Borreliose.nl

Concurrent Infection of the Central Nervous System
by Borrelia burgdorferi and Bartonella henselae
Evidence for a Novel Tick-borne Disease Complex
Eugene Eskow, MD; Raja-Vemkitesh S. Rao, PhD; Eli Mordechai, PhD Objectives: To investigate Bartonella henselae as a po-
disease were evaluated for possible coinfection with Bar- tential human tick-borne pathogen and to evaluate its role tonella species. Elevated levels of B henselae–specific an- as a coinfecting agent of the central nervous system in tibodies were found in these patients using the immu- nofluorescent assay. Bartonella henselae–specific DNA wasdetected in their blood. None of these patients exhib- Design: Case report study.
ited the clinical characteristics of cat-scratch disease. Find-ings of cerebrospinal fluid analysis revealed the pres- Setting: A primary health care center in Flemington, NJ,
ence of both B henselae– and Borrelia burgdorferi– and the Department of Research and Development at specific DNA. Bartonella henselae –specific DNA was also Medical Diagnostic Laboratories LLC in Mt Laurel, NJ.
detected in live deer ticks obtained from the householdsof 2 of these patients.
Subjects: Two male patients (aged 14 and 36 years) and
2 female patients (aged 15 and 30 years, respectively) with
Conclusions: Our data implicate B henselae as a po-
a history of tick bites and Lyme disease.
tential human tick-borne pathogen. Patients with a his-tory of neuroborreliosis who have incomplete resolu- Main Outcome Measures: Laboratory and diagnos-
tion of symptoms should be evaluated for B henselae tic findings before and after antimicrobial therapy.
Results: Patients residing in a Lyme-endemic area of New
Jersey with ongoing symptoms attributed to chronic Lyme
LYMEDISEASEisatick-borne experienceinneuroborreliosistreatment.3
Infections with Bartonella species acute arthritis in southeastern Connecti- ported tick-borne illness in the UnitedStates. There are myriad potential neuro- For editorial comment
see page 1345
meningitis, encephalitis, demyelinatingencephalopathy, chorea, ataxia, seizures, cranial nerve palsies, myelitis, Guillain- als, including bacillary angiomatosis, pe- liosis hepatitis, lymphadenitis, and asep- scratch disease.4 Bartonella species are vector-transmitted, blood-borne, intracel- tom in patients with late-stage Lyme dis- lular, gram-negative bacteria that can in- ease. The symptoms tend to be diffuse and duce prolonged infection in the host. Per- nonspecific, and patients typically report animals result in a substantial reservoir of Mordechai), Flemington, NJ,and the Medical Diagnostic Bartonella organisms in nature that can therapy, is well known to clinicians with (REPRINTED) ARCH NEUROL / VOL 58, SEP 2001 2001 American Medical Association. All rights reserved.
METHODS
were synthesized by Research Genetics (Huntsville, Ala) andpurified by high-performance liquid chromatography. Their BLOOD SAMPLES AND ISOLATION
sequences are given in Table 1.
OF PERIPHERAL BLOOD LYMPHOCYTES
POLYMERASE CHAIN REACTION
Venous blood (10 mL) was obtained by venipuncture andcollected in a yellow-top tube (ACD solution A; Becton Dick- The PCR mixtures (50 µL) contained extracted DNA (5 µL, inson, Franklin Lakes, NJ). Peripheral blood lymphocytes 0.2 µg/µL), P24E and P12B primers (50 nM), 10 mM tris- were isolated by the Ficoll-Hypaque gradient centrifuga- hydrochloride (pH, 8.3), 50 mM potassium chloride, 3 mM tion of the blood (Sigma Chemical, St Louis, Mo) at 1600 magnesium chloride, 0.001% (wt/vol) gelatin, the nucleo- rpm for 30 minutes, in a Centra CL2 labtop centrifuge tides dATP, dCTP, dGTP, and dTTP (each at a concentra- (Fisher Scientific, Pittsburgh, Pa). The lymphocyte ring was tion of 200 mmol/L), and 2.5 U of Taq DNA polymerase isolated and rinsed twice with phosphate-buffered saline, (Perkin-Elmer, Foster City, Calif ). The PCR was carried and cells were stained with trypan blue to determine cel- out in 0.2-mL tubes. The thermocycler was a Perkin- Elmer GeneAMP PCR system 2400. The PCR program ranfor 3 minutes at 94°C, followed by 40 one-minute cycles LYME DISEASE SEROLOGIC EVALUATION
at 94°C, 1 minute at 56°C, and 1.5 minutes at 72°C. Theprogram finished with an additional 10-minute extension Serum samples were obtained from all 4 individuals and step at 72°C. A 30-µL sample of the final reaction product assayed by Western blot analysis for B burgdorferi IgG and was run on 1% agarose gel containing 0.5 µg of ethidium IgM using the commercially available Marblot strip test sys- bromide per milliliter, and the gel was photographed tem (MarDx Diagnostics, Carlsbad, Calif ). The interpre- under UV light. For optimization of the PCR conditions tation of B burgdorferi Western blot results satisfied the sur- for clinical specimens, normal blood was artificially spiked veillance case definition of B burgdorferi infection of the with in vitro–cultivated B henselae. A controlled number Centers for Disease Control and Prevention.
of B henselae (American Type Culture Collection 49882, DNA EXTRACTION
ATCC, Rockville, Md), ranging from 10 to 105 pathogenswas added to 5 mL of whole blood. These spiked samples The lymphocytes were dissolved in 470 µL of tris-EDTA were treated as described above. The PCR analysis of B burg- buffer (10 mM tris-hydrochloride [pH, 8.0] and 1 mM dorferi, B microti, and Ehrlichia was carried out as de- EDTA), 25 µL of 10% sodium dodecyl sulfate, and 12 µL of freshly prepared deoxyonuclease-free proteinase K (10mg/mL). The mixture was incubated at 55°C for 2 hours; HISTONE PCR
DNA was extracted by phenolchloroform extraction andethanol precipitation. The purified DNA was dissolved in Aliquots (5 µL) of the newly extracted DNA were mixed pyrogen-free, double-distilled water, and quantified using in a 50-µL PCR reaction mixture containing 10ϫ PCR buffer a Genesys-5 spectrophotometer (Spectronic Instruments, (Perkin Elmer), 3 mM magnesium chloride, 200 mM dNTP, Rochester, NY). The purified, quantitated DNA was used 2.5 µL of Taq DNA polymerase (5 U/µL), and 1 µL (8 pmol) as a template for Bartonella henselae and B burgdorferi PCR of 5Ј- and 3Јhistone amplifier primer set. The histone prim- analysis. Nucleic acid was extracted for Ehrlichia PCR test- ers are complementary to the DNA of a constitutively ex- ing by the DNAzol method (Invitrogen; Molecular Re- pressed human histone gene H3.3 as described.15 The am- search Center Inc, Grand Island, NY), as described by the plification process was subjected to 30 cycles of PCR (each manufacturer. The DNA extraction process for B microti cycle at 94°C for 45 seconds, 60°C for 45 seconds, and 72°C from human blood specimens was described by Persing et for 90 seconds) in a 2400 Perkin-Elmer DNA thermocy- al.10 Briefly, whole blood (1 mL) was treated with TE, hy- cler. The histone primers served as internal controls for the potonic lysis solution (10 mM tris [pH, 7.4] and 1 mM sample’s DNA integrity, presence of inhibitors, and inters- EDTA) and then centrifuged (at room temperature, 16000g, ample equivalency of total amount of DNA analyzed.
for 5 minutes). The pellet was washed 3 times with TE, tak- PRECAUTIONS AGAINST CONTAMINATION
ing care to remove the erythrocyte ghost layer after eachwash. To the pellet was added 200 µL of buffer K (50 mM The extraction of DNA and PCR were performed under ster- tris [pH, 8.3], 1.5 mM magnesium chloride, 0.45% noni- ile conditions and in separate rooms. In addition, all posi- det P-40, 0.45% Tween 20, and 10 µg of proteinase K tive samples were confirmed by reextraction from the origi- per milliliter). The pellet was dispersed by vortexing and nal sample, followed by amplification in triplicate. Bartonella incubated at 55°C for 1 hour, at 95°C for 10 minutes to henselae DNA–positive status was defined as samples that inactivate the protease and denature the genomic target were positive initially, and in at least 1 of the replicates af- DNA, and then cooled immediately on ice. The purified, ter reextraction. Pyrogen-free water was used in the isola- quantitated DNA was used as a template for B microti PCR tion of DNA from the blood specimen. The Eppendorff mi- crocentrifuge tubes and the PCR tubes were sterilized inan autoclave and UV irradiated. New Finn pipettes were used solely with the filter tips for PCR. Disposable plastic The PCR primers for the identification of B henselae,11 B burg- trays were used to prepare PCRs in a UV-irradiated PCR dorferi,12 B microti,10 and Ehrlichia13 have been described.
biohood. Blood and CSF samples (n = 10: 5 of CSF and 5 The sensitivity and specificity of the B burgdorferi primers are of blood) from individuals with no evidence of tick-borne well described.14 No statistically significant differences be- disease were used in the PCR assays as negative controls.
tween chromosomal gene primer pairs and plasmid primer In addition, the patients in this study were the first in our pairs were seen in CSF and skin specimens.14 The primers laboratory to test positive for B henselae.
(REPRINTED) ARCH NEUROL / VOL 58, SEP 2001 2001 American Medical Association. All rights reserved.
Table 1. Sequences and Positions of Oligonucleotide Primers Used for Bartonella henselae
Polymerase Chain Reaction Amplification
Oligo Name
Oligo Sequence
Target Gene
Equivalent Nucleotide
Position
Ly-1 chromosomal Borrelia burgdorferi *Oligo indicates oligonucleotide primer; rRNA, ribosomal RNA; and rDNA, ribosomal DNA. Arrows indicate the direction of the primer.
can range from 50% to 95% in select rodent, cat, deer, to attend school owing to severe fatigue, headaches, and cognitive dysfunction. He was previously an excellent It has been speculated that ongoing symptoms in student with rare absences from school. Computed chronic Lyme disease may be caused by a second tick- tomographic scans of the brain revealed no distinct borne pathogen.6 A recent study from the Netherlands found a surprisingly high percentage of Ixodes ricinus Results of further testing revealed B henselae in the ticks infected by Bartonella species.7 Bartonella-specific blood (IgG titer, 1:64 using the immunofluorescence DNA has also been amplified from I ricinus ticks in assay [IFA]). Bartonella henselae–specific DNA was suc- Poland.8 A novel Bartonella species has been found in cessfully amplified from his blood and CSF (atraumatic the blood of wild mice (Peromyscus leucopus) exclu- spinal tap). Interestingly, results of PCR analysis of this sively in conjunction with B burgdorferi and Babesia same CSF specimen were positive for B burgdorferi– microti.9 These findings have generated interest in the specific DNA. It should be noted that the patient denied role of Bartonella species as a possible human tick- exposure to cats in the months preceding his illness. He was treated with a 6-week course of cefotaxime sodium Our study was based on clinical and laboratory data (6 g/d) and experienced a prompt resolution of his obtained from patients with chronic Lyme disease resid- ing in central New Jersey. These patients exhibited a va- During his therapy, a live deer tick (I scapularis) was riety of ongoing symptoms despite previous courses of found in his household. Findings of PCR analysis of this antibiotic therapy. One of the coinvestigators, who was tick were positive for both B henselae– and B burgdorferi– unaware of the clinical status of the study subjects, con- ducted polymerase chain reaction (PCR) analyses of ce-rebrospinal fluid (CSF) for both B burgdorferi and Bar- tonella species. Polymerase chain reaction amplificationswere also performed on Ixodes scapularis ticks obtained A 36-year-old man presented with a history of late-stage from the households of 2 of these patients. The clinical Lyme disease. He remained symptomatic despite receiv- course of these patients is described.
ing an 8-week course of intravenous ceftriaxone sodium(2 g/d). Specifically, he continued to report frontal head- aches, fatigue, recent memory loss, depression, andarthralgia. He also reported episodes of confusion and a markedly shortened attention span. He was disabledfrom his job as a truck driver for a period of several Our first patient was a previously healthy 14-year-old male months. Magnetic resonance images of his brain adolescent who developed gradually worsening frontal revealed no distinct abnormality. He exhibited positive headaches, fatigue, and knee arthralgia. These symp- B henselae serologic test results (IgG ratio, 1:128 using toms were accompanied by low-grade fever, insomnia, IFA). Bartonella henselae–specific DNA was successfully and the inability to concentrate in school. He revealed amplified from his blood. Lumbar puncture was per- that 3 months prior to the onset of illness, a small tick formed, and PCR findings revealed the presence of both was removed from his scalp. However, he did not seek B henselae– and B burgdorferi–specific DNA in the same CSF sample. Therapy was initiated with intravenous Results of initial testing for Lyme disease and babe- cefotaxime sodium (8 g/d for 28 days). He became more siosis were negative. There was no improvement in his lucid, and his ability to concentrate improved. He also symptoms following a trial of therapy with doxycycline reported improvement in his recent memory and resolu- hyclate (200 mg/d for 6 weeks). The patient was unable (REPRINTED) ARCH NEUROL / VOL 58, SEP 2001 2001 American Medical Association. All rights reserved.
Figure 2. Detection of a Borrelia burgdorferi–specific DNA target from DNA
isolated from the cerebrospinal fluid (CSF) of patient 3 before (lane 1) and after
Figure 1. Detection of a Bartonella henselae–specific DNA target in DNA
(lane 4) antimicrobial therapy. The arrow indicates a B burgdorferi–specific isolated from the blood and cerebrospinal fluid (CSF) of naturally infected polymerase chain reaction (PCR) product of 231 base pairs (bp). Aliquots of individuals (case reports) before and after antimicrobial therapy. A specific DNA isolated from CSF before and after antimicrobial therapy (lane 1 and lane 4, primer pair was derived from the B henselae 16S ribosomal RNA gene respectively) were subjected to B burgdorferi amplification. Both M lanes fragment. The arrow indicates a B henselae–specific polymerase chain reaction contain a 100-bp ladder DNA marker. The positive controls (lanes 2 and 5) (PCR) product of 279 base pairs (bp). Aliquots of DNA isolated from blood contain an American Type Culture Collection B burgdorferi–positive control. The (lanes 1 and 3) and CSF (lanes 2 and 4 to 5) were subjected to B henselae negative controls (lanes 3 and 6) contain all the PCR components without DNA.
amplification before and after antimicrobial therapy (lanes 1 and 2 and 3 to 5,respectively). Lane M contains a 100-bp ladder DNA marker. The positivecontrol (lane 6) contains an American Type Culture Collection B henselae– method). Treatment was initiated with a 28-day course positive control. The negative control (lane 7) contains a control for the PCR.
of intravenous ceftriaxone sodium (2 g/d). The patientexperienced symptomatic improvement by the end of the However, his arthralgia persisted throughout his ceftriaxone regimen, and a second lumbar puncture was therapy. A second lumbar puncture was done after 28 done. Borrelia burgdorferi–specific DNA was no longer days of cefotaxime treatment. The 16S ribosomal RNA detectable (Figure 2, lane 4, after antimicrobial therapy); of B henselae was successfully amplified from DNA iso- however, B henselae–specific DNA persisted. It should be lated from peripheral blood lymphocytes and CSF mentioned that this lumbar puncture was atraumatic (0 (Figure 1, lanes 1 and 2, respectively). Twenty-eight
red blood cells per high-power field).
days after antimicrobial therapy, B henselae DNA was not At this point, treatment was changed to intrave- detected in the blood and CSF of this patient (Figure 1, nous doxycycline hyclate (100 mg every 12 hours). Most lanes 3 and 4 to 5, respectively). To increase the sensi- of her previously mentioned symptoms returned within tivity of our PCR, the amount of input DNA isolated from 3 days of starting doxycycline therapy, including confu- the CSF was doubled. Bartonella henselae DNA was not sion and the inability to concentrate. Antibiotic therapy detected after therapy (Figure 1, lane 5). In addition, was changed to intravenous azithromycin (500 mg/d for B burgdorferi DNA was no longer detected (data not 14 days). Her symptoms resolved promptly under azithro- mycin treatment. Specifically, her ability to read and per- form mathematical tasks improved greatly. She re-ported improvement in memory, more restful sleep, and The third patient was a 15-year-old female adolescent with a history of Lyme disease treated with an 8-week courseof doxycycline hyclate (200 mg/d). Following this therapy, the patient developed a gradual recurrence of symp-toms over a 3-month period. She described arthralgia pri- Our fourth study subject was a 30-year-old woman who marily affecting the hips, knees, and ankle joints. These became ill within a week after the removal of 2 ticks from symptoms were accompanied by fatigue, night sweats, her skin. She complained of fever, frontal headache, headache, photophobia, menstrual irregularity, de- dizziness, fatigue, and upper extremity arthralgia. She pressed mood, dizziness, insomnia, and the inability to noticed several small ticks on her pet cat, and these were concentrate in school. She was previously an excellent subsequently identified as I scapularis. These ticks were student, but she was unable to attend school for a 2-month positive for B henselae–specific DNA and negative for period owing to this symptom complex.
B burgdorferi–specific DNA. Her headaches and dizzi- There was no history of cat exposure and no known ness intensified, and computed tomographic images of history of tick bite. Bartonella henselae serologic testing the brain were taken, which revealed no distinct brain was done, and the results revealed the presence of abnormality. Nonetheless, her neurologic symptoms B henselae–specific antibodies (IgG titer, 1:64 using IFA).
persisted. Bartonella henselae was found on serologic Neuroborreliosis was suspected, and a lumbar puncture testing (IgG titer, 1:256 using IFA). Bartonella henselae– was performed. Results of CSF analysis revealed the pres- specific DNA was amplified from her blood.
ence of both B burgdorferi– (Figure 2, lane 1, before an-
This patient exhibited no laboratory evidence of ba- timicrobial therapy) and B henselae–specific DNA (PCR besiosis, ehrlichiosis, or Lyme disease by PCR or West- (REPRINTED) ARCH NEUROL / VOL 58, SEP 2001 2001 American Medical Association. All rights reserved.
Table 2. Summary of Pretreatment Laboratory Data and Symptoms*
Bartonella henselae
B henselae
B henselae
Cognitive
Antibody IgG
PCR Blood
Western Blot
Headache
Dysfunction
*PCR indicates polymerase chain reaction; CSF, cerebrospinal fluid; plus sign, positive findings; and minus sign, negative findings.
Table 3. Summary of Posttreatment Laboratory Data and Symptoms*
Bartonella henselae
B henselae
Cognitive
Patient No.
PCR Blood
Headache
Dysfunction
*PCR indicates polymerase chain reaction; CSF, cerebrospinal fluid; plus sign, positive findings; minus sign, negative findings; and ellipses, not applicable.
ern blot analysis. Lumbar puncture was performed, and of Bartonellaorganisms is very incomplete.5 Vector- findings of CSF analysis were negative for B burgdor- mediated transmission of B henselae to cats via fleas feri– and B henselae–specific DNA. She was treated with has been demonstrated.26 Three of our study subjects a 28-day course of oral doxycycline hyclate (300 mg/d), had no prior exposure to cats. Our fourth patient and her symptoms resolved during that period.
removed several small ticks from her cat, and these In summary, the common symptoms before therapy tested positive for B henselae using PCR. This case was for all 4 patients were cognitive dysfunction, headache, included in our study to illustrate that B henselae and fatigue. All of our study subjects had a clinical pre- infection could be acquired as a tick-borne disease sentation consistent with mild encephalopathy (Table 2).
independent of B burgdorferi infection. One of our After antimicrobial therapy, our study subjects exhib- patients found a live deer tick in his household that ited improved cognitive function, resolution of head- tested positive on PCR analysis for both B henselae and aches, and a marked improvement in energy levels B burgdorferi. These findings implicate the deer tick as (Table 3).
a potential carrier of B henselae.
Three of our patients had a history of chronic Lyme disease with persistent symptoms despite previ-ous attempts at antibiotic therapy. The concurrent find- Both B henselae and B burgdorferi have a well-established ing of B henselae– and B burgdorferi–specific DNA in ability to infect the central nervous system, with a variety their CSF probably explains their prior lack of response of resultant neurologic consequences. Cases of encepha- to antibiotic therapy directed exclusively at Lyme dis- lopathy due to B henselae infection have been well de- ease. There were 8 CSF samples obtained from other scribed.16-18 Patients typically complain of persistent gen- patients during the same period that were negative for eralized headache and restlessness and may present with both B burgdorferi and B henselae using PCR analysis.
combative behavior.19 Nearly half of these patients with Our third patient had persistently detectable encephalopathy can develop seizures that may range from B henselae–specific DNA in spinal fluid after a 28-day focal to generalized, and from brief and self-limited to course of ceftriaxone therapy. Our second patient dem- status epilepticus. Bartonella henselae–induced encepha- onstrated the absence of both B henselae– and lopathy may be a relatively frequent cause of status epi- B burgdorferi–specific DNA after a 28-day course of lepticus in school-aged children.20 The ability of this patho- cefotaxime treatment. Interestingly, B henselae has been gen to cause persistent dementia following encephalitis shown to have in vitro susceptibility to cefotaxime has been demonstrated.21 Neuroophthalmic effects, in- (minimal inhibitory concentration [MIC90] of 0.25 cluding loss of vision, have been well documented.22-25 µg/mL).27 One of our patients exhibited prompt resolu- Cat-scratch disease is the most commonly re- tion of symptoms with a trial of azithromycin. A pro- cognized manifestation of human infection with spective, randomized, double-blind, placebo-controlled B henselae. Interestingly, none of our study subjects study has demonstrated azithromycin’s efficacy against displayed the clinical characteristics of cat-scratch B henselae.28 The report by Bass et al28 has been the only disease. There have been no previously reported cases study of its kind describing the efficacy of azithromycin of tick-borne B henselae infection in humans. Vector competency has not been clearly established for tick All of our patients were tested for other tick-borne species, and knowledge related to vector transmission diseases (Babesia and Ehrlichia). The results were nega- (REPRINTED) ARCH NEUROL / VOL 58, SEP 2001 2001 American Medical Association. All rights reserved.
tive on PCR analysis (data not shown). All of our continue to be challenged to explain the pathophysiol- patients exhibited varying levels of B henselae–specific ogy behind chronic Lyme disease. Persistent symptoms antibodies on IFA. However, in a significant number of following even aggressive therapy for Lyme disease con- cases, the diagnosis cannot be made on the basis of tinue to frustrate both patients and their physicians. We IFA antibody testing alone.29 Serologic testing was per- put forth concurrent B henselae infection as one reason formed, including for IgM, and the IgM results were for ongoing symptoms in chronic Lyme disease. We con- negative in these 4 cases. The limitations of serologic sider this an introductory study and look forward to a testing for B henselae have been described.30 The sensi- more comprehensive evaluation of the role B henselae plays tivity of culture for this organism is low when com- as a coinfecting agent in chronic Lyme disease. How- pared with PCR-based detection methods.31 Polymerase ever, we are convinced that concomitant B henselae in- chain reaction detection of B henselae is especially use- fection should be considered in neuroborreliosis cases ful in cases with a broad differential diagnosis32,33 and PCR played a pivotal diagnostic role in our study.
Despite antibiotic treatment, some patients with Accepted for publication May 24, 2001. Lyme disease persistently exhibit symptoms associated Corresponding author and reprints: Eli Mordechai, PhD, with chronic Lyme disease syndrome or post-Lyme syn- Medical Diagnostic Laboratories LLC, 133 Gaither Dr, Suite drome. These symptoms include neurocognitive impair- C, Mt Laurel, NJ 08054 (e-mail: emordechai@aol.com). ment, persistent arthralgia, fatigue, and subjective memoryloss.34 The persistent symptomatology might be attrib- uted to several factors. First, coinfections: in addition totransmitting B burgdorferi, a tick may harbor other patho-gens, including Babesia, Ehrlichia, and Bartonella spe- 1. Bell WE. Parasitic infections of the brain. In: Rudolph A, Hoffman J, Rudolph C, eds. Rudolph’s Pediatrics. 19th ed. Norwalk, Conn: Appleton & Lange; 1991: cies.9 These multiple pathogens may survive Lyme anti- microbial therapy and be responsible for the persistent 2. Kaplan RF, Jones-Woodward L. Lyme encephalopathy: a neuropsychological per- symptoms in individuals with post-Lyme syndrome. The spective. Semin Neurol. 1997;17:31-37.
importance of considering these coinfecting agents in the 3. Treb J, Fernandez A, Haass A, Graner MT, Holzer G, Woessner R. Clinical and differential diagnosis cannot be overstated. Second, ge- serologic follow-up in patients with neuroborreliosis. Neurology. 1998;51:1489-1491.
netic predisposition might play a role in chronicity, patho- 4. Wong MT, Dolan MJ, Lattuada CP, et al. Neuroretinitis, aseptic meningitis, and genesis, antimicrobial resistance, and prognosis for pa- lymphadenitis associated with Bartonella (Rochalimaea) henselae infection in im- munocompetent patients and patients infected with human immunodeficiency There have been no previously reported cases of con- virus type 1. Clin Infect Dis. 1995;21:352-360.
5. Breitschwerd EB, Kordick DL. Bartonella infection in animals: carriership, res- current Lyme disease and B henselae infection. The zoo- ervoir potential, pathogenicity, and zoonotic potential for human infection. Clin notic potential for human infection with Bartonella spe- Microbiol Rev. 2000;13:428-438.
cies has recently been well described.5 High levels of 6. National Institute of Allergy and Infectious Diseases. Research on Chronic Lyme bacteremia are currently being documented in numer- Disease. Bethesda, Md: National Institute of Allergy and Infectious Diseases; May ous domestic and wild animal species.5 Our data impli- 7. Schouls LM, Van De Pol I, Rijpkema SG, Schot CS. Detection and identification cate B henselae as yet another tick-borne pathogen. Fur- of Ehrlichia, Borrelia burgdorferi sensu lato, and Bartonella species in Dutch Ixo- ther vector competency studies are needed. The fact that des ricinus ticks. J Clin Microbiol. 1999;37:2215-2222.
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11. Relman DA, Loutit JS, Schmidt TM, Falkow S, Tompkins LS. The agent of ba- either B burgdorferi or human granulocytic ehrlichiosis cillary angiomatosis. N Engl J Med. 1990;323:1573-1580.
(HGE) in I scapularis ticks did not affect acquisition of 12. Cogswell FB, Banter CE, Hughes TG, et al. Host DNA can interfere with detection the other agents from an infected host. In addition, of Borrelia burgdorferi in skin biopsy specimens by PCR. J Clin Microbiol. 1996; transmission of the agents of Lyme disease and HGE by individual ticks was equally efficient and independent.
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The results presented herein provide evidence for 16. Wheeler SW, Wolf SM, Steinberg EA. Cat-scratch encephalopathy [comments].
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(REPRINTED) ARCH NEUROL / VOL 58, SEP 2001 2001 American Medical Association. All rights reserved.

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