Trained immunity is defined as an enhanced state of the innate system which leads to an improved immune response against related or non-related pathogens. Bacillus Calmette-Guérin (BCG) vaccine, a live attenuated Mycobacterium bovis strain, is currently one of the main inductors of trained immunity. The objective of the present study was to evaluate the protective effects of heat-inactivated M. bovis (HIMB) against Plasmodium berghei and Borrelia burgdorferi and characterize the immunological mechanisms involved. BALB/c and C3H/HeN mice were randomly assigned in similar number to either immunized group receiving two oral doses of HIMB with a 4-week interval, or control group treated with PBS. All the BALB/c mice were intraperitoneally infected with P. berghei while the C3H/HeN mice were subcutaneously infected with B. burgdorferi. Pathogen burden was significantly reduced in both immunized groups when compared to controls. The number of macrophages significantly decreased in the liver or in the spleen of the mice that had been immunized prior to the challenge with P. berghei or B. burgdorferi, respectively. Furthermore, the immunized groups showed an apparent upregulation of IFN-γ, TNF-α and IL-1α in the liver (P. berghei challenge) or a significant increase in IL-1α producing cells in the spleen (B. burgdorferi challenge). Our findings suggest that oral immunization with heat-inactivated mycobacteria limits pathogen burden through stimulation of the innate immune response in two vector-borne diseases in mice.
- MeSH
- adjuvancia imunologická * aplikace a dávkování MeSH
- BCG vakcína * imunologie aplikace a dávkování MeSH
- Borrelia burgdorferi imunologie MeSH
- cytokiny MeSH
- inaktivované vakcíny imunologie aplikace a dávkování MeSH
- interferon gama imunologie MeSH
- interleukin-1alfa imunologie MeSH
- játra imunologie MeSH
- lymeská nemoc * prevence a kontrola imunologie MeSH
- makrofágy imunologie MeSH
- malárie * prevence a kontrola imunologie MeSH
- Mycobacterium bovis * imunologie MeSH
- myši inbrední BALB C MeSH
- myši inbrední C3H MeSH
- myši MeSH
- Plasmodium berghei imunologie MeSH
- protilátky bakteriální krev MeSH
- slezina imunologie mikrobiologie MeSH
- TNF-alfa imunologie MeSH
- vysoká teplota MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Ticks are important vectors of various microorganisms, including bacteria. In this study, we examined Hyalomma aegyptium ticks collected from 240 spur-thighed tortoises Testudo graeca at 42 localities in the Mediterranean and Middle East and analysed them for the presence of bacteria of the genera Anaplasma, Borrelia, Coxiella, and Rickettsia. Altogether, 576 out of 928 analysed ticks (62.1%) were positive for at least one of the tested bacteria. The highest prevalence in individual ticks was found for Borrelia turcica (43.6%), followed by Rickettsia (12.3%) and Anaplasma (6.1%). No sample was positive for Coxiella burnetii. Among Rickettsia, we detected two species, Rickettsia africae and Rickettsia aeschlimannii, and also other unspecified Rickettsia. Anaplasma (100% identity with A. phagocytophilum) was detected at 15 (35%) out of 42 studied localities, any of Rickettsia at 28 (67%), and B. turcica at 32 (76%) localities. The geographic distribution of the studied microorganisms varied, with none of them detected in Syria, and only Rickettsia spp. detected in Morocco. Sequence analysis revealed substantial genetic variability in all detected agents, with the most variable (36 new haplotypes) being glpQ gene used as a marker for B. turcica. We also analysed the prevalence of various co-infections among studied ticks, with the mean number of co-infected ticks per tortoise increased with the number of ticks per tortoise. However, the frequencies of co-infected ticks do not indicate the presence of antagonistic or synergistic facilitative interactions between the agents. According to our data, we could expect that the eco-epidemiological importance of H. aegyptium does not stem from their tortoise hosts but rather from the low host specificity of its larvae and nymphs, feeding on a wider spectrum of reptilian, avian, and mammalian hosts.
- MeSH
- Anaplasma * izolace a purifikace MeSH
- Borrelia izolace a purifikace MeSH
- Coxiella izolace a purifikace genetika MeSH
- infestace klíšťaty veterinární epidemiologie parazitologie MeSH
- Ixodidae * mikrobiologie růst a vývoj MeSH
- Rickettsia * izolace a purifikace MeSH
- želvy * mikrobiologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Střední východ MeSH
- Středomoří MeSH
INTRODUCTION: Lyme borreliosis (LB), an infection caused by Borrelia burgdorferi sensu lato (Bbsl), is the most common tick-borne disease in Europe. To further characterize the LB burden in the Czech Republic, we conducted a seroprevalence study and estimated the incidence of symptomatic Bbsl infections. METHODS: Anti-Bbsl IgM and IgG antibodies were detected in sera collected from the adult population in 2011 -2012 by enzyme-linked immunosorbent assay and immunoblot tests at the National Reference Laboratory. The incidence of symptomatic Bbsl infections was estimated from the seroprevalence results and the symptomatic proportion and duration of persistence of anti-Bbsl IgG antibodies in Bbsl-infected individuals. Surveillance under-detection of symptomatic Bbsl infections was estimated by comparing surveillance-reported and seroprevalence-based incidence. RESULTS: Samples from 1996 adults were tested; the median age (range) was 45 (18 -87) years; 1037 (52.0 %) were female. The prevalence (with 95 % confidence interval) of anti-Bbsl IgG, and IgM and/or IgG (IgM/IgG) antibodies was 6.3 % (5.3 -7.5 %), and 9.5 % (8.3 -10.9 %), respectively. The IgM/IgG prevalence was 7.8 % (6.5 -9.2 %) in Bohemia and 15.3 % (12.2 -19.0 %) in Moravia. There were an estimated 30,563 (26,550 -34,962) symptomatic incident Bbsl infections in adults in the Czech Republic in 2012, for an incidence of 352.2 (306.0 -402.9) symptomatic Bbsl infections per 100,000 adults per year. There were an estimated 11 (10 -13) symptomatic Bbsl infections for each surveillance-reported LB case in the Czech Republic in 2012. CONCLUSIONS: There is high incidence of symptomatic Bbsl infections in the Czech Republic, particularly in Moravia. Interventions are needed to address the substantial burden of LB in the Czech Republic.
- MeSH
- Borrelia burgdorferi komplex * imunologie izolace a purifikace MeSH
- dospělí MeSH
- ELISA * MeSH
- imunoglobulin G * krev MeSH
- imunoglobulin M * krev MeSH
- incidence MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymeská nemoc * epidemiologie mikrobiologie krev MeSH
- mladiství MeSH
- mladý dospělý MeSH
- prevalence MeSH
- protilátky bakteriální * krev MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- séroepidemiologické studie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
Lyme disease, a tick-borne illness caused by Borrelia spirochetes, poses a significant threat to public health. While acaricides effectively control ticks on pets and livestock, their impact on pathogen transmission is often unclear. This study investigated the acaricidal efficacy of fipronil against Ixodes ricinus ticks and its potential to block Borrelia afzelii transmission. Initially, we employed the ex vivo membrane blood-feeding system to assess the dose–response acaricidal activity of ivermectin, fipronil and its metabolite fipronil sulfone, when supplemented in the blood meal throughout tick feeding. To obtain the temporal resolution of their acaricidal activity, ticks were allowed to initiate blood feeding on an artificial membrane before being exposed to a 1-time topical application of these acaricides. Fipronil demonstrated superior speed of acaricidal activity, with onset of tick moribundity within a few hours, prompting its selection for further in vivo testing with Borrelia-infected ticks. The I. ricinus nymphs infected with B. afzelii were topically treated with fipronil shortly after attachment to mice. Four weeks post-feeding, the skin and internal organs were examined for the presence of Borrelia. No spirochetes were detected in any organ of mice exposed to fipronil-treated ticks, while 9 out of 10 control mice, exposed to non-treated infectious ticks, displayed Borrelia infection. The in vitro co-culture experiments confirmed that fipronil had no direct effect on Borrelia viability, indicating a tick-directed effect. Overall, these results underline the potential of fipronil as a valuable tool for tick control strategies and suggest a concept for acaricide-mediated Borrelia-transmission blockers.
- MeSH
- akaricidy * farmakologie MeSH
- Borrelia burgdorferi komplex účinky léků fyziologie MeSH
- klíště * mikrobiologie účinky léků MeSH
- lymeská nemoc * prevence a kontrola přenos mikrobiologie MeSH
- myši MeSH
- nymfa mikrobiologie účinky léků MeSH
- pyrazoly * farmakologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Cíl: Zjistit výskyt potenciálně patogenních druhů babesií pro člověka v klíšťatech a v krvi psů a jelenů ve vybraných regionech České republiky. Prevalenci Babesia spp. v klíšťatech porovnat s výskytem jiných patogenů přenášených klíšťaty jako Borrelia spp., Anaplasma spp., Rickettsia spp. Materiál a metody: Vzorky klíšťat byly jednotlivě homogenizovány, ze vzorků klíšťat a krve živočichů provedena izolace DNA. Detekce Babesia spp. byla stanovena metodou PCR 18S rRNA genu a sekvenační analýzou PCR produktů určeny jednotlivé druhy babesií. Výsledky: V letech 2014–2016 byla analyzována klíšťata a krev psů a jelenů na různých místech České republiky. Ze souboru 675 klíšťat Ixodes ricinus dosahovala pozitivita na přítomnost Babesia spp. hodnot od 0,0 do 3,3 %. Sekvenační analýzou byly v klíšťatech identifikovány druhy Babesia venatorum, Babesia microti (patogenní druhy pro člověka) a druh Babesia capreoli. Prevalence Babesia spp. v klíšťatech byla v porovnání s výskytem jiných patogenů jako Borrelia burgdorferi s. l. (29,3 %), Anaplasma phagocytophilum (4,9 %) nižší a srovnatelná s Rickettsia spp. (1,6 %). U třetiny pozitivních klíšťat na babesie byla zjištěna koinfekce s Borrelia burgdorferi s. l. (B. venatorum – Borrelia garinii, Borrelia afzelii a B. microti – B. afzelii). Ze 109 vzorků krve psů bylo 3,7 % pozitivních na Babesia spp. s výskytem druhů Babesia gibsoni a Babesia vulpes. Z 50 vzorků krve jelenů z přírodního ekosystému dosahovala pozitivita 4,0 %. Identifikován byl druh Babesia divergens, nejvíce patogenní druh Babesia spp. pro člověka. Z 80 vzorků krve jelenů chovaných na farmách bylo pozitivních 5,0 % s výskytem druhu Babesia odocoilei. Nukleotidové sekvence babesií způsobujících humánní babesiózu byly zaslány do genové banky a přijaty pod čísly ON892053 (B. venatorum), ON892061 (B. microti), ON892067 (B. divergens). Závěr: Metodou PCR 18S rRNA genu a sekvenací amplikonů byly na území České republiky detekovány tři druhy babesií patogenních pro člověka: B. divergens, B. venatorum, B. microti. Výskyt těchto druhů babesií znamená potenciální riziko onemocnění babesiózou, zejména pro asplenické a imunokompromitované pacienty. Zjištěné koinfekce s Borrelia burgdorferi s. l. mohou být příčinou komplikovaného průběhu onemocnění.
Aim: To determine the occurrence of species of Babesia potentially pathogenic for humans in ticks and in the blood of dogs and deer in selected regions of the Czech Republic. To compare the prevalence of Babesia spp. in ticks with that of other tick-borne pathogens, such as Borrelia spp., Anaplasma spp., and Rickettsia spp. Material and Methods: Tick samples were individually homogenized. DNA was isolated from tick samples and animal blood. The detection of Babesia spp. was based on PCR of the 18S rRNA gene, and the identification to the species level was done by sequencing analysis of the PCR products. Results: In 2014–2016, ticks and blood of dogs and deer collected in various areas of the Czech Republic were analyzed. In a set of 675 Ixodes ricinus ticks, the positivity rate for Babesia spp. varied from 0.0 to 3.3 %. The species Babesia venatorum, Babesia microti (both pathogenic for humans), and Babesia capreoli were identified in ticks by sequencing analysis. The prevalence of Babesia spp. in ticks compared to that of other pathogens such as Borrelia burgdorferi s. l. (29.3 %) or Anaplasma phagocytophilum (4.9 %) was lower and comparable to that of Rickettsia spp. (1.6 %). Co-infection with Borrelia burgdorferi s.l (B. venatorum – Borrelia garinii, Borrelia afzelii, and B. microti – B. afzelii) was found in a third of Babesia spp. positive ticks. Out of 109 dog blood samples, 3.7 % were positive for Babesia spp., specifically Babesia gibsoni and Babesia vulpes. Of 50 blood samples of wild deer from the natural ecosystem, the positivity rate reached 4.0 %. The species Babesia divergens, a major human pathogen, was identified. Out of 80 blood samples from farmed deer, 5.0 % were positive for the species Babesia odocoilei. Nucleotide sequences of the agents causing human babesiosis were deposited in the gene bank under accession numbers ON892053 (B. venatorum), ON892061 (B. microti), and ON892067 (B. divergens). Conclusions: Using PCR of the 18S rRNA gene and amplicon sequencing, three species of Babesia causing human babesiosis were detected in the Czech Republic: B. divergens, B. venatorum, and B. microti. Babesia spp. pathogenic for humans pose a potential risk especially in asplenic and immunocompromised patients. The detected co-infections with Borrelia spp. can be the cause of a complicated course of the disease.
- MeSH
- Babesia mikrobiologie MeSH
- babezióza * epidemiologie krev přenos MeSH
- Borrelia burgdorferi MeSH
- diagnostické techniky molekulární metody MeSH
- klíšťata * mikrobiologie MeSH
- koinfekce diagnóza přenos MeSH
- krev mikrobiologie MeSH
- lidé MeSH
- nemoci přenášené klíšťaty epidemiologie přenos prevence a kontrola MeSH
- polymerázová řetězová reakce metody MeSH
- psi * mikrobiologie MeSH
- vysoká zvěř * krev mikrobiologie MeSH
- Check Tag
- lidé MeSH
- psi * mikrobiologie MeSH
- Geografické názvy
- Česká republika MeSH
OBJECTIVES: The purpose of the current study was to analyse the risks of Lyme borreliosis (LB) among 1,070 forestry workers, the influence of responsible behaviour (use of repellents, skin self-inspection) on Borrelia screening result status, and the occurrence of immediate and mid-term symptoms after tick bites and LB positive serological screening test. METHODS: The questionnaire was conducted as well as blood tests for LB disease by one-stage serological screening procedure using ELISA for specific B. burgdorferi IgM and IgG antibodies (EuroImmun AG company, Germany). RESULTS: While 39.6% of foresters were LB positive among bitten foresters, as many as 27.0% were LB positive among those, who did not recall any tick attacks at all. Individuals with known history of tick bites had significantly higher odds (1.770×) of being LB positive (p < 0.05), while the use of repellents or skin self-inspection after visiting woods had no influence on LB results. The odds of skin discolouration after tick bites was significantly lower (0.682×) in case of LB positive test compared to LB negative test (p < 0.05), which can be explained by the fact that foresters could be unaware about erythema migrans appearance and timing, considering tick bite and developed later rash as completely separate events. Moreover, 69.1% of the bitten foresters with LB positive result developed no secondary symptoms (excluding those related to the skin), and the most frequent clinical symptoms were arthralgia (24.9%), followed by myalgia (7.6%), headache (5.7%), and damage to facial nerve (2.7%), which are non-specific and can be present in other illnesses. CONCLUSION: Therefore, the recommendations proposed would be the regular laboratory testing for LB of sensitive and at-risk population, who visits endemic woody areas, irrespective of all other factors involved.
- MeSH
- Borrelia burgdorferi imunologie izolace a purifikace MeSH
- dospělí MeSH
- ELISA MeSH
- klíště * MeSH
- kousnutí klíštětem * MeSH
- lesnictví MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymeská nemoc * epidemiologie MeSH
- průzkumy a dotazníky MeSH
- senioři MeSH
- zvířata MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Německo MeSH
UNLABELLED: Lyme disease, caused by spirochetes in the Borrelia burgdorferi sensu lato clade within the Borrelia genus, is transmitted by Ixodes ticks and is currently the most prevalent and rapidly expanding tick-borne disease in Europe and North America. We report complete genome sequences of 47 isolates that encompass all established species in this clade while highlighting the diversity of the widespread human pathogenic species B. burgdorferi. A similar set of plasmids has been maintained throughout Borrelia divergence, indicating that they are a key adaptive feature of this genus. Phylogenetic reconstruction of all sequenced Borrelia genomes revealed the original divergence of Eurasian and North American lineages and subsequent dispersals that introduced B. garinii, B. bavariensis, B. lusitaniae, B. valaisiana, and B. afzelii from East Asia to Europe and B. burgdorferi and B. finlandensis from North America to Europe. Molecular phylogenies of the universally present core replicons (chromosome and cp26 and lp54 plasmids) are highly consistent, revealing a strong clonal structure. Nonetheless, numerous inconsistencies between the genome and gene phylogenies indicate species dispersal, genetic exchanges, and rapid sequence evolution at plasmid-borne loci, including key host-interacting lipoprotein genes. While localized recombination occurs uniformly on the main chromosome at a rate comparable to mutation, lipoprotein-encoding loci are recombination hotspots on the plasmids, suggesting adaptive maintenance of recombinant alleles at loci directly interacting with the host. We conclude that within- and between-species recombination facilitates adaptive sequence evolution of host-interacting lipoprotein loci and contributes to human virulence despite a genome-wide clonal structure of its natural populations. IMPORTANCE: Lyme disease (also called Lyme borreliosis in Europe), a condition caused by spirochete bacteria of the genus Borrelia, transmitted by hard-bodied Ixodes ticks, is currently the most prevalent and rapidly expanding tick-borne disease in the United States and Europe. Borrelia interspecies and intraspecies genome comparisons of Lyme disease-related bacteria are essential to reconstruct their evolutionary origins, track epidemiological spread, identify molecular mechanisms of human pathogenicity, and design molecular and ecological approaches to disease prevention, diagnosis, and treatment. These Lyme disease-associated bacteria harbor complex genomes that encode many genes that do not have homologs in other organisms and are distributed across multiple linear and circular plasmids. The functional significance of most of the plasmid-borne genes and the multipartite genome organization itself remains unknown. Here we sequenced, assembled, and analyzed whole genomes of 47 Borrelia isolates from around the world, including multiple isolates of the human pathogenic species. Our analysis elucidates the evolutionary origins, historical migration, and sources of genomic variability of these clinically important pathogens. We have developed web-based software tools (BorreliaBase.org) to facilitate dissemination and continued comparative analysis of Borrelia genomes to identify determinants of human pathogenicity.
- MeSH
- Borrelia burgdorferi komplex genetika klasifikace MeSH
- Borrelia burgdorferi genetika klasifikace MeSH
- Borrelia genetika klasifikace MeSH
- fylogeneze * MeSH
- genetická variace MeSH
- genom bakteriální * MeSH
- interakce mikroorganismu a hostitele genetika MeSH
- klíště mikrobiologie MeSH
- lidé MeSH
- lipoproteiny * genetika MeSH
- lymeská nemoc * mikrobiologie přenos MeSH
- molekulární evoluce MeSH
- plazmidy genetika MeSH
- rekombinace genetická * MeSH
- sekvenování celého genomu MeSH
- selekce (genetika) * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Evropa MeSH
- Severní Amerika MeSH
- MeSH
- antibakteriální látky aplikace a dávkování terapeutické užití MeSH
- Borrelia burgdorferi komplex MeSH
- imunoanalýza MeSH
- lidé MeSH
- lymeská nemoc * diagnóza epidemiologie farmakoterapie MeSH
- lymská neuroborelióza diagnóza farmakoterapie MeSH
- polymerázová řetězová reakce MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Relapsing fever (RF), a vector-borne disease caused by Borrelia spp., is characterized by recurring febrile episodes due to repeated bouts of bacteremia. RF spirochetes can be geographically and phylogenetically divided into two distinct groups; Old World RF Borrelia (found in Africa, Asia, and Europe) and New World RF Borrelia (found in the Americas). While RF is a rarely reported disease in the Americas, RF is prevalent in endemic parts of Africa. Despite phylogenetic differences between Old World and New World RF Borrelia and higher incidence of disease associated with Old World RF spirochete infection, genetic manipulation has only been described in New World RF bacteria. Herein, we report the generation of genetic tools for use in the Old World RF spirochete, Borrelia duttonii. We describe methods for transformation and establish shuttle vector- and integration-based approaches for genetic complementation, creating green fluorescent protein (gfp)-expressing B. duttonii strains as a proof of principle. Allelic exchange mutagenesis was also used to inactivate a homolog of the Borrelia burgdorferi p66 gene, which encodes an important virulence factor, in B. duttonii and demonstrate that this mutant was attenuated in a murine model of RF. Finally, the B. duttonii p66 mutant was complemented using shuttle vector- and cis integration-based approaches. As expected, complemented p66 mutant strains were fully infectious, confirming that P66 is required for optimal mammalian infection. The genetic tools and techniques reported herein represent an important advancement in the study of RF Borrelia that allows for future characterization of virulence determinants and colonization factors important for the enzootic cycle of Old World RF spirochetes.
