Course Of Lyme Borreliosis Research Articles

Early Lyme Borreliosis in Patients Treated with Tumour Necrosis Factor-Alfa Inhibitors.

The study evaluated the course and outcome of erythema migrans in patients receiving tumour necrosis factor-alpha (TNF-α) inhibitors. Among 4157 adults diagnosed with erythema migrans in the period 2009–2018, 16 (2.6%) patients were receiving TNF-α inhibitors (adalimumab, infliximab, etarnecept, golimumab), often in combination with other immunosuppressants, for rheumatic (13 patients) or inflammatory bowel (three patients) disease. Findings in this group were compared with those in 32 sex- and age-matched immunocompetent patients diagnosed with erythema migrans in the same years. In comparison with the control group, the immunocompromised patients had a shorter incubation period (7 vs. 14 days; p = 0.0153), smaller diameter of erythema migrans (10.5 vs. 15.5 cm; p = 0.0014), and more frequent comorbidities other than immune-mediated diseases (62.5% vs. 25%, p = 0.0269), symptoms/signs of disseminated Lyme borreliosis (18.8% vs. 0%, p = 0.0324), and treatment failure (25% vs. 0%, p = 0.0094). After retreatment with an antibiotic, the clinical course of Lyme borreliosis resolved. Continuing TNF inhibitor treatment during concomitant borrelial infection while using identical approaches for antibiotic treatment as in immunocompetent patients resulted in more frequent failure of erythema migrans treatment in patients receiving TNF inhibitors. However, the majority of treatment failures were mild, and the course and outcome of Lyme borreliosis after retreatment with antibiotics was favourable.

Epidemiology of Lyme borreliosis in France - both certainties and uncertainties

Epidemiological evidence for tick-borne infections, particularly those related to Lyme borreliosis, is heterogeneous. Lyme borreliosis is a tick-born zoonosis transmitted by ticks of the genus Ixodes ricinus. After tick bite, the risk of transmission of an infectious agent remains low, most often represented by Borrelia burgdorferi sensu lato; co-infections in Humans by several different infectious agents (bacterial, viral or parasitic) are possible but a priori rare. In addition, besides well-known tick-borne pathogens, new species or gender of micro-organisms are regularly described in ticks but their pathogenicity in human pathology is not described or not yet established. The clinical presentation of Lyme borreliosis is varied, with localized and disseminated forms occurring long ago after tick bite, making diagnosis sometimes difficult. The natural course of Lyme borreliosis is insufficiently known because of recommendations of antibiotherapy in case of illness; however, some historical studies seem reassuring with possible spontaneous healing and seemingly minor sequelae. The diagnosis of disseminated forms requires paraclinical examinations, in first place serology, whose sensitivity increases with time of evolution of borreliosis; this is all the more interesting as the disseminated forms are of more difficult clinical diagnosis. After antibiotherapy, the clinical course is good, the sequelae remain possible especially in case of late diagnosis or late disseminated form; however, their frequency remains unknown.

Subclinical Lyme borreliosis is common in south-eastern Sweden and may be distinguished from Lyme neuroborreliosis by sex, age and specific immune marker patterns

BackgroundDeterminants of a subclinical course of Lyme borreliosis (LB) remain largely unknown. The aim of this study was to assess the extent, sex and age profiles of subclinical Borrelia seroconversion in a LB endemic area in Sweden and to map blood cellular Borrelia-specific immune marker patterns in individuals with a previous subclinical LB course compared with patients previously diagnosed with Lyme neuroborreliosis (LNB). MethodsA large group of 1113 healthy blood donors was screened for multiple IgG anti-Borrelia antibodies and asked to complete a health inquiry regarding previous LB. A group of subjects with anti-Borrelia-specific IgG antibodies but no previous history of LB (subclinical LB, n = 60) was identified together with 22 cases of previous LNB. Whole Borrelia spirochetes, strains B. afzelii ACA1 and B. garinii Ip90, were used for ex vivo whole blood stimulations, whereas outer surface protein enriched fractions of the same strains were used for stimulation of peripheral blood mononuclear cells (PBMCs). An extensive panel of immune markers was analysed in the supernatants after stimulation using multiplex bead arrays, and Borrelia-specific secretion was determined by subtracting the spontaneous secretion. ResultsA total of 125/1113 blood donors reported previous clinical LB. In contrast, 66 donors denied previous LB but showed multiple IgG anti-Borrelia antibodies; these were defined as subclinical subjects, of whom 60 were available for further studies. The subclinical subjects consisted of significantly more men and had a younger age compared with the LNB patients (p ≤ 0.01). Discriminant analysis revealed a distinct pattern of sex, age and PBMC B. garinii-specific levels of IL-10, IL-17A and CCL20 discriminating subclinical subjects from LNB patients. ConclusionsThis study confirms that subclinical Borrelia seroconversion is common in south-eastern Sweden. The findings further suggest that male sex, younger age together with B. gariniii induced levels of IL-10, IL-17A and CCL20 may be associated with a subclinical course.

Serological and molecular evidence for spotted fever group Rickettsia and Borrelia burgdorferi sensu lato co-infections in The Netherlands

Only a few reported cases indicate that Rickettsia helvetica and Rickettsia monacensis can cause disease in humans. Exposure to these two spotted fever group (SFG) rickettsiae occurs through bites of Ixodes ricinus, also the primary vector of Lyme borreliosis in Europe. To date, it is unclear how often exposure to these two microorganisms results in infection or disease.We show that of all the Borrelia burgdorferi s.l.-positive ticks, 25% were co-infected with rickettsiae. Predominantly R. helvetica was detected while R. monacensis was only found in approximately 2% of the ticks. In addition, exposure to tick-borne pathogens was compared by serology in healthy blood donors, erythema migrans (EM)-patients, and patients suspected of Lyme neuroborreliosis (LNB). As could be expected, seroreactivity against B. burgdorferi sensu lato was lower in blood donors (6%) compared to EM patients (34%) and suspected LNB cases (64%). Interestingly, seroreactivity against SFG Rickettsia antigens was not detected in serum samples from blood donors (0%), but 6% of the EM patients and 21% of the LNB suspects showed anti-rickettsial antibodies. Finally, the presence of B. burgdorferi s.l. and Rickettsia spp. in cerebrospinal fluid samples of a large cohort of patients suspected of LNB (n=208) was investigated by PCR. DNA of B. burgdorferi s.l., R. helvetica and R. monacensis was detected in seventeen, four and one patient, respectively.In conclusion, our data show that B. burgdorferi s.l. and SFG rickettsiae co-infection occurs in Dutch I. ricinus and that Lyme borreliosis patients, or patients suspected of Lyme borreliosis, are indeed exposed to both tick-borne pathogens. Whether SFG rickettsiae actually cause disease, and whether co-infections alter the clinical course of Lyme borreliosis, is not clear from our data, and warrants further investigation.

Propensity to excessive proinflammatory response in chronic Lyme borreliosis

The clinical course of Lyme borreliosis is extremely variable. However, all the clinical manifestations, acute or chronic, are characterized by strong inflammation. Borrelia burgdorferi can induce the production of several proinflammatory and anti-inflammatory cytokines. The aim of our study was to find out whether the balance between inflammatory and regulatory mechanisms is important in determining the course of Lyme borreliosis. 13 patients with early Lyme borreliosis, 8 patients with chronic Lyme disease with neurological or joint manifestations, and 15 age- and sex-matched healthy controls were studied. Chronic forms of Lyme borreliosis were characterized by stronger TNF-alpha response by monocytes to lipopolysaccharide as well as to borrelia antigen compared to early Lyme borreliosis and the healthy state. The percentage of IL-10-secreting monocytes in response to borrelia lysate was lower in the Lyme borreliosis patients than in healthy controls. The percentage of CD4(+) CTLA-4(+) regulatory T cells showed the highest values in early Lyme borreliosis. We conclude that chronic forms of Lyme borreliosis can evolve due to an aberrant innate proinflammatory response.

Pseudo pyoderma gangrenosum, scars and comedones revealing leukocyte adhesion deficiency in adulthood

From 1991 to 1993, we investigated the clinical features of Lyme borreliosis (LB) in 864 patients from the Sverdlovsk region (population 4.5 million) in the middle Urals. Ixodes persulcatus ticks were collected in the vicinity of Yekaterinburg to determine the presence of Borrelia burgdorferi sensu lato species. From 1991 to 1993, the number of patients with LB increased from 91 to 320 and 453, respectively. Nearly all LB patients (97%) recalled a tick bite and the first signs of LB developed between May and August. Erythema migrans (EM) was seen in 820 patients (94.9%) and fever was common (44.6%). Neuroborreliosis, mainly radiculoneuritis, was found in 154 patients (17.8 %), secondary erythema was seen in 53 patients, and Lyme arthritis (LA) was diagnosed in 35 patients. Carditis was rare and acrodermatitis chronica atrophicans (ACA) was not seen. Only 44 patients developed one or more symptoms of LB without a preceding EM. Few patients were seropositive for tick-borne encaphalitis. Borrelial DNA was detected in 67% of I. persulcatus ticks. Infected ticks carried predominantly Borrelia garinn or Borrelia afzelii, mixed infections of both species were common. Borrelia valaisiana was detected once, and B. burgdorferi sensu stricto was not found. Although the course of LB in the middle Urals is comparable to that of European LB, several discrepancies were noted. LB patients often recall tick bites, fever is common, LA is mild and ACA is absent.

Clinical Features of Lyme Borreliosis in the Middle Urals and Distribution of Borrelia burgdorferi sensu lato Species in Local Ixodes persulcatus Ticks

From 1991 to 1993, we investigated the clinical features of Lyme borreliosis (LB) in 864 patients from the Sverdlovsk region (population 4.5 million) in the middle Urals. Ixodes persulcatus ticks were collected in the vicinity of Yekaterinburg to determine the presence of Borrelia burgdorferi sensu lato species. From 1991 to 1993, the number of patients with LB increased from 91 to 320 and 453, respectively. Nearly all LB patients (97%) recalled a tick bite and the first signs of LB developed between May and August. Erythema migrans (EM) was seen in 820 patients (94.9%) and fever was common (44.6%). Neuroborreliosis, mainly radiculoneuritis, was found in 154 patients (17.8%), secondary erythema was seen in 53 patients, and Lyme arthritis (LA) was diagnosed in 35 patients. Carditis was rare and acordermatitis chronica atrophicans (ACA) was not seen. Only 44 patients developed one or more symptoms of LB without a preceding EM. Few patients were seropositive for tick-borne encaphalitis. Borrelial DNA was detected in 67% of I. persulcatus ticks. Infected ticks carried predominantly Borrelia garinii or Borrelia afzelii, mixed infections of both species were common. Borrelia valaisiana was detected once, and B. burgdorferi sensu stricto was not found. Although the course of LB in the middle Urals in comparable to that of European LB, several discrepancies were noted. LB patients often recall tick bites, fever is common, LA is mild and ACA is absent.

Why is chronic Lyme borreliosis chronic?

Chronic Lyme borreliosis (CLB) can present not only in different organs but also in different patterns. Although many theories exist about the mechanisms leading to CLB, it is known that viable Borrelia burgdorferi can persist for decades and cause late skin manifestations of acrodermatitis chronica atrophicans (ACA). Thus, the immunopathogenetic findings in ACA can serve as a model for studying the chronic course of Lyme borreliosis. Recent findings indicate that the most important cell for antigen presentation, the epidermal Langerhans cell (LC), is invaded by B. burgdorferi in early Lyme borreliosis. Therefore, LCs were stained immunohistochemically with different markers to investigate their functional activity. Numbers of CD1a+ LCs were reduced in erythema migrans but normal or slightly elevated in ACA. In both diseases there was also a marked downregulation of major histocompatibility complex class II molecules on LCs, as measured by staining of human leukocyte antigen DR. This phenomenon might be a mechanism that protects against the presentation of autoantigens and may be the cause of the impaired capacity of LCs to eliminate B. burgdorferi antigens, thus explaining why CLB is chronic.

Facial palsy and Lyme borreliosis: long-term follow-up of children with antibiotically untreated "idiopathic" facial palsy.

We report on the follow-up of 28 patients, who were admitted to our hospitals between 1968 and 1984, and who, at that time, were diagnosed as having idiopathic facial palsy. These children were neither tested for Lyme borreliosis (LB) nor did they receive antibiotic treatment. In those days LB was an unfamiliar infection. Today we can assume that approximately 30%-50% of the patients we studied represent actual cases of neuroborreliosis. We, therefore, considered them an appropriate model in studying the spontaneous course of LB in children. the analysis of the questionnaire designed for our study as well as the supplementary clinical and serological reexaminations in some cases provided no evidence that neuroborreliosis led to relevant health disorders in any of the children (follow-up 10 to 26 years, mean 17). The results of our retrospective study led us to conclude that tick-borne facial palsy is relatively benign in children and that neuroborreliosis is insignificantly related to late complications.

Lyme borreliosis in transgenic mice tolerant to Borrelia burgdorferi OspA or B.

The evolution of Lyme borreliosis in transgenic mice tolerant to Borrelia burgdorferi outer surface proteins (Osps) A or B was assessed to investigate the role of immunity to OspA or B in infection and pathogenesis of Lyme disease. Antibodies to OspA or B protect immunocompetent C3H/HeJ or C.B.17 severe combined immunodeficient (scid) mice from challenge with B. burgdorferi. Moreover, arthritis in infected C3H mice resolves with the rise of high titers of B. burgdorferi specific antibodies, including OspA and B, whereas disease persists in scid mice--suggesting that the regression of arthritis may be due to the development of borreliacidal OspA or B antibodies. To evaluate the course of Lyme borreliosis in OspA or B tolerant mice we developed transgenic mice that expressed OspA or B under control of the major histocompatibility complex (MHC) class I promoter. Mice carrying OspA or B transgenes on a C3H/HeJ (C3H, disease-susceptible) or C57BL/6 (B6, disease-resistant) background, immunized with OspA or B, did not mount a humoral or cellular immune response to OspA or B, respectively, but responded normally to other B. burgdorferi antigens. The evolution of Lyme borreliosis, including infection and the development of arthritis and carditis, was similar in transgenic and nontransgenic littermates suggesting that an OspA or B immune response is not singularly involved in either the genesis or regression of Lyme disease in C3H or B6 mice.

Lyme Borreliosis

Lyme borreliosis is a cutaneous-systemic infection that is generally transmitted by a hard-bodied tick and caused by some species of Borrelia, Borrelia burgdorferi (sensu stricto), B. garini , and B. afzelii . Lyme borreliosis is a widespread disease, present in all continents. It can be divided into an early disease, corresponding to the primary stage, and a late disease, including the secondary and tertiary stages. The typical cutaneous lesions are erythema (chronicum) migrans, lymphadenosis benigna cutis, and acrodermatitis chronica atrophicans. The course of Lyme borreliosis depends on the timeliness of both diagnosis and antibiotic treatment.

Mechanism of development of pregnancy complications in chemical workers

From 1991 to 1993, we investigated the clinical features of Lyme borreliosis (LB) in 864 patients from the Sverdlovsk region (population 4.5 million) in the middle Urals. Ixodes persulcatus ticks were collected in the vicinity of Yekaterinburg to determine the presence of Borrelia burgdorferi sensu lato species. From 1991 to 1993, the number of patients with LB increased from 91 to 320 and 453, respectively. Nearly all LB patients (97%) recalled a tick bite and the first signs of LB developed between May and August. Erythema migrans (EM) was seen in 820 patients (94.9%) and fever was common (44.6%). Neuroborreliosis, mainly radiculoneuritis, was found in 154 patients (17.8 %), secondary erythema was seen in 53 patients, and Lyme arthritis (LA) was diagnosed in 35 patients. Carditis was rare and acrodermatitis chronica atrophicans (ACA) was not seen. Only 44 patients developed one or more symptoms of LB without a preceding EM. Few patients were seropositive for tick-borne encaphalitis. Borrelial DNA was detected in 67% of I. persulcatus ticks. Infected ticks carried predominantly Borrelia garinn or Borrelia afzelii, mixed infections of both species were common. Borrelia valaisiana was detected once, and B. burgdorferi sensu stricto was not found. Although the course of LB in the middle Urals is comparable to that of European LB, several discrepancies were noted. LB patients often recall tick bites, fever is common, LA is mild and ACA is absent.

DNA Detected in Skin Lesions of Morphea and LSA

Borrelia burgdorferi infection is associated with erythema chronicum migrans (ECM) and lymphocytoma cutis early in the course of Lyme borreliosis and

<i>Borrelia burgdorfer</i><i>i</i> and Different Types of Morphea

Thirty patients with different clinical manifestations of morphea (circumscribed scleroderma) were investigated for serum antibodies against Borrelia burgdorferi determined by ELISA and Western blot analysis. Forty-six percent of the patients were seropositive. Western blots confirmed the ELISA results in 10 of 25 patients (40%), showing a reactivity pattern which can be seen in the course of Lyme borreliosis. In some cases the outcome after antibiotic treatment suggests a direct correlation between the further development of skin lesions and Borrelia infection. Because of these findings we suggest some morphea types to be possibly due to a B. burgdorferi infection.

Experimental Chronic Lyme Borreliosis in Lewis Rats

The course of Lyme borreliosis in LEW/N rats inoculated intraperitoneally as infants with 10(6) Borrelia burgdorferi was followed for 360 days. Spirochetes were detected in the blood through 30 days, in the brain through 60 days, and persisted in the spleen, liver, kidneys and articular tissue through 360 days. Acute exudative arthritis, tendonitis, and bursitis were evident in multiple joints by day 30. Arthritis regressed thereafter but capsular fibrosis and lymphoplasmacytic infiltrates persisted throughout the study. Several rats developed exacerbations of acute arthritis within days 180-360, a pattern similar to that encountered in human Lyme disease. Rats had a high prevalence of nonsuppurative myocarditis and vasculitis during days 90-360. Spirochetes were visualized by microscopy in joints and other tissues during the first month of infection, but were seen only sporadically thereafter. All rats seroconverted to B. burgdorferi by day 30. IgM titers persisted and IgG titers rose progressively through day 360. Immunoblots revealed IgM reactivity to a single 41 kDa protein until 360 days, when reactivity to a 60 kDa protein emerged. IgG reactivity occurred against progressively more proteins with time, indicating continued antigenic stimulation. Chronic and recurrent arthritic lesions and myocardial involvement suggest that the rat is a reliable model for further investigation.

Lyme disease--another transfusion risk?

Lyme disease (or Lyme borreliosis) is caused by a spirochetal bacteria, Borrelia burgdorferi. Increased recognition of the disease and increased exposure to the vector (ticks) capable of spreading B. burgdorferi from animal hosts have resulted in a rise in the number of cases of Lyme borreliosis reported in the United States. There are three stages of the clinical course of Lyme borreliosis; however, not all those infected will have typical manifestations of each stage, such as the arthritis of the third stage. Routine blood cultures will rarely document bacteremia and serologic testing is not yet reliable. Early treatment can prevent later stages of Lyme borreliosis. There is evidence that transmission of B. burgdorferi by blood transfusion is possible, but, to date, there has been no documentation of transfusion-associated Lyme borreliosis. Thus, no new recommendations for screening donors to identify possible carriers of B. burgdorferi are suggested at this time.