Microbiological and serological diagnosis of Lyme borreliosis

In Europe, Lyme borreliosis is caused by Borrelia burgdorferi sensu stricto, B. afzelii, B. garinii and the recently described species B. spielmanii. For the development of diagnostic tools, the heterogeneity of the causative agents must be considered. The serological diagnosis should follow the principle of a two-step procedure: a sensitive enzyme-linked immunosorbent analysis as the first step, followed by immunoblot (IgM and IgG) if reactive. The sensitivity and standardization of immunoblots have been enhanced by the use of recombinant antigens instead of whole cell lysates. Improved sensitivity has resulted from the use of recombinant proteins primarily expressed in vivo (e.g. VlsE) and the combination of homologous proteins from different strains (e.g. DbpA). At present, detection rates for serum antibodies are 20-50% in localized, 70-90% in disseminated early and nearly 100% in late disease. Detection of the borreliae by culture or PCR should be confined to specific indications. The best results are obtained from skin biopsies (50-70% with culture or PCR) and synovial tissue or fluid (50-70% with PCR). Cerebrospinal fluid is positive in only 10-30%. Methods that are not recommended for diagnostic purposes include antigen tests in body fluids, PCR of urine and lymphocyte transformation tests.     

First experience with ELISA serosurvey for tick-borne borreliosis (Lyme disease) in Czechoslovakia

Antibodies to Borrelia burgdorferi were searched for in the sera from two groups of hospital patients and one group of healthy agricultural workers. The antibody response was measured by the authors' own modification of the ELISA method employing the antigen prepared from Borrelia recurrentis strain propagated in laboratory mice. Positive antibody titres to Borrelia were demonstrated in 5 out of the 44 patients admitted to the Infectious Diseases Clinic, in 8 out of the 32 patients from the Neurologic Clinic and in 16 out of the 52 healthy agricultural workers living in areas infested with ticks. These findings are interpreted as showing the topicality of the Lyme disease problem in Czechoslovakia.     

Lyme borreliosis in Lithuania: its prevalence, clinical picture and treatment efficacy

In 1988 Lyme borreliosis (LA) was diagnosed in 376 patients in Lithuania, including 101 patients who had the first stage of circular migrating erythema. Of this latter group, in 40 patients (39.6%) specific antibodies to the causative agent of LB were detected. All 101 patients were intensively treated with antibiotics for 10-14 days. The effectiveness of treatment was evaluated 4-5 months later. Information was collected only on 90 patients, including 82 patients who had undergone treatment. Complete convalescence was achieved in 52 cases (63.4%). 20 more persons considered themselves to be practically healthy. But in 10 patients (12.2%) the development of the disease continued, among them in 6 patients who stopped the prescribed course of treatment on their own accord. Out of 8 patients who had not yet even started to undergo treatment, 5 patients had signs of the manifest progress of the disease. Besides, information on the incubation period of the disease, its seasonal character, the characteristic features of erythema and concomitant symptoms in presented.     

Lyme borreliosis in central Italy (1995-1998)

From January 1995 to July 1998, 340 serum samples collected in Central Italy from patients clinically suspected of having Lyme borreliosis were investigated. All samples were tested for the presence of antibodies to B. burgdorferi by Elisa. The Elisa positive samples were subjected to further tests by Western Blot for confirmation. Out of 340 patients, 13 (3.8%) proved to be B. burgdorferi positive, while 9 (2.6%) were found to have Lyme disease with seroprevalence being higher in these latter than that of blood donors from Central Italy. Our results indicate that Lyme borreliosis is present in Central Italy. A comparison between Italian and European studies reveals that Lyme disease is still underestimated in Italy, the main reason being that a monitoring system for the study of Lyme borreliosis was only established in 1990.     

Pathological and molecular mechanisms of prostate carcinogenesis: implications for diagnosis, detection, prevention, and treatment

Prostate cancer is an increasing threat throughout the world. As a result of a demographic shift in population, the number of men at risk for developing prostate cancer is growing rapidly. For 2002, an estimated 189,000 prostate cancer cases were diagnosed in the U.S., accompanied by an estimated 30,200 prostate cancer deaths [Jemal et al., 2002]. Most prostate cancer is now diagnosed in men who were biopsied as a result of an elevated serum PSA (>4 ng/ml) level detected following routine screening. Autopsy studies [Breslow et al., 1977; Yatani et al., 1982; Sakr et al., 1993], and the recent results of the Prostate Cancer Prevention Trial (PCPT) [Thompson et al., 2003], a large scale clinical trial where all men entered the trial without an elevated PSA (<3 ng/ml) were subsequently biopsied, indicate the prevalence of histologic prostate cancer is much higher than anticipated by PSA screening. Environmental factors, such as diet and lifestyle, have long been recognized contributors to the development of prostate cancer. Recent studies of the molecular alterations in prostate cancer cells have begun to provide clues as to how prostate cancer may arise and progress. For example, while inflammation in the prostate has been suggested previously as a contributor to prostate cancer development [Gardner and Bennett, 1992; Platz, 1998; De Marzo et al., 1999; Nelson et al., 2003], research regarding the genetic and pathological aspects of prostate inflammation has only recently begun to receive attention. Here, we review the subject of inflammation and prostate cancer as part of a "chronic epithelial injury" hypothesis of prostate carcinogenesis, and the somatic genome and phenotypic changes characteristic of prostate cancer cells. We also present the implications of these changes for prostate cancer diagnosis, detection, prevention, and treatment.     

Laminopathies: The molecular background of the disease and the prospects for its treatment

Laminopathies are rare human degenerative disorders with a wide spectrum of clinical phenotypes, associated with defects in the main protein components of the nuclear envelope, mostly in the lamins. They include systemic disorders and tissue-restricted diseases. Scientists have been trying to explain the pathogenesis of laminopathies and find an efficient method for treatment for many years. In this review, we discuss the current state of knowledge about laminopathies, the molecular mechanisms behind the development of particular phenotypes, and the prospects for stem cell and/or gene therapy treatments.     

Spirochetes in mammals and ticks (Acari: Ixodidae) from a focus of Lyme borreliosis in California

In northern California, antibodies to Borrelia burgdorferi were detected in 58 of 73 (79%), and spirochetemias in one of 26 (4%) black-tailed jackrabbits (Lepus californicus californicus), by indirect and direct immunofluorescence, respectively. Five species of ticks (Dermacentor occidentalis, D. parumapertus, Ixodes neotomae, I. pacificus, and Haemaphysalis leporispalustris) were collected from rabbits. Two of these species of ticks were found to contain spirochetes; two of 10 (20%) I. neotomae and two of 174 (1%) H. leporispalustris. A strain of B. burgdorferi was recovered from I. neotomae. One infected H. leporispalustris female passed spirochetes via eggs to about 67% of her progeny. The widespread distribution of the black-tailed jackrabbit, its infestation by at least four ticks (D. occidentalis, D. parumapertus, I. neotomae, and I. pacificus) known to be infected naturally with B. burgdorferi, and the high prevalence of spirochetal antibody in this lagomorph suggest that it might be useful as a sentinel for surveillance of Lyme borreliosis. Spirochetes were detected in 15% of 40 Columbian black-tailed deer (Odocoileus hemionus columbianus) by direct immunofluorescence bound with a Borrelia-specific monoclonal antibody (H9724), but not with a monoclonal antibody (H5332) specific for B. burgdorferi. The geographical overlap of different borreliae in ticks that bite wildlife such as deer may confound spirochetal serosurveys, and underscores the need for more specific serologic tests than those currently available.     

Protein glycosylation in infectious disease pathobiology and treatment

A host of bacteria and viruses are dependent on O-linked and N-linked glycosylation to perform vital biological functions. Pathogens often have integral proteins that participate in host-cell interactions such as receptor binding and fusion with host membrane. Fusion proteins from a broad range of disparate viruses, such as paramyxovirus, HIV, ebola, and the influenza viruses share a variety of common features that are augmented by glycosylation. Each of these viruses contain multiple glycosylation sites that must be processed and modified by the host post-translational machinery to be fusogenically active. In most viruses, glycosylation plays a role in biogenesis, stability, antigenicity and infectivity. In bacteria, glycosylation events play an important role in the formation of flagellin and pili and are vitally important to adherence, attachment, infectivity and immune evasion. With the importance of glycosylation to pathogen survival, it is clear that a better understanding of the processes is needed to understand the pathogen requirement for glycosylation and to capitalize on this requirement for the development of novel therapeutics.     

Diagnosis,treatment and prevention of Ixodes tick-borne borreliosis in the Ul'ianovsk region

The level of morbidity in Ixodes tick-borne borreliosis, the analysis of the quality of diagnostics and the results of treatment are presented. The necessity of taking prophylactic measures is substantiated.     

Bactericidal properties of neutrophils from peripheral blood (PMN)of patients with Lyme borreliosis

In recent years in Poland, the interest has increased in studies about tick borne diseases, mainly Lyme borreliosis. Immune response and genotype of pathogen play an important role in the course of this disease. Phagocytic cells, especially PMN are dominant in defence mechanisms against bacterial infections. The main feature of PMN is their ability to destroy pathogenic microorganisms by phagocytosis. The aim of this study was to estimate the phagocytic activity of PMN connected with intracellular respiratory burst in patients with Lyme borreliosis. The PMN activity tests completed were: phagocytosis, spontaneous and reduced of nitrotetralizate blue test (NBT). Decreased phagocytic activity and oxygen metabolism of PMN from patients with borreliosis in comparison with values of controls were found. Normalization of these parameters after treatment was observed. Changed phagocytic activity connected with intracellular oxygen metabolism during the course of therapy was the main observation. Depression of phagocytic activity of PMN connected with oxygen metabolism can influence defence reactions in patients with Lyme borreliosis. It is suggested that changes observed are acquired and associated with Borrelia burgdorferi presence.     

Molecular diagnosis of Borrelia burgdorferi infection (Lyme disease).

In spite of significant advances in immunologically based testing, accurate diagnosis of Lyme borreliosis remains problematic. To address this issue, a DNA amplification-based diagnostic test was developed utilizing the polymerase chain reaction (PCR) and oligonucleotide primers specific for the OspA and OspB genes of Borrelia burgdorferi. In this approach, a relatively large DNA fragment is amplified with an outer set of primers, and a "nested" internal sequence of the PCR product subsequently reamplified with an inner set of primers. This nested approach coupled with simple differential centrifugation allowed specific detection of as few as four B. burgdorferi organisms mixed in 2 ml of blood. This methodology was utilized on patients' samples, and it allowed detection of B. burgdorferi in the peripheral blood and urine of several individuals with clinical evidence of Lyme borreliosis. PCR became negative and symptoms improved following antibiotic therapy of treated individuals. These studies suggest that direct detection of Borrelia in infected individuals can aid in diagnosis and evaluation of therapy for Lyme borreliosis.     

Lyme borreliosis agents and the genetics and sex of their vector, Ixodes ricinus

The tick Ixodes ricinus is responsible for the transmission and maintenance of a wide variety of pathogenic organisms in the Northern Hemisphere, among which Lyme disease represents a major threat to humans. Despite numerous studies, the epidemiology of the different bacterial species responsible for this disease remains unclear. Recent evidence for a sex-biased genetic structure of its European vector leads us to analyse the consequences of this pattern on Borrelia transmission. Here we show that male and female ticks are not equivalently infected by Borrelia burgdorferi, that Borrelia afzelii affects tick migration capabilities, especially for the most vagile sex (i.e., male) and that Lyme borreliosis agents are consequently vectorised in a much more complex way than usually thought. Such results change the epidemiological perception of Lyme borreliosis and suggest new co-evolutionary pathways between the ticks and the borrelia.