Multiple factors affecting Ixodes ricinus ticks and associated pathogens in European temperate ecosystems (northeastern France).

In Europe, the main vector of tick-borne zoonoses is Ixodes ricinus, which has three life stages. During their development cycle, ticks take three separate blood meals from a wide variety of vertebrate hosts, during which they can acquire and transmit human pathogens such as Borrelia burgdorferi sensu lato, the causative agent of Lyme borreliosis. In this study conducted in Northeastern France, we studied the importance of soil type, land use, forest stand type, and temporal dynamics on the abundance of ticks and their associated pathogens. Negative binomial regression modeling of the results indicated that limestone-based soils were more favorable to ticks than sandstone-based soils. The highest tick abundance was observed in forests, particularly among coniferous and mixed stands. We identified an effect of habitat time dynamics in forests and in wetlands: recent forests and current wetlands supported more ticks than stable forests and former wetlands, respectively. We observed a close association between tick abundance and the abundance of Cervidae, Leporidae, and birds. The tick-borne pathogens responsible for Lyme borreliosis, anaplasmosis, and hard tick relapsing fever showed specific habitat preferences and associations with specific animal families. Machine learning algorithms identified soil related variables as the best predictors of tick and pathogen abundance.

Nunavimmi puvakkut kaggutimik aanniaqarniq: Qanuilirqitaa? Lung cancer in Nunavik: How are we doing? A retrospective matched cohort study.

BACKGROUND: Whether Inuit in Canada experience disparities in lung cancer survival remains unknown. When requiring investigation and treatment for lung cancer, all residents of Nunavik, the Inuit homeland in Quebec, are sent to the McGill University Health Centre (MUHC), in Montréal. We sought to compare survival among patients with lung cancer at the MUHC, who were residents of Nunavik and Montréal, Quebec, respectively. METHODS: We conducted a retrospective cohort study. Using lung cancer registry data, we identified Nunavik residents with histologically confirmed lung cancer diagnosed between 2005 and 2017. We aimed to match 2 Montréal residents to each Nunavik resident on sex, age, calendar year of diagnosis, and histology (non-small cell lung cancer v. small cell lung cancer). We reviewed medical records for data on additional patient characteristics and treatment, and obtained vital status from a provincial registry. We compared survival using Kaplan-Meier analysis and Cox proportional hazards regression. RESULTS: We included 95 residents of Nunavik and 185 residents of Montréal. For non-small cell lung cancer, median survival times were 321 (95% confidence interval [CI] 184-626) days for Nunavik (n = 71) and 720 (95% CI 536-1208) days for Montréal residents (n = 141). For small cell lung cancer, median survival times were 190 (95% CI 159-308) days for Nunavik (n = 24) and 270 (95% CI 194-766) days for Montréal residents (n = 44). Adjusting for matching variables, stage, performance status, and comorbidity, Nunavik residents had a higher hazard of death (hazard ratio 1.68, 95% CI 1.17-2.41). INTERPRETATION: Nunavik residents experience disparities in survival after lung cancer diagnosis. Although studies in other Inuit Nunangat regions are needed, our findings point to an urgent need to ensure that interventions aimed at improving lung cancer survival, including lung cancer screening, are accessible to Inuit Nunangat residents.

Predictors of clinical deterioration and intensive care unit admission in trauma patients transferred from northern Quebec to a level 1 trauma centre: a retrospective cohort study.

BACKGROUND: Trauma care in Nunavik, Quebec, is highly challenging. Geographic distances and delays in transport can translate into precarious patient transfers to tertiary trauma care centres. The objective of this study was to identify predictors of clinical deterioration during transport and eventual intensive care unit (ICU) admission for trauma patients transferred from Nunavik to a tertiary trauma care centre. METHODS: This is a retrospective cohort study using the Montreal General Hospital (MGH) trauma registry. All adult trauma patients transferred from Nunavik and admitted to the MGH from 2010 to 2019 were included. Main outcomes of interest were hemodynamic and neurologic deterioration during transport and ICU admission. RESULTS: In total, 704 patients were transferred from Nunavik and admitted to the MGH during the study period. The median age was 33 (interquartile range [IQR] 23-47) years and the median Injury Severity Score was 10 (IQR 5-17). On multiple regression analysis, transport time from site of injury to the MGH (odds ratio [OR] 1.04, 95% confidence interval [CI] 1.01-1.06), thoracic injuries (OR 1.75, 95% CI 1.03-2.99), and head and neck injuries (OR 3.76, 95% CI 2.10-6.76) predicted clinical deterioration during transfer. Injury Severity Score (OR 1.04, 95% CI 1.01-1.08), abnormal local Glasgow Coma Scale score (OR 2.57, 95% CI 1.34-4.95), clinical deterioration during transfer (OR 4.22, 95% CI 1.99-8.93), traumatic brain injury (OR 2.44, 95% CI 1.05-5.68), and transfusion requirement at the MGH (OR 4.63, 95% CI 2.35-9.09) were independent predictors of ICU admission. CONCLUSION: Our study identified several predictors of clinical deterioration during transfer and eventual ICU admission for trauma patients transferred from Nunavik. These factors could be used to refine triage criteria in Nunavik for more timely evacuation and higher level care during transport.

Cross-alteration of murine skin and tick microbiome concomitant with pathogen transmission after Ixodes ricinus bite.

BACKGROUND: Ticks are major vectors of diseases affecting humans such as Lyme disease or domestic animals such as anaplasmosis. Cross-alteration of the vertebrate host skin microbiome and the tick microbiome may be essential during the process of tick feeding and for the mechanism of pathogen transmission. However, it has been poorly investigated. METHODS: We used mice bitten by field-collected ticks (nymphs and adult ticks) in different experimental conditions to investigate, by 16S rRNA gene metabarcoding, the impact of blood feeding on both the mouse skin microbiome and the tick microbiome. We also investigated by PCR and 16S rRNA gene metabarcoding, the diversity of microorganisms transmitted to the host during the process of tick bite at the skin interface and the dissemination of the pathogen in host tissues (blood, heart, and spleen). RESULTS: Most of the commensal bacteria present in the skin of control mice were replaced during the blood-feeding process by bacteria originating from the ticks. The microbiome of the ticks was also impacted by the blood feeding. Several pathogens including tick-borne pathogens (Borrelia/Borreliella, Anaplasma, Neoehrlichia, Rickettsia) and opportunistic bacteria (Williamsia) were transmitted to the skin microbiome and some of them disseminated to the blood or spleen of the mice. In the different experiments of this study, skin microbiome alteration and Borrelia/Borreliella transmission were different depending on the tick stages (nymphs or adult female ticks). CONCLUSIONS: Host skin microbiome at the bite site was deeply impacted by the tick bite, to an extent which suggests a role in the tick feeding, in the pathogen transmission, and a potentially important impact on the skin physiopathology. The diversified taxonomic profiles of the tick microbiome were also modified by the blood feeding. Video Abstract.

Surgical, trauma and telehealth capacity in Indigenous communities in Northern Quebec: a cross-sectional survey.

BACKGROUND: Delivering trauma and surgical care to Northern Quebec presents unique challenges owing to the region's remoteness, extreme weather and limited transport; the expansion of telehealth could help address these difficulties. We aimed to evaluate current surgical, trauma and telemedicine capacity in Nunavik, Quebec. METHODS: We used validated assessment tools, including the Personnel, Infrastructure, Procedures, Equipment and Supplies survey, the International Assessment of Capacity for Trauma index and the Maryland Health Care Commission Telemedicine Readiness tool to evaluate surgical, trauma and telemedicine capacity, respectively. We adapted these tools to the Northern Quebec context through discussions with local leadership. Data were collected in 2 regional hospitals - the Ungava Tulattavik Health Centre (UTHC) and the Inuulitsivik Health Centre (IHC) - and 12 Centres locaux de services communautaires (CLSCs; local community services centres) in 6 villages along the Hudson Bay coast and 6 villages along the Ungava Bay coast through iterative discussions with 4 chief nurses from each regional hospital and set of CLSCs; resources were confirmed through on-site evaluation by the respondents. We performed a descriptive analysis of the data. RESULTS: Surgical capacity was highest in the IHC (6.76) and lowest in the Ungava Bay CLSCs (5.52). Personnel (0%-0%) and procedures (13%-33%) were the least available resources. Trauma capacity was highest in the IHC (7.25) and lowest in the Hudson Bay CLSCs (5.58). Although equipment (90%-100%) and supplies (100%-100%) were readily available, personnel (0%-0%) and procedures (25%-56%) were lacking. The UTHC was most prepared for telehealth (67.80%), and the Ungava Bay CLSCs achieved a lower score (51.13%). Underdeveloped telehealth criteria included funding, administrative support, quality improvement and physical spaces (all 33%-67%). CONCLUSION: Acute care capacity in Nunavik appears heterogeneous, with readily available equipment and supplies, but a lack of personnel capable of performing lifesaving procedures. To address the need for telemedicine, future initiatives should focus on improving funding, administrative support, physical spaces and quality-improvement initiatives.

Vaccines against tick-borne diseases: a big step forward?

Ticks and tick-borne diseases are on the rise due to socioecosystemic changes and climate modification and are affecting human and animal health. Few vaccines are available. Two recent articles from Matias et al. and Pine et al. used mRNA technology to explore tick and pathogen proteins as vaccine candidates.

[Anthropization and tick-borne diseases: the example of Lyme borreliosis]. / Anthropisation et maladies à tique : l'exemple de la borréliose de Lyme.

Ticks and tick-borne diseases are on the rise throughout the world. The reasons are multifactorial but all associated with human practices, including climate change and socio-economic and eco systemic changes. In the northern hemisphere, Lyme borreliosis and its vector, the tick belonging to the Ixodes ricinus complex, are particularly studied. Changes in forestry and the expansion of certain wild ungulates since the Second World War could explain the increasing presence of this tick in our environment. As it is likely to transmit other microorganisms potentially pathogenic to humans, an integrated multidisciplinary approach to identify human practices promoting its expansion is critical to control the (re)emergence of infectious diseases. Other ticks also benefit from the same anthropised context to increase their numbers in the environment.

Les tiques et maladies à tiques sont en expansion à travers le monde. Les raisons sont multifactorielles mais toutes associées aux pratiques humaines, notamment les modifications climatiques et les changements socio-économiques et écosystémiques. Dans l'hémisphère nord, la borréliose de Lyme et son vecteur, la tique appartenant au complexe Ixodes ricinus sont particulièrement étudiés. Les modifications de sylviculture et l'expansion de certains ongulés sauvages depuis la seconde guerre mondiale pourraient expliquer la présence de plus en plus importante de la tique dans notre environnement. Cette tique étant susceptible de transmettre d'autres microorganismes potentiellement pathogènes pour l'homme, une approche multidisciplinaire intégrée afin d'identifier les pratiques humaines qui favorisent son expansion est essentielle afin de contrôler la (ré)-émergence de maladies infectieuses. D'autres tiques bénéficient du même contexte anthropisé pour augmenter leur nombre dans l'environnement.

Diversity and phylogeny of the tick-borne bacterial genus Candidatus Allocryptoplasma (Anaplasmataceae).

The family Anaplasmataceae includes tick-borne bacteria of major public and veterinary health interest, as best illustrated by members of the genera Anaplasma and Ehrlichia. Recent epidemiological surveys have also reported on the presence of a novel putative genus in the Anaplasmataceae, Candidatus Allocryptoplasma, previously described as Candidatus Cryptoplasma in the western black-legged tick, Ixodes pacificus. However, the genetic diversity of Ca. Allocryptoplasma and its phylogenetic relationship with other Anaplasmataceae remain unclear. In this study, we developed a multi-locus sequence typing approach, examining the DNA sequence variation at five genes of Ca. Allocryptoplasma found in ticks. Combining this multi-locus sequence typing and genetic data available on public databases, we found that substantial genetic diversity of Ca. Allocryptoplasma is present in Ixodes, Amblyomma and Haemaphysalis spp. ticks on most continents. Further analyses confirmed that the Ca. Allocryptoplasma of ticks, the Ca. Allocryptoplasma of lizards and some Anaplasma-like bacteria of wild mice cluster into a monophyletic genus, divergent from all other genera of the family Anaplasmataceae. Candidatus Allocryptoplasma appears as a sister genus of Anaplasma and, with the genera Ehrlichia and Neoehrlichia, they form a monophyletic subgroup of Anaplasmataceae associated with tick-borne diseases. The detection of genetically distinct Ca. Allocryptoplasma in ticks of significant medical or veterinary interest supports the hypothesis that it is an emergent genus of tick-borne pathogens of general concern.

Title: Diversité et phylogénie du genre bactérien transmis par les tiques Candidatus Allocryptoplasma (Anaplasmataceae). Abstract: La famille des Anaplasmataceae comprend des bactéries transmises par les tiques qui présentent un intérêt majeur pour la santé publique et vétérinaire, comme les membres des genres Anaplasma et Ehrlichia. Des surveillances épidémiologiques récentes ont également signalé la présence d'un nouveau genre putatif dans les Anaplasmataceae, Candidatus Allocryptoplasma, initialement décrit comme Ca. Cryptoplasma chez une tique nord-américaine, Ixodes pacificus. Cependant, la diversité génétique des bactéries Ca. Allocryptoplasma et leurs relations phylogénétiques avec d'autres Anaplasmataceae restent méconnues. Dans cette étude, nous avons développé une approche de typage génétique multi-locus, en examinant la variation nucléotidique pour cinq gènes de bactéries Ca. Allocryptoplasma détectées chez les tiques. En combinant ce typage génétique multi-locus et les données génétiques disponibles dans les bases de données publiques, nous avons mis en évidence qu'une diversité génétique substantielle des bactéries Ca. Allocryptoplasma est présente chez les tiques des genres Ixodes, Amblyomma et Haemaphysalis sur la plupart des continents. Des analyses complémentaires confirment que les bactéries Ca. Allocryptoplasma des tiques, les bactéries Ca. Allocryptoplasma de lézards et des bactéries Anaplasma-like de souris sauvages se regroupent dans un genre monophylétique, divergent de tous les autres genres de la famille Anaplasmataceae. Candidatus Allocryptoplasma apparaît comme un genre frère d'Anaplasma et, avec les genres Ehrlichia et Neoehrlichia, ces trois genres forment un sous-groupe monophylétique d'Anaplasmataceae associé aux maladies transmises par les tiques. La détection de Ca. Allocryptoplasma dans des tiques d'intérêt médical et vétérinaire soutient l'hypothèse qu'il s'agit d'un genre émergent d'agents pathogènes majeurs.

First Expert Elicitation of Knowledge on Possible Drivers of Observed Increasing Human Cases of Tick-Borne Encephalitis in Europe.

Tick-borne encephalitis (TBE) is a viral disease endemic in Eurasia. The virus is mainly transmitted to humans via ticks and occasionally via the consumption of unpasteurized milk products. The European Centre for Disease Prevention and Control reported an increase in TBE incidence over the past years in Europe as well as the emergence of the disease in new areas. To better understand this phenomenon, we investigated the drivers of TBE emergence and increase in incidence in humans through an expert knowledge elicitation. We listed 59 possible drivers grouped in eight domains and elicited forty European experts to: (i) allocate a score per driver, (ii) weight this score within each domain, and (iii) weight the different domains and attribute an uncertainty level per domain. An overall weighted score per driver was calculated, and drivers with comparable scores were grouped into three terminal nodes using a regression tree analysis. The drivers with the highest scores were: (i) changes in human behavior/activities; (ii) changes in eating habits or consumer demand; (iii) changes in the landscape; (iv) influence of humidity on the survival and transmission of the pathogen; (v) difficulty to control reservoir(s) and/or vector(s); (vi) influence of temperature on virus survival and transmission; (vii) number of wildlife compartments/groups acting as reservoirs or amplifying hosts; (viii) increase of autochthonous wild mammals; and (ix) number of tick species vectors and their distribution. Our results support researchers in prioritizing studies targeting the most relevant drivers of emergence and increasing TBE incidence.

Phylogenetic evidence for a clade of tick-associated trypanosomes.

BACKGROUND: Trypanosomes are protozoan parasites of vertebrates that are of medical and veterinary concern. A variety of blood-feeding invertebrates have been identified as vectors, but the role of ticks in trypanosome transmission remains unclear. METHODS: In this study, we undertook extensive molecular screening for the presence and genetic diversity of trypanosomes in field ticks. RESULTS: Examination of 1089 specimens belonging to 28 tick species from Europe and South America led to the identification of two new trypanosome strains. The prevalence may be as high as 4% in tick species such as the castor bean tick Ixodes ricinus, but we found no evidence of transovarial transmission. Further phylogenetic analyses based on 18S rRNA, EF1-α, hsp60 and hsp85 gene sequences revealed that different tick species, originating from different continents, often harbour phylogenetically related trypanosome strains and species. Most tick-associated trypanosomes cluster in a monophyletic clade, the Trypanosoma pestanai clade, distinct from clades of trypanosomes associated with transmission by other blood-feeding invertebrates. CONCLUSIONS: These observations suggest that ticks may be specific arthropod hosts for trypanosomes of the T. pestanai clade. Phylogenetic analyses provide further evidence that ticks may transmit these trypanosomes to a diversity of mammal species (including placental and marsupial species) on most continents.

Clobetasol increases the abundance of Borrelia burgdorferi in the skin 70 times more in male mice compared to female mice.

Lyme borreliosis is caused by the spirochete Borrelia burgdorferi and is transmitted among vertebrate hosts by Ixodes scapularis ticks in eastern North America. Treatment with topical corticosteroids increases the abundance of B. burgdorferi in the skin of lab mice that have been experimentally infected via needle inoculation. In the present study, female and male C3H/HeJ mice were infected with B. burgdorferi via nymphal tick bite. Infected mice were treated with clobetasol on the skin of the right hindleg on days 35 and 36 post-infection and euthanized at days -2, 1, 3, 5, and 7 post-treatment; a group of control mice was infected but not treated with clobetasol. The spirochete abundance was quantified in 8 mouse tissues including bladder, heart, left hindleg skin, right hindleg skin, dorsal skin, ventral skin, left ear and right ear. Averaged across the 8 mouse tissues, the abundance of B. burgdorferi on days 3 and 5 were 21.4x and 14.4x higher in mice treated with clobetasol compared to the untreated control mice, but there were large differences among tissues. There was a dramatic sex-specific effect of the clobetasol treatment; the peak abundance of B. burgdorferi in the skin (left hindleg, right hindleg, dorsal, ventral) was 72.6x higher in male mice compared to female mice. In contrast, there was little difference between the sexes in the tissue spirochete load in the ears, bladder, and heart. Topical application of clobetasol could increase the sensitivity of direct diagnostic methods (e.g., culture, PCR) to detect B. burgdorferi in host skin biopsies.

"Laurin-Sandrow Syndrome - a review of the literature and classification system".

INTRODUCTION: Laurin-Sandrow syndrome also known as tetramelic mirror-image polydactyly is a rare congenital disorder characterized classically by polysyndactyly of the hands, mirror feet and nose anomalies (hypoplasia of the nasal alae and short columella) often associated with ulnar and/or fibular duplication. As a pathologic entity, it is heterogeneous, the patients displaying a variety of symptoms. This review aims to analyze the different aspects of the condition, such as clinical findings and methods of treatment to summarize the principal features of Laurin-Sandrow syndrome. MATERIALS AND METHODS: The review is based on searches on PubMed, Web of Science and Researchgate of the following terms: "Laurin-Sandrow syndrome", "mirror hands", "mirror feet", "tetramelic mirror-image polydactyly", "fibular dimelia" and "ulnar dimelia". Clinical cases, reviews and original articles were included. RESULTS: As a consequence of our findings, we suggest a modification of the Al-Qattan classification system for Mirror Hand-Multiple Hand Spectrum. CONCLUSION: Even though it has an extremely low incidence, a thorough understanding of the syndrome enables the surgeon to choose the appropriate treatment with the ultimate goal to improve the patient's life quality.

Impact of Different Anthropogenic Environments on Ticks and Tick-Associated Pathogens in Alsace, a French Region Highly Endemic for Tick-Borne Diseases.

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 ricinus and Dermacentor reticulatus, as well as to a higher prevalence of pathogens such as Borrelia burgdorferi sensu lato, Anaplasma phagocytophilum, Borrelia miyamotoi, and Rickettsia raoulti.

Trauma in northern Quebec, 2005-2014: epidemiologic features, transfers and patient outcomes.

BACKGROUND: The Inuit people residing in Nunavik, Quebec, are vulnerable to major trauma owing to environmental and social factors; however, there is no systematic data collection for trauma in Nunavik, and, apart from data regarding patients who are transferred to tertiary care centres, no data enter the Quebec trauma registry directly from Nunavik. We performed a study to characterize the epidemiologic features of trauma in Nunavik, and describe indications for transfer and outcomes of patients referred to the tertiary trauma centre. METHODS: We collected data retrospectively for all patients with trauma admitted to the Centre de santé Tulattavik de l'Ungava in Kuujjuaq from 2005 to 2014. Sociodemographic, injury and health services data were extracted. The data were analyzed in conjunction with coroners' reports on death from trauma in Nunavik. RESULTS: A total of 797 trauma cases were identified. The most common causes of injury were motor vehicle collisions (258 cases [32.4%]), falls (137 [17.2%]) and blunt assault (95 [11.9%]). One-third of patients (262 [32.9%]) were transferred to the tertiary care centre in Montréal. The incidence rate of major trauma (Injury Severity Score > 12) was 18.1 and 21.7 per 10 000 person-years in the Kuujjuaq region and the Puvirnituq region, respectively, which translates to a relative risk (RR) of 4 compared to the Quebec population. The disparity observed in trauma mortality rate was even greater, with an RR of 47.6 compared to the Quebec population. CONCLUSION: The study showed major disparity in trauma incidence and mortality rate between Nunavik and the province of Quebec. Our findings allow for a better understanding of the burden of injury and regional trauma mortality in Nunavik, and recommendations for optimization of the trauma system in this unique setting.

The emerging tick-borne pathogen Neoehrlichia mikurensis: first French case series and vector epidemiology.

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.

Induced Transient Immune Tolerance in Ticks and Vertebrate Host: A Keystone of Tick-Borne Diseases?

Ticks and tick transmitted infectious agents are increasing global public health threats due to increasing abundance, expanding geographic ranges of vectors and pathogens, and emerging tick-borne infectious agents. Greater understanding of tick, host, and pathogen interactions will contribute to development of novel tick control and disease prevention strategies. Tick-borne pathogens adapt in multiple ways to very different tick and vertebrate host environments and defenses. Ticks effectively pharmacomodulate by its saliva host innate and adaptive immune defenses. In this review, we examine the idea that successful synergy between tick and tick-borne pathogen results in host immune tolerance that facilitates successful tick infection and feeding, creates a favorable site for pathogen introduction, modulates cutaneous and systemic immune defenses to establish infection, and contributes to successful long-term infection. Tick, host, and pathogen elements examined here include interaction of tick innate immunity and microbiome with tick-borne pathogens; tick modulation of host cutaneous defenses prior to pathogen transmission; how tick and pathogen target vertebrate host defenses that lead to different modes of interaction and host infection status (reservoir, incompetent, resistant, clinically ill); tick saliva bioactive molecules as important factors in determining those pathogens for which the tick is a competent vector; and, the need for translational studies to advance this field of study. Gaps in our understanding of these relationships are identified, that if successfully addressed, can advance the development of strategies to successfully disrupt both tick feeding and pathogen transmission.

Proteomic as an Exploratory Approach to Develop Vaccines Against Tick-Borne Diseases Using Lyme Borreliosis as a Test Case.

Tick-borne diseases affecting humans and animals are on the rise worldwide. Vaccines constitute an effective control measure, but very few are available. We selected Lyme borreliosis, a bacterial infection transmitted by the hard tick Ixodes, to validate a new concept to identify vaccine candidates. This disease is the most common tick-borne disease in the Northern Hemisphere. Although attempts to develop a vaccine exist, none have been successfully marketed. In tick-borne diseases, the skin constitutes a very specific environment encountered by the pathogen during its co-inoculation with tick saliva. In a mouse model, we developed a proteomic approach to identify vaccine candidates in skin biopsies. We identified 30 bacterial proteins after syringe inoculation or tick inoculation of bacteria. Discovery proteomics using mass spectrometry might be used in various tick-borne diseases to identify pathogen proteins with early skin expression. It should help to better develop sub-unit vaccines based on a cocktail of several antigens, associated with effective adjuvant and delivery systems of antigens. In all vector-borne diseases, the skin deserves further investigation to better define its role in the elaboration of protective immunity against pathogens.

Effects of topical corticosteroids and lidocaine on Borrelia burgdorferi sensu lato in mouse skin: potential impact to human clinical trials.

Lyme borreliosis is the most prevalent vector-borne disease in northern hemisphere. Borrelia burgdorferi sensu lato spirochetes are transmitted by Ixodes species ticks. During a blood meal, these spirochetes are inoculated into the skin where they multiply and often spread to various target organs: disseminated skin sites, the central nervous system, the heart and large joints. The usual diagnosis of this disease relies on serological tests. However, in patients presenting persistent clinical manifestations, this indirect diagnosis is not capable of detecting an active infection. If the serological tests are positive, it only proves that exposure of an individual to Lyme spirochetes had occurred. Although culture and quantitative PCR detect active infection, currently used tests are not sensitive enough for wide-ranging applications. Animal models have shown that B. burgdorferi persists in the skin. We present here our targeted proteomics results using infected mouse skin biopsies that facilitate detection of this pathogen. We have employed several novel approaches in this study. First, the effect of lidocaine, a local anesthetic used for human skin biopsy, on B. burgdorferi presence was measured. We further determined the impact of topical corticosteroids to reactivate Borrelia locally in the skin. This local immunosuppressive compound helps follow-up detection of spirochetes by proteomic analysis of Borrelia present in the skin. This approach could be developed as a novel diagnostic test for active Lyme borreliosis in patients presenting disseminated persistent infection. Although our results using topical corticosteroids in mice are highly promising for recovery of spirochetes, further optimization will be needed to translate this strategy for diagnosis of Lyme disease in patients.

A novel Borrelia species, intermediate between Lyme disease and relapsing fever groups, in neotropical passerine-associated ticks.

Lyme disease (LD) and relapsing fevers (RF) are vector-borne diseases caused by bacteria of the Borrelia genus. Here, we report on the widespread infection by a non-described Borrelia species in passerine-associated ticks in tropical rainforests of French Guiana, South America. This novel Borrelia species is common in two tick species, Amblyomma longirostre and A. geayi, which feed on a broad variety of neotropical mammal and bird species, including migratory species moving to North America. The novel Borrelia species is divergent from the LD and RF species, and is more closely related to the reptile- and echidna-associated Borrelia group that was recently described. Genome sequencing showed that this novel Borrelia sp. has a relatively small genome consisting of a 0.9-Mb-large chromosome and an additional 0.3 Mb dispersed on plasmids. It harbors an RF-like genomic organization but with a unique mixture of LD- and RF-specific genes, including genes used by RF Borrelia for the multiphasic antigen-switching system and a number of immune-reactive protein genes used for the diagnosis of LD. Overall, our data indicate that this novel Borrelia is an intermediate taxon between the LD and RF species that may impact a large host spectrum, including American mammals. The designation "Candidatus Borrelia mahuryensis" is proposed for this species.