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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
Arch Neurol. 2001;58:1357-1363.
ABSTRACT
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Objectives To investigate Bartonella henselae as a potential human
tick-borne pathogen and to evaluate its role as a coinfecting agent of the
central nervous system in the presence of neuroborreliosis.
Design Case report study.
Setting A primary health care center in Flemington, NJ, and the Department of
Research and Development at Medical Diagnostic Laboratories LLC in Mt Laurel,
NJ.
Subjects Two male patients (aged 14 and 36 years) and 2 female patients (aged
15 and 30 years, respectively) with a history of tick bites and Lyme disease.
Main Outcome Measures Laboratory and diagnostic findings before and after antimicrobial therapy.
Results Patients residing in a Lyme-endemic area of New Jersey with ongoing
symptoms attributed to chronic Lyme disease were evaluated for possible coinfection
with Bartonella species. Elevated levels of B henselae–specific antibodies were found in these patients using the immunofluorescent
assay. Bartonella henselae–specific DNA was detected in
their blood. None of these patients exhibited the clinical characteristics
of cat-scratch disease. Findings of cerebrospinal fluid analysis revealed
the presence of both B henselae– and Borrelia burgdorferi–specific DNA. Bartonella henselae–specific
DNA was also detected in live deer ticks obtained from the households of 2
of these patients.
Conclusions Our data implicate B henselae as a potential human tick-borne
pathogen. Patients with a history of neuroborreliosis who have incomplete
resolution of symptoms should be evaluated for B henselae infection.
INTRODUCTION
LYME DISEASE is a tick-borne spirochetal disease caused by Borrelia burgdorferi and first recognized in this country in 1975 among
children with acute arthritis in southeastern Connecticut. It is now the most
commonly reported tick-borne illness in the United States. There are myriad
potential neurologic manifestations, including aseptic meningitis, encephalitis,
demyelinating encephalopathy, chorea, ataxia, seizures, cranial nerve palsies,
myelitis, Guillain-Barré syndrome, mononeuritis multiplex, and benign
intracranial hypertension.1 Mild chronic encephalopathy
may be the most common neurologic symptom in patients with late-stage Lyme
disease. The symptoms tend to be diffuse and nonspecific, and patients typically
report memory loss, sleep disturbance, fatigue, and depression.2
The chronicity of these symptoms, despite parenteral antibiotic therapy, is
well known to clinicians with experience in neuroborreliosis treatment.3 The cause of these persistent neurologic symptoms
continues to be elusive.
Infections with Bartonella species have been
reported in both immunocompromised and immunocompetent hosts. A wide spectrum
of disease has been described in immunocompetent individuals, including bacillary
angiomatosis, peliosis hepatitis, lymphadenitis, and aseptic meningitis with
bacteremia and cat-scratch disease.4 Bartonella species are vector-transmitted, blood-borne,
intracellular, gram-negative bacteria that can induce prolonged infection
in the host. Persistent infections in domestic and wild animals result in
a substantial reservoir of Bartonella organisms in
nature that can serve as a source for inadvertent human infection.5 The prevalence of bacteremia can range from 50% to
95% in select rodent, cat, deer, and cattle populations.5
It has been speculated that ongoing symptoms in chronic Lyme disease
may be caused by a second tick-borne pathogen.6
A recent study from the Netherlands found a surprisingly high percentage of Ixodes ricinus ticks infected by Bartonella species.7 Bartonella-specific DNA has also been amplified from I ricinus ticks in Poland.8 A novel Bartonella species has been found in the blood of wild mice (Peromyscus leucopus) exclusively in conjunction with B burgdorferi and Babesia microti.9 These findings have generated interest in the role
of Bartonella species as a possible human tick-borne
pathogen.
Our study was based on clinical and laboratory data obtained from patients
with chronic Lyme disease residing in central New Jersey. These patients exhibited
a variety of ongoing symptoms despite previous courses of antibiotic therapy.
One of the coinvestigators, who was unaware of the clinical status of the
study subjects, conducted polymerase chain reaction (PCR) analyses of cerebrospinal
fluid (CSF) for both B burgdorferi and Bartonella species. Polymerase chain reaction amplifications were also
performed on Ixodes scapularis ticks obtained from
the households of 2 of these patients. The clinical course of these patients
is described.
METHODS
BLOOD SAMPLES AND ISOLATION OF PERIPHERAL BLOOD LYMPHOCYTES
Venous blood (10 mL) was obtained by venipuncture and collected in a
yellow-top tube (ACD solution A; Becton Dickinson, Franklin Lakes, NJ). Peripheral
blood lymphocytes were isolated by the Ficoll-Hypaque gradient centrifugation
of the blood (Sigma Chemical, St Louis, Mo) at 1600 rpm for 30 minutes, in
a Centra CL2 labtop centrifuge (Fisher Scientific, Pittsburgh, Pa). The lymphocyte
ring was isolated and rinsed twice with phosphate-buffered saline, and cells
were stained with trypan blue to determine cellular viability.
LYME DISEASE SEROLOGIC EVALUATION
Serum samples were obtained from all 4 individuals and assayed by Western
blot analysis for B burgdorferi IgG and IgM using
the commercially available Marblot strip test system (MarDx Diagnostics, Carlsbad,
Calif). The interpretation of B burgdorferi Western
blot results satisfied the surveillance case definition of B burgdorferi infection of the Centers for Disease Control and Prevention.
DNA EXTRACTION
The lymphocytes were dissolved in 470 µL of tris-EDTA buffer (10
mM tris-hydrochloride [pH, 8.0] and 1 mM EDTA), 25 µL of 10% sodium
dodecyl sulfate, and 12 µL of freshly prepared deoxyonuclease-free proteinase
K (10 mg/mL). The mixture was incubated at 55°C for 2 hours; DNA was extracted
by phenolchloroform extraction and ethanol precipitation. The purified DNA
was dissolved in pyrogen-free, double-distilled water, and quantified using
a Genesys-5 spectrophotometer (Spectronic Instruments, Rochester, NY). The
purified, quantitated DNA was used as a template for Bartonella
henselae and B burgdorferi PCR analysis. Nucleic
acid was extracted for Ehrlichia PCR testing by the
DNAzol method (Invitrogen; Molecular Research Center Inc, Grand Island, NY),
as described by the manufacturer. The DNA extraction process for B microti from human blood specimens was described by Persing et al.10 Briefly, whole blood (1 mL) was treated with TE,
hypotonic lysis solution (10 mM tris [pH, 7.4] and 1 mM EDTA) and then centrifuged
(at room temperature, 16 000g, for 5 minutes).
The pellet was washed 3 times with TE, taking care to remove the erythrocyte
ghost layer after each wash. To the pellet was added 200 µL of buffer
K (50 mM tris [pH, 8.3], 1.5 mM magnesium chloride, 0.45% nonidet P-40, 0.45%
Tween 20, and 10 µg of proteinase K per milliliter). The pellet was
dispersed by vortexing and incubated at 55°C for 1 hour, at 95°C for
10 minutes to inactivate the protease and denature the genomic target DNA,
and then cooled immediately on ice. The purified, quantitated DNA was used
as a template for B microti PCR analysis.
PRIMERS
The PCR primers for the identification of B henselae,11 B burgdorferi,12 B microti,10 and Ehrlichia13
have been described. The sensitivity and specificity of the B burgdorferi primers are well described.14
No statistically significant differences between chromosomal gene primer pairs
and plasmid primer pairs were seen in CSF and skin specimens.14
The primers were synthesized by Research Genetics (Huntsville, Ala) and purified
by high-performance liquid chromatography. Their sequences are given in Table 1.
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Table 1. Sequences and Positions of Oligonucleotide Primers Used for Bartonella henselae Polymerase Chain Reaction Amplification
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POLYMERASE CHAIN REACTION
The PCR mixtures (50 µL) contained extracted DNA (5 µL,
0.2 µg/µL), P24E and P12B primers (50 nM), 10 mM tris-hydrochloride
(pH, 8.3), 50 mM potassium chloride, 3 mM magnesium chloride, 0.001% (wt/vol)
gelatin, the nucleotides dATP, dCTP, dGTP, and dTTP (each at a concentration
of 200 mmol/L), and 2.5 U of Taq DNA polymerase (Perkin-Elmer, Foster City,
Calif). The PCR was carried out in 0.2-mL tubes. The thermocycler was a Perkin-Elmer
GeneAMP PCR system 2400. The PCR program ran for 3 minutes at 94°C, followed
by 40 one-minute cycles at 94°C, 1 minute at 56°C, and 1.5 minutes
at 72°C. The program finished with an additional 10-minute extension step
at 72°C. A 30-µL sample of the final reaction product was run on
1% agarose gel containing 0.5 µg of ethidium bromide per milliliter,
and the gel was photographed under UV light. For optimization of the PCR conditions
for clinical specimens, normal blood was artificially spiked with in vitro–cultivated B henselae. A controlled number of B
henselae (American Type Culture Collection 49882, ATCC, Rockville,
Md), ranging from 10 to 105 pathogens was added to 5 mL of whole
blood. These spiked samples were treated as described above. The PCR analysis
of B burgdorferi, B microti,
and Ehrlichia was carried out as described.10, 12, 13
HISTONE PCR
Aliquots (5 µL) of the newly extracted DNA were mixed in a 50-µL
PCR reaction mixture containing 10x PCR buffer (Perkin Elmer), 3 mM
magnesium chloride, 200 mM dNTP, 2.5 µL of Taq DNA polymerase (5 U/µL),
and 1 µL (8 pmol) of 5'- and 3'histone amplifier primer
set. The histone primers are complementary to the DNA of a constitutively
expressed human histone gene H3.3 as described.15 The amplification process was subjected to 30 cycles
of PCR (each cycle at 94°C for 45 seconds, 60°C for 45 seconds, and
72°C for 90 seconds) in a 2400 Perkin-Elmer DNA thermocycler. The histone
primers served as internal controls for the sample's DNA integrity, presence
of inhibitors, and intersample equivalency of total amount of DNA analyzed.
PRECAUTIONS AGAINST CONTAMINATION
The extraction of DNA and PCR were performed under sterile conditions
and in separate rooms. In addition, all positive samples were confirmed by
reextraction from the original sample, followed by amplification in triplicate. Bartonella henselae DNA–positive status was defined
as samples that were positive initially, and in at least 1 of the replicates
after reextraction. Pyrogen-free water was used in the isolation of DNA from
the blood specimen. The Eppendorff microcentrifuge tubes and the PCR tubes
were sterilized in an autoclave and UV irradiated. New Finn pipettes were
used solely with the filter tips for PCR. Disposable plastic trays were used
to prepare PCRs in a UV-irradiated PCR biohood. Blood and CSF samples (n =
10: 5 of CSF and 5 of blood) from individuals with no evidence of tick-borne
disease were used in the PCR assays as negative controls. In addition, the
patients in this study were the first in our laboratory to test positive for B henselae.
RESULTS
CASE 1
Our first patient was a previously healthy 14-year-old male adolescent
who developed gradually worsening frontal headaches, fatigue, and knee arthralgia.
These symptoms were accompanied by low-grade fever, insomnia, and the inability
to concentrate in school. He revealed that 3 months prior to the onset of
illness, a small tick was removed from his scalp. However, he did not seek
medical attention at that time.
Results of initial testing for Lyme disease and babesiosis were negative.
There was no improvement in his symptoms following a trial of therapy with
doxycycline hyclate (200 mg/d for 6 weeks). The patient was unable to attend
school owing to severe fatigue, headaches, and cognitive dysfunction. He was
previously an excellent student with rare absences from school. Computed tomographic
scans of the brain revealed no distinct abnormality.
Results of further testing revealed B henselae
in the blood (IgG titer, 1:64 using the immunofluorescence assay [IFA]). Bartonella henselae–specific DNA was successfully
amplified from his blood and CSF (atraumatic spinal tap). Interestingly, results
of PCR analysis of this same CSF specimen were positive for B burgdorferi–specific DNA. It should be noted that the patient
denied exposure to cats in the months preceding his illness. He was treated
with a 6-week course of cefotaxime sodium (6 g/d) and experienced a prompt
resolution of his symptoms.
During his therapy, a live deer tick (I scapularis) was found in his household. Findings of PCR analysis of this tick
were positive for both B henselae– and B burgdorferi–specific DNA.
CASE 2
A 36-year-old man presented with a history of late-stage Lyme disease.
He remained symptomatic despite receiving an 8-week course of intravenous
ceftriaxone sodium (2 g/d). Specifically, he continued to report frontal headaches,
fatigue, recent memory loss, depression, and arthralgia. He also reported
episodes of confusion and a markedly shortened attention span. He was disabled
from his job as a truck driver for a period of several months. Magnetic resonance
images of his brain revealed no distinct abnormality. He exhibited positive B henselae serologic test results (IgG ratio, 1:128 using
IFA). Bartonella henselae–specific DNA was
successfully amplified from his blood. Lumbar puncture was performed, and
PCR findings revealed the presence of both B henselae– and B burgdorferi–specific DNA in the
same CSF sample. Therapy was initiated with intravenous cefotaxime sodium
(8 g/d for 28 days). He became more lucid, and his ability to concentrate
improved. He also reported improvement in his recent memory and resolution
of headache.
However, his arthralgia persisted throughout his therapy. A second lumbar
puncture was done after 28 days of cefotaxime treatment. The 16S ribosomal
RNA of B henselae was successfully amplified from
DNA isolated from peripheral blood lymphocytes and CSF (Figure 1, lanes 1 and 2, respectively). Twenty-eight days after
antimicrobial therapy, B henselae DNA was not detected
in the blood and CSF of this patient (Figure
1, lanes 3 and 4 to 5, respectively). To increase the sensitivity
of our PCR, the amount of input DNA isolated from the CSF was doubled. Bartonella henselae DNA was not detected after therapy
(Figure 1, lane 5). In addition, B burgdorferi DNA was no longer detected (data not shown).
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Figure 1. Detection of a Bartonella
henselae–specific DNA target in DNA isolated from the blood and
cerebrospinal fluid (CSF) of naturally infected individuals (case reports)
before and after antimicrobial therapy. A specific primer pair was derived
from the B henselae 16S ribosomal RNA gene fragment. The arrow
indicates a B henselae–specific polymerase chain reaction
(PCR) product of 279 base pairs (bp). Aliquots of DNA isolated from blood
(lanes 1 and 3) and CSF (lanes 2 and 4 to 5) were subjected to B henselae 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
positive control (lane 6) contains an American Type Culture Collection B henselae–positive control. The negative control (lane 7) contains
a control for the PCR.
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CASE 3
The third patient was a 15-year-old female adolescent with a history
of Lyme disease treated with an 8-week course of doxycycline hyclate (200
mg/d). Following this therapy, the patient developed a gradual recurrence
of symptoms over a 3-month period. She described arthralgia primarily affecting
the hips, knees, and ankle joints. These symptoms were accompanied by fatigue,
night sweats, headache, photophobia, menstrual irregularity, depressed mood,
dizziness, insomnia, and the inability to concentrate in school. She was previously
an excellent student, but she was unable to attend school for a 2-month period
owing to this symptom complex.
There was no history of cat exposure and no known history of tick bite. Bartonella henselae serologic testing was done, and the
results revealed the presence of B henselae–specific
antibodies (IgG titer, 1:64 using IFA). Neuroborreliosis was suspected, and
a lumbar puncture was performed. Results of CSF analysis revealed the presence
of both B burgdorferi– (Figure 2, lane 1, before antimicrobial therapy) and B henselae–specific DNA (PCR method). Treatment was initiated
with a 28-day course of intravenous ceftriaxone sodium (2 g/d). The patient
experienced symptomatic improvement by the end of the ceftriaxone regimen,
and a second lumbar puncture was done. Borrelia burgdorferi–specific DNA was no longer detectable (Figure 2, lane 4, after antimicrobial therapy); however, B henselae–specific DNA persisted. It should be mentioned that
this lumbar puncture was atraumatic (0 red blood cells per high-power field).
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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 (lane 4) antimicrobial
therapy. The arrow indicates a B burgdorferi–specific polymerase
chain reaction (PCR) product of 231 base pairs (bp). Aliquots of DNA isolated
from CSF before and after antimicrobial therapy (lane 1 and lane 4, respectively)
were subjected to B burgdorferi amplification. Both M lanes contain
a 100-bp ladder DNA marker. The positive controls (lanes 2 and 5) contain
an American Type Culture Collection B burgdorferi–positive
control. The negative controls (lanes 3 and 6) contain all the PCR components
without DNA.
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At this point, treatment was changed to intravenous doxycycline hyclate
(100 mg every 12 hours). Most of her previously mentioned symptoms returned
within 3 days of starting doxycycline therapy, including confusion and the
inability to concentrate. Antibiotic therapy was changed to intravenous azithromycin
(500 mg/d for 14 days). Her symptoms resolved promptly under azithromycin
treatment. Specifically, her ability to read and perform mathematical tasks
improved greatly. She reported improvement in memory, more restful sleep,
and no further headache.
CASE 4
Our fourth study subject was a 30-year-old woman who became ill within
a week after the removal of 2 ticks from her skin. She complained of fever,
frontal headache, dizziness, fatigue, and upper extremity arthralgia. She
noticed several small ticks on her pet cat, and these were subsequently identified
as I scapularis. These ticks were positive for B henselae–specific DNA and negative for B burgdorferi–specific DNA. Her headaches and dizziness intensified,
and computed tomographic images of the brain were taken, which revealed no
distinct brain abnormality. Nonetheless, her neurologic symptoms persisted. Bartonella henselae was found on serologic testing (IgG
titer, 1:256 using IFA). Bartonella henselae–specific
DNA was amplified from her blood.
This patient exhibited no laboratory evidence of babesiosis, ehrlichiosis,
or Lyme disease by PCR or Western blot analysis. Lumbar puncture was performed,
and findings of CSF analysis were negative for B burgdorferi– and B henselae–specific DNA. She was
treated with a 28-day course of oral doxycycline hyclate (300 mg/d), and her
symptoms resolved during that period.
In summary, the common symptoms before therapy for all 4 patients were
cognitive dysfunction, headache, and fatigue. All of our study subjects had
a clinical presentation consistent with mild encephalopathy (Table 2). After antimicrobial therapy, our study subjects exhibited
improved cognitive function, resolution of headaches, and a marked improvement
in energy levels (Table 3).
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Table 2. Summary of Pretreatment Laboratory Data and Symptoms*
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Table 3. Summary of Posttreatment Laboratory Data and Symptoms*
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COMMENT
Both B henselae and B burgdorferi have a well-established ability to infect the central nervous system,
with a variety of resultant neurologic consequences. Cases of encephalopathy
due to B henselae infection have been well described.16, 17, 18 Patients typically
complain of persistent generalized headache and restlessness and may present
with combative behavior.19 Nearly half of these
patients with encephalopathy can develop seizures that may range from focal
to generalized, and from brief and self-limited to status epilepticus. Bartonella henselae–induced encephalopathy may be
a relatively frequent cause of status epilepticus in school-aged children.20 The ability of this pathogen to cause persistent
dementia following encephalitis has been demonstrated.21
Neuroophthalmic effects, including loss of vision, have been well documented.22, 23, 24, 25
Cat-scratch disease is the most commonly recognized manifestation of
human infection with B henselae. Interestingly, none
of our study subjects displayed the clinical characteristics of cat-scratch
disease. There have been no previously reported cases of tick-borne B henselae infection in humans. Vector competency has not
been clearly established for tick species, and knowledge related to vector
transmission of Bartonellaorganisms is very incomplete.5 Vector-mediated transmission of B henselae to cats via fleas has been demonstrated.26
Three of our study subjects had no prior exposure to cats. Our fourth patient
removed several small ticks from her cat, and these tested positive for B henselae using PCR. This case was included in our study
to illustrate that B henselae infection could be
acquired as a tick-borne disease independent of B burgdorferi infection. One of our patients found a live deer tick in his household
that tested positive on PCR analysis for both B henselae and B burgdorferi. These findings implicate
the deer tick as a potential carrier of B henselae.
Three of our patients had a history of chronic Lyme disease with persistent
symptoms despite previous attempts at antibiotic therapy. The concurrent finding
of B henselae– and B burgdorferi–specific DNA in their CSF probably explains their prior lack of response
to antibiotic therapy directed exclusively at Lyme disease. There were 8 CSF
samples obtained from other patients during the same period that were negative
for both B burgdorferi and B henselae using PCR analysis. Our third patient had persistently detectable B henselae–specific DNA in spinal fluid after a 28-day
course of ceftriaxone therapy. Our second patient demonstrated the absence
of both B henselae– and B burgdorferi–specific DNA after a 28-day course of cefotaxime
treatment. Interestingly, B henselae has been shown
to have in vitro susceptibility to cefotaxime (minimal inhibitory concentration
[MIC90] of 0.25 µg/mL).27 One of our
patients exhibited prompt resolution of symptoms with a trial of azithromycin.
A prospective, randomized, double-blind, placebo-controlled study has demonstrated
azithromycin's efficacy against B henselae.28 The report by Bass et al28
has been the only study of its kind describing the efficacy of azithromycin
against B henselae.
All of our patients were tested for other tick-borne diseases (Babesia and Ehrlichia). The results
were negative on PCR analysis (data not shown). All of our patients exhibited
varying levels of B henselae–specific antibodies
on IFA. However, in a significant number of cases, the diagnosis cannot be
made on the basis of IFA antibody testing alone.29
Serologic testing was performed, including for IgM, and the IgM results were
negative in these 4 cases. The limitations of serologic testing for B henselae have been described.30
The sensitivity of culture for this organism is low when compared with PCR-based
detection methods.31 Polymerase chain reaction
detection of B henselae is especially useful in cases
with a broad differential diagnosis32, 33
and PCR played a pivotal diagnostic role in our study.
Despite antibiotic treatment, some patients with Lyme disease persistently
exhibit symptoms associated with chronic Lyme disease syndrome or post-Lyme
syndrome. These symptoms include neurocognitive impairment, persistent arthralgia,
fatigue, and subjective memory loss.34 The
persistent symptomatology might be attributed to several factors. First, coinfections:
in addition to transmitting B burgdorferi, a tick
may harbor other pathogens, including Babesia, Ehrlichia, and Bartonella species.9 These multiple pathogens may survive Lyme antimicrobial
therapy and be responsible for the persistent symptoms in individuals with
post-Lyme syndrome. The importance of considering these coinfecting agents
in the differential diagnosis cannot be overstated. Second, genetic predisposition
might play a role in chronicity, pathogenesis, antimicrobial resistance, and
prognosis for patients with Lyme disease.
There have been no previously reported cases of concurrent Lyme disease
and B henselae infection. The zoonotic potential
for human infection with Bartonella species has recently
been well described.5 High levels of bacteremia
are currently being documented in numerous domestic and wild animal species.5 Our data implicate B henselae
as yet another tick-borne pathogen. Further vector competency studies are
needed. The fact that our cases of concomitant central nervous system infection
with B henselae and B burgdorferi were diagnosed in a 1-month period suggests that these coinfections
may occur relatively frequently.
Acquisition of simultaneous coinfection of B burgdorferi and Ehrlichia or Babesia by I scapularis ticks is well documented.35, 36, 37, 38 It
was shown that the presence of either B burgdorferi
or human granulocytic ehrlichiosis (HGE) in I scapularis ticks did not affect acquisition of the other agents from an infected
host. In addition, transmission of the agents of Lyme disease and HGE by individual
ticks was equally efficient and independent. Immunoserologic evidence of coinfection
with B burgdorferi, Babesia, and HGE among individuals
in tick-endemic areas is well documented. In one study it was reported that
of 96 patients with Lyme borreloisis, 9 (9.4%) demonstrated immunoserologic
evidence of coinfection.38
The results presented herein provide evidence for coinfection, perhaps
explaining the variable manifestations and clinical responses noted in some
patients with tick-borne diseases. In certain clinical settings, laboratory
testing for coinfection is of great value to ensure that appropriate antimicrobial
treatment is given. Clinicians continue to be challenged to explain the pathophysiology
behind chronic Lyme disease. Persistent symptoms following even aggressive
therapy for Lyme disease continue to frustrate both patients and their physicians.
We put forth concurrent B henselae infection as one
reason for ongoing symptoms in chronic Lyme disease. We consider this an introductory
study and look forward to a more comprehensive evaluation of the role B henselae plays as a coinfecting agent in chronic Lyme
disease. However, we are convinced that concomitant B henselae infection should be considered in neuroborreliosis cases refractory
to standard therapy.
AUTHOR INFORMATION
Accepted for publication May 24, 2001.
From Hunterdon Medical Center (Dr Eskow) and the Vector-Borne Disease
Research Institute LLC (Drs Eskow and Mordechai), Flemington, NJ, and the
Medical Diagnostic Laboratories LLC, Mt Laurel, NJ (Drs Rao and Mordechai).
Corresponding author and reprints: Eli Mordechai, PhD, Medical Diagnostic
Laboratories LLC, 133 Gaither Dr, Suite C, Mt Laurel, NJ 08054 (e-mail:
emordechai{at}aol.com).
REFERENCES
| |
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; 1991:29.20.7.
2. Kaplan RF, Jones-Woodward L. Lyme encephalopathy: a neuropsychological perspective. Semin Neurol. 1997;17:31-37.
ISI
| PUBMED
3. Treb J, Fernandez A, Haass A, Graner MT, Holzer G, Woessner R. Clinical and serologic follow-up in patients with neuroborreliosis. Neurology. 1998;51:1489-1491.
FREE FULL TEXT
4. Wong MT, Dolan MJ, Lattuada CP, et al. Neuroretinitis, aseptic meningitis, and lymphadenitis associated with Bartonella (Rochalimaea) henselae infection in immunocompetent
patients and patients infected with human immunodeficiency virus type 1. Clin Infect Dis. 1995;21:352-360.
ISI
| PUBMED
5. Breitschwerd EB, Kordick DL. Bartonella infection in animals: carriership,
reservoir potential, pathogenicity, and zoonotic potential for human infection. Clin Microbiol Rev. 2000;13:428-438.
FREE FULL TEXT
6. National Institute of Allergy and Infectious Diseases. Research on Chronic Lyme Disease. Bethesda, Md: National Institute of Allergy and Infectious Diseases;
May 1997. NIAID Fact Sheet 1-3.
7. Schouls LM, Van De Pol I, Rijpkema SG, Schot CS. Detection and identification of Ehrlichia, Borrelia burgdorferi sensu lato, and Bartonella species in Dutch Ixodes ricinus
ticks. J Clin Microbiol. 1999;37:2215-2222.
FREE FULL TEXT
8. Kruszewska D, Tylewska-Wierbanowska S. Unknown species of Rickettsiae isolated from
the Ixodes ricinus tick in Walcz. Rocz Aked Med Bialymst. 1996;41:129-135.
9. Hofmeister EK, Kolbert CP, Abdulkarim AS, et al. Co-segregation of a novel Bartonella species
with Borrelia burgdorferi and Babesia microti in Peromyscus leucopus. J Infect Dis. 1998;177:409-416.
ISI
| PUBMED
10. Persing DH, Mathiesen D, Marshall WF, et al. Detection of Babesia microti by polymerase
chain reaction. J Clin Microbiol. 1992;30:2097-2103.
FREE FULL TEXT
11. Relman DA, Loutit JS, Schmidt TM, Falkow S, Tompkins LS. The agent of bacillary angiomatosis. N Engl J Med. 1990;323:1573-1580.
ABSTRACT
12. Cogswell FB, Banter CE, Hughes TG, et al. Host DNA can interfere with detection of Borrelia
burgdorferi in skin biopsy specimens by PCR. J Clin Microbiol. 1996;34:980-982.
ABSTRACT
13. Chu FK. Rapid and sensitive PCR-based detection and differentiation of aetiologic
agents of human granulocytotropic and monototropic ehrlichiosis. Mol Cell Probes. 1998;12:93-99.
FULL TEXT
|
ISI
| PUBMED
14. Schmidt BL. PCR in laboratory diagnosis of human Borrelia burgdorferi. Clin Microbiol Rev. 1997;10:185-201.
ABSTRACT
15. Pieper RO, Futscher BW, Dong Q, Ellis TM, Erickson LC. Comparison of O-6 methylguanine DNA methyltransferase (MGMT) mRNA levels
in Mer-human tumor cell lines containing the MGMT gene by the polymerase chain
reaction technique. Cancer Commun. 1990;2:13-20.
ISI
| PUBMED
16. Wheeler SW, Wolf SM, Steinberg EA. Cat-scratch encephalopathy [comments]. Neurology. 1997;49:876-878.
FREE FULL TEXT
17. Silver BE, Bean CS. Cat-scratch encephalopathy. Del Med J. 1991;63:365-368.
PUBMED
18. Yagupsky P, Sofer S. Cat-scratch encephalopathy presenting as status epilepticus and lymphadenitis. Pediatr Emerg Care. 1990;6:43-45.
PUBMED
19. Harvey RA, Misselbeck WJ, Uphold RE. Cat-scratch disease: an unusual cause of combative behavior. Am J Emerg Med. 1991;9:52-53.
FULL TEXT
|
ISI
| PUBMED
20. Armengol CE, Hendley JD. Cat-scratch disease encephalopathy: a cause of status epilepticus in
school-aged children. J Pediatr. 1999;134:635-638.
FULL TEXT
|
ISI
| PUBMED
21. Revol A, Vighetto A, Jonvet A, Aimard G, Trillet M. Encephalitis in cat-scratch disease with persistent dementia. J Neurol Neurosurg Psychiatry. 1992;55:133-135.
FREE FULL TEXT
22. Chrousos GA, Drak AV, Young M, Kattah J, Sirdofsky M. Neuroretinitis in cat-scratch disease. J Clin Neuroophthalmol. 1990;10:92-94.
PUBMED
23. Gray AV, Reed JB, Wendel RT, Marse LS. Bartonella henselae infection associated with
peripapillary angioma, branch retinol artery occlusion, and severe vision
loss. Am J Ophthalmol. 1999;127:223-224.
FULL TEXT
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ISI
| PUBMED
24. Golnik KC, Marotto ME, Fanons MM, et al. Ophthalmic manifestations of Rochalimaea species
[comments]. Am J Ophthalmol. 1994;118:145-151.
ISI
| PUBMED
25. Reed JB, Scales DK, Wong MT, Cattuada CP Jr, Dolan MJ, Schwab IR. Bartonella henselae neuroretinitis in cat-scratch
disease: diagnosis, management, and sequelae [comments]. Ophthalmology. 1998;105:459-466.
FULL TEXT
|
ISI
| PUBMED
26. Chomel BB, Kasten RW, Floyd-Hawkins K, et al. Experimental transmission of Bartonella henselae by the cat flea. J Clin Microbiol. 1996;34:1952-1956.
ABSTRACT
27. Maurin M, Gasquet S, Ducco C, Raoult D. MICs of 28 antibiotic compounds for 14 Bartonella (formerly Rochalimaea) isolates. Antimicrob Agents Chemother. 1995;39:2387-2391.
ABSTRACT
28. Bass JW, Freitas BC, Freitas AD, et al. Prospective randomized double-blind placebo-controlled evaluation of
azithromycin for treatment of cat-scratch disease. Pediatr Infect Dis J. 1998;17:447-452.
FULL TEXT
|
ISI
| PUBMED
29. Flexman JP, Chen SC, Dickeson DJ, Pearman JW, Gilbert GL. Detection of antibodies to Bartonella henselae
in clinically diagnosed cat-scratch disease. Med J Aust. 1997;166:532-535.
ISI
| PUBMED
30. Bergmans AM, Peters MF, Schellekens JF, et al. Pitfalls and fallacies of cat-scratch disease serology: evaluation
of Bartonella henselae–based indirect fluorescence
assay and enzyme-linked immunoassay. J Clin Microbiol. 1997;35:1931-1937.
ABSTRACT
31. LaScola B, Raoult D. Culture of Bartonella quintana and Bartonella henselae from human samples: a 5-year experience (1993 to
1998). J Clin Microbiol. 1999;37:1899-1905.
FREE FULL TEXT
32. Gottlieb T, Atkins BL, Robson JM. Cat-scratch disease diagnosed by polymerase chain reaction in a patient
with suspected tuberculous lymphadenitis. Med J Aust. 1999;170:168-170.
ISI
| PUBMED
33. George TI, Manley G, Koehler JE, Hung VS, McDermott M, Bollen A. Detection of Bartonella henselae by polymerase
chain reaction in brain tissue of an immunocompromised patient with multiple
enhancing lesions: case report and review of the literature. J Neurosurg. 1998;89:640-644.
ISI
| PUBMED
34. Bujak DI, Weinstein A, Dornbush RL. Clinical and neurocognitive features of the post Lyme syndrome. J Rheumatol. 1996;23:1392-1397.
ISI
| PUBMED
35. Levin ML, Fish D. Acquisition of coinfection and simultaneous transmission of Borrelia burgdorferi and Ehrlichia phagocytophobia
by Ixodes scapularis ticks. Infect Immun. 2000;68:2183-2186.
FREE FULL TEXT
36. Belongia EA, Reed KD, Mitchell PD, et al. Clinical and epidemiological features of early Lyme disease and human
granulocytic ehrlichiosis in Wisconsin. Clin Infect Dis. 1999;29:1472-1477.
FULL TEXT
|
ISI
| PUBMED
37. Magnarelli LA, Dumler JS, Anderson JF, et al. Coexistence of antibodies to tick-borne pathogens of babesiosis, ehrlichiosis,
and Lyme borreliosis in human sera. J Clin Microbiol. 1995;33:3054-3057.
ABSTRACT
38. Mitchell PD, Reed KD, Hofkes JM. Immunoserologic evidence of coinfection with Borrelia
burgdorferi, Babesia microti, and human granulocytic Ehrlichia species in residents of Wisconsin and Minnesota. J Clin Microbiol. 1996;34:724-727.
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