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Non-specific symptoms in later stages of Lyme disease (LD) may mimic a variety of autoimmune, viral, or complex diseases. Patients lacking erythema migrans or who test negative under CDC guidelines, but suspect LD may search online symptoms in vein. As a result, patients with lingering and undiagnosed symptoms turn to alternative lab tests. This study addresses patient's perceived illness in relation to CDC surveillance data. Extending the literature beyond basic searches for symptoms or disease terms, this study examines spatiotemporal dynamics among symptom, disease, and unconventional lab test searches on Google Trends, in compared with CDC confirmed cases of LD. The search terms used for the Google Trends analysis between 2011 and 2015 include: (1) "lyme" and "lyme disease" for disease, (2) "tick bite," "bone pain," "stiff neck," "circular rash," and "brain fog" for symptoms, and (3) "IGENEX" for the alternative lab test. Spatial and temporal analyses illustrate noticeable similar patterns between the search frequency and the actual LD incidence. Beyond basic searches for symptoms or disease terms, we demonstrate the improved utility of Google Trends analysis in discovering spatial and temporal patterns of perceived LD and comparing with the reported LD cases. The public health and medical communities benefit from this research through improved knowledge of undiagnosed patients who are searching for alternative labs to explain lingering symptoms. This study validates the need for further research into Google Trends data and surveillance protocols of diseases characterized by non-specific symptoms, prompting patients to "self-diagnose."

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.

Lyme borreliosis is the most common zoonosis in Germany with an incidence of up to 138/100 000. More than 90 % of all cases show dermatological manifestations. Early manifestations are erythema migrans, multiple erythemata migrantia, and (less frequently) borrelial lymphocytoma. A typical late manifestation is acrodermatitis chronica atrophicans. Lyme neuroborreliosis is much less common with an incidence of about 0.8/100 000 inhabitants in Germany. Bannwarth's syndrome (painful radiculoneuritis) is the most common manifestation of Lyme neuroborreliosis in adults followed by meningitis. International case definitions exist regarding the likelihood of Lyme neuroborreliosis on the basis of diagnostic test results. A CSF analysis should be performed in patients with suspected Lyme neuroborreliosis. The first line treatment for dermatological manifestations of Lyme borreliosis is doxycycline, in children and pregnant women amoxicillin. Doxycycline and beta-lactam antibiotics show similar efficacy regarding neurological symptoms and adverse effects for treatment of neurological manifestations. Treatment duration for early manifestations is 10 to 14 days, in Lyme neuroborreliosis it should not exceed 21 days. All manifestations, also Lyme neuroborreliosis, usually show a favourable prognosis after antibiotic treatment. Antibiotic treatment does not show any efficacy in patients with unspecific symptoms and concurrent positive anti-borrelial serology.

The majority of suggested mechanisms of

Background Lyme neuroborreliosis (LNB) is often treated with intravenous ceftriaxone even if doxycycline is suggested to be noninferior to ceftriaxone. We evaluated the efficacy of oral doxycycline in comparison to ceftriaxone in the treatment of LNB. Methods Patients with neurological symptoms suggestive of LNB without other obvious reasons were recruited. The inclusion criteria were (1) production of Borrelia burgdorferi–specific antibodies in cerebrospinal fluid (CSF) or serum; (2) B. burgdorferi DNA in the CSF; or (3) an erythema migrans during the past 3 months. Participants were randomized in a 1:1 ratio to receive either oral doxycycline 100 mg twice daily for 4 weeks, or intravenous ceftriaxone 2 g daily for 3 weeks. The participants described their subjective condition with a visual analogue scale (VAS) from 0 to 10 (0 = normal; 10 = worst) before the treatment, and 4 and 12 months after the treatment. The primary outcome was the change in the VAS score at 12 months. Results Between 14 September 2012 and 28 December 2017, 210 adults with suspected LNB were assigned to receive doxycycline (n = 104) or ceftriaxone (n = 106). The per-protocol analysis comprised 82 patients with doxycycline and 84 patients with ceftriaxone. The mean change in the VAS score was −3.9 in the doxycycline group and −3.8 in the ceftriaxone group (mean difference, 0.17 [95% confidence interval, −.59 to .92], which is within the prespecified equivalence margins of −1 to 1 units). Participants in both groups improved equally. Conclusions Oral doxycycline is equally effective as intravenous ceftriaxone in the treatment of LNB. Clinical Trials Registration NCT01635530 and EudraCT 2012-000313-37.

The incidence of Lyme borreliosis remains a matter of debate, but it can be estimated using the incidence of erythema migrans (EM), which is pathognomonic of the first phase. The aim of this prospective pilot study was to assess the feasibility of the on-line declaration of EM in rural areas where the incidence of Lyme borreliosis was previously estimated at 85 per 100,000 inhabitants per year. The study was limited to a rural area (Les Combrailles, Auvergne) of approximately 52,800 inhabitants and was preceded by an information campaign for the inhabitants and the healthcare professionals. Patients who sent a photo of the suspected EM by email or MMS message between April 2017 and April 2018 and who accepted to answer a questionnaire were included in the study. Two physicians then evaluated the quality of the photographs and the probability of EM. In parallel, the number of EM seen by physicians and pharmacists in the area over the given period was recorded. Out of the 113 emails and MMS messages received, 73 people were outside of the trial area or period and 9 did not complete the questionnaire. The photos of the remaining 31 people were analysed. The median age was 51.5 years old ([38–58] IQR) and 18 (58%) were women. Seven people (25%) stated that they did not have a smartphone and in 9 cases (29%) the photo was sent by a third party. The quality of the photos was considered very good in 22 (71%) cases, good in 7 (23%) cases, and average in 2 (6%) cases. The probability of EM was determined to be strong or possible in 12 (38%) cases, i.e. an estimated incidence of 22.7 per 100,000 inhabitants. Over the study period, 40 physicians and 20 pharmacists were contacted on a monthly basis. A median of 5 physicians [3;7] and 4 pharmacists [3 ;7] answered each month for a total of 18 and 36 declared EM respectively. The EM (strong probability/possible) collected by on-line declaration and those declared by healthcare professionals were all sent between April and October 2017. The total time spent on the information campaign and collection has been estimated at 265 h (divided between 10 people) for an overall cost of 10,669 Euros. The incidence of EM recorded by on-line self-declaration in our study seems to be lower than in previous studies, the under-reporting was probably linked to the low use of new technologies in the rural areas. Increasing the human resources and finances appears difficult to achieve in practice over a longer time period but the development of an application for the automatic recognition of EM could be one method for a more exhaustive collection in the long term and at lower cost.

Contains fulltext : 220683.pdf (Publisher’s version ) (Closed access) Lyme borreliosis is the most common vectorborne disease in the northern hemisphere. It usually begins with erythema migrans; early disseminated infection particularly causes multiple erythema migrans or neurologic disease, and late manifestations predominantly include arthritis in North America, and acrodermatitis chronica atrophicans (ACA) in Europe. Diagnosis of Lyme borreliosis is based on characteristic clinical signs and symptoms, complemented by serological confirmation of infection once an antibody response has been mounted. Manifestations usually respond to appropriate antibiotic regimens, but the disease can be followed by sequelae, such as immune arthritis or residual damage to affected tissues. A subset of individuals reports persistent symptoms, including fatigue, pain, arthralgia, and neurocognitive symptoms, which in some people are severe enough to fulfil the criteria for post-treatment Lyme disease syndrome. The reported prevalence of such persistent symptoms following antimicrobial treatment varies considerably, and its pathophysiology is unclear. Persistent active infection in humans has not been identified as a cause of this syndrome, and randomized treatment trials have invariably failed to show any benefit of prolonged antibiotic treatment. For prevention of Lyme borreliosis, post-exposure prophylaxis may be indicated in specific cases, and novel vaccine strategies are under development.

Whether infection with Borrelia burgdorferi sensu lato (sl) can cause nonspecific symptoms is a matter of controversy. We investigated whether individuals infected with B. burgdorferi sl develop unspecific symptoms more frequently than non-infected controls. Eighty-nine persons having presented with B. burgdorferi sl infection between 2015 and 2019 were asked to participate. The infection was defined as erythema migrans diagnosed either in the course of a previous study, during medical visits in the outpatient department, or as seroconversion in asymptomatic subjects. The control group consisted of 85 seronegative individuals without erythema migrans in the past. About two and a half years later, participants were asked to fill out a questionnaire with a list of nonspecific symptoms. The data of 37 persons with previous Borrelia infection and 49 uninfected controls were available for analysis. Muscle pain was significantly (P = 0.040) more frequent in the control group. Fatigue occurred more often in the infected group, but this was not statistically significant (P = 0.109). Likewise, the distribution of other symptoms did not differ considerably. The analysis revealed no difference in the frequency of symptoms of persons who had EM or asymptomatic Borrelia infection 2 years prior assessment in comparison to persons without Borrelia infection.

This case report describes a three-year-old boy with delayed development of language, who developed erythema migrans. Soon after peroral antibiotics was initiated, he also had loss of motoric function, and he developed ataxia. Neuroborreliosis was diagnosed, and antibiotic treatment was changed to intravenous. There was no gain of his motoric skills. A test was made for lysosomal storage disease, and neuronal ceroid lipofuscinosis type 2 was found. The patient started intraventricular enzyme substitution treatment as the first patient in Denmark. Treatment has shown to reduce the progression of functional decline.

The frequency of permanent staining of teeth of young children from doxycycline is thought to be lower than from older tetracyclines, but the precise risk is uncertain. Until more definitive data become available, doxycycline should not be used routinely to treat young children with erythema migrans, a manifestation of Lyme disease for which other antimicrobials are highly effective.

Little is known about the functional symptoms associated with Lyme borreliosis (LB) in Europe. We aimed to assess functional symptoms associated with presumed LB and to compare patients with and without confirmed LB.We performed a retrospective monocenter study. Patients consulting for presumed LB were included.Between November 2015 and June 2018, 355patients were included (mean age: 51years, 52% of women) of which 48had LB: erythema migrans (42%), early disseminated LB (50%; 35% of neuroborreliosis cases), and late disseminated LB (8%). The most frequently reported functional symptoms were neuropathic pain (23%), arthralgia (23%), and asthenia (17%). Other functional symptoms were rare (≤10%). Three hundred and seven (86%) patients did not have LB. Patients with confirmed LB reported fewer functional symptoms than patients without LB (1.8 (±1.7) vs. 3.6 (±2.5), P0.001) with a shorter duration of symptoms (3 months in 48% vs. 16% of cases, P0.001). They less often reported asthenia (17% vs. 59%, P0.001), widespread pain (10% vs. 31%, P=0.003), myalgia (10% vs. 32%, P=0.002), memory disorders (4% vs. 16%, P=0.03), irritability (2% vs. 23%, P±0.001), and sadness (0% vs. 16%, P=0.003).In patients consulting for presumed LB, patients diagnosed with LB had fewer and shorter functional symptoms than patients without LB.

Doxycycline is highly effective treatment for early neurologic Lyme borreliosis (NLB). Nineteen studies were reviewed to determine if treatment of patients with erythema migrans with other oral antibiotics would increase the risk for developing NLB. In the eight studies that directly compared doxycycline to another antibiotic, the pooled difference indicated a 0.2% greater risk of developing NLB in doxycycline-treated patients (95% CI: -1.0%, +1.4%; P = 0.77), with an estimated heterogeneity of 0.0%, P = 0.58. Overall, in the 19 studies, NLB was reported in 8/828 (1.0%; 95% CI: 0.42%, 1.89%) doxycycline-treated patients versus 6/1022 (0.6%; 95% CI: 0.22%, 1.27%) patients treated with other antibiotics (P = 0.42). Based on the 95% CI calculation (-0.5%, +1.40%), patients receiving nondoxycycline treatment regimens collectively might have at most a 0.5% greater risk for developing NLB. Available data suggest that oral doxycycline is not superior to comparators for preventing NLB in patients receiving treatment for erythema migrans.

Background Erythema migrans (EM) is the most common manifestation of Lyme borreliosis (LB), caused by the spirochete Borrelia burgdorferi sensu lato. The infection can disseminate into the nervous system and cause Lyme neuroborreliosis (LNB), the second most frequent LB manifestation in children. The aim of this prospective cohort study is to describe the occurrence of EM among children with LNB and to evaluate possible differences in clinical characteristics or outcome between LNB patients with and without EM. Method Children being evaluated for LNB in southeast Sweden during the period 2010–2014 underwent a clinical examination, laboratory testing and filled out a questionnaire regarding duration and nature of symptoms, EM and the child’s health. Children were classified according to European guidelines for LNB. Clinical recovery was evaluated at a 2-month follow-up. Results The occurrence of EM among children with LNB was 37 out of 103 (36%). Gender, age, observed tick bite, clinical features, duration of neurological symptoms or clinical outcome did not differ significantly between LNB patients with or without EM. However, facial nerve palsy was significantly more common among children with EM in the head and neck area. Conclusion EM occurred in 36% of children with LNB and the location on the head and neck was more common among children with facial nerve palsy. EM was not associated with other specific clinical characteristics or outcome. Thus, the occurrence of EM in children with LNB cannot be useful as a prognostic factor for clinical outcome. This aspect has not previously been highlighted but seems to be relevant for the paediatrician in a clinical setting. Electronic supplementary material The online version of this article (10.1186/s12887-018-1163-2) contains supplementary material, which is available to authorized users.

Background Several guidelines advocate the same treatment approaches for both early disseminated Lyme borreliosis, manifested as multiple erythema migrans (EM), and early localized Lyme borreliosis, manifested as solitary EM. Methods Oral doxycycline (100 mg q12h) was compared on a non-inferiority premise with intravenous ceftriaxone (2 g q24h) for 14 days in 200 adult European patients with multiple EM in an open-label alternate-treatment observational trial performed in a single-centre university hospital. Treatment outcome was assessed at 14 days and at 2, 6 and 12 months post-enrolment. Non-specific symptoms in patients and 192 control subjects without a history of Lyme borreliosis were evaluated and compared. This trial was registered at http://clinicaltrials.gov (identifier NCT01163994). Results At the 12 month visit, 4/82 (4.9%) multiple EM patients prescribed doxycycline and 6/88 (6.8%) multiple EM patients prescribed ceftriaxone showed incomplete response manifested predominantly as post-Lyme symptoms (1.9% difference, upper limit of 95% CI 5.1%). The upper limit of 95% CI for the difference in proportion of patients with incomplete response between doxycycline and ceftriaxone groups did not exceed the predetermined non-inferiority margin of 10%. The frequency of non-specific symptoms in patients was similar to that in controls. Conclusions The 14 day oral doxycycline was not inferior to the 14 day intravenous ceftriaxone in treatment of adult European patients with early disseminated Lyme borreliosis manifested as multiple EM. The frequency of non-specific symptoms in patients was similar to that in controls without a history of Lyme borreliosis.

Background Statins were shown to inhibit borrelial growth in vitro and promote clearance of spirochetes in a murine model of Lyme borreliosis (LB). We investigated the impact of statin use in patients with early LB. Methods In this post-hoc analysis, the association between statin use and clinical and microbiologic characteristics was investigated in 1520 adult patients with early LB manifesting as erythema migrans (EM), enrolled prospectively in several clinical trials between June 2006 and October 2019 at a single-center university hospital. Patients were assessed at enrollment and followed for 12 months. Results Statin users were older than patients not using statins, but statin use was not associated with Borrelia seropositivity rate, Borrelia skin culture positivity rate, or disease severity as assessed by erythema size or the presence of LB-associated symptoms. The time to resolution of EM was comparable in both groups. The odds for incomplete recovery decreased with time from enrollment, were higher in women, in patients with multiple EM, and in those reporting LB-associated symptoms at enrollment, but were unaffected by statin use. Conclusion Statin use was not associated with clinical and microbiologic characteristics or long-term outcome in early LB.

The most common tick-borne human disease in Norway is Lyme borreliosis. Ticks in Norway also harbour less known disease-causing agents such as Candidatus Neoehrlichia mikurensis, Borrelia miyamotoi and Rickettsia helvetica. However, human infections caused by these pathogens have never been described in Norway. The main aims of the study were to evaluate the contribution of several tick-borne bacterial agents, other than Borrelia burgdorferi sensu lato, to zoonotic diseases in Norway and to determine their clinical pictures. Blood samples from 70 symptomatic tick-bitten adults from the Agder counties in southern Norway were screened for seven tick-borne pathogens by using a commercial multiplex PCR-based method and by singleplex real-time PCR protocols. Most patients (65/70) presented with a rash clinically diagnosed as erythema migrans (EM). The most frequently detected pathogen DNA was from Ca. N. mikurensis and was found in the blood of 10% (7/70) of the patients. The Ca. N. mikurensis-infected patients presented with an EM-like rash as the only symptom. B. burgdorferi s.l. DNA was present in the blood of 4% (3/70) of the study participants. None had detectable Anaplasma phagocytophilum, B. miyamotoi, Rickettsia typhus group or spotted fever group, Francisella tularensis, Coxiella burnetii or Bartonella spp. DNA in the blood. The commercially available multiplex PCR bacteria flow chip system failed to identify half of the infected patients detected by corresponding real-time PCR protocols. The recovery of Ca. N. mikurensis DNA was higher in the pellet/plasma fraction of blood than from whole blood. To conclude, Ca. N. mikurensis appeared to be the etiological agent in patients with EM in a surprisingly large fraction of tick-bitten persons in the southern part of Norway.

Both early localized and late disseminated forms of Lyme borreliosis are caused by Borrelia burgdorferi senso lato. Differentiating between the spirochetes that only cause localized skin infection from those that cause disseminated infection, and tracing the group of medically-important spirochetes to a specific vertebrate host species, are two critical issues in disease risk assessment and management. Borrelia burgdorferi senso lato isolates from Lyme borreliosis cases with distinct clinical manifestations (erythema migrans, neuroborreliosis, acrodermatitis chronica atrophicans, and Lyme arthritis) and isolates from Ixodes ricinus ticks feeding on rodents, birds and hedgehogs were typed to the genospecies level by sequencing part of the intergenic spacer region. In-depth molecular typing was performed by sequencing eight additional loci with different characteristics (plasmid-bound, regulatory, and housekeeping genes). The most abundant genospecies and genotypes in the clinical isolates were identified by using odds ratio as a measure of dominance. Borrelia afzelii was the most common genospecies in acrodermatitis patients and engorged ticks from rodents. Borrelia burgdorferi senso stricto was widespread in erythema migrans patients. Borrelia bavariensis was widespread in neuroborreliosis patients and in ticks from hedgehogs, but rare in erythema migrans patients. Borrelia garinii was the dominant genospecies in ticks feeding on birds. Spirochetes in ticks feeding on hedgehogs were overrepresented in genotypes of the plasmid gene ospC from spirochetes in erythema migrans patients. Spirochetes in ticks feeding on hedgehogs were overrepresented in genotypes of ospA from spirochetes in acrodermatitis patients. Spirochetes from ticks feeding on birds were overrepresented in genotypes of the plasmid and regulatory genes dbpA, rpoN and rpoS from spirochetes in neuroborreliosis patients. Overall, the analyses of our datasets support the existence of at least three transmission pathways from an enzootic cycle to a clinical manifestation of Lyme borreliosis. Based on the observations with these nine loci, it seems to be justified to consider the population structure of B. burgdorferi senso lato as being predominantly clonal.

Objective: Promptly treated erythema migrans (EM) has good prognosis. However, some patients report persistent symptoms. Do patients with EM have more symptoms than the general population? We describe individual symptoms and general function in EM-patients at time of diagnosis and one year after treatment. Design: Prospective study with 1-year follow up after treatment. Questionnaires included a modified version of the Subjective Health Complaints Inventory, comprising three additional Lyme borreliosis (LB) related symptoms. General function was assessed using a five-point scale modified from the COOP/WONCA charts. Setting: Norwegian general practice. Subjects: A total of 188 patients were included in a randomized controlled trial comparing three antibiotic regimens for EM, of whom 139 had complete data for this study. Main outcome measures: Individual symptoms, symptom load and general function. Results: Mild symptoms were common, reported by 84.9% at baseline and by 85.6% at follow-up. At baseline, patients reported a mean of 5.4 symptoms, compared with 6.2 after one year. Severely bothersome symptoms and severely impaired general function were rare. Tiredness was the most reported symptom both at baseline and at follow-up. Palsy (other than facial) was the least reported symptom, but the only one with a significant increase. However, this was not associated to the EM. Conclusion: The symptom load was comparable to that reported in the general population. We found an increase in symptom load at follow-up that did not significantly affect general function. Implication: Monitoring patients’ symptom loads prior to treatment reduce the probability of attributing follow-up symptoms to LB.Key points Erythema migrans has a good prognosis.Patients treated for erythema migrans have a slight increase in symptom load one year after treatment. This increase does not affect general function. The levels of subjective health complaints in patients treated for erythema migrans are comparable to the background population.

Tick bites can cause a number of local inflammatory reactions, which are often difficult to differentiate from those induced by other arthropod bites or stings. These include erythematous nodular or pustular lesions, erosive plaques, annular lesions of erythema chronicum migrans, and both scarring and nonscarring inflammatory alopecia. We report a case of nonscarring alopecia in a 21-year-old male who reported a recent history of tick bite to the scalp. The biopsy demonstrated a dense pseudolymphomatous inflammatory infiltrate with numerous eosinophils associated with hair follicle miniaturization and an elevated catagen-telogen count. Signs of external rubbing, including lichen simplex chronicus and the "hamburger sign", were also visualized and are indicative of the associated pruritus. To the authors' knowledge, this is the fifth report of nonscarring tick bite alopecia in the literature and the first in an adult patient. This text will review the classic clinical presentation, histologic findings, and proposed mechanism of tick bite alopecia.

A 56-year-old man was sustained ticks at the left axilla and flank. He did not have a rash. About 3 months after the tick bites, he developed back pain, right leg weakness, right abducens nerve palsy, and left facial palsy. Western blot analysis for serum IgM and IgG antibodies against Borrelia were positive. We diagnosed Lyme borreliosis. The patient was treated with antibiotics and steroids, and the symptoms improved. Our findings demonstrate that, even if erythema migrans is not obvious, neuroborreliosis should be considered when neurological signs, such as multiple cranial nerve palsies, are present.

Lyme disease results from infection of humans with the spirocheteBorrelia burgdorferi. The first and most common clinical manifestation is the circular, inflamed skin lesion referred to as erythema migrans; later manifestations result from infections of other body sites. Laboratory diagnosis of Lyme disease can be challenging in patients with erythema migrans because of the time delay in the development of specific diagnostic antibodies against Borrelia. Reliable blood biomarkers for the early diagnosis of Lyme disease in patients with erythema migrans are needed. Here, we performed selected reaction monitoring, a targeted mass spectrometry-based approach, to measure selected proteins that 1) are known to be predominantly expressed in one organ (i.e., organ-specific blood proteins) and whose blood concentrations may change as a result of Lyme disease, or 2) are involved in acute immune responses. In a longitudinal cohort of 40 Lyme disease patients and 20 healthy controls, we identified 10 proteins with significantly altered serum levels in patients at the time of diagnosis, and we also developed a 10-protein panel identified through multivariate analysis. In an independent cohort of patients with erythema migrans, six of these proteins, APOA4, C9, CRP, CST6, PGLYRP2 and S100A9, were confirmed to show significantly altered serum levels in patients at time of presentation. Nine of the 10 proteins from the multivariate panel were also verified in the second cohort. These proteins, primarily innate immune response proteins or proteins specific to liver, skin or white blood cells, may serve as candidate blood biomarkers requiring further validation to aid in the laboratory diagnosis of early Lyme disease.

Neonatal tick bites place infants at risk for acquiring infections that have rarely or never been documented in this age group. We describe 2 rare cases of tickborne infection in neonates. The first patient presented with multiple erythema migrans and fever, leading to a diagnosis of early disseminated Lyme disease. The second patient presented with irritability, fever, and worsening anemia due to babesiosis. Both infants had been bitten by arthropods fitting the description of ticks before the onset of symptoms. Our cases demonstrate the clinical course of 2 common tickborne infections occurring at an atypical age, opening the door to new, complex questions for which little guiding data exists. As tickborne infections become more prevalent, we expect other clinicians will be faced with similarly challenging neonatal cases. Providers must use past experience and a keen eye to identify neonates with tickborne infections and sort through their optimal diagnosis and management. In this article, we raise some of the questions we faced and discuss our conclusions.

1. Jennifer S. Read, MD, MS, MPH, DTM&H*,† 1. *Department of Pediatrics, University of Vermont Medical Center, Burlington, VT 2. †Infectious Disease Epidemiology, Vermont Department of Health, Burlington, VT * Abbreviations: CSF: : cerebrospinal fluid EM: : erythema chronicum migrans IFA: : immunofluorescent antibody Ig: : immunoglobulin RMSF: : Rocky Mountain spotted fever PCR: : polymerase chain reaction The most common tick-borne infections in the United States are Lyme disease, ehrlichiosis, anaplasmosis, Rocky Mountain spotted fever, and babesiosis. The epidemiology of these infections in the United States is integrally related to the geographic distribution and seasonality of the tick vector of each of the infections. Because these infections can be very serious and sometimes fatal, and because of the inherent delay in obtaining laboratory confirmation (especially with serologic assays requiring acute and convalescent titers), considering early implementation of empirical treatment based on the patient’s clinical presentation is extremely important. Prevention of acquisition of tick-borne diseases requires avoiding tick-infested areas or, if this is not possible or desired, implementing steps to decrease the likelihood of tick bites and the duration of tick attachment. After completing this article, readers should be able to: 1. Understand the etiologic organisms and the associated ticks responsible for transmission, the geographic distribution of and the reported infections associated with the ticks in the United States, and the seasonality and incubation periods of tick-borne infections in the United States. 2. Recognize the clinical manifestations and laboratory abnormalities associated with the infections, especially as they relate to children. 3. Plan for the diagnosis, treatment, and prevention of these infections. Vector-borne diseases, caused by microorganisms transmitted by insects and ticks, are major causes of morbidity and mortality globally. In the United States, vector-borne diseases are occurring more frequently and represent a significant public health concern. (1) The numbers of reported vector-borne disease cases in the United States (tick-borne, mosquito-borne, and flea-borne diseases) are shown in Table 1. (1) The reported incidence of vector-borne diseases most likely significantly underestimates the actual occurrence …

Lyme disease is an emerging problem in Poland. Analysis has been undertaken of the medical documentation of 86 patients hospitalized in the Infectious Diseases Department, University Hospital in Cracow in 2013-2016, suspected of Lyme arthritis. It has especially considered medical history including potential exposure to the infection, detailed characteristics of the symptoms, diagnostic challenges and results of the treatment. Only some patients had a history of erythema migrans and not all of them recalled tick-bite. The majority of the patients had affected large joints, especially knee joints, and polyarthritis was rarely observed. Symptoms were resolved completely or partially after antibiotic treatment in most patients. The diagnosis of Lyme arthritis in areas endemic for Lyme disease is still a diagnostic challenge in patients with other rheumatic diseases, including osteoarthritis.

Background Information on Lyme borreliosis (LB) in patients treated with rituximab is limited to individual case reports. Methods We reviewed data on adult patients diagnosed with typical erythema migrans (EM) at the LB outpatient clinic of the University Medical Center Ljubljana, Slovenia, in the 10-year period 2008–2017. For all patients, clinical and laboratory information was acquired prospectively using a standardized questionnaire. Results Among 4230 adult patients with a diagnosis of EM, 7 patients (0.17%), 5 women and 2 men with a median age of 65 years (range, 55–66 years), were receiving rituximab for an underlying medical condition. In these 7 patients, signs of disseminated LB (43%) and the isolation rates of borreliae from blood before antibiotic treatment (40%) were unusually high compared with corresponding findings in immunocompetent patients who had EM diagnosed at the same institution (8% vs, Although early Lyme borreliosis in patients with erythema migrans who were receiving rituximab for underlying disease is more often disseminated than in immunocompetent patients, the outcome 1 year after antibiotic treatment, as used for immunocompetent patients, is excellent.

Lyme's disease also known as Erythema chronicum Migrans, is a multisystem infectious disease caused by the spirochete "Borrelia burgdorferi" which is transmitted by "Ixodes" tick, with both specific and nonspecific manifestations. Nervous system involvement occurs in 10%-15% of untreated patients and typically involves lymphocytic meningitis, cranial neuritis, and/or polyradiculitis. Here, we are reporting an interesting and challenging case of Neuro-Borreliosis in a young officer cadet, meeting the description for Bannwarth's syndrome and presenting initially as a surgical emergency followed by paraparesis. The diagnosis was finally clinched based on clinical profile of Chronic Myeloradiculopathy with focal myositis in the setting of recent outdoor camping, and confirmed by demonstrating high IgG antibody titres in serum and Cerebro spinal fluid (CSF). The officer cadet was treated successfully with a 6 week course of Ceftriaxone and Doxycycline, and went back to full training.

Background After antibiotic treatment of Lyme borreliosis, a subset of patients report persistent symptoms, also referred to as post-treatment Lyme disease syndrome. The reported prevalence of persistent symptoms varies considerably, and its pathophysiology is under debate. The LymeProspect study has been designed to investigate the prevalence, severity, and a wide range of hypotheses on the etiology of persistent symptoms among patients treated for Lyme borreliosis in the Netherlands. Methods LymeProspect is a prospective, observational cohort study among adults with proven or probable Lyme borreliosis, either erythema migrans or disseminated manifestations, included at the start of antibiotic treatment. During one year of follow-up, participants are subjected to questionnaires every three months and blood is collected repeatedly during the first three months. The primary outcome is the prevalence of persistent symptoms after treatment, assessed by questionnaires online focusing on fatigue (CIS, subscale fatigue severity), pain (SF-36, subscale pain) and neurocognitive dysfunction (CFQ). Potential microbiological, immunological, genetic, epidemiological and cognitive-behavioral determinants for persistent symptoms are secondary outcome measures. Control cohorts include patients with long-lasting symptoms and unconfirmed Lyme disease, population controls, and subjects having reported a tick bite not followed by Lyme borreliosis. Discussion This article describes the background and design of the LymeProspect study protocol. This study is characterized by a prospective, explorative and multifaceted design. The results of this study will provide insights into the prevalence and determinants of persistent symptoms after treatment for Lyme borreliosis, and may provide a rationale for preventive and treatment recommendations. Trial registration NTR4998 (Netherlands Trial Register). Date of registration: 13 February 2015. Electronic supplementary material The online version of this article (10.1186/s12879-019-3949-8) contains supplementary material, which is available to authorized users.

BackgroundPersistent symptoms attributed to presumed tick-bite exposure constitute an unresolved medical controversy. We evaluated whether Swedish adults who met the criteria for post-treatment Lyme disease syndrome (PTLDS) exhibited characteristics distinguishable from adults who did not, but who displayed similar symptoms and disease course after suspected previous tick-bite infection (TBI).Methods and findingsDuring 2015–2018, 255 patients–referred to the Centre for Vector-borne Infections, Uppsala University Hospital, Sweden with symptoms lasting longer than six months–were recruited. Of this group, 224 completed the study. Each patient was examined by an infectious disease specialist and, besides a full medical history, underwent a panel of blood and cerebrospinal fluid laboratory tests including hematological, biochemical, microbiological and immunological analyses, and the RAND-36 scale to measure quality of life. For analysis purposes, patients were divided into five subgroups, of which one represented PTLDS. According to serological results indicating TBI and documented/ reported objective signs of Lyme disease, 85 (38%) patients fulfilled the criteria for PTLDS and were compared with the other 139 (62%) serologically classified patients. In the PTLDS group, erythema chronicum migrans (ECM) was documented/reported in 86% of patients, previous neuroborreliosis in 15%, and acrodermatitis chronica atroficans (ACA) in 3.5%. However, there were no significant differences regarding symptoms, laboratory results or disease course between patients with PTLDS and those without laboratory evidence ofBorreliaexposition. Most reported symptoms were fatigue-related (70%), musculoskeletal (79%), neurological (82%) and neurocognitive (57%). Tick bites were recalled by 74%. The RAND-36 score was significantly below that of the general Swedish population. Signs of immunological/inflammatory reactivity with myositis antibodies were detected in 20% of patients, fibrinogen levels were moderately increased in 21% and elevated rheumatoid factor in 6%.ConclusionsThe PTLDS group did not differ exclusively in any respect from the other subgroups, which either lacked previously documented/reported evidence of borreliosis or even lacked detectable serological signs of exposure to Lyme disease. The results suggest that symptoms often categorized as Chronic-Lyme-Disease (CLD) in the general debate, cannot be uniquely linked to Lyme disease. However, approximately 20% of the total group of patients showed signs of autoimmunity. Further studies are needed to elucidate the underlying causes and mechanisms of PTLDS and there is reason to consider a multifactorial approach.

Background Information on the course and outcome of borrelial lymphocytoma (BL) is limited. Methods The study comprised 144 adult patients (75 female, 69 male; median age, 49 years) who had BL diagnosed at a single center between 1986 and 2014 and were followed up for 1 year. Results BL was located on the breast in 106 patients (73.6%), on the ear lobe in 27 (18.8%), and elsewhere in 11 (7.6%). The median duration of BL before diagnosis was 27 days (interquartile range [IQR], 9-68 days). Concomitant erythema migrans was registered in 104 of 144 patients (72.2%); other objective manifestations of Lyme borreliosis (LB) were present in 11 (7.6%). Immunoglobulin M and/or G borrelial serum antibodies were present in 72 patients (50%). Borreliae were isolated from BL lesions in 14 of 42 patients (33.3%) who had not received antibiotics before skin biopsy. Of 13 typed Borrelia strains, 11 were B. afzelii, 1 was B. garinii, and 1 was B. bissettii The median duration of BL after starting antibiotic treatment was 21 days ([IQR], 10-30 days); the average duration was longer in patients who were older, had longer BL duration before treatment, or had signs of disseminated LB. Treatment failure occurred in 14 of 144 patients (9.7%). Patients with signs or symptoms of disseminated LB before treatment had nearly 4 times higher odds of treatment failure (95% confidence interval, 1.22-13.07) than those without such symptoms. All patients with treatment failure had uneventful outcome after retreatment. Conclusions BL is a rare manifestation of early localized LB. Fourteen-day antibiotic treatment, as used for erythema migrans, is effective.

Strains from the United States are more virulent and have greater inflammatory potential., Borrelia burgdorferi sensu stricto isolates from patients with erythema migrans in Europe and the United States were compared by genotype, clinical features of infection, and inflammatory potential. Analysis of outer surface protein C and multilocus sequence typing showed that strains from these 2 regions represent distinct genotypes. Clinical features of infection with B. burgdorferi in Slovenia were similar to infection with B. afzelii or B. garinii, the other 2 Borrelia spp. that cause disease in Europe, whereas B. burgdorferi strains from the United States were associated with more severe disease. Moreover, B. burgdorferi strains from the United States induced peripheral blood mononuclear cells to secrete higher levels of cytokines and chemokines associated with innate and Th1-adaptive immune responses, whereas strains from Europe induced greater Th17-associated responses. Thus, strains of the same B. burgdorferi species from Europe and the United States represent distinct clonal lineages that vary in virulence and inflammatory potential.

Ein 75-jahriger Patient stellt sich mit seit mehreren Monaten bestehenden, livid-rotlichen, unscharf begrenzten Schwellungen am linken Fus und Unterschenkel vor. Er klagt uber eine verstarkte Schmerzempfindung in dem betroffenen Hautareal und uber leichte Missempfindungen an beiden Handen.

AIMS: Metal absorbable scaffolds constitute a conceptually attractive alternative to polymeric scaffolds. Promising 6-month outcomes of a second-generation drug-eluting absorbable metal scaffold (DREAMS 2G), consisting of an absorbable magnesium scaffold backbone, have been reported. We assessed the 12-month safety and performance of this novel device.METHODS AND RESULTS: The prospective, international, multi-centre, first-in-man BIOSOLVE-II trial enrolled 123 patients with up to two de novo lesions with a reference diameter between 2.2 and 3.7 mm. All patients were scheduled for angiographic follow-up at 6 months, and-if subjects consented-at 12 months. Dual antiplatelet therapy was recommended for 6 months. Quantitative coronary angiography (QCA) parameters remained stable from 6 to 12 months [paired data of 42 patients: in-segment late lumen loss 0.20 ± 0.21 mm vs. 0.25 ± 0.22 mm, P = 0.117, Δ 0.05 ± 0.21 mm (95% CI: -0.01;0.12); in-scaffold late lumen loss 0.37 ± 0.25 mm vs. 0.39 ± 0.27 mm, P = 0.446, Δ 0.03 ± 0.22 (95% CI: -0.04;0.10), respectively]. Intravascular ultrasound and optical coherence tomography findings corroborated the QCA results. Target lesion failure occurred in four patients (3.4%), consisting of one death of unknown cause, one target-vessel myocardial infarction, and two clinically driven target lesion revascularization. No additional event occurred beyond the 6-month follow-up. During the entire follow-up of 12 months, none of the patients experienced a definite or probable scaffold thrombosis.CONCLUSION: The novel drug-eluting metal absorbable scaffold DREAMS 2G showed a continuous favourable safety profile up to 12 months and stable angiographic parameters between 6 and 12 months.CLINICALTRIALSGOV IDENTIFIER: NCT01960504.