A New Orthonairovirus Associated with Human Febrile Illness.

BACKGROUND: In June 2019, a patient presented with persistent fever and multiple organ dysfunction after a tick bite at a wetland park in Inner Mongolia. Next-generation sequencing in this patient revealed an infection with a previously unknown orthonairovirus, which we designated Wetland virus (WELV). METHODS: We conducted active hospital-based surveillance to determine the prevalence of WELV infection among febrile patients with a history of tick bites. Epidemiologic investigation was performed. The virus was isolated, and its infectivity and pathogenicity were investigated in animal models. RESULTS: WELV is a member of the orthonairovirus genus in the Nairoviridae family and is most closely related to the tickborne Hazara orthonairovirus genogroup. Acute WELV infection was identified in 17 patients from Inner Mongolia, Heilongjiang, Jilin, and Liaoning, China, by means of reverse-transcriptase-polymerase-chain-reaction assay. These patients presented with nonspecific symptoms, including fever, dizziness, headache, malaise, myalgia, arthritis, and back pain and less frequently with petechiae and localized lymphadenopathy. One patient had neurologic symptoms. Common laboratory findings were leukopenia, thrombocytopenia, and elevated d-dimer and lactate dehydrogenase levels. Serologic assessment of convalescent-stage samples obtained from 8 patients showed WELV-specific antibody titers that were 4 times as high as those in acute-phase samples. WELV RNA was detected in five tick species and in sheep, horses, pigs, and Transbaikal zokors (Myospalax psilurus) sampled in northeastern China. The virus that was isolated from the index patient and ticks showed cytopathic effects in human umbilical-vein endothelial cells. Intraperitoneal injection of the virus resulted in lethal infections in BALB/c, C57BL/6, and Kunming mice. The Haemaphysalis concinna tick is a possible vector that can transovarially transmit WELV. CONCLUSIONS: A newly discovered orthonairovirus was identified and shown to be associated with human febrile illnesses in northeastern China. (Funded by the National Natural Science Foundation of China and the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences.).

Ticking on Pandora's box: a prospective case-control study into 'other' tick-borne diseases.

BACKGROUND: Tick-borne pathogens other than Borrelia burgdorferi sensu lato - the causative agent of Lyme borreliosis - are common in Ixodes ricinus ticks. How often these pathogens cause human disease is unknown. In addition, diagnostic tools to identify such diseases are lacking or reserved to research laboratories. To elucidate their prevalence and disease burden, the study 'Ticking on Pandora's Box' has been initiated, a collaborative effort between Amsterdam University Medical Center and the National Institute for Public Health and the Environment. METHODS: The study investigates how often the tick-borne pathogens Anaplasma phagocytophilum, Babesia species, Borrelia miyamotoi, Neoehrlichia mikurensis, spotted fever group Rickettsia species and/or tick-borne encephalitis virus cause an acute febrile illness after tick-bite. We aim to determine the impact and severity of these tick-borne diseases in the Netherlands by measuring their prevalence and describing their clinical picture and course of disease. The study is designed as a prospective case-control study. We aim to include 150 cases - individuals clinically suspected of a tick-borne disease - and 3 matched healthy control groups of 200 persons each. The controls consist respectively of a group of individuals with either a tick-bite without complaints, the general population and of healthy blood donors. During a one-year follow-up we will acquire blood, urine and skin biopsy samples and ticks at baseline, 4 and 12 weeks. Additionally, participants answer modified versions of validated questionnaires to assess self-reported symptoms, among which the SF-36, on a 3 monthly basis. DISCUSSION: This article describes the background and design of the study protocol of 'Ticking on Pandora's Box'. With our study we hope to provide insight into the prevalence, clinical presentation and disease burden of the tick-borne diseases anaplasmosis, babesiosis, B. miyamotoi disease, neoehrlichiosis, rickettsiosis and tick-borne encephalitis and to assist in test development as well as provide recommendations for national guidelines. TRIAL REGISTRATION: NL9258 (retrospectively registered at Netherlands Trial Register, trialregister.nl in in February 2021).

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.

Cutaneous histopathology of the tick-bite region in severe fever with thrombocytopenia syndrome.

A case of severe fever with thrombocytopenia syndrome (SFTS) in which a skin biopsy from the tick-bite region was analyzed is reported. The patient was a 72-year-old woman who developed fever and thrombocytopenia after a tick bite. SFTS was diagnosed from polymerase chain reaction (PCR) analysis of a blood sample. Histopathological analysis of a skin biopsy specimen from the tick-bite region showed CD20-positive perivascular and interstitial immunoblastic cells, which were positive to anti-SFTS virus (SFTSV) nucleoprotein antibody. In addition, SFTSV RNA was detected by real-time PCR from this biopsy specimen. Moreover, hemophagocytosis was also found in the tick-bite region. To the best of our knowledge, this is the first report to analyze the details of the tick-bite region of skin in SFTS, and the first to detect virus-infected cells in the skin. The present findings may help elucidate the mechanisms of entry of SFTSV.

Seroprevalence of Borrelia burgdorferi, B. miyamotoi, and Powassan Virus in Residents Bitten by Ixodes Ticks, Maine, USA.

We conducted a serosurvey of 230 persons in Maine, USA, who had been bitten by Ixodes scapularis or I. cookei ticks. We documented seropositivity for Borrelia burgdorferi (13.9%) and B. miyamotoi (2.6%), as well as a single equivocal result (0.4%) for Powassan encephalitis virus.

Case Report: A Case of Colorado Tick Fever Acquired in Southwestern Saskatchewan.

Colorado tick fever virus is transmitted by Dermacentor andersoni ticks. In Canada, these ticks are found in the southern regions of British Columbia (Rocky Mountains) and Alberta, as well as southwestern Saskatchewan. Colorado tick fever should be clinically suspected in patients presenting with a biphasic febrile illness and leukopenia following tick exposure in the appropriate geographic area.

Primary care physician management of tick bites in the Franche-Comté region (Eastern France, 2013).

INTRODUCTION: Tick bites, which may lead to Lyme disease, often prompt patients to consult their primary care physicians (PCPs). The aim of the present study was to assess how and how often PCPs in the Franche-Comté region of France manage tick bites. MATERIAL AND METHODS: Standardized questionnaires were sent to a random sample of 400 PCPs in the Franche-Comté region, requesting their voluntary and anonymous participation. The questionnaires collected socio-demographic details and practice-related information about tick-bite prophylaxis, Lyme serology, and tick-borne encephalitis vaccination. RESULTS: The crude response rate was 54.5% of the PCPs contacted. Tick-bite prophylaxis was prescribed as per current guidelines. However, Lyme serology seemed to be largely overprescribed for tick bites and in case of erythema migrans. A clear lack of knowledge about tick-borne encephalitis vaccination was also observed. DISCUSSION: PCPs provide the first line of care for patients presenting with tick bites. This study showed that although PCPs of the Franche-Comté region manage tick bites as per current guidelines, they need further training on Lyme serology limitations and availability of tick-borne encephalitis vaccination.

Molecular (ticks) and serological (humans) study of Crimean-Congo hemorrhagic fever virus in the Iberian Peninsula, 2013-2015.

INTRODUCTION: Crimean-Congo hemorrhagic fever (CCHF) is a viral disease, mainly transmitted through tick bite, of great importance in Public Health. In Spain, Crimean-Congo hemorrhagic fever virus (CCHFV) was detected for the first time in 2010 in Hyalomma lusitanicum ticks collected from deer in Cáceres. The aim of this study was to investigate the presence of CCHFV in ticks from Cáceres, and from other Spanish areas, and to evaluate the presence of antibodies against the virus in individuals exposed to tick bites. METHODS: A total of 2053 ticks (1333 Hyalomma marginatum, 680 H. lusitanicum and 40 Rhipicephalus bursa) were analyzed using molecular biology techniques (PCR) for CCHFV detection. The determination of specific IgG antibodies against CCHFV in 228 serum samples from humans with regular contact with ticks (at risk of acquiring the infection) was performed by indirect immunofluorescence assay. RESULTS: The CCHFV was not amplified in ticks, nor were antibodies against the virus found in the serum samples analyzed. CONCLUSION: The absence of the CCHFV in the ticks studied and the lack of antibodies against the virus in individuals exposed to tick bites would seem to suggest a low risk of acquisition of human infection by CCHFV in Spain.

Serosurvey of Coxiella burnetii in high risk population in Turkey, endemic to Crimean-Congo haemorrhagic fever virus.

BACKGROUND & OBJECTIVES: Q fever caused by Coxiella burnetii is a zoonotic infection that spreads to human beings from animals. This study was aimed to demographically examine the C. burnetii seroprevalence in the people living in villages where Crimean-Congo haemorrhagic fever virus (CCHFV) is endemic, in terms of various risk factors such as tick bites, tick contact, and occupational groups. METHODS: A total of 440 serum samples from those living in rural areas of Sivas and Tokat regions in Turkey were included in the study as a risk group; 387of them were serologically CCHFV positive (as confirmed in our previous research). Serums of the control group composed of 110 people living in urban areas. In all serum samples, IgG antibodies of C. burnetii against phase-I and phase-II antigens were diagnosed using the ELISA method. RESULTS: Coxiella burnetii seropositivity was detected in 19.09% of those living in rural areas and 4.55% of those living in urban areas (p < 0.001, OR = 4.96). In terms of their approach to the ticks, no statistical difference was observed between the risk groups in the chi-square test (p = 0.787). However, according to univariate analysis, the absorbance means of antibodies reactive to C. burnetii was statistically higher for the rural people who have made contact with ticks than those who have not (p = 0.017). No seroepidemiological relation was found between CCHFV and C. burnetii serology (p = 0.787), and the rate of co-seropositivity between them was 5.43% (21/387). INTERPRETATION & CONCLUSION: The findings of the study showed that C. burnetii infection is epidemic especially in the people living in rural areas. Contact with ticks in various ways might have resulted in the increased risk of C. burnetii infection in the study. Personal protective measures against tick bites may be important for reducing Q fever risk as in other tick-borne infectious disease.

Risk Factors for Bunyavirus-Associated Severe Fever with Thrombocytopenia Syndrome: A Community-Based Case-Control Study.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus. Previous studies about risk factors for SFTSV infection have yielded inconsistent results, and behavior factors have not been fully clarified. METHODS: A community-based, 1:4 matched case-control study was carried out to investigate the risk factors for SFTS in China. Cases of SFTS were defined as laboratory-confirmed cases that tested positive for real-time PCR (RT-PCR) for severe fever with thrombocytopenia syndrome bunyavirus (SFTSV) or positive for IgM antibodies against SFTSV. Controls of four neighborhood subjects were selected by matching for sex, age, and occupation. Standardized questionnaires were used to collect detailed information about their demographics and risk factors for SFTSV infection. RESULTS: A total of 334 subjects participated in the study including 69 cases and 265 controls. The median age of the cases was 59.5 years, 55.1% were male, and 87.0% were farmers. No differences in demographics were observed between cases and controls. In the final multivariate analysis, tick bites two weeks prior to disease onset (OR = 8.04, 95%CI 3.34-19.37) and the presence of weeds and shrubs around the house (OR = 3.46, 95%CI 0.96-12.46) were found to be risk factors for SFTSV infection; taking preventative measures during outdoor activities (OR = 0.12, 95%CI 0.01-1.01) provided greater protection from SFTSV infection. CONCLUSIONS: Our results further confirm that SFTSV is transmitted by tick bites and prove that preventative measures that reduce exposure to ticks can prevent SFTSV infection. More efforts should be directed toward health education and behavior change for high-risk populations, especially outdoor workers, in SFTS endemic areas.

Sero-epidemiological survey of Crimean-Congo hemorrhagic fever virus in Tunisia.

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease associated with a high case fatality rate and transmitted mainly by Hyalomma marginatum. The geographical distribution of H. marginatum covers most of the Western Mediterranean basin. We aimed to investigate whether CCHF virus (CCHFv) is circulating in Tunisia. Samples from unexplained acute febrile patients (n = 181) and a high risk group of humans, mainly slaughter workers (n = 38), were collected in the summer of 2014 and analyzed for exposure to CCHFv using serological tests and real-time RT-PCR. Ticks were collected from Northern and Southern Tunisia during May-June 2014 and examined for the presence of CCHFv by real-time RT-PCR. Of the 181 febrile patients, 5 showed only high titers of IgM suggesting a recent exposure to CCHFv. Among 38 slaughter workers, 2 had IgG anti-CCHFv responses yielding a seroprevalence of 5.2%. No CCHFv was detected in ticks and sera. Our results provide evidence of human exposure to CCHFv in Tunisia.

[Protection against tick bites]. / Protection contre les piqûres de tiques.

There are numerous tick-borne infections, which include viral (TBE), parasitic (babesiosis) and bacterial diseases. Lyme disease (Lyme borreliosis) is the most common tick-borne disease in France. In temperate climates such as in France, ticks bite humans between March and October. Prevention relies on adequate clothing and on repellents. The latter are reviewed in this work. Repellents may be natural, made from eucalyptus, tomato and coconut, or synthetic, among which the most widely used is DEET (N,N,-Diethyl-m-toluamide). Newer, synthetic repellents exist such as IR3535 which, as well as being less toxic, also exhibits greater efficacy against ticks. Some repellents are used on the skin, while others, like permethrin, which is actually an insecticide, may be applied to clothing.

Detailed evaluation of patients admitted to emergency department with a tick bite complaint.

BACKGROUND AND OBJECTIVE. A tick bite has been an emergency of increased importance in recent years since it can cause a progressive, fatal disease such as Crimean-Congo hemorrhagic fever (CCHF). This issue should be considered by physicians working not only in endemic areas but also in the entire world, taking into account immigration, overseas trips, etc. In our study, we aimed to increase the awareness of the issue by evaluating the emergency department admissions of tick bite complaints in an endemic area. MATERIAL AND METHODS. In total, 251 patients who had been admitted to the emergency department with a complaint of a tick bite within 10 months were included into the study. The data were obtained by collecting main complaints, demographic characteristics, cell counts on admission, and biochemical tests as well as CCHF findings in the RT-PCR test. The patients were divided into 2 groups according to the results of real-time polymerase chain reaction (PCR+ and PCR-). RESULTS. All the patients complained of tick bites. As for the additional complaints, 46% of the overall study population had fatigue and 36% experienced fever. Fever was the most common complaint in the PCR+ group (39%). The platelet and white blood cell counts were significantly lower and the AST level was significantly higher in the PCR+ group than the PCR- group (P<0.01). CONCLUSIONS. In CCHF, where an early diagnosis is very important in reducing mortality, and the symptoms such as a tick bite, fever, and fatigue should be taken seriously by emergency medicine physicians. Leukopenia and thrombocytopenia and higher levels of enzymes in the liver function tests should be taken into account.