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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.

Lyme borreliosis (Lyme disease) is caused by spirochaetes of the Borrelia burgdorferi sensu lato species complex, which are transmitted by ticks. The most common clinical manifestation is erythema migrans, which eventually resolves, even without antibiotic treatment. However, the infecting pathogen can spread to other tissues and organs, causing more severe manifestations that can involve a patient's skin, nervous system, joints, or heart. The incidence of this disease is increasing in many countries. Laboratory evidence of infection, mainly serology, is essential for diagnosis, except in the case of typical erythema migrans. Diagnosed cases are usually treated with antibiotics for 2–4 weeks and most patients make an uneventful recovery. No convincing evidence exists to support the use of antibiotics for longer than 4 weeks, or for the persistence of spirochaetes in adequately treated patients. Prevention is mainly accomplished by protecting against tick bites. There is no vaccine available for human beings.

The erythema migrans (EM) skin lesion is the most common clinical manifestation of Lyme borreliosis. Information about EM in Lyme borreliosis reinfection is limited. Of the 12,384 cases with diagnosed EM at an outpatient clinic during 1990-2014 in Slovenia, 1,962 (15.8%) cases occurred in patients who were treated previously for Lyme borreliosis, including 1,849 (94.2%) who had previously had EM. The percentage of reinfected patients who sought care with disseminated Lyme borreliosis at the time of reinfection, as manifested by multiple EM skin lesions, was significantly lower than for EM patients with no history of Lyme borreliosis (5.5% [108/1,962] vs. 7.4% [769/10,427]; p = 0.002). None of the clinical manifestations of Lyme borreliosis in Europe will completely protect against EM developing in patients in the future. The reoccurrence of Lyme borreliosis manifested by multiple EM lesions is significantly less likely than for patients with no history of Lyme borreliosis.

Lyme borreliosis is caused by certain genospecies of the Borrelia burgdorferi sensu lato complex, which are transmitted by hard ticks of the genus Ixodes. The most common clinical manifestation is erythema migrans, an expanding skin redness that usually develops at the site of a tick bite and eventually resolves even without antibiotic treatment. The infecting pathogens can spread to other tissues and organs, resulting in manifestations that can involve the nervous system, joints, heart and skin. Fatal outcome is extremely rare and is due to severe heart involvement; fetal involvement is not reliably ascertained. Laboratory support-mainly by serology-is essential for diagnosis, except in the case of typical erythema migrans. Treatment is usually with antibiotics for 2 to 4 weeks; most patients recover uneventfully. There is no convincing evidence for antibiotic treatment longer than 4 weeks and there is no reliable evidence for survival of borreliae in adequately treated patients. European Lyme borreliosis is a frequent disease with increasing incidence. However, numerous scientifically questionable ideas on its clinical presentation, diagnosis and treatment may confuse physicians and lay people. Since diagnosis of Lyme borreliosis should be based on appropriate clinical signs, solid knowledge of clinical manifestations is essential.

Information on febrile illness caused by tick-borne encephalitis virus (TBEV) without central nervous system involvement is limited. We characterized 98 patients who had TBEV RNA in their blood but no central nervous system involvement at the time of evaluation. Median duration of illness was 7 days; 37 (38%) patients were hospitalized. The most frequent findings were malaise or fatigue (98%), fever (97%), headache (86%), and myalgias (54%); common laboratory findings were leukopenia (88%), thrombocytopenia (59%), and abnormal liver test results (63%). During the illness, blood leukocyte counts tended to improve, whereas thrombocytopenia and liver enzymes tended to deteriorate. At the time of positive PCR findings, 0/98 patients had serum IgG TBEV and 7 serum IgM TBEV; all patients later seroconverted. Viral RNA load was higher in patients with more severe illness but did not differ substantially in relation to several other factors. Illness progressed to tick-borne encephalitis in 84% of patients within 18 days after defervescence.

Lyme neuroborreliosis (LNB) in Europe may manifest with painful meningoradiculoneuritis (also known as Bannwarth syndrome) or lymphocytic meningitis with or without cranial neuritis (peripheral facial palsy). We assessed host immune responses and the prevalence of TLR1 (toll-like receptor 1)–1805GG polymorphism to gain insights into the pathophysiology of these conditions. Regardless of LNB manifestation, most mediators associated with innate and adaptive immune responses were concentrated in cerebrospinal fluid; serum levels were unremarkable. When stratified by specific clinical manifestation, patients with meningoradiculoneuritis had higher levels of B-cell chemoattractants CXC motif chemokine ligand (CXCL) 12 and CXCL13 and T-cell–associated mediators CXCL9, CXCL10, and interleukin 17, compared with those without radicular pain. Moreover, these patients had a higher frequency of TLR1–1805GG polymorphism and more constitutional symptoms. These findings demonstrate that meningoradiculoneuritis is a distinct clinical entity with unique immune and genetic pathophysiology, providing new considerations for the study of LNB and borrelial meningoradiculitis.

[...]the participating hospitals were either university hospitals (n = 9) or large teaching hospitals (n = 3), and 11 EDs had paediatric intensive care facilities. Collected data included age, sex, season, referral, comorbidity (chronic condition expected to last at least 1 year) [22], triage urgency, fever duration, fever measured at ED, presence of “red traffic light” symptoms for identifying risk of serious illness (alarming signs) (from the National Institute for Health and Care Excellence [NICE] guideline on fever [23]: decreased consciousness, ill appearance, work of breathing, meningeal signs, focal neurology, non-blanching rash, dehydration, status epilepticus), previous antibiotic use, vital signs (heart rate, respiratory rate, oxygen saturation, temperature, capillary refill time), laboratory results (white blood cell count, C-reactive protein [CRP], urinalysis), imaging (chest X-ray and other imaging), microbiological investigations (cultures and respiratory viral tests), and disposition (intensive care unit admission, general ward admission or discharge). The focus of infection was categorised as upper respiratory tract (otitis media, tonsillitis/pharyngitis, other), lower respiratory tract, gastrointestinal tract, urinary tract, skin, musculoskeletal, sepsis, central nervous system, flu-like illness, childhood exanthem, inflammatory syndrome, undifferentiated fever, or other. CRP, C-reactive protein; LRTI, lower respiratory tract infection; URTI, upper respiratory tract infection. *Patients could have identified viral co-infection. https://doi.org/10.1371/journal.pmed.1003208.g001 We aimed to improve data quality and standardised data collection by using a training module for the local clinical and research teams to optimise clinical assessment and data collection for febrile children.

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.

Patients who have Lyme neuroborreliosis (LNB) might experience lingering symptoms that persist despite antibiotic drug therapy. We tested whether those symptoms are caused by maladaptive immune responses by measuring 20 immune mediators in serum and cerebrospinal fluid (CSF) in 79 LNB patients followed for 1 year. At study entry, most mediators were highly concentrated in CSF, the site of the infection. Those responses resolved with antibiotic therapy, and associations between CSF cytokines and signs and symptoms of LNB were no longer observed. In contrast, subjective symptoms that persisted after use of antibiotics were associated with increased levels of serum interferon-α (IFN-α), which were already observed at study entry, and remained increased at each subsequent timepoint. Highest IFN-α levels corresponded with severe disease. Although the infection serves as the initial trigger, sequelae after antibiotic therapy are associated with unremitting systemic IFN-α levels, consistent with the pathogenic role of this cytokine in interferonopathies in other conditions.

This paper introduces a uniform evaluation framework for assessing the effectiveness of past non-pharmaceutical interventions (NPIs) in managing infectious diseases, taking into account the cultural and social differences between countries. The framework enables quantifying and finding the optimal balance of both the health and socioeconomic impacts of NPIs. The aim is to assist policymakers in understanding which NPIs lead to the optimal balance by highlighting unnecessary costs - the costs that could be avoided while maintaining the same infection rates. To assess the extent of unnecessary socioeconomic consequences experienced by a country during a past epidemic of infectious diseases, we use the following approach. First, we develop a model that predicts the number of infections from NPIs in a country. Second, we estimate the socioeconomic costs (SEC) of the NPIs universally for countries included in the study. Third, we develop a model that prescribes the NPI plans with the optimal trade-off between the number of infections and the SEC. Fourth, we create a model that specifically adjusts each country’s SEC. Finally, we provide additional analysis to increase comprehension of the effects of NPIs. Demonstrated through an analysis of COVID-19 pandemic responses in 17 countries, the study offers a systematic presentation of the framework and a concrete examination of the integrated effects of NPIs. It provides insights into interventions’ direct and indirect consequences, offering guidance for future epidemic responses. The framework enables a systematic understanding of the effects of the NPIs applied, acknowledging the national diversity in health measure acceptance and implementation. This allows for fair analysis across countries, identifying and displaying the economic, social, and health-related costs of suboptimal NPI strategies, i.e., unnecessary costs. The framework is applicable for any infectious disease, NPIs, or country, assuming the medical interventions are similar, e.g., timing and amount of vaccination.