Self-reported symptoms and health complaints associated with exposure to Ixodes ricinus-borne pathogens

Background: The impact of infections with tick-borne pathogens (TBPs) other than Borrelia burgdorferi (s.l.) and tick-borne encephalitis virus (TBEV) on public health in Europe remains unclear. Our goal is to evaluate whether the presence of these TBPs in ticks can be associated with self-reported health complaints. Methods: We enrolled individuals who were bitten by I. ricinus between 2012 and 2015 and collected their relevant demographic and clinical information using a self-administered online questionnaire. A total of 4163 I. ricinus ticks sent by the participants were subject to molecular analyses for detection of specific TBPs. Associations between the presence of TBPs in ticks and self-reported complaints and symptoms were evaluated by means of a stepwise approach using a generalized linear model (GLM). Results: Of 17 self-reported complaints and symptoms significant in the univariate analyses, 3 had a highly significant association (P < 0.01) with at least one TBP in the multivariate analysis. Self-reported Lyme borreliosis was significantly associated (P < 0.001) with B. burgdorferi (s.l.) infection. Facial paralysis was associated (P < 0.01) with infection with B. miyamotoi, N. mikurensis and R. helvetica. Finally, a significant association (P < 0.001) was found between nocturnal sweating and A. phagocytophilum. Conclusions: We found associations between the presence of TBPs in ticks feeding on humans and self-reported symptoms. Due to the subjective nature of such reports and the fact that infection was determined in the ticks and not in the patient samples, further prospective studies utilizing diagnostic modalities should be performed before any clinical outcome can be causally linked to infection with TBPs. Graphical Abstract: [Figure not available: see fulltext.]

Case report: First case of Borrelia miyamotoi meningitis in an immunocompromised patient in Norway

Background: Tick-borne disease caused by B. miyamotoi (BMD) usually manifest as a febrile illness in humans. Complications include relapsing fever and in rare occasions involvement of the central nervous system. Only a few cases of meningoencephalitis have been described, mostly in immunosuppressed patients. Case presentation: A 70-year-old female receiving immunosuppressive rituximab therapy presented with frontal headache, dizziness, nausea, vomiting and chills. Clinical laboratory blood analyses were normal. Cerebrospinal fluid (CSF) was translucent and analysis showed increased leucocyte count (187 106/L) and elevated level of protein (1056 mg/L). Empiric antibiotic treatment was initiated. The patient showed an early symptomatic relief and 24 h after admission she was discharged from the hospital and antibiotic treatment was discontinued. Two weeks after hospitalisation the B. miyamotoi specific PCR turned out positive in both CSF and serum. At the time, the patient was recovered with mild residual headache. She was treated with high dose doxycycline and her subtle symptoms disappeared. Conclusions: To our knowledge, we present the first patient with BMD-associated meningitis in Norway, one of eight cases reported worldwide. The patient had mild symptoms and received an early diagnosis. A more severe progression or relapse of disease may have been prevented by antibiotic treatment. BMD should be considered as causes of aseptic meningitis, especially in immunosuppressed patients living in endemic areas

Evaluation of Disease Causality of Rare -Borne Infections in Europe.

In Europe, Ixodes ricinus ticks transmit pathogens such as Borrelia burgdorferi sensu lato and tick-borne encephalitis virus (TBEV). In addition, there is evidence for transmission to humans from I. ricinus of Anaplasma phagocytophilum, Babesia divergens, Babesia microti, Babesia venatorum, Borrelia miyamotoi, Neoehrlichia mikurensis, Rickettsia helvetica and Rickettsiamonacensis. However, whether infection with these potential tick-borne pathogens results in human disease has not been fully demonstrated for all of these tick-borne microorganisms. To evaluate the available evidence for a causative relation between infection and disease, the current study analyses European case reports published from 2008 to 2018, supplemented with information derived from epidemiological and experimental studies. The evidence for human disease causality in Europe found in this review appeared to be strongest for A. phagocytophilum and B. divergens. Nonetheless, some knowledge gaps still exist. Importantly, comprehensive evidence for pathogenicity is lacking for the remaining tick-borne microorganisms. Such evidence could be gathered best through prospective studies, for example, studies enrolling patients with a fever after a tick bite, the development of specific new serological tools, isolation of these microorganisms from ticks and patients and propagation in vitro, and through experimental studies

Draft Whole-Genome Sequences of Two Western European Borrelia miyamotoi Isolates.

We report the draft whole-genome sequences of two Borrelia miyamotoi strains isolated in The Netherlands. Using next-generation sequencing, we determined the complete sequence of the chromosomes and several plasmids. The two strains show a genotype typical of European strains, distinct from the genomes of strains from Asia or the United States

Borrelia miyamotoi Disease in an Immunocompetent Patient, Western Europe

Borrelia miyamotoi disease is a hard tick–borne relapsing fever illness that occurs across the temperate climate zone. Human B. miyamotoi disease in immunocompetent patients has been described in Russia, North America, and Japan. We describe a case of B. miyamotoi disease in an immunocompetent patient in western Europe

Two Cases of Borrelia miyamotoi Meningitis, Sweden, 2018

We report 2 human cases of Borrelia miyamotoi disease diagnosed in Sweden, including 1 case of meningitis in an apparently immunocompetent patient. The diagnoses were confirmed by 3 different independent PCR assays and DNA sequencing from cerebrospinal fluid, supplemented by serologic analyses

Control of Lyme borreliosis and other Ixodes ricinus-borne diseases.

Lyme borreliosis (LB) and other Ixodes ricinus-borne diseases (TBDs) are diseases that emerge from interactions of humans and domestic animals with infected ticks in nature. Nature, environmental and health policies at (inter)national and local levels affect the risk, disease burden and costs of TBDs. Knowledge on ticks, their pathogens and the diseases they cause have been increasing, and resulted in the discovery of a diversity of control options, which often are not highly effective on their own. Control strategies involving concerted actions from human and animal health sectors as well as from nature managers have not been formulated, let alone implemented. Control of TBDs asks for a "health in all policies" approach, both at the (inter)national level, but also at local levels. For example, wildlife protection and creating urban green spaces are important for animal and human well-being, but may increase the risk of TBDs. In contrast, culling or fencing out deer decreases the risk for TBDs under specific conditions, but may have adverse effects on biodiversity or may be societally unacceptable. Therefore, in the end, nature and health workers together must carry out tailor-made control options for the control of TBDs for humans and animals, with minimal effects on the environment. In that regard, multidisciplinary approaches in environmental, but also medical settings are needed. To facilitate this, communication and collaboration between experts from different fields, which may include patient representatives, should be promoted

Prevalence and clinical manifestation of Borrelia miyamotoi in Ixodes ticks and humans in the northern hemisphere: a systematic review and meta-analysis

Background: Various studies have evaluated the infection of Ixodes ticks and humans with the relapsing fever spirochaete Borrelia miyamotoi. However, to our knowledge, the prevalence of infection and disease has not been assessed systematically. We aimed to examine the prevalence of B miyamotoi in Ixodes ticks and humans, and the disease it can cause, in the northern hemisphere. Methods: For this systematic review and meta-analysis, we searched PubMed and Web of Science up to March 1, 2021. Studies assessing Ixodes tick infection published since Jan 1, 2011 were eligible, whereas no time limitation was placed on reports of human infection and disease. We extracted B miyamotoi test positivity ratios and used a random-effects model to calculate estimated proportions of infected ticks, infected humans, and human disease with 95% CI. This study was registered with PROSPERO, CRD42021268996. Findings: We identified 730 studies through database searches and 316 additional studies that referenced two seminal articles on B miyamotoi. Of these 1046 studies, 157 were included in the review, reporting on 165 637 questing ticks, 45 608 unique individuals, and 504 well described cases of B miyamotoi disease in humans. In ticks, the highest prevalence of B miyamotoi was observed in Ixodes persulcatus (2·8%, 95% CI 2·4–3·1) and the lowest in Ixodes pacificus (0·7%, 0·6–0·8). The overall seroprevalence in humans was 4·4% (2·8–6·3), with significantly (p<0·0001) higher seroprevalences in the high-risk group (4·6%, 2·6–7·1), participants with confirmed or suspected Lyme borreliosis (4·8%, 1·8–8·8), and individuals suspected of having a different tick-borne disease (11·9%, 5·6–19·9) than in healthy controls (1·3%, 0·4–2·8). Participants suspected of having a different tick-borne disease tested positive for B miyamotoi by PCR significantly more often than did the high-risk group (p=0·025), with individuals in Asia more likely to test positive than those in the USA (odds ratio 14·63 [95% CI 2·80–76·41]). Interpretation: B miyamotoi disease should be considered an emerging infectious disease, especially in North America and Asia. Prospective studies and increased awareness are required to obtain further insights into the burden of disease. Funding: ZonMW and the European Regional Development Fund (Interreg)

Prevalence and clinical manifestation of Borrelia miyamotoi in Ixodes ticks and humans in the northern hemisphere: a systematic review and meta-analysis.

Background: Various studies have evaluated the infection of Ixodes ticks and humans with the relapsing fever spirochaete Borrelia miyamotoi. However, to our knowledge, the prevalence of infection and disease has not been assessed systematically. We aimed to examine the prevalence of B miyamotoi in Ixodes ticks and humans, and the disease it can cause, in the northern hemisphere. Methods: For this systematic review and meta-analysis, we searched PubMed and Web of Science up to March 1, 2021. Studies assessing Ixodes tick infection published since Jan 1, 2011 were eligible, whereas no time limitation was placed on reports of human infection and disease. We extracted B miyamotoi test positivity ratios and used a random-effects model to calculate estimated proportions of infected ticks, infected humans, and human disease with 95% CI. This study was registered with PROSPERO, CRD42021268996. Findings: We identified 730 studies through database searches and 316 additional studies that referenced two seminal articles on B miyamotoi. Of these 1046 studies, 157 were included in the review, reporting on 165 637 questing ticks, 45 608 unique individuals, and 504 well described cases of B miyamotoi disease in humans. In ticks, the highest prevalence of B miyamotoi was observed in Ixodes persulcatus (2·8%, 95% CI 2·4–3·1) and the lowest in Ixodes pacificus (0·7%, 0·6–0·8). The overall seroprevalence in humans was 4·4% (2·8–6·3), with significantly (p<0·0001) higher seroprevalences in the high-risk group (4·6%, 2·6–7·1), participants with confirmed or suspected Lyme borreliosis (4·8%, 1·8–8·8), and individuals suspected of having a different tick-borne disease (11·9%, 5·6–19·9) than in healthy controls (1·3%, 0·4–2·8). Participants suspected of having a different tick-borne disease tested positive for B miyamotoi by PCR significantly more often than did the high-risk group (p=0·025), with individuals in Asia more likely to test positive than those in the USA (odds ratio 14·63 [95% CI 2·80–76·41]). Interpretation: B miyamotoi disease should be considered an emerging infectious disease, especially in North America and Asia. Prospective studies and increased awareness are required to obtain further insights into the burden of disease. Funding: ZonMW and the European Regional Development Fund (Interreg)