S 4

LYME BORRELIOSIS A REAL DISEASE? CLINICAL DIAGNOSIS AND TREATMENT

F. Strle
Department of Infectious Diseases, University Medical Centre, Ljubljana, Slovenia

Lyme borreliosis (LB) is the most common tick-transmitted human disease on the Northern hemisphere. It affects both sexes and all ages. The most common clinical manifestation of LB is erythema migrans. This enlarging erythematous skin lesion develops at the site of a tick-bite, usually 10 days (a few days to more than one month) after the bite, though bites are not noticed by all patients. Initially homogeneous patch lateron often becomes ring-like as a result of central clearing. About 50% of European patients report local symptoms while some patients experience systemic symptoms (more often in the USA than in Europe). Erythema migrans is regularly the first and often – especially when recognized and treated in due time – the only clinical manifestation of LB. When the disease presentation is complete (that is an exception) a tick bite is followed by erythema migrans, which is followed by heart and nervous involvement and later on by arthritis. Eye, late nervous system, joint and skin involvement are also known. When diagnosing Lyme borreliosis one should take into account that LB is a disease and that there is no disease without signs and/or symptoms. Clinical signs and symptoms should obligatory form the basis for the diagnosis of LB – there is no diagnosis of LB in the absence of clinical manifestations. This means that the prove of a borrelial infection is not enough for the diagnosis of LB, because infection may not produce any clinical signs. In addition, the prove of borrelial infection (for example by the presence of borrelial serum antibodies) does not guarantee that (all) symptoms demonstrated by an individual patient are due to LB. Thus, LB is a real disease, however, not all patients diagnosed with this illness really have LB.
Only a reliable diagnosis enables rational treatment, what additionally underscores how important a solid knowledge of the clinical features for rational treatment is.
Treatment with antibiotics is beneficial for all clinical manifestations of LB. However, it is most effective early in the course of the illness. Only antibiotics with in vitro activity against borrelia that showed efficacy in clinical studies should be utilized for treatment of LB. The end result of treatment depends not only upon the location, magnitude and duration of clinical manifestations but also upon several other factors including the choice of antibiotic, its dosage, duration of treatment, potential for adverse effects and compliance. Cost of drug and treatment should also be taken into account. On general, patients with proven or suspected involvement central nervous system are as a rule treated with intravenous antibiotics while for the majority of other manifestations of LB oral antibiotic therapy is usually sufficient.

S 5

LABORATORY SUPPORT IN THE DIAGNOSIS OF LYME BORRELIOSIS

G. Stanek
Institute of Hygiene and Medical Microbiology, University of Vienna, Austria

The microbiological confirmation of infection is needed for all manifestations of Lyme borreliosis with the exception of typical early skin lesions. Ideally, detection of the causative agent by culture or by amplification of specific nucleic acid sequences from lesional skin, other tissue, cerebrospinal fluid, synovial fluid or blood would prove the aetiology. However, direct detection is most successful in early skin manifestations which are usually identified clinically. Cultivation of cerebrospinal fluid in neuroborreliosis is positive shortly after the onset of clinical signs and symptoms but is as a rule successful in less than 10% of patients. Only single isolates are available so far from joint fluid or tissue but PCR was found positive in up to 80% in a retrospective study. However, culture and nucleic acid amplification assays (NAA) can only be performed satisfactorily in specialised laboratories.
Indications for microbiological testing (culture, NAA) related to different clinical signs and suspected clinical manifestations are always given. Positive results will aetiologically confirm the clinical diagnosis, however, negative results with direct detection methods do not exclude a suspected aetiology. Recommended specimens for culture and NAA are usually lesional skin and synovial fluid or synovial tissue. Cerebrospinal fluid and biopsies other than synovial may be useful for culture and NAA under special circumstances.
Despite many new diagnostic approaches and substantial increase in our knowledge about the biology of B. burgdorferi sensu lato, detection of specific antibodies in serum remains the method of choice in the laboratory diagnosis of Lyme borreliosis. The recommended procedure is to support the specificity of a screening test (e.g. ELISA) results with that of an immunoblot. This two tiered testing allows to assess the immune status of a patient suspicious for Lyme borreliosis. However, results obtained by extensive proficiency testing reveal that IgM tests were more difficult to handle than IgG-tests. Moreover, quantification of test results and reporting of specific immunoblot bands is highly variable. Thus, it is urgently needed to increase the medical quality of laboratory testing for Lyme borreliosis and to apply stronger criteria in order to approve the available test systems.

S 6

PREVENTATIVE MEASURES FOR LYME BORRELIOSIS

G. Wormser
New York, USA

Four prospective, randomized, placebo-controlled studies of antibiotic prophylaxis for prevention of Lyme borreliosis (LB) after Ixodes scapularis tick bites in the US have been reported. In the largest of these studies, a single 200 mg dose of doxycycline was 87% effective in preventing LB. Efficacy in patients bitten by Ixodes ticks in Europe is unknown. A fundamental limitation of antibiotic prophylaxis is that up to 75% of patients with LB do not recognize the preceding tick bite. An aluminum hydroxide adjuvanted lipidated recombinant outer surface protein A (OspA) vaccine has been shown to be ~ 75% effective for prevention of definite cases of LB in the US after 3 doses, but immunity is not long lasting, and frequent booster doses are likely to be needed. The vaccine is likely to be less effective in Europe due to the greater heterogeneity of OspA in Lyme borrelia there. Side effects of the vaccine have consisted of local discomfort at the injection site, self-limited systemic reactions, and occasional hypersensitivity. The vaccine has a unique mechanism of action, as its protective effect actually occurs in the tick during the grace period from onset of feeding to spirochete transmission. There has been no evidence that the vaccine causes arthritis, but this concern (based largely on the speculation that an autoimmune mechanism involving a cross-reactive immunologic response to OspA may be operative in the rare patient with “antibiotic refractory” Lyme arthritis) may have contributed to the vaccine’s poor acceptance. The manufacturer discontinued production of the vaccine in February 2002 due to insufficient sales.
In summary, antibiotic prophylaxis with a single 200 mg dose of doxycycline is effective in preventing LB after an I. scapularis tick bite, but can only be used if the bite is recognized. Research needs to be continued to find an effective, well accepted vaccine preparation that will provide long-lasting immunity.