Acute Meningoencephalitis Associated with Borrelia miyamotoi, Minnesota, USA.

Borrelia miyamotoi is an emerging tickborne pathogen that has been associated with central nervous system infections in immunocompromised patients, albeit infrequently. We describe a case-patient in Minnesota, USA, who had meningeal symptoms of 1 month duration. B. miyamotoi infection was diagnosed by Gram staining on cerebrospinal fluid and confirmed by sequencing.

Parasitic manipulation or side effects? The effects of past Toxoplasma gondii and Borrelia spp. infections on human personality and cognitive performance are not mediated by impaired health.

Bacteria Borrelia burgdorferi s. l. and even more the protist Toxoplasma gondii Nicolle et Manceaux, 1908, are known to affect the behaviour and mental health of their animal and human hosts. Both pathogens infect a significant fraction of human population, both are neurotropic and survive in the host's body for a long time. While latent infections were thought to be clinically asymptomatic, recent studies suggest otherwise, revealing adverse effects on human health. It was hypothesised that the specific behavioural effects of these pathogens may be side effects of general health impairments in infected individuals. This hypothesis was tested using about one hour-long survey consisting of questionnaires and performance tests on a cohort of 7,762 members of the internet population. Results showed that individuals infected with T. gondii reported worse physical and mental health, and those infected with Borrelia spp. reported worse physical health than uninfected controls. Furthermore, infected and noninfected individuals differed in several personality traits, including conscientiousness, pathogen disgust, injury disgust, Machiavellianism, narcissism, tribalism, anti-authoritarianism, intelligence, reaction time, and precision. While the majority of behavioural effects associated with Borrelia infection were similar to those associated with Toxoplasma infection, some differences were observed, such as performance in the Stroop test. Path analyses and nonparametric partial Kendall correlation tests showed that these effects were not mediated by impaired health in infected individuals, contradicting the side effects hypothesis.

Morgellons disease etiology and therapeutic approach: a systematic review.

Morgellons disease is characterized by patient reports of fibers embedded in and protruding from the skin. Etiologies from infection to delusion have been endorsed, and treatment guidelines are not well-defined. The objective of this manuscript is to evaluate the existing evidence regarding the etiology and treatment of Morgellons disease in an effort to better inform clinical management. A PubMed search including key words "Morgellons," "delusional parasitosis and fibers," "delusions of parasitosis and fibers," or "delusional infestation and fibers" was completed. Original publications directly assessing etiology or treatment methods of Morgellons disease published between January, 2010 and the time of manuscript preparation were reviewed and evaluated. Sixteen articles regarding etiology were reviewed. All studies were correlative in nature with various limitations. Support for a psychiatric etiology was more widespread than support for an infectious etiology. Eleven articles regarding treatment efficacy were reviewed. Antipsychotic regimens have the most evidence of efficacy. Existing data regarding Morgellons disease suggests a psychiatric etiology and supports treatment with a low-dose antipsychotic agent once non-psychiatric causes have been excluded.

Presence of Borrelia miyamotoi infection in a highly endemic area of Lyme disease.

A series of cases in the Northeast of the US during 2013-2015 described a new Borrelia species, Borrelia miyamotoi, which is transmitted by the same tick species that transmits Lyme disease and causes a relapsing fever-like illness. The geographic expansion of B. miyamotoi in the US also extends to other Lyme endemic areas such as the Midwestern US. Co-infections with other tick borne diseases (TBD) may contribute to the severity of the disease. On Long Island, NY, 3-5% of ticks are infected by B. miyamotoi, but little is known about the frequency of B. miyamotoi infections in humans in this particular region. The aim of this study was to perform a chart review in all patients diagnosed with B. miyamotoi infection in Stony Brook Medicine (SBM) system to describe the clinical and epidemiological features of B. miyamotoi infection in Suffolk County, NY. In a 5 year time period (2013-2017), a total of 28 cases were positive for either IgG EIA (n = 19) or PCR (n = 9). All 9 PCR-positive cases (median age: 67; range: 22-90 years) had clinical findings suggestive of acute or relapsing infection. All these patients were thought to have a TBD, prompting the healthcare provider to order the TBD panel which includes a B. miyamotoi PCR test. In conclusion, B. miyamotoi infection should be considered in the differential diagnosis for flu-like syndromes during the summer after a deer tick bite and to prevent labeling a case with Lyme disease.

Myocarditis secondary to Borrelia infection in a dog: a case report.

The aim of this study was to recognise the etiological factor of a disease with symptoms of lameness and cardiac failure, which occurred in one dog 4 weeks after invasion by ticks. A serological examination as well as molecular examination (PCR) was done. In the sample of the serum, the presence of antibodies specific to Borrelia burgdorferi were detected. Antibiotic therapy with doxycycline did not cause significant improvement, so the owners of the dog decided about its euthanasia. During the necroscopy, a dilated heart was recognised. In the heart samples, the genetic material of Borrelia was detected. The results of serological and molecular examinations showed that in the discussed case, an etiological factor of the disease was spirochetes. In light of the research, veterinary practitioners should keep in mind the presence of Lyme disease in dogs in Poland and include it in differential diagnoses for lameness and cardiological problems.

Infectious stress triggers a POLG-related mitochondrial disease.

A 3-year-old girl presented with severe epilepsy in the context of Borrelia infection. After ceftriaxone/lidocaine administration, she showed secondarily generalized focal crises that led to neurological and motor sequelae. Genetic studies identified in the patient two heterozygous POLG mutations (c.2591A>G; p.Asn864Ser and c.3649G>C; p.Ala1217Pro). Through analysis of POLG activity in cultured fibroblasts, we confirmed that the mutations altered the mtDNA turnover. Moreover, patient fibroblasts were more sensitive than controls in the presence of a mitochondrial replication-affecting drug, the antiretroviral azidothymidine. To test if ceftriaxone treatment could worsen the deleterious effect of the patient mutations, toxicity assays were performed. Cell toxicity, without direct effect on mitochondrial respiratory function, was detected at different antibiotic concentrations. The clinical outcome, together with the different in vitro sensitivity to ceftriaxone among patient and control cells, suggested that the mitochondrial disease symptoms were hastened by the infection and were possibly worsened by the pharmacological treatment. This study underscores the benefit of early genetic diagnosis of the patients with mitochondrial diseases, since they may be a target group of patients especially vulnerable to environmental factors.

Meningoencephalitis in a Royal Marine after skinning reindeer in Norway.

Meningoencephalitis presenting in service personnel overseas may present a diagnostic challenge due to the broad range of potential differential diagnosis as well as the requirement for rapid assessment and treatment. A 25-year-old Royal Marine was evacuated to the Royal Centre for Defence Medicine in Birmingham, UK, with a history of rash consistent with erythema chronicum migrans, a seizure, and lymphocytic pleocytosis after skinning reindeer in Norway. Neuroborreliosis was suspected and empirical antibiotics were administered. Despite subsequent negative serology for Borrelia burgdorferi, given the clinical features and lymphocytic pleocytosis, an atypical presentation of neuroborreliosis remains a possible diagnosis in this scenario. This case serves to illustrate that British military personnel on exercise are potentially at risk of contracting borreliosis both in the UK and abroad, serological tests can be unreliable, and the differential diagnosis of meningoencephalitis can be broad with specialist input often required.

[Tick-borne neuroinfections: Clinical characteristics, immunopathogenesis, and new pharmacotherapeutic strategies]. / Kleshchevye neiroinfektsii: klinicheskaya kharakteristika, immunopatogenez i novye farmakoterapevticheskie strategii.

AIM: To study the semiotics of neurological lesions in patients with tick-borne encephalitis, Ixodes tick-borne borreliosis (ITBB) and mixed infection (MI), their immunopathogenesis, and the possibilities of current pathogenetic pharmacological correction. SUBJECTS AND METHODS: A total of 220 patients with tick-borne encephalitis, ITBB, and MI concurrent with the syndromes of central nervous system lesions were examined. The immunological studies encompassed the examination of mononuclear cells in the cerebrospinal fluid (CSF), the population and subpopulation composition of lymphocytes, and nitroxidergic processes in the serum and CSF from the total level of final stable nitric oxide metabolites. For pharmacotherapeutic correction, the metabolic drug cytoflavin was used as newly indicated. RESULTS: Cytofluorometric analysis of the CSF cellular composition showed the mononuclear cell predominance of CD3+ (58.6%), CD4+ (57.2%), CD8+ (16.8%) lymphocytes and monocytes (34.4%), which expressed the phenotypic marker CD14+. This reflects the nature of a local immune response: an increase in the immunoregulatory index CD4+/CD8+ from 3.4 to 5.6, respectively, while the normal proportion of these cells in the blood ranges from 1.5 to 2.2. CSF lymphocytes were found to be ready for Fas-mediated apoptosis dependent on the receptor (CD95+ was 64.3%).There was a correlation using the pair correlation coefficient between the total concentration of the metabolites of the nitroxide molecule and the percentage of CD14+ (r=0.5; p<0.05). The paired Wilcoxon test was used to analyze serum NO2, NO3, and NOx, which revealed significant differences in nitrites [2.70 (1.90, 2.95; p=0.001)] and total NO metabolites [18.00 (18.00, 22.60; p=0.006)] and statistically significant changes in nitrates [13.29 (15.70. 20.30; p=0.075)] in patients receiving cytoflavin infusions. CONCLUSION: The immune response of Th-1 forms between the CSF phagocytic, antigen-presenting, and immunocompetent lymphocytes in patients with tick-borne neuroinfections. The use of cytoflavin as an agent for neurotransmitter support to correct nitroxidergic processes is pathogenetically justified.

Neurocognitive functions and brain atrophy after proven neuroborreliosis: a case-control study.

BACKGROUND: Patients often report neurocognitive difficulties after neuroborreliosis (NB). The frequency and extent of cognitive problems in European patients have been studied incompletely. METHODS: Sixty patients received a neurological and neuropsychological work-up 6 months or longer after treatment for proven NB. Quality of life, psychiatric symptom load, and brain atrophy were measured. All results were compared with a group of 30 healthy control persons adapted for age, gender and education being serologically negative for Borrelia burgdorferi senso latu. A cognitive sum score and a global sum score including cognitive, psychological results and quality of life data was calculated for both groups. RESULTS: Patients after NB showed a lower (i.e. more impaired) score on the Scripps Neurological rating scale (SNRS), but the observed neurological deficits were generally mild (mean ± SD: 97.1 ± 4.7 vs. 99.1 ± 2.4, p = 0.02). The mean neuropsychological domain results of the NB group were all within the normal range. However, a lower performance was found for the frontal executive function z-values (mean ± SD -0.29 ± 0.60 vs. 0.09 ± 0.60; p = 0.0059) of NB patients. Comparing the global sum score (mean ± SD 11.3 ± 4.2 NB vs. 14.3 ± 2.9 control , p = 0.001) and the cognitive sum score of the NB group with those of the control group (mean ± SD -0.15 ± 0.42 NB vs. 0.08 ± 0.31 control , p = 0.0079), both differences were statistically different. The frequencies of impaired global sum scores and those of the pathological cognitive sum scores (p = 0.07) did not differ statistically. No significant differences were found for health-related quality of life (hrQoL), sleep, psychiatric symptom load, or brain atrophy. CONCLUSION: The mean cognitive functions of patients after proven NB were in the normal range. However, we were able to demonstrate a lower performance for the domain of frontal executive functions, for the mean cognitive sum score and the global sum score as a sign of subtle but measurable sequelae of neuroborreliosis. Brain atrophy is not a common consequence of neuroborreliosis.

Borrelia miyamotoi Disease in the Northeastern United States: A Case Series.

BACKGROUND: The first recognized cases of Borrelia miyamotoi disease (BMD) in North America were reported in the northeastern United States in 2013. OBJECTIVE: To further describe the clinical spectrum and laboratory findings for BMD. DESIGN: Case series. SETTING: Patients presenting to primary care offices, emergency departments, or urgent care clinics in 2013 and 2014. PARTICIPANTS: Acutely febrile patients from the northeastern United States in whom the treating health care providers suspected and ordered testing for tick-transmitted infections. MEASUREMENTS: Whole-blood polymerase chain reaction (PCR) testing was performed for the presence of specific DNA sequences of common tickborne infections (including BMD). Serologic testing for B. miyamotoi was performed using a recombinant glycerophosphodiester phosphodiesterase (rGlpQ) protein. Clinical records were analyzed to identify the major features of acute disease. RESULTS: Among 11,515 patients tested, 97 BMD cases were identified by PCR. Most of the 51 case patients on whom clinical histories were reviewed presented with high fever, chills, marked headache, and myalgia or arthralgia. Twenty-four percent were hospitalized. Elevated liver enzyme levels, neutropenia, and thrombocytopenia were common. At presentation, 16% of patients with BMD were seropositive for IgG and/or IgM antibody to B. miyamotoi rGlpQ. Most (78%) had seropositive convalescent specimens. Symptoms resolved after treatment with doxycycline, and no chronic sequelae or symptoms were observed. LIMITATION: Findings were based on specimens submitted for testing to a reference laboratory, and medical records of only 51 of the 97 case patients with BMD were reviewed. CONCLUSION: Patients with BMD presented with nonspecific symptoms, including fever, headache, chills, myalgia, and arthralgia. Laboratory confirmation of BMD was possible by PCR on blood from acutely symptomatic patients who were seronegative at presentation. Borrelia miyamotoi disease may be an emerging tickborne infection in the northeastern United States. PRIMARY FUNDING SOURCE: IMUGEN.

[The blood coagulation system and microcirculatory disorders in ixodid tick-borne borreliosis caused by Borrelia miyamotoi].

AIM: To study blood coagulation and microcirculatory disorders as a possible cause of transient dysfunctions of organs (the kidney, liver, heart, lung, etc.) in patients with ixodid tick-borne borreliosis caused by Borrelia miyamotoi (Bmt). SUBJECTS AND METHODS; Twenty-four patients with Lyme disease (LD) and 28 Bmt patients treated at Izhevsk City Hospital (Udmurtia) were examined in the study. Platelet counts and the presence of D-dimers were determined; activated partial thromboplastin time, prothrombin time, thrombin time, fibrinogen and antithrombin III levels, and Factor XIIa-dependent fibrin clot lysis time were measured. Slit lamp microscopy of the conjunctiva was. also carried out. Results. Platelet counts'were less than 150,000 per pL of blood in 43% of the Bmt patients. All the Bmt patients had at least one abnormal coagulation parameter of the eight ones that were tested; 64% of them had marked coagulation disorders with three or more abnormal laboratory findings. In contrast, all the eight parameters were normal in 71% of the LD patients. The other seven LD patients had only one or two abnormal coagulation parameters (p < 0.001 in comparison with Bmt patients). Microscopic examination of eye capillary blood flow revealed pathological findings that included aggregates of erythrocytes and obstructed and/or sinuous capillaries in 22 (79%) of the Bmt patients, but none of the LD patients. A total of 14 Bmt patients had both coagulation and microcirculatory abnormalities. Eleven of them also had transient signs of organ dysfunction. CONCLUSION: As far as Borrelia secrete no known toxins, we hypothesized that uncovered disorders of blood coagulation and microcirculation in Bmt patients may contribute to organ dysfunction.

Borrelia miyamotoi infection presenting as human granulocytic anaplasmosis: a case report.

BACKGROUND: The diverse tickborne infections of the northeastern United States can present as undifferentiated flu-like illnesses. In areas endemic for Lyme and other tickborne diseases, patients presenting with acute febrile illness with myalgia, headache, neutropenia, thrombocytopenia, and elevated hepatic aminotransferase levels are presumptively diagnosed as having human granulocytic anaplasmosis (HGA). OBJECTIVE: To assign a cause for illness experienced by 2 case patients who were initially diagnosed with HGA but did not rapidly defervesce with doxycycline treatment and had no laboratory evidence of Anaplasma phagocytophilum infection. DESIGN: Case report. SETTING: 2 primary care medical centers in Massachusetts and New Jersey. PATIENTS: 2 case patients acutely presenting with fever. MEASUREMENTS: Identification of the causative agent by polymerase chain reaction and DNA sequencing. RESULTS: Molecular diagnostic assays detected Borrelia miyamotoi in the peripheral blood of both patients. There was no evidence of infection with other tickborne pathogens commonly diagnosed in the referral areas. LIMITATION: One of the case patients may have had concurrent Lyme disease. CONCLUSION: The presence of B. miyamotoi DNA in the peripheral blood and the patients' eventual therapeutic response to doxycycline are consistent with the hypothesis that their illness was due to this newly recognized spirochete. Samples from tick-exposed patients acutely presenting with signs of HGA but who have a delayed response to doxycycline therapy or negative confirmatory test results for HGA should be analyzed carefully for evidence of B. miyamotoi infection.

Primary cutaneous marginal zone lymphoma associated with juxta-articular fibrotic nodules in a teenager.

Primary cutaneous marginal zone lymphoma (PCMZL) has rarely been reported in teenagers and is occasionally associated with Borrelia burgdorferi infection. Juxta-articular fibrotic nodules represent a unique, localized fibrosing response to spirochete infections, namely Borreliosis. Herein, we report a 15-year-old healthy boy who presented with a 4-year history of progressive acquisition of asymptomatic, erythematous nodules, ≤ 3 cm, beginning with his right forearm (3), then right arm (1) and lastly his right inner thigh (1). Biopsy showed PCMZL in three of five samples, and inflamed, fibrotic nodules, near the elbow in two. The bottom heavy lymphomatous nodules consisted of mostly small CD20+ CD43+ lymphocytes, some with plasmacytoid features. Mature plasma cells were lambda light chain restricted by in situ hybridization. The juxta-articular fibrotic nodules were located in the deep dermis and subcutis, had peripheral plasma cell-rich infiltrates, and showed nodular sclerosis (morphea profunda-like) in one, and lamellar and angiocentric sclerosis in the other reminiscent of quiescent lesions of chronic localized fibrosing leukocytoclastic vasculitis. Immunohistochemistry for B. burgdorferi revealed rare positive organisms; however, polymerase chain reaction (PCR) and serology were negative for B. burgdorferi as were serologic and/or PCR assays for Bartonella henselae, Ba. quintana, Ehrlichia chaffeensis, Treponema pallidum, Helicobacter pylori and Babesia microti. No evidence of extracutaneous disease was found by the review of systems and imaging studies. A 4-week trial of doxycycline therapy failed, whereas intralesional (IL) corticosteroid therapy induced rapid regression of his nodules. After two local recurrences, also treated with IL corticosteroids, he is well, without cutaneous disease, 20 months later. A literature review of 19 pediatric cases PCMZL reveals a similar natural history as adult PCMZL. Despite negative serology and PCR for B. burgdorferi, the occurrence of ipsilateral juxta-articular fibrotic nodules, positive B. burgdorferi immunohistochemistry and rapid response to IL corticosteroids implicate the presence of a replicative or non-replicative infectious (spirochetal) antigen in the initiation and promotion of this teenager's PCMZL.