Are other tick-borne infections overlooked in patients investigated for Lyme neuroborreliosis? A large retrospective study from South-eastern Sweden.

In Europe, the hard tick Ixodes ricinus is considered the most important vector of human zoonotic diseases. Human pathogenic agents spread by I. ricinus in Sweden include Borrelia burgdorferi sensu lato (s.l.), Anaplasma phagocytophilum, Rickettsia helvetica, the recently described Neoehrlichia mikurensis, Borrelia miyamotoi, tick-borne encephalitis virus (TBEV), and Babesia spp. (Babesia microti, Babesia venatorum and Babesia divergens). Since these pathogens share the same vector, co-infections with more than one tick-borne pathogen may occur and thus complicate the diagnosis and clinical management of the patient due to possibly altered symptomatology. Borrelia burgdorferi s.l., TBEV and B. miyamotoi are well-known to cause infections of the central nervous system (CNS), whereas the abilities of other tick-borne pathogens to invade the CNS are largely unknown. The aim of this study was to investigate the presence and clinical impact of tick-borne pathogens other than B. burgdorferi s.l. in the cerebrospinal fluid (CSF) and serum samples of patients who were under investigation for Lyme neuroborreliosis (LNB) in a tick-endemic region of South-eastern Sweden. CSF and serum samples from 600 patients, recruited from the Regions of Östergötland County, Jönköping County and Kalmar County in South-eastern Sweden and investigated for LNB during the period of 2009-2013, were retrospectively collected for analysis. The samples were analysed by real-time PCR for the presence of nucleic acid from B. burgdorferi s.l., B. miyamotoi, A. phagocytophilum, Rickettsia spp., N. mikurensis, TBEV and Babesia spp. Serological analyses were conducted in CSF and serum samples for all patients regarding B. burgdorferi s.l., and for the patients with CSF mononuclear pleocytosis, analyses of antibodies to B. miyamotoi, A. phagocytophilum, spotted fever group (SFG) rickettsiae, TBEV and B. microti in serum were performed. The medical charts of all the patients with CSF mononuclear pleocytosis and patients with positive PCR findings were reviewed. Of the 600 patients, 55 (9%) presented with CSF mononuclear pleocytosis, 13 (2%) of whom had Borrelia-specific antibodies in the CSF. One patient was PCR-positive for N. mikurensis, and another one was PCR-positive for Borrelia spp. in serum. No pathogens were detected by PCR in the CSF samples. Four patients had serum antibodies to B. miyamotoi, four patients to A. phagocytophilum, five patients to SFG rickettsiae, and six patients to TBEV. One patient, with antibodies to SFG rickettsiae, had both clinical and laboratory signs suggestive of a current infection. Nine patients had serum antibodies to more than one pathogen, although none of these was assessed as a current co-infection. We can conclude from this study that tick-borne co-infections are uncommon in patients who are being investigated for suspected LNB in South-eastern Sweden, an area endemic for borreliosis and TBE.

Borrelia hispanica como causa de fiebre recurrente / Borrelia hispanica as a cause of recurrent fever

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Rapid clearance of Borrelia burgdorferi from the blood circulation.

BACKGROUND: Borrelia burgdorferi is a tick-borne spirochete that causes Lyme borreliosis (LB). After an initial tick bite, it spreads from the deposition site in the dermis to distant tissues of the host. It is generally believed that this spirochete disseminates via the hematogenous route. Borrelia persica causes relapsing fever and is able to replicate in the blood stream. Currently the exact dissemination pathway of LB pathogens in the host is not known and controversially discussed. METHODS: In this study, we established a strict intravenous infection murine model using host-adapted spirochetes. Survival capacity and infectivity of host-adapted B. burgdorferi sensu stricto (Bbss) were compared to those of B. persica (Bp) after either intradermal (ID) injection into the dorsal skin of immunocompetent mice or strict intravenous (IV) inoculation via the jugular vein. By in vitro culture and PCR, viable spirochetes and their DNA load in peripheral blood were periodically monitored during a 49/50-day course post-injection, as well as in various tissue samples collected at day 49/50. Specific antibodies in individual plasma/serum samples were detected with serological methods. RESULTS: Regardless of ID or IV injection, DNA of Bp was present in blood samples up to day 24 post-challenge, while no Bbss was detectable in the blood circulation during the complete observation period. In contrast to the brain tropism of Bp, Bbss spirochetes were found in ear, skin, joint, bladder, and heart tissue samples of only ID-inoculated mice. All tested tissues collected from IV-challenged mice were negative for traces of Bbss. ELISA testing of serum samples showed that Bp induced gradually increasing antibody levels after ID or IV inoculation, while Bbss did so only after ID injection but not after IV inoculation. CONCLUSIONS: This study allows us to draw the following conclusions: (i) Bp survives in the blood and disseminates to the host's brain via the hematogenous route; and (ii) Bbss, in contrast, is cleared rapidly from the blood stream and is a tissue-bound spirochete.

Serological evidence of Borrelia circulation among blood donors in the São Paulo state, Brazil.

OBJECTIVE: The objective of this study was to examine the Borrelia seroprevalence among blood donors in Southeast Brazil. BACKGROUND: There is evidence that Borrelia spirochetes are circulating in Brazil; however, there are no studies that characterise these bacteria and investigate their seroprevalence in the Brazilian population. Such a situation, combined with a recent outbreak of tick-borne Rocky Mountain spotted fever in the São Paulo state demonstrates the increasing role of ticks as arthropod vectors in Brazil. METHODS: For the purpose of the study, 452 blood donors from Ribeirão Preto city, São Paulo state were tested using anti-Borrelia immunoglobulin G (IgG) assay. The positive results were also confirmed by Western blot for anti-borrelia IgM/IgG. RESULTS: The anti-Borrelia IgG enzyme-linked immunosorbent assay (ELISA) showed nine positive and nine borderline reactive samples, giving a total seroprevalence of 2·0% of anti-Borrelia IgG among Brazilian blood donors. The confirmation of the seropositive and borderline samples by Borrelia Western blot was demonstrated by IgG-positive results in 16 samples (a seroprevalence of 3.5%). Anti-Borrelia IgM antibodies were also detected in one sample. CONCLUSIONS: Our results demonstrate that Borrelia-like spirochetes may be circulating among blood donors from the São Paulo State and that the ticks have an important epidemiological role as vectors of bacterial infections in this Brazilian region. These results not only alert us to possible actions that might be undertaken in order to completely characterise the aetiological agents of Lyme-like syndromes in Brazil but also the possible impact that these bacterial agents might have on haemotherapy practices.

Seroprevalence of six pathogens transmitted by the Ixodes ricinus ticks in asymptomatic individuals with HIV infection and in blood donors.

The objective of our study was to estimate the seroprevalence of six pathogens transmitted by ticks in HIV-infected persons and blood donors in Poland (B. burgdorferi s.l., A. phagocytophilum, Ehrlichia spp., Babesia spp., Rickettsia spp. Bartonella henselae) to assess the frequency of exposure to such microorganisms in immunocompetent and immunocompromised individuals in endemic regions for I. ricinus ticks. Serum samples were collected from 227 HIV-infected patients and 199 blood donors. All samples were analyzed for antibodies against six tick-borne pathogens and seroprevalence rates were statistically compared between two tested group as well as age, sex and lymphocyte T CD4+ level in HIV infected patients. The seroprevalence of tick-borne infections in HIV-infected patients is higher than that of the healthy population in Poland, although no association between serological status of patients and lymphocyte CD4+ T cell level has been observed. The frequency of tick-borne coinfections and doubtful results of serological tests were significantly higher in HIV-positive individuals. In Poland, the possibility of tick-borne diseases transmission with blood is rather negligible.

An immunocompromised mouse model to infect Ixodes scapularis ticks with the relapsing fever spirochete, Borrelia miyamotoi.

The hard tick-borne relapsing fever spirochete, Borrelia miyamotoi, has recently gained attention as a cause of human illness, but fundamental aspects of its enzootic maintenance are still poorly understood. Challenges to experimental studies with B. miyamotoi-infected vector ticks include low prevalence of infection in field-collected ticks and seemingly inefficient horizontal transmission from infected immunocompetent rodents to feeding ticks. To reliably produce large numbers of B. miyamotoi-infected ticks in support of experimental studies, we developed an animal model where immunocompromised Mus musculus SCID mice were used as a source of B. miyamotoi-infection for larval and nymphal Ixodes scapularis ticks. Following needle inoculation with 1 × 105 spirochetes, the SCID mice developed a high spirochetemia (greater than 1 × 107 copies of B. miyamotoi purB per mL of blood) that persisted for at least 30 d after inoculation. In comparison, immunocompetent M. musculus CD-1 mice developed transient infections, detectable for only 2-8 d within the first 16 d after needle inoculation, with a brief, lower peak spirochetemia (8.5 × 104 - 5.6 × 105purB copies per mL of blood). All larval or nymphal ticks fed on infected SCID mice acquired B. miyamotoi, but frequent loss of infection during the molt led to the proportion infected ticks of the resulting nymphal or adult stages declining to 22-29%. The ticks that remained infected after the molt had well-disseminated infections which then persisted through successive life stages, including transmission to larval offspring.

Dynamics of Spirochetemia and Early PCR Detection of Borrelia miyamotoi.

We investigated whether Borrelia miyamotoi disease can be detected in its early stage by using PCR for borrelial 16S rRNA, which molecule (DNA or RNA) is the best choice for this test, and whether spirochetes are present in blood during the acute phase of B. miyamotoi disease. A total of 473 patients with a suspected tickborne infection in Yekaterinburg, Russia, in 2009, 2010, and 2015 were enrolled in this study. Blood samples were analyzed by using quantitative PCR or ELISA, and a diagnosis of borreliosis was confirmed for 310 patients. For patients with erythema migrans, 5 (3%) of 167 were positive for B. miyamotoi by PCR; for patients without erythema migrans, 65 (45%) of 143 were positive for B. miyamotoi by PCR. The median concentration for RNA was 3.8 times that for DNA. Median time for detection of B. miyamotoi in blood was 4 days.

Evaluation of a serological test for the diagnosis of Borrelia miyamotoi disease in Europe.

BACKGROUND: Borrelia miyamotoi causes systemic febrile illness and is transmitted by the same tick species that transmits Borrelia burgdorferi sensu lato and tick-borne encephalitis virus. We describe a serological test using a fragment of glycerophosphodiester phosphodiesterase (GlpQ) as an antigen, and determined its performance in well-defined patient categories. METHODS: Serum of patients with PCR-confirmed Borrelia miyamotoi disease (BMD), Lyme borreliosis (LB), tick-borne encephalitis (TBE), and healthy blood donors (HBD) were collected in Udmurt Republic, Russia. Sera of BMD and LB patients were collected at hospital admission, one week, one month and one year after admission. RESULTS: The levels of IgM and IgG anti-GlpQ antibodies, determined as optical density values in Luminex bead-based assays, were significantly higher in the BMD patient group than in LB patients, TBE patients or HBD group (all p<0.05). CONCLUSIONS: By using a strict cut-off value, it was possible to exclude B. miyamotoi infection in LB and TBE patients and to serologically confirm B. miyamotoi infection in 44% to 94% of the PCR-positive BMD patients (95% confidence interval). Thus, sensitive serological assays should not solely rely on rGlpQ, to support the diagnosis of acute BMD.

Alterações bioquímicas, anatômicas e histopatológicas em fígado de Gallus gallus Linnaeus, 1758 experimentalmente infectados por Borrelia anserina Sakharoff, 1891 / Biochemical, anatomical and histopathological changes in the liver of Gallus gallus Linnaeus, 1758 experimentally infected by Borrelia anserine Sakharoff, 1891

A espiroquetose aviária é uma enfermidade septicêmica de curso agudo, cosmopolita, que acomete diversas espécies aviárias, causada por Borrelia anserina e transmitida pelo carrapato Argas miniatus. O experimento teve como objetivos avaliar as alterações bioquímicas e anátomo-histopatológicas no fígado de Gallus gallus, causadas pela infecção experimental por B. anserina. Quarenta aves da espécie G. gallus foram divididas em quatro grupos inteiramente casualizados com 10 animais cada: G1 - inoculado com soro infectado com B. anserina; G2 - inoculado com soro fisiológico a 0,9%; G3 - exposto a ninfas de terceiro ínstar de A. miniatus infectados por B. anserina; G4 - exposto a ninfas de terceiro ínstar de A. miniatus livres de B. anserina. As aves dos Grupos 1 e 3 manifestaram no 3º e 6º dias pós-inoculação (DPI) respectivamente, sintomatologia característica da doença como inapetência, perda de peso, sonolência, diarreia esverdeada, mucosas hipocoradas, penas arrepiadas e hipertermia. Os níveis de ALT do Grupo 1 mostraram-se significativamente mais elevados apenas no 12ºDPI e 24ºDPI em relação ao seu grupo controle (Grupo 2) e no Grupo 3 esses níveis se mantiveram elevados até o 20º DPI em comparação ao seu grupo controle (Grupo 4). Os níveis da enzima AST pouco oscilaram nos grupos experimentais, embora tenham sido encontradas elevações no 12ºDPI nos Grupos 1 e 3. Os fígados das aves dos Grupos 1 e 3 apresentaram à necropsia, moderada hepatomegalia, congestão, superfície irregular e coloração vermelha a cianótica; constataram-se ainda pequenos pontos esbranquiçados na superfície. A histopatologia do fígado revelou congestão, infiltrados inflamatórios mononucleares, focos de necrose fibrinoide, dilatação dos sinusoides e vacuolização de hepatócitos. A coloração de Warthin-Starry revelou, nos fígados das aves dos Grupos 1 e 3, a presença de espiroquetas compatíveis com B. anserina, frequentemente no interior de vasos sanguíneos.(AU)

Spirochetosis avian is a septicemic disease of acute course and cosmopolitan can affect various avian species, caused by Borrelia anserina and transmitted by Argas miniatus. The experiment aimed to evaluate the biochemical, anatomical and histopathological changes in the liver of Gallus gallus caused by experimental infection with B. anserina. A total of 40 fowls of the species G. gallus were divided into four randomized groups of ten fowls each: G1 - inoculated with serum infected with B. anserina; G2 - inoculated with 0.9% saline; G3 - exposed to nymphs of 3rd instar of A. miniatus infected with B. anserina; G4 - exposed to ticks nymphs of 3rd instar of A. miniatus free of B. anserina. The fowls of Groups 1 and 3 expressed at 3 and 6 days post-inoculation (DAI) respectively , symptoms characteristic of the disease as lack of appetite , weight loss , drowsiness, greenish diarrhea, pale mucous membranes , ruffled feathers and hyperthermia. ALT of group 1 levels were significantly higher only at the 12º and 24º day after inoculation (DAI) compared with its control group (group 2), and in group 3 these levels remained high until the 20º DAI as compared with its control group (group 4). AST enzyme fluctuated little in the experimental groups, although elevations at 12ºDAI has been found in group 1 and 3. The liver of fowls in groups 1 and 3, presented at necropsy moderate hepatomegaly, congestion, irregular surface and red color to cyanotic. If found even small whitish spots on the surface. The histopathology revealed congestion, mononuclear inflammatory infiltrates, fibrinoid necrotic foci, dilatation of sinusoids, and vacuolation of hepatocytes. The Warthin-Starry staining revealed in the liver of fowls in groups 1 and 3 the presence of spirochetes compatible with B. anserina, often within blood vessels.(AU)

Borrelia miyamotoi sensu lato seroreactivity and seroprevalence in the northeastern United States.

Borrelia miyamotoi sensu lato, a relapsing fever Borrelia sp., is transmitted by the same ticks that transmit B. burgdorferi (the Lyme disease pathogen) and occurs in all Lyme disease-endemic areas of the United States. To determine the seroprevalence of IgG against B. miyamotoi sensu lato in the northeastern United States and assess whether serum from B. miyamotoi sensu lato-infected persons is reactive to B. burgdorferi antigens, we tested archived serum samples from area residents during 1991-2012. Of 639 samples from healthy persons, 25 were positive for B. miyamotoi sensu lato and 60 for B. burgdorferi. Samples from ≈10% of B. miyamotoi sensu lato-seropositive persons without a recent history of Lyme disease were seropositive for B. burgdorferi. Our results suggest that human B. miyamotoi sensu lato infection may be common in southern New England and that B. burgdorferi antibody testing is not an effective surrogate for detecting B. miyamotoi sensu lato infection.

Estimating transitions between states using measurements with imperfect detection: application to serological data.

Classifying the states of an individual and quantifying transitions between states are crucial while modeling animal behavior, movement, and physiologic status. When these states are hidden or imperfectly known, it is particularly convenient to relate them to appropriate quantitative measurements taken on the individual. This task is, however, challenging when quantitative measurements are not available at each sampling occasion. For capture-recapture data, various ways of incorporating such non-discrete information have been used, but they are either ad hoc and/or use a fraction of the available information by relying on a priori thresholds to assign individual states. Here we propose assigning discrete states based on a continuous measurement, and then modeled survival and transition probabilities based on these assignments. The main advantage of this new approach is that a more informative use of the non-discrete information is done. As an illustrative working example, we applied this approach to eco-epidemiological data collected across a series of years in which individuals of a long-lived seabird, the Black-legged Kittiwake (Rissa tridactyla), could either be visually detected or physically recaptured and blood sampled for subsequent immunological analyses. We discuss how this approach opens many perspectives in eco-epidemiology, but also more broadly, in population ecology.

[Interferon inductors in treatment of associative forms of tick-borne infection in children].

Thirty three children with associative forms of thick-borne infection (thick-borne encephalitis with ixodic borreliosis) were clinically observed. The disease was characterized by subfebrile temperature, moderate intoxication, rare erythema (39.5%) and frequent cardiovascular disorders with development of Lyme carditis (32.6 +/- 7.2%) and further rise of hepatomegalia in the diseases dynamics and development of meningeal symptoms. There were observed changes in the cytokine spectrum, characterized by INF-gamma high levels, and hypersecretion of the whole spectrum cytokines in the dynamics, that provided the Th2 type immune response. High clinicoimmunological efficacy of the complex therapy with cycloferon as an immunomodulator providing more balanced production of pro- and anti-inflammatory cytokines (IL-1alpha, INF-gamma and IL-10) was shown.

Niche partitioning of Borrelia burgdorferi and Borrelia miyamotoi in the same tick vector and mammalian reservoir species.

The Lyme borreliosis agent Borrelia burgdorferi and the relapsing fever group species Borrelia miyamotoi co-occur in the United States. We used species-specific, quantitative polymerase chain reaction to study both species in the blood and skin of Peromyscus leucopus mice and host-seeking Ixodes scapularis nymphs at a Connecticut site. Bacteremias with B. burgdorferi or B. miyamotoi were most prevalent during periods of greatest activity for nymphs or larvae, respectively. Whereas B. burgdorferi was 30-fold more frequent than B. miyamotoi in skin biopsies and mice had higher densities of B. burgdorferi densities in the skin than in the blood, B. miyamotoi densities were higher in blood than skin. In a survey of host-seeking nymphs in 11 northern states, infection prevalences for B. burgdorferi and B. miyamotoi averaged approximately 0.20 and approximately 0.02, respectively. Co-infections of P. leucopus or I. scapularis with both B. burgdorferi and B. miyamotoi were neither more nor less common than random expectations.

Molecular and serological evidence of Borrelia burgdorferi sensu lato in wild rodents in the Czech Republic.

The aim of the present study was to determine the frequency and spatial distribution of the Borrelia species in wild rodents in the Czech Republic. In total, 293 muscle tissue samples and 106 sera from 293 wild rodents captured in North Bohemia and North-East and South Moravia were examined for the presence of Borrelia spp. and antibodies. Muscle samples were investigated with real-time polymerase chain reaction (PCR) with a recA primer set, with DNA quantification and melting curve analysis, and with restriction fragment length polymorphism (RFLP) analysis of the 5S-23S rDNA intergenic spacer. Infection with Borrelia burgdorferi sensu lato was found in 16.4% of the muscle samples. The most abundant genospecies was Borrelia afzelii (11.3%), followed by Borrelia burgdorferi sensu stricto (4.8%) and Borrelia garinii (0.7%). Borrelia infection was more frequently observed in Clethrionomys glareolus than in Apodemus spp. Sera were analyzed with an enzyme-linked immunosorbent assay (ELISA) test, yielding the total seropositivity rates of 24.5% for anti-Borrelia IgM antibodies and 25.5% for IgG antibodies. Total seroprevalence was higher in Apodemus spp. than in C. glareolus. In conclusion, our data indicate that in the Czech Republic small wild rodents can serve as hosts for B. burgdorferi s. s. as well as for B. afzelii.

Fibrinolysis and host response in bacterial infections.

The plasminogen activation system is part of the fibrinolysis which is tightly regulated and protected against dysfunction by various activators and inhibitors. However, microorganisms including bacteria, fungi and also parasites have been proven to interact in a specific manner with components of the fibrinolytic pathways. Pathogenic bacteria are capable to subvert the function of proteases, activators or inhibitors for their own benefits including dissemination within the host and evasion of host inflammatory immune response. Here, we provide a state of the art overview of the divers strategies employed by bacteria to interact with components of the fibrinolytic system and to exploit the system for invasion. Moreover, the role of factors of the fibrinolytic cascade in inflammatory host response due to different bacterial infections will be presented.

[Biochemical parameters of hepatobiliary system functions in viral hepatitis or ixodes tick-borne borreliosis concurrent with chronic opisthorchiasis].

The biochemical parameters of hepatobiliary system functions were studied in patients with opisthorchiasis and concomitant diseases, such as chronic viral hepatitis concurrent with chronic opisthorchiasis, as well as Ixodes tick-borne borreliosis in the presence of the same invasion. Although the magnitude ofbiochemical changes is not great in chronic opisthorchiasis or chronic viral hepatitis, the concomitance of these two diseases were ascertained to result in pronounced abnormalities, by demonstrating the exhaustion of spare capacities of the hepatobiliary system in parasitic invasion (or viral infection). When opisthorchiasis was concurrent with Ixodes tickborne borreliosis, some parameters under study differed from those in the groups of patients with monoinfections. Variance analysis showed that chronic opisthorchiasis had a great impact on carbohydrate and lipid metabolisms (glucose and cholesterol levels). The findings suggest that the formation of stable host-parasite relationships in chronic opisthorchiasis alters human metabolic processes and their compensatory capabilities.

Pseudo-borreliosis in patients with malaria.

Malaria and relapsing fever are arthropod-borne infections characterized by fever, myalgia, headache, and a tendency to relapse. Both are diagnosed through examination of stained blood films, and both might respond to tetracycline therapy. In at least four published case reports, the presence of malarial microgametes possibly resulted in misdiagnosis of borreliosis in patients with malaria. An additional case is presented, and the mechanism of microgamete production in clinical specimens is discussed.