Bite Of Infected Tick Research Articles

Deciphering Rickettsia conorii metabolic pathways: a treasure map to therapeutic targets

Indian tick typhus is an infectious disease caused by intracellular gram-negative bacteria Rickettsia conorii (R. conorii). The bacterium is transmitted to humans through bite of infected ticks and sometimes by lice, fleas or mites. The disease is restricted to some areas with few cases but in last decade it is re-emerging with large number of cases from different areas of India. The insight in to genetic makeup of bacterial pathogens can be derived from their metabolic pathways. In the current study 18 metabolic pathways were found to be unique to the pathogen (R. conorii). A comprehensive analysis revealed 163 proteins implicated in 18 unique metabolic pathways of R. conorii. 140 proteins were reported to be essential for the bacterial survival, 46 were found virulent and 10 were found involved in resistance which can enhance the bacterial pathogenesis. The functional analysis of unique metabolic pathway proteins showed the abundance of plasmid conjugal transfer TrbL/VirB6, aliphatic acid kinase short chain, signal transduction response regulator receiver and components of type IV transporter system domains. The proteins were classified into six broad categories on the basis of predicted domains, i.e., metabolism, transport, gene expression and regulation, antimicrobial resistance, cell signalling and proteolysis. Further, in silico analysis showed that 88 proteins were suitable therapeutic targets which do not showed homology with host proteins. The 43 proteins showed hits with the DrugBank database showing their druggable nature and remaining 45 proteins were classified as novel drug targets that require further validation. The study will help to provide the better understanding of pathogens survival and embark on the development of successful therapies for the management of Indian tick typhus.

CD8+ T-cells target the Crimean-Congo haemorrhagic fever virus Gc protein to control the infection in wild-type mice

Crimean-Congo haemorrhagic fever (CCHF) is a serious viral hemorrhagic fever caused by the CCHF virus (CCHFV). Spread by the bites of infected ticks or handling of viremic livestock, human disease is characterized by a non-specific febrile illness that can rapidly progress to fatal hemorrhagic disease. No vaccines or antivirals are available. Case fatality rates can vary but can be higher than 30%, although sub-clinical infections are often unrecognized and unreported. Yet, while most humans infected with CCHFV will survive the infection, often with little-to-no symptoms, the host responses that control the infection are unknown. Here we investigated the role of cellular immunity in control of CCHFV infection in an immunocompetent mouse model. We found that CD8+ T-cells are crucial for efficient control of the acute infection and rapidly acquired CCHFV-specific antiviral effector functions such as production of antiviral cytokines and degranulating in response to CCHFV peptides. We further identified the minimal CD8+ T-cell epitopes in the viral Gc proteins and that infection of mice lacking IFNγ resulted in worsened disease and higher viral loads. Together our data suggest that CD8+ T-cells are important for control of acute CCHFV infection likely through production of antiviral cytokines. This work was supported by the Intramural Research Program of the NIH.

Tick-Borne Encephalitis in a 6-Year-Old Patient: A Case Report.

Background: Tick-Borne Encephalitis virus (TBEV) is a positive-sense single-stranded RNA virus belonging to the Flaviviridae family. TBEV transmission typically occurs through infected Ixodes tick bite or by consumption of unpasteurised milk from infected cattle. Case report: We report the clinical, neuroimaging, electroencephalogram (EEG), and laboratory (microbiological tests and spinal tap) data of a 6- year-old boy with Tick-borne encephalitis. Our patient presented with a biphasic course, initially with a myositis-like picture on his first admission to the emergency department, and after a few days with an encephalitic picture, resulting in a second hospitalization. EEG showed focal slow activity, while his brain magnetic resonance imaging (MRI) showed a signal abnormality, which completely resolved on repeat MRI after 3 months. Conclusion: To our knowledge, this is the youngest patient presenting with myositis in the first phase of Tick-borne encephalitis (TBE). In the presence of a biphasic clinical course, with previous myositis, aspecific MRI changes in the thalamic and midbrain regions and an EEG documenting slowed bioelectrical activity should prompt suspicion of TBEV infection.

West Nile Virus and Other Nationally Notifiable Arboviral Diseases - United States, 2021.

Arthropod-borne viruses (arboviruses) are transmitted to humans primarily through the bites of infected mosquitoes or ticks, and in the continental United States, West Nile virus (WNV) is the leading cause of domestically acquired arboviral disease. Other arboviruses cause sporadic cases of disease as well as occasional outbreaks. This report summarizes 2021 surveillance data reported to CDC by U.S. jurisdictions for nationally notifiable arboviruses; the report excludes chikungunya, dengue, yellow fever, and Zika virus disease cases, because these infections were acquired primarily through travel during 2021. Forty-nine states and the District of Columbia reported 3,035 cases of domestic arboviral disease, including those caused by West Nile (2,911), La Crosse (40), Jamestown Canyon (32), Powassan (24), St. Louis encephalitis (17), unspecified California serogroup (six), and eastern equine encephalitis (five) viruses. Among the WNV disease cases, 2,008 (69%) were classified as neuroinvasive disease, for a national incidence of 0.61 cases per 100,000 population. Because arboviral diseases continue to cause serious illness, maintaining surveillance programs to monitor their transmission and prevalence is important to the direction and promotion of prevention activities. Health care providers should consider arboviral infections in the differential diagnosis of aseptic meningitis and encephalitis, obtain appropriate specimens for laboratory testing, and promptly report cases to public health authorities. Prevention depends on community and household efforts to reduce vector populations and personal protective measures to prevent mosquito and tick bites, such as use of Environmental Protection Agency-registered insect repellent and wearing protective clothing.

Temporal dynamics of antibody level against Lyme disease bacteria in roe deer: Tale of a sentinel?

Changes in the risk of exposure to infectious disease agents can be tracked through variations in antibody prevalence in vertebrate host populations. However, information on the temporal dynamics of the immune status of individuals is critical. If antibody levels persist a long time after exposure to an infectious agent, they could enable the efficient detection of the past circulation of the agent; if they persist only a short time, they could provide snap shots of recent exposure of sampled hosts. Here, we explored the temporal dynamics of seropositivity against Lyme disease agent Borrelia burgdorferi sensu lato (Bbsl) in individuals of a widespread medium-sized mammal species, the roe deer (Capreolus capreolus), in France. Using a modified commercially available immunoassay we tested 1554 blood samples obtained in two wild deer populations monitored from 2010 to 2020. Using multi-event capture-mark-recapture models, we estimated yearly population-, age-, and sex-specific rates of seroconversion and seroreversion after accounting for imperfect detection. The yearly seroconversion rates indicated a higher level of exposure in early (2010-2013) than in late years (2014-2019) to infected tick bites in both populations, without any detectable influence of sex or age. The relatively high rates of seroreversion indicated a short-term persistence of antibody levels against Bbsl in roe deer. This was confirmed by the analysis of samples collected on a set of captive individuals that were resampled several times a few weeks apart. Our findings show the potential usefulness of deer as a sentinel for tracking the risk of exposure to Lyme disease Bbsl, although further investigation on the details of the antibody response to Bbsl in this incompetent host would be useful. Our study also highlights the value of combining long-term capture-mark-recapture sampling and short-time analyses of serological data for wildlife populations exposed to infectious agents of relevance to wildlife epidemiology and human health.

Seroprevalence and risk factors of tick-borne encephalitis in Mongolia between 2016 and 2022

The tick-borne encephalitis virus (TBEV) is a zoonotic agent that causes severe encephalitis in humans and is transmitted through the bites of infected ticks. Ixodes ticks are the primary vector for TBEV in Mongolia, and approximately 3.4% carry the TBEV. The ticks are capable of not only transmitting these viruses but also serve as excellent reservoir hosts. The Dermacenter tick species may have similar properties. TBEV is a significant cause of virus-related diseases of the central nervous system in many European countries as well as in China, Russia, and Mongolia. Our objectives were to investigate TBEV seroprevalence and infection risk factors in different biogeographical zones and provinces, especially in the highly endemic areas of Mongolia. Serum samples were collected from individuals who experienced tick bites (n = 993) in Mongolia between 2016 and 2022. Enzyme-linked immunosorbent assay of the samples was performed to evaluate for TBEV-specific immunoglobulin (Ig)M and IgG. We analyzed the risk factors and seroprevalence of TBEV infection among these individuals using a cross-sectional, questionnaire-based study. Statistical analyses were performed using a multistage cluster sampling survey design, and all data were analyzed using the R software. TBEV IgM and IgG antibodies were detected in 8.1% (80/993) and 20.2% (201/993) of all serum samples, respectively. The seroprevalence was significantly higher in men (68%, 95% confidence interval [CI]: 1.63–3.13, odds ratio [OR]: 2.25) than in women (p < 0.001). Additionally, the seroprevalence was significantly higher among unemployed (35.0%, 95% CI: 0.31–0.84, OR: 0.51) than employed individuals (p < 0.001). The seroprevalence was the highest among the 25–29 and 35–39-year age groups (11%, 95% CI: 1.29–5.51, OR: 2.65 and 11%, 95% CI: 0.94–3.87, OR: 1.9, respectively), and the lowest in the 65–69-year age group (4%, 95% CI: 0.46–6.15, OR: 1.83) (p < 0.001). Furthermore, the seroprevalence was the highest in Selenge province and the capital city Ulaanbaatar (40%, 95% CI: 1.73–21.7, OR: 5.07 and 28%, 95% CI: 0.51–6.89, OR: 1.57, respectively) and the lowest in Bayan-Ulgii and Dornod provinces (0.5%, 95% CI: 0.06–12.4, OR: 1.33 and 0.5%, 95% CI: 0.03–6.24, OR: 0.72, respectively). TBEV infection incidence remained low in most regions of Mongolia but increased in endemic areas. Furthermore, in the univariate subgroup analysis, age, occupation status, and residential area were significantly associated with TBEV seroprevalence.

Similarities and differences in the characteristics of the epidemical process tick-borne encephalitis and Lyme borreliosis

Objective: To identify common and distinctive characteristics of the epidemical process of tick-borne encephalitis and Lyme borreliosis on the example of the Republic of Karelia.Materials and methods. The frequency of infected tick bites, dynamics, intensity, territorial, gender, age and social features of the incidence of tick-borne encephalitis and Lyme borreliosis in 2000–2021 were analyzed according to official statistics, epidemiological examination of foci and laboratory studies. The results of studies of 2379 blood samples of adults who were not ill and not vaccinated against tick-borne encephalitis for the presence of antibodies to the virus were analyzed.Results. The virulence of ticks in 2000–2021 decreased from 23.6 to 1.3%, infection with borrelia at the level of 13.4– 38.4%. The average long-term incidence rates of tick-borne encephalitis and Lyme borreliosis were 6.2 and 6.6 per 100 thousand, the dynamics of incidence had an average pronounced downward trend, correlated with the dynamics of requests for medical care of the population affected by ticks. The main clinical form of tick–borne encephalitis is meningeal (48%). Non-erythemic forms of borreliosis in recent years amounted to 39.1%. Antibodies of class G to tick-borne encephalitis virus were detected in 11.8±0.7% of the examined individuals. The territory of risk of infection with tick-borne encephalitis and Lyme borreliosis is the central and eastern part of the south of the Republic, where I.persulcatus dominates. The proportion of urban residents among patients with both infections is higher, but the incidence of urban and rural populations did not have significant differences. The incidence rates of tick-borne borreliosis in persons aged 40-49, 50-59 and 60 years and older are 1.6-2.2 times higher than those of tick-borne encephalitis, but the difference is not significant. At working age, the percent of men is higher than women, there are no differences among the elderly.Conclusions: Similar and different features of the epidemic process of tick-borne encephalitis and tick-borne borreliosis have been identified, which should be taken to improving the detection of diseases, predicting the situation and planning preventive measures.

Crimean Congo Hemorrhagic Fever Virus in Ticks Isolated from Ruminants in Jahrom, Fars Province, Southern Iran

Background:Crimean Congo Hemorrhagic Fever (CCHF) is an emerging tick-borne viral zoonotic disease that is endemic in Iran. The CCHF virus is spread by an RNA virus of the genus Orthonairovirus , the family Nairoviridae. CCHF has been identified as the most frequent viral hemorrhagic fever in Iran. The route of CCHF transmission to humans is through infected tick bites, contact with infected livestock, infected blood or tissues of humans. Objectives: The aim of this study was to investigate the infection of livestocks with different species of ticks and also to determine the presence of CCHF virus in the ticks in Jahrom township. Methods:A total of 200 ticks were collected from Jahrom township, Fars Province, Southern Iran. To detect virus in infected ticks, total RNA was extracted using the RNeasy Mini Kit Qiagen and subjected to reverse transcriptase-polymerase chain reaction. Results:Of all the ticks tested, twelve (6%) were positive for the virus, 124 (62%) belonged to the species Rhipicephalus sanguineus, 37 (18.5%) belonged to Hyalomma anatolicum, 23 (11.5%) belonged to Hyalomma marginatus, 7 (3.5%) belonged to Hyalomma asiaticum, 4 (2%) belonged to Hyalomma dromedarii, and 5 (2.5%) belonged to Rhipicephalus bursa. Of the 200 ticks collected in the area, 117 (58.5%) were male and 83 (41.5%) were female. Conclusion:In this study, for the first time, we analyzed tick samples collected from Jahrom township for the presence of CCHF virus. The findings of our study might be valuable for designing preventive measures regarding CCHF in Fars province, although further studies are required.

Tick-Borne Encephalitis Virus: A Comprehensive Review of Transmission, Pathogenesis, Epidemiology, Clinical Manifestations, Diagnosis, and Prevention.

Tick-borne encephalitis virus (TBEV), a member of the Flaviviridae family, can cause serious infection of the central nervous system in humans, resulting in potential neurological complications and fatal outcomes. TBEV is primarily transmitted to humans through infected tick bites, and the viral agent circulates between ticks and animals, such as deer and small mammals. The occurrence of the infection aligns with the seasonal activity of ticks. As no specific antiviral therapy exists for TBEV infection, treatment approaches primarily focus on symptomatic relief and support. Active immunization is highly effective, especially for individuals in endemic areas. The burden of TBEV infections is increasing, posing a growing health concern. Reported incidence rates rose from 0.4 to 0.9 cases per 100,000 people between 2015 and 2020. The Baltic and Central European countries have the highest incidence, but TBE is endemic across a wide geographic area. Various factors, including social and environmental aspects, improved medical awareness, and advanced diagnostics, have contributed to the observed increase. Diagnosing TBEV infection can be challenging due to the non-specific nature of the initial symptoms and potential co-infections. Accurate diagnosis is crucial for appropriate management, prevention of complications, and effective control measures. In this comprehensive review, we summarize the molecular structure of TBEV, its transmission and circulation in natural environments, the pathogenesis of TBEV infection, the epidemiology and global distribution of the virus, associated risk factors, clinical manifestations, and diagnostic approaches. By improving understanding of these aspects, we aim to enhance knowledge and promote strategies for timely and accurate diagnosis, appropriate management, and the implementation of effective control measures against TBEV infections.

Багатофакторна модель прогнозування тяжкого перебігу та ураження органів і систем при Лайм-бореліозі в дітей

Lyme disease (tick-borne borreliosis, Lyme borreliosis - LB) is a multisystem zoonotic disease transmitted by the bite of infected ticks. Purpose - to develop a mathematical model for predicting the risk of severity of the course (PRSC) of LB by the risk factor for the development of disseminated LB in children who have had a tick attack. Materials and methods. To build a model for PRSC of LB using multivariate regression analysis, 121 children with LB aged 13±3 years (from 1 to 18 years) were examined, including 51 boys and 70 girls. Groups of patients: 78 children with erythema migrans, 16 - with Lyme arthritis, 27 - with nervous system lesions. The quality of the prognostic model was checked by the Neigelkerk criterion (R2), and the acceptability of the model was assessed using ANOVA analysis of variance. Serological examination of patients bitten by ticks was performed by enzyme-linked immunosorbent assay. To detect immunoglobulins of classes M (IgM) and G (IgG) to B. burgdorferi s.l. complex, test systems from Euroimmun AG (Germany) were used. IgM antibodies were determined by the test system Anti-Borrelia burgdorferi ELISA, IgG - by Anti-Borrelia plus VIsE ELIS. Blood samples with intermediate and positive results of the first stage of work were examined by immune blotting: IgM antibodies were detected using the system Anti-Borrelia EUROLINE Borrelia RN-AT (IgM), and IgG antibodies - Anti-Borrelia EUROLINE RN-AT. Results. The method of multivariate regression analysis for predicting the severe course and damage to organs and systems in children with LB, taking into account the factors and variants of the disease itself, allows to develop a mathematical model of PRSC of LB and to improve the effectiveness of treatment. Thus, all prerequisites have been created for high-quality preventive measures and reducing the risk of severe pulmonary disease. The initial data for predicting the severity of pulmonary disease were 28 factors. According to the results of the regression analysis, 24 factors were included in the model for predicting the severity of the course of pulmonary disease. Conclusions. For the first time, a multivariate regression model for PRSC of LB for pulmonary fibrosis in children was built. The weighting coefficients of each of the factors of the onset and progression of LB were taken into account: 0-10 points indicate the development of a localized stage (primary effect stage), while 11 or more points indicate a disseminated (generalized) stage. The results of the study make it possible to further develop standardized scales of the severity of LB and possible organ and system damage. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

A rare occurrence of Anaplasma-associated peritonitis.

Anaplasmosis or human granulocytic anaplasmosis is a tick-borne illness caused by the bacteria, Anaplasma phagocytophilum, resulting from an infected tick bite. Examination of a blood smear within the first week of exposure may show microcolonies of anaplasmae (morulae) in the cytoplasm of neutrophils that are highly suggestive of anaplasmosis but not definitive. We present the first case describing Anaplasma-related peritonitis and morulae in peritoneal fluid granulocytes in a peritoneal dialysis patient who developed anaplasmosis.

In silico formulation of a next-generation multiepitope vaccine for use as a prophylactic candidate against Crimean-Congo hemorrhagic fever

BackgroundCrimean-Congo hemorrhagic fever (CCHF) is a widespread disease transmitted to humans and livestock animals through the bite of infected ticks or close contact with infected persons’ blood, organs, or other bodily fluids. The virus is responsible for severe viral hemorrhagic fever outbreaks, with a case fatality rate of up to 40%. Despite having the highest fatality rate of the virus, a suitable treatment option or vaccination has not been developed yet. Therefore, this study aimed to formulate a multiepitope vaccine against CCHF through computational vaccine design approaches.MethodsThe glycoprotein, nucleoprotein, and RNA-dependent RNA polymerase of CCHF were utilized to determine immunodominant T- and B-cell epitopes. Subsequently, an integrative computational vaccinology approach was used to formulate a multi-epitopes vaccine candidate against the virus.ResultsAfter rigorous assessment, a multiepitope vaccine was constructed, which was antigenic, immunogenic, and non-allergenic with desired physicochemical properties. Molecular dynamics (MD) simulations of the vaccine-receptor complex show strong stability of the vaccine candidates to the targeted immune receptor. Additionally, the immune simulation of the vaccine candidates found that the vaccine could trigger real-life-like immune responses upon administration to humans.ConclusionsFinally, we concluded that the formulated multiepitope vaccine candidates would provide excellent prophylactic properties against CCHF.

Distribution pattern of Crimean-Congo Hemorrhagic Fever in Asia and the Middle East.

Crimean-Congo Hemorrhagic Fever (CCHF) is one of the most important vector-borne diseases of zoonotic potential that can be acquired following the bite of the Hyalomma species of ticks. It is a highly prevalent disease in Asia and the Middle East. The risk factors of this disease are contact with infected tissue, blood, patient, or livestock in the acute viremic phase, infected tick bites, or the manual removal of ticks. The disease is clinically described as progressive hemorrhages, fever, and pain in musculature. Biochemical tests reveal elevated levels of creatinine phosphokinase, alanine transaminase, aspartate aminotransferase, and lactate dehydrogenase. Clotting time is prolonged in pro-thrombin tests, and pathogenesis is mostly related to the disruption of the epithelium during viral replication and indirectly by secreting cytotoxic molecules. These molecules cause endothelial activation and result in the loss of function. Supportive therapy is given through blood or plasma infusions to treat or manage the patients. According to the most advanced studies, CCHF can be treated by Ribavirin, which is an antiviral drug that shows excellent results in preventing the disease. Health-care staff are more prone to infection. The hemorrhagic phase represents a high risk for accidental exposures. This literature review presents a comprehensive overview of the viral epidemiology, zoonotic perspectives, and significant risk factors of CCHF in various Middle East and Asian countries. Furthermore, the pathophysiology and preventive strategies of CCHF have also been discussed as well as legislation and policies regarding public outreach programs, research, and development aimed at infection prevention and control that are required at a global level.

Seroprevalence of Crimean Congo Hemorrhagic Fever Virus in Livestock, Pakistan

Crimean-Congo Haemorrhagic Fever Virus (CCHFV) is among the deadly human pathogens which cause a highly lethal haemorrhagic fever. CCHFV, a high-priority zoonotic pathogen is distributed widely and is transmitted in a vertical transmission cycle through these animals. Humans get infected by an infected tick bite, contact with viremic livestock blood, and through nosocomial route. Several CCHFV outbreaks have been reported for the past 2 decades in Pakistan and the virus has emerged in previously non-endemic regions as well. It is important to screen animals for CCHFV through an efficient diagnostic assay to prevent the viral zoonotic spill over to humans. Objectives: To screen the presence of CCHFV in sera collected from cattle, goat, and sheep in various regions in Punjab, Khyber Pakhtunkhwa (KP) and Sindh through a pre-established IgG ELISA assay. Methods: A recombinant nucleoprotein (rNP) of CCHFV was used to capture the anti CCFHV IgG antibodies in the animal sera. Results: Among 164 animals tested, 65% (103/164) showed the presence of IgG CCHFV antibodies. From the total 103 animals tested positive, 14.5 % (CI 0-28.2%) were cattle, 63.7% (CI 38.5-60.3%) were goats and 42% (CI 24.4-48.8%) were sheep. Conclusions: High seroprevalence of the CCHFV was expected from these areas as numerous cases of CCHFV have been reported previously. Since no commercial tests are available for the detection of CCHFV-specific antibodies in animals, this IgG ELISA test can be used to screen the animals in areas at risk such as those that have the presence of permissive ticks

Sofosbuvir and its tri-phosphate metabolite inhibit the RNA-dependent RNA polymerase activity of non-structural protein 5 from the Kyasanur forest disease virus

Kyasanur forest disease is a neglected zoonotic disease caused by a single-stranded RNA-based flavivirus, the incidence of which was first recorded in 1957 in the Southern part of India. Kyasanur forest disease virus is transmitted to monkeys and humans through the infected tick bite of Haemophysalis spinigera. Kyasanur forest disease is a febrile illness, which in severe cases, results in neurological complications leading to mortality. The current treatment regimens are symptomatic and supportive, and no targeted therapies are available for this disease. In this study, we evaluated the ability of FDA-approved drugs sofosbuvir (and its active metabolite) and Dasabuvir to inhibit the RNA-dependent RNA polymerase activity of NS5 protein from the Kyasanur forest disease virus. NS5 protein containing the N-terminal methyl transferase domain and C-terminal RNA-dependent RNA polymerase domain was expressed in Escherichia coli, and RNA-dependent RNA polymerase activity was demonstrated with the purified protein. The RNA-dependent RNA polymerase assay conditions were optimized, followed by the determination of apparent Km,ATP to validate the enzyme preparation. Half maximal-inhibitory concentrations against RNA-dependent RNA polymerase activity were determined for Sofosbuvir and its active metabolite. Dasabuvir did not show detectable inhibition with the tested conditions. This is the first demonstration of the inhibition of RNA-dependent RNA polymerase activity of NS5 protein from the Kyasanur forest disease virus with small molecule inhibitors. These initial findings can potentially facilitate the discovery and development of targeted therapies for treating Kyasanur forest disease.

Transmission Cycle of Tick-Borne Infections and Co-Infections, Animal Models and Diseases.

Tick-borne pathogens such as species of Borrelia, Babesia, Anaplasma, Rickettsia, and Ehrlichia are widespread in the United States and Europe among wildlife, in passerines as well as in domestic and farm animals. Transmission of these pathogens occurs by infected ticks during their blood meal, carnivorism, and through animal bites in wildlife, whereas humans can become infected either by an infected tick bite, through blood transfusion and in some cases, congenitally. The reservoir hosts play an important role in maintaining pathogens in nature and facilitate transmission of individual pathogens or of multiple pathogens simultaneously to humans through ticks. Tick-borne co-infections were first reported in the 1980s in white-footed mice, the most prominent reservoir host for causative organisms in the United States, and they are becoming a major concern for public health now. Various animal infection models have been used extensively to better understand pathogenesis of tick-borne pathogens and to reveal the interaction among pathogens co-existing in the same host. In this review, we focus on the prevalence of these pathogens in different reservoir hosts, animal models used to investigate their pathogenesis and host responses they trigger to understand diseases in humans. We also documented the prevalence of these pathogens as correlating with the infected ticks' surveillance studies. The association of tick-borne co-infections with other topics such as pathogens virulence factors, host immune responses as they relate to diseases severity, identification of vaccine candidates, and disease economic impact are also briefly addressed here.

Assessment of Physician Knowledge, Attitudes, and Practice for Lyme Disease in a Low-Incidence State.

Lyme disease (LD), caused by the bacterium Borrelia burgdorferi, is transmitted to humans in California through the bite of infected blacklegged ticks (Ixodes pacificus). Overall, the incidence of LD in California is low: approximately 0.2 confirmed cases per 100,000 population. However, California's unique ecological diversity results in wide variation in local risk, including regions with local foci at elevated risk of human disease. The diagnosis of LD can be challenging in California because the prior probability of infection for individual patients is generally low. Combined with nonspecific symptoms and complicated laboratory testing, California physicians need a high level of awareness of LD in California to recognize and diagnose LD efficiently. This research addresses an under-studied area of physicians' knowledge and practice of the testing and treatment of LD in a low-incidence state. We assessed knowledge and practices related to LD diagnosis using an electronic survey distributed to physicians practicing in California through mixed sampling methods. Overall, responding physicians in California had a general awareness of Lyme disease and were knowledgeable regarding diagnosis and treatment. However, we found that physicians in California could benefit from further education to improve test-ordering practices, test interpretation, and awareness of California's disease ecology with elevated levels of focal endemicity, to improve recognition, diagnosis, and treatment of LD in California patients.

Replicating RNA vaccination elicits an unexpected immune response that efficiently protects mice against lethal Crimean-Congo hemorrhagic fever virus challenge.

SummaryBackgroundCrimean-Congo hemorrhagic fever virus is the cause of a severe hemorrhagic fever with cases reported throughout a wide-geographic region. Spread by the bite of infected ticks, contact with infected livestock or in the health care setting, disease begins as a non-specific febrile illness that can rapidly progress to hemorrhagic manifestations. Currently, there are no approved vaccines and antivirals such as ribavirin have unclear efficacy. Thus treatment is mostly limited to supportive care.MethodsIn this report we evaluated an alphavirus-based replicon RNA vaccine expressing either the CCHFV nucleoprotein or glycoprotein precursor in a stringent, heterologous lethal challenge mouse model.FindingsVaccination with the RNA expressing the nucleoprotein alone could confer complete protection against clinical disease, but vaccination with a combination of both the nucleoprotein and glycoprotein precursor afforded robust protection against disease and viral replication. Protection from lethal challenge required as little as a single immunization with 100ng of RNA. Unexpectedly, analysis of the immune responses elicited by the vaccine components showed that vaccination resulted in antibodies against the internal viral nucleoprotein and cellular immunity against the virion-exposed glycoproteins.InterpretationCumulatively this vaccine conferred robust protection against Crimean-Congo hemorrhagic fever virus and supports continued development of this vaccine candidate.FundingThis research was supported by the Intramural Research Program of the NIAID/NIH and HDT Bio.

Crimean-Congo hemorrhagic fever virus circulating among sheep of Portugal: a nationwide serosurvey assessment.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a widespread zoonotic pathogen that can cause mild to severe hemorrhagic disease in humans. CCHFV may be transmitted through direct contact with tissue or blood of viremic animals; however, the primary transmission route is through infected tick bites. CCHFV RNA has been detected in ticks feeding on domestic and wild animals in western Spain, suggesting an established circulation of CCHFV in Western Europe. Ruminants have been recognized as important CCHFV reservoirs and have been linked to human cases in endemic regions. Given the emergence of CCHF in neighboring Spain, and a report of two CCHFV seropositive humans in southern Portugal in 1985, we investigated the potential circulation of this virus in the country by performing a nationwide anti-CCHFV IgG serosurvey in sentinel sheep of Portugal. Sera (n = 459) randomly selected from widely distributed farms (n = 20) of Portugal were tested using a commercial double-antigen enzyme-linked immunosorbent assay, yielding an overall seroprevalence of 0.4% (95% confidence interval [CI] 0.04-1.56%). Positive sheep were from the southern region of Portugal (Alentejo region), which raise the seroprevalence of this region to 0.74% (95% CI 0.09-2.66%). This is the first study reporting the presence of CCHFV antibodies in sheep of Portugal, thus suggesting a geographical expansion of CCHFV to this country. It seems likely that CCHFV may exist focally in southern Portugal.

Epidemiological Trends of Trans-Boundary Tick-Borne Encephalitis in Europe, 2000-2019.

Tick-borne encephalitis is a neuroinfection widely distributed in the Euro–Asia region. Primarily, the virus is transmitted by the bite of infected ticks. From 2000–2019, the total number of confirmed cases in Europe reported to the European Centre for Disease Prevention and Control was 51,519. The number of cases decreased in 2014 and 2015; however, since 2015, a growing number of cases have been observed, with the involvement of countries in which TBE has not been previously reported. The determinant factors for the spread of TBE are host population size, weather conditions, movement of hosts, and local regulations on the socioeconomic dynamics of the local and travelling people around the foci areas. The mean incidence rate of tick-borne encephalitis from 2000–2019 in Europe was 3.27, while the age-adjusted mean incidence rate was 2.19 per 100,000 population size. This review used several articles and data sources from the European Centre for Diseases Prevention and Control.