Borrelia burgdorferi is the causative agent of Lyme disease and is transmitted to vertebrate hosts by Ixodes spp. ticks. The spirochaete relies heavily on its arthropod host for basic metabolic ...functions and has developed complex interactions with ticks to successfully colonize, persist and, at the optimal time, exit the tick. For example, proteins shield spirochaetes from immune factors in the bloodmeal and facilitate the transition between vertebrate and arthropod environments. On infection, B. burgdorferi induces selected tick proteins that modulate the vector gut microbiota towards an environment that favours colonization by the spirochaete. Additionally, the recent sequencing of the Ixodes scapularis genome and characterization of tick immune defence pathways, such as the JAK-STAT, immune deficiency and cross-species interferon-γ pathways, have advanced our understanding of factors that are important for B. burgdorferi persistence in the tick. In this Review, we summarize interactions between B. burgdorferi and I. scapularis during infection, as well as interactions with tick gut and salivary gland proteins important for establishing infection and transmission to the vertebrate host.
Background
We previously demonstrated a possible therapeutic benefit of VFEM (variable frequency electromagnetic energy) technology for the treatment of Post Treatment Lyme Disease Syndrome (PTLDS) ...or Chronic Lyme Disease (CLD). As a result, we prospectively enrolled 10 patients, all having significant debility, to determine to what extent we could improve their quality of life. Eight patients completed the 10 treatments.
Results
All eight patients had a significant improvement in quality of life within a 4‐month time frame.
Conclusion
VFEM is a stand‐alone modality that appears to demonstrate a significant improvement in quality of life in PTLDS or CLD with little or no risk or side effects of treatment.
There is much confusion and misinformation about the diagnosis of Lyme disease, as well as its treatment. This review explains why one cannot make a correct diagnosis of Lyme disease based on ...symptoms alone. It also provides evidence to support the validity of two-tier testing for the laboratory diagnosis of Lyme disease. The public health consequences of failing to consider these issues are discussed.
One prior study suggests that traumatic events before Lyme disease play an important role in symptom severity. We examined this hypothesis among 60 individuals with persistent symptoms after Lyme ...disease using validated measures of trauma history, mental and physical symptoms, and functional status. Analysis of variance with Tukey-Kramer multiple comparisons test revealed that a greater number of traumatic events were significantly associated with greater symptom severity on the scales of mood (stress, depression, and anxiety), cognition, multisystem symptom burden, and functional status (mental and physical), but not on measures of pain and fatigue. The effect sizes-meaningful but not large (0.17-0.29)-were mostly produced by comparison with individuals reporting multiple prior traumatic events, representing half of the posttreatment Lyme disease syndrome (PTLDS) group. In conclusion, although PTLDS may be exacerbated by past trauma, trauma plays a role in only a subgroup of PTLDS. Whether addressing prior trauma can improve outcomes in this subgroup requires study.
The complement system serves as the first line of defense against invading pathogens by promoting opsonophagocytosis and bacteriolysis. Antibody-dependent activation of complement occurs through the ...classical pathway and relies on the activity of initiating complement proteases of the C1 complex, C1r and C1s. The causative agent of Lyme disease, Borrelia burgdorferi, expresses two paralogous outer surface lipoproteins of the OspEF-related protein family, ElpB and ElpQ, that act as specific inhibitors of classical pathway activation. We have previously shown that ElpB and ElpQ bind directly to C1r and C1s with high affinity and specifically inhibit C2 and C4 cleavage by C1s. To further understand how these novel protease inhibitors function, we carried out a series of hydrogen-deuterium exchange mass spectrometry (HDX-MS) experiments using ElpQ and full-length activated C1s as a model of Elp–protease interaction. Comparison of HDX-MS profiles between unbound ElpQ and the ElpQ/C1s complex revealed a putative C1s-binding site on ElpQ. HDX-MS–guided, site-directed ElpQ mutants were generated and tested for direct binding to C1r and C1s using surface plasmon resonance. Several residues within the C-terminal region of ElpQ were identified as important for protease binding, including a single conserved tyrosine residue that was required for ElpQ- and ElpB-mediated complement inhibition. Collectively, our study identifies key molecular determinants for classical pathway protease recognition by Elp proteins. This investigation improves our understanding of the unique complement inhibitory mechanism employed by Elp proteins which serve as part of a sophisticated complement evasion system present in Lyme disease spirochetes.
The persistence of symptoms in Lyme disease patients following antibiotic therapy, and their causes, continue to be a matter of intense controversy. The studies presented here explore antibiotic ...efficacy using nonhuman primates. Rhesus macaques were infected with B. burgdorferi and a portion received aggressive antibiotic therapy 4-6 months later. Multiple methods were utilized for detection of residual organisms, including the feeding of lab-reared ticks on monkeys (xenodiagnosis), culture, immunofluorescence and PCR. Antibody responses to the B. burgdorferi-specific C6 diagnostic peptide were measured longitudinally and declined in all treated animals. B. burgdorferi antigen, DNA and RNA were detected in the tissues of treated animals. Finally, small numbers of intact spirochetes were recovered by xenodiagnosis from treated monkeys. These results demonstrate that B. burgdorferi can withstand antibiotic treatment, administered post-dissemination, in a primate host. Though B. burgdorferi is not known to possess resistance mechanisms and is susceptible to the standard antibiotics (doxycycline, ceftriaxone) in vitro, it appears to become tolerant post-dissemination in the primate host. This finding raises important questions about the pathogenicity of antibiotic-tolerant persisters and whether or not they can contribute to symptoms post-treatment.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Lyme disease, or Lyme borreliosis, is the most common tickborne disease in the United States and Europe. In both locations, Ixodes species ticks transmit the Borrelia burgdorferi sensu lato bacteria ...species responsible for causing the infection. The diversity of Borrelia species that cause human infection is greater in Europe; the 2 B. burgdorferi s.l. species collectively responsible for most infections in Europe, B. afzelii and B. garinii, are not found in the United States, where most infections are caused by B. burgdorferi sensu stricto. Strain differences seem to explain some of the variation in the clinical manifestations of Lyme disease, which are both minor and substantive, between the United States and Europe. Future studies should attempt to delineate the specific virulence factors of the different species of B. burgdorferi s.l. responsible for these variations in clinical features.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This article reviews events that led to the withdrawal of the only vaccine to prevent Lyme disease licensed in the United States. The primary issues that led to the vaccine's withdrawal appear to be ...a combination of vaccine safety concerns, sparked by a molecular mimicry hypothesis that suggested that the vaccine antigen, outer surface protein A, serves as an autoantigen and hence was arthritogenic; concerns raised by anti-vaccine groups regarding vaccine safety; vaccine cost; a difficult vaccination schedule and the potential need for boosters; class action lawsuits; uncertainty regarding risk of disease; and low public demand. This article reviews lessons learned from these events and proposes that future candidate Lyme disease vaccines are unlikely to be developed, tested, and used within the United States in the near future, thus leaving at-risk populations unprotected.
Background. Lyme disease patients with erythema migrans are said to have post-treatment Lyme disease symptoms (PTLDS) if there is persistence of subjective symptoms for at least 6 months following ...antibiotic treatment and resolution of the skin lesion. The purpose of this study was to characterize PTLDS in patients with culture-confirmed early Lyme disease followed for > 10 years. Methods. Adult patients with erythema migrans with a positive skin or blood culture for Borrelia burgdorferi were enrolled in a prospective study beginning in 1991 and followed up at 6 months and annually thereafter to determine the long-term outcome of this infection. The genotype of the infecting strain of B. burgdorferi was evaluated in subjects with PTLDS. Results. One hundred twenty-eight subjects with culture-confirmed early Lyme disease, of whom 55% were male, were followed for a mean ± SD of 14.98 ± 2.71 years (median = 15 years; range = 11–20 years). Fourteen (10.9%) were regarded as having possible PTLDS, but only 6 (4.7%) had PTLDS documented at their last study visit. Nine (64.3%) had only a single symptom. None of the 6 with PTLDS at their last visit was considered to be functionally impaired by the symptom(s). PTLDS was not associated with a particular genotype of B. burgdorferi. Conclusions. PTLDS may persist for > 10 years in some patients with culture-confirmed early Lyme disease. Such long-standing symptoms were not associated with functional impairment or a particular strain of B. burgdorferi.
Lyme Disease Steere, Allen C
The New England journal of medicine,
07/2001, Letnik:
345, Številka:
2
Journal Article
Recenzirano
Since its original description nearly 25 years ago,
1
Lyme disease has become recognized as an important infectious disease in the United States. The infection, which is caused by the tick-borne ...spirochete
Borrelia burgdorferi,
is now endemic in more than 15 states and has been responsible for focal outbreaks in some eastern coastal areas. Lyme borreliosis is also endemic in Europe and Asia, where certain aspects of the disease (erythema migrans, meningopolyneuritis, and acrodermatitis chronica atrophicans) were described in the early and mid-20th century. These syndromes were linked conclusively in 1982 and 1983 with the recovery of a previously unrecognized spirochete . . .
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