Babesia talk, all are welcome, space limited

ANNOUNCEMENT





I HAVE DECIDED TO OFFER A SERIES OF TALKS FOR PATIENTS AND OTHERS


PLACE: MY OFFICE, DOWNSTAIRS CONFERENCE ROOM
               15245 SHADY GROVE ROAD, ROCKVILLE, MD  (NORTH ENTRANCE)


DATE:  THURSDAY MARCH 24, 2016

TIME: 7PM

PLEASE CALL OFFICE TO RSVP, SEATING LIMITED,  301 528 7111


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


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

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

Western Blots in perspective

Doctor, can you help me understand my Lyme test, Western Blot?

Many patients spend a lot of time on the internet in efforts to understand the significance of mysterious numbered bands. What does it all mean?

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

A Western Blot is a second test, (IDSA/CDC)  a confirmatory test, used to confirm positive results from the initial test an ELISA - according to the IDSA/CDC. The CDC requires the second test because they believe the ELISA is inaccurate, leading to too many false positives, whereas, those in the ILADS camp believe the opposite. On the other side it if felt the ELISA test in nearly completely worthless because of false negative: it misses the majority of cases. Therefore the ELISA is skipped and the Western Blot is ordered directly. In addition, the Western Blot, although more helpful, is still inaccurate in many cases.

The two views are so divergent that mutual understanding and compromise, for the present time, is impossible.

For purposes of this discussion, all of these tests attempt to measure an immune response mounted by a patient who has been exposed to Lyme, or Borrelia burgdorferi. These tests look for antibodies made by an infected person's immune system. These antibodies are tiny proteins, also called immunoglobulins.

These discrepancies are rooted in the early days of the disease. The Lyme bacteria first described in 1982. Soon thereafter scientist went to work developing new diagnostic tests.  Lyme, viewed as a new and emerging disease was thought to be rare and geographically confined. This assumption may have lead to problems with test development from the outset.

The Lyme tests observe reactions between antibodies (from found in patient's blood) and antigens  derived from the Lyme spirochete. This sounds straightforward but it isn't. When a Lyme patient's blood is combined with chopped up pieces of Lyme, an antigen--antibody reactions occur which may be seen as clumping. Many antibodies, ( and there are many thousands), unrelated to Lyme, may still adhere to antigen in the laboratory. This is the nonspecific reactivity or background noise that always occurs with such tests. Scientist are charged with the task of removing the nonspecific clumping, leaving behind the true Lyme-antibody clumping. Not so easy. This call is something of an educated guess. The decision as where to set the bar is made by a committee of experts. To do a good job the experts have to know who has the disease. The experts need control sample taken from truly non-infected persons. If the disease is rampant and difficult to diagnosis and if many control samples are from non-symptomatic persons infected with Lyme the test will perform poorly - or not at all.

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

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

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

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

The researchers had one agenda, the CDC another. The researchers sought a uniform, consistent standard so they could reasonably communicate with each other. The CDC wanted a surveillance standard: a test that they could use to track the disease in different locations over time.

The conference never pretended to be in the business of finding an accurate diagnostic test for Lyme: rather a standard for research purposes only. The test that resulted from this meeting can be fairly called a CDC surveillance test. This test continues to be used erroneously for purposes of diagnosis. To makes matters worse, many clinicians believe the test can be used to reliably diagnose the disease. 

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

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

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

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

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

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

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

Borreliosis, new and emerging species

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

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

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

It is only now that he seeks my help.

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

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

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

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

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

Not your father's Lyme disease

Lone star ticks, (Amblyoma americanum). are taking over. They now comprise more than 80% of the small black legged, hard bodied ticks found in the D.C metro area and elsewhere. These guys are very aggressive. They may be hard to distinguish from their deer tick (Ixodes scapularis) colleagues. Adult females are easy to spot: white spot on top. The shape and coloration is somewhat different. Take a careful look with a magnifying glass and compare to pix on google images. The CDC party line is: Lone stars do not transmit Lyme; they transmit STARI which is a mild disease and easy to treat. The CDC website states it is unknown wich bacteria causes the syndrome. The CDC website says Borrelia lonstari was a suspect but “further research” showed this not to be the case. This “definitive” research is the product of a small study published by Gary Wormser (name familiar) in 2005. Thirty EM rashes were examined for B. burdorferi (classic Lyme) and B. lonestari. Wormser did not find the genetic signature of B. burgdorferi or B. lonstari (or any Borrelia species) Therefore, the case is closed. Incidentally, all cases were from the Cape Girardeau are of Missouri (along the Mississippi river). I leave it to the reader to make sense of this research.  It is said that an inhibitor in lone star tick saliva makes them an inhospitable host for B. burdorferi. Perhaps. Nonethess, multiple studies have shown that B. burdorferi can be found in lone stars.  A patient in my practice with PCR (blood) proven B. lonestari was amongst the sickest patients I have seen. The only lab that I know of that does this test is Clongen. What about Western Blots? This patient was negative except for band 41 at two reference labs.

The Western Blot (as we currently know it) may soon be obsolete as the mix of Borrelia pathogens changes. Clongen found many Babesia organisms in these ticks, species unknown. Laboratory testing for unknown species of Babesia is impossible, except for fresh, properly stained blood smears. Bartonella is already a complete mystery: I say no more here.

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

The coinfections are different and may be complete unknowns.

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

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

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

A 70-year-old male believes he has had Lyme disease for over 10 years, first diagnosed 3 years ago.

He recalls a tick bite 10 years ago which led to chronic symptoms, mild enough to be ignored.

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

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

Despite this scan he remained cognitively sharp and still teaches high level math.

The diagnosis of Lyme was made 3years ago. Prior therapy with Omnicef, Zithromax and Mepron had been unhelpful.

He has numerous concomitant chronic disorders any of which may cause neuropathy: well controlled type 2 diabetes, pernicious anemia, hypothyroidism and MUGUS.

Features of his illness include: daily night sweats for over 10 years after the tick bite and persistently elevated muscle enzymes (CPK), unexplained.   

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

He improved fairly quickly with a doxycycline based cocktail.  Then Rifampin was added.

He reports that this is the first time he has not had night sweats in 10 years. Muscle enzymes normalized, first time in 4 years, and, neuropathy symptoms have improved and he is walking better.

This response was far beyond my most optimistic expectations.

Discussion:

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

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

Muscle enzymes: It is well documented that Lyme can directly infect muscle tissue and elevate muscle enzymes. Bartonella? Bartonella infection causes vasculitis. The bacteria reside within he endothelial cells which line blood vessels. The strange rashes that accompany the infection are a manifestation of inflamed blood vessels. Other causes of vasculitis (medical literature) may cause low grade fevers, night sweats and muscle abnormalities.

PET and SPECT scans may have limited value and be nonspecific. Results should be interpreted in this vane. Cerebral vasculitis may be a consideration.

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

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

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

Lyme is a tragic disease.

The CDC admits there are at least 300,000 new cases a year. There are a lot more. Most cases are missed or misdiagnosed.

The manifestation of this chameleon diseases are protean.

The disease threatens the premises which hold together the gestalt understanding of human disease. An acceptance of these mind bending notions would require serious revisions of uncountable chapters in medical textbooks.

In a sense this may be what the paradigm war is about. It is not about whether Lyme persists or how long patients should be treated etc. It is about a fundamental rethinking of disease with a new found appreciation of the contribution of microorganisms.

This notion both daunting and scary.

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

Bob Dylan

PANS, Lyme and delayed treatment

A lovely 17-year-old young woman presented to my practice about a year ago.  The patient’s mother has a history of Lyme disease and belies that she transmitted Lyme to her daughter in utero. Maybe. The patient suffered with a number of severe infections early in life: pneumonia, age 2 months, periorbital cellulitis age 4 months, chronic tonsillitis age 2 and chronic mycoplasma infection.  Something different also happened at age 6. She experienced an abrupt onset of tics and Tourette’s syndrome. Her pediatrician diagnosed PANDAS and prescribed a course of amoxicillin which seemed to be only somewhat helpful. After 10 days the pediatrician refused to prescribe additional antibiotics because tests for Strep were all negative: rapid strep test, throat culture, ASO titer and aniti-DNAse B.   See a psychiatrist, not PANDAS. Her enlightened pediatrician was aware of PANDAS, pediatric autoimmune neurological disorder associated with streptococcus (grp A, B-hemolytic). The hallmark of the disorder is that it comes on suddenly and is associated with strep. It is an autoimmune condition. Although even this is hotly debated, at least some pediatricians believed PANDAS required long-term antibiotics. The patient's mother always suspected Lyme. PANS (pediatric autoimmune neurological syndrome -- without the strep) was an emerging concept. L:yme and other infections could be alternate culprits. At age 12 the patient experienced transient swelling of a knee and soon thereafter developed severe neuropsychological symptoms which became progressively disabling. My patient developed a strange ailment: confessional OCD, characterized by telling her mother repetitively the same horrible thoughts: “Would I be punished (go to jail) if I drown the cat?” you get the idea. 

The patient subsequently developed frontal lobe symptoms (like pseudo-bulbar dementia). For example, she would burst in laughter or tears, uncontrollably, for no good reason. Despite all, my patient managed to do well in school until 7^th grade. Then her grades took a nose dive from As to Ds.

Mom had daughter tested for Lyme:  10/10 IgG bands on the CDC surveillance test. Her pediatrician made little of this. Mom took her daughter to a variety of Lyme doctors who prescribed a parade of antibiotics and even Mepron for possible babesiosis. None of this was helpful.

Shortly before she saw me a neuro-pediatrician told her about a test from Moeculera Lab which measures anti-neuronal antibodies and is a marker for PANS. Mom had the costly test run and the results were resoundingly positive. More than one Lyme doctor refused to look into IVIG. Getting IVIG for PANS is difficult.  Most insurance companies refuse to cover it because the FDA says they can.  Luckily we also found a defect in humoral immunity via pneumonia vaccine challenge and the insurer now agreed to cover the cost of IVIG (not for PANS).

My patient was prescribed a combination of continuous antibiotics and IVIG.

One year later. She is essentially back to normal. No OCD or inappropriate behavior. Getting straight As in school. Well-adjusted and doing great.

Important note. The patient had a tick bite on her ear age 2.  Lyme can be transmitted by a deer tick in a child in a thin skin region, such as the ear (case report at ILADS conference several years ago) in as little as 4 hours.  Early life severe infections may be explained by an immune defect, shown to be present, not Lyme), My patient had normal growth and development and had no learning disorders.

In my, albeit somewhat limited experience, children who acquire Lyme in utero have autism spectrum disorder (Asburger’s) and/or a learning, developmental disorder.  

The Hallmark of PANS is that it hits suddenly: one day your child is normal and the next neuropsychiatric symptoms occur.

My important take away message is that even though many years passed between the onset of OCD etc... and IVIG therapy, the IVIG therapy may still be very effective. 

I currently have a 31-year-old male patient which a very similar tale, disabled and dysfunctional. Because of money problems the Molecular test is still pending.  He has been treated by numerous Lyme doctors over a period of 15 years. Antibiotics alone have never helped. The diagnosis had never been considered – until now.  

Cyst busters? We had it wrong all along.

Research from Dr. Zhang’s lab at JH shatters many iconic beliefs about Lyme therapies.

We know that Lyme disease, or rather the causative organism, Borrelia burdorferi, is very difficult eradicate. In vitro (in a test tube) it took a combination of 3 antibiotics to accomplish the task. Doxycycline was a requirement. The other drugs are either unavailable or prohibitively expensive, (cefoperazone and daptomycin).

Persistent viability of the spirochete relates to its ability to form round body forms and other pleomorphic variants and to from aggregates of spirochetes protected by a muccopolysaccharide covering. Rather that the terms: L forms, cyst forms and biofilm colonies, Dr. Zhang simplifies: there are two groups,rapidly dividing forms (spirochetes) and stationary forms (persisters).

Cocktails of drugs are needed to eradicate the organism. At this point we know little about the synergy of various combinations.

First off, this is not new, but Lyme does not form L-forms. L forms are bacterial lacking a cell wall, like mycoplasma.  Alternatively, some gram negative bacteria, treated with antibiotics shed their cells walls transforming into L forms. L forms cannot survive outside the milieu of the intracellular cytoplasm of the host cells. Lyme spirochetes are encased in a dual membrane, not a cell wall.  Although the bacteria may have an intracellular location they are primarily extracellular. Cell wall drugs work because the Lyme spirochetes have something like an internal skeleton comprised of cell wall material, peptidoglycans. Lyme does not form true cysts. The terms round body form and pleomorphic variants is more accurate.

I don’t like the term cyst busters (always reminds me of ghost busters). It may be easier to consider Lyme as a dichotomy of spirochetes and persisters.

I am sorry that I have bored you so far. The rest may be of greater interest.

Doxycycline remains the first line when it comes to treating spirochete forms. Doxy has no impact on stationary forms. You already knew this.

New facts:

Flagyl is not a “cyst buster.” It does not kill stationary forms any better than doxycycline. ( you probably did not know this) This also true for amoxicillin. Ceftin does have the ability to kill both active and stationary forms of Lyme. Rifampin does not kill Lyme by itself but confers persister killing effects to doxycycline and amoxicillin.

I was sure that Tindamax must kill stationary forms. It works so well in the clinical setting. So I asked Dr. Zhang and he responded. Unpublished data show that Tindamax is ineffective against stationary form of Lyme, perhaps slightly better than Flagyl. How could I be so wrong?

Then there is a long list of drugs that kill Lyme better than currently used drugs, at least in a test tube. Two drugs stand out: Diflucan and Artemisinin.

Why do Flagyl and Tindamax work so well? These drugs have excellent penetration into tissues and into the brain. Perhaps this property and synergy explain clinical effectiveness.  Tindamax (one of my favorites) is known to concentrate in bodily fluids and tissues extremely well.

Doctors have added Flagyl and Tindamax to Omnicef and Ceftin – for decades, because they are “cyst busters.”  These doctors had wrong the whole time. It was always the other way around.

Ceftin remains a highly touted Lyme drug. It is said to be the only second generation cephalosporin that penetrates the blood brain barrier. Omnicef is a third generation cephalosporin, like Rocephin. All third generation drugs can pass through the BBB. Early studies cited in the literature proved that Ceftin was effective in treating early Lyme patients with EM rash. It was not studied for late state Lyme disease, unlike doxycycline. 

All cephalosporins do a poor job of getting into the brain. They only penetrate the brain when there is active inflammation in the meninges (lining around the brain). Oral drugs like Ceftin and Omnicef have poor uptake into the brain in patients with chronic Lyme encephalopathy. Tindamax and Flagyl may not kill persisters better than the others  but they penetrate hard to reach places including the brain.

Amoxicillin, which like Ceftin/Omnicef does not kill persisters but amoxicillin has slightly better penetration into the brain/central nervous system. I have found it more effective in most patients.

Then we are left with the question: how do we kill Lyme persisters in the brain?

IV Rocephin, with adequate brain penetration does have anti-persister properties. Perhaps IV Ceftin (cefuroxime) Zinacef, works better – worth a try.

Obvioiusly we can’t order IV antibiotics for everybody.

Rifampin crosses the BBB well and should boost the anti-persister effectiveness of drugs such as doxycycline. I have found this clinically to be the case.

Test tube results to not always translate into clinical results. Sulfa drugs kill persister and penetrate well into the brain; clinical efficacy in my practice has been lacking.

What about Diflucan? penetrates well into the brain and kills persisters.  Role in Lyme to be determined.

Artemisinin? This drug has a short half-life. This is why a derivative combined with a longer acting agent (Coartem) has greater efficacy for malaria/babesiosis.  Artemisinin has fair brain penetration. It has activity against Lyme persisters. Clinical use for Lyme unknown.

We had a lot of stuff wrong but new doors have been opened as the search for the best way to treat Lyme goes on.