Serological Diagnostics of Lyme Borreliosis: Comparison of Universal and Borrelia Species-Specific Tests Based on Whole-Cell and Recombinant Antigens.

The study compares diagnostic parameters of different commercial serological kits based on three different antigen types and correlates test results with the status of the patient's Borrelia infection. In total, 8 IgM and 8 IgG kits were tested, as follows: enzyme-linked immunosorbent assay (ELISA) (Euroimmun) based on whole-cell antigen, 3 species-specific enzyme immunoassays (EIAs) (TestLine), Liaison chemiluminescence (DiaSorin), ELISA-Viditest (Vidia), EIA, and Blot-Line (TestLine) using recombinant antigens. All tests were performed on a panel of 90 samples from patients with clinically characterized borreliosis (53 with neuroborreliosis, 32 with erythema migrans, and 5 with arthritis) plus 70 controls from blood donors and syphilis patients. ELISA based on whole-cell antigens has superior sensitivity and superior negative predictive value and serves as an excellent screening test, although its specificity and positive predictive values are low. Species-specific tests have volatile parameters. Their low sensitivity and low negative predictive value handicap them in routine diagnostics. Tests with recombinant antigens are characterized by high specificity and high positive predictive value and have a wide range of use in diagnostic practice. Diagnostic parameters of individual tests depend on the composition of the sample panel. Only a small proportion of contradictory samples giving both negative and positive results is responsible for discrepancies between test results. Correlation of test results with the patient's clinical state is limited, especially in the erythema migrans group with high proportions of negative and contradictory results. In contrast, IgG test results in the neuroborreliosis group, which are more concordant, show acceptable agreement with Borrelia status.

Serum carnitine concentration is decreased in patients with Lyme borreliosis.

BACKGROUND: Lyme borreliosis (LB) is a serious infectious disease. Carnitine plays a crucial role in metabolism and inflammatory responses. Carnitine may be important in improving neuronal dysfunction and loss of neurons. AIM: To evaluate serum carnitine concentration in adult patients with various clinical types of LB. MATERIAL/METHODS: Groups: 1) patients with erythema migrans (EM, n=16), 2) neuroborreliosis (NB, n=10), 3) post-Lyme disease (PLD, n=22) and healthy controls (HC, n=32). Total (TC) and free (FC) carnitine were determined with the spectrophotometric method. RESULTS: TC levels (44.9±10.4, 28.0±8.4, 35.9±15.6 µmol/L) in the EM, NB and PLD patients were lower than in HC (54.0±11.4 µmol/L), p < 0.001. FC levels (32.7±7.7, 23.6±6.8, 26.3±11.2 µmol/L) in the EM, NB and PLD patients were lower than in HC (40.5±7.6 µmol/L), p < 0.001. AC levels (12.2±5.2, 4.4±2.6, 9.6±7.4 µmol/L) in the EM, NB and PLD patients were lower in the NB and PLD patients than in HC (13.5±8.40 µmol/L), p <0.001. AC/FC ratio was 0.31±0.14, 0.18±0.09, 0.39±0.33 in the EM, NB and PLD patients. CONCLUSIONS: LB patients exhibit a significant decrease of their serum carnitine concentrations. The largest changes were in the NB and PLD patients. To prevent late complications of the disease a possibility of early supplementation with carnitine should be considered. Further studies are required to explain the pathophysiological significance of our findings.

[Insights on the management of Lyme disease]. / Actualités sur la prise en charge de la maladie de Lyme.

Lyme disease is currently a hot topic in France due to a high incidence in some areas. Its clinical polymorphism can lead to misdiagnosis on one hand and to unjustified treatment on the other hand. Clinical symptoms vary considerably according to involved organs (skin, central and/or peripheral nervous system, joints, heart, eyes) and may be limited to or associated with general non-specific signs. Biological exams must be guided by clinical symptoms to help diagnosis and treatment decision according to clinical history, presentation, time of onset and duration of symptoms. However, to date, no serologic test can discriminate between past and active disease. The role of the internist is two-fold: make a diagnosis when faced with general or focal symptoms and avoid inappropriate attribution to Lyme disease of symptoms related to alternate diagnoses.

Assessing diagnostic coding practices among a sample of healthcare facilities in Lyme disease endemic areas: Maryland and New York - A Brief Report.

The value of using diagnostic codes in Lyme disease (LD) surveillance in highly endemic states has not been well studied. Surveys of healthcare facilities in Maryland (MD) and New York (NY) regarding coding practices were conducted to evaluate the feasibility of using diagnostic codes as a potential method for LD surveillance. Most respondents indicated that their practice utilized electronic medical records (53%) and processed medical/billing claims electronically (74%). Most facilities were able to search office visits associated with specific ICD-9-CM and CPT codes (74% and 73%, respectively); no discernible differences existed between the healthcare facilities in both states. These codes were most commonly assigned by the practitioner (82%), and approximately 70% of respondents indicated that these codes were later validated by administrative staff. These results provide evidence for the possibility of using diagnostic codes in LD surveillance. However, the utility of these codes as an alternative to traditional LD surveillance requires further evaluation.

[Laboratory methods for the diagnosis of clinical forms of Lyme borreliosis]. / Méthodes du diagnostic biologique au cours des différentes manifestations de la borréliose de Lyme.

Methods used to diagnose Lyme borreliosis (LB) vary according to clinical presentations. A very good basis to clarify this nosological and clinical entity is the study published by the "European Concerted Action on Lyme Borreliosis" (EUCALB). In fact, only few studies were performed on cohorts of patients including all clinical forms of LB. For Erythema migrans, serology sensitivity is low (20% to 50%), while the sensitivity of culture or PCR reaches 50%. In early-complicated forms, serology is more sensitive (70 to 90%) with the presence of concomitant IgG and IgM. Screening for antibodies in CSF is very useful for the diagnosis of neuroborreliosis. For this clinical form, culture or PCR sensitivity is disappointing (10 to 30%). In arthritis and acrodermatitis chronica atrophicans (ACA), IgG serology is 100% positive with very high titers; however IgM serology is only positive in 5 to 10% of the cases. In ACA, culture sensitivity ranges from 20 to 60% and PCR sensitivity from 60 to 90%. Specificity of antibodies, natural exposure to the etiologic agent, and cross-reactivity are critical for the final interpretation of serological assessment. Only the use of "serological profiles" allows the exploitation of detailed results (isotypes, intensity). In this approach, IgG avidity could be constructive. The western-blot is intended to confirm the specificity of antibodies found in screening methods (Elisa).

[Antibiotherapy for early localized Lyme disease]. / Antibiothérapie de la phase primaire de la borréliose de Lyme.

OBJECTIVE: The aim of this article is to provide clinicians with guidelines for the antibiotherapy of early-localized Lyme disease. The outcome measures are the clearance of erythema migrans and associated symptoms of early localized Lyme disease and the prevention rate of late complications, with a low risk of adverse effects. Design. The reviewed studies were selected by Medline with the keywords: "erythema migrans, treatment". Sixteen studies comparing treatment or duration of treatment were analyzed. RESULTS: Amoxicillin, doxycycline, and cefuroxim axetil are equally efficacious for early-localized Lyme disease. Azithromycin is an alternative. Most patients respond completely and less than 10% fail to respond. All antibiotics are associated with a low frequency of adverse effects, with the exception of Jarisch Herxheimer reaction which occurs in about 15% of the patients. CONCLUSIONS: We recommend treating adults with amoxicillin (50 mg/kg/day in 3 intakes) or doxycycline (100 mg bid) for 14 days (erythema migrans) to 21 days (early localized Lyme disease with associated symptoms). For children, we recommend amoxicillin (50 mg/kg/day in 3 intakes) or doxycycline (4 mg/kg/day in 2 intakes, maximum 100 mg/dose) above 8 years of age. Cefuroxim axetil (500 mg twice daily for adults or 30 mg/kg/day in 2 intakes, maximum 500 mg/dose, for children), and azithromycin (500 mg/day for adults and 20 mg/kg/day for children for 7-10 days) are second line treatment.

[Dermatological aspects of Lyme borreliosis]. / Aspects dermatologiques au cours de la maladie de Lyme.

Lyme borreliosis is a tick-borne zoonosis due to bacterial infection by Borrelia (B.) burgdorferi sensu lato The disease presents differently in Europe or North America and may be called European borreliosis when acquired in Europe. Lyme borreliosis evolves in 3 stages. The main manifestations include cutaneous, neurological, and joint involvement. Erythema migrans (EM) is the most specific and most frequent finding in patients with Lyme borreliosis. It is the hallmark of early-localized borreliosis. EM is a slowly expanding red macula that occurs in about 60-80% of patients contracting Lyme borreliosis. Central clearing of the red patch can occur. It appears at the site of the tick bite, 7 to 20 days after the bite. Borrelial lymphocytoma (BL) occur rarely in patients with the early-disseminated stage of the disease. BL is a red or brown nodule or plaque located on the nipple, the earlobe, the scrotum, or the face. It should not be confused with cutaneous B-cell lymphoma. Acrodermatitis chronica atrophicans (ACA) is the cutaneous manifestation of late borreliosis. It starts as a violaceous patch, usually located on the extensor surface of a limb. Periarticular nodules and cords can also be present. Without treatment, it will evolve over weeks or months to the typical atrophic stage with extensive dermo-epidermal atrophy and visibility of superficial veins. Only these 3 manifestations are clearly related to an infection with B. burgdorferi. The relationship between infection with B. burgdorferi and other dermatoses, especially morphea, lichen sclerosus, and interstitial granulomatous dermatitis is still debated.

[Treatment of Lyme borreliosis secondary and tertiary stages]. / Le traitement des phases secondaires et tertiaires de la borréliose de Lyme.

The treatment of secondary and tertiary Lyme borreliosis is difficult because of antibiotic lack of efficacy. This fact may be explained by several factors: the specific pathophysiology, involving not only the presence of bacteria, but also immunological reactions. There is no specific method of diagnosis resulting in difficulties for good indication of treatment and to evaluate treatment efficacy. The literature review shows that ceftriaxone and doxycycline are the two most efficient antibiotics in this indication. Even if the methodology of the published studies is not always convincing, these two antibiotics proved their efficacy in articular as well as in neurological forms of the disease. In the late stage of borreliosis, antibiotics are less efficient. Various treatment modalities with different dosage or duration of treatment cannot let us conclude on a convincing regimen.

[Borreliosis as the cause of disability pensions in Norway]. / Borreliose som årsak til uførepensjon i Norge.

BACKGROUND: Borreliosis is a bacterial infection transferred by tick-bites. Neuroborreliosis is the most frequent disseminated form of the disorder in Norway. Registers exist in Norway on all reported communicable diseases (The Norwegian Surveillance System for Communicable Diseases [MSIS]) and disability pension diagnoses (The Norwegian Directorate of Labour and Welfare). MATERIAL AND METHODS: Geographic distributions of borreliosis and changes over time are presented. Disability pensions (coded by International Classification of Diseases [ICD]) in the period 1998-2005, in which borreliosis was used as the primary or secondary diagnosis (ICD-10), were compared with MSIS-data for borreliosis on municipal and county levels. RESULTS: Borreliosis was the cause of disability pensions in 55 cases. The Vestfold and Agder counties had the highest number of cases. Larvik municipality had 9 cases, Arendal had four and Kristiansand had nine cases. The annual rates of new disability pensions caused by borreliosis were low but increasing in the period 1998-2005. The disability pension rates tended to reflect changes in the number of MSIS-reported cases, with pensions changing 1-2 years after MSIS-changes. Most MSIS-reported cases are in the Agder and Telemark counties. INTERPRETATION: Disability pension are rarely caused by borreliosis. The annual incidence of disability pensions seems to reflect the number of MSIS-reported cases of borreliosis. The Agder and Vestfold counties have the highest incidence.

Metabolic differentiation of early Lyme disease from southern tick-associated rash illness (STARI).

Lyme disease, the most commonly reported vector-borne disease in the United States, results from infection with Borrelia burgdorferi. Early clinical diagnosis of this disease is largely based on the presence of an erythematous skin lesion for individuals in high-risk regions. This, however, can be confused with other illnesses including southern tick-associated rash illness (STARI), an illness that lacks a defined etiological agent or laboratory diagnostic test, and is coprevalent with Lyme disease in portions of the eastern United States. By applying an unbiased metabolomics approach with sera retrospectively obtained from well-characterized patients, we defined biochemical and diagnostic differences between early Lyme disease and STARI. Specifically, a metabolic biosignature consisting of 261 molecular features (MFs) revealed that altered N-acyl ethanolamine and primary fatty acid amide metabolism discriminated early Lyme disease from STARI. Development of classification models with the 261-MF biosignature and testing against validation samples differentiated early Lyme disease from STARI with an accuracy of 85 to 98%. These findings revealed metabolic dissimilarity between early Lyme disease and STARI, and provide a powerful and new approach to inform patient management by objectively distinguishing early Lyme disease from an illness with nearly identical symptoms.

A high frequency of viral agents yet absence of Borrelia burgdorferi is seen within the myocardium of subjects with normal left ventricular systolic function: an electron microscopy study.

A wide range of viral agents is associated with the development of acute myocarditis and its possible chronic sequela, dilated cardiomyopathy (DCM). There is also increasing evidence that Borrelia burgdorferi (Bb) is associated with DCM in endemic regions for Bb infection. This study sought to use electron microscopy to prospectively analyze the presence of viruses and Bb within the myocardium of 40 subjects with preserved left ventricular (LV) ejection fraction and 40 patients with new-onset unexplained DCM during the same time period. Virus particles were found within the myocardium of 23 subjects (58%) of both cohorts studied, yet there was no statistically significant difference in virus family presence between those with DCM versus those with preserved LV systolic function. In contrast, Bb was detected only in those subjects with DCM (0 versus 5 subjects; p ˂ 0.05). Polymerase chain reaction was performed on samples from patients who were positive for Bb according to electron microscopy, and Bb was confirmed in 4 out of 5 individuals. Our results demonstrate that the prevalence of viral particles does not differ between subjects with preserved LV systolic function versus those with DCM and therefore suggests that the mere presence of a viral agent within the myocardium is not sufficient to establish a clear link with the development of DCM. In contrast, the presence of Bb was found only within myocardial samples of patients with DCM; this finding supports the idea of a causal relationship between Bb infection and DCM development.

Lyme disease: clinical features, classification, and epidemiology in the upper midwest.

Lyme disease can be classified using the terminology of syphilis. In this series of 95 cases from the upper midwest, early cases, defined as an illness of less than 2 months, were more likely to have lived in or recently visited a highly endemic area. Unlike late cases, early cases presented entirely in the nonwinter months (p less than .001). Early disease was further subdivided into primary and secondary disease. Ninety percent of primary and 43% of secondary cases had erythema migrans, while no late cases had active erythema migrans (p less than .001). Clinical manifestations of nonspecific inflammation, except for arthralgia, were more common in early than late disease (p less than .01). In secondary cases, monoarticular arthritis was slightly more common than polyarticular arthritis, with the reverse occurring in late disease (p less than .05). Indirect fluorescent antibody testing revealed a ratio of IgM to IgG antibodies to be helpful in distinguishing early from late disease. Antibacterial therapy in early, primary cases caused Jarisch-Herxheimer reaction 7% of the time. Despite longer and more frequent parenteral therapy, late Lyme disease frequently required retreatment, owing to poor clinical response (p less than .05).

Neurologic manifestations in children with North American Lyme disease.

To delineate the spectrum of neurologic manifestations and the relative frequencies of different syndromes associated with North American Lyme disease, we describe 96 children referred for neurologic problems in the setting of Borrelia burgdorferi infection. The most frequent neurologic symptom was headache, and the most common sign was facial palsy. Less common manifestations were sleep disturbance, and papilledema associated with increased intracranial pressure. Signs and symptoms of peripheral nervous system involvement were infrequent. The most common clinical syndromes were mild encephalopathy, lymphocytic meningitis, and cranial neuropathy (facial nerve palsy). In contrast with adult patients with neurologic Lyme disease, meningoradiculitis (Bannwarth's syndrome) and peripheral neuropathy syndromes were rare. However, a "pseudotumor cerebri-like" syndrome seems to be unique to North American pediatric Lyme disease.

Early Lyme disease: a flu-like illness without erythema migrans.

The existence of a form of early Lyme disease characterized by a flu-like illness without erythema migrans is controversial. To confirm the existence and define the clinical characteristics of the flu-like illness without erythema migrans of localized Lyme disease, the authors studied patients from a Lyme disease endemic area of Connecticut who visited their primary care physicians with an undefined flu-like illness. Patients kept a diary of their symptoms. Acute and convalescent sera were obtained. The diagnosis of Lyme disease was based on the appearance of IgM or IgG antibodies to Borrelia burgdorferi as demonstrated by both enzyme-linked immunosorbent assay and immunoblot assay. Twenty-four untreated patients were studied. In five patients acute serologic evidence of Lyme disease developed. The flu-like illness in these five patients was characterized by fever and fatigue and resolved spontaneously in 5 to 21 days. Symptoms recurred in three of these five patients. The existence of a flu-like illness without erythema migrans of early Lyme disease has been clearly established. Prospective, controlled studies are needed to better define its incidence, characteristics, and prognosis so that appropriate diagnostic and therapeutic strategies can be developed.

IgM and IgG significant reactivity to Borrelia burgdorferi sensu stricto, Borrelia garinii and Borrelia afzelii among Italian patients affected by Lyme arthritis or neuroborreliosis.

This survey evaluates the specificity of band patterns in immunoblot of sera taken from clinically defined cases of Lyme arthritis and neuroborreliosis, towards three locally isolated strains of Borrelia burgdorferi, belonging to the three species: Borrelia sensu stricto, Borrelia garinii and Borrelia afzelii. To assess specificity, patient sera were statistically (X2, P < or = 0.05) compared with blood donors sera samples. Both IgG and IgM antibodies were considered. The overall reactivity of the three Borrelia strains in IgG immunoblots indicated that ten protein bands were significant, with a different prevalence of some of them in the two groups of patient sera: bands at 60-58, 30-33, 36-37 and 28-27 kDa were markers for neuroborreliosis sera; proteins at 100-83, 72-70 and 18-17 kDa behaved like markers for Lyme arthritis. The IgM Immunoblots revealed significant bands at 100-83, 72-70, 51, 24-21 and 18-17 kDa only with neuroborreliosis sera. Though there were variable band reactivities in each strain, a correlation emerged between the three genospecies and the clinical symptoms: in fact B. afzelii and B. garinii were prevalent in Lyme arthritis sera, (IgG Immunoblots); B. garinii was associated to neuroborreliosis (IgG and IgM Immunoblots); B. sensu stricto was strongly reactive with neuroborreliosis in IgM immunoblots. These data indicate that the three locally strains of Borrelia representing the three genospecies should be used together in immunoblot to detect antibodies elicited in neuroborreliosis and Lyme arthritis.

[The classification of Lyme borreliosis (Lyme disease)]. / O klassifikatsii Laim-borrelioza (laimskoi bolezni).

A new version of Lyme's disease classification based on the authors' experience and other classifications is proposed. It distinguishes periods of the disease (acute, subacute, chronic) and stages (I--isolated erythema migrans, II--local disseminated infection, III--generalized disseminated infection) as well as the signs which are significant in Lyme's disease diagnosis: erythematous and nonerythematous form, seropositivity or seronegativity against Borrelia burgdorferi. Subclinical (latent) infection, complications of Lyme's disease (fibromyalgia syndrome, chronic fatigue syndrome, etc.) and mixed-infection with tick-borne viral encephalitis are included as well.

[Therapy of Lyme borreliosis]. / Therapie der Lyme-Borreliose.

Lyme Borreliosis is an infectious disorder caused directly by Borrelia burgdorferi. Secondary immunological mechanisms might play an additional pathogenetic role. The natural course of the disease in stage I and II is in most cases benign, therefore the influence of antibiotic therapy is difficult to assess. Double-blind, placebo-controlled randomized studies were performed rarely. However, by comparing untreated and treated patient groups it seems, that antibiotic therapy shortens the disease duration and prevents late complications. In stage III the course of the disease is usually chronic progressive (central nervous system, joint, skin), if no antibiotic therapy is applied. Currently performed clinical trials were up to now unable to determine the optimal antimicrobial agent, route of application, dosage and optimal duration of therapy for the different manifestations of the disease. Susceptibility testing, antimicrobial pharmacokinetic considerations (e. g. CSF penetration, half-life) and clinical experiences are therefore the basis of our recommendations. Stage I: Doxycyclin 2 x 100 mg p. o. or if contraindicated Cefuroxim 2 x 500 mg, at least 14 days. In case of systemic symptoms (e. g. fever) a intravenous therapy is indicated. Stage II and III: Ceftriaxon 1 x 2--2 x 2 g i. v. or Cefotaxim 3 x 2 g i. v., at least 14 days. Corticosteroids can be given in defined cases (pain syndrome!) additionally. Therapy failure was described regarding all used antibiotics, therefore clinical and laboratory follow up is mandatory. Residual symptoms can disappear over months and are usually not due to refractory disease.(ABSTRACT TRUNCATED AT 250 WORDS)

[Diagnosis of Lyme borreliosis. How to corroborate suspected borreliosis]. / Diagnostik der Lyme-Borreliose. Wie Sie den Verdacht auf Borreliose erhärten.

Lyme borreliosis is a zoonosis transmitted via lxodes ticks. The causal agent--the spirochete Borrelia burgdorferi sensu lato--triggers a multisystem disease that manifests in particular in the skin, heart, nervous system and joints. Lyme borreliosis is the most common tick-borne infectious disease in the Northern hemisphere. In Europe the Lyme disease spirochetes are heterogeneous and comprise three species that infect humans: Borrelia burgdorferi sensu stricto, B. garinii and B. afzelii. The microbiological diagnosis is based primarily on the detection of antibodies, and secondarily on the detection of the pathogen. Suitable material for the detection of the pathogen are various body fluids (cerebrospinal fluid, joint fluid) and biopsy material (in particular skin). Antibodies are usually detected in the serum. Negative serology does not exclude an early manifestation, and a positive finding is no proof of a clinically manifest infection--it may simply reflect an earlier Lyme infection.