Mysteria bugs

In the past I talked about mystery bugs -- I know a few things I didn't before. One researcher at NIH, still unpublished, came upon the issue through serendipity. He was looking at some stem cells and found they were "contaminated" with a protozoan. But his samples were not contaminated. The bug was a consistent finding.  He then spent a lot of time trying to identify the bug. Its DNA sequencing, not complete, shows something novel. Definitely not Babesia. What is paradgm shattering and probably wont be recognized for decades, is that humans are born with symbiotic organisms. This is something not known to occur in any family of living organism higher than cockroaches! Symbionts are not necessarily bad: in fact they are likely necessary for good health. Symbiotic organisms can be comensual: no harm, no foul. Or they can be mutualistic: you scratch my back, I'll scratch yours. They might  be pathological, maybe only in immune suppressed or opportunistic scenarios. As it turns out, some observations have been made that the numbers are high is some disease states and low in others. In other words, the bug count is not predictably high in all disease states. The idea of blindly trying to kill all the bugs may be a very bad idea. Mainstream scientist, with electron microscopes and large DNA sequencing labs are onto all this, but not yet talking. It appears Dr. Fry has independently found the same thing. We are born with the organism in our cells, tissues. It appears the same applies to at least one bacteria and one virus. Described as Chinese dolls: the protozoan within human cells, the bacteria within the protozoan and the virus within the bacteria.

This should not be confused with the human microbiome. It is widely reported that our bodies host 10 times more procaryotic/bacterial cells, than eucaryotic/human cells. A huge diversity of bacteria, thought of as our normal "fauna and flora," inhabits our bodies carrying out comensual and mutalistic roles. These bacteria are believed to be acquired after birth and occupy specific niches. Mostly the bacteria are found in the gut, skin and mucous membrane surfaces. They do not live in other compartments considered sterile such as bone marrow elements and blood.

The mystery bugs discussed above are present inside our cells, are apparently passed from mother to fetus inter-utero and are apparently present in large numbers but not previously observed. I have been told these organisms are camouflaged within the nuclei of human cells.

Then there is the issue of mystery bacteria. They don't show up in stains like Bartonella and DNA identification has been elusive. My sense that many of these are symbionts and.they may seen in large numbers in  patients whom are ill or immunosuppressed. At least one symbiotic bacteria has been observed, an unknown L-form. These unknowns are not something we need to target per se, but may be seem as a bell-weather, marking the severity of disease.They may not stain because their basic structure is something we do not yet understand: we don't have the right strain. Some bacteria have very unusual structures.

This leads me to the next Blog.

Goodbye Family Practice, after 30 years

I have now transitioned from primary/care to a Lyme consultative practice.

I don't get to diagnose patients in the "general population."

The chief complaint of patients visiting a primary doctor is musculoskeletal in nature about 30% of the time. For some reason, the incidence of peripheral neuropathy is on the rise; I was surprised to read that "idiopathic." unknown cause, is found more often than diabetes. ( old joke: idiopathic means the patient is pathological and the the doctor is an idiot). OK, so how many of these patients and others have Lyme disease?

Then there is the growing population diagnosed with fibromyalgia:  many treated with drugs that are supposed to help but only make things worse.

The really sick patients might see 40 doctors before visiting with an "LLMD" if they are lucky.

Many patients will be left disabled with "mystery diagnoses."

Of course if I am not there to diagnose a few,  my former patients will suffer the fate of so many others. Perhaps when patients hear I have left primary care to treat Lyme disease it might communicate something.

HMOs and managed care allows for 6-8 minute visits with a primary care doctor and focused evaluations by specialists who never see the bigger picture. Even the more open minded physicians operate in a system which deprives them of the energy or time to look elsewhere.

This is all rather depressing so I will turn my attention elsewhere.

Peripheral neuropathy: a very common Lyme problem

In my practice, one of the most common set of symptoms, or a syndrome relate to peripheral neuropathy. Peripheral neuropathy is caused by nerve damage, which may be temporary, stable, progressive, mildly bothersome or disabling: Nerves are comprized of two parts which may be damaged: 1) axons, the body of the nerve and 2) myelin, the sheath around the axons of nerves. Nerves are then divided into sensory neurons ( associated with sensation) and motor neurons( associated with muscle activity). The nerves can come from different pathways: spinal nerve roots, the dorsal ganglia, peripheral nerve trunks and branches, autonomic nerves. Neuropathies can effect sensory nerves, motor nerves or more commonly both.

Differences between axonal and demylinating neuropathy can be seen with a routine exam:  large sensory fibers abnormalities may be associated with decreased sensation to pin prick, light touch and vibration. All that is needed is something sharp and a tuning fork. Small, unmylinated sensory fiber abnormalities associated with decreased temperature sensation.

Sensory symptoms of axonal small fiber neuropathy, may for exmple, inclde:   burning pain, radiating/lancinating/ electrical like sensations, pins and needles, increased sensation to light touch, numbness and reduced sensation.

Motor symptoms may include: weakness, muscle wasting, cramps, fasiculations, difficulty climbing stairs, decreased hand grip and restless leg syndrome.

Major characteristics of axonal vs demylelinating neurve damage can be seen with the EMG/NCV. Simply put: Axonal problems are seen with needle portion of the test and demyelinating problems are seen with the shocking part of the exam.

Some patients, with clear symptoms and abnormal physical examinations have negative EMGs. There is another test.

Patients may have small-fiber neuropathy not visable on an EMG.  This can be diagnosed with a biopsy of 2-3 areas of skin sent to a specialty lab.

The lab reports the "ENFD" - Epidermal Nerve Fiber Density. The test is fairly accurate.( I can perform this simple test in my office).

Most treatments for neuropathy are only symptomatic. The only therapy I have found to be curative is IViG. This therapy is extraordinarily expensive, costing $10,000 per dose given every 3-4 weeks. The FDA has approved IViGfor a limited number of conditions. It may be possible to get insurance coverage for some forms of neuropathy like CIDP which is discussed elswhere.

Babesia: an example of failed “evidence based medicine.”

When I was a 3rd year med student, some 33 years ago, we wouldn’t be having this conversation. Medicine, as practiced at that time would have understood we are in the midst of a devastating epidemic. Medicine, as an art, was practiced in a slower, more methodical fashion - when MRI machines, managed care, the debasement of physicians as “providers” and “evidence based medicine” were not on the horizon. In an era devoid of CT scanners patients were admitted to hospitals for diagnostic evaluation - old fashioned tools (and emerging technology) were at least equal partners. The new and improved practice of medicine is “evidence based,” which encompasses the opinions of experts as evidence. Evidence is not truth. Evidence relates to facts or interpretations of facts. Inevitably, the “truth” hinges on which evidence one chooses to consider. Medicine is ever evolving: the state of the art is always a moving target. The clinical practice of medicine should consider evidence from a wide variety of sources. Studies in laboratory animals is evidence. The clinical experience of many patients and physicians is evidence; and published studies are evidence. In the final analysis: medicine is still at its core, a healing art; it is not a science. When I was a medical student a patient suffering with multiple complaints: fatigue, fevers, sweats, headaches, shortness of breath, joint and muscle pain, numbness and tingling, mental changes, hallucinations - would be seen as sick - not crazy, because of a life-long relationship with a personal physician who knew the patient well. Patterns would be uncovered with many patients admitted to hospitals with overlapping features. I think blood would have been examined by non-rushed, hospital employed pathologists looking for parasitic illness: a basic tool. Malaria-like parasites within red blood cells would be seen: Babesia species. In “Clinical Vaccine Immunology,” November 2010, the authors report that evidence of Babesia duncani was found in 2% of blood donor samples and 27% of clinical samples. B. duncani was found to be distributed throughout the United States, including my state of Maryland. Contrary to dictum, Babesia microti was found much less frequently. In the Medscape “peer reviewed” reference, April, 2012, “Drugs, Disease and Procedures,” Dr. Cunha,and colleagues provide a topical summary of Babesiosis. Other, CDC accepted species of Babesia, MO1, CA1 and Divergens have been shown to cause human disease in the United States for which do not test at all. In Europe, human disease is associated with various species, including B. bovis, once only known as a cattle disease. (B. divergens, also from cattle, is the predominant agent). The authors report B. microti and “B.microti-like agents” in Europe causing human disease. At least one unknown Babesia species has been linked to human disease. Over 100 species of Babesia are known to exist. The 27% number for B.duncani presented above, may represent only be the tip of the iceberg. Currently used high tech procedures: IFA, PCR, FISH are of limited diagnostic value. The definitive diagnosis of Babesiosis hinges on the observation of organisms seen in a fresh (less than an hour old) meticulously stained blood smear, carefully screened by an experienced observer; numerous fields, over 100 must frequently be screened. Degraded blood smears examined by busy, mill lab techs are of no value. Bartonella are much easier: species jump off the slide as soon as you look. In bygone days, physicians used the tools readily available: a tuning fork, a stethoscope, a microscope and something else, much more important - our brains. In this day and age of “evidence based medicine,” where medicine is considered a science; where limited studies(which are not science) are taken out of context, the results of which unreasonably generalized; where physicians work on corporate/HMO time clocks; where the autonomy of individual physicians has been relinquished to “the experts;” where doctors are encouraged not to think for themselves; where medicine has become a job, not a calling; where the art of medicine has been tossed out like the proverbial baby in the bath water - much is lost. Discoveries which might otherwise be clear, are lost in the muddied waters of “mainstream” medicine, blinded by a dysfunctional system and by its own arrogance.

Babesia and menopause

I recently started treating a 53 year old woman with a clear history of Lyme disease; and she had also tested positive for B.duncani  at the lowest cut-off point of 1:256 via Labcorp. She was perimenopausal and  had hot flashes and night sweats.  She thought the night sweats were due to menopause. A single 3 day course of  Coartem did not make any difference. We discussed a strategy for sorting things out. I suggested she go on estrogen therapy for 1-2 months to see if the sweats would abate. If the sweats went away then the likely cause was menopause; if they did not active Babesia infection was more likely.

She went to her GYN to try HRT. She did not like straight estrogen and started bio-identical HRT. Almost immediately she started feeling much better.

Her energy level increased, her mood improved -  as did  her overall sense of well-being. The hot flashes went away. The night sweats got better but persisted. At this point she decided to stay on HRT.

A rule of thumb with Lyme patients is to treat all the other stuff and  see what remains.

The same patient had a history of borderline hypothyroidism on no replacement therapy at the time.  A TSH level was 3.4: low dose of Cytomel, T3 thyroid was started and this perhaps also helped with mood and energy.

This patient had clear other evidence of Lyme disease, with a CDC positive test. Psychological symptoms including depression, severe, with  hopeless were described. Luckily, the depression quickly resolved. Her Lyme had only been treated with a low dose of doxycycline.  It seemed treating thyroid dysfunction and menopause made the biggest difference.

Of course I did recommend further treatment for Babesia: not urgently.

I will veer off the usual topics  for a moment.

Is hormone replacement safe for menopausal women?

When I was a medical resident you were almost committing malpractice if you didn't prescribe it: it lowered the risk of heart disease, decreased the likelihood of osteoporosis - all without increasing the risk of breast cancer.

Things have changed. Now if you prescribe it you are almost committing malpractice. Perhaps the pendulum has swung too far. HRT was found to increase heart attacks in women with known heart disease. This should have been expected since estrogen increases blot clots. Estrogen is associated with a tiny increase in the incidence of breast cancer, but not mortality. Maybe HRT isn't so bad after all.

I have previously discussed the controversy regarding an optimal TSH level.

Beating Lyme is always easier when one's general state of health is better. Optimal management of hormonal issues may make treatment easier and more effective (or not). Anyway, she is very grateful because she feels a lot better.

Blood brain barrier

A lot of patients are concerned about the blood brain barrier (BBB). They want to know which antibiotics pass through it and/or if only intravenous antibiotics are able to traverse it.

Well then, what is the BBB? It is a diffusion barrier created by special features of small blood vessels leading to the brain. The lining of these vessels, the endothelium, contains unique cellular elements. Tight junctions in the endothelium (inside walls of blood vessels) are made up of a number of factors including "astrocyte end-feet." Astrocytes are supporting cells found in the brain. Most importantly, the BBB keeps out most blood borne substances including antibodies. Antibiotics that cross the BBB tend to have certain physical characteristics including: small molecular size, being lipophilic, binding to fatty molecules on cell membranes, low plasma protein binding and other specialized characteristics.

One of the best drugs is the original, used to syphilis, penicillin. Penicillin derivatives like amoxicillin are also effective. Cephalosporins do not do as good a job; there is some penetration. Then for brain penetration amoxicillin is a better choice than the popular Ceftin and Omnicef. Quinolones do an excellent job crossing the BBB (Levaquin, Cipro and others). Tetracylines are at the top of the list, especially doxycycline. Macrolides, (Biaxin, Zithromax) do a poor job because of their size. Flagyl and Tindamax,which are small and lipophilic, do a great job of passing through the BBB.  Rifamycins (Rifampin) are large and penetrates poorly into the brain. Sulfonomides and Trimethoprim, the ingredients in Bactrim, fulfil the right criteria and pass well through the BBB. This is by no means a comprehensive list of all antibiotics which has been used for Lyme disease.

I haven't talked about Rocephin, our favorite intravenous Lyme drug. It is a cephalosporin. Above I state above this class of drugs generally has poor penetration into the brain. Apparently some cephalosporins penetrate better than others. Literature about Rocephin is mixed;  but contrary to many claims, it does pass the blood brain barrier. Let me mention that Rocephin is used a lot for meningitis. In typical meningitis with active inflammation, there is a breakdown of the BBB and most antibiotics penetrate. With typical chronic Lyme, neuroborreliosis patients, there is no active inflammation. High doses of the drug, with high serum levels obviates the BBB problem. Rocephin is generally tolerated at high doses. Rocephin has other favorable properties: the long half life with once daily dosing,  makes it easy to use this effective intravenous therapy at home. Even though some oral medications have better penetration through the BBB:  the IV route makes Rocephin work better.

Quinolones are the only class of antibiotics I am familiar with when given orally achieve serum concentrations which approach those of IV infusion.

The susceptibility of the organisms to the drug being used is the most important factor.

In reading about the BBB it is fascinating to learn that many other brain diseases may be due to defects in the integrity of the BBB. For example autoimmune brain diseases like MS only occur when antibodies pass through the brain's shield. The same may be true for Alzheimer's disease and other neuro-degenerative diseases which could be characterized primarily, as disorders of the blood brain barrier.

One last point: in general, large bacteria cannot pass through the BBB;  but thin, slippery Borrelia spirochetes, including of course, Borrelia burdorferi, drill through the gauntlet with ease. The brain is a safe haven for Lyme but very few other bacteria are able to get in. But it seems that intraerythrocytic germs like Bartonella and Babesia might hitch-hike in on the backs of red blood cells.

Babesia, chronic daily headache, Lyme tests and Virginia politics

Two years symptom free and now she is beginning to relapse. She did her best to ignore her symptoms willing them to go away -- to no avail. Four years ago after two years of disability, having seen 20 doctors, she came to me for the treatment of Lyme disease. Numerous doctors thought she had Lyme disease but they all ruled it out when the test was negative. There was certainly exposure: she lives in a suburb of Northern Virginia and routinely sees scores of deer running through the back yard, even lying on the flower beds. But she never tested positive. Early 13 band tests showed no reactivity. A better Western Blot showed indeterminate reactivity at the IgM 39,41 positions and now, a 52 band blot from Stony Brook (done prior to the relapse) showed 5 first timer IgG bands. She had 4/5 of the CDC surveillance criteria bands plus -- the 37 band, the highly specific band which can only be gotten from SB. She also had a few less specific IgM bands.

It started with headache, new onset chronic daily headache, other neurological symptoms, twitching and tingling, some joint pain and some brain fog. She really didn't tell me about the night sweats until the second visit. Interestingly, if the Lyme tests were wanting, this was not the case for Babesia. She tested positive for both B. duncani and B. microti. She responded well to Zithromax and Mepron then; I'll see if it still works. We are seeing a lot of resistance to Mepron and having to use other therapies these days.

The fatigue has returned. Her muscles have started twitching again and she can't feel hot or cold on her hands. And --- no headaches or air hunger, but night sweats have started up again.

Her examination confirms signs of peripheral neuropathy.

Since she has lived a cloistered life I don't think she was reinfected. So why did she have both Babesias?. Same tick, different tick? An academic question. We now know -  if we didn't know it then, duncani is much more prevalent than microti here in Midatlantic ground zero-ville.
We have talked about a lot of co-infection with multiple strains of Lyme but not much about multiple species of Babesia. It is still troubling: we don't have a narrative to explain chronic, persistent Babesia.

I have made a conscious decision to keep this blog apolitical --  but...

The bill on Governor McDonnell's desk is important. Friends from Natcaplyme.org are asking you to go to their website and vote. I think the best feature of the bill is that it may open the door for patients to look further. And -- just maybe -- it will educate a few doctors as well.

Babesia relapses just like Lyme. Where-ever the one goeth the other doth surely follow. New onset of chronic daily headaches, not on the radar of neurologists and mainstream medicine, should always raise the question of Babesia. This symptoms can be as disabling as any other Lyme symptoms; and in this case, a young woman lost two years of life because of it. People are coinfected with multiple Babesia species. Maybe, as with Lyme strains, the different Babesia are associated with different syndromes. We know that repeating the wrong Lyme test, the 13 bander designed for surveillance by the CDC is very unlikely to be helpful;  patients and doctors targeted by the new bill in VA need to hear this. And again we see, chronic Lyme can be associated with either IgG or IgM bands or both and the CDC cutoff is arbitrary. The bill is a great start.