First case report of inducible heart block in Lyme disease and an update of Lyme carditis.

BACKGROUND: Lyme disease (LD), is the most common vector-borne illness in the US and Europe, with predominantly cutaneous, articular, cardiac and neuro-psychiatric manifestations. LD affects all layers of the heart and every part of the conducting system. Carditis is a less common manifestation of LD. Heart block (HB) as the initial and sole manifestation of LD is rare. Inducible HB has never been reported in LD. We report a case of heart block (HB) inducible with exercise and reversible with rest. CASE PRESENTATION: A 37-year-old male presented to the emergency department after experiencing two episodes of syncope while at work. He presented, with a heart rate of 57 bpm, and the ECG showed sinus bradycardia with first degree AV block. The PR interval was 480 ms (NL 120-200 ms). Physical exam was unremarkable. The cardiologist's initial impression was vaso-vagal attack. He developed high degree AV block during a stress test for the initial work up, which resolved on cessation of exercise. A similar episode while walking in the hallway, resolved at rest. The high degree AV block appeared inducible with exercise and reversible with rest. His Lyme serology was strongly positive. He was treated with ceftriaxone and doxycycline. After completing treatment, the patient had a normal ECG and returned to work without limitations, doing manual labor. CONCLUSIONS: Manifestations of Lyme carditis (LC) vary from asymptomatic and symptomatic electrocardiographic changes and heart block (HB) reversible with treatment, to sudden death. HB as the sole and initial presentation of LC is rare. There have been no reports of inducible HB in LD. Here we present a case of inducible and reversible high degree HB in a case of LC and an update of literature. Exercise and stress testing should be avoided in suspected cases of LC until resolution of carditis. Lyme carditis should be suspected in individuals with cardiac manifestations in an endemic area, particularly in the younger patients with no other etiology evident.

Tick-Borne Pathogens Associated with Medically Important Ticks in Alabama: A Four-Year Survey.

Background: Tick-borne diseases (TBDs) represent a significant threat to human health in the United States. Based on reported cases of notifiable TBDs to the Centers for Disease Control and Prevention (CDC) the state of Alabama is no exception, yet previously there has been no active surveillance program in place to comprehensively assess the presence and prevalence of tick vectors and their associated TBD pathogens in Alabama. Here we summarize initial findings from a 4-year survey to address this unmet need. Materials and Methods: Beginning in 2018 and proceeding through 2021, ticks were collected throughout the state of Alabama and pooled before being screened for a panel of TBD pathogens known to circulate in the United States. Results: Consistent with previously reported cases, TBD pathogens associated with anaplasmosis, babesiosis, ehrlichiosis, and spotted fever rickettsiosis were detected in ticks of Alabama. Causative agents for tularemia and Lyme disease were not detected despite previously reported human disease cases. There was also no evidence of Heartland virus despite recent reports of the virus being detected in ticks in Northwestern counties. Conclusions: While these results serve to provide some insights into TBD pathogens associated with ticks in Alabama, they also raise many questions that highlight the need for additional studies and continued surveillance to fully understand the TBD threat to human health in Alabama.

First Data on Human Lyme Borreliosis in Kosovo: Prospective Evaluation of the Disease from a Tick Bite Perspective.

Purpose: Lyme borreliosis (LB) occurs throughout Europe. No clinical and seroprevalence studies for LB in Kosovo have been publicly available thus far. Therefore, this study aimed to investigate LB from a tick bite perspective in the Pristina region, Kosovo. Methods: This single-center prospective observational study enrolled consecutive adult participants (≥18 years of age) with tick bite (embedded tick in the skin), who were examined at the Clinic of Infectious Diseases, Pristina, between January 2015 and August 2018. At the first visit related to the index tick bite, ticks (the complete ticks or parts of the ticks) were removed from the skin, blood samples were taken for serological tests, and antibiotic treatment was started when deemed necessary. The complete, undamaged ticks removed were proceeded for entomological identification. Participants were followed up at 2 months (serological tests were repeated) and 6 months after the index event for the development of clinical manifestations of LB and/or seroconversion against Borrelia burgdorferi. Results: A total of 380 subjects were included in the study. Most cases were seen in May and June in all study years. All 117 preserved ticks were identified as Ixodes ricinus. Immunoglobulin G seroprevalence among subjects during the first visit in the study was 28/380 (7.4%). Erythema migrans (EM) was clinically diagnosed in 74/380 patients (19.5%, 95% confidence interval 15.6-23.8). Only 15 clinically diagnosed EM (in seronegative patients) were serologically confirmed with seroconversion (2 months later), 3.9% of all subjects included in the study. There were three cases with clinical manifestation between the second and third visit: EM recidivans, multiple erythema, or several nonspecific systemic symptoms. Doxycycline and amoxicillin were mainly used for the treatment of borrelial skin lesions. Conclusion: This assessment can help indicate the need for disease awareness and reinforce the importance of primary prevention measures, early diagnosis, and appropriate treatment.

Passive Tick Surveillance and Detection of Borrelia Species in Ticks from British Columbia, Canada: 2002-2018.

Lyme disease, caused by Borrelia burgdorferi sensu lato (s.l.) complex, is the most common vector-borne disease in North America. This disease has a much lower incidence in western compared with eastern North America. Passive tick surveillance data submitted over 17 years from 2002 to 2018 were analyzed to determine the occurrence of tick species and the prevalence of Borrelia spp. in ticks in British Columbia (BC), Canada. The BC Centre for Disease Control Public Health Laboratory received tick submissions from physicians, veterinarians, and BC residents. Ticks were identified to species, and all ticks, except Dermacentor andersoni, were tested using generic B. burgdorferi s.l. primer sets and species-specific PCR primer sets for B. burgdorferi sensu stricto (s.s.). Tick submission data were analyzed to assess temporal and geographical trends, tick life stages, and tick species. Poisson regression was used to assess temporal trends in annual tick submissions. A total of 15,464 ticks were submitted. Among these, 0.29% (n = 10,235) of Ixodes spp. ticks and 5.3% (n = 434) of Rhipicephalus sanguineus ticks were found carrying B. burgdorferi s.s. B. burgdorferi s.s. was primarily detected in Ixodes pacificus (52%; n = 16) and Ixodes angustus ticks (19%; n = 6) retrieved from humans (n = 5) and animals (n = 26). B. burgdorferi was found in ticks submitted throughout the year. Ixodes spp. ticks were primarily submitted from the coastal regions of southwestern BC, and D. andersoni ticks were primarily submitted from southern interior BC. The number of human tick submissions increased significantly (p < 0.001) between 2013 and 2018. The annual prevalence of B. burgdorferi in ticks remained stable during the study period. These findings correspond to those observed in US Pacific Northwestern states. Passive tick surveillance is an efficient tool to monitor long-term trends in tick distribution and B. burgdorferi prevalence in a low endemicity region.

Report of Non-Lyme, Erythema Migrans Rashes from New Jersey with a Review of Possible Role of Tick Salivary Toxins.

Erythema migrans (EM) rashes once considered pathognomonic of Lyme disease (LD) have been reported following bites of arthropods that do not transmit LD and in areas with no LD. Also, EM rashes have been reported in association with organisms other than members of Borrelia burgdorferi sensu lato complex. Arthropod saliva has chemicals that have effects on the host and pathogen transmission. Tick saliva has protein families similar to spiders and scorpions and even substances homologous to those found in snakes and other venomous animals. Ticks "invertebrate pharmacologists" have a sophisticated arsenal of chemicals that assist in blood feeding, pathogen transmission, and suppressing host defenses. No organisms have been isolated from many EM rashes. We propose that tick salivary toxins may play a role in the causation of rashes and laboratory abnormalities in tick-borne diseases. The role of tick salivary toxins needs further exploration. Cases of Lyme-like EM rashes referred to as STARI (Southern Tick-Associated Rash Illness) following bites of the lone star tick, Amblyomma americanum, in the United States have been reported predominantly in Southeastern Missouri and a few in South Carolina, North Carolina, Georgia, and one case each in Mississippi and Long Island, New York. Although there is one report of Borrelia lonestari in a patient with a rash, biopsies of 31 cases of STARI, with cultures and PCR, failed to show a relationship. Distribution of A. americanum, whose bites are associated with STARI, now extends along the East Coast of the United States, including New Jersey, up to the Canadian border. As far as we are aware, there have been no prior reports of Lyme-like rashes in New Jersey. In this study, we present case examples of 2 Lyme-like rashes, variations of EM rashes, and a brief review of studies that suggest a role of tick salivary toxins in tick-borne diseases.

Seroprevalence of Borrelia burgdorferi, Anaplasma phagocytophilum, and Francisella tularensis Infections in Belgium: Results of Three Population-Based Samples.

To estimate the seroprevalence of Borrelia burgdorferi (Bb), Anaplasma phagocytophilum (Ap), and Francisella tularensis (Ft) in Belgium, we tested sera from three population-based samples in which exposure to pathogen is assumed to vary: 148 samples from workers professionally exposed, 209 samples from rural blood donors, and 193 samples from urban blood donors. Sera were tested using ELISA or the immunofluorescence assay test. The seroprevalence of Bb was 5.4% in workers professionally exposed, 2.9% in rural blood donors, and 2.6% in urban blood donors, which is similar to other studies. The fraction of negative results decreases significantly from urban blood donors and rural blood donors to workers. Regarding the seroprevalence of Ap, the cutoff titer of 1:64 recommended by the manufacturer may be set too low and produces artificially high seroprevalence rates. Using a cutoff titer of 1:128, the seroprevalence of Ap was estimated at 8.1% for workers professionally exposed, 6.2% for rural blood donors, and 5.7% for urban blood donors. Tularemia sera confirmed the presence of the pathogen in Belgium at 2.0% for workers and 0.5% for rural and urban blood donors. Our study is one of the few providing an estimation of the seroprevalences of Bb, Ap, and Ft in three different populations in Belgium, filling the gap in seroprevalence data among those groups. Our findings provide evidence that the entire Belgian population is exposed to Bb, Ap, and Ft infections, but a higher exposure is noticed for professionals at risk. Education on the risk factors for tick bites and preventive measures for both professionals exposed and the general population is needed.

Guidelines for the Detection of Rickettsia spp.

The genus Rickettsia (Rickettsiales: Rickettsiaceae) includes Gram-negative, small, obligate intracellular, nonmotile, pleomorphic coccobacilli bacteria transmitted by arthropods. Some of them cause human and probably also animal disease (life threatening in some patients). In these guidelines, we give clinical practice advices (microscopy, serology, molecular tools, and culture) for the microbiological study of these microorganisms in clinical samples. Since in our environment rickettsioses are mainly transmitted by ticks, practical information for the identification of these arthropods and for the study of Rickettsia infections in ticks has also been added.

Heterogeneous Associations of Ecological Attributes with Tick-Borne Rickettsial Pathogens in a Periurban Landscape.

The variations in prevalence levels of two tick-borne rickettsial pathogens, Ehrlichia chaffeensis and Ehrlichia Ewingii, in a periurban environment were evaluated along with their ecological determinants. Tick life stage and sex, month of tick collection, landscape fragmentation, and ecological covariates specific to pasture and woodland sites were considered as explanatory covariates. Questing lone star ticks (Amblyomma americanum) were collected by flagging for an hour once every week during mid-April through mid-August in years 2013 and 2014. A total of 4357 adult and nymphal ticks (woodland = 2720 and pasture = 1637) were collected and assessed for pathogen prevalence by molecular methods. Female A. americanum ticks were more infected with E. chaffeensis than males or nymphs in woodland areas [♂ = 6.05%; ♀ = 12.0%; nymphs = 2.09%] and pastures [♂ = 8.05%; ♀ = 12.03%; nymphs = 3.33%], and the prevalence was influenced by edge density in the landscape. Higher E. ewingii infection was noted among female A. americanum ticks within woodland areas [♂ = 1.89%; ♀ = 2.14%; nymphs = 1.57%], but no such difference was evident in pastures [♂ = 1.03%; ♀ = 1.33%; nymphs = 1.12%]. Prevalence of E. ewingii was influenced by edge contrast index, and the percentage of pasture perimeter that was less than 20 meters from woodland areas. This study elucidates the complexity of tick-borne pathogen ecology and points to the need for further studies on the role of reservoir hosts, particularly that played by small vertebrates, which is not fully understood in the region.

Incident Tick-Borne Infections in a Cohort of North Carolina Outdoor Workers.

Tick-borne diseases cause substantial morbidity throughout the United States, and North Carolina has a high incidence of spotted fever rickettsioses and ehrlichiosis, with sporadic cases of Lyme disease. The occupational risk of tick-borne infections among outdoor workers is high, particularly those working on publicly managed lands. This study identified incident tick-borne infections and examined seroconversion risk factors among a cohort of North Carolina outdoor workers. Workers from the North Carolina State Divisions of Forestry, Parks and Recreation, and Wildlife (n = 159) were followed for 2 years in a randomized controlled trial evaluating the effectiveness of long-lasting permethrin-impregnated clothing. Antibody titers against Rickettsia parkeri, Rickettsia rickettsii, "Rickettsia amblyommii," and Ehrlichia chaffeensis were measured at baseline (n = 130), after 1 year (n = 82), and after 2 years (n = 73). Titers against Borrelia burgdorferi were measured at baseline and after 2 years (n = 90). Baseline seroprevalence, defined as indirect immunofluorescence antibody titers of 1/128 or greater, was R. parkeri (24%), R. rickettsii (19%), "R. amblyommii" (12%), and E. chaffeensis (4%). Incident infection was defined as a fourfold increase in titer over a 1-year period. There were 40 total seroconversions to at least one pathogen, including R. parkeri (n = 19), "R. amblyommii" (n = 14), R. rickettsii (n = 9), and E. chaffeensis (n = 8). There were no subjects whose sera were reactive to B. burgdorferi C6 antigen. Thirty-eight of the 40 incident infections were subclinical. The overall risk of infection by any pathogen during the study period was 0.26, and the risk among the NC Division of Forest Resources workers was 1.73 times that of workers in other divisions (95% confidence interval [CI]: 1.02, 2.92). The risk of infection was lower in subjects wearing permethrin-impregnated clothing, but not significantly (risk ratio = 0.81; 95% CI: 0.47, 1.39). In summary, outdoor workers in North Carolina are at high risk of incident tick-borne infections, most of which appear to be asymptomatic.

A Review of Methods for Detecting Tick-Borne Encephalitis Virus Infection in Tick, Animal, and Human Specimens.

Tick-borne encephalitis virus (TBEV) is the most important tick-transmitted arbovirus causing human disease in Europe and Asia. Over the past decades, the incidence of TBEV infection has significantly increased, with over 13,000 annual hospital referrals in endemic countries and cases emerging in previously unaffected regions. Specific detection of TBEV is required to diagnose suspected human cases or during surveillance of tick vectors and/or susceptible animal species. Widely used techniques for diagnosis comprise serological methods to detect viral antigens or antibodies and nucleic acid tests to detect viral RNA in target specimens. Moreover, virus isolation using susceptible cell lines or vertebrates, electron microscopy, or immunohistochemistry can also be employed on specific occasions. The purpose of this review is to compile and outline various approaches and techniques for detecting TBEV infection in ticks, wild animals, and humans. Specific sections for specimen collection and storage, nucleic acid testing, and serological assays cover various aspects of dynamics, performance characteristics, and utility in the diagnostic workup of suspected cases. Impact of immunoglobulin M testing and quantification, immunoglobulin G avidity, and real-time and quantitative polymerase chain reaction methods were overviewed with assay comparisons. Recent advances in serological assays to mitigate the impact of cross-reactions were further discussed along with the detailed interpretation of laboratory test results in human infections.

Crimean Congo Hemorrhagic Fever Virus and Alkhurma (Alkhumra) Virus in Ticks in Djibouti.

Crimean Congo hemorrhagic fever virus and Alkhumra virus, not previously reported in Djibouti, were detected among 141 (infection rate = 15.7 per 100, 95% CI: 13.4-18.1) tick pools from 81 (37%) cattle and 2 (infection rate = 0.2 per 100, 95% CI: 0.0-0.7) tick pools from 2 (1%) cattle, respectively, collected at an abattoir in 2010 and 2011.

Tick-Borne Encephalitis Virus Diversity in Ixodid Ticks and Small Mammals in South-Western Siberia, Russia.

UNLABELLED: The persistence of tick-borne encephalitis virus (TBEV) in nature is maintained by numerous species of reservoir hosts, multiple transmissions between vertebrates and invertebrates, and the virus adaptation to its hosts. Our Aim: was to compare TBEV isolates from ticks and small wild mammals to estimate their roles in the circulation of the viral subtypes. METHODS: TBEV isolates from two species of ixodid ticks, four species of rodents, and one species of shrews in the Novosibirsk region, South-Western Siberia, Russia, were analyzed using bioassay, hemagglutination, hemagglutination inhibition, neutralization tests, ELISA, reverse transcription with real-time PCR, and phylogenetic analysis. RESULTS: TBEV RNA and/or protein E were found in 70.9% ± 3.0% of mammals and in 3.8% ± 0.4% of ticks. The TBEV infection rate, main subtypes, and neurovirulence were similar between ixodid tick species. However, the proportions of the virus that were pathogenic for laboratory mice and of the Far-Eastern (FE) subtype, as well as the viral loads with the Siberian and the European subtypes for the TBEV in Ixodes pavlovskyi Pomerantsev, 1946 were higher than in Ixodes persulcatus (P. Schulze, 1930). Percentages of infected Myodes rutilus, Sicista betulina, and Sorex araneus exceeded those of Apodemus agrarius and Myodes rufocanus. Larvae and nymphs of ticks were found mainly on rodents, especially on Myodes rufocanus and S. betulina. The proportion of TBEV-mixed infections with different subtypes in the infected ticks (55.9% ± 6.5%) was higher than in small mammals (36.1% ± 4.0%) (p < 0.01). CONCLUSIONS: Molecular typing revealed mono- or mixed infection with three main subtypes of TBEV in ticks and small mammals. The Siberian subtype was more common in ixodid ticks, and the FE subtype was more common in small mammals (p < 0.001). TBEV isolates of the European subtype were rare. TBEV infection among different species of small mammals did not correlate with their infestation rate with ticks in the Novosibirsk region, Russia.

Two Introductions of Lyme Disease into Connecticut: A Geospatial Analysis of Human Cases from 1984 to 2012.

Lyme disease has become the most prevalent vector-borne disease in the United States and results in morbidity in humans, especially children. We used historical case distributions to explain vector-borne disease introductions and subsequent geographic expansion in the absence of disease vector data. We used geographic information system analysis of publicly available Connecticut Department of Public Health case data from 1984, 1985, and 1991 to 2012 for the 169 towns in Connecticut to identify the yearly clusters of Lyme disease cases. Our analysis identified the spatial and temporal origins of two separate introductions of Lyme disease into Connecticut and identified the subsequent direction and rate of spread. We defined both epidemic clusters of cases using significant long-term spatial autocorrelation. The incidence-weighted geographic mean analysis indicates a northern trend of geographic expansion for both epidemic clusters. In eastern Connecticut, as the epidemic progressed, the yearly shift in the geographic mean (rate of epidemic expansion) decreased each year until spatial equilibrium was reached in 2007. The equilibrium indicates a transition from epidemic Lyme disease spread to stable endemic transmission, and we associate this with a reduction in incidence. In western Connecticut, the parabolic distribution of the yearly geographic mean indicates that following the establishment of Lyme disease (1988) the epidemic quickly expanded northward and established equilibrium in 2009.