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Annals of Clinical Microbiology and... Mar 2022Lyme borreliosis is the most prevalent arthropod-borne infection in the Northern Hemisphere. In Europe, Borrelia afzelii is predominantly involved in cutaneous...
BACKGROUND
Lyme borreliosis is the most prevalent arthropod-borne infection in the Northern Hemisphere. In Europe, Borrelia afzelii is predominantly involved in cutaneous manifestations, Borrelia garinii and Borrelia bavariensis in neurological manifestations, and Borrelia burgdorferi sensu stricto in articular ones. Liver impairement is not classical in Lyme borreliosis. Diagnosis is currently mainly based on serological testing, and is challenging in immunocompromised patients.
CASE PRESENTATION
We report the first case of B. garinii infection revealed by liver involvement in an immunocompromised man. A 73-year-old man with marginal zone lymphoma, treated with bendamustine and rituximab, developed intermittent fever and inflammatory syndrome. Microbial investigations were all negative and FDG-PET showed complete remission of the lymphoma. Three months later, liver biopsy was performed and histology revealed spirochetes-like bacteria. Microbial diagnosis was performed by 16S rDNA sequencing, flagellin (flaB) gene sequencing and multi-locus sequence typing and identified B. garinii. The patient recovered successfully after a three weeks course of antibiotics. Diagnosis was challenging because Borrelia hepatic involvement is unusual and no erythema migrans nor tick bite were notified.
CONCLUSION
This case highlights that unexplained fever and inflammatory syndrome in immunocompromised patients warrants specific investigations to identify bacteria such as spirochetes.
Topics: Aged; Borrelia burgdorferi; Borrelia burgdorferi Group; Humans; Liver; Lyme Disease; Male; Multilocus Sequence Typing
PubMed: 35346214
DOI: 10.1186/s12941-022-00506-6 -
MBio Oct 2022Relapsing fever, caused by diverse Borrelia spirochetes, is prevalent in many parts of the world and causes significant morbidity and mortality. To investigate the...
Relapsing fever, caused by diverse Borrelia spirochetes, is prevalent in many parts of the world and causes significant morbidity and mortality. To investigate the pathoetiology of relapsing fever, we performed a high-throughput screen of Borrelia-binding host factors using a library of human extracellular and secretory proteins and identified CD55 as a novel host binding partner of Borrelia crocidurae and Borrelia persica, two agents of relapsing fever in Africa and Eurasia. CD55 is present on the surface of erythrocytes, carries the Cromer blood group antigens, and protects cells from complement-mediated lysis. Using flow cytometry, we confirmed that both human and murine CD55 bound to B. crocidurae and B. persica. Given the expression of CD55 on erythrocytes, we investigated the role of CD55 in pathological B. crocidurae-induced erythrocyte aggregation (rosettes), which enables spirochete immune evasion. We showed that rosette formation was partially dependent on host cell CD55 expression. Pharmacologically, soluble recombinant CD55 inhibited erythrocyte rosette formation. Finally, CD55-deficient mice infected with B. crocidurae had a lower pathogen load and elevated proinflammatory cytokine and complement factor C5a levels. In summary, our results indicate that CD55 is a host factor that is manipulated by the causative agents of relapsing fever for immune evasion. Borrelia species are causative agents of Lyme disease and relapsing fever infections in humans. B. crocidurae causes one of the most prevalent relapsing fever infections in parts of West Africa. In the endemic regions, B. crocidurae is present in ~17% of the ticks and ~11% of the rodents that serve as reservoirs. In Senegal, ~7% of patients with acute febrile illness were found to be infected with B. crocidurae. There is little information on host-pathogen interactions and how B. crocidurae manipulates host immunity. In this study, we used a high-throughput screen to identify host proteins that interact with relapsing fever-causing Borrelia species. We identified CD55 as one of the host proteins that bind to B. crocidurae and B. persica, the two causes of relapsing fever in Africa and Eurasia. We show that the interaction of B. crocidurae with CD55, present on the surface of erythrocytes, is key to immune evasion and successful infection . Our study further shows the role of CD55 in complement regulation, regulation of inflammatory cytokine levels, and innate immunity during relapsing fever infection. Overall, this study sheds light on host-pathogen interactions during relapsing fever infection .
Topics: Humans; Animals; Mice; Relapsing Fever; Immune Evasion; Borrelia; Rodentia; Blood Group Antigens; Cytokines
PubMed: 36036625
DOI: 10.1128/mbio.01161-22 -
Frontiers in Cellular and Infection... 2020Spirochetes of the genus are divided into relapsing fever borreliae and Lyme disease borreliae. Immunoserological assays have been poorly developed for relapsing fever... (Review)
Review
Spirochetes of the genus are divided into relapsing fever borreliae and Lyme disease borreliae. Immunoserological assays have been poorly developed for relapsing fever borreliae, where direct detection methods are more adapted to the pathophysiology of these infections presenting with massive bacteraemia. However, emergence of the novel agent of relapsing fever has renewed interest in serology in this context. In Lyme disease, because direct detection methods show low sensitivity, serology plays a central role in the diagnostic strategy. This diagnostic strategy is based on a two-tier methodology involving a first test (ELISA) with high sensitivity and acceptable specificity and a second, more specific test (western blot) for diagnostic confirmation. The most frequent limitations and pitfalls of serology are cross reactions, false IgM positivity, a seronegative window period at the early time of the infection, and serologic scars with a suspicion of reinfection. International guidelines have thus been proposed to avoid these difficulties with interpretation. Finally, unconventional diagnostic tests have been developed recently in the context of a highly publicized disease, with widely varying results, some of which have no available evidence-based data. New two-tier testing strategies using two ELISA tests (C6 and WCS for example) to replace immunoblot are currently proposed by some authors and guidelines, and promising new tests such as CXCL-13 in CSF are promising tools for the improvement of the diagnosis of Lyme borreliosis.
Topics: Antibodies, Bacterial; Borrelia; Borrelia burgdorferi Group; Enzyme-Linked Immunosorbent Assay; Humans; Lyme Disease; Relapsing Fever
PubMed: 32509603
DOI: 10.3389/fcimb.2020.00241 -
Current Issues in Molecular Biology 2021The mammalian host responds to infection with spirochetes through a highly orchestrated immune defense involving innate and adaptive effector functions aimed toward...
The mammalian host responds to infection with spirochetes through a highly orchestrated immune defense involving innate and adaptive effector functions aimed toward limiting pathogen burdens, minimizing tissue injury, and preventing subsequent reinfection. The evolutionary adaptation of spirochetes to their reservoir mammalian hosts may allow for its persistence despite this immune defense. This review summarizes our current understanding of the host immune response to , the most widely studied spp. and etiologic agent of Lyme borreliosis. Pertinent literature will be reviewed with emphasis on , and animal studies that influenced our understanding of both the earliest responses to as it enters the mammalian host and those that evolve as spirochetes disseminate and establish infection in multiple tissues. Our focus is on the immune response of inbred mice, the most commonly studied animal model of infection and surrogate for one of this pathogen's principle natural reservoir hosts, the white-footed deer mouse. Comparison will be made to the immune responses of humans with Lyme borreliosis. Our goal is to provide an understanding of the dynamics of the mammalian immune response during infection with and its relation to the outcomes in reservoir (mouse) and non-reservoir (human) hosts.
Topics: Animals; Biological Evolution; Borrelia; Borrelia Infections; Disease Reservoirs; Host-Pathogen Interactions; Humans; Lyme Disease; Organ Specificity
PubMed: 33289684
DOI: 10.21775/cimb.042.145 -
Journal of Clinical Microbiology Jun 2021diagnostic imaging of bacterial infections is currently reliant on targeting their metabolic pathways, an ineffective method to identify microbial species with low...
diagnostic imaging of bacterial infections is currently reliant on targeting their metabolic pathways, an ineffective method to identify microbial species with low metabolic activity. Here, we establish HS-198 as a small-molecule fluorescent conjugate that selectively targets the highly conserved bacterial protein HtpG (high-temperature protein G), within Borrelia burgdorferi, the bacterium responsible for Lyme disease. We describe the use of HS-198 to target morphologic forms of B. burgdorferi in both the logarithmic growth phase and the metabolically dormant stationary phase as well as in inactivated spirochetes. Furthermore, in a murine infection model, systemically injected HS-198 identified B. burgdorferi as revealed by imaging in postnecropsy tissue sections. These findings demonstrate how small-molecule probes directed at conserved bacterial protein targets can function to identify the microbe using noninvasive imaging and potentially as scaffolds to deliver antimicrobial agents to the pathogen.
Topics: Animals; Bacterial Proteins; Borrelia burgdorferi; Diagnostic Imaging; Humans; Lyme Disease; Mice
PubMed: 33910962
DOI: 10.1128/JCM.02313-20 -
Journal of the American Veterinary... Sep 2022To determine the prevalence of Anaplasma phagocytophilum and Borrelia burgdorferi infections in Pennsylvania horses.
OBJECTIVE
To determine the prevalence of Anaplasma phagocytophilum and Borrelia burgdorferi infections in Pennsylvania horses.
ANIMALS
271 horses.
PROCEDURES
A survey was conducted with PCR and serology to evaluate anaplasmosis and Lyme disease infections in horses from Pennsylvania that were suspected for tick-borne infection.
RESULTS
A phagocytophilum was detected in 19/271 (7.0%) Pennsylvania horses tested by the duplex PCR. B burgdorferi was not detected in any horse blood tested by PCR. Overall, 120/271 (44.3%) horses tested positive for presence of A phagocytophilum antibodies by at least the IDEXX SNAP 4Dx Plus lateral flow immunosorbent (SNAP) or indirect fluorescent antibody (IFA) assay, with 69 (25.5%) testing positive by both SNAP and IFA; 43 (15.9%) tested positive by IFA only, and 8 (3.0%) tested positive by SNAP only. Similarly, 209/271 (77.1%) horses tested positive for the presence of B burgdorferi antibodies by at least 1 test, with 139 (51.3%) testing positive by both SNAP and IFA; 45 (16.6%) tested positive by SNAP only, and 25 (9.2%) tested positive by IFA.
CLINICAL RELEVANCE
Both A phagocytophilum and B burgdorferi are important tick-borne infections. The study provides prevalence data for both A phagocytophilum and B burgdorferi and compares test performance. For serologic detection, IFA detected antibodies to A phagocytophilum in a higher proportion (41.3%) of horses compared to SNAP (28.4%), while SNAP detected antibodies to B burgdorferi in a higher proportion (67.9%) of horses compared to IFA (60.5%). Both diseases showed a high seroprevalence in all areas surveyed.
Topics: Horses; Animals; Anaplasma phagocytophilum; Borrelia burgdorferi; Ehrlichiosis; Seroepidemiologic Studies; Prevalence; Pennsylvania; Antibodies, Bacterial; Lyme Disease; Tick-Borne Diseases; Horse Diseases
PubMed: 36094906
DOI: 10.2460/javma.22.06.0232 -
Clinical Microbiology and Infection :... May 2009Tick-borne relapsing fever (TBRF) has been reported in Eurasia and attributed mainly to Borrelia persica, although other entities have also been described. Ornithodoros... (Review)
Review
Tick-borne relapsing fever (TBRF) has been reported in Eurasia and attributed mainly to Borrelia persica, although other entities have also been described. Ornithodoros tholozani is the most important tick vector, found in India and Kashmir, the southern countries of the former USSR, Iran, Iraq, Syria, Jordan, Turkey, Israel, Egypt, and Cyprus. It inhabits caves, ruins, and burrows of rodents and small mammals. In the northern countries, O. tholozani also lives in houses and cowsheds. In Israel, 30-60% of caves were found to be infested. PCR studies of Borrelia infection of O. tholozani ticks collected in caves showed very variable rates, ranging from less than 2% to 40%. The number of human cases reported varies among countries, from eight cases per year in Israel to 72 cases per year in Iran. The incubation period is 5-9 days. The fever attacks last from several hours to 4 days, and are accompanied by chills, headache, nausea and vomiting, sweating, abdominal pain, arthralgia, and cough; complications are rare. Other described Borrelia species are Borrelia caucasica, Borrelia latyschewii, Borrelia microtii, and Borrelia baltazardi. The classic taxonomy based on the co-speciation concept is very complex and very confusing. For this reason, 16S rRNA and flaB genes were used for taxonomic clarification. Sequencing of Israeli TBRF flaB genes, from human and tick samples, has demonstrated a third cluster corresponding to the Eurasia strains, in addition to both New World and Old World clusters. Thin and thick blood smears remain the most frequently used methods for laboratory diagnosis, with a sensitivity of 80%. PCR-based diagnosis is the most sensitive method, and has the advantage of allowing species identification.
Topics: Animals; Asia; Bacterial Typing Techniques; Borrelia; Case Management; Cluster Analysis; DNA, Bacterial; Disease Vectors; Europe; Genotype; Humans; Incidence; Ornithodoros; Relapsing Fever; Sequence Analysis, DNA
PubMed: 19489923
DOI: 10.1111/j.1469-0691.2009.02767.x -
Veterinary Medicine and Science Nov 2018Tick-borne relapsing fever (TBRF) caused by the bacteria Borrelia, is poorly documented in veterinary medicine. Given the widespread presence of the soft tick vectors -... (Review)
Review
Tick-borne relapsing fever (TBRF) caused by the bacteria Borrelia, is poorly documented in veterinary medicine. Given the widespread presence of the soft tick vectors - Ornithodoros and the recently discovered hard tick vectors, as well as their close association with animal hosts, it is highly likely that infection occurs, but is rarely reported to be of veterinary importance. Sporadic reports of canine infection, some being fatal through to probable cause of abortion in horses have been published. Some of these pathogens exist in regions where there are limited diagnostic facilities, hence, they are likely to be missed and their impact on productivity may be unquantified. Here we review available literatures on cases of TBRF in domestic and wild animals in order to show their potential veterinary medical impact. Future efforts using field and laboratory surveys are needed to determine pathogenesis, vector competence and distribution in animals, their impact on animal health and productivity as well as to prevent further spill to the human population, where it is already a public health problem in some parts of the world.
Topics: Animals; Animals, Domestic; Animals, Wild; Borrelia; Relapsing Fever
PubMed: 29943903
DOI: 10.1002/vms3.108 -
The Veterinary Clinics of North... Jul 2019The Lyme disease spirochetes are a highly diverse group of bacteria with unique biological properties. Their ability to cycle between ticks and mammals requires that... (Review)
Review
The Lyme disease spirochetes are a highly diverse group of bacteria with unique biological properties. Their ability to cycle between ticks and mammals requires that they adapt to variable and constantly changing environmental conditions. Outer surface protein C is an essential virulence determinant that has received considerable attention in vaccine and diagnostic assay development. Knowledge of OspC diversity, its antigenic determinants, and its production patterns throughout the enzootic cycle, as well as in the laboratory setting, is essential for understanding immune responses induced by infection or vaccination.
Topics: Animals; Bacterial Vaccines; Borrelia burgdorferi; Lyme Disease; Pets
PubMed: 30967254
DOI: 10.1016/j.cvsm.2019.02.007 -
Euro Surveillance : Bulletin Europeen... May 2019Background clusters phylogenetically among relapsing fever borreliae, but is transmitted by hard ticks. Recent recognition as a human pathogen has intensified research... (Review)
Review
Background clusters phylogenetically among relapsing fever borreliae, but is transmitted by hard ticks. Recent recognition as a human pathogen has intensified research into its ecology and pathogenic potential.AimsWe aimed to provide a timely critical integrative evaluation of our knowledge on , to assess its public health relevance and guide future research.MethodsThis narrative review used peer-reviewed literature in English from January 1994 to December 2018.Results occurs in the world's northern hemisphere where it co-circulates with sensu lato, which causes Lyme disease. The two borreliae have overlapping vertebrate and tick hosts. While ticks serve as vectors for both species, they are also reservoirs for . Three genotypes are described, but further diversity is being recognised. The lack of sufficient cultivable isolates and vertebrate models compromise investigation of human infection and its consequences. Our understanding mainly originates from limited case series. In these, human infections mostly present as influenza-like illness, with relapsing fever in sporadic cases and neurological disease reported in immunocompromised patients. Unspecific clinical presentation, also occasionally resulting from Lyme- or other co-infections, complicates diagnosis, likely contributing to under-reporting. Diagnostics mainly employ PCR and serology. infections are treated with antimicrobials according to regimes used for Lyme disease.ConclusionsWith co-infection of tick-borne pathogens being commonplace, diagnostic improvements remain important. Developing in vivo models might allow more insight into human pathogenesis. Continued ecological and human case studies are key to better epidemiological understanding, guiding intervention strategies.
Topics: Amoxicillin; Animals; Anti-Bacterial Agents; Borrelia; Borrelia Infections; Borrelia burgdorferi; Disease Reservoirs; Disease Vectors; Humans; Ixodidae; Salivary Glands; Tick Bites; Ticks
PubMed: 31064634
DOI: 10.2807/1560-7917.ES.2019.24.18.1800170