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.

Sunday, June 24, 2018

C. Diff and doxycycline magic

C diff is a dread complication of antibiotic therapy. Clostridia difficile, an anaerobic bacterium may reside in gut as an innocent bystander, causing no trouble unless something happens.  We call this germ an opportunistic pathogen.  It causes disease only when favorable circumstances present.  The degree of illness varies.  It may present as diarrhea which resolves when antibiotics are stopped or a life threatening disease. 
Risk factors  for C diff are well known.  Antibiotics are at the top of the lists. Other risk factors include age (greater than 65), chronic medical illness, hospitalization and admission to long-term care facilities, including nursing homes. 
C diff patients may have diarrhea:  frequent, watery stools. There may be associated mucous and/or blood and stools may be fowl swelling.  Symptoms and signs of more serious infection include:  fever, elevated white blood cell count, abdominal pain, abdominal swelling and shock. 
In the past Flagyl and Vancomycin were effective therapy. A new drug, Dificid is approved for C. diff.  Drug resistance strains have started appearing, of great concern. 
Sometimes infection is like a runaway wildfire and very hard to stop.  Surgery may be required. Fecal transplants are sometimes used.  Fatal cases occur. 
We like to think probiotics ward off the disease, but this is far from certain.  Traditional probiotics may have some benefits, but limited.  Florastor or Saccharomyces boulardii may be slightly beneficial.
There is something else to consider before we discard long-term antibiotics. 
The choice of antibiotic makes an enormous difference. 
When first described, C diff was tied to clindamycin. Later it was learned that other or most antibiotics can cause C diff colitis. Sometimes it is writ that “any antibiotic” can cause C diff.  Maybe not.
There is a hierarchy of which antibiotics and classes of antibiotics are most likely to cause C diff.
Clindamycin is at the top. Quinolones including Cipro and Levaquin are a close second. Cephalosporins, including Ceftin are next. Penicillins like amoxicillin are on the next rung. These drugs are all considered high-risk.  The next group, medium-risk, includes Macrolides such as Biaxin and Zithromax and Sulfa drugs such as Bactrim. Low-risk drugs include tetracyclines, doxycycline and minocycline, rifamycin including rifampin and certain antiparasitic drugs including Flagyl. 
And this brings us to my next topic. Doxycycline: the magical drug. 
It turns out that studies show not only that doxycycline is a C diff low-risk drug, but doxycycline seems to reduce the incidence of acquiring C diff when compared to a control group taking no antibiotics.  In other words, doxycycline may protect against getting C diff. 
This is huge.
No wonder dermatologists prescribe doxycycline to armies of 15-year-olds with impunity. 
Rifampin may have a similar benefit, lowering the risk of C diff. 
 Although there is not data regarding Flagyl, claims to the contrary, it is likely the risk of Flagyl is very low since this is one of the traditional drugs used to treat C diff. 
The prejudice against doxycycline percolating up through internet sources is unfounded.
It stems from the fact that doxycycline is ineffective against Lyme persister forms, round forms and biofilm communities. Take another look.
Doxycycline is the most active drug against spirochete forms.  No one drug does a great job killing persister forms, except daptomycin which is not a realistic option.  Cocktail therapy always works best. There is one drug which shows up in every cocktail group proposed through Zang’s research, with on exception, that is doxycycline. In the other group minocycline was used instead. 
Doxycycline appears to have unique, broad synergy when combined with a host of other antibiotics from other classes. 
Lyme killing cocktails rely on synergy between or amongst chosen antimicrobial agents. The above data show possible advantages of cocktail combining doxycycline, rifampin and Flagyl (Tindamax) and/or artemisinin, in some form (in theory).  Informational purposes. I am not recommending any specific therapy.  

Test tube data are really important, especially at this stage of our understanding,. This data cannot be and should not be translated directly into clinical recommendations. Please. 
There are other factors the Zhang data cannot take into account.  Antibiotics in a test tube are judged based on concentration in a culture broth, a surrogate for serum concentration. It turns out that the ability of drugs to concentrate in tissue is extremely variable.  Tissue concentration of an antibiotic, for example doxycycline, are frequently many fold higher than serum level.
This might seem irrelevant because after all, doxycycline has no impact on non-spirochete forms. Right? 
Maybe not.  In the 2017 study round forms of Borrelia burgdorferi, Lyme bacteria were cultivated the effects of many agents tested.  A goal of the study was to test the effects of sulfa drugs. Sulfa drugs performed poorly.  Drugs were tested at three different concentrations: low, medium and high. Concentrations are reported in molar values and I have no idea how this compares to real life serum values. The data show that as serum concentration increase the ability of the drugs to kill the round, persister form increases. At higher concentration doxycycline starts to diverge from the control and show benefits comparable to other drugs and drug combinations (still poor), having an impact on round forms. 
 Other factors are: bioavailability, tolerability and toxicity, clinical factors outside the sphere of test tube studies. Clinically, these are all very important.
Doxycycline has unique bioavailability, nearly 100% when taken orally. It is not metabolized by either the liver or kidneys. It has very low toxicity and is often well tolerated. These factors are clinically very important. 
Then there is the other thing, when it comes to treating and/or preventing tickborne infections.
Only one drug can kill germs associated with:  ehrlichiosis, anaplasmosis, STARI associated Borrelia species, Rickettsia (including Rocky Mountain Spotted Fever), Mycoplasma, Chlamydia pneumonia, tularemia, brucellosis and prevent early bartonellosis and babesiosis. 
You guessed it:  Doxycycline. 
Sure, a lot of people don’t tolerate it well in the summer and a lot of people experience GI upset.
Minocycline may be second choice, although I can’t say it has all the same benefits.
Keep this is mind when amoxicillin is offered as the second choice drug after a tick bite.

Tuesday, June 19, 2018

A 24 year old male with brain fog and more

Dear readers:

Thank you for reading my Blog which is now in its 10th year.

I am trying something different:  talking rather than writing. I am more experienced with the latter.

For those who live nearby:

I will be giving a presentation in the conference room in the basement of my office building in Rockville, MD

15245 Shady Grove Road (North entrance) on June 26, 2018 -- one week from today, 6PM.
The talk will not be recorded.

I am planning on doing a series of talks over the ensuing months.

Last month I discussed an approach to patients suffering with fatigue, pain and cognitive symptoms.

This talk is something different.

I present the case of a 24 year old male complaining of brain fog.  Symptoms are added one at a time leading us in different directions as the case unfolds.

I am adding a brief talk (I just put together) called Lyme the Big Picture to precede the other.

I will be taking Q&A at the end.

We do have limited space.  If possible call my office and gives us a heads up.  Reservations not required.  There is no charge.

I will continue to write the blog as well.

Dr. Jaller