An Evaluation of the Hitit Index in Differential Diagnosis of Crimean-Congo Hemorrhagic Fever in the Emergency Department.

Background and Objectives: Crimean-Congo Hemorrhagic Fever (CCHF) is a viral zoonotic infection, which is seen over a wide geographic area. The mortality rate is in inverse proportion to the ability of patients to access healthcare services. Therefore, early identification of patients is extremely important. The aim of this study was to test the sensitivity and specificity of the Hitit Index in the differentiation of CCHF cases at the time of presentation at the Emergency Department and to evaluate the agreement of this index with molecular (CCHFV RNA) and/or serological diagnostic tests (ELISA-CCHF IgM). Materials and Methods: The patients included were those who presented at the Emergency Department (ED) with the complaint of a tick bite or those identified as potential CCHF cases as a result of complaints and/or laboratory findings. For cases that met the study inclusion criteria, the Hitit Index score was calculated automatically from the parameters included in the index formula uploaded to the automation system in the ED at the time of presentation. Through comparisons of the agreement of the Hitit Index with the CCHFV-RNA and/or IgM results the power of the Hitit Index for differentiation of CCHF cases in ED was evaluated. Results: The data of 273 patients were analyzed. There was a history of tick bite in 236 (86%) cases. Of the evaluated cases, 110 (40.2%) were hospitalized; CCHF positivity was determined in 72 (26.4%). The Hitit Index values calculated in ED and at 24 h after hospitalization were determined to be significant in the prediction of the CCHF cases (p < 0.001, AUC = 0.919 (0.887-0.951); p < 0.001, AUC = 0.902 (0.841-0.962). For a cut-off point of 0 of the Hitit Index evaluated in ED, the classification success was found to have a sensitivity of 75% and specificity of 88% (PPV-NPV). For a cut-off point of 0 of the Hitit Index evaluated at 24 h after hospitalization, the classification success was found to have a sensitivity of 79.7% and specificity of 84% (PPV-NPV). Conclusions: The defined form of the Hitit Index can be used in the differentiation of CCHF cases in ED with high sensitivity and specificity levels. Just as evaluation with the Hitit Index prevents unnecessary hospitalization, it can also contribute to reducing mortality rates with the early identification of CCHF cases.

The social representations of diagnosing Lyme disease.

Social science studies on the controversy surrounding Lyme disease (LD) focused on the opposition between the "mainstream" and biomedical approach on one side and the "Lyme-literate" one on the other side, the latter claiming the existence of the chronic form of LD. The qualitative and exploratory study 'C18-48 Quali-Explo-PIQTIQ' (2019) investigated the social representations of LD in patients bitten by a tick. Twenty-four semi-structured interviews were conducted in three French medical units. Thematic and patient trajectory analyses were performed. Our results showed that, after the tick bite, some patients presented an "illness without disease" condition, characterised by uncertainty. In some cases, they consulted "Lyme-literate" health providers and received a diagnosis of chronic LD. This diagnosis was obtained by prescribing unassessed biological testing, providing an objective result and clinical categorisation. Unlike literature on the "Lyme-literate" approach, this diagnostic procedure involved some biomedical operations.

Cutaneous Lymphoid Hyperplasia With T-Cell Clonality and Monotypic Plasma Cells Secondary to a Tick Bite: A Hidden Critter and the Power of Deeper Levels.

ABSTRACT: Cutaneous lymphoid hyperplasia (CLH) is a benign reactive process with T-cell or B-cell lymphocytic infiltration in the skin, which can simulate cutaneous lymphomas both clinically and histologically. Various antigenic stimuli have been implicated in the development of CLH, including tick bites. Finding histologic evidence of such triggering factors, however, is often difficult. Moreover, the presence of clonality in CLH can potentially be interpreted as a neoplastic process, posing a further diagnostic challenge to dermatopathologists, if one is not aware of such peculiar phenomena. Herein, we describe a case of CLH secondary to a tick bite, featuring both T-cell clonality and monotypic plasma cells with lambda light chain restriction; the diagnostic clue being tick parts, which became evident on assessment of deeper levels. To the best of our knowledge, this is the first reported case of a tick-associated clonal CLH with simultaneous detection of monoclonal T cells and monotypic lambda light chain restriction, mimicking primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder and Borrelia-associated primary cutaneous marginal zone B-cell lymphoma, respectively.

Analysis of selected serological parameters in patients with diagnosed Lyme borreliosis and in seropositive patients with no clinical symptoms.

OBJECTIVES: The aim of the study was to analyze some metalloproteinases, cytokines, and chemokines in LB patients and healthy seropositive subjects. The presence of IgM/IgG antibodies against specific Borreliella antigens was analyzed in the presence or absence of clinical manifestations of LB. MATERIAL AND METHODS: The study involved 38 patients diagnosed with LB and arthralgia and/or arthritis symptoms, and 57 foresters presenting no clinical symptoms of LB. The ELISA test was applied for general screening of anti-Borreliella IgM/IgG. Western blot was used for confirmatory diagnosis of LB for the positive and borderline results. Serum IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ, TNF, IL-8, CCL5, CXCL9/MIG, CCL2/MCP-1, CXCL10/IP-10 concentrations were measured with the use of the Human Cytometric CBA test. The concentration of MMP-2 and MMP-9 in the serum was determined with the use of ELISA tests. RESULTS: Analysis of the cytokines and chemokines revealed that only the concentration of IL-2 was significantly higher (2.4 pg/m; p=0.00641) in patients with LB symptoms than in the seropositive individuals (0.4 pg/ml). The MMP2 concentration was significantly higher (233.3 ng/ml; p=0.00294) in patients with clinical manifestations of LB than in those occupationally exposed to tick bites, but did not have anti-Borreliella antibodies (192.0 ng/ml). CONCLUSIONS: The presence of IgG antibodies against a number of Borreliella antigens and the differences in the IL-2 and MMP2 levels in seropositive or seronegative individuals and symptomatic LB patients, may indicate differences in the intensity of the immune response to the infection and, consequently, may induce development of clinical manifestations of the disease in seropositive and seronegative individuals.

Two Atypical Cases of Tick Bites: A Fully Engorged Tick and Multiple Ticks.

Ticks have a cosmopolitan distribution and, as such, are also found in Japan. Ticks are typically ectoparasites of wild animals, however, humans can also be bitten when visiting environments inhabited by ticks. Herein, we describe two cases with atypical tick bites. Case 1 was an elderly Japanese male patient who presented with a fully engorged tick measuring 20 × 17 × 8 mm; it is rare for ticks to attain a length of 20 mm. Case 2 was an elderly Japanese female with severe dementia who presented with multiple tick bites, which is rare, after going missing for 6 days before being found in a densely wooded area. Ticks are responsible for the transmission of many infectious agents, such as bacteria, viruses and parasites. The National Institute of Infectious Diseases and the Ministry of Health, Labour and Welfare regularly inform citizens of the risks posed by tick bites. However, the tick bites could not be prevented in our patients. Further edification about tick bites, tick-borne diseases, and their prevention are considered necessary in Japan.

Optimización del manejo de la mordedura de garrapata: estudio pre-postintervención / Optimisation of the management of tick bites: A pre-post intervention study

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Alpha-gal syndrome: An emerging cause of food and drug allergy.

Alpha-gal syndrome (AGS) describes a wide spectrum of hypersensitivity reactions mediated by specific IgE to the α-gal epitope (galactose-α-1,3-galactose) ubiquitously expressed on glycolipids/glycoproteins of most mammals. This fascinating new entity has completely changed the paradigms of allergy as allergic response is directed against an oligosaccharide and the reactions can be both immediate and delayed. They appear to be stimulated only by tick bites which induce production of α-gal specific IgE antibodies that lead to (at times fatal) hypersensitivity response. AGS is completely different to previously described anaphylaxis to tick saliva. It provides unique insight into the interplay between different arms of the immune system and the role of ectoparasites in the development of anaphylaxis to food and medication in patients at risk of tick bites including travellers. This review summarises recent advances in our understanding of its clinical presentation, pathomechanism and role of various tick species in the development of AGS.

A rickettsia infection from Saudi Arabia.

We here present a young patient who developed fever, headache, maculopapular skin rash and an eschar 3 days following a tick bite. Serology for Rickettsia was consistent with acute spotted fever group (SFG) infection. He had a dramatic response to doxycycline. Vectors for rickettsia transmission are shown in a number of studies from Saudi Arabia while human serological studies from Oman revealed that these infections are common among the rural population. Surprisingly, despite the existence of potential vectors, this disease is rarely reported from the Arab Gulf countries. To the best of our knowledge this is the first case report of SFG acquired within Saudi Arabia. SFG should be considered in the differential diagnosis of febrile illness and exposure history.

Systematic review and meta-analysis of tick-borne disease risk factors in residential yards, neighborhoods, and beyond.

BACKGROUND: Exposure to blacklegged ticks Ixodes scapularis that transmit pathogens is thought to occur peri-domestically. However, the locations where people most frequently encounter infected ticks are not well characterized, leading to mixed messages from public health officials about where risk is highest. METHODS: We conducted a systematic review and meta-analysis on spatial risk factors for tick-borne disease and tick bites in eastern North America. We examined three scales: the residential yard, the neighborhood surrounding (but not including) the yard, and outside the neighborhood. Nineteen eligible studies represented 2741 cases of tick-borne illness and 1447 tick bites. Using random effects models, we derived pooled odds ratio (OR) estimates. RESULTS: The meta-analysis revealed significant disease risk factors at the scale of the yard (OR 2.60 95% CI 1.96 - 3.46), the neighborhood (OR 4.08 95% CI 2.49 - 6.68), and outside the neighborhood (OR 2.03 95% CI 1.59 - 2.59). Although significant risk exists at each scale, neighborhood scale risk factors best explained disease exposure. Analysis of variance revealed risk at the neighborhood scale was 57% greater than risk at the yard scale and 101% greater than risk outside the neighborhood. CONCLUSIONS: This analysis emphasizes the importance of understanding and reducing tick-borne disease risk at the neighborhood scale. Risk-reducing interventions applied at each scale could be effective, but interventions applied at the neighborhood scale are most likely to protect human health. TRIAL REGISTRATION: The study was registered with PROSPERO: CRD42017079169 .

A case with neurological abnormalities caused by Rickettsia raoultii in northwestern China.

BACKGROUND: The number of new rickettsial species are rapidly increasing, and increasing numbers of Rickettsia raoultii (R. raoultii) infection cases have been detected in humans. However, neurological abnormalities caused by R. raoultii are rarely reported, especially in northwestern China. CASE PRESENTATION: A 36-year-old Kazakh shepherd with an attached tick on part temporalis, presented with right eyelid droop, lethargy, fever, headache, fever (38.0-41.0 °C) and erythematous rash. The examination of cerebrospinal fluid (CSF) showed cerebrospinal pressure of 200 mm H2O, leukocyte count of 300.0 × 106/L, adenosine deaminase of 2.15 U/L, and total protein concentration of 0.93 g/L. The diagnosis of R. raoultii infection was confirmed by six genetic markers, and semi-quantified by enzyme-linked immunosorbent assay for rickettsial antigen. The patient gradually recovered after treatment with doxycycline and ceftriaxone. R. raoultii DNA was found both in a tick detached from this patient and in 0.18% (2/1107) of blood samples collected from local shepherds. CONCLUSIONS: This is the first reported case with neurological abnormalities caused by R. raoultii in northwestern China. It is vital to detect rickettsial agents both in blood and CSF for tick bite patients with neurological abnormalities. Public health workers and physicians should pay attention to neurological abnormalities caused by Rickettsia.

Seropositivity to Midichloria mitochondrii (order Rickettsiales) as a marker to determine the exposure of humans to tick bite.

Ixodes ricinus is the most common tick species parasitizing humans in Europe, and the main vector of Borrelia burgdorferi sensu lato, the causative agent of Lyme disease in the continent. This tick species also harbors the endosymbiont Midichloria mitochondrii, and there is strong evidence that this bacterium is inoculated into the vertebrate host during the blood meal. A high proportion of tick bites remains unnoticed due to rarity of immediate symptoms, implying the risk of occult tick-borne infections in turn a potential risk factor for the onset of chronic-degenerative diseases. Since suitable tools to determine the previous exposure to I. ricinus bites are needed, this work investigated whether seropositivity toward a protein of M. mitochondrii (rFliD) could represent a marker for diagnosis of I. ricinus bite. We screened 274 sera collected from patients from several European countries, at different risk of tick bite, using an ELISA protocol. Our results show a clear trend indicating that positivity to rFliD is higher where the tick bite can be regarded as certain/almost certain, and lower where there is an uncertainty on the bite, with the highest positivity in Lyme patients (47.30%) and the lowest (2.00%) in negative controls. According to the obtained results, M. mitochondrii can be regarded as a useful source of antigens, with the potential to be used to assess the exposure to ticks harboring this bacterium. In prospect, additional antigens from M. mitochondrii and tick salivary glands should be investigated and incorporated in a multi-antigen test for tick bite diagnosis.

Citizen science informs human-tick exposure in the Northeastern United States.

BACKGROUND: Tick-borne disease is the result of spillover of pathogens into the human population. Traditionally, literature has focused on characterization of tick-borne disease pathogens and ticks in their sylvatic cycles. A limited amount of research has focused on human-tick exposure in this system, especially in the Northeastern United States. Human-tick interactions are crucial to consider when assessing the risk of tick-borne disease since a tick bite is required for spillover to occur. METHODS: Citizen scientists collected ticks from the Northeastern US through a free nationwide program. Submitted ticks were identified to species, stage, and sex. Blacklegged ticks, Ixodes scapularis, were tested for the presence of Borrelia burgdorferi sensu lato (s.l.) and hard-tick relapsing fever Borrelia. Seasonality of exposure and the citizen science activity during tick exposure was recorded by the citizen scientist. A negative binomial model was fit to predict county level CDC Lyme disease cases in 2016 using citizen science Ixodes scapularis submissions, state, and county population as predictor variables. RESULTS: A total of 3740 submissions, comprising 4261 ticks, were submitted from the Northeastern US and were reported to be parasitizing humans. Of the three species submitted, blacklegged ticks were the most prevalent followed by American dog ticks and lone star ticks. Submissions peaked in May with the majority of exposure occurring during every-day activities. The most common pathogen in blacklegged ticks was B. burgdorferi s.l. followed by hard-tick relapsing fever Borrelia. Negative binomial model performance was best in New England states followed by Middle Atlantic states. CONCLUSIONS: Citizen science provides a low-cost and effective methodology for describing the seasonality and characteristics of human-tick exposure. In the Northeastern US, everyday activities were identified as a major mechanism for tick exposure, supporting the role of peri-domestic exposure in tick-borne disease. Citizen science provides a method for broad pathogen and tick surveillance, which is highly related to human disease, allowing for inferences to be made about the epidemiology of tick-borne disease.

Functional neuroimaging in patients presenting with somatoform disorders: A model for investigating persisting symptoms after tick bites and post-treatment Lyme disease syndrome?

Approximately 10% of patients presenting with Lyme disease experience fatigue, musculoskeletal pain, concentration disorders, or short-term memory deficits in the six months following treatment. This entity has been defined as post-Lyme disease syndrome or post-treatment Lyme disease syndrome. The pathophysiology of this syndrome is unknown, but neither persistence of the bacterium nor effectiveness of antibiotics are currently reported in the literature. The French High Council for Public Health (French acronym HCSP) has recently defined a new entity called "persistent polymorphic symptoms after a tick bite" allowing for designing studies to better understand these subjective presentations, for which objective biomarkers are currently lacking. This entity encompasses patients experiencing fatigue and generalized pain in the months following a tick bite and can be associated with several subjective symptoms with major impact on the quality of life. In the field of somatoform disorders, this article reviews functional neuroimaging studies in patients presenting with subjective complaints and discusses potential clinical implications for persisting symptoms after tick bites and post-treatment Lyme disease syndrome.

Alpha gal specific IgE positivity due to tick bites and red meat allergy: the first case report in Turkey.

Keles S, Gündüz M. Alpha gal specific IgE positivity due to tick bites and red meat allergy: the first case report in Turkey. Turk J Pediatr 2019; 61: 615-617. Galactose-alpha-1,3-galactose is a carbohydrate moiety found in the cell membranes of many organisms, commonly known as alpha-gal (α-Gal). This oligosaccharide is not found in the group of primates in which humans are involved. It has been found that α-Gal plays a key role in delayed IgE-mediated red meat allergy and this allergen is triggered by tick bites. Here we present a 7-year-old boy with alpha-gal allergy from Turkey.

An updated meta-analysis of the distribution and prevalence of Borrelia burgdorferi s.l. in ticks in Europe.

BACKGROUND: The bacteria of the group Borrelia burgdorferi s.l. are the etiological agents of Lyme borreliosis in humans, transmitted by bites of ticks. Improvement of control measures requires a solid framework of the environmental traits driving its prevalence in ticks. METHODS: We updated a previous meta-analysis of the reported prevalence of Borrelia burgdorferi s.l. in questing nymphs of Ixodes ricinus with a literature search from January 2010-June 2017. This resulted in 195 new papers providing the prevalence of Bb for 926 geo-referenced records. Previously obtained data (878 records, years 2000-2010) were appended for modelling. The complete dataset contains data from 82,004 questing nymphs, resulting in 558 records of B. afzelii, 404 of B. burgdorferi s.s. (only 80 after the year 2010), 552 of B. garinii, 78 of B. lusitaniae, 61 of B. spielmanii, and 373 of B. valaisiana. We associated the records with explicit coordinates to environmental conditions and to a categorical definition of European landscapes (LANMAP2) looking for a precise definition of the environmental niche of the most reported species of the pathogen, using models based on different classification methods. RESULTS: The most commonly reported species are B. afzelii, B. garinii and B. valaisiana largely overlapping across Europe. Prevalence in ticks is associated with portions of the environmental niche. Highest prevalence occurs in areas of 280°-290° (Kelvin) of mean annual temperature experiencing a small amplitude, steady spring slope, together with high mean values and a moderate spring rise of vegetation vigor. Low prevalence occurs in sites with low and a noteworthy annual amplitude of temperature and the Normalized Difference Vegetation Index (colder areas with abrupt annual changes of vegetation). Models based on support vector machines provided a correct classification rate of the habitat and prevalence of 89.5%. These results confirm the association of prevalence of the three most commonly reported species of B. burgdorferi s.l. in Europe to parts of the environmental niche and provide a statistically tractable framework for analyzing trends under scenarios of climate change.

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.

An unusual case of positive sIgE to Galactose-alpha-1,3-galactose from South Italy.

Summary: We report the case of a 38-year-old man who was bitten several times during his life by a tick. He didn't report any previous history of anaphylaxis after the ingestion of red meat. The serum specific IgE showed positivity to α-Gal. The proximity of the bits didn't increase the titer of IgE antibodies to alpha-gal. We could hypothesize that the frequency of the exposure to the tick Corresponding author bites and the amount of tick bites during his lifetime induced a sort of tolerance in this patient.