Bartonella | Frequently Asked Questions
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This disease is incredibly difficult to understand and even more complex to navigate. This list of Frequently Asked Questions is not all inclusive and will be added to and updated accordingly as the research continues to advance and evolve; For now, here is what we currently know. I have done my best to accurately summarize the current literature in a causal format that is not overly scientific. Check back for new updates!
What is Bartonella?
Bartonella are a group of stealth, slow-growing, intracellular bacteria. To date, over 40 species have been identified, 14 of which cause human illness. Bartonella is best known for causing Cat Scratch Disease. This is usually self-limiting or resolves with short-course antibiotics. However, some of these infections progress into something more serious causing systemic disease known as Bartonellosis. The symptoms can manifest acutely or develop much later in life.
What is Bartonellosis?
A chronic, disseminated systemic infection with bartonella is referred to as Bartonellosis. Bartonellosis can cause a plethora of wide-ranging symptoms spanning multiple body systems and can lead to chronic inflammation, immune dysregulation, neuroendocrine dysfunction, chronic pain, nutritional deficiencies, vessel inflammation, neuropathy, autoimmune disease and connective tissue disorders.
What are Bartonella's important bacterial characteristics?
- Bartonella is slow-growing
Bacteria can divide rapidly or slowly, the "replication rate" refers to the amount of time it takes to double it's population.
Bartonella require 24 hours to replicate - This replication occurs within the cells it has infected rather than the blood stream itself
For comparison E.coli can double its population every 20-40 minutes
- Bartonella is a Facultative Intracellular Bacteria: This means it prefers to live inside cells but does not have to
- Bartonella is a Gram-Negative Bacteria
This class of bacteria have great ability to cause human disease and can reach almost all organ systems in the body, especially in immune compromised patients.
They are enclosed in a protective capsule
This capsule prevents white blood cells (immune cells that fight infection) from ingesting the bacteria
Their outer membrane protects against certain antibiotics, like penicillin and allow the bacteria to learn and build resistance
Gram-Negative Bacteria share and acquire genes from that have become resistant and are able to genetically mutate as it learns new threats
When this outer membrane is disrupted, it releases toxic substances (endotoxins) responsible for a Jarisch-Herxheimer Reaction
These endotoxins contribute to the severity of symptoms during infection and treatment
- Chronic Bacteremia develops in 3 phases:
Invasion - Bacteria invade or colonize initial sites of infection which can be local or distant to the site of inoculation
Dissemination - These bacteria overcome host barriers and manipulate our immune response, this allows it to spread from one body site to another
Survival - They adapt to survive in the blood and organs through specialized factors (like adhesins) that prevent detection and immune clearance
- Bartonella performs a 'Coordinated Release': Every 4-8 days this bacteria simultaneously releases bacteria into the blood stream from all infected sites where it can seed new infection, typically in areas of existing or new inflammation.
- Bartonella has evolved to avoid immune detection: It is typically present in low levels and cycles in-and-out of the tissues and blood stream
Which cells are Bartonella known to infect in the human body?
Research has shown Bartonella can infect CD34+ progenitor cells, fibroblasts, monocytes, red blood cells, macrophages, microglial cells, dendritic cells and endothelial cells
Invading these cells is a pathogenic strategy that allows bartonella to manipulate our cellular function but also subvert our immune system. This leads to unrivaled systemic involvement affecting multiple organ systems
What are common syndromes associated with Bartonellosis?
Some of the correlating collateral consequences seen with Bartonellosis include Mast Cell Activation Syndrome, Small Vessel Inflammation, Connective Tissue Abnormalities and collagen disruption (acquired hypermobility similar to hEDS), Autonomic Neuropathy or Dysautonomia (Postural Orthostatic Tachycardia Syndrome), Painful Bladder Syndrome (Interstitial Cystitis like symptoms), Chronic Pain or Complex Pain Syndrome, Neuro-psychiatric Disorders, Peripheral Neuropathies, Intestinal Dysbiosis and Auto-Immune Conditions (ie - Lupus, RA, MS, Celiac, Scleroderma). It is important to note that many bartonella patients exhibit vague autoimmune changes that, often, are not able to fit into one of the well-defined rheumatic categories.
What are Co-Infections?
In the simplest of terms, a co-infection refers to when an organism (like a human or animal) has simultaneous infections by two or more pathogen species. This may be a virus, parasite, fungus or other bacteria. While in the context of tick-borne disease (TBD) we tend to focus on Lyme and it's confections since a tick typically passes more than one pathogen while having a blood meal. However, the medical significance goes well beyond TBD and can occur independent of each other over the course of one's life. This complicates how each disease acts within it's host, the symptomology, disease recognition, as well as the diagnostic process.
Which co-infections are commonly seen with Bartonella?
Bartonella can occur on it's own or as a co-infection. Some common examples of co-infections seen with Bartonella include HHV-6, EBV, CMV, Lyme Disease, Babesia, Ehrlichia, Anaplasma, Mycoplasma and Mycotoxins. Each co-infection needs to be tested for, diagnosed, and treated on its own.
It can often times be the difference between a person achieving remission or failing treatment all together. In those cases, patients tend to exhibit persistent symptoms related to an undiagnosed co-infection rather than a true failure of treatment.
Can you have Bartonellosis without Lyme disease or other co-infections?
Yes, you can be infected with bartonella without Lyme Disease!
Historically, Bartonella has been referred to as a co-infection of Lyme but Bartonella does not need a co-infection to cause serious and debilitating symptoms. An infection with Bartonella can occur independently of other vector-borne tick-borne or zoonotic disease. Anecdotally, physician's clinical experience with Bartonella report it as one of the hardest infections to treat and when seen as a 'co-infection', can be the primary culprit of a patient's most debilitating symptoms
Is it physically painful?
Yes, This disease can cause a myriad of complex symptoms and unrelenting pain, especially in severe cases. It is a painful disease.
What are the symptoms?
Most chronically ill patients will show non-specific or vague 'flu-like' symptoms such as headaches, muscle aches, joint pain, fatigue, difficulty sleeping, feet pain and poor concentration. As the disease progresses, the symptom profile expands which eventually affects multiple body systems. Each patient presents differently, however most will experience neurologic, rheumatic, immunologic and endocrine dysfunction.
Below is a comprehensive chart of symptoms created through the use of multiple publications. For an expanded view, scroll to the bottom of this page.
References
1. Anderson W. Bartonella like organisms (BLO): consideration, signs and symptoms [online article]. Feb. 17, 2013.
2. Griffith JA. Lyme and co-infection check list [online document]. Neurology Health Center.
3. Burrascano JJ. Lyme and associated co-infections bartonella like organisms (blo): consideration, signs and symptoms
4. Breitschwerdt et al.. Bartonella sp. bacteremia in patients with neurological and neurocognitive dysfunction. 2008
5. Singleton KB. The Lyme Disease Solution. Booksurge; 2008.
6. Breitschwerdt et al. Bartonella Associated Cutaneous Lesions in People with Neuropsychiatric Symptoms. Dec 4, 2020
7. Maggi RG etal. Bartonella spp. Bacteremia in high-risk immunocompetent patients. September 1, 2011
8. Johnson et al. Disseminated Cat Scratch Disease in pediatric Patients in Hawaii. May 19, 2020
9. Minnick MF, Battisti JM. Pestilence, persistence and pathogenicity: infection strategies of Bartonella
10. Maman et al. Musculoskeletal Manifestations of Cat Scratch Disease. Clinical Infectious Disease. Dec 15, 2007
Additional Literature and sources referenced:
1. Battling Bartonellosis: Neurologic Manifestations. April 22, 2020 and Rheumatologic Manifestations. April 24, 2020
2. Dr Daniel Kinderlehrer: Recovery from Lyme Disease. 2021
3. Stephen Buhner: Healing Lyme Disease Coinfections, Complementary/Holistic Treatments for Bartonella/Mycoplasma. 2013
4. Galaxy Advance Microbial Diagnostics. Understanding hidden infection: Cat Scratch Disease (Bartonella) 2021
5. Bartonella: new science revives a neglected infection. ILADS Winter 2014 Newsletter.
6 Burrascano JJ. Advanced Topics in Lyme Disease. 16th ed. ILADS
Are there 'Hallmark symptoms' associated with Bartonellosis?
Yes. As you can tell from the chart above, many of these symptoms overlap with multiple other syndromes and disease processes. This is one of the many reasons why chronic bartonella infections are under-recognized. However, there are a few hallmark symptoms that can be a 'red-flag' and indication of Bartonellosis, especially when seen in combination with each other; some of these stand-out hallmark symptoms can include:
Excruciating Feet Pain (in the soles of your feet)
Shin Bone Pain (or deep bone pain along your lower leg)
Skin Lesions or Striations (secondary to collagen disruption) that appear similar to stretch marks (initially bright red, then fading overtime)
Shifting or Migrating Joint Pain (mainly in the medium and large joints) not typically associated with joint swelling
Recurrent Soft Tissue Injuries
New and Progressive Acquired Joint Hypermobility
Neuropsychiatric Shifts (new anxiety, depression, bouts of unexplained rage)
New (seemingly random) Allergic Reactions
Eye Pain and Photosensitivity
'Flu-like Symptoms' (with or without a low-grade fever) that presents in a cyclic fashion, typically after a period of immune suppression or a stressful event (ie- a cold, trauma, surgery, etc).
Why are symptoms variable from person-to-person?
Each individual is different on how their body adapts and responds to a chronic infection with bartonella. In some, symptoms can range from asymptomatic to mild while other's can develop symptoms that are severely debilitating. This is highly dependent on the host-response (person infected), their immune status and complicating co-factors (severe stress, immune suppression, malnutrition, exposure to toxins, concurrent infection with other organisms, etc). There are a plethora of deficiencies, hormonal dysregulations and a variable level of nutritional depletion leading to many secondary issues that further plague Bartonellosis patients.
What is meant by "host response"?
The host-response is a process by which the host (the person or mammal infected) interacts and responds to the pathogen it is encountering. Differences in lifestyle, stress, underlying health status, genetics and nutrition can all impact the host response.
Can symptoms emerge or re-emerge?
Yes, Symptoms may emerge, resolve/improve and re-emerge (seeming cyclic or like a "flare-up"). Typically this occurs after a complicating event or period of immune suppression. A complicating event is defined as severe stress (physical, emotional or mental), malnutrition, exposure to toxins or other illnesses.
Is it okay to use steroids when infected with Bartonella?
The use, function and side effects of steroids are dose-dependent. Steroids can be physiologic (low doses), anti-inflammatory (moderate doses) and immunosuppressive (high doses).
High-Dose Steroids:
While not absolute, generally, the use of high dose steroids in bartonella patients is not recommended. It can cause further suppression of a patient's already poor immune response and lead to an increase in bacterial growth with progressive systemic and symptomatic decline, acutely likened to "flu-like" features, but with long-term ramifications.
Low-Dose Steroids:
Low-dose or physiologic steroid use is very common in Bartonella treatment protocols. As a consequence of infection-related chronic inflammation and chronic stress, bartonella patients can develop adrenal insufficiency and hormonal imbalances. Supplemental low-dose hydrocortisone is often necessary to help maintain cellular function, regulation of other hormones, blood sugar, blood pressure, energy level and oxidative stress. Most importantly, these lower supplemental doses WILL NOT suppress the immune response, but will actually help enhance patient function and improve treatment outcome.
Which labs are the best for testing for Bartonella?
Galaxy Advanced Microbial Diagnostics serves as the 'Gold Standard' for bartonella testing. This laboratory was founded by Dr Ed Breitschwerdt (an internist and infectious disease veterinarian) and Dr Robert Mozayeni (an internist and human rheumatologist). who are amongst the world’s leading experts on the research, diagnostics, treatment and evolutions of Bartonella. Galaxy utilizes proprietary techniques that help enhance the detection bartonella, determine active infection and account for bartonella's bacterial requirements which help decrease the incidence of false negatives. They offer both human and animal testing.
Other laboratory facilities offering bartonella testing include IgeneX, Armin, MDL and Vibrant America Lab Testing
What is Galaxy Diagnostic's Triple Draw considered the best?
"Testing at a single point in time can result in false negatives simply because the bacteria are not in the blood at the time of patient sampling".
One of Bartonella's defining characteristics is it's ability to simultaneously release new bacteria into the blood stream from infected cells every 4-8 days. During this coordinated cycle, some bacteria leave the cells they have infected and enter the bloodstream unprotected. Within a short window, these bacteria find new homes, typically in places of new inflammation and quickly invade new cells; all of which minimize immune detection.
Galaxy Diagnostics' Triple Draw accounts for this cycle and requires blood to be drawn 3 times - every other day for a week - which increases the likelihood of capturing this release and collecting free-floating bacteria from the blood. Galaxy Diagnostics Triple Draw uses a proprietary BAPGM blood culture to help bartonella thrive outside of a host (ie-on the culture plate), thus enhancing replication. This increases the likelihood of identifying it.
All 3 samples are subjected to PCR, BAPGM Culture and ePCR testing which is much more sensitive and specific than looking at antibodies alone (meaning less false negatives and more true positives, respectively).
Does a negative result rule-out the possibility of a Bartonella infection?
No, a negative does not rule-out the possibility of infection. Chronic Bartonella cases are tremendously difficult to diagnose, especially with traditional antibody methods, like IFA (Immunofluorescence Antibody Assay), antiquated PCR or traditional blood cultures.
What is the difference between IFA, PCR and Blood Cultures testing methods?
1. Traditional IFA (antibody) Testing:
Testing for an antibody response has a high false negative rate, meaning if IFA results are negative, this does not rule out Bartonella. Available testing through conventional labs (like Labcorp or Quest) only look for IgG and IgM antibodies for 2 of the 14 bartonella species capable of causing human illness; B. hensalae (the causative agent of cat scratch disease) and B. quintana. Galaxy Diagnostics is a great resource and specializes in advanced testing for intracellular pathogens. They site a "false negative antibody rate of 83% in chronically infected patients".
Why is this? In chronic Bartonellosis, Bartonella bacteria are rarely freely circulating in the blood stream without protection (remember it primarily lives within our cells and tissues), thus immune response and antibody production is LOW. Bartonella utilize the exact system meant to detect/kill it as it's own personal transit system. This is one of the reasons why diagnosis is so difficult, coining the term "Stealth Pathogen". If the immune system cannot find it then it cannot mount an antibody response against it (leading to a negative IFA test result in chronic presentations).
It is very common for a chronic bartonella patient to have negative antibody results but a positive PCR or Blood Culture. During treatment patients may seroconvert and have a measurable immune response (ie positive IFA antibody testing)
2. Traditional Blood Cultures:
A blood culture tests for the presence of disease-causing pathogens (like bacteria) in your blood. The blood is mixed with a material (culture medium) and placed in an incubator. This is intended to help the bacteria grow if they are present in your blood.
Bartonella require complex nutritional elements and proper temperature conditions in order to grow. Specifically, growth of bartonella species needs to be incubated in fresh media at a temperature of 95 - 98.6 F with 5-10 percent CO2 concentrations and greater than 40 percent humidity for a minimum of 21 days to account for it's slow replication rate.
Traditional blood cultures do not offer such optimal growth conditions and are plated for only 5-7 days. This is not enough time for bartonella to grow and will result in a negative blood culture. A negative blood culture does not mean 'no infection'; In a traditional sense, if the bacteria is in your blood, a negative culture just means the bacteria did not have the specific conditions necessary for it to thrive, grow and be identified.
Galaxy Diagnostics BAPGM cultures offer Bartonella exactly what it needs to thrive, thereby increasing the likelihood of finding it. Even in the best conditions, bartonella are incredibly difficult to grow on blood cultures.
3. PCR Testing:
This method detects bacterial DNA in the blood and tissues of patients. Not all PCR testing is created equal - Conventional PCR lack specific detail in identification, making it less reliable. They are typically performed on a single source blood draw, which increases the likelihood of missing bartonella's cyclic release of bacteria into the bloodstream. Galaxy Diagnostics has the most advanced PCR detection system for bartonellosis/chronic bacteremia and accounts for bartonella's cyclic release by attaining patient blood samples every other day for a week (coined "Triple Draw")
A positive PCR and blood culture confirm active infection.
Which testing methods truly confirm active infection?
Blood Culture with PCR testing
Is there a set protocol to treat Bartonella?
There is no set standard of care or specific protocol (set forth by CDC) for battling Bartonellosis although experts in the area advise combination antibiotics (synthetic, herbal or both) over a long duration are generally necessary. It is very individualized to the host factors, presence of co-infections and severity of pathology present. All underlying derangements, imbalances, chronic inflammation, syndromes and sequelae must also be addressed and the body supported. This is extrapolated from human case-based treatment evidence. When a protocol is referenced it typically has to do with Stephen Buhner (natural herbal therapies) or Dr. Mozayeni (Clarithromycin with Rifamycin). There are no absolutes, multiple therapies exist and each practicing physician tends to have a baseline preference with a tailored approach.
While I recognize there are multiple other alternative therapies to which patients have had success, the focus of my treatment responses are extrapolated from my current treatment plan which is a modified approach combining Buhner and Dr Mozayeni's Protocol.
Are antibiotics alone the answer?
No, antibiotics alone are not the answer.
Treatment consists of complementary and alternative therapies to address all the sequala of chronic illness and Bartonella's disease profile. Patients typically require hormone replacement therapy, aggressive gut health, medications to help quell Mast Cell Activation Syndrome, vitamin/mineral supplementation (for deficiencies and immune support), a multitude of antioxidants, joint support, and herbal therapy to mitigate chemical toxic effects of long term antibiotic (abx) use.
It is quite comprehensive, also addressing underlying co-infections, nutrition, (anti-inflammatory diet which is mainly gluten free, diary free, minimal sugar, organic, no processed foods, no alcohol) and aggressive organ support.
While I recognize there are multiple other alternative therapies to which patients have had success, the focus of my treatment responses are extrapolated from my current treatment plan which is a modified approach combining Buhner and Dr Mozayeni's Protocol.
What is the difference between Rifampin and Rifabutin?
Rifampin and Rifabutin are both part of the antibiotic class called “rifamycins.” In comparison to Rifampin, Rifabutin has a higher potency, is longer acting (has a half-life of 45 hours) and is fat-soluble (allowing it to be well distributed within the intracellular tissue). Because of this, Rifabutin can penetrate areas 20-50% more than Rifampin (especially in the nervous system - brain, spinal fluid and connective tissue) leading to a larger die-off (this is why you hear most people start with rifampin and work up to rifabutin). Herx reactions can be expected around day 8-9. A high fever may be accompanied by the standard variety "flu-like symptoms", increased body pains (arthralgia/myalgias) and skin rash (compared to Rifampin which was associated with low-grade fevers). Because it is longer acting, the herx reactions can take weeks to resolve.
Attached below is a more in-depth handout chart:
Why is Clarithromycin and Hydroxychloroquine often used in combination with Rifabutin?
Clarithromycin:</