Molecular Subtyping of Borrelia burgdorferi sensu lato Isolates from Five Patients with Solitary Lymphocytoma

Solitary lymphocytoma is a rare cutaneous manifestation of Lyme borreliosis that has been reported almost exclusively from Europe. This suggests that its etiologic agent may be absent or extremely rare on the North American continent. All three species of B. burgdorferi sensu lato known to be associated with human Lyme borreliosis (B. burgdorferi sensu stricto, B. garinii and B. afzelii) have been isolated in Europe, whereas only B. burgdorferi sensu stricto has been found in North America. This suggests that either B. garinii or B. afzelii might be the etiologic agent of borrelial lymphocytoma. To investigate this hypothesis we characterized five strains of B. burgdorferi sensu lato isolated from lymphocytoma lesions of patients residing in Slovenia. The methods used included: large restriction fragment pattern analysis of restriction enzyme MlnI-digested genomic DNA, plasmid profiling, protein profiling, ribotyping using 5S, 16S and 23S rDNA probes and polymerase chain reaction amplification of the rrf (5S)-rrl (23S) inter-genic spacer region. Molecular subtyping showed that four of the five isolates belonged to the species B. afzelii; however, this species is the predominant patient isolate in Slovenia and therefore, may not represent a preferential association with lymphocytoma. The fifth isolate appeared to be most closely related to the DN127 genomic group of organisms. Further characterization of the isolate revealed that it possessed a unique molecular “fingerprint.” The results not only show that borrelial lymphocytoma can be caused by B. afzelii but also demonstrate an association with another genomic group of B. burgdoiferi sensu lato that is present in North America as well

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 daysp = 0.0153), smaller diameter of erythema migrans (10.5 vs. 15.5 cmp = 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

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

Course and Outcome of Erythema Migrans in Pregnant Women

Information on Lyme borreliosis (LB) during pregnancy is limited. In the present study, the course and outcome of erythema migrans (EM) in 304 pregnant women, diagnosed in the period 1990–2015, was assessed and compared with that in age-matched non-pregnant women. The frequency of unfavorable outcome of pregnancies was also evaluated. The pregnant women reported constitutional symptoms less frequently than the non-pregnant women (22.4% vs. 37.2%, p < 0.001). Pregnant women diagnosed with EM later during pregnancy had a lower probability of reporting constitutional symptoms (odds ratio = 0.97 for 1-week difference in gestation week at diagnosis of EM, 95% CI: 0.94–0.99, p = 0.02). The outcome of pregnancy was unfavorable in 42/304 (13.8%) patients: preterm birth in 22/42 (52.4%), fetal/perinatal death in 10/42 (23.8%), and/or anomalies in 15/42 (35.7%). Several patients had potential explanation(s) for the unfavorable outcome. In conclusion, the course of early LB during pregnancy is milder than in age-matched non-pregnant women. The outcome of pregnancy with the treatment approach used in the present study (i.v. ceftriaxone 2 g once daily for 14 days) is favorable

Course and outcome of erythema migrans in pregnant women

Information on Lyme borreliosis (LB) during pregnancy is limited. In the present study, the course and outcome of erythema migrans (EM) in 304 pregnant women, diagnosed in the period 1990-2015, was assessed and compared with that in age-matched non-pregnant women. The frequency of unfavorable outcome of pregnancies was also evaluated. The pregnant women reported constitutional symptoms less frequently than the non-pregnant women (22.4% vs. 37.2%, p < 0.001). Pregnant women diagnosed with EM later during pregnancy had a lower probability of reporting constitutional symptoms (odds ratio = 0.97 for 1-week difference in gestation week at diagnosis of EM, 95% CI: 0.94-0.99, p = 0.02). The outcome of pregnancy was unfavorable in 42/304 (13.8%) patients: preterm birth in 22/42 (52.4%), fetal/perinatal death in 10/42 (23.8%), and/or anomalies in 15/42 (35.7%). Several patients had potential explanation(s) for the unfavorable outcome. In conclusion, the course of early LB during pregnancy is milder than in age-matched non-pregnant women. The outcome of pregnancy with the treatment approach used in the present study (i.v. ceftriaxone 2 g once daily for 14 days) is favorable

Comparison of Borrelia burgdorferi Sensu Lato Strains Isolated from Specimens Obtained Simultaneously from Two Different Sites of Infection in Individual Patients

The aim of the present study was to analyze and compare Borrelia strains isolated from two different specimens obtained simultaneously from individual patients with Lyme borreliosis. Fifty such patients and 50 corresponding pairs of Borrelia isolates (100 low-propagated strains) were subjected to genotypic and phenotypic analysis, including pulsed-field gel electrophoresis for species identification and plasmid profile determination and protein profile electrophoresis for the assessment of the presence and molecular masses of separated proteins. The strains were isolated from two distinct skin lesions (12 patients), skin and blood (28 patients), skin and cerebrospinal fluid (8 patients), and blood and cerebrospinal fluid (2 patients). Out of 100 isolates, 63 were typed as B. afzelii and 37 as B. garinii. From each individual specimen only a single Borrelia species was cultured. Comparison of 50 Borrelia strain pairs isolated from two different specimens of an individual patient revealed that 12/50 (24%) patients were simultaneously infected with two different Borrelia strains; in 3/50 (6%) patients strains differed at the species level, in 4 out of the remaining 47 (9%) patients a strain difference in plasmid profile was established, while 5 out of the remaining 43 (11%) patient strain pairs differed in regard to the protein profiles of the two concurrently isolated strains. The results of the present study indicate that human patients with Lyme borreliosis may simultaneously harbor different B. burgdorferi sensu lato strains

Correlation of Culture Positivity, PCR Positivity, and Burden of Borrelia burgdorferi Sensu Lato in Skin Samples of Erythema Migrans Patients with Clinical Findings.

Limited data are available regarding the relationship of Borrelia burden in skin of patients with erythema migrans (EM) and the disease course and post-treatment outcome.We studied 121 adult patients with EM in whom skin biopsy specimens were cultured and analyzed by quantitative PCR for the presence of Borreliae. Evaluation of clinical and microbiological findings were conducted at the baseline visit, and 14 days, 2, 6, and 12 months after treatment with either amoxicillin or cefuroxime axetil.In 94/121 (77.7%) patients Borrelia was detected in skin samples by PCR testing and 65/118 (55.1%) patients had positive skin culture result (96.8% B. afzelii, 3.2% B. garinii). Borrelia culture and PCR results correlated significantly with the presence of central clearing and EM size, while Borrelia burden correlated significantly with central clearing, EM size, and presence of newly developed or worsened symptoms since EM onset, with no other known medical explanation (new or increased symptoms, NOIS). In addition, the logistic regression model for repeated measurements adjusted for time from inclusion, indicated higher Borrelia burden was a risk factor for incomplete response (defined as NOIS and/or persistence of EM beyond 14 days and/or occurrence of new objective signs of Lyme borreliosis). The estimated association between PCR positivity and unfavorable outcome was large but not statistically significant, while no corresponding relationship was observed for culture positivity.Higher Borrelia burden in EM skin samples was associated with more frequent central clearing and larger EM lesions at presentation, and with a higher chance of incomplete response