Bartonella infection is associated with neuropsychological symptoms


Bartonella bacteria are increasingly recognized as an emerging infectious disease threat.

A new study by North Carolina State University researchers has found additional instances of Bartonella infection in humans who exhibited neuropsychiatric symptoms, a subset of whom also had skin lesions.

This research adds to the body of evidence that not only can Bartonella infection mimic a spectrum of chronic illnesses – including mental illness – but also that dermatological symptoms may accompany infection.

Bartonella henselae is a bacterium historically associated with cat-scratch disease, which until recently was thought to be a short-lived (or self-limiting) infection. There are at least 30 different known Bartonella species, of which 13 have been found to infect humans.

Improved methods for detecting Bartonella infection in animals and humans – it is notorious for “hiding” in the linings of blood vessels and potentially the skin – has led to the diagnosis of bartonelloses in patients with a host of chronic illnesses.

In 2019, Dr. Edward Breitschwerdt, Melanie S. Steele Distinguished Professor of Internal Medicine at NC State, published a case study involving an adolescent boy diagnosed with rapid onset schizophrenia, who had accompanying skin lesions.

After Breitschwerdt’s research group documented Bartonella henselae infection, the patient received antimicrobial therapy and all neuropsychiatric symptoms resolved.

The new study is a follow-up to the 2019 work and is published in the journal Pathogens. Thirty-three participants suffering from neuropsychiatric symptoms ranging from sleep disorders and migraines to depression and anxiety enrolled in the study.

Twenty-nine of 33 participants were found to have Bartonella infections based upon serology and enrichment blood culture polymerase chain reaction (PCR) testing. Twenty-four of the 29 Bartonella-positive participants (83%) reported the appearance of skin lesions during their illness.

Skin lesions ranged from cutaneous eruptions to red, irregular linear lesions randomly located on various parts of the patient’s body. Many of these lesions resembled striae distensae (stretch marks); however, typical risk factors for striae distensae, such as body building activities, obesity, pregnancy, prednisone treatment and other known disease associations, were either infrequently or not reported by study participants.

“This research, a follow-up to our initial case report of Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS), was initiated to further investigate a possible association between neuropsychiatric illness, skin lesions and a bacterial infection of emerging biomedical importance,” Breitschwerdt says. “We hope that this research will enable physicians to suspect connections between disparate symptoms involving the nervous system and skin that could be associated with an underlying bacterial cause.”

Bartonella bacteria are gram-negative, meaning they have a double cell wall that’s like a protective capsule that prevents the immune system’s white blood cells from ingesting them.

They are slow growing, come in different shapes, and are very difficult to isolate in the lab. They can live inside cells and in isolated locations in the body, protected from the immune system and antibiotics.

Inside an average medical textbook, you will find references to three conditions caused by different strains of bartonella: cat scratch fever (Bartonella henselae), trench fever (Bartonella quintana), and Carrion’s disease (Bartonella bacilliformis). But research over the past 20 years has shown that bartonella is quite a bit more complex. 

Though some people develop acute symptoms associated with the classic bartonella infections, many people with symptoms of chronic illness who are found to harbor bartonella species have no memory of acute illness.

There are actually many species of bartonella that are widespread in all mammal populations, including whales and dolphins. More than a dozen species have been isolated that can infect humans, hence the broader-named category called bartonella-like organisms (BLO).

Bartonella is typically spread by biting insects (fleas, ticks, mosquitoes, sandflies, lice, chiggers, biting flies, scabies, mites, and even louse-eating spiders), but it can also be transmitted by contaminated bites (of animals), scratches (cat scratch), and ingestion.

Infection by any bartonella species is called Bartonellosis. Let’s examine some of the strains that impact human health.

Bartonella henselae

The most common bartonella strain (as far as anyone knows) is Bartonella henselae. It is the cause of cat scratch fever.

Classically, a scratch from a cat carrying B. henselae develops into a rash, followed about 3 to 10 days after the scratch by symptoms that include low-grade fever, headache, sore throat, and conjunctivitis. Swollen lymph nodes are typical and take weeks to months to subside. In most cases, symptoms are not generally debilitating and resolve without treatment.

Classic cat scratch fever is common, with more than 20,000 cases reported in the U.S. each year. About a third of domestic cats are carriers, along with their fleas. Of course, cats are commonly bitten by ticks, and B. henselae is readily transmitted along with other tick-borne microbes.

When Bartonellosis with B. henselae is caused by an insect bite (ticks, fleas, mosquitoes, etc.), the symptom complex is less well defined and highly variable. Most cases are not reported, and the actual incidence of B. henselae infection may be 10 to 100 times or even a 1,000 times greater than that reported for classic cat scratch fever.

Beyond cats, dogs and other mammals — including humans — also carry B. henselae. Different studies of human populations around the world have shown that the carrier rate for B. henselae in asymptomatic individuals is anywhere from 10% to 30%.

But in certain circumstances, B. henselae may pose serious risks to your health. Emerging insights, like those reported in the journal Cancer Research, suggest B. henselae may be implicated in the development of inflammatory breast cancer (IBC), an aggressive form of breast cancer.

It may be that bartonella facilitates the dispersal of breast tumor cells through the lymphatic system and initiates an acute, cellular inflammatory response, leading to a state of chronic inflammation in patients with IBC. Although more research is needed to determine B. henselae’s contributions to IBC in humans, this preliminary information underscores the importance of understanding how bartonella species may be connected to other health conditions.

Bartonella quintana

Another common species of bartonella, Bartonella quintana is the cause of trench fever. The name comes from the trenches of WWI, where soldiers lived in desperate and debilitating conditions and the spread of Bartonellosis by B. quintana was rampant.

B. quintana, spread by body lice, causes severe fever, headache, muscle aches, leg and back pain, skin rashes, conjunctivitis, and, rarely, heart failure. Today, it’s common in homeless people, again, transmitted by body lice. About 10% to 20% of homeless populations in the U.S. harbor chronic infection with B. quintana. (Estimates suggest that the number of homeless people may be as high as 3.5 million.)

B. quintana can be transmitted directly by the bite of a louse as well as by infected bodies of dead lice scratched into abraded skin. The bacteria becomes tightly interwoven into the feces of the louse, which also is a transmission vector. Louse feces-bound bartonella is infectious for more than a year and can be inhaled or ingested with dust particlesB. quintana has also been found in cats, dogs, monkeys, gerbils, and rats, and it can be transmitted by other insect vectors.

What Bartonella Does to the Body

After entering the body (by whatever means), bartonella infects specialized white blood cells called CD 34+. These blood cells are precursors for cells that line blood vessels and other tissues (endothelial cells).

The microbe enters the cell and creates a cyst around itself (called a vacuole) to gain protection. It also turns off the ability of the cell to self-destruct. Chemical messengers stimulated by bartonella microbes cause more CD 34+ cells to congregate. These messengers simultaneously suppress other key parts of the immune response.

CD 34+ migrate throughout the body and replace damaged endothelial cells. This places bartonella exactly where it wants to be. Once established inside blood vessels, bartonella starts scavenging red blood cells as a nutrient source.

While all of this sounds highly threatening, B. henselae or B. quintana are actually not highly virulent microbes. If the person’s immune system is healthy, the cells of the immune system quickly gain the upper hand, and the microbe is dispatched within a couple of weeks. After a brief low-grade illness, the person is back to full health. Because the illness is rarely debilitating, a doctor and the healthcare system are generally not involved, and a formal diagnosis is never made.

If immune function is not up to par, however, chronic, low-grade infection can occur. It’s insidious The person has mild illness initially but then never gets completely better. The degree of debility is variable and dependent on immune status. It is possible (even common) to have chronic infection without having noticeable symptoms.

Bartonella gains protection from the immune system by invading cells that line blood vessels. Symptoms are mostly related to damage caused to small blood vessels (small vessel disease). Types of symptoms are related to the organs involved. Typical organs that can be affected include:

  • Liver
  • Spleen
  • Bone marrow
  • Eyes
  • Skin
  • Vascular system, including the heart

Stealth Characteristics of Bartonella

With only one known exception (see “The Exception” section, below), bartonella bacteria meet all the characteristics of stealth, low-virulence microbes, opportunistic pathogens with the advantage of persistence to gain a foothold in the body instead of relying on an aggressive attack. The characteristics of stealth microbes are as follows:

  • Widely prevalent in the natural world
  • Ancient host-vector relationship with multiple hosts and vectors
  • Initial infection is generally mild
  • Slow growing
  • Occurs in low concentrations in the body (even in very symptomatic individuals)
  • Associated with chronic infection in immunocompromised hosts
  • Symptoms of chronic infection are very nonspecific and similar to other low-virulence microbes
  • Have the ability to live and thrive inside cells in the body, shielded from the immune system
  • Both difficult to diagnose and difficult to eradicate, low-virulence microbes are very covert

Like other stealth microbes, bartonella is not much of a threat by itself. Virulence is additive, however; coinfection with multiple low-virulence microbes like bartonella and borrelia (the primary bacteria responsible for Lyme disease) can result in significant chronic illness. Bartonella occurs as a coinfection in at least 25% of Lyme disease cases.

Symptoms of Chronic Bartonella Infection

Symptoms of bartonella infection are highly variable, and some people who have it might not experience any signs of illness. The spectrum of symptoms widely overlaps with other low-virulence microbes and may include:

  • Skin rash at the site of initial infection
  • Low-grade fever (100℉ – 102℉)
  • Swollen lymph nodes near the initial infection site are hallmarks of initial infection; lymph nodes can be filled with pus and drain in severe cases.
  • Severe fatigue
  • Muscle pain
  • Body aches
  • Abdominal pain
  • Loose stools, constipation, or impaired general intestinal function
  • Eye infection (conjunctivitis)
  • Liver and spleen enlargement in acute or chronic infection
  • Relapsing low-grade fever
  • Chronic eye problems, including blurred vision, photophobia, and eye irritation
  • Bartonella commonly infects bone marrow with resulting bone pain; the most common location is the shin bone.
  • Pain in the soles of feet upon waking in the morning. This is associated with trauma to blood vessels in the soles of the feet with walking and is a classic bartonella symptom.
  • Ankle and knee pain on one or both sides
  • Anemia can occur from bartonella scavenging nutrients from red blood cells.
  • Small vessel disease, affecting the brain and nervous system
  • Headaches
  • Depression and rage
  • Anxiety
  • Neurological symptoms like poor balance, brain fog, decreased cognition, memory impairment, insomnia, and restlessness
  • Poor stress tolerance
  • Demineralization of teeth and jaw, causing chronic face and neck pain
  • Transient tooth pain
  • Chronic bartonella infections are associated with higher rates of root canals (due to compromise of small vessels supplying the tooth).
  • Small vessel disease can affect the function of the autonomic nervous system (sympathetic and parasympathetic systems), resulting in postural orthostatic tachycardia syndrome (POTS).
  • Vascular system issues such as infection of cells lining the heart (endocarditis), leading to chest pain, shortness of breath, palpitations, and, in some cases, damage to heart valves
  • Respiratory symptoms, including unexplained cough
  • Urogenital problems like irritable bladder, kidney disease, pelvic pain, and infertility
  • Bartonella may be passed during pregnancy and between partners.
  • Severely immunocompromised individuals (mainly AIDS patients) can develop cranberry-like skin lesions from the proliferation of infected blood vessels under the skin.

With such an expansive list of symptoms that intersects with other microbes and health conditions, an average doctor isn’t going to consider bartonella. They would likely chalk it up to aging and offer only prescriptions to control the symptoms, nothing more.

A Word About Other Bartonella Species

Research over the past 20 years has revealed bartonella species other than B. henselae and B. quintana. New ones are added to the list every year. A partial list includes B. clarridgeiae, B. elizabethae, B. vinsonii, B. berkhoffi, B. grahamii, and B. washoensis.

All but one bartonella species cause similar symptom profiles as the two better-known bartonella species and are somewhat interchangeable. In other words, other species of bartonella can cause cat scratch fever or trench fever. All bartonella species infect mammals via biting insect vectors. Ticks are known to transmit several different species of bartonella.

Bartonella is so prevalent that most people will cross paths with some form of it during a lifetime (but in most cases never know it).

But there is one exception: Bartonella bacilliformis, which causes Carrion’s disease. It is a highly virulent microbe that only occurs in the Andes regions of Peru, Ecuador, and Colombia.

A bite from a sandfly transmits B. bacilliformis, causing a high fever (called Oroya fever). This is accompanied by severe anemia from the destruction of red blood cells, severe enlargement of the spleen and liver, bleeding into lymph nodes, and destruction of blood vessels. Mortality is 40% without treatment.

Bartonella bacilliformis is an exception compared to other species of bartonella, but fortunately, it holds to the rule that higher-virulence microbes tend to be uncommon or rare.

Like Lyme disease and other stealth microbes, bartonella is notoriously difficult to diagnose. 

Testing is species-specific and generally only looks for the most common species of bartonella. Because concentrations of the organism in the body are so low, it can be hard to find. The following are tests and methods to help gain some more information.

Indirect Fluorescence Assay (IFA)

IFA tests for antibodies (IgG and IgM) to bartonella. IFA is not very sensitive because antibodies levels tend to be lowFry Laboratories (Scottsdale, Az) offers both IFA and standard PCA.

Polymerase Chain Reaction (PCR)

Standard PCR detects bartonella DNA in a blood sample. Because concentrations of the microbe are very low with chronic infection, this test is unreliable. However, Galaxy Diagnostics (based in Research Triangle, NC) performs an amplified version of PCR called ePCR that is more reliable.

The presence of bartonella in blood is amplified with special culture media and then tested with PCR. The test takes 2 to 4 weeks to perform and tests for all known forms of bartonella. Additionally, Armin Labs (Augsburg, Germany) offers several testing methods, including PCR and IFA tests.


This test uses an amplified version of PCR and immunofluorescence testing (FISH), together for improved accuracy of testing for multiple species of bartonella. FISH testing is unique in that it evaluates for bartonella RNA, as opposed to relying on an immune response from the host. The primary drawbacks to testing with IGeneX are high expense and lack of coverage by insurance.

As a general rule of thumb, positive testing can help direct therapy, but a negative test does not rule out the presence of bartonella. The expense of testing must be weighed against money directed at comprehensive therapy. As with other low-virulent microbes, sometimes it’s best just to assume that it is there and develop a comprehensive recovery protocol that addresses it.

Conventional Medical Solutions

As a general rule, two antibiotics at one time are superior to one for bartonella infection, most commonly doxycycline and rifampin for 2 to 4 weeks. Individuals with serious or debilitating symptoms, such as those consistent with endocarditis, should be evaluated by a healthcare provider and should receive antibiotic therapy. Note that some people with chronic bartonella infection do respond to conventional antibiotic therapy, too.

Antibiotic-resistant bartonella is common, and because the microbes are slow growing, occur in low concentrations in the body, and concentrate in areas where antibiotics do not penetrate, nonresponders are common. Many people who do respond relapse later.

Natural Solutions for Bartonella

The best alternative solution to overcoming a bartonella infection is supporting the natural healing potential of the body. That calls for minimizing exposure to the modern-day factors that disrupt immune function and allow low- virulence microbes like bartonella to flourish, including artificially created food products, petrochemicals and other toxins, artificial sources of radiation, and constant daily stress . In fact, avoiding these factors as much as possible is an essential step for controlling the present epidemic of all chronic diseases like Lyme disease, fibromyalgia, fatigue syndromes, and autoimmune diseases.

Natural herbal therapy offers a good alternative for chronic bartonella infection. Herbs reduce inflammation, restore normal immune function, and suppress a wide range of stealth microbes. Here are some top choices to get you started.

green Cryptolepis


Traditionally used to treat malaria in Africa, cryptolepis demonstrates systemic antibacterial properties and antiprotozoal properties. The herb is anti-inflammatory and provides antimicrobial activity, and new research in bioRxiv suggests it might defend against B. henselae as well.

Suggested dosage: Cryptolepis is available as a powder, tea, capsule, or tincture, so the dose varies depending on the preparation.

Side effects: It tends to be well tolerated in most people.

Black Walnut with green leaves

Black Walnut (Juglans nigra)

Native to North America, black walnut trees may be found in your own yard. Integrative healthcare professionals have long used black walnut anecdotally to combat intestinal parasites, however, the same research mentioned above indicates it may combat bartonella. In addition to antiparasitic and antibacterial properties, black walnut also demonstrates antioxidant and anti-inflammatory qualities.

Suggested dosage: Black walnut usually is found in tinctures and dried powders. The dose will likely depend upon the preparation and the professional expertise of your healthcare provider. Standard doses may range from 250 mg to 500 mg, two to three times daily.

Side effects: Because there is some potential for toxicity with black walnut, it is best used in conjunction with other herbs and for a shorter duration, like a couple of weeks to a couple of months at a time.

Japanese Knotweed with white flower blooms

Japanese Knotweed (Polygonum cuspidatum)

Japanese knotweed with resveratrol has been used for centuries in traditional Asian medicine, and it’s a potent antioxidant with antimicrobial and anti-inflammatory properties. Japanese Knotweed may eradicate various phases of bartonella bacteria, according to the bioRxiv study.

Suggested dosage: 200-800 mg Japanese knotweed (standardized to 50% trans-resveratrol), two to three times daily

Side effects: They’re rare, with low potential for toxicity. Caution is advised if you’re also taking anticoagulants, because resveratrol has blood-thinning properties. Avoid it during pregnancy.

Bartonella Reactions to Treatment

Bartonella has a very low potential to cause Herxheimer reactions. The outer coat from dead bacteria is much less reactive than most other bacteria involved with Lyme disease. The bacteria does not form biofilms, but it can form vacuoles that are similar in the liver. Generally, vacuoles are broken down by the body when healing occurs.

Breitschwerdt is the first and corresponding author of the research, which was supported by the Bartonella/Vector-Borne Diseases Research Fund at NC State’s College of Veterinary Medicine. NC State research technician Julie Bradley, postdoctoral researcher Erin Lashnits, and research professor Ricardo Maggi, as well as dermatologist Paul Reicherter of the University of Missouri Kansas City Truman Medical Center, contributed to the work.

Source:North Carolina State University


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