Meningitis after acute Borrelia burgdorferi infection in HIV infection

HISTORY AND CLINICAL FINDINGS: A 39-year-old HIV positive patient developed myalgia, headache and cough 4 weeks after a tick bite. His temperature was 37.4 degrees C and a circular pale erythema was noted over the left lower leg. INVESTIGATIONS: C-reactive protein was raised to 120 mg/l, white blood cell count was 5860/microliter, CD4-lymphocyte count 250/microliter. The chest radiogram showed pneumonitic infiltration in the left lower lobe. There were IgM antibodies against Borrelia burgdorferi. TREATMENT AND COURSE: Left lower lobe pneumonia and chronic erythema migrans were diagnosed and he was given oral azithromycin (500 mg on the first day and 250 mg for 4 days). The pneumonia cleared up, but 2 weeks later he developed symptoms of meningitis (496 cells per microliter, 87% lymphocytes, positive Borrelia burgdorferi antibody titer), which quickly and lastingly responded to ceftriaxon (2 g daily by brief infusion for 14 days). CONCLUSION: This immune-compromised HIV-infected patient developed disseminated borreliosis with CNS involvement 2 weeks after the occurrence of chronic erythema migrans. The initial treatment of the latter with azithromycin was unable to prevent the meningitis. It is unlikely that there was a causal connection between the borreliosis and the pneumonia.     

Concomitant infection with tick-borne encephalitis virus and Borrelia burgdorferi sensu lato in patients with acute meningitis or meningoencephalitis

Chronic lymphocytic leukemia involves the skin in a small percentage of patients and may portend an ominous prognosis in some patients. We report a series of eight biopsies from seven different patients in which the cutaneous leukemic infiltrate was confined exclusively to the region immediately surrounding primary epithelial neoplasms including squamous cell carcinoma (6), basal cell carcinoma (1) and actinic keratosis (1). The malignant lymphocytes appear to constitute a host response to these neoplasms and do not appear to suggest a rapid downhill course for these patients. These observations serve to 1) suggest a new pattern of cutaneous involvement by leukemic cells and 2) offer some insights into potential cellular trafficking patterns of these neoplastic cells.     

Geographical incidence of infection with Borrelia burgdorferi in Europe

Sudden deafness and vertigo are a challenge for the otolaryngologist. With its high fluid content, the membranous labyrinth is best evaluated through Magnetic Resonance Imaging (MRI). Recently gadolinium-enhanced MRI has opened new perspectives in the imaging of the pathological labyrinth, able to directly detect labyrinthine lesions. To date the main role of MRI has been to rule out the presence of retrocochlear involvement in patients with sudden deafness and/or vertigo. However, in the past few years, several authors, reporting on gadolinium-enhanced MRI, have described better labyrinthine imaging, revealing direct labyrinth or nerve bundle involvement in all such patients. On the contrary, other studies have not revealed any enhancement of post-contrast labyrinthine images upon MRI but have shown an increase in signal intensity upon T2-weighted images. In this light, the purpose of the present study has been a) to evaluate the prevalence of labyrinthine abnormalities found upon MRI in consecutive patients with sudden deafness and vertigo and b) to assess the correlation between the severity of clinical and audiological findings and the MRI abnormalities encountered. Twelve consecutive patients with sudden hearing loss and/or vertigo were included in the study (age range 9-59 years; 6 males and 6 females). All subjects underwent complete otoneurological examination. MRI was performed with a 0.5 T superconducting magnet system allowing 2 mm-thick sections through the temporal bone. Within 29 days of onset of the complaints all patients were studied both before and after administration of the contrast medium (gadolinium-DTPA, 0.01 mmol/l, i.v.). Two of the 12 subjects had sudden deafness, 5 sudden deafness and vertigo while 5 had vertigo alone. Gadolinium enhancement and/or a high signal intensity upon T2-weighted images of the pathological labyrinth and nerve bundle was observed in 4 patients. The patients were divided into groups by etiology. MRI abnormalities were only found in the group where the etiology was viral. There was no correlation between the severity of clinical findings and the presence of MRI abnormalities nor between MRI and ABR findings. Analysis of such controversial data is discussed, stressing the importance of gadolinium-enhanced MRI of the labyrinth as a new diagnostic tool in sudden deafness and vertigo.     

Prevalence of Borrelia burgdorferi infection in Ixodes ricinus in central Italy

A scalp tumor from a 24-year-old male presenting unusual histological finding is described. The tumor was mostly composed of corpuscles resembling Meissner tactile bodies and contained almost no other components. Immunohistochemical studies revealed the tumor cells to be positive for S-100 protein and neuron-specific enolase, so we considered the tumor to be an unusual nevocellular nevus mostly comprised of nevic corpuscles.     

A preliminary report on Borrelia burgdorferi infection in the Taiwan area

A 68-year-old man presents slight memory problems and behavioural change over a period of a year. A history of boxing is identified. Neuropsychological examination confirms slight frontal cognitive damage and damage at the level of the motor signs of the upper left hemicorpus. This symptomatology should, in differential diagnosis, raise the possibility of chronic punch-drunk syndrome. Further studies should be done to better document this little-characterized clinical entity and arrive at a clearer definition of this syndrome.     

Microbiology of Borrelia burgdorferi

The acute (single bout of exercise) and chronic (exercise training) effects of exercise on plasma leptin were investigated in 97 sedentary adult men (n = 51) and women (n = 46) participating in the HERITAGE Family Study. Exercise training consisted of a standardized 20-wk endurance training program performed in the laboratory on a computer-controlled cycle ergometer. Maximal oxygen uptake, body composition assessed by hydrostatic weighing, and fasting insulin level were also measured before and after training. Pre- and posttraining blood samples were obtained before and after completion of a maximal exercise test on the cycle ergometer. Exercise training resulted in significant changes in maximal oxygen uptake (increase in both genders) and body composition (reduction of fat mass in men and increase in fat-free mass in women). There were considerable interindividual differences in the leptin response to acute and chronic effects of exercise, some individuals showing either increase or reduction in leptin, others showing almost no change. On average, leptin levels were not acutely affected by exercise. After endurance training was completed, leptin levels decreased significantly in men (from 4.6 to 3.9 ng/ml; P = 0.004) but not in women. However, after the training-induced changes in body fat mass were accounted for, the effects of exercise training were no longer significant. Most of the variation observed in leptin levels after acute exercise or endurance training appears to be within the confidence intervals of the leptin assay. We conclude that there are no meaningful acute or chronic effects of exercise, independent of the amount of body fat, on leptin levels in humans.     

An OspA-based DNA vaccine protects mice against infection with Borrelia burgdorferi

A single and simple procedure for the determination of both carbendazim and imazalil is described. The proposed analytical methodology is based on a liquid-liquid extraction with ethyl acetate and further analysis with HPLC-UV in the case of carbendazim, and GC-nitrogen-phosphorus detection in the case of imazalil. Detection levels have been 0.01 mg/kg for carbendazim and 0.005 mg/kg for imazalil. Recoveries have been no less than 77% for carbendazim and 92% for imazalil. The method has been validated with fortified samples at different concentration levels. Different confirmation criteria have been studied and applied in routine analysis. The analytical procedure proposed has been applied to the analysis of 200 fruit samples belonging to the Residue Monitoring of Hygiene Food Program 1995 of the Spanish Ministry of Health, which has been performed in our laboratory. The results obtained have confirmed the viability of the method in routine analysis for these pesticides. A first evaluation of the presence of residues of both fungicides in fruits produced in Spain has been made.     

Borrelia burgdorferi induces chemokines in human monocytes

Lyme disease is clinically and histologically characterized by strong inflammatory reactions that contrast the paucity of spirochetes at lesional sites, indicating that borreliae induce mechanisms that amplify the inflammatory response. To reveal the underlying mechanisms of chemoattraction and activation of responding leukocytes, we investigated the induction of chemokines in human monocytes exposed to Borrelia burgdorferi by a dose-response and kinetic analysis. Lipopolysaccharide (LPS) derived from Escherichia coli was used as a positive control stimulus. The release of the CXC chemokines interleukin-8 (IL-8) and GRO-alpha and the CC chemokines MIP-1alpha, MCP-1, and RANTES was determined by specific enzyme-linked immunosorbent assays, and the corresponding gene expression patterns were determined by Northern blot analysis. The results showed a rapid and strong borrelia-inducible gene expression which was followed by the release of chemokines with peak levels after 12 to 16 h. Spirochetes and LPS were comparably effective in stimulating IL-8, GRO-alpha, MCP-1, and RANTES expression, whereas MIP-1alpha production preceded and exceeded chemokine levels induced by LPS. Unlike other bacteria, the spirochetes themselves did not bear or release factors with intrinsic chemotactic activity for monocytes or neutrophils. Thus, B. burgdorferi appears to be a strong inducer of chemokines which may, by the attraction and activation of phagocytic leukocytes, significantly contribute to inflammation and tissue damage observed in Lyme disease.     

Intrauterine transmission of Borrelia burgdorferi in dogs

To determine whether intrauterine transmission of Borrelia burgdorferi could exist in dogs, 10 female Beagles were inoculated intradermally with approximately 1,000 B burgdorferi on day 1 of proestrus; inoculation was repeated every 2 weeks during the gestation period. Ten female control Beagles were similarly inoculated with phosphate-buffered saline solution. Prior to the start of the study, all females and 3 males used for breeding were seronegative for B burgdorferi on the basis of results of the indirect fluorescent antibody test and immunoblot (western analysis. Similarly, results of culture of blood for B burgdorferi were negative. All 20 of the females were bred naturally. Blood samples were collected weekly for serologic testing and culture. Blood samples were obtained from live pups on day 1 of life, then weekly until pups were 6 weeks old when they were euthanatized. Tissues were obtained for culture and testing by use of polymerase chain reaction (PCR). Of 10 spirochete-inoculated (SI) females, 8 became infected with B burgdorferi as evidenced by spirochete culture results and/or PCR-detected B burgdorferi DNA in the tissues of females or their pups. Of the 10 SI females, 8 delivered litters (3 to 7 pups) that had at least 1 neonatal or 6-week-old pup with B burgdorferi DNA-positive tissues (by PCR), and spirochetes were cultured from tissues from pups of 2 litters.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cutaneous fibroses induced by Borrelia burgdorferi

Three cases of chronic infection with Borrelia burgdorferi are described. The patients presented with nodular or discoid fibrosis, partly in conjunction with acrodermatitis chronica atrophicans (ACA). Juxta-articular fibrotic nodules may develop within a few months of the onset of ACA. Nodular, discoid morphoea-like, and widespread cutaneous fibroses in chronic Borrelia infection may be provoked by trauma, surgery or electromagnetic radiation. They respond well to antibiotic therapy. These lesions offer an in vivo model for studying the evolution of immunologically induced fibrosis.     

Fatal encephalitis caused by concomitant infection with tick-borne encephalitis virus and Borrelia burgdorferi

We describe a 38-year-old farmer from the southwestern archipelago of Finland where both tick-borne encephalitis (TBE) virus and Borrelia burgdorferi are endemic. He presented with fever and headache, developed severe meningoencephalitis in 3 days, and, after 1 month, died without regaining consciousness. High titers of IgG and IgM antibodies to TBE virus were present in both serum and CSF. Serology for Borrelia was negative. Autopsy revealed necrotizing encephalitis and myelitis with involvement of the dorsal root ganglion. With use of polymerase chain reaction tests, segments of two separate genes of B. burgdorferi were amplified from the patient's CSF. This case demonstrates that the possibility of dual infection should be considered for patients residing in geographic areas where Ixodes ticks may carry both the TBE virus and B. burgdorferi. We believe that the most severe damage in this case was caused by TBE virus rather than by B. burgdorferi. Nevertheless, the coinfection might have contributed to the fatal outcome that has not been previously observed in Finnish patients with TBE.     

Identification of superoxide dismutase activity in Borrelia burgdorferi

Infective and noninfective strains of Borrelia burgdorferi, along with Borrelia afzelii and Borrelia garinii, possessed a single iron-containing superoxide dismutase (SOD). None of the Lyme disease spirochetes tested possessed catalase or peroxidase activities. The borrelial SOD was not inducible by growth with increased oxygen concentrations and thus appeared to be produced constitutively.     

Seroprotective groups among isolates of Borrelia burgdorferi

We demonstrated that different seroprotective groups exist among isolates of Borrelia burgdorferi and Borrelia garinii. The major group was composed of isolates 297, B31, S-1-10, MMTI, IPT, and ATCC 35211 and 21 isolates obtained from California, Illinois, New York, Texas, and Wisconsin. A second group was composed of European isolates PBi and G25. A third group was composed of a single isolate, C-1-11. These groupings were supported by Western immunoblot findings. In addition, the seroprotective groups were confirmed by passive transfer of immune sera and challenge of recipient hamsters with the homologous isolate or other isolates of B. burgdorferi or B. garinii. These studies demonstrate that a monovalent vaccine will not provide complete protection against infection with all isolates of B. burgdorferi.     

Activation of natural killer cells in arthritis-susceptible but not arthritis-resistant mouse strains following Borrelia burgdorferi infection

Infection of susceptible mouse strains with Borrelia burgdorferi, the agent of Lyme disease, results in the development of arthritis. Components of the innate immune system may be important mediators of this pathology. To investigate the potential role of NK cells in development of experimental Lyme arthritis, we examined their activation in vivo in both resistant and susceptible mouse strains. Following inoculation of B. burgdorferi into the footpad, lymph node NK cells from susceptible C3H/HeJ (C3H) mice produced more gamma interferon than NK cells from resistant DBA/2J mice. Lymph node cells from susceptible C3H and AKR mice also had increased ability to lyse YAC-1 target cells 2 days following infection. Antibody depletion of NK cells from susceptible mice, however, did not alter the development of arthritis following B. burgdorferi challenge. In addition, NK cell depletion had little effect on spirochete burden. Thus, there is a marked activation of NK cells in susceptible mouse strains following infection. Although NK cells are not absolutely required for arthritis, events occurring prior to NK cell activation might be important in mediating pathology in experimental Lyme disease.     

Humoral immunity to Borrelia burgdorferi N40 decorin binding proteins during infection of laboratory mice

A Borrelia burgdorferi N40 genomic expression library was screened with serum from actively infected mice to identify gene products that elicit protective immunity. A clone that contained a putative bicistronic operon containing two genes that encoded 20- and 22-kDa lipoproteins was identified and sequenced. These genes showed homology with the genes encoding decorin binding proteins DbpB and DbpA, respectively, of B. burgdorferi 297 and B31. N40-dbpA DNA hybridized with B. burgdorferi N40 DNA on a single 48-kb linear plasmid. Homologous genes could be amplified under various degrees of stringency by PCR or hybridized by Southern blotting from B. burgdorferi sensu stricto N40 and B31, and from B. burgdorferi sensu lato PBi and 25015, but not PKo. Recombinant N40-DbpB and N40-DbpA were reactive with antibody in serum from infected mice, and serum was more reactive against N40-DbpA than against B. burgdorferi N40 recombinant P39, OspC, or OspA. Sera from mice infected with B. burgdorferi sensu lato strains PKo and PBi were weakly reactive against N40-DbpB and N40-DbpA, and sera from mice infected with 25015 were moderately reactive, compared to sera from mice infected with B. burgdorferi N40. Hyperimmunization of mice with N40-DbpA, but not N40-DbpB, induced protective immunity against syringe challenge with cultured B. burgdorferi N40. DbpA may therefore be one of the antigens responsible for eliciting protective antibody known to exist in serum from infected mice. DNA amplification and serology suggest that DbpB and DbpA are likely to have homologs throughout the B. burgdorferi sensu lato family, but they are likely to be heterogeneous.     

Development of enzyme-linked immunosorbent assays using recombinant borrelial antigens for serodiagnosis of Borrelia burgdorferi infection

The basic tenet of continuous quality improvement is that there is always room for additional improvement in the clinical care provided to patients. The opportunities for this improvement come from the analysis of information collected during the ongoing monitoring of important elements of care. The provision of clinical psychiatric care is seen as a complex process that is dependent on the effective functioning of all of the health and mental health care organization. The concept of continuous quality improvement is the most recent stage in a long process of defining and redefining the basic goals and tenants of medical and psychiatric quality assurance. The determination of the actual improvement of psychiatric and mental health care due to quality assurance is a substantial and important technical problem. The determination of the value of this improvement in mental health care is an even greater ethical and social problem.     

Performance of a Borrelia burgdorferi bacterin in borreliosis-endemic areas

The safety and efficacy of a commercially available Borrelia burgdorferi bacterin were examined under field conditions in 1,969 dogs that received a total of 4,033 doses of bacterin during a 20-month period. For comparison, 4,498 dogs that were not vaccinated also were evaluated. All dogs were examined at 1 of 3 veterinary practices in borreliosis-endemic areas. Owners of all dogs were educated about the benefits of and methods for avoiding infected ticks. Vaccination was found to be safe regardless of previous exposure to B burgdorferi or history of borreliosis. Thirty-eight (1.9%) of the 1,969 dogs had minor reactions; 1 of these dogs had a reaction after the first and second doses of B burgdorferi bacterin. Reactions resolved without complications immediately or within 72 hours after vaccination. Cumulative incidence of borreliosis was 1.0% (20/1,969) in vaccinated dogs and 4.7% (211/4,498) in nonvaccinated dogs. Preventable fraction, a measure of the reduction of incidence of disease in vaccinated dogs vs nonvaccinated dogs, was 78%. Preventable fraction in dogs that were seropositive prior to vaccination (ie, previously exposed to B burgdorferi) was 58% and in dogs that were seronegative prior to vaccination (ie, without evidence of prior exposure to B burgdorferi) was 86%. This suggested that, in borreliosis-endemic areas, dogs may be most effectively protected by vaccinating them when they are young and before they are exposed to infected ticks, and that in areas where borreliosis is not endemic, it may be useful to initiate vaccination programs so that dogs will be protected prior to exposure to infected ticks.     

Borrelia burgdorferi, taxonomy, pathogenicity and spread

In connection with the development of transdermal delivery systems (TTS) of the laminated adhesive patches type, HPLC was selected for analytical evaluation of active principles. It was employed for analysis of glycerol trinitrate (GTN) as one of the drugs administered in the form of medicinal adhesive patches. After isolation from the patch, GTN was analysed by reverse phase HPLC, employing methanol and water as the mobile phase, and detected at 206 nm. The total amount of GTN in the patch was evaluated and its concentrations in a lactose trituration and the reservoir layer were determined. In the patches manufactured in a test series, the elaborated HPLC method was used to investigate the release of GTN in a liberation study and its permeation through excised human skin in experiments performed in vitro. In connection with the stability study, the decomposition products of GTN were also determined.     

Molecular cloning and characterization of Borrelia burgdorferi rpoB

To examine the association of vascular endothelial growth factor (VEGF) expression with tumor angiogenesis, survival and thymidine phosphorylase/platelet-derived endothelial cell growth factor (dThdPase/PD-ECGF) expression in human colorectal cancer, immunohistochemical studies were performed on 136 cases of resected colorectal cancer specimens using antibodies for VEGF, KDR, CD34 and dThdPase/PD-ECGF. Fifty-nine cases (43%) were evaluated as positive for VEGF staining and 71 cases (52%) were evaluated as positive for dThdPase/PD-ECGF staining. The expression of VEGF correlated significantly with vessel counts and the expression of dThdPase/PD-ECGF (P = 0.01 and 0.01, respectively). Cox proportional hazards model analysis showed that vessel counts and VEGF expression were significant and independent prognostic factors, but that KDR expression was not.     

Borrelia burgdorferi shows specificity of binding to glycosphingolipids

Live but not fixed or heat-killed Borrelia burgdorferi bound to galactocerebroside, lactosylceramide, and ceramide trihexoside. In addition, this organism bound to the disialoganglioside GD1a and the trisialoganglioside GT1b but not to gangliosides GM1, GD1b, GM2, and GM3 and not to asialo GM1. This adhesion pattern confirmed earlier findings of binding to galactocerebroside and places this organism within a prokaryotic group which binds to lactosylceramide. The binding to GD1a and GT1b, both of which carry terminal as well as multiple sialic acids, indicates that B. burgdorferi can show specificity of binding within a group of acidic gangliosides. Adhesion could not be inhibited by several concentrations of sugars and sialic acid, indicating more complex binding requirements than for terminal carbohydrates alone. Low-passage strains adhered to the four substrates in greater numbers than strains in culture for long periods of time. OspB mutants in general bound better or at least equally well to several of the glycosphingolipids, and preincubation of substrates with soluble recombinant and affinity-purified Osp did not inhibitor or weakly inhibited the binding of the organisms. These findings suggest that outer surface lipoproteins A and B are not directly involved in adhesion to glycosphingolipids.