated in test tube studies. Even a human study demonstrated persistence. 

The logic SHOULD be clear.  It is not controversial that people touched by Lyme can be miserable and disabled.  It is not controversial that Lyme bacteria persist. It is not controversial that additional courses of antibiotics have led to clinical improvements in patients -- the best CRTs.

The clinical trials have not helped us find an optimal therapy. But that was not really their purpose. Their purpose was to determine if chronic Lyme is real (not known at the time of the studies) and if patients  improve with additional courses of antibiotics. This was the big question of the day. 

Further research will likely be guided by empiric evidence garnered by practicing physicians. 

The optimal therapy for Lyme is a very complex clinical question and it will take many years or decades for us to get there.

PTLDS patients have a real illness. The patients are suffering with a chronic disabling illness robbing them of any vestige of a quality of life.  Antibiotics have the potential to make their lives better,

PTLDS or chronic Lyme disease?  Not exactly equivalent but heading in that direction. Post Lyme syndrome: RIP.

Any serious discussion about Lyme controversies between the two camps should start here. Chronic Lyme disease --  persistent infection is proved by science.

I will be working on a talk on: How to treat Lyme. I hope some will attend.

Tuesday, November 13, 2018

Medical EMF therapy: Should you use it?

Patients are increasingly using pulsed electromagnetic frequency devices.  They have been doing so for a long time.  The question for me is: what is it all about?

EMF, electromagnetic frequencies are a form of energy which made come from a variety of sources.  It is made up of waves (which are also particles photons-- quantum mechanics – skip this part).
Think of waves on the ocean. If the waves are close together the frequency is higher. When the waves are more spaced out the frequency is lower.  Taller waves have more energy than shorter ones.

EMF is similar.

The waves are usually invisible to our eyes, the exception is light.  Color is determined by frequency of the related EMF wave.
The properties of these waves of energy are amazingly different.  Very high frequency waves are harmful to our tissues and DNA – we call this radiation.  Other frequencies are responsible for infrared saunas, microwaves, radio and TV, medical devices and much more.

Sound is also transmitted by waves but is not considered EMF energy directly.

Devices using EMF and sound (ultrasound) are promoted for medical reasons.  The intensity of the waves – the amount of energy makes a huge difference.
There is a lot of good published evidence regarding potential uses of very low frequency electromagnetic energy and very low wave (ultra-low wave) sound energy in the treatment of various ailments.  I can find no peer reviewed data for rife.

Magnets produce EMF and are in clinical use, especially for depression (transcranial magnetic therapy).  Of note, scientist still don’t know how magnets work.
Doctors swear an oath “first do no harm.”

People can get sick from EMF waves, including childhood leukemia. This energy is usually intense and constant, e.g. electrical transformer next to house.  Some people feel they are so sensitive to EMF energy that they “get off the grid” and live in homes without electricity.  
EMF medical devices appear to be safe – so far.

I am conservative, so I like treatments I consider safe like ultrasound therapy (which also speeds up bone healing) and hyperbaric oxygen therapy.

People with Lyme and its various manifestations can be desperate looking for a magic bullet. We have not found it. Patient usually require a multi-modal approach.  
I am not a naysayer.  I am not saying EMF therapy is quackery. It may work well for you. 

I am a fan TMS therapy for depression: it really works. 

I do worry about slick purveyors overselling benefits of devices. If it sounds to good to be true it is likely untrue. 

If well informed patients want to use or try EMF devices go for it.  

Friday, October 12, 2018

Babesiosis, in color

Symptoms of human babesiosis are frequently crippling and disabling and rival those caused by Lyme borreliosis. Antibody testing is available for 2 species, B. microti and B. duncani. 
The most common species might be: Babesia species (unknown). 

Common symptoms of babesiosis include:  Night sweats, persistent low grade fevers, air hunger and becoming more emotional.  

Treatment can be challenging.  I think we are getting better at eradicating it with changing, complex approaches. 

Blood Giemsa staining frequently allows us a close up look.  We are able to provide the test in our CLIA blood parasitology lab.  All of these slides (images by me) from patient blood samples show pleomorphic variations of the red blood cell parasite/protozoan. 

Thursday, September 13, 2018

Vancomycin: the cure?

A study released from Northeastern University looked at the use of Vancomycin for Lyme. 

The drug which can only be administered intravenously and is more toxic than most commonly used alternatives.   IM therapy may be used but is perhaps very painful.  Oral vancomycin does not leave the GI tract and is only for C. diff. 
Studies are not in agreement.  Zhang found the drug to be relatively ineffective in vitro, as have others. 
The new study found that both Rocephin and vancomycin are effective against stationary phase cells – round forms and biofilms. Vancomycin was combined with a quinolone to sterilize a culture. In an immune deficient mouse doxycycline did not clear disseminated but both ceftriaxone (Rocephin) and Vancomycin were effective.  
Vancomycin may be slightly better than Rocephin but this far from clear.  Both inhibit peptidoglycan synthesis, the basis for cell walls.
In 2017, the Biophysical Journal published a study about the impact of Vancomycin on Lyme spirochete motility, significantly impaired.  The Peptidoglycan – cell wall material (under an outer membrane) was weakened with low concentrations, subtherapeutic, of vancomycin which also inhibited the formation of round forms or blebs.  Wounded spirochetes, unable to swim very far may do little harm. 
The drug may prove very useful, especially with subtherapeutic dosing, within a cocktail approach.
Vancomycin has been used for decades in the treatment of MRSA, a feared superbug.
The drug is very nephrotoxic and can cause irreversible kidney failure: serum concentrations and renal functions must be watched carefully. 
Although vancomycin is not hoarded over by ID docs like daptomycin, ID doctors will be concerned about sudden wild use of the drug.
Going back further, 1996 – A G Barbour, an IDSA stalwart, found the following. Vancomycin eliminated Lyme in immunodeficient mice only when given within 3 days of infection. When given at 7 days post infection the germs persisted; viable spirochetes were found in the mouse brains. 
In 1993 Barbour demonstrated that in vitro vancomycin was an effective anti-Lyme therapy.
It has been long known that vancomycin has anti-Lyme activity. 
We need to know a lot more. 
Treating Lyme falls within the large purview of “the art of medicine.” In “the system” so called evidence-based guidelines dictate medical practice. The guidelines dictate what the disease looks like and how it is to be treated. 
The existence of chronic Lyme as we know it is soundly rejected. Nothing has changed. 
Doctors who believe in chronic Lyme agree on a several things:  Lyme is a tragic, underappreciated epidemic; Lyme is very difficult to treat; Lyme has many faces, the “great imitator;” coinfections are an unappreciated huge factor and I am sure a few other things. 
Doctors collectively known as LLMDs are a heterogenous group.  They don’t agree on how best to treat the illness(es).  Doctors who treat the disease(s) realize we still know very little as we try to improve our approaches as times moves on. 
It is important not to jump on every new therapy as “the answer” and be mindful of toxicity and First do no harm
I ask readers to refrain from jumping from preliminary preclinical small, limited basic science trial data and making quantum leaps to a new people therapy. 
Vancomycin, unfortunately, is not the cure. 

Monday, September 10, 2018

Babesia cocktail therapy

A 56 year old male has suffered with Lyme off and on for the better part of 10 years.  Symptoms come and go but have fairly easy to control.

He suffers with a mood disorder.  Bipolar 2.  He has a history of mild manic episodes alternating with depression and the disorder is chemically controlled.

He has complained of recurrent low grade fevers and night sweats recently. He came in to my office stating his Babesia was relapsing.

He was right. The patient's blood smear confirmed the self diagnosis.

Some Lyme-literate people are quick to blame tickborne illness for everything - including all mental illness. It is easy to go overboard. Bipolar illness exists apart from tickborne disease in this case.

Babesia and other central nervous system infections may exacerbate preexisting mood disorders.

Lyme and associated infections have been associated with every neuropsychiatric syndrome reported.  Clues that infection is not the primary cause include: strong family history and mood disorder predates Lyme infection. 

Babesia is frequently associated with depression, especially increased tearfulness.

Babesiosis, the clinical syndrome associated with Babesia infection is frequently persistent, resistant to therapy and prone to relapse or recurrence. (Relapse same infection, recurrence new infection).

I have found multiple, simultaneous agents are needed.  Antimalaria agents are added sequentially creating a "cocktail" in much the same manner Lyme is treated

A new study was released last week ( UCLA) which amazingly discussed a new paradigm.  In the case of E. coli:  perhaps it best to hit highly resistant superbugs with 3-4 antibiotics, which all work by different mechanisms rather than a single drug which works only by one.

Some agents include: Mepron, Malarone, artemisinin, artemisia (bioavailability), Coartem - more bioavailable, cryptolepis,  "Buhner herbs" including sida acuta, Daraprim, Zithromax, Clindamycin, Quinine and low dose heparin.

For example, when Mepron doesn't do the job adequately it is not discontinued, rather something else is added. Patients may be on 3-4 agents simultaneously to get the job done.

We think human Babesia develop rapid resistance to various agents.

We don't know.There is no human data. Animal data supports the thesis.

The disease is underappreciated.  I suspect if suffers with guilt by association (Lyme).

As with Lyme, most experts believe in acute Babesia, not chronic babesiosis.

The Babesia lifecycle is presented below.  In mice the lifecycle is more interesting -- sexual reproduction. This allows for the transfer of genes from one organism to another. This is an evolutionary advantage RE the development of resistance.

In the human host the cells reproduce via an asexual process. The slides can look quite different at times. Most commonly small, dark staining round bodies are seen with Giemsa staining.

Resistance develops because random mutations -- mistakes made copying DNA -- occur with great regularity.

Sporozoites are released from an infected red blood cell.  The small forms attach to the cells and gain entry morphing into the larger merozoites. The merozoites divide in cells, rarely 2 at a time (Maltese Cross). The red cells rupture and the cycle repeats.

Additional information: sporozoites morph into an intermediary ring form, trophozoite before becoming a merozoite.  Ring form are readily observed.  Mature merozoites can rupture creating vermicules, small infective particles. These are harder to pick out. Intermediary morphological forms can present in many ways.

Friday, September 7, 2018

Are you a tick magnet?

Do mosquitoes make a beeline for you and ignore your companion?

You are not crazy.  Ticks do like you. 
A recent European study showed a species of Ixodes ticks preferentially seek out certain blood types.  From the ABO Rh subgroups ticks prefer type O blood and type B blood is relatively protective. Ticks find type A blood only slightly less appealing. Ticks, mosquitoes and other blood sucking insects are primarily attracted by CO2 but there are other important factors. The insects can detect hundreds of volatile organic compounds which emit signature scents from our skin. Sweat plays a role. Skin flora play a role. Other genetic factors may be in play. 
I am lucky and have type B blood – 9% of the US population.  You are probably not so lucky. 
It is true:  some of us smell sweeter to ticks and mosquitoes than others of us. 
Certain chemicals make us less attractive.  DEET and Picardin are well known insect repellents and are moderately effective. Other natural substances may be effective, such as: lemongrass, citronella, cedar, peppermint, lavender and geranium. 
I have no specific recommendation here.  There is a lot of discussion on the internet.  A patient recently told me he combines several of these substances and has good results. 
The most important preventative is permethrin. Permethrin is applied to clothes and allowed to dry overnight.  Clothes pretreated with permethrin are commercially available.  Permethrin persists in/on fabric for a month or more – even if clothes are washed. 

Wednesday, August 15, 2018

Lyme and the rule of 3s.

I had this conversation today. 
“Are Babesia symptoms better?”
“Which are those?”
“You have had Lyme for 10 years. Let me try to make it simple.”
Here is -- I hope -- an easy way to remember Babesia symptoms and others.

Rule of 3s.

3 pathogens.
Each pathogen has 3 prototypic, characteristic symptoms.
A patient yesterday what to know if she was different because she has Rocky Mountain Spotted Fever. 
First off, she does not have and never did have Rocky Mountain Spotted Fever.  The positive test shows cross reactivity to other related species of Rickettsia.  
As a rule, it doesn’t matter what else you tested positive for, outside of the big 3.  They get better. Almost always. 
The big 3 pathogens may not get better.  They are tenacious and hang on despite best efforts. 
Lyme is variably pathogenic.  The other two are opportunistic conspirators.  They hit you when Lyme has knocked you down and jump into the fray. 
We start with an alliteration. 
Borrelia (Lyme), Babesia and Bartonella. 
These are stereotypic symptoms. You may have a few or none of the above. But here it goes:
Lyme:  Fatigue.  Pain (tends to come and go) and brain fog (cognitive dysfunction).
Babesia:  Night sweats (at times fevers).  Air hunger.  Depression, especially random tearfulness. 
Bartonella: Pain, not joint (shin, heel, neck, headache), craziness (irritability, anger, rage, psychosis and others) and rashes.
After I presented my rules of 3s, the patient said:  Yes. Nigh sweats and air hunger are improving.  Mood is better.  Babesia symptoms. 
You might want to know why these pathogens are different from all others. Why won’t they just leave?
Narrative of persistence. 
We explain persistence of pathogenic microbes with a science based, biologically plausible explanation. 
Lyme:  Context is always important.  A few points.  Doctors have argued about the existence of chronic or persistent Lyme symptoms for decades.  First: no such thing.  Then: Post-Lyme syndrome, autoimmune residua. Now: Post treatment Lyme disease syndrome.  The new term is a concession to science. Science informs it has thus far been impossible to eliminate Lyme from mice, dogs and monkeys. Further, some studies prove persistence in humans after treatment. Lastly, Lyme is about impossible to eliminate in a test tube. The experts who propose no chronic Lyme have been wrong on the first two account are sure that got it right this time.  Even if organisms persist, additional treatment hurts patients and doesn’t help them.  Patients have chronic persisting infection.  Long-term antibiotics make symptoms go away, frequently only temporarily. The other side has been wrong 2/2 times. Shall we go for 3?
Babesia:  If I failed to mention it. I did. Lyme is pantropic, meaning it goes everywhere, infects virtually every tissue and organ.  Babesia is organ specific – blood system.  It’s minions exclusively inhabit red blood cells.  Clinically we know it doesn’t go away because it keeps coming back.  We side it hides or sequesters in small blood vessels (capillaries), the spleen and bone marrow.  The mechanism is not fully understood. In general, the immune system functions poorly within cells. 
Bartonella: Lives in cells lining blood vessels.  Hides inside cells or sequestered in the intracellular milieu. This is a safe harbor against the immune system.  Clinically the thing is difficult to kill. 
We have effective treatments for the all the above. Some new things are working. If you would like to learn more call our office for a consultation.