Clinical Manifestations Of Lyme Disease Research Articles

Whole genome sequencing of human Borrelia burgdorferi isolates reveals linked blocks of accessory genome elements located on plasmids and associated with human dissemination.

Lyme disease is the most common vector-borne disease in North America and Europe. The clinical manifestations of Lyme disease vary based on the genospecies of the infecting Borrelia burgdorferi spirochete, but the microbial genetic elements underlying these associations are not known. Here, we report the whole genome sequence (WGS) and analysis of 299 B. burgdorferi (Bb) isolates derived from patients in the Eastern and Midwestern US and Central Europe. We develop a WGS-based classification of Bb isolates, confirm and extend the findings of previous single- and multi-locus typing systems, define the plasmid profiles of human-infectious Bb isolates, annotate the core and strain-variable surface lipoproteome, and identify loci associated with disseminated infection. A core genome consisting of ~900 open reading frames and a core set of plasmids consisting of lp17, lp25, lp36, lp28-3, lp28-4, lp54, and cp26 are found in nearly all isolates. Strain-variable (accessory) plasmids and genes correlate strongly with phylogeny. Using genetic association study methods, we identify an accessory genome signature associated with dissemination in humans and define the individual plasmids and genes that make up this signature. Strains within the RST1/WGS A subgroup, particularly a subset marked by the OspC type A genotype, have increased rates of dissemination in humans. OspC type A strains possess a unique set of strongly linked genetic elements including the presence of lp56 and lp28-1 plasmids and a cluster of genes that may contribute to their enhanced virulence compared to other genotypes. These features of OspC type A strains reflect a broader paradigm across Bb isolates, in which near-clonal genotypes are defined by strain-specific clusters of linked genetic elements, particularly those encoding surface-exposed lipoproteins. These clusters of genes are maintained by strain-specific patterns of plasmid occupancy and are associated with the probability of invasive infection.

Comparative effectiveness and complications of intravenous ceftriaxone compared with oral doxycycline in Lyme meningitis in children: a multicentre prospective cohort study

IntroductionLyme disease is the most common vectorborne disease in the Northern hemisphere with more than 400 000 new cases in the USA annually. Lyme meningitis is an uncommon but potentially...

Repeated Tick Infestations Impair Borrelia burgdorferi Transmission in a Non-Human Primate Model of Tick Feeding.

The blacklegged tick, Ixodes scapularis, is the predominant vector of Borrelia burgdorferi, the agent of Lyme disease in the USA. Natural hosts of I. scapularis such as Peromyscus leucopus are repeatedly infested by these ticks without acquiring tick resistance. However, upon repeated tick infestations, non-natural hosts such as guinea pigs, mount a robust immune response against critical tick salivary antigens and acquire tick resistance able to thwart tick feeding and Borrelia burgdorferi transmission. The salivary targets of acquired tick resistance could serve as vaccine targets to prevent tick feeding and the tick transmission of human pathogens. Currently, there is no animal model able to demonstrate both tick resistance and diverse clinical manifestations of Lyme disease. Non-human primates serve as robust models of human Lyme disease. By evaluating the responses to repeated tick infestation, this animal model could accelerate our ability to define the tick salivary targets of acquired resistance that may serve as vaccines to prevent the tick transmission of human pathogens. Towards this goal, we assessed the development of acquired tick resistance in non-human primates upon repeated tick infestations. We report that following repeated tick infestations, non-human primates do not develop the hallmarks of acquired tick resistance observed in guinea pigs. However, repeated tick infestations elicit immune responses able to impair the tick transmission of B. burgdorferi. A mechanistic understanding of the protective immune responses will provide insights into B. burgdorferi-tick-host interactions and additionally contribute to anti-tick vaccine discovery.

Serological Analysis Identifies Consequential B Cell Epitopes on the Flexible Linker and C-Terminus of Decorin Binding Protein A (DbpA) from Borrelia burgdorferi.

ABSTRACTDecorin binding protein A (DbpA) is a surface adhesin of Borrelia burgdorferi, the causative agent of Lyme disease. While DbpA is one of the most immunogenic of B. burgdorferi’s nearly 100 lipoproteins, the B cell epitopes on DbpA recognized by humans following B. burgdorferi infection have not been fully elucidated. In this report we profiled ~270 B. burgdorferi-seropositive human serum samples for IgM and IgG reactivity with a tiled DbpA 18-mer peptide array derived from B. burgdorferi sensu stricto strains B31 and 297. Using enzyme-linked immunosorbent assays (ELISA) and multiplex immunoassays (MIA), we identified 12 DbpA-derived peptides whose antibody reactivities were significantly elevated (generally <10-fold) in B. burgdorferi-seropositive sera, compared to those measured in a healthy cohort. The most reactive peptide (>80-fold IgG, 10-fold IgM) corresponded to residues 64 to 81, which map to an exposed flexible loop between DbpA’s α-helix 1 and α-helix 2. This loop, whose sequence is identical between strains B31 and 297, overhangs DbpA’s substrate binding pocket. A second strongly reactive antibody target (>80-fold IgG, 3 to 5-fold IgM) mapped to DbpA’s C-terminus, a lysine rich tail implicated in attachment to glycosaminoglycans. We postulate that antibody responses against these two targets on DbpA could limit B.burgdorferi’s ability to attach to and colonize distal tissues during the early stages of infection.IMPORTANCE The bacterium, Borrelia burgdorferi, is the causative agent of Lyme disease, the most reported tick-borne illness in the United States. In humans, clinical manifestations of Lyme disease are complex and can persist for months, even in the face of a robust antibody response directed against numerous B. burgdorferi surface proteins, including decorin binding protein A (DbpA), which is involved in the early stages of infection. In this study we employed ~270 serum samples from B. burgdorferi-seropositive individuals to better understand human antibody reactivity to specific regions (called epitopes) of DbpA and how such antibodies may function in limiting B. burgdorferi dissemination and tissue colonization.

Lyme disease: modern approaches to treatment and prevention (based on international recommendations of 2020)

Lyme disease (LD) or tick-borne borreliosis affects thousands of people every year in different regions of the world, primarily in the United States and Europe. Given the great social and medical importance of this problem, an updated version of the clinical guidelines for the prevention, diagnosis and treatment of PD was published in November 2020 by a committee of experts of the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN) and the American College of Rheumatology (ACR). This article discusses the main issues of the use of antibacterial drugs in LD. The most commonly used medications are doxycycline, amoxicillin, cefuroxime axetil, and ceftriaxone. Patients with erythema migrans receive appropriate antibiotics for 7–14 days, depending on the medication used. In case of other clinical manifestations of LD, the duration of treatment is extended to 14–28 days. Antibiotic prophylaxis is carried out using a single oral dose of 200 mg doxycycline for adults and 4.4 mg/kg (with a maximum of 200 mg) for children. This treatment scheme is highly efficient, easy to administer, and has a relatively low risk of adverse events.

Comparison of Lyme Disease in the United States and Europe.

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.

Physical Therapist Recognition and Referral of Individuals With Suspected Lyme Disease.

The most commonly reported vector-borne and tick-borne disease in the United States is Lyme disease. Individuals with Lyme disease may present with a wide array of symptoms with resultant musculoskeletal, neurological, and cardiac manifestations that may cause them to seek physical therapist services. The symptoms may develop insidiously and with a variable presentation among individuals. Many persons with Lyme disease do not recall a tick bite or present with an erythema migrans rash, which is considered pathognomonic for the disease. Even if they do, they may fail to associate either with their symptoms, making the diagnosis elusive. It is important to diagnose individuals early in the disease process when antibiotic treatment is most likely to be successful. Physical therapists are in a unique position to recognize the possibility that individuals may have Lyme disease and refer them to another practitioner when appropriate. The purpose of this article is to (1) present an overview of the etiology, incidence, and clinical manifestations of Lyme disease, (2) review evaluation findings that should raise the index of suspicion for Lyme disease, (3) discuss the use of an empirically validated tool for differentiating those with Lyme disease from healthy individuals, (4) discuss the current state of diagnostic testing, and (5) review options for diagnosis and treatment available to individuals for whom referral is recommended.

Documentation of a false positive Lyme disease serologic test in a patient with untreated Babesia microti infection carries implications for accurately determining the frequency of Lyme disease coinfections

Although many infections may potentially cause a false positive Borrelia burgdorferi antibody test, particularly for IgM antibody, babesiosis is not regarded as an infection that does this. A patient with untreated babesiosis is described here who developed transient IgM seropositivity for antibodies to B. burgdorferi. Thus, the diagnosis of Lyme disease coinfection in patients with active babesiosis, as in patients with human granulocytic anaplasmosis, is more convincingly accomplished if an objective clinical manifestation of Lyme disease is present, such as an erythema migrans skin lesion.

LYME BORRELIOSIS: CLINICAL MANIFESTATIONS AND ADVANCES IN DIAGNOSIS AND CONTROL

Lyme disease or borreliosis is presumed one of the most significant vector-borne diseases globally. The disease is re-emerging in numerous parts of world. It has expanded dramatically in newer areas in recent decades. Lyme disease is caused by Borrelia burgdorferi yet additionally by other borrelial species, B. afzelii and B. garini which cause diverse clinical syndromes. Spatial distribution and clinical presentations differ depending on the causative species. Clinical manifestations of Lyme disease can be delineated in three stages. The first stage is presented in the form of erythema migrans at the site of tick bite. Early dispersed stage can lead to multiple lesions of erythema migrans, neuroborreliosis, lymphocytoma, arthritis or carditis. The manifestation at later stage shows acordermatitis chronica atrophicans, arthritis and neurological involvement. Diagnosis is challenging owing the several clinical presentations and could require multiple tests. The antibiotics that are currently under use, help in the clearance of bacteria from the affected host and stop further spread of the disease. Although several antibiotics are being used for Lyme disease, doxycycline is the widely used antimicrobial in early stage of the disease. Several attempts have been made to develop a vaccine against Lyme disease, however, none of them have been successfully marketed. The present review discusses clinical manifestations, and advances in diagnosis and control of Lyme disease.

Patients with Erythema Migrans: Characterizing the Impact of Initiation of Antibiotic Therapy Prior to Study Enrollment.

Erythema migrans is the most common clinical manifestation of Lyme disease, with concomitant subjective symptoms occurring in ∼65% of cases in the United States. We evaluated the impact of having been started on antibiotic treatment before study enrollment on 12 particular symptoms for 38 subjects with erythema migrans versus 52 untreated subjects. There were no significant differences in the frequency of having at least one symptom or in the symptom severity score on study entry. However, the frequency of having at least one symptom was significantly greater for those who had received <7 days of antibiotic treatment than for those who had been treated for ≥7 days (23/24 [95.8%] versus 8/14 [57.1%], P = 0.006). In addition, the percentage of subjects who were males was significantly lower among the group on treatment than among the untreated study subjects (13/38 [34.2%] versus 34/52 [65.4%], P = 0.005). In conclusion, based on these findings, combining untreated and treated groups of patients with erythema migrans for research study analyses may have limitations and, depending on the study objectives, might not be preferred. Additional studies are warranted to better understand the day-to-day impact of antibiotic treatment on the presence, type, and severity of symptoms in patients with early Lyme disease.

Local Population Structure and Seasonal Variability of Borrelia garinii Genotypes in Ixodes ricinus Ticks, Slovakia.

Lyme disease (LD) is the most common tick-borne human disease in Europe, and Borrelia garinii, which is associated with avian reservoirs, is one of the most genetically diverse and widespread human pathogenic genospecies from the B. burgdorferi sensu lato (s.l.) complex. The clinical manifestations of LD are known to vary between regions and depend on the genetic strain even within Borrelia genospecies. It is thus of importance to explore the genetic diversity of such pathogenic borreliae for the wide range of host and ecological contexts. In this study, multilocus sequence typing (MLST) was employed to investigate the local population structure of B. garinii in Ixodes ricinus ticks. The study took place in a natural wetland in Slovakia, temporally encompassing spring and autumn bird migration periods as well as the breeding period of resident birds. In total, we examined 369 and 255 ticks collected from 78 birds and local vegetation, respectively. B. burgdorferi s.l. was detected in 43.4% (160/369) of ticks recovered from birds and in 26.3% (67/255) of questing ticks, respectively. Considering the ticks from bird hosts, the highest prevalence was found for single infections with B. garinii (22.5%). Infection intensity of B. garinii in bird-feeding ticks was significantly higher than that in questing ticks. We identified ten B. garinii sequence types (STs) occurring exclusively in bird-feeding ticks, two STs occurring exclusively in questing ticks, and one ST (ST 244) occurring in both ticks from birds and questing ticks. Four B. garinii STs were detected for the first time herein. With the exception of ST 93, we detected different STs in spring and summer for bird-feeding ticks. Our results are consistent with previous studies of the low geographic structuring of B. garinii genotypes. However, our study reveals some consistency in local ST occurrence and a geographic signal for one of the clonal complexes.

Prospective Evaluation of the Frequency and Severity of Symptoms in Lyme Disease Patients With Erythema Migrans Compared With Matched Controls at Baseline, 6 Months, and 12 Months.

Erythema migrans is the most common clinical manifestation of Lyme disease. Despite antibiotic therapy, typically at least 10% of adult patients with erythema migrans experience persistence of at least 1 subjective symptom for ≥6 months (posttreatment Lyme disease symptoms [PTLDS]). This study was designed to determine whether the frequency and severity (based on a visual analogue scale) of 12 particular symptoms in patients with erythema migrans (n = 52) differed from matched control subjects (n = 104) followed prospectively for 12 months. At baseline, patients with Lyme disease were more likely than controls to have at least 1 symptom (P = .006). Among symptomatic subjects, Lyme disease patients had a higher mean number of symptoms (P < .001) and a higher mean total symptom severity score (P < .001). At both 6 and 12 months, however, there were no significant differences for these variables and no significant differences in the frequency or severity of any of the 12 individual symptoms assessed. However, 10 patients were clinically assessed as having possible PTLDS. Patients with erythema migrans were more likely than matched control subjects to be symptomatic at baseline with a greater symptom severity score, but this was not found at ≥6 months. Use of symptom survey data alone, however, was less likely to identify patients with possible PTLDS compared with individual clinical assessments. Because it is very challenging to be certain that the presence of long-term symptoms in a particular patient is correctly attributable to having had Lyme disease, an objective biomarker would be highly desirable.

Laboratory diagnosis and research progress of Lyme disease

Lyme disease is a natural zoonotic disease transmitted by the bite of tick. The clinical manifestations of Lyme disease are complex and varied, and it is easy to be misdiagnosed. Based on the review of the background knowledge of Lyme disease, this paper reviews the current situation of its diagnosis and the research progress of detection. Key words: Borrelia borrelia; Serologic testing; Polymerase chain reaction; Immuno PCR; Metabonomics

Infections Caused by Spirochetes: Syphilis, Lyme Disease, Leptospirosis

Syphilis is caused by the spirochete Treponema pallidum. It is classified as primary, secondary, tertiary, and latent infection. If left untreated, syphilis can cause devastating injury to the fetus. The drug of choice for treatment of syphilis in pregnancy is penicillin. Lyme disease is caused by Borrelia burgdorferi and is transmitted by the Ixodes scapularis tick. The principal clinical manifestation of Lyme disease is erythema migrans, but patients may also develop arthritis and cardiac and neurologic abnormalities. Congenital Lyme disease has not been reported. The drug of choice for treatment of Lyme disease in pregnancy is amoxicillin. Leptospirosis is usually acquired from direct contact with urine of infected animals or through contaminated water, soil, or vegetation. Pregnant women with mild disease should be treated with oral amoxicillin. Patients with severe disease should be hospitalized and treated with intravenous penicillin or ampicillin. This review contains 5 figures, 5 tables, and 19 references. Key Words: clinical infection, congenital syphilis, latent infection, leptospirosis, Lyme disease, syphilis

Infections Caused by Spirochetes: Syphilis, Lyme Disease, Leptospirosis

Syphilis is caused by the spirochete Treponema pallidum. It is classified as primary, secondary, tertiary, and latent infection. If left untreated, syphilis can cause devastating injury to the fetus. The drug of choice for treatment of syphilis in pregnancy is penicillin. Lyme disease is caused by Borrelia burgdorferi and is transmitted by the Ixodes scapularis tick. The principal clinical manifestation of Lyme disease is erythema migrans, but patients may also develop arthritis and cardiac and neurologic abnormalities. Congenital Lyme disease has not been reported. The drug of choice for treatment of Lyme disease in pregnancy is amoxicillin. Leptospirosis is usually acquired from direct contact with urine of infected animals or through contaminated water, soil, or vegetation. Pregnant women with mild disease should be treated with oral amoxicillin. Patients with severe disease should be hospitalized and treated with intravenous penicillin or ampicillin. This review contains 5 figures, 5 tables, and 19 references. Key Words: clinical infection, congenital syphilis, latent infection, leptospirosis, Lyme disease, syphilis

Ticks and bacterial tick-borne pathogens in Piemonte region, Northwest Italy.

A molecular screening for tick-borne pathogens was carried out in engorged and in questing ticks collected in Verbano Cusio Ossola county, Piemonte region, Italy. Engorged ticks were removed from wild and domestic animal hosts. The most abundant and common tick species in the area was Ixodes ricinus (192 adults, 907 nymphs). Few individuals of Ixodes hexagonus (15) and Rhipicephalus sanguineus (7) were found among the ticks removed from domestic animals (46 examined ticks). The presence of Rickettsia spp., Borrelia burgdorferi sensu latu, Francisella tularensis and Coxiella burnetii was evaluated by PCR and sequencing in 392 individuals of I. ricinus (adult and nymphal stages) and 22 individuals of the two other tick species. Five Borrelia species (i.e. B. burgdorferi sensu stricto, B. garinii, B. afzelii, B. valaisiana and B. lusitaniae), proved or suspected to cause clinical manifestations of Lyme disease in humans, showed 10.5 and 2.2% combined prevalence in questing and engorged I. ricinus, respectively. In addition, two species of rickettsiae (R. helvetica and R. monacensis) were identified and reported with 14.5 and 24.8% overall prevalence in questing and in engorged ticks. The prevalence of F. tularensis in the ticks collected on two wild ungulate species (Capreolus capreolus and Cervus elaphus) was 5.7%. This work provided further data and broadened our knowledge on bacterial pathogens present in ticks in Northwest Italy.

Lyme Meningoradiculitis: Case Reports and Literature Review

Abstract The clinical manifestations of Lyme disease are protean. The meningoradiculitis is a common and well-recognized complication of neuroborreliosis but can be easily misdiagnosed without a high degree of clinical suspicion, mainly if the tick bite is not present in the medical history. We report two cases of Lyme meningoradiculitis with excellent outcome after appropriate antibiotic therapy. In an endemic area in case of neurological manifestations suggestive for neuroborreliosis the serological testing for B. burgdorferi in serum and cerebrospinal fluid is imperative for the correct diagnosis.

Texas Occurrence of Lyme Disease and Its Neurological Manifestations.

Today, Lyme disease is the most commonly reported tick-borne disease in the United States and Europe. The culprits behind Lyme disease are the Borrelia species of bacteria. In the USA, Borrelia burgdorferi causes the majority of cases, while in Europe and Asia Borrelia afzelii and Borrelia garinii carry the greatest burden of disease. The clinical manifestations of Lyme disease have been identified as early localized, early disseminated, and late chronic. The neurological effects of Lyme disease include both peripheral and central nervous systems involvement, including focal nerve abnormalities, cranial neuropathies, painful radiculoneuritis, meningitis, and/or toxic metabolic encephalopathy, known as Lyme encephalopathy. Given the geographic predominance of Lyme disease in the Northeast and Midwest of the USA, no major studies have been conducted regarding Southern states. Between 2005 and 2014, the Center for Disease Control has reported 582 confirmed cases of Lyme disease in Texas. Because of the potential for increased incidence and prevalence in Texas, it has become essential for research and clinical efforts to be diverted to the region. The Texas A&M College of Veterinary Medicine and Biomedical Sciences Lyme Lab has been investigating the ecology of Lyme disease in Texas and developing a pan-specific serological test for Lyme diagnosis. This report aimed to exposure materials and raise awareness of Lyme disease to healthcare providers.

Canine Filamentous Dermatitis Associated with Borrelia Infection

Canine Filamentous Dermatitis Associated with Borrelia Infection Background: Although canine clinical manifestations of Lyme disease vary widely, cutaneous manifestations are not well documented in dogs. In contrast, a variety of cutaneous manifestations are reported in human Lyme disease caused by the spirochete Borrelia burgdorferi. A recently recognized dermopathy associated with tickborne illness known as Morgellons disease is characterized by brightly-colored filamentous inclusions and projections detected in ulcerative lesions and under unbroken skin. Recent studies have demonstrated that the dermal filaments are collagen and keratin biofibers produced by epithelial cells in response to spirochetal infection. We now describe a similar filamentous dermatitis in canine Lyme disease. Methods and Results: Nine dogs were found to have cutaneous ulcerative lesions containing embedded or projecting dermal filaments. Spirochetes characterized as Borrelia spp. were detected in skin tissue by culture, histology, immunohistochemistry, polymerase chain reaction (PCR) and gene sequencing performed at five independent laboratories. Borrelia DNA was detected either directly from skin specimens or from cultures inoculated with skin specimens taken from the nine canine study subjects. Amplicon sequences from two canine samples matched gene sequences for Borrelia burgdorferi sensu stricto. PCR amplification failed to detect spirochetes in dermatological specimens from four healthy asymptomatic dogs. Conclusions: Our study provides evidence that a filamentous dermatitis analogous to Morgellons disease may be a manifestation of Lyme disease in domestic dogs.

Borrelia burgdorferi (Lyme disease).

1. Eugene D. Shapiro, MD* 1. *Departments of Pediatrics, Epidemiology of Microbial Diseases, and Investigative Medicine, Yale University Schools of Medicine and of Public Health and Graduate School of Arts and Sciences, New Haven, CT. * Abbreviations: DEET: : N,N-diethyl-meta-toluamide ELISA: : enzyme-linked immunosorbent assay EM: : erythema migrans STARI: : southern tick–associated rash illness 1. Although Lyme disease, caused by Borrelia burgdorferi , is the most common vector-borne disease in the United States, there is considerable misunderstanding about the clinical manifestations and consequences of this infection. (1)(2) 2. When to perform diagnostic tests and how to interpret the results for antibodies against B burgdorferi are common sources of confusion for physicians and patients. (3)(4)(5) 3. Misinformation about chronic Lyme disease on the Internet and in popular media has led to publicity and anxiety about Lyme disease that is out of proportion to the actual morbidity that it causes. (6)(7)(8) After completing this article, readers should be able to: 1. Understand the ecology and the epidemiology of Lyme disease. 2. Know when to order and how to interpret serologic tests for the diagnosis of Lyme disease. 3. Understand the clinical manifestations of Lyme disease and appropriate treatment Lyme disease is the most common vector-borne disease in the United States. In the United States, the spirochete Borrelia burgdorferi sensu stricto (hereafter termed B burgdorferi ) is the only pathogen that causes Lyme disease. However, in Europe and Asia, Borrelia afzelii , Borrelia garinii, and other related species, in addition to B burgdorferi , cause Lyme disease. In the United States, these bacteria are transmitted by hard-bodied ticks, including Ixodes scapularis (the black-legged tick, commonly called a deer …