Post by LymeEnigma on Dec 16, 2007 11:34:25 GMT -8
Another great find by Lymenet Europe's Yvonne:
Thread: www.lymeneteurope.org/forum/
viewtopic.php?f=6&t=436&p=2633#p2633
Article: archneur.ama-assn.org/cgi/content/full/58/9/1357
Thread: www.lymeneteurope.org/forum/
viewtopic.php?f=6&t=436&p=2633#p2633
Article: archneur.ama-assn.org/cgi/content/full/58/9/1357
Concurrent Infection of the CNS by Bb and Bartonella h.
ABSTRACT
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.
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.
ABSTRACT
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.
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.