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 illness known as Bartonellosis.
Recent research shows that bartonella can cause a wide range of chronic symptoms (involving muscles, joints, connective tissue, bone marrow, nervous system, liver, spleen, eyes, skin, psychological status, and the entire vascular system). In this form, it is classified as a Small Vessel Inflammatory Disease and can lead to an Undifferentiated Connective Tissue Disorder with preference for endothelial tissue and collagen, respectively.
This bacteria is a slow-growing, aerobic, nonmotile, pleomorphic, non-spore forming, hemotropic, facultative intracellular coccobacillus. Stephen Harrod Buhner explains it well. Basically this means "they are choosy in what they eat, like oxygen, take 24 hours to reproduce, have variations in their size and shape, don't form spores, love blood, usually exist inside other cells but do not have to (facultative) and are intermediate in shape, roundish (cocco) and elongated (bacillus)"
Bartonella has many pathogenic strategies. While the pathogenesis still remains poorly understood, recent research has confirmed some of their highly evolved host interactions. One of those strategies involves using our host cytokine pathways for it’s own benefit. Cytokines are responsible for signaling inflammation. Through a series of interactions bartonella intentionally induces an inflammatory response releasing substances like Interleukin-8 (IL-8). This cytokine is one of the major substances necessary for mounting inflammation, an environment bartonella thrives in. This can lead to endothelial proliferation (reproduction of endothelia cells), inhibition of our host cells to undergo apoptosis (decreases the body's controlled process to eliminate questionable cells), stimulation of endothelial migration (new capillary or blood source formation) and increased epidermal growth factor (stimulates cell growth). Not only does it exploit our natural host interactions to cause inflammation and cellular recruitment, but it also uses existing inflammation in our body to seed new infections.
The collateral of chronic inflammation is tissue injury. Bartonella’s ability to manipulate host inflammation is one of the ways it targets our connective tissue’s extracellular matrix and collagen. This contributes to the development of bursitis, tendinosis, meniscal instability, joint pain, hypermobility, migraines, bone pain and neuropathy in patients suffering from this infection.
When Bartonella gains access to the human circulatory system, it can colonize secondary infections in locations distant and remote from the primary site of exposure (ie away from the location of the initial cat bite, cat scratch, tick bite etc). It targets and infects a multitude of cells in the body. This includes CD34+, fibroblasts, monocytes, macrophages, red blood cells, microglial cells, dendritic cells and endothelial cells . The significance of this lays within their cellular function:
CD34+: These are also known as 'Hematopoietic Progenitor Cells or HPC's'. This cell is capable of producing multiple cell lines in our body, forming our red blood cells, white blood cells, platelets, lymphocytes
Fibroblasts: These cells create the extracellular matrix and collagen in connective tissues; is critical in wound healing
Monocytes: Type of white blood cell responsible for fighting bacteria, viruses and other infections
Macrophages: Cell responsible for the detection, phagocytosis (engulfing) and destruction of pathogens and dead (apoptotic) cells. They assist in initiating inflammation through the release of cytokines that activate a slew of other cells
Red Blood Cells: Responsible for delivering oxygen to- and removing carbon dioxide from- our tissues
Microglial Cells: Macrophage of the nervous system
Dendritic Cells: These cells process antigens (or threats) and present them to our immune system so our body can mount a response to clear said threat; assists in communication between our innate and adaptive immune system
Endothelial Cells: These are found anywhere we have blood vessels and lymphatic vessels; It makes up a thin layer of cells lining the vessel interior
Invading these cells allow this bacteria to manipulate our cellular function but also subvert our immune system. This leads to unrivaled systemic involvement affecting multiple organ systems.
In addition to the Small Vessel Inflammatory Disease and Connective Tissue abnormalities (which can lead to a plethora of rheumatic and neurologic symptoms), patients with bartonellosis are often plagued with other sequela and syndromes. Some of the correlating collateral consequences include Mast Cell Activation Syndrome, Postural Orthostatic Tachycardia Syndrome, Painful Bladder Syndrome (Interstitial Cystitis like symptoms), Chronic Pain or Complex Pain Syndrome, Neuropsychiatric disorders, neuropathies, intestinal dysbiosis, dysautonomia and auto-immune conditions (Lupus, RA, MS, Celiac, Scleroderma) or one develops symptoms similar to autoimmunity but do not fit into a known category.
Chronic infections can be well-tolerated. Symptoms can range from asymptomatic - mild -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). In chronic infections, symptoms may emerge or re-emerge (seeming cyclic or like a "flare-up") after a complicating event or period of immune suppression. It can cause a myriad of complex, unrelenting pain, especially in severe cases. 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.
Below is a comprehensive chart of possible symptoms. Since the start of this blog, I have kept a running list of symptoms discussed within a plethora of research and educational sources. It was assimilated using multiple publications and peer-reviewed articles read over the last few years.
As you can tell, many of these symptoms overlap with multiple other illnesses and contribute to the high incidence of misdiagnosis. Additionally, Bartonella have multiple mechanisms aiding in its constant evolution and host adaptations. This manipulates the human body into being quite the accommodating host which assists in this intracellular bacterial infection's long-term survival. It is tremendously difficult to diagnose, especially with traditional antibody methods, like IFA (Immunofluorescence Antibody Assay). Because the bacteria is so slow to replicate, traditional blood cultures are not sufficient. Traditional blood cultures are plated for 5-7 days, bartonella needs at least 21 days, but that is not the standard operating procedure for most labs.
Advanced diagnostics have become available through Galaxy Diagnostics Triple Draw Microbial Testing which uses PCR and proprietary BAPGM blood culture to detect the DNA of bartonella. BAPGM is a special growth medium to help bartonella thrive on the culture plate, thus enhancing replication. This increases the likelihood of identifying it. 'Triple draw' means a blood sample is pulled every other day for a week (essentially three blood draws). Each sample is subjected to Direct PCR, BAPGM Culture and ePCR testing which is much more sensitive and specific than IFA (meaning less false negatives and more true positives, respectively). Why is this? Well, in large, it relates back to the cells it invades and it's highly adaptive mechanisms. Remember that Bartonella can evade immune detection by infecting specific cells. Let's take CD34+ cells for instance. While inside these cells, it is protected. Bartonella then uses CD34+ cells for transport to areas of inflammation (exactly where it thrives), infecting endothelial tissue. Bartonella is rarely freely circulating in the blood stream without protection, thus antibody production is diminished with chronic infections. It literally uses the 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 in chronic presentations). It is important to know a negative result DOES NOT rule-out bartonella. In science and medicine, there is a lag between emerging research and practical application in a clinical setting. Hopefully, as awareness builds, Galaxy Diagnostics Advanced Microbial Testing will become the 'Gold Standard" over traditional antibody testing methods.
Additionally, bartonella is a highly sophisticated and elegant pathogen. In chronic, disseminated infections, bartonella simultaneously releases bacteria from all infected locations into the blood stream which can lead to an intermittent bacteremia with or without a low-grade fever. Think about that...a coordinated, simultaneous release! This occurs every 4-8 days and is why the 'triple draw method' is a superior process. It accounts for Bartonella's cycle and makes it more likely to capture the bacteria in the blood stream vs a single draw which can miss it all together.
Routes of transmission have traditionally been classified as vector-borne (ie-biting insects like sand flies or human lice) or zoonotic (ie animal to human - being bitten or scratched by a cat, typically associated with previous or current flea presence) However new research discovered transmission routes associated with needle stick, animal saliva, pregnancy, potentially blood transfusions and other vectors (spiders, ticks).
Treatment: I have intentionally elected to not summarize the literature on the details of possible treatments. DVM's walk a fine line in this area. While animal medicine has provided an extensive foundation for human therapies (and vice versa), I do not want any of the information shared here to be misinterpreted as medical advice or treatment recommendations. Always seek consult with your physician. I do provide an extensive outline of my treatment plan in the post named 'Part 2' in My Journey. You can scroll down to the 2nd half to learn more about my doctor's multi-modal approach to this disease, which is individualized to my case profile.
What I can share with you is that 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. Antimicrobial Chemotherapy is very individualized to the host factors, presence of co-infections and severity of pathology present. This typically includes antibiotics, antifungals and anti-parasitics. Stephen Harrod Buhner and Dr. Robert Mozayeni have extensive treatment guidelines available and are considered experts in this field. In my situation, we are doing a modified protocol combining Buhner and Dr. Mozayeni's recommendations for Neurobartonellosis. This is rifamycin-based, and combines eastern and western medicine (both an herbal and synthetic antibiotic approach).
Antibiotics alone do not seem to be the answer. Chronic infections cause collateral damage which need to be addressed. In addition to the combination antibiotics, patients may need hormone replacement therapy, aggressive gut health (pro and prebiotics), medications to help quell Mast Cell Activation Syndrome, vitamin/mineral supplementation (for deficiencies and immune support), a multitude of antioxidants, joint support, aggressive organ support (ie- adrenal function, liver and detox) and herbal therapy to mitigate chemical toxic effects of long term antibiotic (abx) use. Nutrition also plays a role, an anti-inflammatory diet with low histamine foods is typically recommended (ie- gluten free, diary free, minimal sugar, organic, no processed foods, no alcohol).
Prognosis is unclear and relapse is quite common. It very much depends on your response to treatment and underlying complicating variables specific to each case. A common theme in the literature advise that symptoms can be put into remission or resolve, but there is no certainty that the bacteria is truly gone. Just as hard as Bartonellosis is to diagnosis, it is equally hard to eradicate.
Dr. Edward Breitschwerdt, DVM, DACVIM is one of the world’s leading experts in Bartonella. He has been researching every aspect of this bacteria for decades. While the research is mounting, there is still so much to learn and a general lack of awareness within the human and veterinary medical community continues to exist. Hopefully, we will see a tipping point as this research continues to unmask Bartonella's abilities and correlation to inflammatory-, autoimmune- and MS-like disease.
Prior to- and since diagnosis, I've spent countless hours reading Bartonella publications and case reports. It has reshaped my approach to medicine and understanding of alternative therapies. The more I learn about bartonellosis and other stealth vector-borne pathogens, the more I believe anyone experiencing vague, inflammatory symptoms, migratory joint pain/muscle pain/long bone pain, psychological changes or auto-immune like illness, should be tested.
As a veterinarian, I have always tried to stay up-to-date on the newest presentations of disease, especially that with zoonotic potential. The Information I outlined above combines that with a summary of all research and case reports I’ve learned by researching aspects of my own disease. It is by no means absolute, but I did my best to summarize the disease profile both for patients and our family members. Infectious disease has always been a interest of mine, which proved of great significance these last few years. Even with that knowledge, my path to a diagnosis could not have been more challenging (and frustrating).
I've learned to never dismiss a pathogen's ability. The second you do, it is already evolving beyond your understanding. The Bartonellosis section of this blog provides a singular space to share the information I've found most useful in understanding this disease (and further elaborates by applying my clinical picture). Additional research on vector-borne pathogens is underway and absolutely needed, many have and continue to dedicate their lives to that mission alone.
Here are a couple of my favorite links further explaining the disease process and variability in disease symptoms. The first 8 links are very reader friendly, light on medical verbiage and will provide a general overview (mostly geared toward non-medical). I did provide one scientific article below (#9) for anyone thirsting for more of an in-depth discussion and 6 webinar links to didactic lectures presented by Dr. Ed Breitschwerdt. Additionally, each post within the Bartonellosis Education section of this blog contains associated literature centered around that specific topic (links below).
Resources:
Bartonella is Everywhere, So why don’t we hear more about it?
Clues about Bartonella infections. Seattle times, 2010
Human Bartonellosis: An Underappreciated Public Health Problem? (Scientific Article)
"Bartonella is initiated by colonization of the still enigmatic primary niche where the bacteria reside, persist and are periodically seeded into the bloodstream to cause the typical relapsing Bartonella spp. bacteremia [105]. Endothelial cells, lymph nodes, liver, spleen, kidney, dermis and the bone marrow are some of the proposed niches where Bartonella spp. have been isolated from mammals [106,107,108,109,110,111,112].Bartonella henselae has been shown to infect erythrocytes, endothelial cells, macrophages, microglial cells and even human CD 34+progenitor cells [113,114,115,116]" - Citing Article
Bartonellosis Education:
Emerging Concern- Animal Workers and Veterinary Professionals
Jarisch-Herxheimer Reactions (Coming soon)
Didactic Lectures Presented by Dr. Breitschwerdt:
CME credit is available for medical professionals but anyone can create an account to attend these webinars for free.
Bartonellosis: History of a hidden epidemic
1.0 CME. This module provides an overview of the history of Bartonella spp infection, It describes the medically relevant history of bartonelloses prior to the recognition of the Human Immunodeficiency Virus (HIV) epidemic in the 1980’s. Gives an overview of medical history associated with the discovery of Cat Scratch Disease and the eventual identification of Bartonella henselae as the definitive causative agent.
Bartonelloses: Vectors and other modes of transmission
1.0 CME. This module provides an overview of key vectors and modes of transmission associated with Bartonella spp. infection, with special attention to ongoing debates surrounding tick transmission, perinatal transmission, and other modes, like transfusion and needlesticks.
Bartonelloses reservoir hosts: Bats, cats, dogs, mice and men
1.0 CME. This module provides an overview of Bartonella spp. infection, both pathogenic and species-adapted, in various hosts and reservoirs, including bats, cats, dogs, and people.
Bartonelloses and comparative infectious disease causation
1.0 CME. This module introduces a new postulate of comparative infectious disease for elusive, slow-growing, zoonotic, vector-borne diseases like Bartonella spp infection and describes the comparative features of Bartonellosis in dogs and people with particular attention to geographic and occupational risk factors.
Bartonella species, disease expression and host immunity
1.0 CME/ 1 AAFP: This module provides an overview of the major factors that influence disease expression resulting from Bartonella spp infection with particular attention to bacterial infection strategies and the histopathological progression of lesions observed in both immunocompetent and severely immunodeficient patients.
Diagnosis of Bartonella species infections
1.0 CME/ 1AAFP: This module describes the advantages and limitations of different diagnostic methodologies for confirmation of Bartonella spp. infection, as well as recent advances in sample enrichment for direct detection of infection of this immune-evasive, slow-growing bacterial infection.
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