Clinical Manifestations Of Lyme Borreliosis Research Articles

Enzootic origins for clinical manifestations of Lyme borreliosis

Both early localized and late disseminated forms of Lyme borreliosis are caused by Borrelia burgdorferi senso lato. Differentiating between the spirochetes that only cause localized skin infection from those that cause disseminated infection, and tracing the group of medically-important spirochetes to a specific vertebrate host species, are two critical issues in disease risk assessment and management. Borrelia burgdorferi senso lato isolates from Lyme borreliosis cases with distinct clinical manifestations (erythema migrans, neuroborreliosis, acrodermatitis chronica atrophicans, and Lyme arthritis) and isolates from Ixodes ricinus ticks feeding on rodents, birds and hedgehogs were typed to the genospecies level by sequencing part of the intergenic spacer region. In-depth molecular typing was performed by sequencing eight additional loci with different characteristics (plasmid-bound, regulatory, and housekeeping genes). The most abundant genospecies and genotypes in the clinical isolates were identified by using odds ratio as a measure of dominance. Borrelia afzelii was the most common genospecies in acrodermatitis patients and engorged ticks from rodents. Borrelia burgdorferi senso stricto was widespread in erythema migrans patients. Borrelia bavariensis was widespread in neuroborreliosis patients and in ticks from hedgehogs, but rare in erythema migrans patients. Borrelia garinii was the dominant genospecies in ticks feeding on birds. Spirochetes in ticks feeding on hedgehogs were overrepresented in genotypes of the plasmid gene ospC from spirochetes in erythema migrans patients. Spirochetes in ticks feeding on hedgehogs were overrepresented in genotypes of ospA from spirochetes in acrodermatitis patients. Spirochetes from ticks feeding on birds were overrepresented in genotypes of the plasmid and regulatory genes dbpA, rpoN and rpoS from spirochetes in neuroborreliosis patients. Overall, the analyses of our datasets support the existence of at least three transmission pathways from an enzootic cycle to a clinical manifestation of Lyme borreliosis. Based on the observations with these nine loci, it seems to be justified to consider the population structure of B. burgdorferi senso lato as being predominantly clonal.

Imbalanced presence of Borrelia burgdorferi s.l. multilocus sequence types in clinical manifestations of Lyme borreliosis

In this study we used typing based on the eight multilocus sequence typing scheme housekeeping genes (MLST) and 5S-23S rDNA intergenic spacer (IGS) to explore the population structure of Borrelia burgdorferi sensu lato isolates from patients with Lyme borreliosis (LB) and to test the association between the B. burgdorferi s.l. sequence types (ST) and the clinical manifestations they cause in humans. Isolates of B. burgdorferi from 183 LB cases across Europe, with distinct clinical manifestations, and 257 Ixodes ricinus lysates from The Netherlands, were analyzed for this study alone. For completeness, we incorporated in our analysis also 335 European B. burgdorferi s.l. MLST profiles retrieved from literature. Borrelia afzelii and Borrelia bavariensis were associated with human cases of LB while Borrelia garinii, Borrelia lusitaniae and Borrelia valaisiana were associated with questing I. ricinus ticks. B. afzelii was associated with acrodermatitis chronica atrophicans, while B. garinii and B. bavariensis were associated with neuroborreliosis. The samples in our study belonged to 251 different STs, of which 94 are newly described, adding to the overall picture of the genetic diversity of Borrelia genospecies. The fraction of STs that were isolated from human samples was significantly higher for the genospecies that are known to be maintained in enzootic cycles by mammals (B. afzelii, B. bavariensis, and Borrelia spielmanii) than for genospecies that are maintained by birds (B. garinii and B. valaisiana) or lizards (B. lusitaniae). We found six multilocus sequence types that were significantly associated to clinical manifestations in humans and five IGS haplotypes that were associated with the human LB cases. While IGS could perform just as well as the housekeeping genes in the MLST scheme for predicting the infectivity of B. burgdorferi s.l., the advantage of MLST is that it can also capture the differential invasiveness of the various STs.

Our experience with enzyme-linked immunospot assay in the laboratory diagnostics of lyme borreliosis

Background Lyme borreliosis (LB) is multisystem infectious disease with various clinical manifestations. In Europe, LB is caused by gram-negative spirochetal bacteria of the complex Borrelia burgdorferi sensu lato. The most important for human pathogenicity are B. garinii, B. afzelii and B.burgdorferi sensu stricto. Indirect laboratory diagnostics of LB is based on serological methods such as Enzyme-Linked ImmunoSorbent Assay (ELISA) and Western Blot Assay (WB) that detect specific antibodies. Another method in the diagnostics of LB is a new test LymeSpot. This test is based on Enzyme-Linked ImmunoSpot Assay (ELISPOT). We present our first experience with the test LymeSpot. Methods From November 2013 to June 2014 we performed LymeSpot on the group of 42 patients who were tested for suspicion of LB presence. LymeSpot is based on specific cell immune response of T-lymphocytes after stimulation by Borrelia antigens. The result is a number of antigen specific effector T-cells producing IFN-g in the form of spots. We compared the results of LymeSpot test with the level of specific IgM and IgG antibodies detected by ELISA and WB with using recombinant antigens B. burgdorferi sl. Results From the number of 42 patients we detected positive LymeSpot test only in 4o f them (9,5%), ac utoff value in 3 patients (7,1%). From the group of 42 patients were simultaneously performed ELISA and WB in 26 persons. In this group we found positive LymeSpot in 4 patients and cutoff value in 2p atients. In the group of 4p atients with positive LymeSpot was detected higher level of IgM antibodies in 3 patients and only IgG antibodies in 1 patient. They were patients with clinical manifestations of LB who were treated with antibiotics afterwards. Among 20 patients with negative results of LymeSpot these findings correlated with antibody response in 8 patients (40%). In this group we detected seronegative finding (IgM-IgG-) or finding of passing through LB (IgM-IgG+). In other 12 patients with negative LymeSpot test we detected serological finding of beginning (IgM +IgG-) or running LB (IgM+IgG+). They were mostly patients without clear symptoms of LB, patients with long-term positivity of IgM antibodies without clinical manifestations of LB or patients after antibiotic therapy. Conclusions

Lyme borreliosis: Epidemiology, clinical manifestations and treatment

Lyme borreliosis is a multisystem disorder characterized by a wide spectrum of clinical manifestations. In Europe, the main aetiological agents are Borrelia afzelii, Borrelia garinii and B. burgdorferi sensu stricto, but Borrelia spielmanii, Borrelia valaisiana, Borrelia lusitaniae and Borrelia bissettii have also been reported as rare or potential causes of human disease. In North America, B. burgdorferi sensu stricto is the only human pathogen. The most common clinical manifestation of Lyme borreliosis is a skin lesion, erythema migrans, which may resolve spontaneously without antibiotic treatment. However, the pathogen can spread to other tissues and organs, causing more severe manifestations that can involve a skin, nervous system, joints, and/or heart, requiring antibiotic therapy. The most commonly used antibiotics in the treatment of Lyme borreliosis are: amoxicillin, ceftriaxone, cefuroxime, doxycycline and azithromycin.

Epidemiological features and clinical manifestations of Lyme borreliosis in Korea during the period 2005-2012.

Lyme borreliosis is one of the most common tick-borne infections in the northern hemisphere. However, the epidemiological features and clinical manifestations of this disease in Korea are unknown. The present study is the first to investigate the characteristics of Lyme borreliosis in Korea. We traced suspected cases of Lyme borreliosis during the period 2005-2012. Of the 16 identified patients with the disease, 11 had acquired autochthonous infection within Korea, while 5 patients were infected outside Korea. The history of past exposure was investigated in 8 of the 11 patients with autochthonous infection; 5 of these 8 patients (62.5%) were suspected to have acquired the infection in the northeastern alpine region. Clinically, of 11 patients with autochthonous infection, 6 (54.5%) showed early skin manifestations, 4 (36.4%) showed neurological manifestations, and 1 (9.1%) showed acrodermatitis chronica atrophicans. In conclusion, Lyme borreliosis could be endemic in the northeastern alpine region of Korea, and neurological and early skin manifestations are likely to be the major clinical characteristics of autochthonous Lyme borreliosis in Korea.

Lyme borreliosis caused by diverse genospecies of Borrelia burgdorferi sensu lato in northeastern China

The variety of Borrelia burgdorferi sensu lato (B. burgdorferi) genospecies leads to distinction in clinical manifestations of Lyme borreliosis (LB). There are reports of LB clinical characteristics in China, where the B. burgdorferi genospecies in ticks and animal hosts are different from those in Europe and North America. During May to September in 2010 and 2011, all patients who had erythema migrans (EM, more than 5 cm in diameter) after a recent tick-bite, and sought medical care at Mudanjiang Forestry Central Hospital, Heilongjiang Province of northeastern China, were enrolled in the study. Specific PCR was used to determine the B. burgdorferi genospecies in the disseminated patients. Of 265 EM patients, B. burgdorferi DNA was detected in blood specimens from 15 of 55 disseminated patients. Sequence analyses of 5S–23S rRNA, flagellin, ospC, 16S rRNA and ospA genes revealed that 11 patients were infected with Borrelia garinii, three with Borrelia afzelii and one with Borrelia valaisiana-related genospecies. Among 15 patients, 40%, 13.3% and 13.3% manifested pruritus, pain and ulceration, respectively. Systemic symptoms, arthralgia or a swollen joint and lymphadenopathy were observed in 26.7%, 13.3% and 6.7% patients, respectively. In northeastern China, three genospecies of LB patients were detected. The B. burgdorferi genospecies identified in this study was predominantly B. garinii. A case infected with B. valaisiana-related genospecies was reported for the first time.

Strain diversity of Borrelia burgdorferi sensu lato in Serbia

The geographic distribution of Borrelia burgdorferi sensu lato species in Europe shows very dynamic spatial and temporal variations. Since different Borrelia species usually correlate with different clinical manifestation of Lyme borreliosis, knowledge of the geographic distribution of the pathogen is very important for understanding the ecology and epidemiology of the disease. Our previous studies, based on direct molecular methods, revealed high diversity of species of the B. burgdorferi s.l. complex and unexpected high prevalence of B. lusitaniae in Ixodes ricinus ticks from Serbia. The aim of the present study was further isolation and typization of viable B. burgdorferi s.l. strains from vectors in Serbia as a basis for studies of biological, genetic and ecological variations. A total of 248 adult I. ricinus ticks collected from 24 localities were processed for cultivation. Prior to cultivation, all ticks were disinfected, then triturated in BSK H medium. The culture tubes were incubated at 33°C for 3 months. Cultures were periodically examined by dark field microscopy. For confirmation of isolated strains, seminested PCR for the flaB gene was performed. Determination of B. burgdorferi s.l. species was carried out by the RFLP technique, using restriction enzymes MseI and DraI on the previously amplified 5-23S rDNA intergenic spacer (Postic et al., 1994). For Borrelia identification by RT-PCR targeting, the hbb gene protocol of Portnoi et al. (2006) was followed. Sequencing of the 5-23S rDNA intergenic spacer and flaB gene was performed for phylogenetic analysis. Thirty-four spirochete cultures were isolated and subjected to further genotyping analyses. According to the RFLP patterns of the 5S-23S rDNA intergenic spacer, specimens were determined as: B. lusitaniae, B. afzelii, B. burgdorferi s.s., B. garinii and B. valaisiana. For all strains identified as B. lusitaniae, B. garinii, B. afzelii and B. valaisiana according to the MseI-RFLP method, results of RT-PCR were in absolute agreement. However, Tm values for all strains identified as B. burgdorferi s.s. according to RFLP patterns were in the range for B. lusitaniae strains (64.17 to 64.58 °C). Thus, it was impossible to distinguish B. burgdorferi s.s. and B. lusitaniae strains by this method. Sequencing analysis for strains identified as B. lusitaniae, B. garinii, B. afzelii and B. valaisiana was in agreement with MseI-RFLP and RT-PCR results. In cases of uncoordinated MseI-RFLP and RT-PCR results, sequencing analysis confirmed unclear strains as B. lusitaniae. The results of this study showed B. lusitaniae to be the species with highest prevalence in I. ricinus ticks from Serbia.

Gender Disparity between Cutaneous and Non-Cutaneous Manifestations of Lyme Borreliosis

Cutaneous manifestations of Lyme borreliosis in Europe include erythema migrans (EM) and acrodermatitis chronica atrophicans (ACA); the most common non-cutaneous manifestations are Lyme neuroborreliosis (LNB) and Lyme arthritis. The purpose of this study was to evaluate the gender distribution of patients with these clinical manifestations of Lyme borreliosis. Data on gender were obtained from the clinical records of patients with Lyme borreliosis aged ≥15 years who had been evaluated at the University Medical Center Ljubljana, Ljubljana, Slovenia.Among 10,539 patients diagnosed with EM, 6,245 (59.3%) were female and among 506 ACA patients 347 (68.6%) were female. In contrast, among the 60 patients with Lyme arthritis only 15 (25%) were female (p<0.0001 for the comparison of gender with EM or ACA) and among the 130 patients with LNB only 51 (39.2%) were females (p<0.0001for the comparison of gender with EM or ACA). Although the proportion that was female in the LNB group was greater than that of patients with Lyme arthritis, this difference did not reach statistical significance (p = 0.10). Although older individuals are more likely to be female in the general Slovenian population, the age of patients with cutaneous versus non-cutaneous manifestations was not the explanation for the observed differences in gender.In conclusion, patients with cutaneous manifestations of Lyme borreliosis were predominantly female, whereas those with non-cutaneous manifestations were predominantly male. This provocative finding is unexplained but may have direct relevance to the pathogenesis of Lyme borreliosis.

Lyme Borreliosis: An Update for Canadian Dermatologists

Lyme borreliosis is a multisystemic tick-borne spirochetosis, which may result in dermatologic, musculoskeletal, cardiovascular, and neurologic manifestations. Patients with suspected acute Lyme borreliosis infection may be referred for urgent dermatologic review. Canadian dermatologists should be aware of the latest information regarding the diagnosis and management of Lyme borreliosis. This review is based on a PubMed database search combining the word "Lyme" with variations of the word "Canada." Data sources included articles from the fields of ecology, epidemiology, laboratory diagnostics, and clinical management. In this review, the ecological basis of spirochete transmission by tick vectors is described. The latest available Canadian epidemiologic data are summarized. North American clinical manifestations of Lyme borreliosis are contrasted with European presentations. The Canadian Public Health Laboratory Network's diagnostic guidelines are summarized. Finally, treatment recommendations are outlined.

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

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.

Adaptive and Innate Immune Responsiveness toBorrelia burgdorferi sensu latoin Exposed Asymptomatic Children and Children with Previous Clinical Lyme Borreliosis

Why some individuals develop clinical manifestations in Lyme borreliosis (LB) while others remain asymptomatic is largely unknown. Therefore, we wanted to investigate adaptive and innate immune responsiveness to Borrelia burgdorferi sensu lato in exposed Borrelia-antibody-positive asymptomatic children (n = 20), children with previous clinical LB (n = 24), and controls (n = 20). Blood samples were analyzed for Borrelia-specific interferon (IFN)-γ, interleukin (IL)-4, and IL-17 secretion by ELISPOT and Borrelia-induced IL-1β, IL-6, IL-10, IL-12(p70), and tumor necrosis factor (TNF) secretion by Luminex. We found no significant differences in cytokine secretion between groups, but a tendency towards an increased spontaneous secretion of IL-6 was found among children with previous clinical LB. In conclusion, the adaptive or innate immune responsiveness to Borrelia burgdorferi sensu lato was similar in Borrelia-exposed asymptomatic children and children with previous clinical LB. Thus, the immunological mechanisms of importance for eradicating the spirochete effectively without developing clinical manifestations of LB remain unknown.

PREVALENCE AND GENETIC HETEROGENEITY OF BORRELIA BURGDORFERI SENSU LATO IN IXODES TICKS IN BELGIUM

Borrelia burgdorferi sensu lato is a genetically diverse group of spirochetes that includes the agent of Lyme borreliosis in which genospecies tend to be associated with specific clinical features. The aim of the study was to determine the prevalence and genetic diversity of Borrelia burgdorferi sensu lato in 524 ticks collected in woods of a western province of Belgium. Presence of spirochetes in ticks was determined by phase contrast microscopy. The mean infection rate of ticks was 12.0%. Variability was observed in the prevalence of infection among the five sites examined, ranging from 2.8 to 21.6%. Identification to genospecies was determined by PCR and sequencing. The most common genomospecies were Borrelia afzelii (55%) and Borrelia garinii (21%). For the first time in Belgium, we detected Borrelia valaisiana and Borrelia spielmanii, representing 14% and 2%, respectively. Borrelia burgdorferi sensu stricto counted only for 2%. Co-infections were present in 8% of ticks. We emphasize the need for clinical studies to assess the prevalence of specific genospecies-related clinical manifestations of Lyme borreliosis in Belgium.

Borréliose de Lyme : recensement des cas adultes hospitalisés en Indre-et-Loire, à partir du PMSI (1999–2006)

Background To describe the clinical forms and epidemiology of Lyme borreliosis, in French adult patients hospitalized in Indre-et-Loire (Centre region). Methods Patients were recruited from standardized discharge summaries collected in the hospital database. All adult patients, hospitalized in public hospitals of the Indre-et-Loire administrative district, over a period of 8 years (1999–2006), who satisfied the European diagnostic criteria of Lyme borreliosis, were included. Results Encoding of Lyme borreliosis had a poor positive predictive value (65%). Forty-seven adult patients presented with the 50 following clinical forms: erythema migrans ( n = 5), neuroborreliosis ( n = 32), knee single-joint arthritis ( n = 4), acrodermatitis chronica atrophicans ( n = 3), carditis ( n = 2), ocular borreliosis ( n = 2), miscellaneous ( n = 2). Three patients had a combination of two different clinical forms. Meningoradiculitis was the most frequent neurologic manifestation. When a cranial nerve was involved, it was constantly the facial nerve, and mainly bilaterally. Few patients in our study had erythema migrans: these patients are usually treated in a general medicine setting. Although the incidence in the Centre region was lower than in some other regions of France and Europe, the clinical spectrum of the disseminated forms was similar. Conclusion This cohort illustrates the diversity of clinical manifestations of Lyme borreliosis in hospitalized patients, particularly at disseminated and late stages as well as the complexity of its diagnosis and its epidemiological surveillance.

Borrelia burgdorferiStimulates Macrophages to Secrete Higher Levels of Cytokines and Chemokines thanBorrelia afzeliiorBorrelia garinii

To delineate the inflammatory potential of the 3 pathogenic species of Borrelia burgdorferi sensu lato, we stimulated monocyte-derived macrophages from healthy human donors with 10 isolates each of B. burgdorferi, Borrelia afzelii, or Borrelia garinii recovered from erythema migrans skin lesions of patients with Lyme borreliosis from the United States or Slovenia. B. burgdorferi isolates from the United States induced macrophages to secrete significantly higher levels of interleukin (IL)-8, CCL3, CCL4, IL-6, IL-10, and tumor necrosis factor than B. garinii or B. afzelii isolates. Consistent with this response in cultured macrophages, chemokine and cytokine levels in serum samples of patients from whom the isolates were obtained were significantly greater in B. burgdorferi-infected patients than in B. afzelii- or B. garinii-infected patients. These results demonstrate in vitro and in vivo that B. burgdorferi has greater inflammatory potential than B. afzelii and B. garinii, which may account in part for variations in the clinical manifestations of Lyme borreliosis.

Study of Lyme borreliosis in Ukraine

Cases of human Lyme borreliosis (LB) are registered in all administrative regions of Ukraine and in the Autonomous Republic of Crimea with an increasing tendency. The hard tick Ixodes ricinus was proved as the main vector of Borrelia burgdorferi s.l., the causative agents of LB. We identified active natural LB foci, in which almost 25% of the adult I. ricinus ticks contained borrelias and more than 30% of the human population were seropositive for Lyme borreliae. The role of Mus musculus, Microtus arvalis, Myodes glareolus, Apodemus agrarius, and A. sylvaticus in the transmission cycle of the LB agent(s) was revealed. Combined foci and cases of LB/TBE (tick-borne encephalitis) mixed infection were registered in 8 oblasts. A considerable spectrum of different clinical manifestations of LB has been found including erythema migrans in 64.9% of cases, neurologic symptoms in 26.1%, rheumatic affliction in 24.7%, and cardiovascular problems in 8.3%.

Epidemiological Characteristics and Clinical Manifestations of Lyme Borreliosis in Croatia

The goal was to show the epidemiological characteristics and clinical manifestations of Lyme borreliosis in Croatia. Data on registered Lyme borreliosis cases were analyzed and the most common clinical manifestations of the disease, based on meta-analysis of the data collected, are described. A total of 3,317 cases were reported from 1987 to the end of 2003. Northwestern Croatia is an area in which Lyme borreliosis is endemic, but the disease has also been recorded in the other parts of the country, with the exception of the area south of Zadar. The clinical picture of Lyme borreliosis in Croatia is dominated by erythema migrans, followed by neurological manifestations. The diversified clinical picture is consistent with reports from other European countries, as is the isolation of Borrelia afzelii and Borrelia garinii, which are causally related to these forms of the disease. Tick density and tick infection rates of Borrelia burgdorferi have not yet been investigated in the part of Croatia free from the occurrence of Lyme borreliosis.

Comparison of immunofluorescence assay (IFA) and LIAISON® in patients with different clinical manifestations of Lyme borreliosis

Serological tests for detection of borrelial antibodies are frequently used in laboratory diagnostics of Lyme borreliosis. Unfortunately these tests are not standardized and the results obtained with different assays may not be concordant. The aim of the present study was to compare two different serological tests, IFA and LIAISON, for detection of Borrelia burgdorferi sensu lato IgM and IgG antibody. We analyzed the serological immune response in 383 patients with different clinical manifestations of Lyme borreliosis and in 49 healthy blood donors. LIAISON detected IgM and IgG antibodies more often than IFA in all groups of patients except those with chronic Lyme borreliosis. The differences were significant for IgM and IgG antibodies in patients with solitary erythema migrans and in those with early disseminated Lyme borreliosis. There was no significant difference in the specificity of the two tests.

Epidemiology of Tick Bites and Borreliosis in Children Attending Kindergarten or So-Called “Forest Kindergarten” in Southwest Germany

The so-called "forest kindergartens" have been increasingly popular in Germany since the beginning of the 1990s. These are nurseries located in forested areas where children spend all-season full-time outdoors. Fifty-three kindergartens in the state of Baden-Württemberg, Germany participated in this study. In a prospective clinical cohort study, the child's personal data, history, protective parental habits concerning tick bites, number of tick bites, and cases of borreliosis were recorded monthly (March-October 2004) using a questionnaire. Altogether, 1,707 children of 25 "forest kindergartens" (506 children) and 28 conventional kindergartens (1,201 children) were included. The response rate was 75% in "forest kindergartens" and 65% in conventional kindergartens. In the "forest kindergartens", 1,503 tick bites especially on the trunk and on the head were found, whereas 502 tick bites were registered in conventional kindergartens. Sixteen cases of borreliosis were diagnosed (10 in "forest kindergartens", six in conventional kindergarten), most frequently manifesting as erythema migrans. Children attending a "forest kindergarten" have a 2.8 times increased risk of experiencing tick bites and a 4.6 times increased risk of suffering from borreliosis compared to conventional kindergarten in Germany, although protective parental behavior in "forest kindergarten" children was significantly better than that in conventional kindergarten.

Diagnosis of lyme borreliosis.

A large amount of knowledge has been acquired since the original descriptions of Lyme borreliosis (LB) and of its causative agent, Borrelia burgdorferi sensu stricto. The complexity of the organism and the variations in the clinical manifestations of LB caused by the different B. burgdorferi sensu lato species were not then anticipated. Considerable improvement has been achieved in detection of B. burgdorferi sensu lato by culture, particularly of blood specimens during early stages of disease. Culturing plasma and increasing the volume of material cultured have accomplished this. Further improvements might be obtained if molecular methods are used for detection of growth in culture and if culture methods are automated. Unfortunately, culture is insensitive in extracutaneous manifestations of LB. PCR and culture have high sensitivity on skin samples of patients with EM whose diagnosis is based mostly on clinical recognition of the lesion. PCR on material obtained from extracutaneous sites is in general of low sensitivity, with the exception of synovial fluid. PCR on synovial fluid has shown a sensitivity of up to >90% (when using four different primer sets) in patients with untreated or partially treated Lyme arthritis, making it a helpful confirmatory test in these patients. Currently, the best use of PCR is for confirmation of the clinical diagnosis of suspected Lyme arthritis in patients who are IgG immunoblot positive. PCR should not be used as the sole laboratory modality to support a clinical diagnosis of extracutaneous LB. PCR positivity in seronegative patients suspected of having late manifestations of LB most likely represents a false-positive result. Because of difficulties in direct methods of detection, laboratory tests currently in use are mainly those detecting antibodies to B. burgdorferi sensu lato. Tests used to detect antibodies to B. burgdorferi sensu lato have evolved from the initial formats as more knowledge on the immunodominant antigens has been collected. The recommendation for two-tier testing was an attempt to standardize testing and improve specificity in the United States. First-tier assays using whole-cell sonicates of B. burgdorferi sensu lato need to be standardized in terms of antigen composition and detection threshold of specific immunoglobulin classes. The search for improved serologic tests has stimulated the development of recombinant protein antigens and the synthesis of specific peptides from immunodominant antigens. The use of these materials alone or in combination as the source of antigen in a single-tier immunoassay may someday replace the currently recommended two-tier testing strategy. Evaluation of these assays is currently being done, and there is evidence that certain of these antigens may be broadly cross-reactive with the B. burgdorferi sensu lato species causing LB in Europe.

Do Antiborrelial Antibodies Suggest Lyme Disease in Cuba?

Do Antiborrelial Antibodies Suggest Lyme Disease in Cuba?