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Persistent symptoms after an infection have been described for a number of infectious diseases, including Lyme disease. Studies have confirmed a moderate but consistent increase in the prevalence of such symptoms after Lyme disease, though the risk increase varies dependent on study design and the definition of persistent symptoms. Various possible predictors have been proposed, including a dysregulation of the immune system, metabolic changes, increased sensitization to pain signals, cognitive-behavioral factors, or-controversially-the persistence of the causative Borrelia bacteria or remnants thereof. Research on the precise roles of any of these factors is still ongoing. The lack of biological underpinning also makes it difficult to assess with certainty which patients' (generally nonspecific) persistent symptoms are etiologically related to the previous Lyme disease episode and which are not, particularly as these symptoms occur in the general population relatively frequently. The diagnostic criteria for posttreatment Lyme disease syndrome have shown their usefulness in both clinical and research settings but leave out a number of patients whose symptoms may fall just outside said criteria. Though the relationship between these symptoms and the previous Lyme disease episode may be very uncertain, we would argue that a uniform description and classification of these patients will aid in future research and patient management, regardless of the eventual underlying cause. Thus, we argue for an inclusive classification system for all persistent symptoms attributed to Lyme disease in order to promote validation of patient experiences and perspectives, while also maintaining scientific nuance regarding the very uncertain etiology of these patients' symptoms., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Previous studies have shown that monocytes can be 'trained' or tolerized by certain stimuli to respond stronger or weaker to a secondary stimulation. Rewiring of glucose metabolism was found to be important in inducing this phenotype. As we previously found that Borrelia burgdorferi (B. burgdorferi), the causative agent of Lyme borreliosis (LB), alters glucose metabolism in monocytes, we hypothesized that this may also induce long-term changes in innate immune responses. We found that exposure to B. burgdorferi decreased cytokine production in response to the TLR4-ligand lipopolysaccharide (LPS). In addition, B. burgdorferi exposure decreased baseline levels of glycolysis, as assessed by lactate production. Using GWAS analysis, we identified a gene, microfibril-associated protein 3-like (MFAP3L) as a factor influencing lactate production after B. burgdorferi exposure. Validation experiments proved that MFAP3L affects lactate- and cytokine production following B. burgdorferi stimulation. This is mediated by functions of MFAP3L, which includes activating ERK2 and through activation of platelet degranulation. Moreover, we showed that platelets and platelet-derived factors play important roles in B. burgdorferi-induced cytokine production. Certain platelet-derived factors, such chemokine C-X-C motif ligand 7 (CXCL7) and (C-C motif) ligand 5 (CCL5), were elevated in the circulation of LB patients in comparison to healthy individuals., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Immunology.)

Background: Our objectives were to improve the following outcomes in patients with Lyme borreliosis (LB) through an educational intervention in general practice: (i) increase the number of hospital referrals on suspicion of LB, (ii) increase the number of cerebrospinal fluid (CSF) tests examined for Borrelia burgdorferi antibody index, (iii) decrease the number of serum-B. burgdorferi antibody tests ordered, (iv) shorten delay from symptom onset to hospital in Lyme neuroborreliosis (LNB) patients, (v) increase LB knowledge among general practitioners., Methods: A prospective non-blinded non-randomized intervention trial on the island of Funen, Denmark. The intervention included oral and written education about LB and was carried out in areas with an LNB incidence ≥4.7/100.000 between 22 January 2019 and 7 May 2019. Results were compared between the intervention group (49 general practices) and the remaining general practices in Funen (71 practices) 2 years before and after the intervention., Results: In the study period, 196 patients were referred on suspicion of LB, a 28.9% increase in the intervention group post-intervention, 59.5% increase in the control group (P = 0.47). The number of CSF-Borrelia-antibody index tests increased 20.8% in the intervention group, 18.0% in the control group (P = 0.68), while ordered serum-B. burgdorferi antibody tests declined 43.1% in the intervention group, 34.5% in the control group (P = 0.30). 25.1% had the presence of serum-B. burgdorferi antibodies. We found no difference in LNB pre-hospital delay before and after intervention or between groups (P = 0.21). The intervention group performed significantly better on a follow-up questionnaire (P = 0.02)., Conclusion: We found an overall improvement in LB awareness and referrals among general practitioners but could not show any effect of the intervention on clinical outcomes of LNB., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Public Health Association.)

Lyme disease, caused by some Borrelia burgdorferi sensu lato, is the most common tick-borne illness in the Northern Hemisphere and the number of cases, and geographic spread, continue to grow. Previously identified B. burgdorferi proteins, lipid immunogens, and live mutants lead the design of canonical vaccines aimed at disrupting infection in the host. Discovery of the mechanism of action of the first vaccine catalyzed the development of new strategies to control Lyme disease that bypassed direct vaccination of the human host. Thus, novel prevention concepts center on proteins produced by B. burgdorferi during tick transit and on tick proteins that mediate feeding and pathogen transmission. A burgeoning area of research is tick immunity as it can unlock mechanistic pathways that could be targeted for disruption. Studies that shed light on the mammalian immune pathways engaged during tick-transmitted B. burgdorferi infection would further development of vaccination strategies against Lyme disease., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background We aimed to identify the prevalence of cardiovascular risk factors, and investigate preventive cardiovascular medication use and achievement of targets as per Dutch cardiovascular risk management guidelines among human immunodeficiency virus (HIV)-positive and HIV-negative individuals. Design The design was a cross-sectional analysis within an ongoing cohort study. Methods Data on medication use and cardiovascular disease prevalence were available for 528 HIV-positive and 521 HIV-negative participants. We identified cardiovascular risk factors and applied cardiovascular risk management guidelines, mainly focusing on individuals eligible for (a) primary prevention because of high a priori cardiovascular risk, or for (b) secondary prevention. Results One hundred and three (20%) HIV-positive and 77 (15%) HIV-negative participants were classified as having high cardiovascular risk; 53 (10%) HIV-positive and 27 (5%) HIV-negative participants were eligible for secondary prevention. Of HIV-positive individuals 57% at high cardiovascular risk and 42% of HIV-positive individuals eligible for secondary prevention had systolic blood pressures above guideline-recommended thresholds. Cholesterol levels were above guideline-recommended thresholds in 81% of HIV-positive individuals at high cardiovascular risk and 57% of HIV-positive individuals eligible for secondary prevention. No statistically significant differences were observed between HIV-positive and HIV-negative participants regarding achievement of targets, except for glycaemic control (glycated haemoglobin ≤ 53 mmol/mol) among individuals using diabetes medication (90% vs 50%, p = 0.017) and antiplatelet/anticoagulant use for secondary prevention (85% vs 63%, p = 0.045), which were both superior among HIV-positive participants. Conclusions Cardiovascular risk management is suboptimal in both HIV-positive and HIV-negative individuals and should be improved.

Several microorganisms have been shown to manipulate their host or vector to enhance their own transmission. Here we examined whether an infection with Borrelia afzelii affects its transmission between its bank vole (Myodes glareolus, Schreber, 1780) host and tick vector. Captive-bred bank voles were inoculated with B. afzelii or control medium, after which host preference of Ixodes ricinus L. nymphs was determined in a Y-tube olfactometer. Thereafter, infected and uninfected bank voles were placed in a semifield arena containing questing larvae to measure larval tick attachment. Engorged larvae were collected from these bank voles, molted into nymphs, weighed, and analyzed for infection by PCR.Nymphs were attracted to the odors of a bank vole compared to ambient air and preferred the odors of an infected bank vole over that of an uninfected bank vole. In the semifield arena, infected male bank voles had greater larval tick burdens then uninfected males, while similar larval tick burdens were observed on females regardless of infection status. Nymphal ticks that acquired a B. afzelii infection had higher body weight than nymphs that did not acquire an infection regardless of the infection status of the vole. These results show that a B. afzelii infection in bank voles increases larval tick burden and that a B. afzelii infection in larvae increases nymphal body weight. This finding provides novel ecological insights into the enzootic cycle of B. afzelii., (© The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Ixodes ticks are the main vectors for Borrelia burgdorferi sensu lato. In the United States, B. burgdorferi is the sole causative agent of Lyme borreliosis and is transmitted by Ixodes scapularis. In Europe, 3 Borrelia species-B. burgdorferi, B. garinii, and B. afzelii-are prevalent, which are transmitted by Ixodes ricinus. The I. scapularis salivary protein Salp15 has been shown to bind to B. burgdorferi outer surface protein (Osp) C, protecting the spirochete from antibody-mediated killing., Methods and Results: We recently identified a Salp15 homologue in I. ricinus, Salp15 Iric-1. Here, we have demonstrated, by solid-phase overlays, enzyme-linked immunosorbent assay, and surface plasmon resonance, that Salp15 Iric-1 binds to B. burgdorferi OspC. Importantly, this binding protected the spirochete from antibody-mediated killing in vitro and in vivo; immune mice rechallenged with B. burgdorferi preincubated with Salp15 Iric-1 displayed significantly higher Borrelia numbers and more severe carditis, compared with control mice. Furthermore, Salp15 Iric-1 was capable of binding to OspC from B. garinii and B. afzelii, but these Borrelia species were not protected from antibody-mediated killing., Conclusions: Salp15 Iric-1 interacts with all European Borrelia species but differentially protects B. burgdorferi from antibody-mediated killing, putatively giving this Borrelia species a survival advantage in nature.