What is Bartonella?

What is Bartonella? When one forays into the world of chronic Lyme disease the word Bartonella immediately comes up. What is it? I have written about it from time to time and treated it for a long time. What do we know?  Medical textbooks and published papers are at odds with “Lyme” literature. Bartonella is classified as a new and emerging infectious disease. Clinical infection is largely seen as opportunistic. This means that Bartonella under normal circumstances is unlikely to cause clinical disease: it has low pathogenicity. Commercial laboratories only offer serological tests for two species, B. henselae and B. quintana.  Newer information informs us that numerous other species, including: B. koehlerae, B. vinsonii and B. berkhoffi have been found in the blood of Lyme patients. Doctors have known about the prevalence of Bartonella species in some populations for some time. A study published in 1996 looked at the incidence of three species of Bartonella found in inner-city IV drug users in Baltimore: 33% showed antibodies for Bartonella elizabethae, 11% B. henselae and 10% B. quintanta. This population was not tested for scores of other Bartonella species; infection may be universal in this population. Unlike Lyme, it is well known that Bartonella is transmitted by other biting insects, fleas, flies and mosquitoes, not just ticks. IDSA types still like to argue about whether or not Bartonella is a tickborne illness. Some people like to argue about everything. It is fact, not conjecture, that Bartonella may be transmitted by tick bite. Severe forms of the disease are well described by mainstream medicine: cat scratch fever, trench fever, angiomatosis, endocarditis and others. The more nuanced forms of disease, including those seen in Lyme sufferers, are invisible to mainstream medicine. Mainstream doctors need to look a little closer.  In 2007 a paper in “Infection,” described vasculitis and polyneuropathy caused by B. henselae. A well-known paper published in a CDC journal in 2012 made connections between Bartonella and Lyme. The paper connected non-specific symptoms: fatigue, neurologic and neurocognitive abnormalities and joint and muscle pain previously described in occupationally at-risk patient populations.  The Bartonella I think of has greater specificity. A characteristic rash, shown below, parallel red lines or discolored stretch marks, is not described in mainstream medical literature. Red bumps or papules may be seen in life-threatening disease (angiomatosis) according to the usual sources, not the rash pictured below. The Bartonella which causes tendinitis, typically plantar fasciitis (pain on the bottom of the feet) and shin splints is not described in mainstream medical literature. 

 Bartonella, as I know it, is frequently associated with specific neuropsychiatric symptoms, which may include:  irritability, anxiety, rage and many others. This too is not described in mainstream literature. Bartonella as a potential cause of other medical syndromes, for example, interstitial cystitis is also not described in mainstream in medical literature. Then there is the issue of treatment. Bartonella is supposed to respond to tetracycalines and Biaxin according to standard sources. In my world Bartonella responds best to Rifampin and the other drugs do not work.

Although many think of Bartonella as primarily a red blood cell bacteria, it actually primarily resides primarily within endothelial cells, the cells that line the inside of blood vessels. The bacteria is transmitted by an influx of red blood cells which play a role in its life-cycle.  Because of its intracellular locus Bartonella can be as intractable as the other Lyme-associated microbes. 

Here is a snapshot from one of my patients last week. 

This 30 year old male had been in clinical remission from Lyme disease for over a year, after 2 years of extensive treatment. A perfect storm of emotionally stressful events occurred in his life and symptoms returned. He complained of severe fatigue, cognitive difficulties, muscle and joint pains and severe depression. He suffered with anxiety, most Lyme patients do, but he denied irritability, anger, rage and foot pain. And, he had never had a rash like this before. He does have a history of a prior Bull’s eye rash.

Bartonella causes inflammation of blood vessels, a form of vasculitis which likely causes this characteristic rash, undiscovered by mainstream medicine. Vasculitis in the brain is well known to cause neuropsychiatric symptoms, for example, lupus vasculitis. The mechanism of synergy, by which Lyme and Bartonella seem to cause specific psychiatric symptoms is unknown. 

In this patient, Bartonella was always there, even though clinical Lyme was conquered.  Unfortunately, emotional stress weakened the immune system and the tiger got of the cage. 

Specific treatment may not always be needed; therapy decisions are based on the clinical scenario of the patient undergoing treatment.

Here are some general pointers regarding treatment. I have found that rifampin works the best. It must always be given with another antibiotic (to prevent rapidly occurring resistance). Commonly prescribed co-therapies include Zithromax, doxycycline and Bactrim. Bactrim has mild anti-Bartonella effects and is a good add on to rifampin.  Quinolones, including the widely touted Levaquin may be used. I do not like to use this class of drugs because of side effects, which include: spontaneous tendon rupture and high rate of causing C. diff colitis. When I do use a quinolone I usually reach for Cipro because it is a little less toxic and can be started at lower doses and gradually ramped up. When these measure failure, gentamycin or tobramycin are usually very effective. These drugs can only been given IV or IM, have toxicity and requiring close monitoring. 

Atypical syndromes, like interstitial cystitis, may respond best to combinations of Zithromax, rifampin and doxycycline or minocycline. 

The question, “what is Bartonella?” has certainly not fully been answered. But, clinical approaches to what I like to call “Bartonella syndrome,” have evolved and generally perform well in the clinical setting. 

Much of this piece is based on the clinical experience of many doctors and patients, not what is considered medical "evidence." A patient I spoke with last week thought this kind of information constituted evidence as defined by evidence based medicine. "Evidence based medicine," which underpins mainstream medical practices relies on published studies but primarily on the opinion of experts who have interpreted the published studies, especially the ones they like.

Lyme, the heart and simple screening and monitoring

A complication of Lyme disease, well accepted by both sides of the debate is Lyme carditis. Typically, EKG changes are found on the EKG. Some proponents recommend that all Lyme patients have an EKG. This is probably a good idea.  I have had several patients in my practice who have developed this disorder of electrical conduction of the heart. One patient nearly had a permanent pacemaker inserted but the third degree heart block cleared with courses of IV Rocephin. A current patient has a permanent pacemaker.

It seems that most chronic Lyme patients complain of palpitations. Occasionally disturbances of rhythm are found: generally EKGs are normal which is reassuring.

I have seen other cardiac complications. One patient with sudden chest pain and difficulty breathing required an urgent surgical procedure. Inflammation of the sack around the heart, the pericardium, had resulted in a constricting build up of fluid around the heart. This was quickly relieved when a "window" was incised through the pericardial sack.

Other patients have had Lyme myocarditis, inflammation of the heart muscle. This condition may have serious, even fatal consequences. Three cases of sudden cardiac death in young men was reported last year by the CDC. The repeated insistence by many on the other side: "Lyme has never killed anyone," speaks volumes regarding the lack of credibility and the "expertise" of the "experts" affiliated with the IDSA. 

Generally, the biggest cardiac concern with out patients is not Lyme per say, but complications associated with medications used to treat Lyme. Many, if not most Lyme patients, take a cocktail of drugs which may have numerous interactions. Cardiac complications may occur. For example, the FDA sent out a warning about the cardio-toxicity of Zithromax last year. My greatest concern, "first do not harm," is the remote possibility that drug(s) may cause serious rhythm disturbances in the heart rhythm, including. V-tach/V-fib. These events may be heralded by a prolongation of Q-T interval, an alteration in normal electrical functioning of the heart.

This tracing was taken from a 32 year old female seen in my office today. She has been complaining of palpitations.  This tracing shows an irregular rhythm with PVCs. PVCs, premature ventricular contractions. These are generally benign but require cardiac evaluation.  More importantly, the last value recorded under waveform analysis, QTc, the corrected QT interval. (This measures the time it takes the ventricles to electrically repolarize after depolarizing) is 475. The interval should measure 460 or less. This may be a drug affect.

Her medication list was reviewed. She takes the anti-depressant nortriptyline, prescribed by another physician. She takes a cocktail of other drugs prescribed by me, at least one of which is on the very lengthy list of drugs associated with QT prolongation. It can be challenging finding drugs not on the list.

Based this information she was instructed to hold two drugs and follow up with a cardiologist.

This is me -- having an EKG done with our new(ish) device sitting on the arm of the phlebotomy chair.  Only 2 electrodes are used on each wrist to obtain a single channel EKG;  the procedure takes only minutes. The charge is a fraction of a full 12 lead EKG which is not needed for screening and monitoring patients.

It seems that that most Lyme patients experience palpitations at one time or another and that this symptom improves with treatment. In the vast majority of cases there is nothing to worry about. But EKGs, along with blood counts and liver tests should be considered when monitoring effects of treatment.

Chronic fatigue, low grade fever and babesiosis

I have been treating this 45 year old woman for about a year. For the previous year she had been treated with pulsed, low dose antibiotics prescribed by another physician. She sought my help because she was not feeling better. She was well until 2010. At that time she had a tick bite and bull’s eye rash. Because the Lyme test and even a skin biopsy were negative she was told she did not have Lyme disease. Her symptoms started atypically with abdominal pain and sinusitis. Early on she experienced a loss of sense of smell. After this she developed more typical symptoms, cognitive issues, dizziness and hyperaccusis (extreme sensitivity to loud sounds). An MRI of her brain showed white matter disease. The diagnosis of MS was considered and dismissed. She developed palpitation but had a negative cardiac workup. In 2012 her previous physician diagnosed Lyme on clinical grounds. Western Blot testing for Lyme by various laboratories, including IgeneX was negative. She did however test positive through Pharmasan Labs on the ISpot test for Lyme. Coinfection testing was also negative. At the time I saw her previous antibiotic therapy had included: Omnicef, Mycobutin, Minocin, Biaxin and Flagyl. She had stopped antibiotics because of a lack of improvement. When we met chief complaints included: fatigue, nausea, vertigo, weakness, migratory joint pain, numbness and tingling and cognitive impairment. She also reported flulike symptoms with fevers and chills. She experienced low grade, daily, low grade fevers of 99.5 to 100 F. She was treated for chronic depression with medicine which was effective. She was worked as a professional writer, was functioning poorly and ultimately took a leave from work. 

Over the ensuing months Lyme was the working diagnosis. I treated her aggressively with a variety of antibiotics beyond those already prescribed. I treated her for coinfections. Including Babesia with Mepron and Malarone. Ultimately she did not improve. Over time the diagnosis of chronic fatigue syndrome was added to the top of her problem list. Viral causes were considered and she was treated with months of antiviral therapy; nothing helped substantially. 

During a recent office visit I thought about those persistent low grade fevers and suggested we repeat a blood smear (a prior one many months ago was negative). A photomicrograph is included here.  

Discussion: Did she have Lyme? I am frequently asked, can you just have a coinfection, like Babesia and not have Lyme. This is certainly possible but seems unlikely. A large percent of the population is silently infected with Babesia species. My sense is that the compromised immune system of Lyme tends to make Babesia more active and symptomatic. Usually you don’t get one with the other (probably others as well).

I have relied heavily on Lyme Western Blots, C6 ELISA tests and clinical judgment to diagnose Lyme. I have not used the ISpot which I thought was too nonspecific.  This test measures interferon responses of killer T-cells when provoked by specific Lyme antigens. The ISpot may be useful, especially when other tests yield negative results. 

No commercial tests are available for other common Borrelia species which I believe are more and more responsible clinical Lyme disease, Borrreliosis. Alternative Lyme species (like B. lonstari) may be tested by PCR but this is a low yield test.

Standard Babesia tests, antibodies for B. microti, B. duncani and FISH tests may detect only 2 species of Babesia; there are an untold varieties of Babesia which hold clinical importance. The CDC recognizes the existence of at least 3 other species of Babesia causes disease in the U.S.: B. CA1, B. MO1 and B. divergens. Countless species are known to cause animal illness (more than 100) and many non-speciated varieties of Babesia have been found in local ticks using broad DNA/PCR probes/primers. I am fairly sure that there are many, yet unknown, species of Babesia associated with human disease.I think the blood smear above is consistent with this phenomenon.

A lot is known about the 5 common species of Malaria including distribution patterns and drug resistance. These facts well known by organizations including: IDSA, CDC and WHO. This is not to say that Malaria is not one of the largest, if not the largest public health problem in the world.

It is said that Malaria has been eradicated in the US; still, about 2000 cases are reported to the CDC each years, mostly for foreign travelers. In 2013 the CDC states that 1700 cases of Babesia from 27 states was reported. From this data one can infer the CDC  thinks we have no Babesia problem.

This tremendous epidemic of human babesiosis of unimaginable proportion goes completely unseen by the CDC and Mainstream Medicine. One reason may be its association with the four letter word:  (Lyme) – guilt by association. 

This unknown epidemic, of which we know very little, is wildly out of control and ravaging the health of patients I see daily. 

Babesia, a blood parasite, is also a brain parasite. It is carried into the blood on the back of red blood cells, called the Trojan horse effect. The parasites are carried into tiny blood vessels where they become impacted and fixed. 

Brain parasites are mysteriously associated with reliably specific symptoms. Toxoplasmosis suicide and car accidents (published). Babesia depression. Bartonella irritability and rage. The mechanism may be specific effects on molecular signalling in the brain. Action at a distance. 

Bartonella enters the brain by the same mechanism. Bartonella is not limited to blood cells, it also invades the lining of blood vessels, endothelium, taking up residence.

My comments here are about Babesia.

Babesiosis is frequently intractable. It is resilient and becoming increasingly resistant to our standard drugs. Mepron is frequently ineffective. Malarone may work only a little better. Coartem seems to be more effective but it usually fails to eradicate the parasites. We add herbal remedies, artemisinin and a triple concoction recommended by Buhner. The parasites persist. Larium has been effective but side effects (depression) have frequently been intolerable. Babesia patients are depressed to start with. Recommended doses of quinine are intolerable. I have tried adding low doses of quinine adjunctively which seems to help some. The antiparasitic drug albendazole has anti-malaria activity and can also be helpful adjunctively for babesiosis. Babesia relapses are notorious.

The classic knee-jerk symptoms I always look for are night sweats and air hunger. Other common symptoms include muscle pain, headache, mood swings and depression. The depression seems to have a propensity for causing sudden tearfulness. A plethora of other symptoms may be associated with Babesia, include chronic, low grade fever. 

This seems to be relevant to the patient described above. 

Babesia brain Herxheimer reactions are frequently dreadful and very challenging to manage. 

This patient, as so many others, experience palpitations and other cardiac symptoms. I will explore this topic in my next post.

Cognitive dysfunction

The majority of chronic Lyme patients suffer with some degree of cognitive dysfunction.  The term “brain fog” is commonly used. Patients don’t feel as sharp. It becomes difficult to think clearly. Short term memory and working memory are poor. Finding words, completing sentences becomes difficult. Patients feel like they have the sudden onset of ADD (attention deficit disorder). Patients frequently experience disorientation and confusion and a long list of other symptoms. 

It has been suggested that all patients with “neuro-lyme” should be given IV antibiotics. This is not realistic since most patients have brain symptoms. Spirochetes may cross the blood brain barrier within days of infection.

Coinfections alter the clinical p

icture and must be dealt with separately, in specific ways.

Cognitive changes may correlate with white matter spots seen on brain MRI or with poor blood perfusion on nuclear medicine SPECT scans.  

Cognitive symptoms for the most part are due to inflammation, not permanent structural damage; so, in most cases, these symptoms are reversible with appropriate therapy. 

In most cases I like to start with oral antibiotics, ones that are effective against the pleomorphic forms of Borrelia (round body forms and others), and ones that pass the blood brain barrier.  I will talk about treatment in a subsequent BLOG. 

Unfortunately many patients get worse with treatment: we refer to this as a brain Herxheimer reaction. 

The best thing to do may be to hold antibiotics for several days and then restart at a lower dose, as tolerated.    Intravenous glutathione, (only IV), and I have tried all other forms, liposomal, oral, intranasal and even rectal is the only form that works. Glutathione (GTH) when it works, can seem like magic.  HBOT, hyperbaric oxygen therapy can be very effective. I have also found that Welchol works for some patients. 

Welchol is interesting. Being in the field (of chronic Lyme doctors), early on I was told that Welchol and related drugs remove biotoxins.  This is plainly incorrect. The important biotoxin, quinolinic acid (QUIN), does not cross the blood brain barrier. QUIN binds to NMDA receptors, it promotes action of the neurotransmitter NMDA. Drugs that antagonize NMDA are well known to many. These drugs include phencyclidine (angel dust and others). In the Lyme brain the opposite is happening. Excessive activation of NMDA receptors causes (glutamate-excito-toxicity) with increased cell death, associated with a wide spectrum of neurodegenerative disorders, including Alzheimer’s disease.

It turns out that bile acids, thought to be detergents to emulsify fat have neuro-regulatory function. Cholesterol also has neuro-regulatory effects. Welchol may help neuro-inflammation by unanticipated mechanisms.

Other drugs which help moderate the effects of QUIN include the mood stabilizer Lamictal and the Alzheimer’s drug Namenda. Both have a role in the treatment of QUIN toxicity.

It is perfectly OK to treat symptoms as the patient heals. A word of caution with depression: SSRIs, typically used for depression may have a paradoxical effect in the “Lyme brain.” Lamictal, discussed above may be effective. Also, Wellbutrin may be better tolerated. 

Stimulants are very effective for ADD symptoms as well as for fatigue, including: Ritalin, Adderall and others. 

Brain fog and cognitive problems (a patient told me she felt her brain is broken) hopefully improve, incrementally, over time, with active treatment, supportive therapies with an active effort not to make sure the patient does not become worse.  (Do no harm)

Although I do not like to start with IV antibiotics, if patients show no improvement after 4-6 months, and I am sure the diagnosis is correct, it is time to consider IV antibiotic therapy.