Lyme borreliosis and Bartonella

By Barbara L. Fitzmaurice, R. N.

We are not textbook diseases anymore!

Co-infection with multiple vector-borne organisms mayoccur in animals and in humans. We now realize it is very possible to be infected with bacterial, rickettsial, parasitic, viral, and protozoal organisms following the attachment of a single tick. Borrelia burgdorferi, a spirochetal bacteria, other strains of Borrelia species, and additional infectious organisms such as the protozoa, Babesia spp.(18) (babesiosis), Francisella tularensis (tularemia), Rickettsia rickettsii (Rocky Mountain spotted fever)(1) and ehrlichiosis (an intracellular bacteria causing human monocytic ehrlichiosis (HME) and human granulocytic ehrlichiosis (HGE)),mycoplasma (parasitic bacteria), and Powassan-like virus also are spread by ticks.(2) More recently, bartonella, an intracellular organismtransmitted via the tick,has also been found to infect humans.(3)(4)(5)

The organisms in the genus bartonella have emerged in importance as opportunistic pathogenic infections in humans. Seven species, with a possibility of an eighth, exist in the genus bartonella and are known to cause illness in humans: Bartonella bacilliformis, B. elizabethae, B. henselae,B. quintana, B. washoensis, B. vinsonii subsp. Berkhoffii, B. vinsonii subsp. Arupensis. (Table 1) A widening spectrum in the bartonella species and subspecies of organisms causes infections in mammals as well. Birds, which carry lice and ticks, no doubt play a major role in transporting and disseminating these infected vectors, resulting in widespread disease. Numerous animals, both domestic and wild, act as reservoirs for the bartonella species. With the apparent ability of insects also to act as bartonella reservoirs, a much higher prevalence of this infectious disease is becoming evident.

Another possibility is that many of the infectious diseases mentioned above could have the potential tobe sexually transmitted. Research into transmission of some of the above diseases through other vectors, such as the mosquito,(6) flea, sand fly, and louse, as well as via blood transfusions,(8)(9(10) mother to fetus transmission,(13)(14), and transmission through breast-feeding, has been documented. A few early studies looked at direct contact as a mode of transmission of spirochetes. (15) (19) It is possible that bartonella infections or the other pathogenic organisms found in Lyme disease patients may also be transmitted between species by other mechanisms than those known or suspected. (6) (12) Clearly, the growth in the numbers of ticks in the United States and worldwide is alarming. (11) Increasing tick populations, along with other vectors capable of transmitting Lyme disease and other infectious illnesses to humans, has reached a level that no prudent public or private healthcare professional should ignore.

The bartonella species are not free-living organisms and require a reservoir host that is transferred by vectors such as body lice, flies, and ticks. Fleas have been found infected with Bartonella henselae in both dogs and cats, indicating that Bartonella henselae maybetransmittedto humans and pets via the flea vector. (15) (16) While researchers still dispute this, there is a growing number of reports of patients proving positive for bartonella infection having no history of contact with cats. Scratches from a cat and exposure to the saliva were thought to be the only means of transmission of bartonella infection for a very long period. It has since been established that fleas carry the organism in their midgut, and bartonella has also been found in the feces of fleas.(16) (21)(39) Other small and large animals that carry fleas and ticks may undoubtedly act as hosts as well. (Table 1)

Table 1 - The genus bartonella with species and subspecies listed. As research is ongoing, undoubtedly more strains will be discovered and more information will be forthcoming on the specific illnesses these organisms are capable of causing in humans.

Bartonella bacilliformis (also called Bartonellesis) / Flies in South America / Oroyo fever (acute hemolytic anemia), Carrion’s disease (chronic – verruga peruana) (3)(15)(20)
B. Elizabethae /
Tick and Rodent
/ Endocarditis (26)
B. henselae (11 strains)* / Fleas, ticks, animals / Cat scratch disease, endocarditis, (3)(19) bacillary angiomatosis (24)
B. quintana (7 strains)* / Body louse, tick / Trench fever, endocarditis, (3)(23) bacillary angiomatosis (46)
B. clarridgeiae / Fleas, cats. Isolated from a patient / Found in cat scratch disease. Found in a patient with endocarditis
B. alsatica sp. nov. / Isolated from the blood of wild rabbits / Unknown if disease in humans
B. birtlesii / Isolated from small mammals / Unknown if disease in humans
B. bovis / Isolated from European & American ruminants / Unknown if disease in humans
B. capreoli / Isolated from European ruminants / Unknown if disease in humans
B. doshiae / Isolated from the blood of animals and man / Unknown if disease in humans
B. grahamii (5 strains)* / Isolated from the blood of animals / Neuroretinitis(54)
B. koehlerae / Isolated from the blood of animals / Unknown if disease in humans
B. peromysci / Isolated from the blood of animals / Unknown if disease in humans
B. schoenbuchii sp. nov. / Isolated from the blood of wild roe deer / (45)
B. talpae / Isolated from the blood of animals / Unknown if disease in humans
B. taylorii (6 strains)* / Isolated from the blood of animals / Unknown if disease in humans
B. tribocorum / Isolated from the blood of animals / Unknown if disease in humans
B. vinsonii subsp. arupensis / Isolated from the blood of animals and man / Valvular disease, heart, fever, and neurological signs(3)
B. vinsonii subsp. berkhoffii / Isolated from the blood of the canine, rodents, and ticks / Endocarditis(3)(19)(26)
B. vinsonii subsp. vinsonii / Isolated from the blood of animals, transmission via tick / Unknown if disease in humans
B. washoensis / Rodents, I. pacificus ticks / Myocarditis (3)

(1) (26) (27) (37) (43)*

Relationship of Bartonella Species

Similar protein profiles have been established and a dendrogram (comparison of relationships based on immunoreactive bands) demonstrated that the Bartonella species canbe divided into three groups:

  • Bartonella bacilliformis is distinct from the other bartonella species
  • Bartonella grahamii, Bartonella taylorii, Bartonella doshiae, and Bartonella Vinsonii are related and form a cluster
  • Bartonella henselae,Bartonella quintana, Bartonella elizabethae and Bartonella clarridgeiae also form a cluster

.(Bartonella henselae is related closely to Bartonella quintana, Bartonella clarridgeiae is closely related to Bartonella henselae,andBartonella elizabethae is closely related to Bartonella quintana and Bartonella henselae)

ITS, or intergenic spacer sequencing, may be an effective method for the further sub-typing and identification of the Bartonella spp. For instance, B. henselae has further been found to have 11 strains of the organism.(43)(56)

Western blotting appears to be an effective method to identify the phenotype of the bartonella group down to the species.(43)

  • Bartonella bacilliformes: Oroyo fever, or Carrion’s disease, is transmitted from the sand fly in South America and can cause severe progressive anemia and high fevers with muscle, tendon, and joint pain. Skin eruptions or internal lesions that bleed profusely may be present, and the result can be fatal. The organism attaches to red blood cells and destroys them. If disseminated into the brain, neurological problems may develop causing seizures, paralysis, and death. In 1926 research by H. Noguchi, the tick Dermacentor andersoni was experimentally infected with Bartonella bacilliformis, which then transmitted the organism to a non-human primate.(20)

The term “bartonellosis” has been used to describe the frequently fatal syndrome caused by B. bacilliformis. It has only been reported in South America, although with the emergence and increase in illness due to vector-borne disease worldwide, it may someday have no boundaries. One treatment and another consideration worth noting is that chloramphenicol is effective against Salmonella, and this organism has been found as a secondary infection along with B. bacilliformis.(25)

  • Trench fever due toBartonella quinata(formerly Rickettsia, Rochalimaea)can be contracted after exposure to the body louse and may cause prolonged or recurrent fevers. Transmission commonly occurs when infected lice feces are rubbed into an open area on the skin or in the eyes. The organism can persist in humans for months after recovery and relapses have been reported as many as ten years later. This illness was seen in military personnel during World War I and World War II. The incubation period is 14-30 days, but problems may appear sooner. Onset is sudden, with fever, weakness, dizziness, and headache. There may be severe back and leg pains, bone pain, and an enlarged spleen. Fever may reach 40.5° C (105° F) and persist for five to six days. Fever has been reported to reoccur at intervals. Rash is possible. The liver and the spleen may enlarge, and recently endocarditis, an infection involving the heart, has been documented.(19)(22)(25) Recommendations for treatment are chloramphenicol and the tetracyclines, although currently there have been no studies to prove that this disease can be overcome completely.(18)(19)(24)
  • Bacillary angiomatosis (BA), due specifically to B. henselae and B. quintana,was the name used when first recognized in immunocompromised AIDS patients. These patients either developed nodules under the skin or vascular lesions, meaning bartonella infection had entered the blood vessels or lymph system. The nodules includedpapular, nodular, or polypoid lesions. (23) BA may also occur as a septicemia, infection that has disseminated into the blood, which if left untreated may lead to death. A patient with BA may have anincrease in lesions, rashes, abscesses, chills, fever, sweats, lack of appetite, nausea, and vomiting as well as weight loss. BA is now reported to be an illness found in immunocompetent patients as well (32)
  • B. elizabethae can cause endocarditis. B. vinsonii has been reported recently to be another cause of human endocarditis. Two Bartonella species, B. henselae and B. clarridgeiae, have been isolated from the blood of cats. B. henselae DNA has been amplified from fleas isolated from bacteremic cats. Transmission of B. henselae by the cat flea, or Ctenocephalides felis, has been demonstrated. Recently, B. clarridgeiae was isolated from the blood of a cat. It was present in the bloodstream of a healthy cat involved in a human case of cat-scratch disease (CSD) caused by B. henselae. It is not known whether B. clarridgeiae can be transmitted to man via cat or whether it actually does induce disease in humans.(26)(27) However, it is highly suspect since B. clarridgeiae antibodies recently have been found in a chest wall abscess.(35)
  • Bartonella henselae, or cat -scratch disease (CSD), originally named Rochalimaea henselae in 1992, was renamed Bartonella henselae after the entire genus of Rochalimaea was merged with the genus of Bartonella in 1993. This organism is a gram-negative rod-like bacillus. Cat-scratch disease was described in 1950, but not until some 43 years later was a primary pathogen found. In the 1990s, it was determined that this infectious agent could be widespread in humans after AIDS patients were observed exhibiting symptoms that affected virtually every organ system in the body, including the brain, heart, lymph, bone, bone marrow, muscle, soft tissue, liver, and spleen. (20)(21)(25) The same organism has been identified as a cause of encephalitis following dissemination of Bartonella henselae into the central nervous system.

CSDcan be transmitted by kittens and cats and, most likely, by fleas and ticks. This illness is closely related to Bacillary angiomatosis, which has mainly been seen in AIDS and other immunocompromised patients.(20)(27) It should be noted that the saliva of the cat might also contain the organism. Therefore, if an open area on the body is exposed to the Bartonella organism, transmission can also occur in that fashion.

Earlier papers discussed theidea that immunocompromised individuals would be the most susceptible population at risk for contracting cat-scratch fever if exposed to the organism Bartonella. First recognized in AIDS patients and later in individuals with chronic illnesses such as cancer, it has most recently been detected in patients with chronic infections including Lyme disease. This population of patients most likely would have more complications in fighting this infection. Still some physicians continue to insist that infection with a Bartonella species is a self-limiting illness in an otherwise healthy individual.

After a superficial scratch from cat or kitten, a raised lesion or papule may form near the point of injury, reportedly, in about half of the CSD patients. The lesion becomes red and crusty. One to two weeks later, swollen painful lymph glands, along with fever, may appear.Conjunctivitis, meningitis, or pneumonia, all serious complications, may develop.(24)

Patients complain of fatigue, headache, sore throat, swollen and painful lymph glands and, sometimes, loss of appetite, with weight loss due to nausea and vomiting occurring in some individuals. Reddish, berry-like lesions on the skin can bleed very easily if the skin is injured. In other patients, no rashes or lesions develop. Infections occur in bone, liver, and brain. Abscesses may form. Endocarditis may develop in AIDS patients or the immunocompromised patient infected with Bartonella henselae and Bartonella quinata. As this pathogenic organism may not bewell recognized, it could present as a very serious illness in the immunocompetent person as well.(33)(34)

Other symptoms include inflammation of the optic nerve and the retina, myelitis leading to paraplegia, and cerebral arteritis, an inflammation of an artery in the brain. Cranial or peripheral nerve involvement may be present. Facial palsy or peripheral facial nerve paralysis, known as Bell’s palsy, has been commonly reported in patients with Lyme disease and is alsoreported in Cat Scratch Disease.(22)(24)(36))(37)(38)(49)

Cats can be infected with Bartonella henselae but remain without symptoms. With the latest findings that a flea or tick may carry the disease and transmit it to humans, potential infection with this disease should not be overlooked. This is an important fact for all clinicians to take into account. Families that have pets or may have contact with small animals that carry lice and ticks need to take action to eliminate these parasites from their pets.

Testing and Diagnosing

“For many years, CSD has been clinically diagnosed when three of the following four criteria are met in a patient: 1) history of traumatic cat contact; 2) positive skin-test response to CSD skin-test antigen; 3) characteristic lymph node lesions; and 4) negative laboratory investigation for unexplained lymphadenopathy.”(32) Quoted from Russell Regnery, Ph.D., and Jordan Tappero, M.D., 1995

Blood serology has commonly been used to look for the antibodies to bothBartonella henselae and Bartonella quintana.It was not until fairly recently that testing for antibodies in other species was undertaken. Bartonella henselae can be cultured from lymph nodes or the papule area of a scratch. Positive antibody titers can help confirm the diagnosis, but may or may not be present. CT scans may be normal or EEG’s may show some slowing, but the all-important medical history and physical exam are essential in determining the diagnosis of cat-scratch disease. An antibody titer test may be ordered to see if the person is producing antibodies to Bartonella henselae. A polymerase chain reaction test (PCR) can be performed but it still may not reflect with absolute certainty an infection with the Bartonella organism unless histology and serology testing is also done. Using special techniques, the bacteria can sometimes be seen in a biopsy specimen from the affected body part.

Still, it is possible to have routine laboratory cultures reported as “negative.” Bartonella organisms from the many species and strains have not all been differentiated, and so the exact infecting species or strain may not be known in patients. Enhanced methodologies in the future may help answer these questions and decrease confusion. Coxiella or Chlamydiaaretwo infections that are difficult to differentiate from bartonella even with testing. All can be a cause of endocarditis, but different antibiotics are used in treatment. Development of reliable tests to distinguish between these organisms is very much needed.(44)

Spinal fluid may also show an increase in protein, but minimal pleocytosis (a small increase in the number of lymphocytes in cerebral spinal fluid) may be observed. New testing methods that distinguish between B. henselaeand closely related B.quintana cells might be more sensitive in PCR testing. The organism itself can be viewed in tissues.(43)(44) Other illnesses due to Bartonella henselae are bacillary angiomatosis (BA) and Parinaud’s oculoglandular syndrome (eye involvement with red, irritated eye). There may be excessive tears, similar to conjunctivitis. Sometimes swelling of the lymph glands occurs nearby, often in front of the ear. A fever and generalized illness may be present.(3)

Using indirect fluorescence assay (IFA), IgG antibody positive titers in the acute phase of B. henselae infection have been reported to be high after two weeks. IgG antibodies were lower after 25 weeks. IgM antibodies demonstrated less sensitivity using IFA serology testing.(45) PCR sensitivity and specificity from the lesions or nodes, may be even more accurate if fine needle aspiration is employed. (32)Bartonella henselae and Bartonella quinata can be tested in the blood of immunocompromised patients by obtaining blood cultures and using special stains that are allowed to grow for 21 days or longer. This may delay much needed treatment. In summary, this infection can be present in the immunocompetent patient and not easily identified by a lab test alone.