Lyme borreliosis

Lyme borreliosis is a multi-organ infection caused by spirochetes of the Borrelia burgdorferi sensu lato group with its species B burgdorferi sensu stricto, Borrelia garinii, and Borrelia afzelii, which are transmitted by ticks of the species Ixodes. Laboratory testing of Lyme borreliosis includes culture, antibody detection using ELISA with whole extracts or recombinant chimeric borrelia proteins, immunoblot, and PCR with different levels of sensitivity and specificity for each test. Common skin manifestations of Lyme borreliosis include erythema migrans, lymphocytoma, and acrodermatitis chronica atrophicans. The last two conditions are usually caused by B garinii and B afzelii, respectively, which are seen more frequently in Europe than in America. Late extracutaneous manifestations of Lyme borreliosis are characterised by carditis, neuroborreliosis, and arthritis. We present evidence-based treatment recommendations for Lyme borreliosis and review the prevention of Lyme borreliosis, including the Lyme vaccines.     

Surveillance of Lyme borreliosis in Germany, 2002 and 2003

Lyme borreliosis is a potentially serious infection common in Germany, but little data about its incidence, distribution, and clinical manifestations are available. Lyme borreliosis is not a notifiable disease in Germany, but six of Germany's 16 states - Berlin, Brandenburg, Mecklenburg-Vorpommern, Sachsen, Sachsen-Anhalt and Thüringen, have enhanced notification systems, which do include Lyme borreliosis. The efforts made in these states to monitor confirmed cases through notification are therefore an important contribution to understanding the epidemiology of Lyme borreliosis in Germany. This report summarises the analysis of Lyme borreliosis cases submitted to the Robert Koch-Institut during 2002-2003. The average incidence of Lyme borreliosis of the six East German states was 17.8 cases per 100,000 population in 2002 and increased by 31% to 23.3 cases in 2003, respectively. Patient ages were bimodally distributed, with incidence peaks among children aged 5- 9 and elderly patients, aged 60- 64 in 2002, and 65- 69 in 2003. For both years, 55% of patients were female. Around 86% of notified cases occurred from May to October. Erythema migrans affected 2697 patients (89.3%) in 2002 and 3442 (86.7%) in 2003. For a vector-borne disease, like Lyme borreliosis, the risk of infection depends on the degree and duration of contact between humans and ticks harbouring Borrelia burgdorferi. As infectious ticks probably occur throughout Germany, it is likely that the situation in the remaining 10 German states is similar to that of the states in this study.     

Local immunoglobulin production in synovial tissue in patients with Lyme borreliosis

A study was made to find out whether immunoglobulins are produced locally in synovial tissue in patients with Lyme borreliosis. Synovial fluid specimens from six patients with Lyme borreliosis were compared with those from 25 patients with rheumatoid arthritis, psoriatic arthritis, unspecified oligoarthritis or arthrosis (control group). Agarose electrophoresis revealed local oligoclonal IgG and IgM bands in the synovial fluid of two patients with Lyme borreliosis, but no local bands were observed in the control group. An index for local synthesis of immunoglobulins in synovial fluid was calculated in analogy with the IgG index for cerebrospinal fluid. The two patients with Lyme borreliosis in whom oligoclonal bands were seen in the synovial fluid showed the highest synovial fluid IgG indices and the highest concentrations of specific IgG antibodies against Borrelia spirochetes in synovial fluid. The presence of local oligoclonal immunoglobulin bands and a high synovial fluid IgG index suggest that immunoglobulins are produced locally within the synovial tissue in some patients with Lyme borreliosis. The increase in immunoglobulins may be a response to a local invasion of Borrelia spirochetes or may represent an immune reaction which continues after the spirochetes no longer are viable.     

Clinical implications of delayed growth of the Lyme borreliosis spirochete, Borrelia burgdorferi

Lyme borreliosis, a spirochetal infection caused by Borrelia burgdorferi, may become clinically active after a period of latency in the host. Active cases of Lyme disease may show clinical relapse following antibiotic therapy. The latency and relapse phenomena suggest that the Lyme disease spirochete is capable of survival in the host for prolonged periods of time. We studied 63 patients with erythema migrans, the pathognomonic cutaneous lesion of Lyme borreliosis, and examined in vitro cultures of biopsies from the active edge of the erythematous patch. Sixteen biopsies yielded spirochetes after prolonged incubations of up to 10.5 months, suggesting that Borrelia burgdorferi may be very slow to divide in certain situations. Some patients with Lyme borreliosis may require more than the currently recommended two to three week course of antibiotic therapy to eradicate strains of the spirochete which grow slowly.     

Lyme-Borreliose

Lyme borreliosis is a multisystem infectious disease affecting mainly the skin, nervous system, joints and heart. It is caused by spirochetes of the Borrelia burgdorferi sensu lato complex which are transmitted by ticks. The diagnosis of Lyme borreliosis is based primarily on typical clinical symptoms and signs with serological confirmation. Antibiotic therapy is beneficial for all manifestations and treatment refractory cases are rare. The diagnosis “chronic Lyme borreliosis” is increasingly being misused for all conceivable medically unexplained symptoms.     

Clinical picture of Lyme boreliosis

Prevalence of Lyme borreliosis in Europe has been well esablished during the last decade. The highest morbidity in Poland, exceeding 100 cases (100.000) year, was demonstrated in north-estern part of the country. Additional small endemic areas were also described in south-western and central part of the country. Clinical picture of the disease do not differ significantly from observed in other parts of Europe. Lyme borreliosis is characterized with a wide variety of manifestations recognized as typical: erythema migrans, borrelial lymphocytoma, acrodermatitis chronica atrophicans, arthritis, facial palsy, lymphocytic meningitis and cardiac transduction disturbances. However there are also controversial syndroms, that have confirmed etiology of Borrelia burgdorferi but only in some cases, such as: morphea sclerodermatous lesions, cardiomyopathy and some neurologic disorders. Diagnosis of Lyme borreliosis is still based on typical signs of the disease and laboratory techniques can not solve clinical doubts.     

Direct detection methods for Lyme Borrelia,including the use of quantitative assays

Direct detection of Borrelia burgdorferi sensu lato, the etiologic agent of Lyme borreliosis, is the most reliable laboratory diagnostic tool. Several methods have been developed for direct detection of B. burgdorferi in infected vectors, host tissues, and clinical specimens from patients with Lyme borreliosis. These include microscope-based assays, antigen detection assays, in vitro cultivation, and nucleic acid-based detection of B. burgdorferi. The sensitivity and specificity of these methods depend on various factors and are also variable among laboratories. To date, only in vitro cultivation of B. burgdorferi has been widely accepted to confirm clinical diagnosis of Lyme borreliosis. Nevertheless, various polymerase chain reaction-based molecular assays have shown increasing significance in the laboratory diagnosis of Lyme borreliosis because of their high sensitivity, specificity, and capability for quantification and typing of spirochetes in clinical specimens. In this review, the currently available methods for direct detection of B. burgdorferi in clinical samples and quantitative analysis of spirochete load in different biological sources are discussed.     

Lyme disease (Lyme borreliosis)

Lyme borreliosis (Lyme disease) is a systemic infectious disease with a wide spectrum of symptoms affecting the skin, the heart, and the nervous and musculoskeletal systems. Lyme borreliosis is caused by the spirochaete Borrelia burgdorferi and transmitted by ticks. The disease occurs in endemic pockets with an incidence of from 50 to more than 100 cases per 100,000 inhabitants. Despite increasing knowledge about the virulence factors of the spirochaetes and the immune response of the host, many aspects of the pathogenesis, for example of chronic treatment-resistant disease, are still a matter of debate.The diagnosis is based on clinical findings and confirmed by serology. Diagnostic problems arise from patients with non-specific symptoms and a positive IgG serology.In about 80% of the patients, the disease can be cured by adequate antibiotic therapy. Evidence-based guidelines for treatment have been recently published. The only vaccine to prevent Lyme disease, licensed in the USA, has been discontinued due to disappointing sales despite good efficacy and tolerability.     

Human granulocytic ehrlichiosis as a common cause of tick-associated fever in Southeast Sweden: report from a prospective clinical study

Between May and December 1998, tick-associated febrile illness was prospectively studied in Southeast Sweden in order to assess the occurrence of human granulocytic ehrlichiosis (HGE). Inclusion criteria were fever (> or = 38.0 degrees C), with or without headache, myalgia or arthralgia in patients with an observed tick bite or tick exposure within 1 month prior to onset of symptoms. Patients with clinical signs of Lyme borreliosis were included. Of the 27 patients included, we identified 4 cases of HGE. Three of the patients had coinfection with Lyme borreliosis, which presented as erythema migrans. All 27 patients presented with a 2-5 d history of fever. None of the clinical signs or laboratory parameters monitored was helpful in predicting ehrlichiosis in this group with tick-associated fever conditions. Within the HGE-negative group (n = 23), 12 patients had clinical or laboratory signs of Lyme borreliosis. For 11 patients, the aetiology of the fever remained unclear. Our results suggest that HGE is common in tick-infested areas of Southeast Sweden, and may occur as a coinfection of Lyme borreliosis. Granulocytic ehrlichiosis should be suspected in patients who present with tick-associated fever, with or without erythema migrans. Ehrlichia serology and PCR should be employed to confirm the diagnosis.     

Acute facial nerve palsy in children: how often is it lyme borreliosis?

Acute facial nerve palsy in children may be caused by infection by Borrelia burgdorferi, but the incidence of facial nerve palsy and the proportion of facial nerve palsy caused by Lyme borreliosis may vary considerably between areas. Furthermore, it is not well known how often facial nerve palsy caused by Lyme borreliosis is associated with meningitis. In this population-based study, children admitted for acute facial nerve palsy to Stavanger University Hospital during 9 y from 1996 to 2004 were investigated by a standard protocol including a lumbar puncture. A total of 115 children with facial nerve palsy were included, giving an annual incidence of 21 per 100,000 children. 75 (65%) of these were diagnosed as Lyme borreliosis, with all cases occurring from May to November. Lymphocytic meningitis was present in all but 1 of the children with facial nerve palsy caused by Lyme borreliosis where a lumbar puncture was performed (n = 73). In this endemic area for Borrelia burgdorferi, acute facial nerve palsy in children was common. The majority of cases were caused by Lyme borreliosis, and nearly all of these were associated with lymphocytic meningitis.     

The prevalence and incidence of clinical and asymptomatic Lyme borreliosis in a population at risk

A past history of clinical Lyme borreliosis and the 6-month incidence of clinical and asymptomatic Lyme borreliosis was studied prospectively in a high-risk population. In the spring, blood samples were drawn from 950 Swiss orienteers, who also answered a questionnaire. IgG anti-Borrelia burgdorferi antibodies were detected by ELISA. Positive IgG antibodies were seen in 248 (26.1%), in contrast to 3.9%-6.0% in two groups of controls (n = 101). Of the orienteers, 1.9%-3.1% had a past history of definite or probable clinical Lyme borreliosis. Six months later a second blood sample was obtained from 755 participants, 558 (73.9%) of whom were seronegative initially; 45 (8.1%) had seroconverted from negative to positive. Only 1 (2.2%) developed clinical Lyme borreliosis. Among all participants, the 6-month incidence of clinical Lyme borreliosis was 0.8% (6/755) but was much higher (8.1%) for asymptomatic seroconversion (45/558). In conclusion, positive Lyme serology was common in Swiss orienteers, but clinical disease occurred infrequently.     

Diagnosis of Lyme disease based on dermatologic manifestations

Lyme disease, or Lyme borreliosis, is an infection caused by the spirochete Borrelia burgdorferi, which is most commonly transmitted to humans by a tick bite. Characterized by early and late phases, Lyme disease is a multisystem illness involving the skin, heart, joints, and nervous system. Diagnosis is based predominantly on clinical manifestations, the most specific being dermatologic. Thus, recognizing the dermatologic manifestations of Lyme disease is important for diagnosis and institution of appropriate, effective therapy. Approximately 75% of patients with Lyme disease present with the pathognomonic skin lesion erythema migrans, an expanding erythematous lesion. During early infection, secondary erythema migrans lesions or Borrelia lymphocytoma may occur. Borrelia lymphocytoma commonly presents as an erythematous nodule on the ear lobe or nipple. During late infection, acrodermatitis chronica atrophicans, an erythematous, atrophic plaque unique to Lyme disease may appear; it has been described in about 10% of patients with Lyme disease in Europe. Fibrotic nodules associated with acrodermatitis chronica atrophicans as well as other sclerotic and atrophic lesions, such as morphea, lichen sclerosus et atrophicus, anetoderma, and atrophoderma of Pasini and Pierini, have been seen late in the course of Lyme disease. In a few cases, other sclerodermatous lesions, such as eosinophilic fasciitis and progressive facial hemiatrophy, have been linked to B. burgdorferi infection. We review the cutaneous lesions associated with Lyme disease.     

Lyme borreliosis in Europe. Neurologic disorders

In Europe the tick-transmitted neurologic disorders MPN-GBB or Bannwarth's syndrome and ACA-associated neuropathy have been identified as clinical entities long before their causative agent was discovered. When Lyme disease and its neurologic manifestations were recognized in the United States, differences in the clinical pattern between North American and European cases with Lyme borreliosis were described in the initial reports. In the same way with the availability of serodiagnostic tests as the clinical spectrum of Lyme borreliosis was enlarging in Europe and in North America, these clinical differences became less prominent.     

Lyme borreliosis--a possible cause of atrioventricular block

Eight cases of Lyme borreliosis of clinical certainty with carditis are reported. In six patients, AV-blocks were predominant, two patients had a myopericarditis. Six acute cases were seropositive, but one case remained seronegative. The titer was border-line in that patient, who was studied 4 years after the acute disease. A Lyme carditis should be considered in each case, in which AV-blocks appear acutely.     

Tired of Lyme borreliosis. Lyme borreliosis in the Netherlands

Lyme borreliosis has become the most common vector-borne illness in North Eastern USA and Europe. It is a zoonotic disease, with well-defined symptoms, caused by B. burgdorferi sensu lato, and transmitted by ticks. Lyme borreliosis is endemic in the Netherlands with a yearly incidence of approximately 133 cases/100,000 inhabitants. Similar to another spirochetal disease, syphilis, it can be divided into three stages; early, early disseminated and late disseminated manifestations of disease, of which the specific clinical presentations will be discussed in detail. The diagnosis of Lyme borreliosis is based on a history of potential exposure to ticks and the risk of infection with B. burgdorferi s.l., development of specific symptoms, exclusion of other causes, and when appropriate, combined with serological and/or other diagnostic tests. The specific indications for, but also the limitations of, serology and other diagnostic tests, including the polymerase chain reaction (PCR), are detailed in this review. Lyme borreliosis is treated with antibiotics, which are usually highly effective. Recent literature discussing the indications for antibiotic treatment, the dosage, duration and type of antibiotic, as well as indications to withhold antibiotic treatment, are reviewed. This review presents the most recent, and when available Dutch, evidence-based information on the ecology, pathogenesis, clinical presentation, diagnosis, treatment and prevention of Lyme borreliosis, argues against the many misconceptions that surround the disease, and provides a framework for the Dutch physician confronted with a patient with putative Lyme borreliosis.     

T cell proliferation induced by Borrelia burgdorferi in patients with Lyme borreliosis. Autologous serum required for optimum stimulation

The cellular immune response to Borrelia burgdorferi was studied in 24 patients with seropositive and seronegative Lyme borreliosis, 30 patients with arthritides of different origin (non-Lyme arthritides), and 20 normal blood donors. By far, the strongest T cell stimulation was induced by incubation with autologous serum; there was a significantly lower response or no response after incubation with allogeneic or heterologous sera. In patients with Lyme borreliosis, including seronegative patients, there was a strikingly elevated proliferation in response to whole B burgdorferi bacteria (mean 64,750 dpm) compared with that of normal donors (mean 19,700 dpm; P less than 0.0001) and especially that of non-Lyme arthritis patients (mean 11,600 dpm; P less than 0.0001). Levels of proliferation declined significantly in patients with Lyme borreliosis after successful antibiotic treatment. Parallel cultures using B burgdorferi and Treponema phagedenis as antigens showed that cells from patients with Lyme borreliosis responded significantly more to B burgdorferi than to T phagedenis, but this did not occur with cells from individuals with non-Lyme arthritides. There was no correlation between disease stages and proliferation values. These data indicate that lymphocyte proliferation assays may provide an important tool for the diagnosis of Lyme borreliosis, most notably in patients with arthritides and in those who are seronegative. Conversely, the lack of reactivity appears to be a strong indicator of the absence of active Lyme disease. It seems to be crucial, however, to use autologous sera in these assays.     

The epidemiology, prevention, investigation and treatment of Lyme borreliosis in United Kingdom patients: a position statement by the British Infection Association

This paper is a position statement of the British Infection Association on the epidemiology, prevention, investigation and treatment of Lyme borreliosis in United Kingdom patients. It is written to help patients and their doctors to understand the present state of knowledge concerning Lyme borreliosis and to attempt to allay the anxiety that is sometimes associated with this disease.     

Utilization of serology for the diagnosis of suspected Lyme borreliosis in Denmark: Survey of patients seen in general practice

Background  

Serological testing for Lyme borreliosis (LB) is frequently requested by general practitioners for patients with a wide variety of symptoms.     

Joint manifestations of Lyme borreliosis in Czechoslovakian patients

Involvement of the musculoskeletal system in 50 Lyme borreliosis patients seen in Czechoslovakia is described. Thirty-three patients reported tick bites or that they had removed a tick, four patients had been bitten by some other insect. Skin reaction following tick bite were found in 29 patients. Neurologic involvements have been described in 40 subjects. In one patient complete heart block developed after ECM, so that a permanent pacemaker was necessary for two weeks. Mainly three types of involvement of the musculoskeletal system were observed, mostly as intermittent episodes of arthralgia or migratory musculoskeletal pain. In 37 patients brief attacks of monoarthritis or asymmetrical oligoarthritis were seen, chiefly of intermittent subacute course. Chronic arthritis was diagnosed in seven cases, sacroiliitis in four patients. The authors discuss differential diagnosis, especially in patients with chronic joint involvement.     

Isolation of <Emphasis Type="Italic">Borrelia burgdorferi</Emphasis> sensu lato from blood of adult patients with borrelial lymphocytoma,Lyme neuroborreliosis,Lyme arthritis and acrodermatitis chronica atrophicans

Background  

Reports on patients with European Lyme borreliosis in whom borreliae were isolated from the blood are rare and nearly exclusively limited to those with solitary or multiple erythema migrans. Here we report on patients with other manifestations of Lyme borreliosis in whom borreliae were isolated from their blood.