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Abstract In Lyme borreliosis, the skin constitutes a major interface for the host, the bacteria and the tick. Skin immunity is provided by specialized immune cells but also by the resident cells: the keratinocytes and the fibroblasts. Discoveries on the role of the microbiome in the modulation of skin inflammation and immunity have reinforced the potential importance of the skin in vector-borne diseases. In this study, we analyzed in vitro the interaction of human primary keratinocytes and fibroblasts with Borrelia burgdorferi sensu stricto N40 in presence or absence of bacterial commensal supernatants. We aimed to highlight the role of resident skin cells and skin microbiome on the inflammation induced by B. burgdorferi s.s.. The secretomes of Staphylococcus epidermidis, Corynebacterium striatum and Cutibacterium acnes showed an overall increase in the expression of IL-8, CXCL1, MCP-1 and SOD-2 by fibroblasts, and of IL-8, CXCL1, MCP-1 and hBD-2 in the undifferentiated keratinocytes. Commensal bacteria showed a repressive effect on the expression of IL-8, CXCL1 and MCP-1 by differentiated keratinocytes. Besides the inflammatory effect observed in the presence of Borrelia on all cell types, the cutaneous microbiome appears to promote a rapid innate response of resident skin cells during the onset of Borrelia infection.

Objectives: Neoehrlichia mikurensis (NM) is an emerging intracellular bacterium member of the Anaplasmatacecae family. So far, only four cases have been described in France, all of them retrospectively., Methods: This study describes two new cases of NM discovered following implementation of a biplex PCR targeting both Anaplasma and NM., Results: Two immunocompetent patients developed a flu-like illness within 14 days after an identified tick bite. Both had negative Anaplasma PCR, but by using this biplex PCR NM, infection was diagnosed in both cases. One patient recovered spontaneously while the second was successfully treated by a seven-day course of doxycycline., Conclusion: Present in Eastern France, NM is underdiagnosed. Biplex PCR screening of NM with A.phagocytophilum could effectively address this issue., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

In Lyme borreliosis, the skin constitutes a major interface for the host, the bacteria and the tick. Skin immunity is provided by specialized immune cells but also by the resident cells: the keratinocytes and the fibroblasts. Discoveries on the role of the microbiome in the modulation of skin inflammation and immunity have reinforced the potential importance of the skin in vector-borne diseases. In this study, we analyzed in vitro the interaction of human primary keratinocytes and fibroblasts with Borrelia burgdorferi sensu stricto N40 in presence or absence of bacterial commensal supernatants. We aimed to highlight the role of resident skin cells and skin microbiome on the inflammation induced by B. burgdorferi s.s.. The secretomes of Staphylococcus epidermidis, Corynebacterium striatum and Cutibacterium acnes showed an overall increase in the expression of IL-8, CXCL1, MCP-1 and SOD-2 by fibroblasts, and of IL-8, CXCL1, MCP-1 and hBD-2 in the undifferentiated keratinocytes. Commensal bacteria showed a repressive effect on the expression of IL-8, CXCL1 and MCP-1 by differentiated keratinocytes. Besides the inflammatory effect observed in the presence of Borrelia on all cell types, the cutaneous microbiome appears to promote a rapid innate response of resident skin cells during the onset of Borrelia infection., (© 2023. Springer Nature Limited.)

Background: Serological testing of patients consulting for typical erythema migrans (EM) is not recommended in European recommendations for diagnosis of Lyme borreliosis (LB). Little is known on the level of adherence of French general practitioners to these recommendations. The objectives were to estimate the proportion of Lyme borreliosis serological test prescription in patients with erythema migrans seen in general practice consultations in France, and to study the factors associated with this prescription., Methods: LB cases with an EM reported by the French general practitioners (GPs) of the Sentinelles network between January 2009 and December 2020 were included. To assess the associations with a prescription of a serological test, multilevel logistic regression models were used., Results: Among the 1,831 EM cases included, a prescription for a LB serological test was requested in 24.0% of cases. This proportion decreased significantly over the study period, from 46.8% in 2009 to 15.8% in 2020. A LB serological prescription was associated with patients with no reported tick bite (Odds Ratio (OR): 1.95; 95% confidence interval [1.23-3.09]), multiple EM (OR: 3.82 [1.63-8.92]), EM of five centimeters or more (OR: 4.34 [2.33-8.08]), and GPs having diagnosed less than one EM case per year during the study period (OR: 5.28 [1.73-16.11])., Conclusions: Serological testing of patients consulting for EM is not recommended in European recommendations for diagnosis of Lyme borreliosis. Therefore, the significant decrease in the rate of LB serological test for EM over the study period is encouraging. The factors identified in this study can be used to improve messaging to GPs and patients. Further efforts are needed to continue to disseminate diagnostic recommendations for LB to GPs, especially those who rarely see patients with EM., (© 2023. BioMed Central Ltd., part of Springer Nature.)

BackgroundLyme borreliosis (LB) is the most common tick-borne disease (TBD) in France. Forestry workers are at high risk of TBD because of frequent exposure to tick bites.AimWe aimed to estimate the seroprevalence of Borrelia burgdorferi sensu lato and tick-borne encephalitis virus (TBEV) antibodies among forestry workers in northern France. We compared seroprevalence by geographical area and assessed factors associated with seropositivity.MethodsBetween 2019 and 2020, we conducted a randomised cross-sectional seroprevalence survey. Borrelia burgdorferi sl seropositivity was defined as positive ELISA and positive or equivocal result in western blot. Seropositivity for TBEV was defined as positive result from two ELISA tests, confirmed by serum neutralisation. We calculated weighted seroprevalence and adjusted prevalence ratios to determine association between potential risk factors and seropositivity.ResultsA total of 1,778 forestry workers participated. Seroprevalence for B. burgdorferi sl was 15.5% (95% confidence interval (CI): 13.9-17.3), 3.5 times higher in the eastern regions than in the western and increased with seniority and with weekly time in a forest environment. Seroprevalence was 2.5 times higher in forestry workers reporting a tick bite during past years and reporting usually not removing ticks rapidly. Seroprevalence for TBEV was 0.14% (95% CI: 0.05-0.42).ConclusionWe assessed for the first time seroprevalence of B. burgdorferi sl and TBEV antibodies among forestry workers in northern France. These results will be used, together with data on LB and tick-borne encephalitis (TBE) incidence and on exposure to tick-bites, to target prevention programmes.

BackgroundLyme borreliosis (LB) is the most widespread hard tick-borne zoonosis in the northern hemisphere. Existing studies in Europe have focused mainly on acarological risk assessment, with few investigations exploring human LB occurrence.AimWe explored the determinants of spatial and seasonal LB variations in France from 2016 to 2021 by integrating environmental, animal, meteorological and anthropogenic factors, and then mapped seasonal LB risk predictions.MethodsWe fitted 2016-19 LB national surveillance data to a two-part spatio-temporal statistical model. Spatial and temporal random effects were specified using a Besag-York-Mollie model and a seasonal model, respectively. Coefficients were estimated in a Bayesian framework using integrated nested Laplace approximation. Data from 2020-21 were used for model validation.ResultsA high vegetation index (≥ 0.6) was positively associated with seasonal LB presence, while the index of deer presence (> 60%), mild soil temperature (15-22 °C), moderate air saturation deficit (1.5-5 mmHg) and higher tick bite frequency were associated with increased incidence. Prediction maps show a higher risk of LB in spring and summer (April-September), with higher incidence in parts of eastern, midwestern and south-western France.ConclusionWe present a national level spatial assessment of seasonal LB occurrence in Europe, disentangling factors associated with the presence and increased incidence of LB. Our findings yield quantitative evidence for national public health agencies to plan targeted prevention campaigns to reduce LB burden, enhance surveillance and identify further data needs. This approach can be tested in other LB endemic areas.

We report a case of unusual human anaplasmosis in the Amazon rainforest of French Guiana. Molecular typing demonstrated that the pathogen is a novel Anaplasma species, distinct to all known species, and more genetically related to recently described Anaplasma spp. causing infections in rainforest wild fauna of Brazil.

When it comes to tick-borne diseases, co-infections are often mentioned. This concept includes several entities. On the one hand, tick vectors or vertebrate reservoir host can harbor several microorganisms that can be pathogenic for humans. On the other hand, human co-infections can also be understood in different ways, ranging from seropositivity without clinical symptoms to co-disease, i.e., the simultaneous clinical expression of infections by two tick-borne microorganisms. The latter, although regularly speculated, is not often reported. Hence, we conducted a systematic review on co-infections between B. burgdorferi s.l., the etiological agent of Lyme borreliosis, and other microorganisms potentially transmitted to humans by Ixodes spp. ticks. A total of 68 relevant articles were included, presenting 655 cases of possible co-infections. Most cases of co-infections corresponded to patients with one tick-borne disease and presenting antibody against another tick-borne microorganism. Co-disease was particularly frequent in two situations: patients with clinical symptoms of high fever and erythema migrans (EM), and patients with neurological symptoms linked to the TBEv or a neuroborreliosis. No impact on severity was evidenced. Further studies are needed to better appreciate the frequency and the impact of co-infections between several tick-borne microorganisms.

Objectives: To compare two learning methods for Lyme disease (e-learning versus face-to-face training) to assess knowledge and know-how., Methods: The study population was volunteer general medicine residents and family physicians (FP). Face-to-face training on Lyme disease was offered to each group. E-learning training was then offered to those who had not attended the face-to-face training. Theoretical knowledge was assessed by an identical pre- and post-test questionnaire and know-how by a script concordance test., Results: Seventy learners (47 FPs and 23 general medicine residents) were included in the face-to-face training group and 61 (33 FPs and 28 general medicine residents) in the e-learning group. The pre- and post-test scores were significantly improved in the FP group (difference of 29.3±1.9 [P<0.0001] out of 100) as well as in the general medicine resident group (difference of 38.2±2.7 [P<0.0001] out of 100). E-learning was more effective than face-to-face training, particularly among general medicine residents (progression of mean difference of 44.3±3.4/100 vs. 30.9±4.0/100; P=0.0138) and to a lesser extent among FPs (progression of 25.3±2.3/100 vs. 31.9±2.7/100; P=0.0757). Forty-six script concordance tests were completed by FPs and 20 by general medicine residents. Script concordance test results did not seem significant between the subgroups., Conclusions: E-learning seems to be a good alternative to face-to-face training for Lyme disease. It seems to be more effective than face-to-face training for the acquisition of theoretical knowledge. The script concordance test evaluation of know-how did not show any difference between the two learning methods., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Ticks and tick-borne diseases have spread over the last decades. In parallel, the incidence in humans, accidental hosts for most of these zoonotic diseases, has increased. This epidemiological intensification can be associated with anthropogenic alterations of forest ecosystems and animal biodiversity, but also with socioeconomic changes. Their proliferation is largely due to human-induced effects on the factors that favor the circulation of these infectious agents. We selected different types of anthropogenic environments in Alsace, a region endemic for tick-borne diseases in France, to better understand the impact of human interventions on tick populations and tick-borne disease incidence. Ticks were collected in one golf course, three urban parks, one mid-mountain forest, and one alluvial forest that is currently part of a protected natural area. Ixodes ricinus was found primarily in humid vegetation, which is favorable for tick survival, such as grounds populated with trees and covered with leaf litter. We also observed that reforestation and high animal biodiversity in a protected area such as the alluvial forest led to a greater number of ticks, including both Ixodes &nbsp; ricinus and Dermacentor reticulatus , as well as to a higher prevalence of pathogens such as Borrelia burgdorferi sensu lato, Anaplasma &nbsp; phagocytophilum , Borrelia miyamotoi , and Rickettsia raoulti .

Neoehrlichia mikurensis is an intracellular bacterium transmitted in Europe and Asia by ticks of the Ixodes ricinus complex. Interest in this bacterium has increased since it was demonstrated to be responsible for febrile syndromes in patients. To date, most clinical cases have been reported in northern Europe, but case series have also been described in central Europe and China. Notably, thrombotic events occurred during the course of the disease. We investigated the presence of N. mikurensis in 10,885 I. ricinus nymphs in two regions of France (Alsace and Brittany) collected between 2013 and 2020 and in 934 patients suspected of human granulocytic anaplasmosis in Alsace, an endemic area for Lyme borreliosis, using a specific PCR assay. N. mikurensis was detected in 5.42% of the ticks from Alsace, whereas only one (0.03%) tick was found to be positive in Brittany. Spatiotemporal disparities were also noticed within the Alsace region over the four collection sites investigated, and a significant increase in the prevalence of nymphs carrying N. mikurensis was also observed in the last three years of collection. Four out of 934 screened patients were found to be positive for N. mikurensis . Two had malignancies, and the other two were apparently immunocompetent. Superficial thrombosis was noticed in one patient, and long-lasting bacteremia was noted in another patient. These four patients are the first clinical cases of neoehrlichiosis described in France. We suggest including N. mikurensis in the differential diagnosis of post-tick bite febrile syndromes to treat patients and prevent the occurrence of thrombotic complications.