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1.
Oecologia ; 200(3-4): 471-478, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36242620

RESUMO

In seasonal environments, appropriate adaptations are crucial for organisms to maximize their fitness. For instance, in many species, the immune function has been noticed to decrease during winter, which is assumed to be an adaptation to the season's limited food availability. Consequences of an infection on the health and survival of the host organism could thus be more severe in winter than in summer. Here, we experimentally investigated the effect of a zoonotic, endemic pathogen, Borrelia afzelii infection on the survival and body condition in its host, the bank vole (Myodes glareolus), during late autumn-early winter under semi-natural field conditions in 11 large outdoor enclosures. To test the interaction of Borrelia infection and energetic condition, four populations received supplementary nutrition, while remaining seven populations exploited only natural food sources. Supplementary food during winter increased the body mass independent of the infection status, however, Borrelia afzelii infection did not cause severe increase in the host mortality or affect the host body condition in the late autumn-early winter. While our study suggests that no severe effects are caused by B. afzelii infection on bank vole, further studies are warranted to identify any potentially smaller effects the pathogen may cause on the host fitness over the period of whole winter.


Assuntos
Infecções por Borrelia , Grupo Borrelia Burgdorferi , Ixodes , Doença de Lyme , Animais , Doença de Lyme/veterinária , Doença de Lyme/epidemiologia , Estações do Ano , Roedores , Arvicolinae
2.
Diagn Microbiol Infect Dis ; 104(3): 115782, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35970019

RESUMO

We used definite Lyme neuroborreliosis (LNB) adult patient acute and convalescent phase serum (n = 63 and 61, respectively) and cerebrospinal fluid (CSF; acute n = 63, 3 weeks timepoint n = 41) samples to characterize Borrelia burgdorferi specific antibody responses in patient subgroups categorized by demographics, infection manifestation and phase, infecting B. burgdorferi genospecies, received antibiotic treatments, and treatment outcome. B. burgdorferi antibodies were analyzed using 4 different assays incorporating a large array of antigens. We observed that B. burgdorferi specific serum antibodies show a universal, antigen independent declining trend after antibiotic treatment of LNB at 1 year. Antibodies declined similarly among women and men over time, and the decline was independent of patient age. The antibody responses were independent of the predominant LNB manifestation, treatment received by the patient, infecting B. burgdorferi genospecies, or the subjective improvement experienced by the patients. Finally, the antibody specificities in CSF reflected the specificities observed in serum samples.


Assuntos
Grupo Borrelia Burgdorferi , Borrelia burgdorferi , Neuroborreliose de Lyme , Adulto , Antibacterianos/uso terapêutico , Anticorpos Antibacterianos , Líquido Cefalorraquidiano , Feminino , Humanos , Neuroborreliose de Lyme/diagnóstico , Masculino
3.
Diagn Microbiol Infect Dis ; 103(1): 115657, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35228132

RESUMO

We evaluated the analytical accuracy and the clinical performance of a ReaScan+ C6 LYME IgG point-of-care immunoassay (Reagena; index test). Analytical accuracy was evaluated in comparison to a C6 Lyme ELISA™ reference method (Oxford Immunotec) with retrospectively identified serum and CSF samples. The clinical performance was evaluated by using Lyme borreliosis patient and control subject serum and CSF samples. The study was conducted by following the 2015 Standards for Reporting of Diagnostic Accuracy Studies procedure. The sensitivity and specificity of the index test with serum samples were 83% and 91.6%, respectively, when C6 Lyme ELISA™ was used as a reference. The clinical sensitivity of the index test was 97.2%/96.8% for identifying Borrelia specific antibodies in definite/possible Lyme neuroborreliosis. With CSF samples, the clinical sensitivity was 97.2% for definite and 87.1% for possible Lyme neuroborreliosis. The clinical specificity of the assay was 96.1% with serum and 100% with CSF samples.


Assuntos
Doença de Lyme , Neuroborreliose de Lyme , Anticorpos Antibacterianos , Humanos , Imunoensaio , Doença de Lyme/diagnóstico , Neuroborreliose de Lyme/diagnóstico , Peptídeos , Sistemas Automatizados de Assistência Junto ao Leito , Estudos Retrospectivos , Sensibilidade e Especificidade
4.
Infect Dis (Lond) ; 54(6): 448-454, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35045784

RESUMO

BACKGROUND: Health care workers are at risk of acquiring SARS-CoV-2 infection. Our aim was to study the prevalence of SARS-CoV-2 nucleoprotein and spike protein specific antibodies in health care workers with occupational exposure to COVID-19 in Turku, Finland, from May to December 2020. METHODS: Health care workers of Turku University Hospital units caring for COVID-19 patients or handling clinical SARS-CoV-2 samples were invited to participate in the study. The presence of SARS-CoV-2 nucleoprotein and spike protein specific IgG antibodies were analysed with in-house enzyme immunoassay. RESULTS: At study enrolment, only one of the 222 (0.5%) study participants was seropositive for SARS-CoV-2 protein specific antibodies. Two additional study participants (2/222, 0.9%) seroconverted during the follow-up. All these participants were diagnosed with a RT-PCR-positive COVID-19 infection before turning seropositive. CONCLUSION: In our study population, the prevalence of SARS-CoV-2 seropositivity remained low. The absence of seropositive cases without previous RT-PCR confirmed infections demonstrate good access to diagnostics. In addition to high vaccine coverage, high standards of infection prevention practices and use of standard personal protective equipment seem sufficient in preventing occupational SARS-CoV-2 infection in a setting with low number of circulating virus. However, it remains unclear whether similar protective practices would also be effective against more transmissible SARS-CoV-2 variants.


Assuntos
COVID-19 , SARS-CoV-2 , Anticorpos Antivirais , COVID-19/epidemiologia , COVID-19/prevenção & controle , Finlândia/epidemiologia , Pessoal de Saúde , Humanos , Nucleoproteínas , Estudos Prospectivos , Estudos Soroepidemiológicos , Glicoproteína da Espícula de Coronavírus , Vacinação
5.
Ticks Tick Borne Dis ; 12(6): 101809, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34454337

RESUMO

Francisella tularensis subsp. holarctica is the causative agent of tularaemia in Europe. Finland is a high-incidence region for tularaemia, with mosquito bites as the most common sources of infection. However, in Central and Western Europe, ticks (Acari: Ixodidae) have been suggested as the main vectors. Indeed, several studies have reported the pathogen from the locally most common human-biting tick species, Ixodes ricinus. In Finland, the occurrence of the pathogen in ticks has started receiving attention only recently. Here, we collate previous tick screening data from Finland regarding F. tularensis as well as present the results from a novel screening of roughly 15 000 I. ricinus and I. persulcatus collected from across the country. In total, 14 878 ticks collected between 2015 and 2020 were screened for F. tularensis using a TaqMan-based qPCR assay targeting the 23 KDa gene. The combined screening efforts of the current and previous studies, encompassing roughly 20 000 ticks, did not find any positive ticks. Given the negative results despite the considerable sample size, it appears that the pathogen is not circulating in local tick populations in Finland. We discuss some possible reasons for the lack of the bacterium in ticks in this high-incidence region of tularaemia.


Assuntos
Francisella/isolamento & purificação , Ixodes/microbiologia , Animais , Finlândia , Ixodes/crescimento & desenvolvimento , Larva/crescimento & desenvolvimento , Larva/microbiologia , Ninfa/crescimento & desenvolvimento , Ninfa/microbiologia , Especificidade da Espécie , Tularemia/microbiologia
6.
J Infect Dis ; 224(2): 218-228, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-33905505

RESUMO

BACKGROUND: Primary diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is based on detection of virus RNA in nasopharyngeal swab samples. In addition, analysis of humoral immunity against SARS-CoV-2 has an important role in viral diagnostics and seroprevalence estimates. METHODS: We developed and optimized an enzyme immunoassays (EIA) using SARS-CoV-2 nucleoprotein (N), S1 and receptor binding domain (RBD) of the viral spike protein, and N proteins from SARS, Middle East respiratory syndrome (MERS), and 4 low-pathogenic human CoVs. Neutralizing antibody activity was compared with SARS-CoV-2 IgG, IgA, and IgM EIA results. RESULTS: The sensitivity of EIA for detecting immune response in COVID-19 patients (n = 101) was 77% in the acute phase and 100% in the convalescent phase of SARS-CoV-2 infection when N and RBD were used as antigens in IgG and IgA specific EIAs. SARS-CoV-2 infection significantly increased humoral immune responses against the 229E and NL63 N proteins. S1 and RBD-based EIA results had a strong correlation with microneutralization test results. CONCLUSIONS: The data indicate a combination of SARS-CoV-2 S1 or RBD and N proteins and analysis of IgG and IgA immunoglobulin classes in sera provide an excellent basis for specific and sensitive serological diagnostics of COVID-19.


Assuntos
Teste Sorológico para COVID-19/métodos , COVID-19/diagnóstico , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Imunoglobulina A/sangue , Imunoglobulina G/sangue , SARS-CoV-2/isolamento & purificação , Glicoproteína da Espícula de Coronavírus/imunologia , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Humanos , Técnicas Imunoenzimáticas , Imunoglobulina A/imunologia , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Testes de Neutralização , Fosfoproteínas/imunologia , SARS-CoV-2/imunologia , Sensibilidade e Especificidade
7.
Commun Biol ; 4(1): 268, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33649506

RESUMO

As opposed to pathogens passively circulating in the body fluids of their host, pathogenic species within the Spirochetes phylum are able to actively coordinate their movement in the host to cause systemic infections. Based on the unique morphology and high motility of spirochetes, we hypothesized that their surface adhesive molecules might be suitably adapted to aid in their dissemination strategies. Designing a system that mimics natural environmental signals, which many spirochetes face during their infectious cycle, we observed that a subset of their surface proteins, particularly Decorin binding protein (Dbp) A/B, can strongly enhance the motility of spirochetes in the extracellular matrix of the host. Using single-molecule force spectroscopy, we disentangled the mechanistic details of DbpA/B and decorin/laminin interactions. Our results show that spirochetes are able to leverage a wide variety of adhesion strategies through force-tuning transient molecular binding to extracellular matrix components, which concertedly enhance spirochetal dissemination through the host.


Assuntos
Adesinas Bacterianas/metabolismo , Aderência Bacteriana , Borrelia burgdorferi/metabolismo , Matriz Extracelular/microbiologia , Ixodes/microbiologia , Doença de Lyme/microbiologia , Adesinas Bacterianas/genética , Animais , Borrelia burgdorferi/genética , Borrelia burgdorferi/patogenicidade , Decorina/metabolismo , Matriz Extracelular/metabolismo , Feminino , Interações Hospedeiro-Patógeno , Cinética , Laminina/metabolismo , Doença de Lyme/metabolismo , Movimento , Ligação Proteica , Coelhos , Imagem Individual de Molécula
8.
Mol Microbiol ; 115(6): 1395-1409, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33512032

RESUMO

Lyme borreliosis is a tick-borne disease caused by Borrelia burgdorferi sensu lato spirochetes (Lyme borreliae). When the disease affects the central nervous system, it is referred to as neuroborreliosis. In Europe, neuroborreliosis is most often caused by Borrelia garinii. Although it is known that in the host Lyme borreliae spread from the tick bite site to distant tissues via the blood vasculature, the adherence of Lyme borreliae to human brain microvascular endothelial cells has not been studied before. Decorin binding proteins are adhesins expressed on Lyme borreliae. They mediate the adhesion of Lyme borreliae to decorin and biglycan, and the lysine residues located in the binding site of decorin binding proteins are important to the binding activity. In this study, we show that lysine residues located in the canonical binding site can also be found in decorin binding proteins of Borrelia garinii, and that these lysines contribute to biglycan and decorin binding. Most importantly, we show that the lysine residues are crucial for the binding of Lyme borreliae to decorin and biglycan expressing human brain microvascular endothelial cells, which in turn suggests that they are involved in the pathogenesis of neuroborreliosis.


Assuntos
Adesinas Bacterianas/metabolismo , Aderência Bacteriana/fisiologia , Biglicano/metabolismo , Grupo Borrelia Burgdorferi/metabolismo , Decorina/metabolismo , Neuroborreliose de Lyme/patologia , Adesinas Bacterianas/genética , Sequência de Aminoácidos , Sítios de Ligação/genética , Grupo Borrelia Burgdorferi/genética , Encéfalo/irrigação sanguínea , Células Cultivadas , Células Endoteliais/metabolismo , Humanos , Neuroborreliose de Lyme/microbiologia , Lisina/química , Simulação de Dinâmica Molecular , Alinhamento de Sequência , Doenças Transmitidas por Carrapatos/microbiologia
9.
J Microbiol Methods ; 180: 106122, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33326821

RESUMO

The cut-off values used in C6 peptide-based enzyme immunoassay (EIA), a widely used test in Lyme borreliosis (LB) serology, have not been thoroughly analysed. The objective of the study was to examine the performance of the C6 EIA, and to determine optimal cut-off values for the test. The analysed data contained results of 1368 serum samples. C6 EIA index values were compared statistically with the immunoblot (IB) test results. The identified cut-off values were further tested in a well-defined LB patient cohort. Cut-off value 1.6 appeared to be optimal when C6 EIA was used as a stand-alone test. When using C6 EIA as the first-tier test, the optimal cut-off values were 0.9 and 2.4 for negative and positive results. When C6 EIA was used as a second-tier test, samples yielding C6 index values ≥3.0 could be considered positive. The identified cut-off values had also a high sensitivity to identify seropositivity among definite LB patients. The identified cut-off values refine the role of C6 EIA in LB serology. Importantly, the use of C6 EIA leads to a reduction in the number of samples that need to be analysed using an IB, thus also reducing the costs. Two alternative workflows for LB serology including the C6 EIA are suggested.


Assuntos
Técnicas Imunoenzimáticas/métodos , Doença de Lyme/sangue , Doença de Lyme/diagnóstico , Peptídeos , Testes Sorológicos/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/isolamento & purificação , Técnicas Bacteriológicas/métodos , Borrelia burgdorferi/isolamento & purificação , Criança , Pré-Escolar , Feminino , Finlândia , Humanos , Immunoblotting , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
10.
Clin Infect Dis ; 72(8): 1323-1331, 2021 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-32133487

RESUMO

BACKGROUND: Lyme neuroborreliosis (LNB) is often treated with intravenous ceftriaxone even if doxycycline is suggested to be noninferior to ceftriaxone. We evaluated the efficacy of oral doxycycline in comparison to ceftriaxone in the treatment of LNB. METHODS: Patients with neurological symptoms suggestive of LNB without other obvious reasons were recruited. The inclusion criteria were (1) production of Borrelia burgdorferi-specific antibodies in cerebrospinal fluid (CSF) or serum; (2) B. burgdorferi DNA in the CSF; or (3) an erythema migrans during the past 3 months. Participants were randomized in a 1:1 ratio to receive either oral doxycycline 100 mg twice daily for 4 weeks, or intravenous ceftriaxone 2 g daily for 3 weeks. The participants described their subjective condition with a visual analogue scale (VAS) from 0 to 10 (0 = normal; 10 = worst) before the treatment, and 4 and 12 months after the treatment. The primary outcome was the change in the VAS score at 12 months. RESULTS: Between 14 September 2012 and 28 December 2017, 210 adults with suspected LNB were assigned to receive doxycycline (n = 104) or ceftriaxone (n = 106). The per-protocol analysis comprised 82 patients with doxycycline and 84 patients with ceftriaxone. The mean change in the VAS score was -3.9 in the doxycycline group and -3.8 in the ceftriaxone group (mean difference, 0.17 [95% confidence interval, -.59 to .92], which is within the prespecified equivalence margins of -1 to 1 units). Participants in both groups improved equally. CONCLUSIONS: Oral doxycycline is equally effective as intravenous ceftriaxone in the treatment of LNB. CLINICAL TRIALS REGISTRATION: NCT01635530 and EudraCT 2012-000313-37.


Assuntos
Eritema Migrans Crônico , Neuroborreliose de Lyme , Adulto , Antibacterianos/uso terapêutico , Ceftriaxona , Doxiciclina , Eritema Migrans Crônico/tratamento farmacológico , Humanos , Neuroborreliose de Lyme/tratamento farmacológico
11.
BMC Infect Dis ; 20(1): 819, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33167874

RESUMO

BACKGROUND: In Finland, the routine surveillance of Lyme borreliosis (LB) is laboratory-based. In addition, we have well established national health care registers where countrywide data from patient visits in public health care units are collected. In our previous study based on these registers, we reported an increasing incidence of both microbiologically confirmed and clinically diagnosed LB cases in Finland during the past years. Here, we evaluated our register data, refined LB incidence estimates provided in our previous study, and evaluated treatment practices considering LB in the primary health care. METHODS: Three national health care registers were used. The Register for Primary Health Care Visits (Avohilmo) and the National Hospital Discharge Register (Hilmo) collect physician-recorded data from the outpatient and inpatient health care visits, respectively, whereas the National Infectious Diseases Register (NIDR) represents positive findings in LB diagnostics notified electronically by microbiological laboratories. We used a personal identification number in register-linkage to identify LB cases on an individual level in the study year 2014. In addition, antibiotic purchase data was retrieved from the Finnish Social Insurance Institution in order to evaluate the LB treatment practices in the primary health care in Finland. RESULTS: Avohilmo was found to be useful in monitoring clinically diagnosed LB (i.e. erythema migrans (EM) infections), whereas Hilmo did not add much value next to existing laboratory-based surveillance of disseminated LB. However, Hilmo gave valuable information about uncertainties related to physician-based surveillance of disseminated LB and the total annual number of EM infections in our country. Antibiotic purchases associated with the LB-related outpatient visits in the primary health care indicated a good compliance with the recommended treatment guidelines. CONCLUSIONS: Avohilmo and laboratory-based NIDR together are useful in monitoring LB incidence in Finland. A good compliance was observed with the recommended treatment guidelines of clinically diagnosed LB in the primary health care. In 2018, Avohilmo was introduced in the routine surveillance of LB in Finland next to laboratory-based surveillance of disseminated LB.


Assuntos
Borrelia burgdorferi/imunologia , Doenças Transmissíveis/epidemiologia , Monitoramento Epidemiológico , Eritema Migrans Crônico/epidemiologia , Sistema de Registros , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Doenças Transmissíveis/tratamento farmacológico , Doenças Transmissíveis/microbiologia , Eritema Migrans Crônico/tratamento farmacológico , Eritema Migrans Crônico/microbiologia , Feminino , Finlândia/epidemiologia , Humanos , Incidência , Lactente , Recém-Nascido , Laboratórios , Masculino , Cooperação do Paciente , Alta do Paciente , Médicos , Atenção Primária à Saúde , Estudos Retrospectivos , Testes Sorológicos , Adulto Jovem
12.
Infect Immun ; 88(4)2020 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-31988175

RESUMO

Borrelia burgdorferisensu lato, the causative agent of tick-borne Lyme borreliosis (LB), has a limited metabolic capacity and needs to acquire nutrients, such as amino acids, fatty acids, and nucleic acids, from the host environment. Using X-ray crystallography, liquid chromatography-mass spectrometry, microscale thermophoresis, and cellular localization studies, we show that basic membrane protein D (BmpD) is a periplasmic substrate-binding protein of an ABC transporter system binding to purine nucleosides. Nucleosides are essential for bacterial survival in the host organism, and these studies suggest a key role for BmpD in the purine salvage pathway of B. burgdorferi sensu lato Because B. burgdorferisensu lato lacks the enzymes required for de novo purine synthesis, BmpD may play a vital role in ensuring access to the purines needed to sustain an infection in the host. Furthermore, we show that, although human LB patients develop anti-BmpD antibodies, immunization of mice with BmpD does not confer protection against B. burgdorferi sensu lato infection.


Assuntos
Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Grupo Borrelia Burgdorferi/enzimologia , Proteínas de Transporte de Nucleosídeos/química , Proteínas de Transporte de Nucleosídeos/metabolismo , Purinas/metabolismo , Animais , Anticorpos Antibacterianos/sangue , Proteínas de Bactérias/imunologia , Transporte Biológico Ativo , Cromatografia Líquida , Cristalografia por Raios X , Humanos , Doença de Lyme/imunologia , Doença de Lyme/prevenção & controle , Espectrometria de Massas , Camundongos , Proteínas de Transporte de Nucleosídeos/imunologia , Ligação Proteica , Conformação Proteica
13.
Pediatr Infect Dis J ; 38(12): 1195-1198, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31634297

RESUMO

BACKGROUND: Lyme borreliosis (LB) is a common cause of acute facial palsy in children living in endemic areas for Borrelia burgdorferi. The need for lumbar puncture in diagnostics of LB in children with facial palsy has been questioned. Our aim was to evaluate the prevalence of LB and the diagnostic value of a cerebrospinal fluid (CSF) sample among children with an acute facial palsy. METHODS: We collected medical records and laboratory data of children and adolescents 0-16 years of age (n = 94) diagnosed with facial palsy between 2002 and 2016 in the Turku University Hospital. A positive B. burgdorferi serology in serum or CSF or a positive B. burgdorferi polymerase chain reaction in CSF were considered as signs of definite LB. C-X-C motif chemokine ligand 13 (CXCL13) values were measured in CSF samples from 28 children during 2014-2016. RESULTS: Lumbar puncture was performed on 84 of 94 children with facial palsy. LB was confirmed in 29 of 42 children with, and in 4 of 42 without, pleocytosis. The sensitivity and specificity of pleocytosis to predict LB were 88% (95% confidence interval, 78%-98%) and 75% (62%-88%), respectively, and the positive and negative predictive values were 69% (55%-83%) and 90% (81%-99%), respectively. An increased CSF CXCL13 value had 67% (51%-83%) sensitivity and 100% specificity for LB. CONCLUSIONS: Because serum serology can be negative at presentation, lumbar puncture is a valuable tool when diagnosing LB among children with facial palsy. Pleocytosis and increased protein and CXCL13 values in the CSF suggest LB as the cause of facial palsy.


Assuntos
Quimiocina CXCL13/líquido cefalorraquidiano , Paralisia Facial/microbiologia , Leucocitose/líquido cefalorraquidiano , Neuroborreliose de Lyme/líquido cefalorraquidiano , Neuroborreliose de Lyme/diagnóstico , Adolescente , Anticorpos Antibacterianos/sangue , Borrelia burgdorferi/imunologia , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Hospitais Universitários , Humanos , Neuroborreliose de Lyme/complicações , Masculino , Sensibilidade e Especificidade , Punção Espinal
14.
Sci Rep ; 9(1): 8049, 2019 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-31142787

RESUMO

Lyme borreliosis (LB), caused by bacteria of the Borrelia burgdorferi sensu lato (Borrelia) species, is the most common tick-borne infection in the northern hemisphere. LB diagnostics is based on clinical evaluation of the patient and on laboratory testing, where the main method is the detection of Borrelia specific antibodies in patient samples. There are, however, shortcomings in the current serology based LB diagnostics, especially its inability to differentiate ongoing infection from a previously treated one. Identification of specific biomarkers of diseases is a growing application of metabolomics. One of the main methods of metabolomics is nuclear magnetic resonance (NMR) spectroscopy. In the present study, our aim was to analyze whether Borrelia growth in vitro and infection in vivo in mice causes specific metabolite differences, and whether NMR can be used to detect them. For this purpose, we performed NMR analyses of in vitro culture medium samples, and of serum and urine samples of Borrelia infected and control mice. The results show, that there were significant differences in the concentrations of several amino acids, energy metabolites and aromatic compounds between Borrelia culture and control media, and between infected and control mouse serum and urine samples. For example, the concentration of L-phenylalanine increases in the Borrelia growth medium and in serum of infected mice, whereas the concentrations of allantoin and trigonelline decrease in the urine of infected mice. Therefore, we conclude that Borrelia infection causes measurable metabolome differences in vitro and in Borrelia infected mouse serum and urine samples, and that these can be detected with NMR.


Assuntos
Borrelia burgdorferi/isolamento & purificação , Doença de Lyme/diagnóstico , Metaboloma , Metabolômica/métodos , Animais , Técnicas Bacteriológicas/métodos , Biomarcadores/análise , Biomarcadores/metabolismo , Borrelia burgdorferi/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Doença de Lyme/sangue , Doença de Lyme/microbiologia , Doença de Lyme/urina , Espectroscopia de Ressonância Magnética , Camundongos
15.
J Infect Dis ; 220(1): 116-126, 2019 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-30698707

RESUMO

BACKGROUND: Borrelia burgdorferi sensu lato spirochetes (Borrelia) causing Lyme borreliosis are able to disseminate from the initial entry site to distant organs in the host. Outer-surface adhesins are crucial in the bacterial dissemination and adhesion to various tissues. Two well-characterized Borrelia adhesins, decorin-binding proteins A and B, have been shown to bind to 2 host receptors, decorin and biglycan. However, the role of biglycan in Borrelia infection has not been characterized in vivo. METHODS: We infected biglycan knockout (KO) and wild-type (WT) C3H mice with strains representing 3 Borrelia genospecies, Borrelia burgdorferi sensu stricto, Borrelia garinii, and Borrelia afzelii. The infection was monitored by measuring joint swelling, Borrelia culture, polymerase chain reaction analysis, and serologic analysis. The host immune responses were analyzed by histological scoring of the inflammation in tissues and by cytokine profiling. RESULTS: B. burgdorferi sensu stricto and B. garinii established long-term infection in mice of both genotypes, while B. afzelii failed to disseminate in KO mice. Further, the B. burgdorferi sensu stricto-infected KO mice had persistent inflammation in the joints. CONCLUSIONS: The dissemination and tissue colonization of Borrelia and the inflammatory response of the host differ in a mouse biglycan expression- and Borrelia genospecies-dependent manner.


Assuntos
Biglicano/genética , Borrelia burgdorferi/patogenicidade , Doença de Lyme/microbiologia , Adesinas Bacterianas/genética , Animais , Decorina/genética , Feminino , Doença de Lyme/genética , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Knockout , Reação em Cadeia da Polimerase/métodos
16.
J Theor Biol ; 462: 97-108, 2019 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-30419249

RESUMO

Bacteria of the genus Borrelia cause vector-borne infections like the most important hard tick-borne disease in the northern hemisphere, Lyme borreliosis (LB), and soft tick or louse transmitted relapsing fevers (RF), prevalent in temperate and tropical areas. Borrelia burgdorferi sensu lato (s.l.) includes several genospecies and causes LB in humans. In infected patients, Borrelia burgdorferi sensu stricto (s.s.) expresses the BmpA, BmpB, BmpC and BmpD proteins. The role of these proteins in the pathogenesis of LB remains incompletely characterized, but they are, however, closely related to Treponema pallidum PnrA (Purine nucleoside receptor A), a substrate-binding lipoprotein of the ATP-binding cassette (ABC) transporter family preferentially binding purine nucleosides. Based on 3D homology modeling, the Bmp proteins share the typical fold of the substrate-binding protein family and the ligand-binding properties of BmpA, BmpB and BmpD are highly similar, whereas those of BmpC differ markedly. Nevertheless, these residues are highly conserved within the genus Borrelia and the inferred phylogenetic tree also reveals that the RF Borrelia lack BmpB proteins but has an additional Bmp protein (BmpA2) missing in LB-causing Borrelia burgdorferi s.l. Our results indicate that the Bmp proteins could bind nucleosides, although BmpC might have a different ligand-binding specificity and, therefore, a distinct function. Furthermore, the work provides a means for classifying the Bmp proteins and supports further elucidation of the roles of these proteins.


Assuntos
Proteínas de Bactérias/metabolismo , Borrelia burgdorferi/química , Homologia Estrutural de Proteína , Borrelia/química , Humanos , Ligantes , Doença de Lyme/etiologia , Nucleosídeos/metabolismo , Ligação Proteica
17.
Parasit Vectors ; 11(1): 556, 2018 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-30355331

RESUMO

BACKGROUND: Almost 3500 tick samples, originally collected via a nationwide citizen science campaign in 2015, were screened to reveal the prevalence and distribution of a wide spectrum of established and putative tick-borne pathogens vectored by Ixodes ricinus and I. persulcatus in Finland. The unique geographical distribution of these two tick species in Finland allowed us to compare pathogen occurrence between an I. ricinus-dominated area (southern Finland), an I. persulcatus-dominated area (northern Finland), and a sympatric area (central Finland). RESULTS: Of the analysed ticks, almost 30% carried at least one pathogen and 2% carried more than one pathogen. A higher overall prevalence of tick-borne pathogens was observed in I. ricinus than in I. persulcatus: 30.0% (604/2014) versus 24.0% (348/1451), respectively. In addition, I. ricinus were more frequently co-infected than I. persulcatus: 2.4% (49/2014) versus 0.8% (12/1451), respectively. Causative agents of Lyme borreliosis, i.e. bacterial genospecies in Borrelia burgdorferi (sensu lato) group, were the most prevalent pathogens (overall 17%). "Candidatus Rickettsia tarasevichiae" was found for the first time in I. ricinus ticks and in Finnish ticks in general. Moreover, Babesia divergens, B. venatorum and "Candidatus Neoehrlichia mikurensis" were reported for the first time from the Finnish mainland. CONCLUSIONS: The present study provides valuable information on the prevalence and geographical distribution of various tick-borne pathogens in I. ricinus and I. persulcatus ticks in Finland. Moreover, this comprehensive subset of ticks revealed the presence of rare and potentially dangerous pathogens. The highest prevalence of infected ticks was in the I. ricinus-dominated area in southern Finland, while the prevalence was essentially equal in sympatric and I. persulcatus-dominated areas. However, the highest infection rates for both species were in areas of their dominance, either in south or north Finland.


Assuntos
Ixodes/microbiologia , Ixodes/parasitologia , Animais , Vetores Aracnídeos/microbiologia , Vetores Aracnídeos/parasitologia , Feminino , Finlândia , Humanos , Ixodes/classificação , Masculino , Prevalência , Simpatria
18.
Proc Biol Sci ; 285(1884)2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-30068677

RESUMO

The impact of a pathogen on the fitness and behaviour of its natural host depends upon the host-parasite relationship in a given set of environmental conditions. Here, we experimentally investigated the effects of Borrelia afzelii, one of the aetiological agents of Lyme disease in humans, on the fitness of its natural rodent host, the bank vole (Myodes glareolus), in semi-natural conditions with two contrasting host population densities. Our results show that B. afzelii can modify the reproductive success and spacing behaviour of its rodent host, whereas host survival was not affected. Infection impaired the breeding probability of large bank voles. Reproduction was hastened in infected females without alteration of the offspring size at birth. At low density, infected males produced fewer offspring, fertilized fewer females and had lower mobility than uninfected individuals. Meanwhile, the infection did not affect the proportion of offspring produced or the proportion of mating partner in female bank voles. Our study is the first to show that B. afzelii infection alters the reproductive success of the natural host. The effects observed could reflect the sickness behaviour due to the infection or they could be a consequence of a manipulation of the host behaviour by the bacteria.


Assuntos
Arvicolinae/microbiologia , Grupo Borrelia Burgdorferi/fisiologia , Reprodução/fisiologia , Doenças dos Roedores/microbiologia , Animais , Arvicolinae/fisiologia , Grupo Borrelia Burgdorferi/patogenicidade , Feminino , Interações Hospedeiro-Patógeno/fisiologia , Doença de Lyme/microbiologia , Masculino , Densidade Demográfica , Comportamento Sexual Animal/fisiologia
19.
Diagn Microbiol Infect Dis ; 91(3): 226-228, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29567125

RESUMO

Cerebrospinal fluid chemokine (C-X-C motif) ligand 13 (CXCL13) is a marker for Lyme neuroborreliosis (LNB). CXCL13 lateral flow immunoassay (LFA) was compared with CXCL13 ELISA. CXCL13 LFA results correlated strongly with CXCL13 ELISA results. CXCL13 LFA is a rapid and easy-to-perform test, which is suitable for routine point-of-care diagnostics of suspected LNB patients.


Assuntos
Biomarcadores/líquido cefalorraquidiano , Quimiocina CXCL13/líquido cefalorraquidiano , Cromatografia de Afinidade/métodos , Neuroborreliose de Lyme/diagnóstico , Testes Imediatos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo , Adulto Jovem
20.
Ticks Tick Borne Dis ; 9(2): 275-280, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29153461

RESUMO

Lyme borreliosis (LB) is caused by Borrelia burgdorferi sensu lato (Bb-sl) and is the most common vector-borne disease in Europe. The objectives of this study were to determine the Bb-sl seroprevalence among the general Finnish adult population and to identify risk factors associated with Bb-sl-seropositive status. Two thousand sera from a nationwide health survey from 2011 were tested by whole-cell sonicate IgG ELISA, C6 peptide ELISA, and recomBead IgG 2.0 and test results were linked to a general health questionnaire. A multivariable logistic regression model was used to identify risk factors. The median age of the study population was 56 years (range 29-97) and the Bb-sl weighted seroprevalence was 3.9% (95% confidence interval (CI) 3.03-5.08). The weighted seroprevalence was significantly higher among males than females (adjusted odds ratio 1.91, 95%CI 1.21-3.04). The seroprevalence was highest in Southern, Central, and Eastern regions. The first Bb-sl seroprevalence study in Finland showed a seroprevalence of 3.9% (regional range 0.87%-6.12%). The results of this study can be used, together with previous data on LB incidence and spatial tick distribution, to target public health communication about preventive measures.


Assuntos
Grupo Borrelia Burgdorferi/isolamento & purificação , Doença de Lyme/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antibacterianos/sangue , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Finlândia/epidemiologia , Humanos , Imunoglobulina G/sangue , Doença de Lyme/microbiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Estudos Soroepidemiológicos , Fatores Sexuais , Adulto Jovem
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