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1.  Neurogenic Bladder in Lyme Disease 
Lyme disease is a multi-systemic, tick-borne infectious disease caused by a spirochete, Borrelia burgdorferi. Various urologic symptoms are associated with Lyme disease, which can be primary or late manifestations of the disease. Although voiding dysfunction is a rarely reported symptom in patients with Lyme disease, it is one of the most disabling complications of Lyme disease. Korea is not an endemic area of Lyme disease, thus, fewer cases have been reported. Herein, we report a case of a 32-year-old man with rapidly progressive bilateral ptosis, dysphagia, spastic paraparesis, and voiding difficulty in whom Lyme disease was diagnosed through serologic tests for antibodies and Western blot testing. A urodynamic study demonstrated detrusor areflexia and bulbocavernosus reflex tests showed delayed latency, indicating demyelination at S2-S4 levels. He received a 4-week course of intravenous ceftriaxone (2 g/day). The patient has recovered from the bilateral ptosis and spastic paraparesis but still suffers from neurogenic bladder.
PMCID: PMC3547183  PMID: 23346488
Lyme disease; Neurogenic urinary bladder; Urodynamics
2.  Two Cases of Orbital Myositis as a Rare Feature of Lyme Borreliosis 
Myositis has been reported as a rare manifestation of Lyme disease, and the Lyme disease spirochetes can be an important consideration in the differential diagnosis of unusual cases of myositis, especially in patients who live in or travel to endemic areas. We report the case of two patients who presented with focal orbital myositis which are rare localization for Lyme disease. Myositis were confirmed by magnetic resonance imaging. Diagnosis criteria for Borrelia burgdorferi (B. burgdorferi) infection was supported by (i) medical history (tick bite in an endemic area), (ii) systemic clinical findings (Erythema migrans, neurological manifestation or arthritis), (iii) positive Lyme serology and/or the detection of B. burgdorferi DNA by polymerase chain reaction, as well as (iv) exclusion of other infectious and inflammatory causes. The current cases are reviewed in the context of findings from previous myositis descriptions.
PMCID: PMC3336248  PMID: 22567470
3.  Lyme Disease and the Orthopaedic Implications of Lyme Arthritis 
Lyme disease is the most common tick-borne disease in the United States and Europe. Increased awareness of the clinical manifestations of the disease is needed to improve detection and treatment. In the acute and late stages, Lyme disease may be difficult to distinguish from other disease processes. The epidemiology and pathophysiology of Lyme disease are directly related to the Borrelia burgdorferi spirochete and its effects on the integumentary, neurologic, cardiac, and musculoskeletal systems. Lyme arthritis is a common clinical manifestation of Lyme disease and should be considered in the evaluation of patients with monoarticular or pauciarticular joint complaints in a geographic area in which Lyme disease is endemic. Management of Lyme arthritis involves eradication of the spirochete with antibiotics. Generally, the prognosis is excellent. Arthroscopic synovectomy is reserved for refractory cases that do not respond to antibiotics.
PMCID: PMC3656475  PMID: 21292932
4.  Brief, recurrent, and spontaneous episodes of loss of consciousness in a healthy young male 
Lyme disease is caused by bacterial spirochete Borrelia burgdorferi and is transmitted by Ixodes scapularis and Ixodes pacificus ticks, which get infected while feeding on the reservoir host of the bacteria.1 About 248,074 cases of Lyme disease were reported by the US Centers for Disease Control and Prevention from 1992–2006.2 Over 95% of these cases are reported from the Northeastern and upper Midwestern United States.3 Carditis is usually a clinical manifestation/complication of Lyme disease and is seen in approximately 5% of untreated cases.4
Case presentation
A 32-year-old male Hispanic from Chile presented with brief episodes of loss of consciousness and awareness of irregular heart beat, and denied any history of tick bite. The patient was found to have a heart rate of 40 beats per minute and fluctuating variable atrioventricular blocks. A transvenous pacemaker was placed with good capture. The diagnosis was made with serological testing and gallium scanning. Treatment with antibiotics and continuous cardiac monitoring resulted in remarkable symptomatic improvement of the patient.
Absence of history or evidence of tick bite must not rule out the possibility of Lyme carditis in a patient with a transient heart block. Prompt recognition of this reversible cause of heart block is essential for avoiding implantation of an unnecessary, permanent pacemaker.
PMCID: PMC3658225  PMID: 23754893
Lyme carditis; transient heart block
5.  Diagnostic challenges of early Lyme disease: Lessons from a community case series 
Lyme disease, the most common vector-borne infection in North America, is increasingly reported. When the characteristic rash, erythema migrans, is not recognized and treated, delayed manifestations of disseminated infection may occur. The accuracy of diagnosis and treatment of early Lyme disease in the community is unknown.
A retrospective, consecutive case series of 165 patients presenting for possible early Lyme disease between August 1, 2002 and August 1, 2007 to a community-based Lyme referral practice in Maryland. All patients had acute symptoms of less than or equal to 12 weeks duration. Patients were categorized according to the Centers for Disease Control and Prevention criteria and data were collected on presenting history, physical findings, laboratory serology, prior diagnoses and prior treatments.
The majority (61%) of patients in this case series were diagnosed with early Lyme disease. Of those diagnosed with early Lyme disease, 13% did not present with erythema migrans; of those not presenting with a rash, 54% had been previously misdiagnosed. Among those with a rash, the diagnosis of erythema migrans was initially missed in 23% of patients whose rash was subsequently confirmed. Of all patients previously misdiagnosed, 41% had received initial antibiotics likely to be ineffective against Lyme disease.
For community physicians practicing in high-risk geographic areas, the diagnosis of Lyme disease remains a challenge. Failure to recognize erythema migrans or alternatively, viral-like presentations without a rash, can lead to missed or delayed diagnosis of Lyme disease, ineffective antibiotic treatment, and the potential for late manifestations.
PMCID: PMC2698836  PMID: 19486523
6.  Antibiotic Treatment of Animals Infected with Borrelia burgdorferi 
Clinical Microbiology Reviews  2009;22(3):387-395.
Summary: Despite resolution of the objective manifestations of Lyme disease after antibiotic treatment, a minority of patients have fatigue, musculoskeletal pain, and/or difficulties with concentration or short-term memory of uncertain etiology; these are called post-Lyme disease symptoms or, in more severe cases, post-Lyme disease syndrome or “chronic Lyme disease.” Several recent studies in which Borrelia burgdorferi-infected animals were treated with antibiotic therapy have demonstrated the presence of PCR positivity for B. burgdorferi DNA in the absence of culture positivity. In mice that were treated with antibiotic therapy, residual spirochetes could be taken up by ticks during a blood meal and could be transmitted to SCID mice. These spirochetes are attenuated; their presence is not associated with either inflammation or disease. In this review the methodology and findings of these studies are critically analyzed, and the significance of the results with regard to human Lyme disease is evaluated, with special emphasis on whether these studies provide useful insights into post-Lyme disease syndrome. A serious methodological concern is the failure to consider the pharmacokinetic-pharmacodynamic properties of the antibiotic in choosing the dosage regimen used. We conclude that there is no scientific evidence to support the hypothesis that such spirochetes, should they exist in humans, are the cause of post-Lyme disease syndrome.
PMCID: PMC2708393  PMID: 19597005
7.  Chronic or Late Lyme Neuroborreliosis: Analysis of Evidence Compared to Chronic or Late Neurosyphilis 
The Open Neurology Journal  2012;6:146-157.
Whether spirochetes persist in affected host tissues and cause the late/chronic manifestations of neurosyphilis was the subject of long-lasting debate. Detection of Treponema pallidum in the brains of patients with general paresis established a direct link between persisting infection and tertiary manifestations of neurosyphilis.
Today, the same question is in the center of debate with respect to Lyme disease. The goal of this review was to compare the established pathological features of neurosyphilis with those available for Lyme neuroborreliosis. If the main tertiary forms of neurosyphilis also occur in Lyme neuroborreliosis and Borrelia burgdorferi can be detected in brain lesions would indicate that the spirochete is responsible for the neuropsychiatric manifestations of late/chronic Lyme neuroborreliosis.
The substantial amounts of data available in the literature show that the major forms of late/chronic Lyme neuroborreliosis (meningovascular and meningoencephalitis) are clinically and pathologically confirmed. Borrelia burgdorferi was detected in association with tertiary brain lesions and cultivated from the affected brain or cerebrospinal fluid. The accumulated data also indicate that Borrelia burgdorferi is able to evade from destruction by the host immune reactions, persist in host tissues and sustain chronic infection and inflammation. These observations represent evidences that Borrelia burgdorferi in an analogous way to Treponema pallidum is responsible for the chronic/late manifestations of Lyme neuroborreliosis.
Late Lyme neuroborreliosis is accepted by all existing guidelines in Europe, US and Canada. The terms chronic and late are synonymous and both define tertiary neurosyphilis or tertiary Lyme neuroborreliosis. The use of chronic and late Lyme neuroborreliosis as different entities is inaccurate and can be confusing. Further pathological investigations and the detection of spirochetes in infected tissues and body fluids are strongly needed.
PMCID: PMC3551238  PMID: 23346260
Borrelia burgdorferi; Chronic Lyme disease; Late Lyme disease; Lyme neuroborrelisosis; Chronic infection; Neurosyphilis; Syphilis; Treponema pallidum.
8.  Laboratory aspects of Lyme borreliosis. 
Clinical Microbiology Reviews  1988;1(4):399-414.
Lyme borreliosis (Lyme disease), a common tick-borne disorder of people and domestic animals in North America and Europe, is caused by the spirochete Borrelia burgdorferi. Following the discovery and initial propagation of this agent in 1981 came revelations that other tick-associated infectious disorders are but different forms of Lyme borreliosis. A challenge for the clinician and microbiology laboratory is confirmation that a skin rash, a chronic meningitis, an episode of myocarditis, or an arthritic joint is the consequence of B. burgdorferi infection. The diagnosis of Lyme borreliosis may be established by (i) directly observing the spirochete in host fluid or tissue, (ii) recovering the etiologic spirochete from the patient in culture medium or indirectly through inoculation of laboratory animals, or (iii) carrying out serologic tests with the patient's serum or cerebrospinal fluid. The last method, while lacking in discriminatory power, is the most efficacious diagnostic assay for most laboratories at present.
PMCID: PMC358062  PMID: 3069200
9.  Human Lyme Arthritis and the Immunoglobulin G Antibody Response to the 37-Kilodalton Arthritis-Related Protein of Borrelia burgdorferi  
Infection and Immunity  2005;73(5):2951-2957.
In Borrelia burgdorferi-infected C3H-scid mice, antiserum to a differentially expressed, 37-kDa spirochetal outer-surface protein, termed arthritis-related protein (Arp), has been shown to prevent or reduce the severity of arthritis. In this study, we determined the immunoglobulin G (IgG) antibody responses to this spirochetal protein in single serum samples from 124 antibiotic-treated human patients with early or late manifestations of Lyme disease and in serial serum samples from 20 historic, untreated patients who were followed longitudinally from early infection through the period of arthritis. These 20 patients were representative of the spectrum of the severity and duration of Lyme arthritis. Among the 124 antibiotic-treated patients, 53% with culture-proven erythema migrans (EM) had IgG responses to recombinant glutathione S-transferase (GST)-Arp, as did 59% of the patients with facial palsy and 68% of those with Lyme arthritis. In addition, 75 to 80% of the 20 past, untreated patients had reactivity with this protein when EM was present, during initial episodes of joint pain, or during the maximal period of arthritis. There was no association at any of these three time points between GST-Arp antibody levels and the severity of the maximal attack of arthritis or the total duration of arthritis. Thus, after the first several weeks of infection, 60 to 80% of patients had IgG antibody responses to GST-Arp, but this response did not correlate with the severity or duration of Lyme arthritis.
PMCID: PMC1087337  PMID: 15845501
10.  Lyme Neuroborreliosis: Preliminary Results from an Urban Referral Center Employing Strict CDC Criteria for Case Selection 
Lyme neuroborreliosis or “neurological Lyme disease” was evidenced in 2 of 23 patients submitted to strict criteria for case selection of the Centers for Disease Control and Prevention employing a two-tier test to detect antibodies to Borrelia burgdorferi at a single institution. One patient had symptomatic polyradiculoneuritis, dysautonomia, and serological evidence of early infection; and another had symptomatic small fiber sensory neuropathy, distal polyneuropathy, dysautonomia, and serological evidence of late infection. In the remaining patients symptoms initially ascribed to Lyme disease were probably unrelated to B. burgdorferi infection. Our findings suggest early susceptibility and protracted involvement of the nervous system most likely due to the immunological effects of B. burgdorferi infection, although the exact mechanisms remain uncertain.
PMCID: PMC2989654  PMID: 21188224
11.  Differential spirochetal infectivities to vector ticks of mice chronically infected by the agent of Lyme disease. 
Journal of Clinical Microbiology  1995;33(12):3164-3168.
We determined whether the infectivity of the Lyme disease spirochete (Borrelia burgdorferi) to vector ticks varies with the duration of infection in laboratory mice. Thus, noninfected nymphal deer ticks were permitted to feed on two strains of early (2 months after infection) and late (8 months after infection) spirochete-infected mice. The attached ticks were removed from their hosts at specified time intervals and were thereafter examined for spirochetes by direct immunofluorescence microscopy. Spirochetes can be acquired by nymphal ticks as fast as 8 h after attachment. More than 80% of the attached ticks acquired spirochetal infection within 48 h after feeding on early spirochete-infected mice. In contrast, spirochetal infectivity to ticks was less than 50% after feeding on late spirochete-infected mice. The overall infectivity of spirochete-infected mice to ticks correlated with the duration of tick attachment. In addition, there was no adverse effect on the spirochetal infectivity to ticks by high levels of host antibody against spirochetes, and no obvious differences in infectivity to ticks was observed by the site of tick feeding. We conclude that the span of spirochetal infectivity to ticks varies with the duration of infection in mice and suggest that spirochetes may persist and may be evenly distributed in the skin of infected hosts, regardless of prominent host immunity.
PMCID: PMC228665  PMID: 8586694
12.  Lyme Disease 
Clinics in laboratory medicine  2010;30(1):311-328.
Lyme disease, caused by spirochete Borrelia burgdorferi, is the most common vector-borne disease in the United States. The clinical presentation varies depending on the stage of the illness: early disease includes erthyma migrans, early disseminated disease includes multiple erythema migrans, meningitis, cranial nerve palsies and carditis; late disease is primarily arthritis. The symptoms and signs of infection resolve in the vast majority of patients after appropriate treatment with antimicrobials for from 2-4 weeks. Serologic testing should be used judiciously as it often results in misdiagnosis when performed on blood from patients with a low prior probability of disease and those with non-specific symptoms such as fatigue or arthralgia without signs of infection.
PMCID: PMC3652387  PMID: 20513553
Lyme Disease; Borrellia burdorferi; tick-borne infections; erythema migrans; serologic testing; misdiagnosis
13.  Implications of Gender in Chronic Lyme Disease 
Journal of Women's Health  2009;18(6):831-834.
“Post-Lyme disease syndrome” refers to prolonged subjective symptoms after antibiotic treatment and resolution of an objective manifestation of Borrelia burgdorferi infection (Lyme disease). “Chronic Lyme disease” is a vaguely defined term that has been applied to patients with unexplained prolonged subjective symptoms, whether or not there was or is evidence of B. burgdorferi infection.
To determine if the population of patients with chronic Lyme disease differs from the populations of patients with either Lyme disease or post-Lyme disease syndrome by examining the gender of patients with these diagnoses.
Data on gender were compiled in this cross-sectional study based on a systematic review of published studies of antibiotic treatment in United States patients with post-Lyme disease syndrome (n = 184) or chronic Lyme disease (n = 490), and on cases of adults with Lyme disease reported to the Centers for Disease Control and Prevention from 2003 to 2005 (n = 43,282).
Patients with chronic Lyme disease were significantly more likely to be female than were patients diagnosed with either Lyme disease (odds ratio [OR] 2.42, 95% confidence interval [CI] 1.98–2.94, p < 0.0001) or with post-Lyme disease syndrome (OR 2.32, 95% CI 1.62–3.34, p < 0.0001).
Patients with chronic Lyme disease differ with regard to gender from those with either B. burgdorferi infection or post-Lyme disease syndrome. This finding suggests that illnesses with a female preponderance, such as fibromyalgia, chronic fatigue syndrome, or depression, may be misdiagnosed as chronic Lyme disease.
PMCID: PMC2913779  PMID: 19514824
14.  Lyme Borreliosis in Human Patients in Florida and Georgia, USA 
The aim of this study was to determine the cause of illness in several human patients residing in Florida and Georgia, USA, with suspected Lyme disease based upon EM-like skin lesions and/or symptoms consistent with early localized or late disseminated Lyme borreliosis. Using polymerase chain reaction (PCR) assays developed specifically for Lyme group Borrelia spp., followed by DNA sequencing for confirmation, we identified Borrelia burgdorferi sensu lato DNA in samples of blood and skin and also in lone star ticks (Amblyomma americanum) removed from several patients who either live in or were exposed to ticks in Florida or Georgia. This is the first report to present combined PCR and DNA sequence evidence of infection with Lyme Borrelia spp. in human patients in the southern U.S., and to demonstrate that several B. burgdorferi sensu lato species may be associated with Lyme disease-like signs and symptoms in southern states. Based on the findings of this study, we suggest that human Lyme borreliosis occurs in Florida and Georgia, and that some cases of Lyme-like illness referred to as southern tick associated rash illness (STARI) in the southern U.S. may be attributable to previously undetected B. burgdorferi sensu lato infections.
PMCID: PMC3675506  PMID: 23781138
Lyme borreliosis; Florida; Georgia
15.  Overview of the clinical manifestations of Borrelia burgdorferi infection 
Lyme disease, caused by the spirochete Borrelia burgdorferi, has classically been divided into three stages: erythema migrans; neurological or cardiac involvement; and arthritis. Rather than defining a set disease pattern, however, one should, more logically, conceptualize a progressive infection that may be localized or disseminated, acute or chronic. Erythema migrans, the earliest and most easily recognized manifestation of B burgdorferi infection, is an expanding annular erythematous skin lesion with a central clearing that develops soon after the bite of an infected ixodes tick. Musculoskeletal manifestations are common, with approximately one-half of untreated individuals developing arthritis. Of these, only 10% have chronic arthritis. Invasion of the central nervous system occurs as the infection disseminates hematogenously, with encephalitis, myelitis and meningopolyneuritis being the most severe results. Acute cardiac involvement is recognized in up to 8% of adult patients, and less often in children. Early antibiotic treatment of the infection is highly effective.
PMCID: PMC3327997  PMID: 22529711
Clinical manifestations; Disease stages; Lyme disease; Progressive infectious disease
16.  Lyme disease 
Clinical Evidence  2004;2004:0910.
Lyme disease is caused by infection with Borrelia burgdorferi transmitted by ticks in temperate areas, typically causing an expanding circular rash around the infectious tick attachment site. Early disseminated infection can cause neuropathies, meningitis, arthralgia and cardiac disease, although spontaneous resolution usually occurs over time. Untreated or inadequately treated Lyme disease can cause late disseminated infection, with arthritis, polyneuropathy and encephalopathy.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: what are the effects of measures to prevent Lyme disease? What are the effects of antibiotic treatment for Lyme disease arthritis? What are the effects of antibiotic treatments for late neurological Lyme disease? We searched: Medline, Embase, The Cochrane Library and other important databases up to September 2003 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
We found 11 systematic reviews, RCTs or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
In this systematic review we present information relating to the effectiveness and safety of the following interventions: prophylactic antibiotic treatment of tick bite, treatment of Lyme disease arthritis with antibiotics, and treatment of late neurological Lyme disease with antibiotics.
Key Points
Lyme disease is caused by infection with Borrelia burgdorferi transmitted by ticks in temperate areas, typically causing an expanding circular rash around the infectious tick attachment site. Early disseminated infection can cause neuropathies, meningitis, arthralgia and cardiac disease, although spontaneous resolution usually occurs over time.Untreated or inadequately treated Lyme disease can cause late disseminated infection, with arthritis, polyneuropathy and encephalopathy.
Prophylactic antibiotics such as single dose doxycycline reduce the risk of developing early Lyme disease in people exposed to tick bites but increase the risk of adverse effects. Limiting prophylactic treatment to people with engorged nymphal ticks may be the best strategy to maximise benefit and minimise harm from adverse effects.
In people with Lyme arthritis, penicillin increases resolution of symptoms compared with placebo. Cefotaxime and ceftriaxone may improve symptoms compared with penicillin, but few good quality studies have been found.Doxycycline may be as effective as amoxicillin plus probenecid at improving symptoms of Lyme arthritis.
In people with late neurological Lyme disease, cefotaxime may be more effective than penicillin at improving symptoms, but we don't know whether ceftriaxone is also beneficial. Ceftriaxone may be no more effective than placebo at improving cognitive functioning in people with late neurological Lyme disease who had received prior treatment.Ceftriaxone plus doxycycline has not been shown to improve health related quality of life in people with late neurological Lyme disease who have previously received treatment.
PMCID: PMC2907555
17.  Case report: papillitis as the sole ocular sign in Lyme disease 
Lyme disease is a spirochetal disease responsible for a multitude of ocular and systemic manifestations, and patients may present to ophthalmologists and general clinicians with a wide variety of generalized and ocular signs which can result in chronic and disabling sequelae. Here we report two cases of patients suffering with Lyme disease who developed a rare associated papillitis.
A 48-year-old Scottish man presented with diminished visual acuity, painful ocular eye movements, photophobia, and mild ataxia. Fundus examination revealed bilateral disc swelling with associated hemorrhages in the right eye. Following exclusion of raised intracranial pressure as the cause of the findings, enzyme-linked immunosorbent assay and Western blot serology confirmed a positive result for Borrelia burgdorferi which, along with ophthalmic signs and exposure to an endemic area, confirmed the diagnosis of Lyme disease. A 79-year-old gentleman presented with intermittent short-duration “gray film” in his left eye. Fundus examination revealed left optic disc swelling. He was positive for Lyme’s serology and his condition was treated with 2 weeks of intravenous ceftriaxone.
The first patient’s inflammation resolved and visual acuity returned to normal following a course of high-dose steroids and intravenous ceftriaxone, followed by oral doxycycline. The second patient’s condition improved with high-dose intravenous ceftriaxone.
These patients highlight the fact that Lyme disease should be considered as a differential diagnosis for patients presenting with papillitis. With the incidence of this disease rising and more cases being reported, practitioners in Lyme-endemic areas need to be aware of the various manifestations so that appropriate referrals for treatment can be made.
PMCID: PMC3413342  PMID: 22888207
Lyme disease; ocular papillitis; Borrelia burgdorferi
18.  Allelic Variation of the Lyme Disease Spirochete Adhesin DbpA Influences Spirochetal Binding to Decorin, Dermatan Sulfate, and Mammalian Cells▿ 
Infection and Immunity  2011;79(9):3501-3509.
After transmission by an infected tick, the Lyme disease spirochete, Borrelia burgdorferi sensu lato, colonizes the mammalian skin and may disseminate systemically. The three major species of Lyme disease spirochete—B. burgdorferi sensu stricto, B. garinii, and B. afzelii—are associated with different chronic disease manifestations. Colonization is likely promoted by the ability to bind to target tissues, and Lyme disease spirochetes utilize multiple adhesive molecules to interact with diverse mammalian components. The allelic variable surface lipoprotein decorin binding protein A (DbpA) promotes bacterial binding to the proteoglycan decorin and to the glycosaminoglycan (GAG) dermatan sulfate. To assess allelic variation of DbpA in GAG-, decorin-, and cell-binding activities, we expressed dbpA alleles derived from diverse Lyme disease spirochetes in B. burgdorferi strain B314, a noninfectious and nonadherent strain that lacks dbpA. Each DbpA allele conferred upon B. burgdorferi strain B314 the ability to bind to cultured kidney epithelial (but not glial or endothelial) cells, as well as to purified decorin and dermatan sulfate. Nevertheless, allelic variation of DbpA was associated with dramatic differences in substrate binding activity. In most cases, decorin and dermatan sulfate binding correlated well, but DbpA of B. afzelii strain VS461 promoted differential binding to decorin and dermatan sulfate, indicating that the two activities are separable. DbpA from a clone of B. burgdorferi strain N40 that can cause disseminated infection in mice displayed relatively low adhesive activity, indicating that robust DbpA-mediated adhesive activity is not required for spread in the mammalian host.
PMCID: PMC3165495  PMID: 21708995
19.  Rational diagnostic strategies for Lyme borreliosis in children and adolescents: recommendations by the Committee for Infectious Diseases and Vaccinations of the German Academy for Pediatrics and Adolescent Health 
European Journal of Pediatrics  2012;171(11):1619-1624.
The varying clinical manifestations of Lyme borreliosis, transmitted by Ixodes ricinus and caused by Borrelia burgdorferi, frequently pose diagnostic problems. Diagnostic strategies vary between early and late disease manifestations and usually include serological methods. Erythema migrans is pathognomonic and does not require any further laboratory investigations. In contrast, the diagnosis of neuroborreliosis requires the assessment of serum and cerebrospinal fluid. Lyme arthritis is diagnosed in the presence of newly recognized arthritis and high-titer serum IgG antibodies against B. burgdorferi. The committee concludes the following recommendations: Borrelial serology should only be ordered in case of well-founded clinical suspicion for Lyme borreliosis, i.e., manifestations compatible with the diagnosis. Tests for borrelial genomic sequences in ticks or lymphocyte proliferation assays should not be ordered. When results of such tests or of serological investigations that were not indicated are available, they should not influence therapeutic decisions. Laboratories should be cautious when interpreting results of serological tests and abstain from giving therapeutic recommendations and from proposing retesting after some time without intimate knowledge of patient's history and disease manifestations.
PMCID: PMC3491193  PMID: 22782450
Lyme borreliosis; Borrelia burgdorferi; Neuroborreliosis; Lyme arthritis; Diagnosis; Children; Recommendations
20.  Clinical Features of 705 Borrelia burgdorferi Seropositive Patients in an Endemic Area of Northern Italy 
The Scientific World Journal  2014;2014:414505.
Background. Lyme Borreliosis is a multisystemic infection caused by spirochetes of Borrelia burgdorferi sensu lato complex. The features of Lyme Borreliosis may differ in the various geographical areas, primarily between the manifestations found in America and those found in Europe and Asia. Objective. to describe the clinical features of Lyme Borreliosis in an endemic geographic area such as Friuli-Venezia Giulia in the Northeastern part of Italy. Methods. The medical records of patients resulted seropositive for Borrelia burgdorferi have been retrospectively recorded and analyzed. Results. Seven hundred and five patients met the inclusion criteria, 363 males and 342 females. Erythema migrans was the most common manifestation, detected in 437 patients. Other classical cutaneous manifestations included 58 cases of multiple erythema migrans, 7 lymphadenosis benigna cutis, and 18 acrodermatitis chronica atrophicans. The musculoskeletal system was involved in 511 patients. Four hundred and sixty patients presented a neurological involvement. Flu-like symptoms preceded or accompanied or were the only clinical feature in 119 patients. Comments. The manifestations of Lyme borreliosis recorded in this study are similar to the ones of other endemic areas in Europe, even if there are some peculiar features which are different from those reported in Northern Europe and in the USA.
PMCID: PMC3914583  PMID: 24550705
21.  Serologic Proteome Analysis of Borrelia burgdorferi Membrane-Associated Proteins  
Infection and Immunity  2006;74(7):3864-3873.
Lyme disease, a global health concern, is caused by infection with Borrelia burgdorferi, B. afzelii, or B. garinii. The spirochete responsible for the disease in the United States is B. burgdorferi and is spread by the bite of an infected Ixodes tick. We utilized multiple two-dimensional gel techniques combined with proteomics to reveal the full humoral immune response of mice and Lyme patients to membrane-associated proteins isolated from Borrelia burgdorferi. Our studies indicated that a subset of immunogenic membrane-associated proteins (some new and some previously identified) was recognized by mice experimentally infected with Borrelia burgdorferi either by low-dose needle inoculation or by tick infestation. Moreover, the majority of these immunogenic membrane-associated proteins were recognized by sera from patients diagnosed with early-disseminated Lyme disease. These included RevA, ErpA, ErpP, DbpA, BmpA, FtsZ, ErpB, LA7, OppA I, OppA II, OppA IV, FlhF, BBA64, BBA66, and BB0323. Some immunogens (i.e., BBI36/38) were more reactive with sera from mice than Lyme patients, while additional membrane proteins (i.e., FlaB, P66, LA7, and Hsp90) were recognized more strongly with sera from patients diagnosed with early-localized, early-disseminated, or late (chronic)-stage Lyme disease. We were able to examine the humoral response in Lyme patients in a temporal fashion and to identify the majority of immunoreactive proteins as the disease progresses from early to late stages. This serologic proteome analysis enabled the identification of novel membrane-associated proteins that may serve as new diagnostic markers and, more importantly, as second-generation vaccine candidates for protection against Lyme disease.
PMCID: PMC1489744  PMID: 16790758
22.  Minimal-Change Disease Secondary to Borrelia burgdorferi Infection 
Case reports in nephrology  2012;2012:294532.
Lyme borreliosis is a chronic illness caused by tick-transmitted spirochete Borrelia burgdorferi. Borreliosis can be extremely threatening if it is not diagnosed and treated in early stages. Kidneys are not typically involved in the disease. However, in infected dogs, Lyme nephritis is present in 5–10% of cases. It is associated with rapidly progressing renal failure. Histopathological examination shows mesangial proliferative glomerulonephritis with diffuse tubular necrosis, (Dambach et al. (1997)). In available literature, there were reports of human's glomerulonephritis associated with Borrelia burgdorferi infection. These cases refer to membranous and mesangial proliferative glomerulonephritis (Kirmizis and Chatzidimitriou (2010), Zachäus (2008), and Kirmizis et al. (2004)). In this paper, we present the case of minimal-change disease (MCD) as a result of Borrelia burgdorferi infection.
PMCID: PMC3914252  PMID: 24527240
23.  Identification of membrane associated drug targets in Borrelia burgdorferi ZS7- subtractive genomics approach 
Bioinformation  2011;6(9):356-359.
Lyme disease is an infectious disease caused by a spirochete Borrelia burgdorferi ZS7. This spirochete is most often spread by ticks. Single antibiotic therapy is sufficient for containment of the early stage progression of the disease but combinational therapy is more preferred in later stages. Research is in progress for the development of drugs against the pathogen, but till date no vaccines have been developed to effect the late stage infections. There is a rapid rise in the cases of antibiotic-resistant population which is more than 10% of the total infected individuals. In such condition vaccine becomes the sole alternative for prevention. Therefore effective treatment includes antibiotic combination and combination of antigenic surfaces (for vaccine preparation). Thus, a comprehensive list of drug targets unique to the microorganisms is often necessary. Availability of Borrelia burgdorferi ZS7 proteome has enabled insilico analysis of protein sequences for the identification of drug targets and vaccine targets. In this study, 272 essential proteins were identified out of which 42 proteins were unique to the microorganism. The study identified 15 membrane localized drug targets. Amongst these 15, molecular modeling and structure validation of the five membrane localized drug target proteins could only be achieved because of the low sequence identity of the remaining proteins with RCSB structures. These 3D structures can be further characterized by invitro and invivo studies for the development of novel vaccine epitopes and novel antibiotic therapy against Borrelia burgdorferi.
PMCID: PMC3143400  PMID: 21814395
Borrelia burgdorferi; Lyme disease; Insilico; Homology modeling; subtractive genomics
24.  Quantitative Detection of Borrelia burgdorferi in 2-Millimeter Skin Samples of Erythema Migrans Lesions: Correlation of Results with Clinical and Laboratory Findings 
Journal of Clinical Microbiology  2002;40(4):1249-1253.
Variability of disease manifestations has been noted in patients with Lyme disease. A contributing factor to this variation may be the number of spirochetes present in infected patients. We evaluated clinical and laboratory findings for patients with erythema migrans with regard to the number of Borrelia burgdorferi organisms detected by quantitative PCR (qPCR) in 2-mm skin biopsy specimens. B. burgdorferi was detected in 80% (40 of 50) of the specimens tested; the mean number of spirochetes in these specimens ranged over 3 orders of magnitude (10 to 11,000 spirochetes per 2-mm biopsy specimen). Larger numbers of spirochetes were significantly associated with a shorter duration of the erythema migrans skin lesion (P = 0.020), smaller skin lesions (P = 0.020), and infection with a specific genotype of B. burgdorferi (P = 0.008) but not with the number or severity of symptoms. Skin culture positivity was significantly associated with skin lesions containing larger numbers of spirochetes (P = 0.019).
PMCID: PMC140402  PMID: 11923340
25.  Borrelia burgdorferi Complement Regulator-Acquiring Surface Protein 2 (CspZ) as a Serological Marker of Human Lyme Disease▿  
Serological diagnosis of Lyme disease may be complicated by antigenic differences between infecting organisms and those used as test references. Accordingly, it would be helpful to include antigens whose sequences are well conserved by a broad range of Lyme disease spirochetes. In the present study, line blot analyses were performed using recombinant complement regulator-acquiring surface protein 2 (BbCRASP-2) from Borrelia burgdorferi sensu stricto strain B31 and serum samples from human Lyme disease patients from throughout the United States and Germany. The results indicated that a large proportion of the patients had produced antibodies recognizing recombinant BbCRASP-2. In addition, Lyme disease spirochetes isolated from across North America and Europe were found to contain genes encoding proteins with high degrees of similarity to the B. burgdorferi type strain B31 BbCRASP-2, consistent with the high percentage of serologically positive patients. These data indicate that BbCRASP-2 may be valuable for use in a widely effective serological assay.
PMCID: PMC2268266  PMID: 18160620

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