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Sample records for borreliae human relapsing

  1. Relapsing Fever Borreliae in Africa

    PubMed Central

    Elbir, Haitham; Raoult, Didier; Drancourt, Michel

    2013-01-01

    The study of relapsing fever borreliae in Africa has long suffered from the use of non-specific laboratory tools for the direct detection of these spirochetes in clinical and vector specimens. Accordingly, Borrelia hispanica, Borrelia crocidurae, Borrelia duttonii, and Borrelia recurrentis have traditionally been distinguished on the basis of geography and vector and the unproven hypothesis that each species was exclusive to one vector. The recent sequencing of three relapsing fever Borrelia genomes in our laboratory prompted the development of more specific tools and a reappraisal of the epidemiology in Africa. Five additional potential species still need to be cultured from clinical and vector sources in East Africa to further assess their uniqueness. Here, we review the molecular evidence of relapsing fever borreliae in hosts and ectoparasites in Africa and explore the diversity, geographical distribution, and vector association of these pathogens for Africans and travelers to Africa. PMID:23926141

  2. Borrelia hispanica Relapsing Fever, Morocco

    PubMed Central

    Sarih, M’hammed; Garnier, Martine; Boudebouch, Najma; Bouattour, Ali; Rihani, Abdelaziz; Hassar, Mohammed; Gern, Lise; Postic, Danièle

    2009-01-01

    We found that 20.5% of patients with an unexplained fever in northwestern Morocco had tick-borne relapsing fever. Molecular detection specific for the 16S rRNA gene identified Borrelia hispanica. The noncoding intergenic spacer sequence domain showed high sensitivity and good resolution for this species. PMID:19861058

  3. Borrelia hispanica relapsing fever, Morocco.

    PubMed

    Sarih, M'hammed; Garnier, Martine; Boudebouch, Najma; Bouattour, Ali; Rihani, Abdelaziz; Hassar, Mohammed; Gern, Lise; Postic, Danièle; Cornet, Muriel

    2009-10-01

    We found that 20.5% of patients with an unexplained fever in northwestern Morocco had tick-borne relapsing fever. Molecular detection specific for the 16S rRNA gene identified Borrelia hispanica. The noncoding intergenic spacer sequence domain showed high sensitivity and good resolution for this species. PMID:19861058

  4. African Relapsing Fever Borreliae Genomospecies Revealed by Comparative Genomics

    PubMed Central

    Elbir, Haitham; Abi-Rached, Laurent; Pontarotti, Pierre; Yoosuf, Niyaz; Drancourt, Michel

    2014-01-01

    Background: Relapsing fever borreliae are vector-borne bacteria responsible for febrile infection in humans in North America, Africa, Asia, and in the Iberian Peninsula in Europe. Relapsing fever borreliae are phylogenetically closely related, yet they differ in pathogenicity and vectors. Their long-term taxonomy, based on geography and vector grouping, needs to be re-apprised in a genomic context. We therefore embarked into genomic analyses of relapsing fever borreliae, focusing on species found in Africa. Results: Genome-wide phylogenetic analyses group Old World Borrelia crocidurae, Borrelia hispanica, B. duttonii, and B. recurrentis in one clade, and New World Borrelia turicatae and Borrelia hermsii in a second clade. Accordingly, average nucleotide identity is 99% among B. duttonii, B. recurrentis, and B. crocidurae and 96% between latter borreliae and B. hispanica while the similarity is 86% between Old World and New World borreliae. Comparative genomics indicates that the Old World relapsing fever B. duttonii, B. recurrentis, B. crocidurae, and B. hispanica have a 2,514-gene pan genome and a 933-gene core genome that includes 788 chromosomal and 145 plasmidic genes. Analyzing the role that natural selection has played in the evolution of Old World borreliae species revealed that 55 loci were under positive diversifying selection, including loci coding for membrane, flagellar, and chemotaxis proteins, three categories associated with adaption to specific niches. Conclusion: Genomic analyses led to a reappraisal of the taxonomy of relapsing fever borreliae in Africa. These analyses suggest that B. crocidurae, B. duttonii, and B. recurrentis are ecotypes of a unique genomospecies, while B. hispanica is a distinct species. PMID:25229054

  5. Chromosome and Linear Plasmid Sequences of a 2015 Human Isolate of the Tick-Borne Relapsing Fever Spirochete, Borrelia turicatae.

    PubMed

    Kingry, Luke C; Batra, Dhwani; Replogle, Adam; Sexton, Christopher; Rowe, Lori; Stermole, Benjamin M; Christensen, Anna M; Schriefer, Martin E

    2016-01-01

    The sequences of the complete linear chromosome and 7 linear plasmids of the relapsing fever spirochete Borrelia turicatae are presented in this report. The 925,547 bp of chromosome and 380,211 bp of plasmid sequence were predicted to contain a total of 1,131 open reading frames, with an average G+C content of 29.7%. PMID:27417836

  6. Chromosome and Linear Plasmid Sequences of a 2015 Human Isolate of the Tick-Borne Relapsing Fever Spirochete, Borrelia turicatae

    PubMed Central

    Batra, Dhwani; Replogle, Adam; Sexton, Christopher; Rowe, Lori; Stermole, Benjamin M.; Christensen, Anna M.

    2016-01-01

    The sequences of the complete linear chromosome and 7 linear plasmids of the relapsing fever spirochete Borrelia turicatae are presented in this report. The 925,547 bp of chromosome and 380,211 bp of plasmid sequence were predicted to contain a total of 1,131 open reading frames, with an average G+C content of 29.7%. PMID:27417836

  7. Endemic Foci of the Tick-Borne Relapsing Fever Spirochete Borrelia crocidurae in Mali, West Africa, and the Potential for Human Infection

    PubMed Central

    Schwan, Tom G.; Anderson, Jennifer M.; Lopez, Job E.; Fischer, Robert J.; Raffel, Sandra J.; McCoy, Brandi N.; Safronetz, David; Sogoba, Nafomon; Maïga, Ousmane; Traoré, Sékou F.

    2012-01-01

    Background Tick-borne relapsing fever spirochetes are maintained in endemic foci that involve a diversity of small mammals and argasid ticks in the genus Ornithodoros. Most epidemiological studies of tick-borne relapsing fever in West Africa caused by Borrelia crocidurae have been conducted in Senegal. The risk for humans to acquire relapsing fever in Mali is uncertain, as only a few human cases have been identified. Given the high incidence of malaria in Mali, and the potential to confuse the clinical diagnosis of these two diseases, we initiated studies to determine if there were endemic foci of relapsing fever spirochetes that could pose a risk for human infection. Methodology/Principal Findings We investigated 20 villages across southern Mali for the presence of relapsing fever spirochetes. Small mammals were captured, thin blood smears were examined microscopically for spirochetes, and serum samples were tested for antibodies to relapsing fever spirochetes. Ornithodoros sonrai ticks were collected and examined for spirochetal infection. In total, 11.0% of the 663 rodents and 14.3% of the 63 shrews tested were seropositive and 2.2% of the animals had active spirochete infections when captured. In the Bandiagara region, the prevalence of infection was higher with 35% of the animals seropositive and 10% infected. Here also Ornithodoros sonrai were abundant and 17.3% of 278 individual ticks tested were infected with Borrelia crocidurae. Fifteen isolates of B. crocidurae were established and characterized by multi-locus sequence typing. Conclusions/Significance The potential for human tick-borne relapsing fever exists in many areas of southern Mali. PMID:23209863

  8. Relapsing Fever Borreliae: A Global Review.

    PubMed

    Cutler, Sally J

    2015-12-01

    Relapsing fever borreliae were notorious and feared infectious agents that earned their place in history through their devastating impact as causes of both epidemic and endemic infection. They are now considered more as an oddity, and their burden of infection is largely overshadowed by other infections such as malaria, which presents in a similar clinical way. Despite this, they remain the most common bacterial infection in some developing countries. Transmitted by soft ticks or lice, these fascinating spirochetes have evolved a myriad of mechanisms to survive within their diverse environments. PMID:26593261

  9. Fibronectin-Binding Protein of Borrelia hermsii Expressed in the Blood of Mice with Relapsing Fever

    PubMed Central

    Lewis, Eric R. G.; Marcsisin, Renee A.; Campeau Miller, Shelley A.; Hue, Fong; Phillips, April; AuCoin, David P.

    2014-01-01

    To identify and characterize surface proteins expressed by the relapsing fever (RF) agent Borrelia hermsii in the blood of infected mice, we used a cell-free filtrate of their blood to immunize congenic naive mice. The resultant antiserum was used for Western blotting of cell lysates, and gel slices corresponding to reactive bands were subjected to liquid chromatography-tandem mass spectrometry, followed by a search of the proteome database with the peptides. One of the immunogens was identified as the BHA007 protein, which is encoded by a 174-kb linear plasmid. BHA007 had sequence features of lipoproteins, was surface exposed by the criteria of in situ protease susceptibility and agglutination of Vtp− cells by anti-BHA007 antibodies, and was not essential for in vitro growth. BHA007 elicited antibodies during experimental infection of mice, but immunization with recombinant protein did not confer protection against needle-delivered infection. Open reading frames (ORFs) orthologous to BHA007 were found on large plasmids of other RF species, including the coding sequences for the CihC proteins of Borrelia duttonii and B. recurrentis, but not in Lyme disease Borrelia species. Recombinant BHA007 bound both human and bovine fibronectin with Kd (dissociation constant) values of 22 and 33 nM, respectively, and bound to C4-binding protein with less affinity. The distant homology of BHA007 and its orthologs to BBK32 proteins of Lyme disease species, as well as to previously described BBK32-like proteins in relapsing fever species, indicates that BHA007 is a member of a large family of multifunctional proteins in Borrelia species that bind to fibronectin as well as other host proteins. PMID:24686059

  10. Fatal spirochetosis due to a relapsing fever-like Borrelia sp. in northern spotted owl

    USGS Publications Warehouse

    Thomas, N.J.; Bunikis, J.; Barbour, A.G.; Wolcott, M.J.

    2002-01-01

    Acute septicemic spirochetosis was diagnosed in an adult male northern spotted owl (Strix occidentalis caurina) found dead in Kittitas County, Washington, USA. Gross necropsy findings included marked enlargement of the liver and spleen and serofibrinous deposits on the serous membranes lining the body cavities and the pericardial and perihepatic sacs. Microscopic observations included macrophage infiltration in the liver and spleen with mild thrombosis and multifocal necrosis, as well as hemorrhage and acute inflammation in the choroid plexus of the brain. No viruses or pathogenic bacteria were isolated from brain, liver, or spleen, and no parasites were found in blood smears or impression smears of the liver. Chlamydial culture attempts were unsuccessful and no chlamydial antibodies were detected in serum. In silver-stained microscopic sections and by transmission electron microscopy of liver, numerous long, thin, spiral-shaped bacteria were seen in the liver, spleen, cerebral ventricles, and within blood vessels in many organs. The organism was identified as a member of the Borrelia genus by sequence analysis of the PCR-amplified 16S rRNA gene. The most closely related species is B. hermsii, an agent of relapsing fever in humans in the western United States. This is the first report of a relapsing fever-related Borrelia in a wild bird.

  11. Louse-borne relapsing fever (Borrelia recurrentis) in asylum seekers from Eritrea, the Netherlands, July 2015.

    PubMed

    Wilting, K R; Stienstra, Y; Sinha, B; Braks, M; Cornish, D; Grundmann, H

    2015-01-01

    Two patients from Eritrea, recently arrived in the Netherlands, presented with fever and were investigated for malaria. Bloodfilms showed spirochetes but no blood parasites. Louse-borne relapsing fever caused by Borrelia recurrentis was diagnosed. Treatment was complicated by severe Jarisch-Herxheimer reactions in both patients. Physicians should be aware of the possibility of B. recurrentis infection in migrant populations who travel under crowded conditions, especially after passing through endemic areas such as Ethiopia and neighbouring countries. PMID:26250069

  12. Tick Surveillance for Relapsing Fever Spirochete Borrelia miyamotoi in Hokkaido, Japan

    PubMed Central

    Konnai, Satoru; Ohashi, Kazuhiko; Nakao, Minoru; Ito, Takuya; Andoh, Masako; Maeda, Ken; Watarai, Masahisa; Sato, Kozue; Kawabata, Hiroki

    2014-01-01

    During 2012–2013, a total of 4325 host-seeking adult ticks belonging to the genus Ixodes were collected from various localities of Hokkaido, the northernmost island of Japan. Tick lysates were subjected to real-time PCR assay to detect borrelial infection. The assay was designed for specific detection of the Relapsing fever spirochete Borrelia miyamotoi and for unspecific detection of Lyme disease-related spirochetes. Overall prevalence of B. miyamotoi was 2% (71/3532) in Ixodes persulcatus, 4.3% (5/117) in Ixodes pavlovskyi and 0.1% (1/676) in Ixodes ovatus. The prevalence in I. persulcatus and I. pavlovskyi ticks were significantly higher than in I. ovatus. Co-infections with Lyme disease-related spirochetes were found in all of the tick species. During this investigation, we obtained 6 isolates of B. miyamotoi from I. persulcatus and I. pavlovskyi by culture in BSK-M medium. Phylogenetic trees of B. miyamotoi inferred from each of 3 housekeeping genes (glpQ, 16S rDNA, and flaB) demonstrated that the Hokkaido isolates were clustered with Russian B. miyamotoi, but were distinguishable from North American and European B. miyamotoi. A multilocus sequence analysis using 8 genes (clpA, clpX, nifS, pepX, pyrG, recG, rplB, and uvrA) suggested that all Japanese B. miyamotoi isolates, including past isolates, were genetically clonal, although these were isolated from different tick and vertebrate sources. From these results, B. miyamotoi-infected ticks are widely distributed throughout Hokkaido. Female I. persulcatus are responsible for most human tick-bites, thereby I. persulcatus is likely the most important vector of indigenous relapsing fever from tick bites in Hokkaido. PMID:25111141

  13. Detection of a Borrelia miyamotoi sensu lato relapsing-fever group spirochete from Ixodes pacificus in California.

    PubMed

    Mun, Jeomhee; Eisen, Rebecca J; Eisen, Lars; Lane, Robert S

    2006-01-01

    We investigated whether host-seeking nymphs and adults of the western blacklegged tick, Ixodes pacificus Cooley & Kohls, the primary vector of Lyme disease spirochetes in far-western North America, are infected naturally with relapsing-fever group spirochetes in Mendocino County, California. Relapsing-fever group borreliae were detected in four (1.7%) of 234 nymphal and two (0.7%) of 282 adult host-seeking I. pacificus ticks by polymerase chain reaction and sequence analysis of the 16S rRNA and flagellin genes, respectively, exhibiting 99 and 98.5% sequence homology to Borrelia miyamotoi Fukunaga. Phylogenetic analysis based on these two genes revealed that the borreliae detected in these ticks belong to the relapsing-fever group and that these are closely related to, if not identical with, B. miyamotoi. PMID:16506458

  14. Tick-borne Relapsing Fever and Borrelia hermsii, Los Angeles County, California, USA

    PubMed Central

    Raffel, Sandra J.; Schrumpf, Merry E.; Webster, Larry S.; Marques, Adriana R.; Spano, Robyn; Rood, Michael; Burns, Joe; Hu, Renjie

    2009-01-01

    The primary cause of tick-borne relapsing fever in western North America is Borrelia hermsii, a rodent-associated spirochete transmitted by the fast-feeding soft tick Ornithodoros hermsi. We describe a patient who had an illness consistent with relapsing fever after exposure in the mountains near Los Angeles, California, USA. The patient’s convalescent-phase serum was seropositive for B. hermsii but negative for several other vector-borne bacterial pathogens. Investigations at the exposure site showed the presence of O. hermsi ticks infected with B. hermsii and the presence of rodents that were seropositive for the spirochete. We determined that this tick-borne disease is endemic to the San Gabriel Mountains near the greater Los Angeles metropolitan area. PMID:19624916

  15. Borrelia miyamotoi Infection in Nature and in Humans

    PubMed Central

    Krause, Peter J.; Fish, Durland; Narasimhan, Sukanya; Barbour, Alan G.

    2015-01-01

    Borrelia miyamotoi is a relapsing fever Borrelia group spirochete that is transmitted by the same hard-bodied (ixodid) tick species that transmit the agents of Lyme disease. It was discovered in 1994 in Ixodes persulcatus ticks in Japan. B. miyamotoi species phylogenetically cluster with the relapsing fever group spirochetes, which usually are transmitted by soft-bodied (argasid) ticks or lice. B. miyamotoi infects at least six Ixodes tick species in North America and Eurasia that transmit Lyme disease group spirochetes and may use small rodents and birds as reservoirs. Human cases of B. miyamotoi infection were first reported in 2011 in Russia and subsequently in the United States, Europe, and Japan. These reports document the public health importance of B. miyamotoi, as human B. miyamotoi infection appears to be comparable in frequency to babesiosis or human granulocytic anaplasmosis in some areas and may cause severe disease, including meningoencephalitis. The most common clinical manifestations of B. miyamotoi infection are fever, fatigue, headache, chills, myalgia, arthralgia, and nausea. Symptoms of B. miyamotoi infection generally resolve within a week of the start of antibiotic therapy. B. miyamotoi infection should be considered in patients with acute febrile illness who have been exposed to Ixodes ticks in a region where Lyme disease occurs. Because clinical manifestations are non-specific, etiologic diagnosis requires confirmation by blood smear examination, PCR, antibody assay, in vitro cultivation, and/or isolation by animal inoculation. Antibiotics that have been used effectively include doxycycline for uncomplicated B. miyamotoi infection in adults and ceftriaxone or penicillin G for meningoencephalitis. PMID:25700888

  16. Molecular identification of Borrelia genus in questing hard ticks from Portugal: Phylogenetic characterization of two novel Relapsing Fever-like Borrelia sp.

    PubMed

    Nunes, Mónica; Parreira, Ricardo; Maia, Carla; Lopes, Nádia; Fingerle, Volker; Vieira, M Luísa

    2016-06-01

    In the last decades, several studies have reported pathogenic species of Borrelia related to those that cause Tick-borne Relapsing Fever (RF), but unexpectedly suggesting their transmission by hard ticks, known vectors of Borrelia burgdorferi sensu lato (B. burgdorferi s.l.) species, rather than by soft ticks. This study was designed to update the presence of B. burgdorferi s.l. species in ticks from several districts of mainland Portugal, where Ixodes ricinus had been previously described. Ticks (a total of 2915 specimens) were collected in seven districts throughout the country, and analyzed using molecular methods. Three nested-PCR protocols, targeting the flagellin gene (flaB), the intergenic spacer region (IGS) located between 5S and 23S rRNA, and the glpQ gene, and a conventional PCR targeting the 16S rRNA, were used for Borrelia DNA detection. Borrelia DNA was detected in 3% of the ticks from Braga, Vila Real, Lisboa, Setúbal, Évora and Faro districts. The obtained amplicons were sequenced and analyzed by BLASTn, and 15/63 (24%) matched with homologous sequences from Borrelia lusitaniae and 15/63 (24%) with B. garinii, being these the most prevalent species. DNA from B. burgdorferi sensu stricto (s.s.), B. valaisiana and B. afzelii were detected in 7/63 (11%), 6/63 (10%), and 2/63 (3%) of the specimens, respectively. Unexpectedly, DNA sequence (flaB) analysis from eight (13%) samples, two from Rhipicephalus sanguineus and six from Haemaphysalis punctata tick species, revealed high homology with RF-like Borrelia. Phylogenetic analyses obtained from three genetic markers (16S rRNA, flaB, and glpQ) confirmed their congruent inclusion in a strongly supported RF cluster, where they segregated in two subgroups which differ from the other Relapsing Fever species. Therefore, the results confirm the circulation of multiple species of B. burgdorferi s.l. over a wide geographic range, covering most of the Portuguese mainland territory. Surprisingly, the obtained data

  17. First isolation of Borrelia lusitaniae from a human patient.

    PubMed

    Collares-Pereira, M; Couceiro, S; Franca, I; Kurtenbach, K; Schäfer, S M; Vitorino, L; Gonçalves, L; Baptista, S; Vieira, M L; Cunha, C

    2004-03-01

    The first human isolate of Borrelia lusitaniae recovered from a Portuguese patient with suspected Lyme borreliosis is described. This isolate, from a chronic skin lesion, is also the first human isolate of Borrelia in Portugal. Different phenotypic and molecular methods are used to characterize it. PMID:15004107

  18. First Isolation of Borrelia lusitaniae from a Human Patient

    PubMed Central

    Collares-Pereira, M.; Couceiro, S.; Franca, I.; Kurtenbach, K.; Schäfer, S. M.; Vitorino, L.; Gonçalves, L.; Baptista, S.; Vieira, M. L.; Cunha, C.

    2004-01-01

    The first human isolate of Borrelia lusitaniae recovered from a Portuguese patient with suspected Lyme borreliosis is described. This isolate, from a chronic skin lesion, is also the first human isolate of Borrelia in Portugal. Different phenotypic and molecular methods are used to characterize it. PMID:15004107

  19. Hypercholesterolemia and ApoE deficiency result in severe infection with Lyme disease and relapsing-fever Borrelia

    PubMed Central

    Toledo, Alvaro; Monzón, Javier D.; Coleman, James L.; Garcia-Monco, Juan C.; Benach, Jorge L.

    2015-01-01

    The Lyme disease (Borrelia burgdorferi) and relapsing-fever (Borrelia hispanica) agents have distinct infection courses, but both require cholesterol for growth. They acquire cholesterol from the environment and process it to form cholesterol glycolipids that are incorporated onto their membranes. To determine whether higher levels of serum cholesterol could enhance the organ burdens of B. burgdorferi and the spirochetemia of B. hispanica in laboratory mice, apolipoprotein E (apoE)-deficient and low-density lipoprotein receptor (LDLR)-deficient mice that produce large amounts of serum cholesterol were infected with both spirochetes. Both apoE- and LDLR-deficient mice infected with B. burgdorferi had an increased number of spirochetes in the joints and inflamed ankles compared with the infected wild-type (WT) mice, suggesting that mutations in cholesterol transport that result in high serum cholesterol levels can affect the pathogenicity of B. burgdorferi. In contrast, elevated serum cholesterol did not lead to an increase in the spirochetemia of B. hispanica. In the LDLR-deficient mice, the course of infection was indistinguishable from the WT mice. However, infection of apoE-deficient mice with B. hispanica resulted in a longer spirochetemia and increased mortality. Together, these results argue for the apoE deficiency, and not hypercholesterolemia, as the cause for the increased severity with B. hispanica. Serum hyperlipidemias are common human diseases that could be a risk factor for increased severity in Lyme disease. PMID:25870274

  20. Lyme disease and relapsing fever Borrelia elongate through zones of peptidoglycan synthesis that mark division sites of daughter cells.

    PubMed

    Jutras, Brandon Lyon; Scott, Molly; Parry, Bradley; Biboy, Jacob; Gray, Joe; Vollmer, Waldemar; Jacobs-Wagner, Christine

    2016-08-16

    Agents that cause Lyme disease, relapsing fever, leptospirosis, and syphilis belong to the phylum Spirochaetae-a unique lineage of bacteria most known for their long, spiral morphology. Despite the relevance to human health, little is known about the most fundamental aspects of spirochete growth. Here, using quantitative microscopy to track peptidoglycan cell-wall synthesis, we found that the Lyme disease spirochete Borrelia burgdorferi displays a complex pattern of growth. B. burgdorferi elongates from discrete zones that are both spatially and temporally regulated. In addition, some peptidoglycan incorporation occurs along the cell body, with the notable exception of a large region at the poles. Newborn cells inherit a highly active zone of peptidoglycan synthesis at midcell that contributes to elongation for most of the cell cycle. Concomitant with the initiation of nucleoid separation and cell constriction, second and third zones of elongation are established at the 1/4 and 3/4 cellular positions, marking future sites of division for the subsequent generation. Positioning of elongation zones along the cell is robust to cell length variations and is relatively precise over long distances (>30 µm), suggesting that cells ‟sense" relative, as opposed to absolute, cell length to establish zones of peptidoglycan synthesis. The transition from one to three zones of peptidoglycan growth during the cell cycle is also observed in relapsing fever Borrelia. However, this mode of growth does not extend to representative species from other spirochetal genera, suggesting that this distinctive growth mode represents an evolutionary divide in the spirochete phylum. PMID:27506799

  1. Conversion of a linear to a circular plasmid in the relapsing fever agent Borrelia hermsii.

    PubMed Central

    Ferdows, M S; Serwer, P; Griess, G A; Norris, S J; Barbour, A G

    1996-01-01

    Spirochetes of the genus Borrelia have genomes composed of both linear and circular replicons. We characterized the genomic organization of B. burgdorferi, B. hermsii, B. turicatae, and B. anserina with pulsed-field gel electrophoresis. All four species contained a linear chromosome approximately 1 Mb in size and multiple linear plasmids in the 16- to 200-kb size range. Plasmids 180 and 170 kb in size, present in the relapsing fever agents B. hermsii and B. turicatae but not in the other two species, behaved as linear duplex DNA molecules under different electrophoretic conditions. A variant of strain HSI of B. hermsii had a 180-kb circular instead of linear plasmid. There were no detectable differences in the growth rates or in the expression of cellular proteins between cells bearing linear forms and those bearing circular forms of the plasmid. The conversion to a circular conformation of monomeric length was demonstrated by the introduction of strand breaks with irradiation, restriction endonuclease analysis, and direct observation of the DNA molecules by fluorescent microscopy. Consideration of different models for the replication of linear DNA suggests that circular intermediates may be involved in the replication of linear replicons in Borrelia spp. PMID:8550515

  2. Genetic control of the innate immune response to Borrelia hermsii influences the course of relapsing fever in inbred strains of mice.

    PubMed

    Benoit, Vivian M; Petrich, Annett; Alugupalli, Kishore R; Marty-Roix, Robin; Moter, Annette; Leong, John M; Boyartchuk, Victor L

    2010-02-01

    Host susceptibility to infection is controlled in large measure by the genetic makeup of the host. Spirochetes of the genus Borrelia include nearly 40 species of vector-borne spirochetes that are capable of infecting a wide range of mammalian hosts, causing Lyme disease and relapsing fever. Relapsing fever is associated with high-level bacteremia, as well as hematologic manifestations, such as thrombocytopenia (i.e., low platelet numbers) and anemia. To facilitate studies of genetic control of susceptibility to Borrelia hermsii infection, we performed a systematic analysis of the course of infection using immunocompetent and immunocompromised inbred strains of mice. Our analysis revealed that sensitivity to B. hermsii infections is genetically controlled. In addition, whereas the role of adaptive immunity to relapsing fever-causing spirochetes is well documented, we found that innate immunity contributes significantly to the reduction of bacterial burden. Similar to human infection, the progression of the disease in mice was associated with thrombocytopenia and anemia. Histological and fluorescence in situ hybridization (FISH) analysis of infected tissues indicated that red blood cells (RBCs) were removed by tissue-resident macrophages, a process that could lead to anemia. Spirochetes in the spleen and liver were often visualized associated with RBCs, lending support to the hypothesis that direct interaction of B. hermsii spirochetes with RBCs leads to clearance of bacteria from the bloodstream by tissue phagocytes. PMID:19995898

  3. Insights into Borrelia miyamotoi infection from an untreated case demonstrating relapsing fever, monocytosis and a positive C6 Lyme serology.

    PubMed

    Sudhindra, Praveen; Wang, Guiqing; Schriefer, Martin E; McKenna, Donna; Zhuge, Jian; Krause, Peter J; Marques, Adriana R; Wormser, Gary P

    2016-09-01

    We describe a patient from the United States with PCR- and serology-confirmed Borrelia miyamotoi infection who recovered without antibiotics. Our findings suggest that B. miyamotoi infection may cause relapsing fever, blood monocytosis and antibody reactivity to the C6 peptide. Further studies are required to better define the spectrum of clinical and laboratory findings for this emerging tick-transmitted infection. PMID:27412815

  4. A relapsing fever group Borrelia sp. similar to Borrelia lonestari found among wild sika deer (Cervus nippon yesoensis) and Haemaphysalis spp. ticks in Hokkaido, Japan.

    PubMed

    Lee, Kyunglee; Takano, Ai; Taylor, Kyle; Sashika, Mariko; Shimozuru, Michito; Konnai, Satoru; Kawabata, Hiroki; Tsubota, Toshio

    2014-10-01

    A relapsing fever Borrelia sp. similar to Borrelia lonestari (herein referred to as B. lonestari-like) was detected from wild sika deer (Cervus nippon yesoensis) and Haemaphysalis ticks in the eastern part of Hokkaido, Japan. The total prevalence of this Borrelia sp. in tested deer blood samples was 10.6% using conventional PCR and real-time PCR. The prevalence was significantly higher in deer fawns compared to adults (21.9% and 9.4%, respectively). Additionally, there was significant regional difference between our two sampling areas, Shiretoko and Shibetsu with 17% and 2.8% prevalence, respectively. Regional differences were also found in tick species collected from field and on deer. In the Shiretoko region, Haemaphysalis spp. were more abundant than Ixodes spp., while in Shibetsu, Ixodes spp. were more abundant. Using real-time PCR analysis, B. lonestari-like was detected from 2 out of 290 adult Haemaphysalis spp. ticks and 4 out of 76 pools of nymphs. This is the first report of a B. lonestari-like organism in Haemaphysalis spp. ticks, and the first phylogenetic analysis of this B. lonestari-like organism in Asia. Based on our results, Haemaphysalis spp. are the most likely candidates to act as a vector for B. lonestari-like; furthermore, regional variation of B. lonestari-like prevalence in sika deer may be dependent on the population distribution of these ticks. PMID:25108784

  5. Identification of conserved antigens for early serodiagnosis of relapsing fever Borrelia

    PubMed Central

    Lopez, Job E.; Porcella, Stephen F.; Schrumpf, Merry E.; Raffel, Sandra J.; Hammer, Carl H.; Zhao, Ming; Robinson, Mary Ann; Schwan, Tom G.

    2009-01-01

    Borrelia hermsii is a blood-borne pathogen transmitted by the argasid tick Ornithodoros hermsi. Since spirochaete clearance in mice is associated with an IgM-mediated response, an immunoproteomic analysis was used to identify proteins reactive with IgM. We report that IgM from both mice and human patients infected with B. hermsii not only reacted with the previously identified variable membrane proteins but also identified candidate antigens including heat-shock proteins, an adhesin protein, ABC transporter proteins, flagellar proteins, housekeeping proteins, an immune evasion protein, and proteins with unknown function. Furthermore, IgM reactivity to recombinant glycerophosphodiester phosphodiesterase was detected during early spirochaete infection and prior to a detectable IgG response. Lastly, a conserved hypothetical protein was produced in Escherichia coli and tested with immune serum against B. hermsii and Borrelia recurrentis. These results identify a much larger set of immunoreactive proteins, and could help in the early serodiagnosis of this tick-borne infection. PMID:19443544

  6. Chromosome and Plasmids of the Tick-Borne Relapsing Fever Agent Borrelia hermsii

    PubMed Central

    2016-01-01

    The zoonotic pathogen Borrelia hermsii bears its multiple paralogous genes for variable antigens on several linear plasmids. Application of combined long-read and short-read next-generation sequencing provided complete sequences for antigen-encoding plasmids as well as other linear and circular plasmids and the linear chromosome of the genome. PMID:27284141

  7. Chromosome and Plasmids of the Tick-Borne Relapsing Fever Agent Borrelia hermsii.

    PubMed

    Barbour, Alan G

    2016-01-01

    The zoonotic pathogen Borrelia hermsii bears its multiple paralogous genes for variable antigens on several linear plasmids. Application of combined long-read and short-read next-generation sequencing provided complete sequences for antigen-encoding plasmids as well as other linear and circular plasmids and the linear chromosome of the genome. PMID:27284141

  8. Whole-Genome Sequences of Borrelia bissettii Borrelia valaisiana and Borrelia spielmanii

    SciTech Connect

    Schutzer S. E.; Dunn J.; Fraser-Liggett C. M.; Qiu W.-G.; Kraiczy P.; Mongodin E. F.; Luft B. J.; Casjens S. R.

    2012-01-01

    It has been known for decades that human Lyme disease is caused by the three spirochete species Borrelia burgdorferi, Borrelia afzelii, and Borrelia garinii. Recently, Borrelia valaisiana, Borrelia spielmanii, and Borrelia bissettii have been associated with Lyme disease. We report the complete genome sequences of B. valaisiana VS116, B. spielmanii A14S, and B. bissettii DN127.

  9. Inactivation of Genes for Antigenic Variation in the Relapsing Fever Spirochete Borrelia hermsii Reduces Infectivity in Mice and Transmission by Ticks

    PubMed Central

    Raffel, Sandra J.; Battisti, James M.; Fischer, Robert J.; Schwan, Tom G.

    2014-01-01

    Borrelia hermsii, a causative agent of relapsing fever of humans in western North America, is maintained in enzootic cycles that include small mammals and the tick vector Ornithodoros hermsi. In mammals, the spirochetes repeatedly evade the host’s acquired immune response by undergoing antigenic variation of the variable major proteins (Vmps) produced on their outer surface. This mechanism prolongs spirochete circulation in blood, which increases the potential for acquisition by fast-feeding ticks and therefore perpetuation of the spirochete in nature. Antigenic variation also underlies the relapsing disease observed when humans are infected. However, most spirochetes switch off the bloodstream Vmp and produce a different outer surface protein, the variable tick protein (Vtp), during persistent infection in the tick salivary glands. Thus the production of Vmps in mammalian blood versus Vtp in ticks is a dominant feature of the spirochete’s alternating life cycle. We constructed two mutants, one which was unable to produce a Vmp and the other was unable to produce Vtp. The mutant lacking a Vmp constitutively produced Vtp, was attenuated in mice, produced lower cell densities in blood, and was unable to relapse in animals after its initial spirochetemia. This mutant also colonized ticks and was infectious by tick-bite, but remained attenuated compared to wild-type and reconstituted spirochetes. The mutant lacking Vtp also colonized ticks but produced neither Vtp nor a Vmp in tick salivary glands, which rendered the spirochete noninfectious by tick bite. Thus the ability of B. hermsii to produce Vmps prolonged its survival in blood, while the synthesis of Vtp was essential for mammalian infection by the bite of its tick vector. PMID:24699793

  10. Inactivation of genes for antigenic variation in the relapsing fever spirochete Borrelia hermsii reduces infectivity in mice and transmission by ticks.

    PubMed

    Raffel, Sandra J; Battisti, James M; Fischer, Robert J; Schwan, Tom G

    2014-04-01

    Borrelia hermsii, a causative agent of relapsing fever of humans in western North America, is maintained in enzootic cycles that include small mammals and the tick vector Ornithodoros hermsi. In mammals, the spirochetes repeatedly evade the host's acquired immune response by undergoing antigenic variation of the variable major proteins (Vmps) produced on their outer surface. This mechanism prolongs spirochete circulation in blood, which increases the potential for acquisition by fast-feeding ticks and therefore perpetuation of the spirochete in nature. Antigenic variation also underlies the relapsing disease observed when humans are infected. However, most spirochetes switch off the bloodstream Vmp and produce a different outer surface protein, the variable tick protein (Vtp), during persistent infection in the tick salivary glands. Thus the production of Vmps in mammalian blood versus Vtp in ticks is a dominant feature of the spirochete's alternating life cycle. We constructed two mutants, one which was unable to produce a Vmp and the other was unable to produce Vtp. The mutant lacking a Vmp constitutively produced Vtp, was attenuated in mice, produced lower cell densities in blood, and was unable to relapse in animals after its initial spirochetemia. This mutant also colonized ticks and was infectious by tick-bite, but remained attenuated compared to wild-type and reconstituted spirochetes. The mutant lacking Vtp also colonized ticks but produced neither Vtp nor a Vmp in tick salivary glands, which rendered the spirochete noninfectious by tick bite. Thus the ability of B. hermsii to produce Vmps prolonged its survival in blood, while the synthesis of Vtp was essential for mammalian infection by the bite of its tick vector. PMID:24699793

  11. Molecular Typing of Borrelia burgdorferi

    PubMed Central

    Wang, Guiqing; Liveris, Dionysios; Mukherjee, Priyanka; Jungnick, Sabrina; Margos, Gabriele; Schwartz, Ira

    2015-01-01

    Borrelia burgdorferi sensu lato is a group of spirochetes belonging to the genus Borrelia in the family of Spirochaetaceae. The spirochete is transmitted between reservoirs and hosts by ticks of the family Ixodidae. Infection with B. burgdorferi in humans causes Lyme disease or Lyme borreliosis. Currently, 20 Lyme disease-associated Borrelia species and more than 20 relapsing fever-associated Borrelia species have been described. Identification and differentiation of different Borrelia species and strains is largely dependent on analyses of their genetic characteristics. A variety of molecular techniques have been described for Borrelia isolate speciation, molecular epidemiology, and pathogenicity studies. In this unit, we focus on three basic protocols, PCR-RFLP-based typing of the rrs-rrlA and rrfA-rrlB ribosomal spacer, ospC typing, and MLST. These protocols can be employed alone or in combination for characterization of B. burgdorferi isolates or directly on uncultivated organisms in ticks, mammalian host reservoirs, and human clinical specimens. PMID:25082003

  12. Laboratory Diagnosis of Tick-Borne African Relapsing Fevers: Latest Developments.

    PubMed

    Fotso Fotso, Aurélien; Drancourt, Michel

    2015-01-01

    In Africa, relapsing fevers caused by ectoparasite-borne Borrelia species are transmitted by ticks, with the exception of Borrelia recurrentis, which is a louse-borne spirochete. These tropical diseases are responsible for mild to deadly spirochetemia. Cultured Borrelia crocidurae, Borrelia duttonii, and Borrelia hispanica circulate alongside at least six species that have not yet been cultured in vectors. Direct diagnosis is hindered by the use of non-specific laboratory tools. Indeed, microscopic observation of Borrelia spirochaeta in smears of peripheral blood taken from febrile patients lacks sensitivity and specificity. Although best visualized using dark-field microscopy, the organisms can also be detected using Wright-Giemsa or acridine orange stains. PCR-based detection of specific sequences in total DNA extracted from a specimen can be used to discriminate different relapsing fever Borreliae. In our laboratory, we developed a multiplex real-time PCR assay for the specific detection of B. duttonii/recurrentis and B. crocidurae: multispacer sequence typing accurately identified cultured relapsing fever borreliae and revealed diversity among them. Other molecular typing techniques, such as multilocus sequence analysis of tick-borne relapsing fever borreliae, showed the potential risk of human infection in Africa. Recent efforts to culture and sequence relapsing fever borreliae have provided new information for reassessment of the diversity of these bacteria. Recently, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry has been reported as a means of identifying cultured borreliae and of identifying both vectors and vectorized pathogens such as detecting relapsing fever borreliae directly in ticks. The lack of a rapid diagnosis test restricts the management of such diseases. We produced monoclonal antibodies against B. crocidurae in order to develop cheap assays for the rapid detection of relapsing fever borreliae. In this paper, we

  13. Laboratory Diagnosis of Tick-Borne African Relapsing Fevers: Latest Developments

    PubMed Central

    Fotso Fotso, Aurélien; Drancourt, Michel

    2015-01-01

    In Africa, relapsing fevers caused by ectoparasite-borne Borrelia species are transmitted by ticks, with the exception of Borrelia recurrentis, which is a louse-borne spirochete. These tropical diseases are responsible for mild to deadly spirochetemia. Cultured Borrelia crocidurae, Borrelia duttonii, and Borrelia hispanica circulate alongside at least six species that have not yet been cultured in vectors. Direct diagnosis is hindered by the use of non-specific laboratory tools. Indeed, microscopic observation of Borrelia spirochaeta in smears of peripheral blood taken from febrile patients lacks sensitivity and specificity. Although best visualized using dark-field microscopy, the organisms can also be detected using Wright–Giemsa or acridine orange stains. PCR-based detection of specific sequences in total DNA extracted from a specimen can be used to discriminate different relapsing fever Borreliae. In our laboratory, we developed a multiplex real-time PCR assay for the specific detection of B. duttonii/recurrentis and B. crocidurae: multispacer sequence typing accurately identified cultured relapsing fever borreliae and revealed diversity among them. Other molecular typing techniques, such as multilocus sequence analysis of tick-borne relapsing fever borreliae, showed the potential risk of human infection in Africa. Recent efforts to culture and sequence relapsing fever borreliae have provided new information for reassessment of the diversity of these bacteria. Recently, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry has been reported as a means of identifying cultured borreliae and of identifying both vectors and vectorized pathogens such as detecting relapsing fever borreliae directly in ticks. The lack of a rapid diagnosis test restricts the management of such diseases. We produced monoclonal antibodies against B. crocidurae in order to develop cheap assays for the rapid detection of relapsing fever borreliae. In this paper, we

  14. Variable Tick Protein in Two Genomic Groups of the Relapsing Fever Spirochete Borrelia hermsii in Western North America

    PubMed Central

    Porcella, Stephen F.; Raffel, Sandra J.; Anderson, Donald E.; Gilk, Stacey D.; Bono, James L.; Schrumpf, Merry E.; Schwan, Tom G.

    2005-01-01

    Borrelia hermsii is the primary cause of tick-borne relapsing fever in North America. When its tick vector, Ornithodoros hermsi, acquires these spirochetes from the blood of an infected mammal, the bacteria switch their outer surface from one of many bloodstream variable major proteins (Vmps) to a unique protein, Vtp (Vsp33). Vtp may be critical for successful tick transmission of B. hermsii; however, the gene encoding this protein has been described previously in only one isolate. Here we identified and sequenced the vtp gene in 31 isolates of B. hermsii collected over 40 years from localities throughout much of its known geographic distribution. Seven major Vtp types were found. Little or no sequence variation existed within types, but between them significant variation was observed, similar to the pattern of diversity described for the outer surface protein C (OspC) gene in Lyme disease spirochetes. The pattern of sequence relatedness among the Vtp types was incongruent in two branches compared to two genomic groups identified among the isolates by multilocus sequence typing of the 16S rRNA, flaB, gyrB, and glpQ genes. Therefore, both horizontal transfer and recombination within and between the two genomic groups were responsible for some of the variation observed in the vtp gene. O. hermsi ticks were capable of transmitting spirochetes in the newly identified genomic group. Therefore, given the longevity of the tick vector and persistent infection of spirochetes in ticks, these arthropods rather than mammals may be the likely host where the exchange of spirochetal DNA occurs. PMID:16177341

  15. Expression of the Tick-Associated Vtp Protein of Borrelia hermsii in a Murine Model of Relapsing Fever

    PubMed Central

    Marcsisin, Renee A.; Lewis, Eric R. G.; Barbour, Alan G.

    2016-01-01

    Borrelia hermsii, a spirochete and cause of relapsing fever, is notable for its immune evasion by multiphasic antigenic variation within its vertebrate host. This is based on a diverse repertoire of surface antigen genes, only one of which is expressed at a time. Another major surface protein, the Variable Tick Protein (Vtp), is expressed in the tick vector and is invariable at its genetic locus. Given the limited immune systems of ticks, the finding of considerable diversity among the Vtp proteins of different strains of B. hermsii was unexpected. We investigated one explanation for this diversity of Vtp proteins, namely expression of the protein in mammals and a consequent elicitation of a specific immune response. Mice were infected with B. hermsii of either the HS1 or CC1 strain, which have antigenically distinctive Vtp proteins but otherwise have similar repertoires of the variable surface antigens. Subsequently collected sera were examined for antibody reactivities against Vtp and other antigens using Western blot analysis, dot blot, and protein microarray. Week-6 sera of infected mice contained antibodies that were largely specific for the Vtp of the infecting strain and were not attributable to antibody cross-reactivities. The antibody responses of the mice infected with different strains were otherwise similar. Further evidence of in vivo expression of the vtp gene was from enumeration of cDNA sequence reads that mapped to a set of selected B. hermsii genes. This measure of transcription of the infecting strain’s vtp gene was ~10% of that for the abundantly-expressed, serotype-defining variable antigen gene but similar to that of genes known for in vivo expression. The findings of Vtp expression in a vertebrate host and elicitation of a specific anti-Vtp antibody response support the view that balancing selection by host adaptive immunity accounts in part for the observed diversity of Vtp proteins. PMID:26918760

  16. Sensitivity of Borrelia genospecies to serum complement from different animals and human: a host-pathogen relationship.

    PubMed

    Bhide, Mangesh R; Travnicek, Milan; Levkutova, Maria; Curlik, Jan; Revajova, Viera; Levkut, Mikulas

    2005-02-01

    Different Borrelia species and serotypes were tested for their sensitivity to serum complement from various animals and human. Complement-mediated Borrelia killing in cattle, European bison and deer was higher irrespective of the Borrelia species whereas in other animals and human it was intermediate and Borrelia species-dependent. Activation of the alternative complement pathway by particular Borrelia strain was in correlation with its sensitivity or resistance. These results support the incompetent reservoir nature of cattle, European bison, red, roe and fallow deer, at the same time present the probable reservoir nature of mouflon, dog, wolf, cat and lynx. In short, this study reviews Borrelia-host relationship and its relevance in reservoir competence nature of animals. PMID:15681146

  17. PCR in laboratory diagnosis of human Borrelia burgdorferi infections.

    PubMed Central

    Schmidt, B L

    1997-01-01

    The laboratory diagnosis of Lyme borreliosis, the most prevalent vector-borne disease in the United States and endemic in parts of Europe and Asia, is currently based on serology with known limitations. Direct demonstration of Borrelia burgdorferi by culture may require weeks, while enzyme-linked immunosorbent assays for antigen detection often lack sensitivity. The development of the PCR has offered a new dimension in the diagnosis. Capable of amplifying minute amounts of DNA into billions of copies in just a few hours, PCR facilitates the sensitive and specific detection of DNA or RNA of pathogenic organisms. This review is restricted to applications of PCR methods in the diagnosis of human B. burgdorferi infections. In the first section, methodological aspects, e.g., sample preparation, target selection, primers and PCR methods, and detection and control of inhibition and contamination, are highlighted. In the second part, emphasis is placed on diagnostic aspects, where PCR results in patients with dermatological, neurological, joint, and ocular manifestations of the disease are discussed. Here, special attention is given to monitoring treatment efficacy by PCR tests. Last, specific guidelines on how to interpret PCR results, together with the advantages and limitations of these new techniques, are presented. PMID:8993863

  18. Babesia microti, human babesiosis, and Borrelia burgdorferi in Connecticut.

    PubMed Central

    Anderson, J F; Mintz, E D; Gadbaw, J J; Magnarelli, L A

    1991-01-01

    Babesia microti was isolated from a white-footed mouse (Peromyscus leucopus) that was captured in southeastern Connecticut in 1988, when the first human case of babesiosis acquired in Connecticut was recognized. To date, 13 cases of babesiosis have been reported in Connecticut, the largest number of human cases reported on the mainland United States. Two of nine patients quiried remembered a prior tick bite. Since Babesia parasites are known to be vectored only by ticks, we surmise that 12 of these infections were acquired via tick bites; 1 was obtained by blood transfusion (the patient was 46 years of age) from an endemically infected donor. The ages of the patients with tick-acquired babesiosis ranged from 61 to 95 years. Two patients died with active infections, and one patient died from chronic obstructive pulmonary disease soon after treatment with clindamycin and quinine. Indirect fluorescent-antibody titers of blood samples drawn at the time of hospitalization for 11 patients and at the time of active infection for 1 asymptomatic person ranged from 1:1,024 to 1:4,096. Five of eight patients with babesiosis also had significant immunoglobulin G or immunoglobulin M titers (1:640 to 1:5,120) to Borrelia burgdorferi. B. microti was isolated in Syrian hamsters inoculated with blood from 7 of 12 patients tested and was also isolated from mice captured in six towns. The peridomestic nature of the disease was demonstrated by isolating the parasite from white-footed mice captured in or near the yards of eight different patients. Of 59 mice tested, 27 were positive and 25 were coinfected with B. burgdorferi. The isolation of B. microti from a white-footed mouse captured in north-central Connecticut (West Hartford), away from the focus of human infections in southeastern Connecticut, suggests that this pathogen may spread into other areas where Ixodes dammini, the tick vector, becomes established. PMID:1757548

  19. Borrelia miyamotoi–Associated Neuroborreliosis in Immunocompromised Person

    PubMed Central

    Lobenstein, Sabine; Hermann, Beate; Margos, Gabriele; Fingerle, Volker

    2016-01-01

    Borrelia miyamotoi is a newly recognized human pathogen in the relapsing fever group of spirochetes. We investigated a case of B. miyamotoi infection of the central nervous system resembling B. burgdorferi–induced Lyme neuroborreliosis and determined that this emergent agent of central nervous system infection can be diagnosed with existing methods. PMID:27533748

  20. Borrelia miyamotoi-Associated Neuroborreliosis in Immunocompromised Person.

    PubMed

    Boden, Katharina; Lobenstein, Sabine; Hermann, Beate; Margos, Gabriele; Fingerle, Volker

    2016-09-01

    Borrelia miyamotoi is a newly recognized human pathogen in the relapsing fever group of spirochetes. We investigated a case of B. miyamotoi infection of the central nervous system resembling B. burgdorferi-induced Lyme neuroborreliosis and determined that this emergent agent of central nervous system infection can be diagnosed with existing methods. PMID:27533748

  1. Risk Factors for Relapse of Human Brucellosis

    PubMed Central

    Hasanjani Roushan, Mohammad Reza; Moulana, Zahra; Afshar, Zeinab Mohseni; Ebrahimpour, Soheil

    2016-01-01

    Background & Propose: Brucellosis is serious disease around the world, especially in underdeveloped countries. Relapse is major problem in therapy of brucellosis. This study aimed to evaluate risk factors of relapse after treatment in patients. Methods: It is a descriptive-analytic study from 1990 to 2014, in Ayatolla Rohani hospital in Babol, Iran. We studied 980 patients with brucellosis. The studied community included patients infected with brucellosis and the required information was gathered based on their hospital files. The base for recognizing Malta fever were clinical symptoms and Para-clinical sign congruent with infection like as, titer SAT>1:320 and 2-ME>1:160. Patients with relapse and patients without relapse were placed separately in two groups. The data were statistically compared with Spss 16, by Chi-square and Cox–regression tests. Results: Based on this study, treatment regimen is a preventive factor (P=0.000). Moreover, Based on some statistical methods, regimens no. 3 and 4 were introduce preventive factors (P=0.001) and (P=0.004). It should also be noted that findings the same statistical model, factors like gender, age, residence, professional contacts, complications and delay in treatment were also analyzed but none of them are considered as preventive factors. Conclusion: Based our finding, we suggest aminoglycosides (gentamicin or streptomycin with doxycycline) are associated with lower rate of relapse in brucellosis.

  2. The bdr gene families of the Lyme disease and relapsing fever spirochetes: potential influence on biology, pathogenesis, and evolution.

    PubMed

    Roberts, D M; Carlyon, J A; Theisen, M; Marconi, R T

    2000-01-01

    Species of the genus Borrelia cause human and animal infections, including Lyme disease, relapsing fever, and epizootic bovine abortion. The borrelial genome is unique among bacterial genomes in that it is composed of a linear chromosome and a series of linear and circular plasmids. The plasmids exhibit significant genetic redundancy and carry 175 paralogous gene families, most of unknown function. Homologous alleles on different plasmids could influence the organization and evolution of the Borrelia genome by serving as foci for interplasmid homologous recombination. The plasmid-carried Borrelia direct repeat (bdr) gene family encodes polymorphic, acidic proteins with putative phosphorylation sites and transmembrane domains. These proteins may play regulatory roles in Borrelia. We describe recent progress in the characterization of the Borrelia bdr genes and discuss the possible influence of this gene family on the biology, pathogenesis, and evolution of the Borrelia genome. PMID:10756144

  3. Tick-borne relapsing fever in a premature infant.

    PubMed

    Brasseur, D

    1985-09-01

    Relapsing fever is caused by the Borrelia species of spirochetes. Louse-born epidemics of the disease may occur but the endemic disease is usually transmitted to humans by the bite of an infected tick (Ornithodorus). Transplacental infection was suggested more than 75 years ago (1) but has been rarely documented (2). We describe a case of neonatal relapsing fever where maternal infection was the probable cause of the premature delivery and infection in the infant. PMID:2415056

  4. Borrelia garinii Induces CXCL13 Production in Human Monocytes through Toll-Like Receptor 2▿

    PubMed Central

    Rupprecht, Tobias A.; Kirschning, Carsten J.; Popp, Bernadette; Kastenbauer, Stefan; Fingerle, Volker; Pfister, Hans-Walter; Koedel, Uwe

    2007-01-01

    Recent studies have suggested an important role for the B-cell-attracting chemokine CXCL13 in the B-cell-dominated cerebrospinal fluid (CSF) infiltrate in patients with neuroborreliosis (NB). High levels of CXCL13 were present in the CSF of NB patients. It has not been clear, however, whether high CSF CXCL13 titers are specific for NB or are a characteristic of other spirochetal diseases as well. Furthermore, the mechanisms leading to the observed CXCL13 expression have not been identified yet. Here we describe similarly elevated CSF CXCL13 levels in patients with neurosyphilis, while pneumococcal meningitis patient CSF do not have high CXCL13 levels. In parallel, challenge of human monocytes in vitro with two of the spirochetal causative organisms, Borrelia garinii (the Borrelia species most frequently found in NB patients) and Treponema pallidum, but not challenge with pneumococci, induced CXCL13 release. This finding implies that a common spirochetal motif is a CXCL13 inducer. Accordingly, we found that the lipid moiety N-palmitoyl-S-(bis[palmitoyloxy]propyl)cystein (Pam3C) (three palmitoyl residues bound to N-terminal cysteine) of the spirochetal lipoproteins is critical for the CXCL13 induction in monocytes. As the Pam3C motif is known to signal via Toll-like receptor 2 (TLR2) and an anti-TLR2 monoclonal antibody blocked CXCL13 production of human monocytes incubated with B. garinii, this suggests that TLR2 is a major mediator of Borrelia-induced secretion of CXCL13 from human monocytes. PMID:17562761

  5. Borrelia burgdorferi clinical isolates induce human innate immune responses that are not dependent on genotype.

    PubMed

    Mason, Lauren M K; Herkes, Eduard A; Krupna-Gaylord, Michelle A; Oei, Anneke; van der Poll, Tom; Wormser, Gary P; Schwartz, Ira; Petzke, Mary M; Hovius, Joppe W R

    2015-10-01

    Borrelia burgdorferi can be categorized based on restriction fragment length polymorphism analysis into ribosomal spacer type (RST) 1, 2 and 3. A correlation between RST type and invasiveness of Borrelia isolates has been demonstrated in clinical studies and experimental models, and RST 1 isolates are more likely to cause disseminated disease than RST 3 isolates. We hypothesized that this could partially be due to increased susceptibility of RST 3 isolates to killing by the innate immune system early in infection. Thus, we investigated the interaction of five RST 1 and five RST 3 isolates with various components of the human innate immune system in vitro. RST 3 isolates induced significantly greater upregulation of activation markers in monocyte-derived dendritic cells compared to RST 1 isolates at a low multiplicity of infection. However, RST 1 isolates stimulated greater interleukin-6 production. At a high multiplicity of infection no differences in dendritic cell activation or cytokine production were observed. In addition, we observed no differences in the ability of RST 1 and RST 3 isolates to activate monocytes or neutrophils and all strains were phagocytosed at a comparable rate. Finally, all isolates tested were equally resistant to complement-mediated killing, as determined by dark-field microscopy and a growth inhibition assay. In conclusion, we demonstrate that the RST 1 and 3 isolates showed no distinction in their susceptibility to the various components of the human immune system studied here, suggesting that other factors are responsible for their differential invasiveness. PMID:26093919

  6. Specific adherence of Borrelia burgdorferi extracellular vesicles to human endothelial cells in culture.

    PubMed Central

    Shoberg, R J; Thomas, D D

    1993-01-01

    Borrelia burgdorferi produces extracellular vesicles which contain some of the outer surface proteins of the bacterium (e.g., OspA and OspB). Borrelial vesicles, isolated by differential centrifugation and filtration, were tested for the ability to bind to cultured human umbilical vein endothelial (HUVE) cells in culture. The recently described lipoprotein OspD was expressed on vesicles. Vesicles exhibited differential expression of OspB and OspD in a relationship with passage number and medium serum supplement type, respectively. Qualitative immunoblotting analyses demonstrated dose-dependent, passage number-dependent adsorption of vesicles by HUVE cells. This adsorption was demonstrated to be dependent upon a borrelial component of the vesicle and not due to the presence of minor contamination with intact spirochetes. Quantitative experiments examining inhibition of B. burgdorferi-HUVE association as a function of prior vesicle-HUVE association demonstrated dependence upon (i) a borrelial component(s) in the vesicle, (ii) low passage number, and (iii) vesicle protein concentration. However, vesicle pretreatment of the HUVE cell monolayer was not requisite for this inhibition. Vesicles from highly passaged borrelias were noninhibitory for B. burgdorferi-HUVE cell association, regardless of the serum used to supplement the medium. The use of vesicles as a tool for studying B. burgdorferi pathogenesis and/or physiology is proposed. Images PMID:8359911

  7. Blood-Borne Candidatus Borrelia algerica in a Patient with Prolonged Fever in Oran, Algeria.

    PubMed

    Fotso Fotso, Aurélien; Angelakis, Emmanouil; Mouffok, Nadjet; Drancourt, Michel; Raoult, Didier

    2015-11-01

    To improve the knowledge base of Borrelia in north Africa, we tested 257 blood samples collected from febrile patients in Oran, Algeria, between January and December 2012 for Borrelia species using flagellin gene polymerase chain reaction sequencing. A sequence indicative of a new Borrelia sp. named Candidatus Borrelia algerica was detected in one blood sample. Further multispacer sequence typing indicated this Borrelia sp. had 97% similarity with Borrelia crocidurae, Borrelia duttonii, and Borrelia recurrentis. In silico comparison of Candidatus B. algerica spacer sequences with those of Borrelia hispanica and Borrelia garinii revealed 94% and 89% similarity, respectively. Candidatus B. algerica is a new relapsing fever Borrelia sp. detected in Oran. Further studies may help predict its epidemiological importance. PMID:26416117

  8. Borrelia burgdorferi sensu lato in humans in a rural area of Paraná State, Brazil

    PubMed Central

    Gonçalves, Daniela Dib; Moura, Rodrigo Assunção; Nunes, Mônica; Carreira, Teresa; Vidotto, Odilon; Freitas, Julio Cesar; Vieira, Maria Luísa

    2015-01-01

    This study describes the detection of Borrelia garinii and Borrelia burgdorferi sensu stricto (s.s.) in Brazilian individuals using PCR and DNA sequencing. Our results suggest that these species are emerging pathogens in this country, and additional studies are necessary to determine the epidemiological characteristics of this disease in Brazil. PMID:26273276

  9. Borrelia burgdorferi sensu lato in humans in a rural area of Paraná State, Brazil.

    PubMed

    Gonçalves, Daniela Dib; Moura, Rodrigo Assunção; Nunes, Mônica; Carreira, Teresa; Vidotto, Odilon; Freitas, Julio Cesar; Vieira, Maria Luísa

    2015-06-01

    This study describes the detection of Borrelia garinii and Borrelia burgdorferi sensu stricto (s.s.) in Brazilian individuals using PCR and DNA sequencing. Our results suggest that these species are emerging pathogens in this country, and additional studies are necessary to determine the epidemiological characteristics of this disease in Brazil. PMID:26273276

  10. Monoclonal Antibodies for the Diagnosis of Borrelia crocidurae.

    PubMed

    Fotso Fotso, Aurélien; Mediannikov, Oleg; Nappez, Claude; Azza, Saïd; Raoult, Didier; Drancourt, Michel

    2016-01-01

    Relapsing fever borreliae, produced by ectoparasite-borne Borrelia species, cause mild to deadly bacteremia and miscarriage. In the perspective of developing inexpensive assays for the rapid detection of relapsing fever borreliae, we produced 12 monoclonal antibodies (MAbs) against Borrelia crocidurae and characterized the two exhibiting the highest titers. P3A10 MAb reacts with the 35.6-kDa flagellin B (flaB) of B. crocidurae while P6D9 MAb recognizes a 35.1-kDa variable-like protein (Vlp) in B. crocidurae and a 35.2-kDa Vlp in Borrelia duttonii. Indirect immunofluorescence assay incorporating relapsing fever and Lyme group borreliae and 11 blood-borne organisms responsible for fever in West Africa confirmed the reactivity of these two MAbs. Combining these two MAbs in indirect immunofluorescence assays detected relapsing fever borreliae including B. crocidurae in ticks and the blood of febrile Senegalese patients. Both antibodies could be incorporated into inexpensive and stable formats suited for the rapid point-of-care diagnosis of relapsing fever. These first-ever MAbs directed against African relapsing fever borreliae are available for the scientific community to promote research in this neglected field. PMID:26598566

  11. The Borrelia hermsii Factor H Binding Protein FhbA Is Not Required for Infectivity in Mice or for Resistance to Human Complement In Vitro

    PubMed Central

    Fine, Lindy M.; Miller, Daniel P.; Mallory, Katherine L.; Tegels, Brittney K.; Earnhart, Christopher G.

    2014-01-01

    The primary causative agent of tick-borne relapsing fever in North America is Borrelia hermsii. It has been hypothesized that B. hermsii evades complement-mediated destruction by binding factor H (FH), a host-derived negative regulator of complement. In vitro, B. hermsii produces a single FH binding protein designated FhbA (FH binding protein A). The properties and ligand binding activity of FhbA suggest that it plays multiple roles in pathogenesis. It binds plasminogen and has been identified as a significant target of a B1b B cell-mediated IgM response in mice. FhbA has also been explored as a potential diagnostic antigen for B. hermsii infection in humans. The ability to test the hypothesis that FhbA is a critical virulence factor in vivo has been hampered by the lack of well-developed systems for the genetic manipulation of the relapsing fever spirochetes. In this report, we have successfully generated a B. hermsii fhbA deletion mutant (the B. hermsii YORΔfhbA strain) through allelic exchange mutagenesis. Deletion of fhbA abolished FH binding by the YORΔfhbA strain and eliminated cleavage of C3b on the cell surface. However, the YORΔfhbA strain remained infectious in mice and retained resistance to killing in vitro by human complement. Collectively, these results indicate that B. hermsii employs an FhbA/FH-independent mechanism of complement evasion that allows for resistance to killing by human complement and persistence in mice. PMID:24866803

  12. New Borrelia species detected in ixodid ticks in Oromia, Ethiopia.

    PubMed

    Kumsa, Bersissa; Socolovschi, Cristina; Raoult, Didier; Parola, Philippe

    2015-04-01

    Little is known about Borrelia species transmitted by hard ticks in Ethiopia. The present study was conducted from November 2011 through March 2014 to address the occurrence and molecular identity of these bacteria in ixodid ticks infesting domestic animals in Oromia, Ethiopia. A total of 767 ixodid ticks collected from domestic animals were screened for Borrelia DNA by quantitative (q) real-time PCR followed by standard PCR and sequencing to identify the species. Overall, 3.8% (29/767) of the tested ticks were positive for Borrelia DNA, including 8/119 (6.7%) Amblyomma cohaerens, 1/42 (2.4%) Am. gemma, 3/53 (5.7%) Am. variegatum, 5/22 (22.7%) Amblyomma larvae, 3/60 (5%) Amblyomma nymphs, 2/139 (1.4%) Rhipicephalus (Boophilus) decoloratus, 2/31 (6.4%) Rh. decoloratus nymphs, and 5/118 (4.2%) Rh. pulchellus using 16S genus-specific qPCR. The prevalence of Borrelia DNA was significantly higher in genus Amblyomma (20/298, 6.7%) than in the genus Rhipicephalus (9/417, 2.1%) ticks (P=0.001). Sequencing of PCR products from the flaB and 16S rRNA genes of Borrelia spp. from Amblyomma ticks showed the presence of a new species between the relapsing fever and Lyme disease groups. However, Borrelia sp. detected in Rhipicephalus ticks clustered with B. theileri/B. lonestari. The human pathogenicity of the Borrelia sp. detected in Amblyomma ticks from Ethiopia has not yet been investigated, whereas the Borrelia sp. detected in Rhipicephalus ticks in our study is the causative agent of bovine borreliosis in cattle and may have veterinary importance in different parts of Ethiopia. Furthermore, the detection of previously unrecognized Borrelia species in Amblyomma and Rhipicephalus ticks in Ethiopia generates additional questions concerning the bacterial fauna in hard ticks and will prompt researchers to perform detailed studies for better understanding of ixodid ticks associated bacteria. PMID:25843811

  13. Human seroprevalence against Borrelia burgdorferi sensu lato in two comparable regions of the eastern Alps is not correlated to vector infection rates.

    PubMed

    Sonnleitner, S T; Margos, G; Wex, F; Simeoni, J; Zelger, R; Schmutzhard, E; Lass-Flörl, C; Walder, G

    2015-04-01

    Seroprevalences were determined by testing sera of 1607 blood donors from North, East, and South Tyrol. In the Tyrols, the continental divide delimitates areas with high seroprevalences of IgG antibodies against Borrelia burgdorferi sensu lato in the North (7.2%) from areas with low seroprevalences in the South (1.5%). To determine Borrelia prevalences in unfed Ixodes ricinus ticks, 755 questing ticks were tested by PCR. Prevalences in nymphal and adult ticks were found to be 19.7% (n=132) and 21.5% (n=205) in North Tyrol and 23% (n=43) and 23.7% (n=376) in South Tyrol, respectively. Sequencing of 46 Borrelia-positive ticks yielded 74% Borrelia (B.) afzelii, 11% B. garinii, 7% B. lusitaniae, 7% B. burgdorferi sensu stricto, and 2% B. valaisiana infections. Distinct genetic clusters could not be delimitated on either side of the continental divide. This study describes occurrence and geographic dispersion of Borrelia spp. in the Tyrols, discusses possible reasons for significant differences in human seroprevalence, and indicates that prevalence of Borrelia in vector ticks is not a direct predictive factor for the local seroprevalence in humans. PMID:25661649

  14. Borrelia burgdorferi infection regulates CD1 expression in human cells and tissues via IL1-β

    PubMed Central

    Yakimchuk, Konstantin; Roura-Mir, Carme; Magalhaes, Kelly Grace; De Jong, Annemieke; Kasmar, Anne G.; Granter, Scott R.; Budd, Ralph; Steere, Allen; Pena-Cruz, Victor; Kirschning, Carsten; Cheng, Tan-Yun; Moody, D. Branch

    2011-01-01

    The appearance of newly translated group 1 CD1 proteins (CD1a, CD1b, CD1c) on maturing myeloid DC to effective lipid antigen presenting cells. Here we show that Borrelia burgdorferi, the causative agent of Lyme disease, triggers appearance of group 1 CD1 proteins at high density on the surface of human myeloid DC during infection. Within human skin, CD1b and CD1c expression was low or absent prior to infection, but increased significantly after experimental infections and in erythema migrans lesions from Lyme Disease patients. The induction of CD1 was initiated by borrelial lipids acting through TLR-2 within minutes, but required 3 days for maximum effect. The delay in CD1 protein appearance involved a multi-step process whereby TLR-2 stimulated cells release soluble factors, which are sufficient to transfer the CD1-inducing effect in trans to other cells. Analysis of these soluble factors identified IL-1β as a previously unknown pathway leading to group 1 CD1 protein function. These studies establish that upregulation of group 1 CD1 proteins is an early event in B. burgdorferi infection and suggest a stepwise mechanism whereby bacterial cell walls, TLR activation and cytokine release cause DC precursors to express group 1 CD1 proteins. PMID:21246541

  15. Human Coinfection with Borrelia burgdorferi and Babesia microti in the United States

    PubMed Central

    Knapp, Kristen L.; Rice, Nancy A.

    2015-01-01

    Borrelia burgdorferi, the causative agent of Lyme disease, and Babesia microti, a causative agent of babesiosis, are increasingly implicated in the growing tick-borne disease burden in the northeastern United States. These pathogens are transmitted via the bite of an infected tick vector, Ixodes scapularis, which is capable of harboring and inoculating a host with multiple pathogens simultaneously. Clinical presentation of the diseases is heterogeneous and ranges from mild flu-like symptoms to near-fatal cardiac arrhythmias. While the reason for the variability is not known, the possibility exists that concomitant infection with both B. burgdorferi and B. microti may synergistically increase disease severity. In an effort to clarify the current state of understanding regarding coinfection with B. burgdorferi and B. microti, in this review, we discuss the geographical distribution and pathogenesis of Lyme disease and babesiosis in the United States, the immunological response of humans to B. burgdorferi or B. microti infection, the existing knowledge regarding coinfection disease pathology, and critical factors that have led to ambiguity in the literature regarding coinfection, in order to eliminate confusion in future experimental design and investigation. PMID:26697208

  16. [Diseases produced by Borrelia].

    PubMed

    Escudero-Nieto, Raquel; Guerrero-Espejo, Antonio

    2005-04-01

    Lyme borreliosis, caused by Borrelia burgdorferi sensu lato, is a multi-organ infection with dermatological, rheumatological, neurological, and cardiac manifestations. The main characteristic is a skin lesion, named erythema migrans. Relapsing fever, caused by numerous species of Borrelia, is characterized by a periodic cycle of acute and afebrile episodes. The serological diagnosis of these infections has limited value in sensitivity, specificity and predictive values. Lyme borreliosis is usually diagnosed by recognition of a characteristic clinical picture with serological confirmation, and the diagnosis of relapsing fever relies on direct observation of spirochetes in peripherical blood. The elected treatment is almost always tetracycline for the young or for adults but not for pregnant women, although betalactamic (such as penicillin or 3rd generation cephalosporin for the central nervous system) or macrolides are indicated in several situations. The prognosis, with adequate treatment, is good. In the majority of Spanish regions, due to the low incidence of these diseases, the prophylactic antimicrobial treatment after a tick bite is not indicated. PMID:15826549

  17. High seroprevalence of Borrelia miyamotoi antibodies in forestry workers and individuals suspected of human granulocytic anaplasmosis in the Netherlands

    PubMed Central

    Jahfari, S; Herremans, T; Platonov, A E; Kuiper, H; Karan, L S; Vasilieva, O; Koopmans, M P G; Hovius, J W R; Sprong, H

    2014-01-01

    Substantial exposure to Borrelia miyamotoi occurs through bites from Ixodes ricinus ticks in the Netherlands, which also transmit Borrelia burgdorferi sensu lato and Anaplasma phagocytophilum. Direct evidence for B. miyamotoi infection in European populations is scarce. A flu-like illness with high fever, resembling human granulocytic anaplasmosis, has been attributed to B. miyamotoi infections in relatively small groups. Borrelia miyamotoi infections associated with chronic meningoencephalitis have also been described in case reports. Assuming that an IgG antibody response against B. miyamotoi antigens reflects (endured) infection, the seroprevalence in different risk groups was examined. Sera from nine out of ten confirmed B. miyamotoi infections from Russia were found to be positive with the recombinant antigen used, and no significant cross-reactivity was observed in secondary syphilis patients. The seroprevalence in blood donors was set at 2.0% (95% CI 0.4–5.7%). Elevated seroprevalences in individuals with serologically confirmed, 7.4% (2.0–17.9%), or unconfirmed, 8.6% (1.8–23%), Lyme neuroborreliosis were not significantly different from those in blood donors. The prevalence of anti-B. miyamotoi antibodies among forestry workers was 10% (5.3–16.8%) and in patients with serologically unconfirmed but suspected human granulocytic anaplasmosis was 14.6% (9.0–21.8%); these were significantly higher compared with the seroprevalence in blood donors. Our findings indicate that infections with B. miyamotoi occur in tick-exposed individuals in the Netherlands. In addition, B. miyamotoi infections should be considered in patients reporting tick bites and febrile illness with unresolved aetiology in the Netherlands, and other countries where I. ricinus ticks are endemic. PMID:25356364

  18. High seroprevalence of Borrelia miyamotoi antibodies in forestry workers and individuals suspected of human granulocytic anaplasmosis in the Netherlands.

    PubMed

    Jahfari, S; Herremans, T; Platonov, A E; Kuiper, H; Karan, L S; Vasilieva, O; Koopmans, M P G; Hovius, J W R; Sprong, H

    2014-09-01

    Substantial exposure to Borrelia miyamotoi occurs through bites from Ixodes ricinus ticks in the Netherlands, which also transmit Borrelia burgdorferi sensu lato and Anaplasma phagocytophilum. Direct evidence for B. miyamotoi infection in European populations is scarce. A flu-like illness with high fever, resembling human granulocytic anaplasmosis, has been attributed to B. miyamotoi infections in relatively small groups. Borrelia miyamotoi infections associated with chronic meningoencephalitis have also been described in case reports. Assuming that an IgG antibody response against B. miyamotoi antigens reflects (endured) infection, the seroprevalence in different risk groups was examined. Sera from nine out of ten confirmed B. miyamotoi infections from Russia were found to be positive with the recombinant antigen used, and no significant cross-reactivity was observed in secondary syphilis patients. The seroprevalence in blood donors was set at 2.0% (95% CI 0.4-5.7%). Elevated seroprevalences in individuals with serologically confirmed, 7.4% (2.0-17.9%), or unconfirmed, 8.6% (1.8-23%), Lyme neuroborreliosis were not significantly different from those in blood donors. The prevalence of anti-B. miyamotoi antibodies among forestry workers was 10% (5.3-16.8%) and in patients with serologically unconfirmed but suspected human granulocytic anaplasmosis was 14.6% (9.0-21.8%); these were significantly higher compared with the seroprevalence in blood donors. Our findings indicate that infections with B. miyamotoi occur in tick-exposed individuals in the Netherlands. In addition, B. miyamotoi infections should be considered in patients reporting tick bites and febrile illness with unresolved aetiology in the Netherlands, and other countries where I. ricinus ticks are endemic. PMID:25356364

  19. Molecular Identification of Borrelia miyamotoi in Ixodes ricinus from Portugal.

    PubMed

    Nunes, Mónica; Parreira, Ricardo; Lopes, Nádia; Maia, Carla; Carreira, Teresa; Sousa, Carmelita; Faria, Sofia; Campino, Lenea; Vieira, M Luísa

    2015-08-01

    Borrelia miyamotoi, a relapsing fever spirochete, has been found recently in Ixodes ricinus ticks; however, little is known about its spatial distribution and potential local impact on human health. A total of 640 ticks (447 nymphs and 193 adults) collected throughout Portugal were analyzed using two nested PCR protocols, one targeting the flagellin gene and the other the internal transcribed space region between the 5S and the 23S rRNA. As a result, B. miyamotoi was detected, for the first time, in one guesting I. ricinus nymph collected in the Lisboa district. In addition, a prevalence of 11% (71/640) for B. burgdorferi sensu lato was obtained. Even though no human relapsing fever cases due to infection by B. miyamotoi have been reported yet in Portugal, surveillance must be improved to provide better insight into the prevalence and distribution of this spirochete in ticks. PMID:26273814

  20. Real-Time Monitoring of Disease Progression in Rhesus Macaques Infected With Borrelia turicatae by Tick Bite

    PubMed Central

    Lopez, Job E.; Vinet-Oliphant, Heather; Wilder, Hannah K.; Brooks, Christopher P.; Grasperge, Britton J.; Morgan, Timothy W.; Stuckey, Kerstan J.; Embers, Monica E.

    2014-01-01

    The hallmark of disease caused by tick- and louse-borne relapsing fever due to Borrelia infection is cyclic febrile episodes, which in humans results in severe malaise and may lead to death. To evaluate the pathogenesis of relapsing fever due to spirochetes in an animal model closely related to humans, disease caused by Borrelia turicatae after tick bite was compared in 2 rhesus macaques in which radiotelemetry devices that recorded body temperatures in 24-hour increments were implanted. The radiotelemetry devices enabled real-time acquisition of core body temperatures and changes in heart rates and electrocardiogram intervals for 28 consecutive days without the need to constantly manipulate the animals. Blood specimens were also collected from all animals for 14 days after tick bite, and spirochete densities were assessed by quantitative polymerase chain reaction. The complexity of disease caused by relapsing-fever spirochetes was demonstrated in the nonhuman primates monitored in real time. The animals experienced prolonged episodes of hyperthermia and hypothermia; disruptions in their diurnal patterns and repolarization of the heart were also observed. This is the first report of the characterizing disease progression with continuous monitoring in an animal model of relapsing fever due to Borrelia infection. PMID:24879799

  1. Louse-borne relapsing fever (Borrelia recurrentis) diagnosed in 15 refugees from northeast Africa: epidemiology and preventive control measures, Bavaria, Germany, July to October 2015.

    PubMed

    Hoch, Martin; Wieser, Andreas; Löscher, Thomas; Margos, Gabriele; Pürner, Friedrich; Zühl, Jürgen; Seilmaier, Michael; Balzer, Lukas; Guggemos, Wolfgang; Rack-Hoch, Anita; von Both, Ulrich; Hauptvogel, Katja; Schönberger, Katharina; Hautmann, Wolfgang; Sing, Andreas; Fingerle, Volker

    2015-01-01

    We report 15 imported louse-borne relapsing fever (LBRF) cases in refugees in Bavaria, Germany. One patient died. Epidemiological findings confirmed that all were young males from the Horn of Africa (12 from Somalia), who had similar migration routes converging in Sudan continuing through Libya and Italy. The majority likely acquired their infection during migration. Healthcare workers should be aware of LBRF in refugees passing through north Africa to ensure correct treatment and preventive measures. PMID:26538532

  2. Borrelia recurrentis in Head Lice, Ethiopia

    PubMed Central

    Boutellis, Amina; Mediannikov, Oleg; Bilcha, Kassahun Desalegn; Ali, Jemal; Campelo, Dayana; Barker, Stephen C.

    2013-01-01

    Since the 1800s, the only known vector of Borrelia recurrentis has been the body louse. In 2011, we found B. recurrentis DNA in 23% of head lice from patients with louse-borne relapsing fever in Ethiopia. Whether head lice can transmit these bacteria from one person to another remains to be determined. PMID:23648147

  3. Acylated proteins in Borrelia hermsii, Borrelia parkeri, Borrelia anserina, and Borrelia coriaceae.

    PubMed Central

    Sambri, V; Stefanelli, C; Rossoni, C; La Placa, M; Cevenini, R

    1993-01-01

    Borrelia hermsii, Borrelia parkeri, Borrelia anserina, and Borrelia coriaceae produced several lipoproteins identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography of bacteria grown in [3H]palmitate. Five major acylated proteins were demonstrated by sequential alkaline and acid hydrolysis. High-pressure liquid chromatography of isolated proteins confirmed that covalently bound radioactivity was represented by fatty acids. Images PMID:8285697

  4. Periplasmic Flagellar Export Apparatus Protein, FliH, Is Involved in Post-Transcriptional Regulation of FlaB, Motility and Virulence of the Relapsing Fever Spirochete Borrelia hermsii

    PubMed Central

    Guyard, Cyril; Raffel, Sandra J.; Schrumpf, Merry E.; Dahlstrom, Eric; Sturdevant, Daniel; Ricklefs, Stacy M.; Martens, Craig; Hayes, Stanley F.; Fischer, Elizabeth R.; Hansen, Bryan T.; Porcella, Stephen F.; Schwan, Tom G.

    2013-01-01

    Spirochetes are bacteria characterized in part by rotating periplasmic flagella that impart their helical or flat-wave morphology and motility. While most other bacteria rely on a transcriptional cascade to regulate the expression of motility genes, spirochetes employ post-transcriptional mechanism(s) that are only partially known. In the present study, we characterize a spontaneous non-motile mutant of the relapsing fever spirochete Borrelia hermsii that was straight, non-motile and deficient in periplasmic flagella. We used next generation DNA sequencing of the mutant’s genome, which when compared to the wild-type genome identified a 142 bp deletion in the chromosomal gene encoding the flagellar export apparatus protein FliH. Immunoblot and transcription analyses showed that the mutant phenotype was linked to the posttranscriptional deficiency in the synthesis of the major periplasmic flagellar filament core protein FlaB. Despite the lack of FlaB, the amount of FlaA produced by the fliH mutant was similar to the wild-type level. The turnover of the residual pool of FlaB produced by the fliH mutant was comparable to the wild-type spirochete. The non-motile mutant was not infectious in mice and its inoculation did not induce an antibody response. Trans-complementation of the mutant with an intact fliH gene restored the synthesis of FlaB, a normal morphology, motility and infectivity in mice. Therefore, we propose that the flagellar export apparatus protein regulates motility of B. hermsii at the post-transcriptional level by influencing the synthesis of FlaB. PMID:24009690

  5. Borrelia infection in small mammals in West Africa and its relationship with tick occurrence inside burrows.

    PubMed

    Diatta, Georges; Duplantier, Jean-Marc; Granjon, Laurent; Bâ, Khalilou; Chauvancy, Gilles; Ndiaye, Mady; Trape, Jean-François

    2015-12-01

    Tick-borne relapsing fever (TBRF) is a zoonotic disease caused by several Borrelia species transmitted to humans by Ornithodoros tick vectors. In West Africa, Borrelia crocidurae is a common cause of disease in many rural populations. Small mammals act as reservoirs of infection. We report here the results of surveys that investigated the occurrence of B. crocidurae infection in rodents and insectivores from eight countries of West and Central Africa. Animals were identified at the species level and tested for Borrelia either by examination of thick blood film, intra-peritoneal inoculation of blood or brain tissues into laboratory mice, or by molecular techniques. A total of 4358 small mammals belonging to 38 species and 7 families were collected, including 3225 specimens collected in areas where the occurrence of Ornithodoros sonrai tick in rodent burrows was documented, and 1133 in areas where this tick was absent. In areas with O. sonrai, Borrelia infection was demonstrated in 287 of 3109 (9.2%) small mammals tested, and none was documented in 1004 animals tested from other areas. There was no relationship between the occurrence of Rhipicephalus, Hyaloma and Argas ticks in burrows and the distribution of Borrelia infection in small mammals. The 287 specimens infected by Borrelia belonged to 15 rodent and shrew species, including three Saharo-Sahelian species - Gerbillus gerbillus, Gerbillus occiduus and Gerbillus tarabuli - identified as reservoirs for TBRF with a distribution restricted to this area. In Sudan and Sudano-Sahelian areas, Arvicanthis niloticus, Mastomys erythroleucus and Mastomys huberti were the main reservoir of infection. Although most small mammals species collected had a large distribution in West and Central Africa, the fact that only animals collected in areas with O. sonrai were found infected suggest that this tick is the only vector of TBRF in rodents and insectivores in this part of Africa. PMID:26327444

  6. Use of peroxidase-labelled antigen for the detection of antibodies to Borrelia burgdorferi in human and animal sera.

    PubMed

    Eiffert, H; Lotter, H; Thomssen, R

    1991-01-01

    We have developed a modified ELISA for the detection of anti-Borrelia burgdorferi (Bb) antibodies based on a peroxidase enzyme labelled antigen (ELAT). Microtiter plates were coated with antigen of Bb. The immunoglobulins of the serum samples were bound to the antigen and specific antibodies were detected by an enzyme labelled antigen. The test principle facilitates the recognition of specific antibodies in different collectives of human and animal sera. We performed epidemiological studies with the ELAT on 231 sera from mothers in maternity wards (9.5% positive), 219 patient sera sent to the Bb routine diagnostics (15% positive) and 230 sera from forestry workers (21.3% positive). We further investigated sera from red deer from South Lower Saxony which remained 55% Bb-antibody positive; deer were 37% and fallow deer were 29% positive. PMID:2028231

  7. Interferon-α curbs production of interleukin-22 by human peripheral blood mononuclear cells exposed to live Borrelia burgdorferi.

    PubMed

    Berner, Anika; Bachmann, Malte; Pfeilschifter, Josef; Kraiczy, Peter; Mühl, Heiko

    2015-10-01

    Cytokine networks initiated by means of innate immunity are regarded as a major determinant of host defence in response to acute infection by bacteria including Borrelia burgdorferi. Herein, we demonstrate that interferon (IFN)-α, either endogenously produced after exposure of cells to toll-like receptor-9-activating CpG oligonucleotides or provided as recombinant cytokine, weakens activation of the anti-bacterial interleukin (IL)-1/IL-22 axis in human peripheral blood mononuclear cells exposed to viable B. burgdorferi. As IFN-α has been related to pathological dissemination of the spirochaete, data suggest an immunoregulatory role of type I IFN in this context that is able to significantly modify cytokine profiles thereby possibly determining early course of B. burgdorferi infection. PMID:26152778

  8. GlpQ: an antigen for serological discrimination between relapsing fever and Lyme borreliosis.

    PubMed Central

    Schwan, T G; Schrumpf, M E; Hinnebusch, B J; Anderson, D E; Konkel, M E

    1996-01-01

    Tick-borne relapsing fever is caused by numerous Borrelia species maintained in nature by Ornithodoros tick-mammal cycles. Serological confirmation is based on either an immunofluorescence assay or an enzyme-linked immunosorbent assay using whole cells or sonicated Borrelia hermsii as the antigen. However, antigenic variability of this bacterium's outer surface proteins and antigens shared with the Lyme disease spirochete (B. burgdorferi), may cause both false-negative and false-positive results when testing sera of patients suspected to have either relapsing fever or Lyme disease. To develop a specific serological test for relapsing fever, we created a genomic DNA library of B. hermsii, screened transformed Escherichia coli cells for immunoreactivity with high-titered (> or = 1:2,048) human anti-B. hermsii antiserum, and selected an immunoreactive clone (pSPR75) expressing a 39-kDa protein. DNA sequencing, subcloning, and serum adsorption experiments identified the immunoreactive protein as a homolog of GlpQ, a glycerophosphodiester phosphodiesterase identified previously in E. coli, Haemophilus influenzae, and Bacillus subtilis. Serum samples from humans and mice infected with B. hermsii or other species of relapsing fever spirochetes contained antibodies recognizing GlpQ, whereas serum samples from Lyme disease and syphilis patients were nonreactive. Serologic tests based on this antigen will identify people exposed previously to relapsing fever spirochetes and help clarify the distribution of relapsing fever and Lyme disease in situations in which the occurrence of their causative agents is uncertain. PMID:8880505

  9. The Epidemiology and Geographic Distribution of Relapsing Fever Borreliosis in West and North Africa, with a Review of the Ornithodoros erraticus Complex (Acari: Ixodida)

    PubMed Central

    Trape, Jean-François; Diatta, Georges; Arnathau, Céline; Bitam, Idir; Sarih, M’hammed; Belghyti, Driss; Bouattour, Ali; Elguero, Eric; Vial, Laurence; Mané, Youssouph; Baldé, Cellou; Pugnolle, Franck; Chauvancy, Gilles; Mahé, Gil; Granjon, Laurent; Duplantier, Jean-Marc

    2013-01-01

    Background Relapsing fever is the most frequent bacterial disease in Africa. Four main vector / pathogen complexes are classically recognized, with the louse Pediculus humanus acting as vector for B. recurrentis and the soft ticks Ornithodoros sonrai, O. erraticus and O. moubata acting as vectors for Borrelia crocidurae, B. hispanica and B. duttonii, respectively. Our aim was to investigate the epidemiology of the disease in West, North and Central Africa. Methods And Findings From 2002 to 2012, we conducted field surveys in 17 African countries and in Spain. We investigated the occurrence of Ornithodoros ticks in rodent burrows in 282 study sites. We collected 1,629 small mammals that may act as reservoir for Borrelia infections. Using molecular methods we studied genetic diversity among Ornithodoros ticks and Borrelia infections in ticks and small mammals. Of 9,870 burrows investigated, 1,196 (12.1%) were inhabited by Ornithodoros ticks. In West Africa, the southern and eastern limits of the vectors and Borrelia infections in ticks and small mammals were 13°N and 01°E, respectively. Molecular studies revealed the occurrence of nine different Ornithodoros species, including five species new for science, with six of them harboring Borrelia infections. Only B. crocidurae was found in West Africa and three Borrelia species were identified in North Africa: B. crocidurae, B. hispanica, and B. merionesi. Conclusions Borrelia Spirochetes responsible for relapsing fever in humans are highly prevalent both in Ornithodoros ticks and small mammals in North and West Africa but Ornithodoros ticks seem absent south of 13°N and small mammals are not infected in these regions. The number of Ornithodoros species acting as vector of relapsing fever is much higher than previously known. PMID:24223812

  10. Relapsing fever borreliosis in Eurasia--forgotten, but certainly not gone!

    PubMed

    Assous, M V; Wilamowski, A

    2009-05-01

    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. PMID:19489923

  11. Human cord blood contains an IGM antibody to the 41KD flagellar antigen of Borrelia burgdorferi.

    PubMed

    Cooke, W D; Orr, A S; Wiseman, B L; Rouse, S B; Murray, W C; Ranck, S G

    1993-10-01

    Natural antibodies are the IgM products of fetal and neonatal B cells. These are germline encoded low affinity antibodies with multiple specificities to self and exogenous antigens. Lyme borreliosis is the disease resulting from infection with the spirochete, Borrelia burgdorferi. The humoral response to this organism is brisk, directed at multiple proteins, and persistent. Antibody to the 41kd flagellar antigen is found early in disease, but may also be found in non-exposed individuals. These properties suggest that the anti-41kd antibody may be a natural antibody. We report here the finding of an IgM anti-41kd reactivity in 29% of cord blood samples from patients in an area non-endemic for Lyme disease. The results are consistent with the hypothesis that antibody to flagellin may be a germline encoded natural antibody, and could be important in the immunopathogenesis of Lyme arthritis and other arthritides. PMID:8211003

  12. Transmission risk of Borrelia burgdorferi sensu lato from Ixodes ricinus ticks to humans in southwest Germany.

    PubMed Central

    Maiwald, M.; Oehme, R.; March, O.; Petney, T. N.; Kimmig, P.; Naser, K.; Zappe, H. A.; Hassler, D.; von Knebel Doeberitz, M.

    1998-01-01

    The risk of Borrelia burgdorferi infection and the value of antibiotic prophylaxis after tick bite are controversial. In this study, performed in two areas of southwestern Germany, ticks were collected from 730 patients and examined by the polymerase chain reaction (PCR) for B. burgdorferi. To assess whether transmission of B. burgdorferi occurred, the patients were clinically and serologically examined after tick removal and during follow-up examinations. Data from all tick bites gave a total transmission rate of 2.6% (19 patients). Eighty-four ticks (11.3%) were PCR positive. Transmission occurred to 16 (26.7%) of 60 patients who were initially seronegative and could be followed up after the bite of an infected tick. These results indicate that the transmission rate from infected ticks in Europe is higher than previously assumed. Examination of ticks and antibiotic prophylaxis in the case of positivity appears to be indicated. PMID:9747761

  13. Multiple and Diverse vsp and vlp Sequences in Borrelia miyamotoi, a Hard Tick-Borne Zoonotic Pathogen

    PubMed Central

    Barbour, Alan G.

    2016-01-01

    Based on chromosome sequences, the human pathogen Borrelia miyamotoi phylogenetically clusters with species that cause relapsing fever. But atypically for relapsing fever agents, B. miyamotoi is transmitted not by soft ticks but by hard ticks, which also are vectors of Lyme disease Borrelia species. To further assess the relationships of B. miyamotoi to species that cause relapsing fever, I investigated extrachromosomal sequences of a North American strain with specific attention on plasmid-borne vsp and vlp genes, which are the underpinnings of antigenic variation during relapsing fever. For a hybrid approach to achieve assemblies that spanned more than one of the paralogous vsp and vlp genes, a database of short-reads from next-generation sequencing was supplemented with long-reads obtained with real-time DNA sequencing from single polymerase molecules. This yielded three contigs of 31, 16, and 11 kb, which each contained multiple and diverse sequences that were homologous to vsp and vlp genes of the relapsing fever agent B. hermsii. Two plasmid fragments had coding sequences for plasmid partition proteins that differed from each other from paralogous proteins for the megaplasmid and a small plasmid of B. miyamotoi. One of 4 vsp genes, vsp1, was present at two loci, one of which was downstream of a candiate prokaryotic promoter. A limited RNA-seq analysis of a population growing in the blood of mice indicated that of the 4 different vsp genes vsp1 was the one that was expressed. The findings indicate that B. miyamotoi has at least four types of plasmids, two or more of which bear vsp and vlp gene sequences that are as numerous and diverse as those of relapsing fever Borrelia. The database and insights from these findings provide a foundation for further investigations of the immune responses to this pathogen and of the capability of B. miyamotoi for antigenic variation. PMID:26785134

  14. Associations of passerine birds, rabbits, and ticks with Borrelia miyamotoi and Borrelia andersonii in Michigan, U.S.A.

    PubMed Central

    2012-01-01

    Background Wild birds contribute to maintenance and dissemination of vectors and microbes, including those that impact human, domestic animal, and wildlife health. Here we elucidate roles of wild passerine birds, eastern cottontail rabbits (Sylvilagus floridanus), and Ixodes dentatus ticks in enzootic cycles of two spirochetes, Borrelia miyamotoi and B. andersonii in a region of Michigan where the zoonotic pathogen B. burgdorferi co-circulates. Methods Over a four-year period, wild birds (n = 19,631) and rabbits (n = 20) were inspected for tick presence and ear tissue was obtained from rabbits. Samples were tested for Borrelia spirochetes using nested PCR of the 16S-23S rRNA intergenic spacer region (IGS) and bidirectional DNA sequencing. Natural xenodiagnosis was used to implicate wildlife reservoirs. Results Ixodes dentatus, a tick that specializes on birds and rabbits and rarely bites humans, was the most common tick found, comprising 86.5% of the 12,432 ticks collected in the study. The relapsing fever group spirochete B. miyamotoi was documented for the first time in ticks removed from wild birds (0.7% minimum infection prevalence; MIP, in I. dentatus), and included two IGS strains. The majority of B. miyamotoi-positive ticks were removed from Northern Cardinals (Cardinalis cardinalis). Borrelia andersonii infected ticks removed from birds (1.6% MIP), ticks removed from rabbits (5.3% MIP), and rabbit ear biopsies (5%) comprised twelve novel IGS strains. Six species of wild birds were implicated as reservoirs for B. andersonii. Frequency of I. dentatus larval and nymphal co-feeding on birds was ten times greater than expected by chance. The relatively well-studied ecology of I. scapularis and the Lyme disease pathogen provides a context for understanding how the phenology of bird ticks may impact B. miyamotoi and B. andersonii prevalence and host associations. Conclusions Given the current invasion of I. scapularis, a human biting species that serves as a

  15. Multiplex Real-Time PCR Diagnostic of Relapsing Fevers in Africa

    PubMed Central

    Elbir, Haitham; Henry, Mireille; Diatta, Georges; Mediannikov, Oleg; Sokhna, Cheikh; Tall, Adama; Socolovschi, Cristina; Cutler, Sally J.; Bilcha, Kassahum D.; Ali, Jemal; Campelo, Dayana; Barker, Steven C.; Raoult, Didier; Drancourt, Michel

    2013-01-01

    Background In Africa, relapsing fever borreliae are neglected arthropod-borne pathogens causing mild to deadly septicemia and miscarriage. The closely related Borrelia crocidurae, Borrelia duttonii, Borrelia recurrentis and Borrelia hispanica are rarely diagnosed at the species level, hampering refined epidemiological and clinical knowledge of the relapsing fevers. It would be hugely beneficial to have simultaneous detection and identification of Borrelia to species level directly from clinical samples. Methodology/Principal Findings We designed a multiplex real-time PCR protocol targeting the 16S rRNA gene detecting all four Borrelia, the glpQ gene specifically detecting B. crocidurae, the recN gene specifically detecting B. duttonii/B. recurrentis and the recC gene specifically detecting B. hispanica. Compared to combined 16S rRNA gene and flaB gene sequencing as the gold standard, multiplex real-time PCR analyses of 171 Borrelia-positive and 101 Borrelia-negative control blood specimens yielded 100% sensitivity and specificity for B. duttonii/B. recurrentis and B. hispanica and 99% sensitivity and specificity for B. crocidurae. Conclusions/Significance The multiplex real-time PCR developed in this study is a rapid technique for both molecular detection and speciation of relapsing fever borreliae from blood in Africa. It could be incorporated in point-of-care laboratory to confirm diagnosis and provide evidence of the burden of infection attributed to different species of known or potentially novel relapsing fever borreliae. PMID:23390560

  16. Purine Salvage Pathways among Borrelia Species▿

    PubMed Central

    Pettersson, Jonas; Schrumpf, Merry E.; Raffel, Sandra J.; Porcella, Stephen F.; Guyard, Cyril; Lawrence, Kevin; Gherardini, Frank C.; Schwan, Tom G.

    2007-01-01

    Genome sequencing projects on two relapsing fever spirochetes, Borrelia hermsii and Borrelia turicatae, revealed differences in genes involved in purine metabolism and salvage compared to those in the Lyme disease spirochete Borrelia burgdorferi. The relapsing fever spirochetes contained six open reading frames that are absent from the B. burgdorferi genome. These genes included those for hypoxanthine-guanine phosphoribosyltransferase (hpt), adenylosuccinate synthase (purA), adenylosuccinate lyase (purB), auxiliary protein (nrdI), the ribonucleotide-diphosphate reductase alpha subunit (nrdE), and the ribonucleotide-diphosphate reductase beta subunit (nrdF). Southern blot assays with multiple Borrelia species and isolates confirmed the presence of these genes in the relapsing fever group of spirochetes but not in B. burgdorferi and related species. TaqMan real-time reverse transcription-PCR demonstrated that the chromosomal genes (hpt, purA, and purB) were transcribed in vitro and in mice. Phosphoribosyltransferase assays revealed that, in general, B. hermsii exhibited significantly higher activity than did the B. burgdorferi cell lysate, and enzymatic activity was observed with adenine, hypoxanthine, and guanine as substrates. B. burgdorferi showed low but detectable phosphoribosyltransferase activity with hypoxanthine even though the genome lacks a discernible ortholog to the hpt gene in the relapsing fever spirochetes. B. hermsii incorporated radiolabeled hypoxanthine into RNA and DNA to a much greater extent than did B. burgdorferi. This complete pathway for purine salvage in the relapsing fever spirochetes may contribute, in part, to these spirochetes achieving high cell densities in blood. PMID:17502392

  17. Quantification of Borrelia burgdorferi Membrane Proteins in Human Serum: A New Concept for Detection of Bacterial Infection.

    PubMed

    Cheung, Crystal S F; Anderson, Kyle W; Benitez, Kenia Y Villatoro; Soloski, Mark J; Aucott, John N; Phinney, Karen W; Turko, Illarion V

    2015-11-17

    The Borrelia burgdorferi spirochete is the causative agent of Lyme disease, the most common tick-borne disease in the United States. The low abundance of bacterial proteins in human serum during infection imposes a challenge for early proteomic detection of Lyme disease. To address this challenge, we propose to detect membrane proteins released from bacteria due to disruption of their plasma membrane triggered by the innate immune system. These membrane proteins can be separated from the bulk of serum proteins by high-speed centrifugation causing substantial sample enrichment prior to targeted protein quantification using multiple reaction monitoring mass spectrometry. This new approach was first applied to detection of B. burgdorferi membrane proteins supplemented in human serum. Our results indicated that detection of B. burgdorferi membrane proteins, which are ≈10(7) lower in abundance than major serum proteins, is feasible. Therefore, quantitative analysis was also carried out for serum samples from three patients with acute Lyme disease. We were able to demonstrate the detection of ospA, the major B. burgdorferi lipoprotein at the level of 4.0 fmol of ospA/mg of serum protein. The results confirm the concept and suggest that the proposed approach can be expanded to detect other bacterial infections in humans, particularly where existing diagnostics are unreliable. PMID:26491962

  18. Borrelia burgdorferi lipoprotein BmpA activates pro-inflammatory responses in human synovial cells through a protein moiety

    PubMed Central

    Yang, Xiuli; Izadi, Hooman; Coleman, Adam S.; Wang, Penghua; Ma, Yongsheng; Fikrig, Erol; Anguita, Juan; Pal, Utpal

    2008-01-01

    Borrelia burgdorferi invasion of mammalian joints results in genesis of Lyme arthritis. Other than spirochete lipids, existence of protein antigens, which are abundant in joints and participate in B. burgdorferi-induced host inflammatory response, is unknown. Here, we report that major products of the B. burgdorferi basic membrane protein (bmp) A/B operon that are induced in murine and human joints, possess inflammatory properties. Compared to the wild type B. burgdorferi, an isogenic bmpA/B mutant induced significantly lower levels of pro-inflammatory cytokines TNF-α and IL-1β in cultured human synovial cells, which could be restored using bmpA/B-complemented mutants, and more directly, upon addition of recombinant BmpA, but not BmpB or control spirochete proteins. Non-lipidated and lipidated versions of BmpA induced similar levels of cytokines, and remained unaffected by treatment with lipopolysaccharide inhibitor, polymyxin B. The bmpA/B mutant was also impaired in the induction of NF-κB and p38 MAP kinase signaling pathways in synovial cells, which were activated by non-lipidated BmpA. These results show that a protein moiety of BmpA can induce cytokine responses in synovial cells via activation of the NF-κB and p38 MAP kinase pathways and thus, could potentially contribute to the genesis of Lyme arthritis. PMID:18725314

  19. Do animal models provide a valid analogue for human drug lapse and relapse? Comment on Leri and Stewart (2002).

    PubMed

    Marlatt, G Alan

    2002-11-01

    Prior research on animal models of drug relapse has demonstrated that passive exposure to an addictive substance following acquisition and extinction of drug self-administration has a "priming effect" on subsequent drug use. The validity of this animal analogue of human relapse can be criticized, however, because most human drug relapses are precipitated by the user's voluntary self-administration of a substance. The results of the present study by F. Leri and J. Stewart (2002) clearly show that if the initial heroin lapse is self-administered by rats, subsequent heroin seeking during the relapse test is significantly greater than if the heroin is externally administered. These results help bridge the gap between animal and human models of drug use and highlight the significance of both behavioral and environmental determinants of relapse. PMID:12498331

  20. CspA-Mediated Binding of Human Factor H Inhibits Complement Deposition and Confers Serum Resistance in Borrelia burgdorferi▿

    PubMed Central

    Kenedy, Melisha R.; Vuppala, Santosh R.; Siegel, Corinna; Kraiczy, Peter; Akins, Darrin R.

    2009-01-01

    Borrelia burgdorferi has developed efficient mechanisms for evading the innate immune response during mammalian infection and has been shown to be resistant to the complement-mediated bactericidal activity of human serum. It is well recognized that B. burgdorferi expresses multiple lipoproteins on its surface that bind the human complement inhibitors factor H and factor H-like protein 1 (FH/FHL-1). The binding of FH/FHL-1 on the surface of B. burgdorferi is thought to enhance its ability to evade serum-mediated killing during the acute phase of infection. One of the key B. burgdorferi FH/FHL-1 binding proteins identified thus far was designated CspA. While it is known that CspA binds FH/FHL-1, it is unclear how the interaction between CspA and FH/FHL-1 specifically enhances serum resistance. To better understand how CspA mediates serum resistance in B. burgdorferi, we inactivated cspA in a virulent strain of B. burgdorferi. An affinity ligand blot immunoassay and indirect immunofluorescence revealed that the CspA mutant does not efficiently bind human FH to its surface. Consistent with the lack of FH binding, the CspA mutant was also highly sensitive to killing by human serum. Additionally, the deposition of complement components C3, C6, and C5b-9 was enhanced on the surface of the CspA mutant compared to that of the wild-type strain. The combined data lead us to conclude that the CspA-mediated binding of human FH confers serum resistance by directly inhibiting complement deposition on the surface of B. burgdorferi. PMID:19451251

  1. Laboratory Cultivation and Maintenance of Borrelia miyamotoi.

    PubMed

    Stone, Brandee L; Brissette, Catherine A

    2016-01-01

    Borrelia miyamotoi is a relapsing fever tick-borne pathogen found in Ixodes spp. (hard) ticks. In vitro culturing has proven difficult despite initial reports of cultures maintained in Barbour-Stoenner-Kelly-II (BSK-II) medium. The ability to culture in vitro opens many avenues for investigating the genetics and physiology of bacterial species. This unit describes methods for the maintenance and cultivation of B. miyamotoi in liquid medium. © 2016 by John Wiley & Sons, Inc. PMID:27517334

  2. Phagocytosis of Borrelia burgdorferi, the Lyme Disease Spirochete, Potentiates Innate Immune Activation and Induces Apoptosis in Human Monocytes▿

    PubMed Central

    Cruz, Adriana R.; Moore, Meagan W.; La Vake, Carson J.; Eggers, Christian H.; Salazar, Juan C.; Radolf, Justin D.

    2008-01-01

    We have previously demonstrated that phagocytosed Borrelia burgdorferi induces activation programs in human peripheral blood mononuclear cells that differ qualitatively and quantitatively from those evoked by equivalent lipoprotein-rich lysates. Here we report that ingested B. burgdorferi induces significantly greater transcription of proinflammatory cytokine genes than do lysates and that live B. burgdorferi, but not B. burgdorferi lysate, is avidly internalized by monocytes, where the bacteria are completely degraded within phagolysosomes. In the course of these experiments, we discovered that live B. burgdorferi also induced a dose-dependent decrease in monocytes but not a decrease in dendritic cells or T cells and that the monocyte population displayed morphological and biochemical hallmarks of apoptosis. Particularly noteworthy was the finding that apoptotic changes occurred predominantly in monocytes that had internalized spirochetes. Abrogation of phagocytosis with cytochalasin D prevented the death response. Heat-killed B. burgdorferi, which was internalized as well as live organisms, induced a similar degree of apoptosis of monocytes but markedly less cytokine production. Surprisingly, opsonophagocytosis of Treponema pallidum did not elicit a discernible cell death response. Our combined results demonstrate that B. burgdorferi confined to phagolysosomes is a potent inducer of cytosolic signals that result in (i) production of NF-κB-dependent cytokines, (ii) assembly of the inflammasome and activation of caspase-1, and (iii) induction of programmed cell death. We propose that inflammation and apoptosis represent mutually reinforcing components of the immunologic arsenal that the host mobilizes to defend itself against infection with Lyme disease spirochetes. PMID:17938216

  3. Telomerase inhibition effectively targets mouse and human AML stem cells and delays relapse following chemotherapy.

    PubMed

    Bruedigam, Claudia; Bagger, Frederik O; Heidel, Florian H; Paine Kuhn, Catherine; Guignes, Solene; Song, Axia; Austin, Rebecca; Vu, Therese; Lee, Erwin; Riyat, Sarbjit; Moore, Andrew S; Lock, Richard B; Bullinger, Lars; Hill, Geoffrey R; Armstrong, Scott A; Williams, David A; Lane, Steven W

    2014-12-01

    Acute myeloid leukemia (AML) is an aggressive and lethal blood cancer maintained by rare populations of leukemia stem cells (LSCs). Selective targeting of LSCs is a promising approach for treating AML and preventing relapse following chemotherapy, and developing such therapeutic modalities is a key priority. Here, we show that targeting telomerase activity eradicates AML LSCs. Genetic deletion of the telomerase subunit Terc in a retroviral mouse AML model induces cell-cycle arrest and apoptosis of LSCs, and depletion of telomerase-deficient LSCs is partially rescued by p53 knockdown. Murine Terc(-/-) LSCs express a specific gene expression signature that can be identified in human AML patient cohorts and is positively correlated with patient survival following chemotherapy. In xenografts of primary human AML, genetic or pharmacological inhibition of telomerase targets LSCs, impairs leukemia progression, and delays relapse following chemotherapy. Altogether, these results establish telomerase inhibition as an effective strategy for eliminating AML LSCs. PMID:25479751

  4. Telomerase Inhibition Effectively Targets Mouse and Human AML Stem Cells and Delays Relapse Following Chemotherapy

    PubMed Central

    Bruedigam, Claudia; Bagger, Frederik O.; Heidel, Florian H.; Kuhn, Catherine Paine; Guignes, Solene; Song, Axia; Austin, Rebecca; Vu, Therese; Lee, Erwin; Riyat, Sarbjit; Moore, Andrew S.; Lock, Richard B.; Bullinger, Lars; Hill, Geoffrey R.; Armstrong, Scott A.; Williams, David A.; Lane, Steven W.

    2014-01-01

    SUMMARY Acute myeloid leukemia (AML) is an aggressive and lethal blood cancer maintained by rare populations of leukemia stem cells (LSCs). Selective targeting of LSCs is a promising approach for treating AML and preventing relapse following chemotherapy, and developing such therapeutic modalities is a key priority. Here, we show that targeting telomerase activity eradicates AML LSCs. Genetic deletion of the telomerase subunit Terc in a retroviral mouse AML model induces cell cycle arrest and apoptosis of LSCs, and depletion of telomerase-deficient LSCs is partially rescued by p53 knockdown. Murine Terc−/− LSCs express a specific gene expression signature that can be identified in human AML patient cohorts and is positively correlated with patient survival following chemotherapy. In xenografts of primary human AML, genetic or pharmacological inhibition of telomerase targets LSCs, impairs leukemia progression, and delays relapse following chemotherapy. Together, these results establish telomerase inhibition as an effective strategy for eliminating AML LSCs. PMID:25479751

  5. Whole-Genome Sequences of Two Borrelia afzelii and Two Borrelia garinii Lyme Disease Agent Isolates

    PubMed Central

    Casjens, Sherwood R.; Mongodin, Emmanuel F.; Qiu, Wei-Gang; Dunn, John J.; Luft, Benjamin J.; Fraser-Liggett, Claire M.; Schutzer, Steve E.

    2011-01-01

    Human Lyme disease is commonly caused by several species of spirochetes in the Borrelia genus. In Eurasia these species are largely Borrelia afzelii, B. garinii, B. burgdorferi, and B. bavariensis sp. nov. Whole-genome sequencing is an excellent tool for investigating and understanding the influence of bacterial diversity on the pathogenesis and etiology of Lyme disease. We report here the whole-genome sequences of four isolates from two of the Borrelia species that cause human Lyme disease, B. afzelii isolates ACA-1 and PKo and B. garinii isolates PBr and Far04. PMID:22123755

  6. Whole-Genome Sequences of Two Borrelia afzelii and Two Borrelia garinii Lyme Disease Agent Isolates

    SciTech Connect

    Casjens, S.R.; Dunn, J.; Mongodin, E. F.; Qiu, W.-G.; Luft, B. J.; Fraser-Liggett, C. M.; Schutzer, S. E.

    2011-12-01

    Human Lyme disease is commonly caused by several species of spirochetes in the Borrelia genus. In Eurasia these species are largely Borrelia afzelii, B. garinii, B. burgdorferi, and B. bavariensis sp. nov. Whole-genome sequencing is an excellent tool for investigating and understanding the influence of bacterial diversity on the pathogenesis and etiology of Lyme disease. We report here the whole-genome sequences of four isolates from two of the Borrelia species that cause human Lyme disease, B. afzelii isolates ACA-1 and PKo and B. garinii isolates PBr and Far04.

  7. Induction of indoleamine 2,3-dioxygenase by Borrelia burgdorferi in human immune cells correlates with pathogenic potential

    PubMed Central

    Love, Andrea C.; Schwartz, Ira; Petzke, Mary M.

    2015-01-01

    Borrelia burgdorferi, the bacterial agent of Lyme disease, induces the production of type I IFNs by human DCs through TLR7 and TLR9 signaling. This type I IFN response occurs in a genotype-dependent manner, with significantly higher levels of IFN-α elicited by B. burgdorferi strains that have a greater capacity for causing disseminated infection. A B. burgdorferi strain that was previously shown to induce IFN-α was found to elicit significantly higher levels of IDO1 protein and its downstream metabolite, kynurenine, compared with a B. burgdorferi mutant that lacks a single linear plasmid (lp36); this mutant is unable to induce IFN-α and is severely attenuated for infectivity in mice. Production of IDO by mDC and pDC populations, present within human PBMCs, was concomitant with increased expression of the DC maturation markers, CD83 and CCR7. The defects in IDO production and expression of CD83 and CCR7 could be restored by complementation of the mutant with lp36. Maximal IDO production in response to the wild-type strain was dependent on contributions by both type I IFN and IFN-γ, the type II IFN. Induction of IDO was mediated by the same TLR7-dependent recognition of B. burgdorferi RNA that contributes to the production of type I IFNs by human DCs. The ability of IFN-α-inducing B. burgdorferi strains to stimulate production of IDO and kynurenines may be a mechanism that is used by the pathogen to promote localized immunosuppression and facilitate hematogenous dissemination. PMID:25420916

  8. Complications of pregnancy and transplacental transmission of relapsing-fever borreliosis.

    PubMed

    Larsson, Christer; Andersson, Marie; Guo, Betty P; Nordstrand, Annika; Hagerstrand, Inga; Carlsson, Sara; Bergstrom, Sven

    2006-11-15

    Relapsing-fever borreliosis caused by Borrelia duttonii is a common cause of complications of pregnancy, miscarriage, and neonatal death in sub-Saharan Africa. We established a murine model of gestational relapsing fever infection for the study of the pathological development of these complications. We demonstrate that B. duttonii infection during pregnancy results in intrauterine growth retardation, as well as placental damage and inflammation, impaired fetal circulation, and decreased maternal hemoglobin levels. We show that spirochetes frequently cross the maternal-fetal barrier, resulting in congenital infection. Furthermore, we compared the severity of infection in pregnant and nonpregnant mice and show that pregnancy has a protective effect. This model closely parallels the consequences of human gestational infection, and our results provide insight into the mechanisms behind the complications of pregnancy that have been reported in human relapsing-fever infection. PMID:17054065

  9. The Borrelia afzelii outer membrane protein BAPKO_0422 binds human factor-H and is predicted to form a membrane-spanning β-barrel

    PubMed Central

    Dyer, Adam; Brown, Gemma; Stejskal, Lenka; Laity, Peter R.; Bingham, Richard J.

    2015-01-01

    The deep evolutionary history of the Spirochetes places their branch point early in the evolution of the diderms, before the divergence of the present day Proteobacteria. As a spirochete, the morphology of the Borrelia cell envelope shares characteristics of both Gram-positive and Gram-negative bacteria. A thin layer of peptidoglycan, tightly associated with the cytoplasmic membrane, is surrounded by a more labile outer membrane (OM). This OM is rich in lipoproteins but with few known integral membrane proteins. The outer membrane protein A (OmpA) domain is an eight-stranded membrane-spanning β-barrel, highly conserved among the Proteobacteria but so far unknown in the Spirochetes. In the present work, we describe the identification of four novel OmpA-like β-barrels from Borrelia afzelii, the most common cause of erythema migrans (EM) rash in Europe. Structural characterization of one these proteins (BAPKO_0422) by SAXS and CD indicate a compact globular structure rich in β-strand consistent with a monomeric β-barrel. Ab initio molecular envelopes calculated from the scattering profile are consistent with homology models and demonstrate that BAPKO_0422 adopts a peanut shape with dimensions 25×45 Å (1 Å=0.1 nm). Deviations from the standard C-terminal signature sequence are apparent; in particular the C-terminal phenylalanine residue commonly found in Proteobacterial OM proteins is replaced by isoleucine/leucine or asparagine. BAPKO_0422 is demonstrated to bind human factor H (fH) and therefore may contribute to immune evasion by inhibition of the complement response. Encoded by chromosomal genes, these proteins are highly conserved between Borrelia subspecies and may be of diagnostic or therapeutic value. PMID:26181365

  10. [Clinical aspects of Borrelia burgdorferi infections].

    PubMed

    Neubert, U

    1989-08-15

    Skin lesions due to Borrelia burgdorferi-like erythema migrans, lymphadenosis cutis benigna, and acrodermatitis chronica atrophicans - are hall-marks of a systemic infection, which tends to a chronically relapsing course. Even if the skin lesions are missing, or disappear spontaneously, the infection may persist and affect other organs. This presumption is supported by the outcome of a long-term follow-up study on seropositive forest workers. In association with meningopolyneuritis (Garin-Bujadoux-Bannwarth disease) and acrodermatitis chronica atrophicans - myositis and fasciitis have been recently reported as further possible manifestations of Borrelia burgdorferi infection. Borrelial infection during pregnancy should promptly be treated with antibiotics in high dosages, in order to prevent maternal-fetal transmission of borrelial organisms resulting in stillbirth or congenital defects of the newborn. PMID:2678790

  11. Borrelia persica Infection in Immunocompetent Mice - A New Tool to Study the Infection Kinetics In Vivo

    PubMed Central

    Schwarzer, Sandra; Overzier, Evelyn; Hermanns, Walter; Baneth, Gad; Straubinger, Reinhard K.

    2016-01-01

    Borrelia persica, a bacterium transmitted by the soft tick Ornithodoros tholozani, causes tick-borne relapsing fever in humans in the Middle East, Central Asia and the Indian peninsula. Immunocompetent C3H/HeOuJ mice were infected intradermally with B. persica at varying doses: 1 x 106, 1 x 104, 1 x 102 and 4 x 100 spirochetes/mouse. Subsequently, blood samples were collected and screened for the presence of B. persica DNA. Spirochetes were detected in all mice infected with 1 x 106, 1 x 104 and 1 x 102 borrelia by real-time PCR targeting the flaB gene of the bacterium. Spirochetemia developed with a one- to two-day delay when 1 x 104 and 1 x 102 borrelia were inoculated. Mice injected with only four organisms were negative in all tests. No clinical signs were observed when infected mice were compared to negative control animals. Organs (heart, spleen, urinary bladder, tarsal joint, skin and brain) were tested for B. persica-specific DNA and cultured for the detection of viable spirochetes. Compiled data show that the target organs of B. persica infections are the brain and the skin. A newly developed serological two-tiered test system (ELISA and western blot) for the detection of murine IgM, IgG and IgA antibody titers against B. persica showed a vigorous antibody response of the mice during infection. In conclusion, the infection model described here for B. persica is a platform for in vivo studies to decipher the so far unexplored survival strategies of this Borrelia species. PMID:26890814

  12. Relapsing fever in pregnancy: analysis of high-risk factors.

    PubMed

    Melkert, P W

    1988-10-01

    The diagnosis of tick-borne relapsing fever was established in 27 pregnant patients by demonstration of Borrelia spirochaetes in a thick blood smear and the borrelia index was estimated to calculate the density of the spirochaetaemia. Clinical findings are described and compared with those reported from Rwanda. The results suggest that the density of the spirochaetaemia and the gestational age are the main high-risk factors. PMID:3191046

  13. BB0347, from the Lyme Disease Spirochete Borrelia burgdorferi, Is Surface Exposed and Interacts with the CS1 Heparin-Binding Domain of Human Fibronectin

    PubMed Central

    Gaultney, Robert A.; Gonzalez, Tammy; Floden, Angela M.; Brissette, Catherine A.

    2013-01-01

    The causative agent of Lyme disease, Borrelia burgdorferi, codes for several known fibronectin-binding proteins. Fibronectin a common the target of diverse bacterial pathogens, and has been shown to be essential in allowing for the development of certain disease states. Another borrelial protein, BB0347, has sequence similarity with these other known fibronectin-binding proteins, and may be important in Lyme disease pathogenesis. Herein, we perform an initial characterization of BB0347 via the use of molecular and biochemical techniques. We found that BB0347 is expressed, produced, and presented on the outer surface of intact B. burgdorferi. We also demonstrate that BB0347 has the potential to be important in Lyme disease progression, and have begun to characterize the nature of the interaction between human fibronectin and this bacterial protein. Further work is needed to define the role of this protein in the borrelial infection process. PMID:24086600

  14. Genetics of Borrelia burgdorferi

    PubMed Central

    Brisson, Dustin; Drecktrah, Dan; Eggers, Christian H.; Samuels, D. Scott

    2013-01-01

    The spirochetes in the Borrelia burgdorferi sensu lato genospecies group cycle in nature between tick vectors and vertebrate hosts. The current assemblage of B. burgdorferi sensu lato, of which three species cause Lyme disease in humans, originated from a rapid species radiation that occurred near the origin of the clade. All of these species share a unique genome structure that is highly segmented and predominantly composed of linear replicons. One of the circular plasmids is a prophage that exists as several isoforms in each cell and can be transduced to other cells, likely contributing to an otherwise relatively anemic level of horizontal gene transfer, which nevertheless appears to be adequate to permit strong natural selection and adaptation in populations of B. burgdorferi. Although the molecular genetic toolbox is meager, several antibiotic-resistant mutants have been isolated, and the resistance alleles, as well as some exogenous genes, have been fashioned into markers to dissect gene function. Genetic studies have probed the role of the outer membrane lipoprotein OspC, which is maintained in nature by multiple niche polymorphisms and negative frequency-dependent selection. One of the most intriguing genetic systems in B. burgdorferi is vls recombination, which generates antigenic variation during infection of mammalian hosts. PMID:22974303

  15. Diversity and Distribution of Borrelia hermsii

    PubMed Central

    Raffel, Sandra J.; Schrumpf, Merry E.; Porcella, Stephen F.

    2007-01-01

    Borrelia hermsii is the most common cause of tickborne relapsing fever in North America. DNA sequences of the 16S–23S rDNA noncoding intergenic spacer (IGS) region were determined for 37 isolates of this spirochete. These sequences distinguished the 2 genomic groups of B. hermsii identified previously with other loci. Multiple IGS genotypes were identified among isolates from an island, which suggested that birds might play a role in dispersing these spirochetes in nature. In support of this theory, all stages of the tick vector Ornithodoros hermsi fed successfully on birds in the laboratory and advanced in their life cycle. B. hermsii produced a detectable spirochetemia in 1 chicken inoculated subcutaneously. Additional work is warranted to explore the role of birds as enzootic hosts for this relapsing fever spirochete. PMID:17552097

  16. Prevalence of Borrelia miyamotoi in Ixodes Ticks in Europe and the United States

    PubMed Central

    Crowder, Chris D.; Carolan, Heather E.; Rounds, Megan A.; Honig, Vaclav; Mothes, Benedikt; Haag, Heike; Nolte, Oliver; Luft, Ben J.; Grubhoffer, Libor; Ecker, David J.; Schutzer, Steven E.

    2014-01-01

    Borrelia miyamotoi, a relapsing fever-related spirochete transmitted by Ixodes ticks, has been recently shown to be a human pathogen. To characterize the prevalence of this organism in questing Ixodes ticks, we tested 2,754 ticks for a variety of tickborne pathogens by PCR and electrospray-ionization mass spectrometry. Ticks were collected from California, New York, Connecticut, Pennsylvania, and Indiana in the United States and from Germany and the Czech Republic in Europe from 2008 through 2012. In addition, an isolate from Japan was characterized. We found 3 distinct genotypes, 1 for North America, 1 for Europe, and 1 for Japan. We found B. miyamotoi infection in ticks in 16 of the 26 sites surveyed, with infection prevalence as high as 15.4%. These results show the widespread distribution of the pathogen, indicating an exposure risk to humans in areas where Ixodes ticks reside. PMID:25280366

  17. Detection of Borrelia burgdorferi Sensu Stricto ospC Alleles Associated with Human Lyme Borreliosis Worldwide in Non-Human-Biting Tick Ixodes affinis and Rodent Hosts in Southeastern United States

    PubMed Central

    Golovchenko, Maryna; Hönig, Václav; Mallátová, Nadja; Krbková, Lenka; Mikulášek, Peter; Fedorova, Natalia; Belfiore, Natalia M.; Grubhoffer, Libor; Lane, Robert S.; Oliver, James H.

    2013-01-01

    Comparative analysis of ospC genes from 127 Borrelia burgdorferi sensu stricto strains collected in European and North American regions where Lyme disease is endemic and where it is not endemic revealed a close relatedness of geographically distinct populations. ospC alleles A, B, and L were detected on both continents in vectors and hosts, including humans. Six ospC alleles, A, B, L, Q, R, and V, were prevalent in Europe; 4 of them were detected in samples of human origin. Ten ospC alleles, A, B, D, E3, F, G, H, H3, I3, and M, were identified in the far-western United States. Four ospC alleles, B, G, H, and L, were abundant in the southeastern United States. Here we present the first expanded analysis of ospC alleles of B. burgdorferi strains from the southeastern United States with respect to their relatedness to strains from other North American and European localities. We demonstrate that ospC genotypes commonly associated with human Lyme disease in European and North American regions where the disease is endemic were detected in B. burgdorferi strains isolated from the non-human-biting tick Ixodes affinis and rodent hosts in the southeastern United States. We discovered that some ospC alleles previously known only from Europe are widely distributed in the southeastern United States, a finding that confirms the hypothesis of transoceanic migration of Borrelia species. PMID:23263953

  18. Borrelia persica Infection in Immunocompetent Mice--A New Tool to Study the Infection Kinetics In Vivo.

    PubMed

    Schwarzer, Sandra; Overzier, Evelyn; Hermanns, Walter; Baneth, Gad; Straubinger, Reinhard K

    2016-02-01

    Borrelia persica, a bacterium transmitted by the soft tick Ornithodoros tholozani, causes tick-borne relapsing fever in humans in the Middle East, Central Asia and the Indian peninsula. Immunocompetent C3H/HeOuJ mice were infected intradermally with B. persica at varying doses: 1 x 10(6), 1 x 10(4), 1 x 10(2) and 4 x 10(0) spirochetes/mouse. Subsequently, blood samples were collected and screened for the presence of B. persica DNA. Spirochetes were detected in all mice infected with 1 x 10(6), 1 x 10(4) and 1 x 10(2) borrelia by real-time PCR targeting the flaB gene of the bacterium. Spirochetemia developed with a one- to two-day delay when 1 x 10(4) and 1 x 10(2) borrelia were inoculated. Mice injected with only four organisms were negative in all tests. No clinical signs were observed when infected mice were compared to negative control animals. Organs (heart, spleen, urinary bladder, tarsal joint, skin and brain) were tested for B. persica-specific DNA and cultured for the detection of viable spirochetes. Compiled data show that the target organs of B. persica infections are the brain and the skin. A newly developed serological two-tiered test system (ELISA and western blot) for the detection of murine IgM, IgG and IgA antibody titers against B. persica showed a vigorous antibody response of the mice during infection. In conclusion, the infection model described here for B. persica is a platform for in vivo studies to decipher the so far unexplored survival strategies of this Borrelia species. PMID:26890814

  19. Whole genome sequence of an unusual Borrelia burgdorferi sensu lato isolate

    SciTech Connect

    Casjens, S.R.; Dunn, J.; Fraser-Liggett, C. M.; Mongodin, E. F.; Qiu, W. G.; Luft, B. J.; Schutzer, S. E.

    2011-03-01

    Human Lyme disease is caused by a number of related Borrelia burgdorferi sensu lato species. We report here the complete genome sequence of Borrelia sp. isolate SV1 from Finland. This isolate is to date the closest known relative of B. burgdorferi sensu stricto, but it is sufficiently genetically distinct from that species that it and its close relatives warrant its candidacy for new-species status. We suggest that this isolate should be named 'Borrelia finlandensis.'

  20. Epitope-Specific Evolution of Human B Cell Responses to Borrelia burgdorferi VlsE Protein from Early to Late Stages of Lyme Disease.

    PubMed

    Jacek, Elzbieta; Tang, Kevin S; Komorowski, Lars; Ajamian, Mary; Probst, Christian; Stevenson, Brian; Wormser, Gary P; Marques, Adriana R; Alaedini, Armin

    2016-02-01

    Most immunogenic proteins of Borrelia burgdorferi, the causative agent of Lyme disease, are known or expected to contain multiple B cell epitopes. However, the kinetics of the development of human B cell responses toward the various epitopes of individual proteins during the course of Lyme disease has not been examined. Using the highly immunogenic VlsE as a model Ag, we investigated the evolution of humoral immune responses toward its immunodominant sequences in 90 patients with a range of early to late manifestations of Lyme disease. The results demonstrate the existence of asynchronous, independently developing, Ab responses against the two major immunogenic regions of the VlsE molecule in the human host. Despite their strong immunogenicity, the target epitopes were inaccessible to Abs on intact spirochetes, suggesting a lack of direct immunoprotective effect. These observations document the association of immune reactivity toward specific VlsE sequences with different phases of Lyme disease, demonstrating the potential use of detailed epitope mapping of Ags for staging of the infection, and offer insights regarding the pathogen's possible immune evasion mechanisms. PMID:26718339

  1. Epitope-Specific Evolution of Human B Cell Responses to Borrelia burgdorferi VlsE Protein from Early to Late Stages of Lyme Disease

    PubMed Central

    Jacek, Elzbieta; Tang, Kevin S.; Komorowski, Lars; Ajamian, Mary; Probst, Christian; Stevenson, Brian; Wormser, Gary P.; Marques, Adriana R.

    2016-01-01

    Most immunogenic proteins of Borrelia burgdorferi, the causative agent of Lyme disease, are known or expected to contain multiple B cell epitopes. However, the kinetics of the development of human B cell responses toward the various epitopes of individual proteins during the course of Lyme disease has not been examined. Using the highly immunogenic VlsE as a model Ag, we investigated the evolution of humoral immune responses toward its immunodominant sequences in 90 patients with a range of early to late manifestations of Lyme disease. The results demonstrate the existence of asynchronous, independently developing, Ab responses against the two major immunogenic regions of the VlsE molecule in the human host. Despite their strong immunogenicity, the target epitopes were inaccessible to Abs on intact spirochetes, suggesting a lack of direct immunoprotective effect. These observations document the association of immune reactivity toward specific VlsE sequences with different phases of Lyme disease, demonstrating the potential use of detailed epitope mapping of Ags for staging of the infection, and offer insights regarding the pathogen’s possible immune evasion mechanisms. PMID:26718339

  2. Borrelia burgdorferi sensu lato and co-infections with Anaplasma phagocytophilum and Rickettsia spp. in Ixodes ricinus in Hamburg, Germany.

    PubMed

    May, K; Jordan, D; Fingerle, V; Strube, C

    2015-12-01

    To obtain initial data on Borrelia burgdorferi sensu lato (Spirochaetales: Spirochaetaceae) in Ixodes ricinus (Ixodida: Ixodidae) ticks in Hamburg, Germany, 1400 questing ticks were collected by flagging at 10 different public recreation areas in 2011 and analysed using probe-based quantitative real-time polymerase chain reaction. The overall rate of infection with B. burgdorferi s.l. was 34.1%; 30.0% of adults were infected (36.7% of females and 26.0% of males), as were 34.5% of nymphs. Significant differences in tick infection rates were observed between the spring and summer/autumn months, as well as among sampling locations. Borrelia genospecies identification by reverse line blotting was successful in 43.6% of positive tick samples. The most frequent genospecies was Borrelia garinii/Borrelia bavariensis, followed by Borrelia afzelii, Borrelia valaisiana, B. burgdorferi sensu stricto, Borrelia spielmanii, Borrelia bissettii and Borrelia lusitaniae. Based on previously published data, co-infection of Borrelia and Rickettsiales spp. was determined in 25.8% of ticks. Overall, 22.9% of ticks were co-infected with Rickettsia spp. (Rickettsiales: Rickettsiaceae), 1.7% with Anaplasma phagocytophilum (Rickettsiales: Anaplasmataceae), and 1.2% with both pathogens. Study results show a high prevalence of Borrelia-positive ticks in recreation areas in the northern German city of Hamburg and the potential health risk to humans in these areas should not be underestimated. PMID:26096626

  3. Immunohistochemistry and real-time PCR as diagnostic tools for detection of Borrelia burgdorferi sensu lato in ticks collected from humans.

    PubMed

    Briciu, Violeta T; Sebah, Daniela; Coroiu, Georgiana; Lupşe, Mihaela; Cârstina, Dumitru; Ţăţulescu, Doina F; Mihalca, Andrei D; Gherman, Călin M; Leucuţa, Daniel; Meyer, Fabian; Hizo-Teufel, Cecilia; Fingerle, Volker; Huber, Ingrid

    2016-05-01

    The objective of this study was to evaluate different methods used for detection of Borrelia burgdorferi sensu lato (s.l.) in ticks: immunohistochemistry followed by focus floating microscopy (FFM) and real-time polymerase chain reaction (real-time PCR) targeting the ospA and hbb genes. Additionally, an optimized ospA real-time PCR assay was developed with an integrated internal amplification control (IAC) for the detection of inhibition in the PCR assay and was validated as an improved screening tool for B. burgdorferi. One hundred and thirty-six ticks collected from humans in a hospital from Cluj-Napoca, Romania, were investigated regarding genus, stage of development and sex, and then tested by all three assays. A poor quality of agreement was found between FFM and each of the two real-time PCR assays, as assessed by concordance analysis (Cohen's kappa), whereas the agreement between the two real-time PCR assays was moderate. The present study argues for a low sensitivity of FFM and underlines that discordant results of different assays used for detection of B. burgdorferi in ticks are frequent. PMID:26801157

  4. Borrelia burgdorferi Induces TLR1 and TLR2 in human microglia and peripheral blood monocytes but differentially regulates HLA-class II expression.

    PubMed

    Cassiani-Ingoni, Riccardo; Cabral, Erik S; Lünemann, Jan D; Garza, Zoila; Magnus, Tim; Gelderblom, Harald; Munson, Peter J; Marques, Adriana; Martin, Roland

    2006-06-01

    The spirochete Borrelia burgdorferi is the agent of Lyme disease, which causes central nervous system manifestations in up to 20% of patients. We investigated the response of human brain microglial cells, glial progenitors, neurons, astrocytes, as well as peripheral blood monocytes to stimulation with B. burgdorferi. We used oligoarrays to detect changes in the expression of genes important for shaping adaptive and innate immune responses. We found that stimulation with B. burgdorferi lysate increased the expression of Toll-like receptors (TLRs) 1 and 2 in all cell types except neurons. However, despite similarities in global gene profiles of monocytes and microglia, only microglial cells responded to the stimulation with a robust increase in HLA-DR, HLA-DQ, and also coexpressed CD11-c, a dendritic cell marker. In contrast, a large number of HLA-related molecules were repressed at both the RNA and the protein levels in stimulated monocytes, whereas secretion of IL-10 and TNF-alpha was strongly induced. These results show that signaling through TLR1/2 in response to B. burgdorferi can elicit opposite immunoregulatory effects in blood and in brain immune cells, which could play a role in the different susceptibility of these compartments to infection. PMID:16783164

  5. Human Granulocytic Ehrlichiosis Agent Infection in a Pony Vaccinated with a Borrelia burgdorferi Recombinant OspA Vaccine and Challenged by Exposure to Naturally Infected Ticks

    PubMed Central

    Chang, Yung-Fu; McDonough, Sean P.; Chang, Chao-Fu; Shin, Kwang-Soon; Yen, William; Divers, Thomas

    2000-01-01

    A pony was vaccinated with recombinant OspA vaccine (rOspA) and then exposed 3 months later to Borrelia burgdorferi-infected ticks (Ixodes scapularis) collected in Westchester County, N.Y. At 2 weeks after tick exposure, the pony developed a high fever (105°F). Buffy coat smears showed that 20% of neutrophils contained ehrlichial inclusion bodies (morulae). Flunixin Meglumine (1 g daily) was given for 2 days, and the body temperature returned to normal. PCR for ehrlichial DNA was performed on blood samples for 10 consecutive days beginning when the pony was first febrile. This pony was monitored for another 3.5 months but developed no further clinical signs. The 44-kDa immunodominant human granulocytic ehrlichiosis antigen gene was amplified by PCR and cloned into a pCR2.1 vector. DNA sequence analysis of this gene showed it was only 8 bp different (99% identity) from the results reported by others (J.W. Ijdo et al., Infect. Immun. 66:3264–3269, 1998). Western blot analysis, growth inhibition assays, and repeated attempts to isolate B. burgdorferi all demonstrated the pony was protected against B. burgdorferi infection. These results highlight the potential for ticks to harbor and transmit several pathogens simultaneously, which further complicates the diagnosis and vaccination of these emerging tick-borne diseases. PMID:10618280

  6. Autophagy suppresses host adaptive immune responses toward Borrelia burgdorferi.

    PubMed

    Buffen, Kathrin; Oosting, Marije; Li, Yang; Kanneganti, Thirumala-Devi; Netea, Mihai G; Joosten, Leo A B

    2016-09-01

    We have previously demonstrated that inhibition of autophagy increased the Borrelia burgdorferi induced innate cytokine production in vitro, but little is known regarding the effect of autophagy on in vivo models of Borrelia infection. Here, we showed that ATG7-deficient mice that were intra-articular injected with Borrelia spirochetes displayed increased joint swelling, cell influx, and enhanced interleukin-1β and interleukin-6 production by inflamed synovial tissue. Because both interleukin-1β and interleukin-6 are linked to the development of adaptive immune responses, we examine the function of autophagy on Borrelia induced adaptive immunity. Human peripheral blood mononuclear cells treated with autophagy inhibitors showed an increase in interleukin-17, interleukin-22, and interferon-γ production in response to exposure to Borrelia burgdorferi. Increased IL-17 production was dependent on IL-1β release but, interestingly, not on interleukin-23 production. In addition, cytokine quantitative trait loci in ATG9B modulate the Borrelia induced interleukin-17 production. Because high levels of IL-17 have been found in patients with confirmed, severe, chronic borreliosis, we propose that the modulation of autophagy may be a potential target for anti-inflammatory therapy in patients with persistent Lyme disease. PMID:27101991

  7. Human herpes virus-8-associated multicentric Castleman's disease in an HIV-positive patient presenting with relapsing and remitting hyponatraemia.

    PubMed

    Sasaki, Hiroaki; Maeda, Takuya; Hara, Yu; Osa, Morichika; Imai, Kazuo; Moriguchi, Kota; Mikita, Kei; Fujikura, Yuji; Kaida, Kenichi; Kawana, Akihiko

    2015-10-01

    We report a case of human herpes virus-8-associated multicentric Castleman's disease in an HIV-positive patient with hyponatraemia. A 65-year-old man was admitted with relapsing and remitting fever, scattered skin eruptions and hepatosplenomegaly following combination antiretroviral therapy for his HIV infection. Based on histopathological findings, he was diagnosed as having human herpes virus-8-associated multicentric Castleman's disease and was treated with four-weekly infusions of rituximab. Prior to receiving chemotherapy, we observed several suspected biomarkers of disease activity, positive correlations between plasma human herpes virus-8 viral load and the levels of plasma interleukin-6, C-reactive protein and soluble interleukin-2 receptor, and negative correlations between platelet count, albumin levels and especially serum sodium levels. We hypothesize that non-osmotic release of plasma antidiuretic hormone is a cause of hyponatraemia in human herpes virus-8-associated multicentric Castleman's disease and that relapsing and remitting hyponatraemia could be correlated with plasma human herpes virus-8 viral load. PMID:25504830

  8. Validate or falsify: Lessons learned from a microscopy method claimed to be useful for detecting Borrelia and Babesia organisms in human blood.

    PubMed

    Aase, Audun; Hajdusek, Ondrej; Øines, Øivind; Quarsten, Hanne; Wilhelmsson, Peter; Herstad, Tove K; Kjelland, Vivian; Sima, Radek; Jalovecka, Marie; Lindgren, Per-Eric; Aaberge, Ingeborg S

    2016-06-01

    Background A modified microscopy protocol (the LM-method) was used to demonstrate what was interpreted as Borrelia spirochetes and later also Babesia sp., in peripheral blood from patients. The method gained much publicity, but was not validated prior to publication, which became the purpose of this study using appropriate scientific methodology, including a control group. Methods Blood from 21 patients previously interpreted as positive for Borrelia and/or Babesia infection by the LM-method and 41 healthy controls without known history of tick bite were collected, blinded and analysed for these pathogens by microscopy in two laboratories by the LM-method and conventional method, respectively, by PCR methods in five laboratories and by serology in one laboratory. Results Microscopy by the LM-method identified structures claimed to be Borrelia- and/or Babesia in 66% of the blood samples of the patient group and in 85% in the healthy control group. Microscopy by the conventional method for Babesia only did not identify Babesia in any samples. PCR analysis detected Borrelia DNA in one sample of the patient group and in eight samples of the control group; whereas Babesia DNA was not detected in any of the blood samples using molecular methods. Conclusions The structures interpreted as Borrelia and Babesia by the LM-method could not be verified by PCR. The method was, thus, falsified. This study underlines the importance of doing proper test validation before new or modified assays are introduced. PMID:27030913

  9. Variable Major Proteins as Targets for Specific Antibodies against Borrelia miyamotoi.

    PubMed

    Wagemakers, Alex; Koetsveld, Joris; Narasimhan, Sukanya; Wickel, Melvin; Deponte, Kathleen; Bleijlevens, Boris; Jahfari, Seta; Sprong, Hein; Karan, Lyudmila S; Sarksyan, Denis S; van der Poll, Tom; Bockenstedt, Linda K; Bins, Adriaan D; Platonov, Alexander E; Fikrig, Erol; Hovius, Joppe W

    2016-05-15

    Borrelia miyamotoi is a relapsing fever spirochete in Ixodes ticks that has been recently identified as a human pathogen causing hard tick-borne relapsing fever (HTBRF) across the Northern Hemisphere. No validated serologic test exists, and current serologic assays have low sensitivity in early HTBRF. To examine the humoral immune response against B. miyamotoi, we infected C3H/HeN mice with B. miyamotoi strain LB-2001 expressing variable small protein 1 (Vsp1) and demonstrated that spirochetemia was cleared after 3 d, coinciding with anti-Vsp1 IgM production. Clearance was also observed after passive transfer of immune sera to infected SCID mice. Next, we showed that anti-Vsp1 IgG eliminates Vsp1-expressing B. miyamotoi, selecting for spirochetes expressing a variable large protein (VlpC2) resistant to anti-Vsp1. The viability of Asian isolate B. miyamotoi HT31, expressing Vlp15/16 and Vlp18, was also unaffected by anti-Vsp1. Finally, in nine HTBRF patients, we demonstrated IgM reactivity to Vsp1 in two and against Vlp15/16 in four ∼1 wk after these patients tested positive for B. miyamotoi by PCR. Our data show that B. miyamotoi is able to express various variable major proteins (VMPs) to evade humoral immunity and that VMPs are antigenic in humans. We propose that serologic tests based on VMPs are of additional value in diagnosing HTBRF. PMID:27076681

  10. Characterization of a Novel Relapsing Fever Spirochete in the Midgut, Coxal Fluid, and Salivary Glands of the Bat Tick Carios kelleyi

    PubMed Central

    Raffel, Sandra J.; Schrumpf, Merry E.; Gill, James S.; Piesman, Joseph

    2009-01-01

    Abstract Bat ticks, Carios kelleyi, from Iowa were examined for the presence of relapsing fever group borreliae. A novel spirochete was characterized by DNA sequence analysis of polymerase chain reaction amplicons for the 16S rRNA, flaB, and glpQ genes in either triturated tick pools or single ticks. All loci and the concatenated DNA sequence of 3,289 bases identified the Carios bacterium as a relapsing fever spirochete most closely related to, but distinct from, Borrelia turicatae. Spirochetes reactive with a Borrelia-specific monoclonal antibody were observed microscopically in the coxal fluid and salivary glands from one tick. These data confirm the presence of a novel species of relapsing fever spirochete in bat ticks and the potential for new enzootic foci for endemic relapsing fever that warrants further investigation. The name Borrelia johnsonii is proposed for this novel spirochete in honor of Dr. Russell C. Johnson. PMID:19281412

  11. Evidence of In Vivo Existence of Borrelia Biofilm in Borrelial Lymphocytomas.

    PubMed

    Sapi, E; Balasubramanian, K; Poruri, A; Maghsoudlou, J S; Socarras, K M; Timmaraju, A V; Filush, K R; Gupta, K; Shaikh, S; Theophilus, P A S; Luecke, D F; MacDonald, A; Zelger, B

    2016-03-01

    Lyme borreliosis, caused by the spirochete Borrelia burgdorferi sensu lato, has grown into a major public health problem. We recently identified a novel morphological form of B. burgdorferi, called biofilm, a structure that is well known to be highly resistant to antibiotics. However, there is no evidence of the existence of Borrelia biofilm in vivo; therefore, the main goal of this study was to determine the presence of Borrelia biofilm in infected human skin tissues. Archived skin biopsy tissues from borrelial lymphocytomas (BL) were reexamined for the presence of B. burgdorferi sensu lato using Borrelia-specific immunohistochemical staining (IHC), fluorescent in situ hybridization, combined fluorescent in situ hybridization (FISH)-IHC, polymerase chain reaction (PCR), and fluorescent and atomic force microscopy methods. Our morphological and histological analyses showed that significant amounts of Borrelia-positive spirochetes and aggregates exist in the BL tissues. Analyzing structures positive for Borrelia showed that aggregates, but not spirochetes, expressed biofilm markers such as protective layers of different mucopolysaccharides, especially alginate. Atomic force microscopy revealed additional hallmark biofilm features of the Borrelia/alginate-positive aggregates such as inside channels and surface protrusions. In summary, this is the first study that demonstrates the presence of Borrelia biofilm in human infected skin tissues. PMID:27141311

  12. Evidence of In Vivo Existence of Borrelia Biofilm in Borrelial Lymphocytomas

    PubMed Central

    Sapi, E.; Balasubramanian, K.; Poruri, A.; Maghsoudlou, J. S.; Socarras, K. M.; Timmaraju, A. V.; Filush, K. R.; Gupta, K.; Shaikh, S.; Theophilus, P. A. S.; Luecke, D. F.; MacDonald, A.; Zelger, B.

    2016-01-01

    Lyme borreliosis, caused by the spirochete Borrelia burgdorferi sensu lato, has grown into a major public health problem. We recently identified a novel morphological form of B. burgdorferi, called biofilm, a structure that is well known to be highly resistant to antibiotics. However, there is no evidence of the existence of Borrelia biofilm in vivo; therefore, the main goal of this study was to determine the presence of Borrelia biofilm in infected human skin tissues. Archived skin biopsy tissues from borrelial lymphocytomas (BL) were reexamined for the presence of B. burgdorferi sensu lato using Borrelia-specific immunohistochemical staining (IHC), fluorescent in situ hybridization, combined fluorescent in situ hybridization (FISH)–IHC, polymerase chain reaction (PCR), and fluorescent and atomic force microscopy methods. Our morphological and histological analyses showed that significant amounts of Borrelia-positive spirochetes and aggregates exist in the BL tissues. Analyzing structures positive for Borrelia showed that aggregates, but not spirochetes, expressed biofilm markers such as protective layers of different mucopolysaccharides, especially alginate. Atomic force microscopy revealed additional hallmark biofilm features of the Borrelia/alginate-positive aggregates such as inside channels and surface protrusions. In summary, this is the first study that demonstrates the presence of Borrelia biofilm in human infected skin tissues. PMID:27141311

  13. Chronic lymphomonocytic meningoencephalitis, oligoarthritis and erythema nodosum: report of Baggio-Yoshinari syndrome of long and relapsing evolution.

    PubMed

    Rosa Neto, Nilton Salles; Gauditano, Giancarla; Yoshinari, Natalino Hajime

    2014-01-01

    The Brazilian human borreliosis, also known as Baggio-Yoshinari Syndrome (BYS), is a tickborne disease but whose ticks do not pertain to the Ixodes ricinus complex. It is caused by Borrelia burgdorferi sensu lato microorganisms and resembles clinical and laboratory features of Lyme disease (LD). BYS is also distinguished from LD by its prolonged clinical evolution, with relapsing episodes and autoimmune dysfunction. We describe the case of a young female who, over one year, progressively presented with oligoarthritis, cognitive impairment, menigoencephalitis and erythema nodosum. Diagnosis was established by means of the clinical history and a positive serology to Borrelia burgdorferi sensu strictu. The patient received Ceftriaxone 2 g IV/day during 30 days, followed by 2 months of doxicycline 100 mg bid. Symptoms remitted and the Borrelia serology tests returned to normality. BYS is a new disease described only in Brazil, which has a raising frequency and deserves the attention from the country´s medical board because of clinical, epidemiological and laboratory differences from LD. Despite the fact that it is a hard-to-diagnose zoonosis, it is important to pursuit an early diagnosis because the symptoms respond well to antibiotics or it might be resistant to treatment and may evolve to a chronic phase with both articular and neurological sequelae. PMID:24878862

  14. Borrelia burgdorferi outer membrane protein A induces nuclear translocation of nuclear factor-kappa B and inflammatory activation in human endothelial cells.

    PubMed

    Wooten, R M; Modur, V R; McIntyre, T M; Weis, J J

    1996-11-15

    Lyme disease is caused by infection with Borrelia burgdorferi, and is characterized by bacterial persistence and inflammation in a number of host tissues. B. burgdorferi outer surface lipoproteins possess cytokine stimulatory properties that may be responsible for localized inflammation. B. burgdorferi presence is correlated with severity of disease, and the pathology of many tissues, particularly the arthritic joint, is consistent with localized cytokine production. Spirochete invasion of tissues requires interaction with and penetration of vascular endothelium, suggesting endothelial cells may participate in the inflammation of Lyme disease. In this study, outer surface protein A (OspA), a model B. burgdorferi lipoprotein, was found to be a potent stimulant of nuclear factor-kappa B (NF-kappa B) nuclear translocation in human endothelial cells, resulting in nuclear levels similar to those seen in response to known inflammatory mediators. Only the lipid-modified OspA had activity, and activity was not due to contamination with LPS. Nuclear NF-kappa B was detectable within 15 min, suggesting that OspA directly mediates NF-kappa B nuclear translocation. OspA also rapidly up-regulated endothelial cell production of several proteins whose transcription is dependent on NF-kappa B: the cytokine IL-6; the chemokine IL-8; and the adhesion molecules E-selectin, VCAM-1, and ICAM-1. The adhesion molecules were functional, as demonstrated by enhanced binding of neutrophils to OspA-stimulated endothelial monolayers. These data suggest that OspA may initiate synthesis of many proteins essential for localized inflammation via the direct activation of NF-kappa B-dependent transcription. These observations suggest that the interaction of B. burgdorferi lipoproteins with the endothelium may directly induce the inflammation responsible for the symptoms of Lyme disease. PMID:8906837

  15. Transovarial transmission of Borrelia spirochetes by Ixodes scapularis: a summary of the literature and recent observations.

    PubMed

    Rollend, Lindsay; Fish, Durland; Childs, James E

    2013-02-01

    Transovarial transmission (TOT) of Borrelia burgdorferi (sensu lato), the agent of Lyme disease, by the Ixodes persulcatus group of hard ticks (Ixodidae) has frequently been reported in the literature since the discovery of Lyme disease 1982. Evidence for and against TOT by B. burgdorferi has led to uncertainty and confusion in the literature, causing misconceptions that may have public health consequences. In this report, we review the published information implicating B. burgdorferi as a bacterium transovarially transmitted among ticks of the Ixodes persulcatus group and present new data indicating the transovarially transmitted agent is actually Borrelia miyamotoi. B. miyamotoi, first described in 1995, is antigenically and phylogenetically related to B. burgdorferi, although more closely related to the relapsing fever-group Borrelia typically transmitted by soft ticks (Argasidae). Borrelia infections of unfed larvae derived from egg clutches of wild-caught Ixodes scapularis are demonstrated to result from transovarial transmission of B. miyamotoi, not B. burgdorferi. The presence of this second Borrelia species, apparently sympatric with B. burgdorferi worldwide also may explain other confusing observations reported on Borrelia/Ixodes relationships. PMID:23238242

  16. Antigenic variation with a twist--the Borrelia story.

    PubMed

    Norris, Steven J

    2006-06-01

    A common mechanism of immune evasion in pathogenic bacteria and protozoa is antigenic variation, in which genetic or epigenetic changes result in rapid, sequential shifts in a surface-exposed antigen. In this issue of Molecular Microbiology, Dai et al. provide the most complete description to date of the vlp/vsp antigenic variation system of the relapsing fever spirochaete, Borrelia hermsii. This elaborate, plasmid-encoded system involves an expression site that can acquire either variable large protein (vlp) or variable small protein (vsp) surface lipoprotein genes from 59 different archival copies. The archival vlp and vsp genes are arranged in clusters on at least five different plasmids. Gene conversion occurs through recombination events at upstream homology sequences (UHS) found in each gene copy, and at downstream homology sequences (DHS) found periodically among the vlp/vsp archival genes. Previous studies have shown that antigenic variation in relapsing fever Borrelia not only permits the evasion of host antibody responses, but can also result in changes in neurotropism and other pathogenic properties. The vlsE antigenic variation locus of Lyme disease spirochaetes, although similar in sequence to the relapsing fever vlp genes, has evolved a completely different antigenic variation mechanism involving segmental recombination from a contiguous array of vls silent cassettes. These two systems thus appear to represent divergence from a common precursor followed by functional convergence to create two distinct antigenic variation processes. PMID:16796669

  17. Mapping the Ligand-Binding Region of Borrelia hermsii Fibronectin-Binding Protein

    PubMed Central

    Brenner, Christiane; Bomans, Katharina; Habicht, Jüri; Simon, Markus M.; Wallich, Reinhard

    2013-01-01

    Many pathogenic microorganisms express fibronectin-binding molecules that facilitate their adherence to the extracellular matrix and/or entry into mammalian cells. We have previously described a Borrelia recurrentis gene, cihC that encodes a 40-kDa surface receptor for both, fibronectin and the complement inhibitors C4bp and C1-Inh. We now provide evidence for the expression of a group of highly homologues surface proteins, termed FbpA, in three B. hermsii isolates and two tick-borne relapsing fever spirochetes, B. parkeri and B. turicatae. When expressed in Escherichia coli or B. burgdorferi, four out of five proteins were shown to selectively bind fibronectin, whereas none of five proteins were able to bind the human complement regulators, C4bp and C1-Inh. By applying deletion mutants of the B. hermsii fibronectin-binding proteins a putative high-affinity binding site for fibronectin was mapped to its central region. In addition, the fibronectin-binding proteins of B. hermsii were found to share sequence homology with BBK32 of the Lyme disease spirochete B. burgdorferi with similar function suggesting its involvement in persistence and/or virulence of relapsing fever spirochetes. PMID:23658828

  18. Global ecology and epidemiology of Borrelia garinii spirochetes

    PubMed Central

    Comstedt, Pär; Jakobsson, Tobias; Bergström, Sven

    2011-01-01

    Lyme borreliosis (LB) is a tick-transmitted infectious disease caused by Borrelia burgdorferi sensu lato (s. l.). In Europe, three different Borrelia species are the main causative agents of LB: B. burgdorferi sensu stricto (s.s.), Borrelia afzelii, and Borrelia garinii. The latter depends heavily on birds as its main reservoir hosts. In fact, birds can act both as biological carriers of Borrelia and transporters of infected ticks. The seasonal migration of many bird species not only aid in the spread of B. garinii to new foci but also influence the high level of diversity found within this species. B. garinii have been isolated not only from terrestrial birds in Europe, but also from seabirds worldwide, and homology between isolates in these two different infection cycles suggests an overlap and exchange of strains. In addition, it has been shown that birds can maintain and spread B. garinii genotypes associated with LB in humans. This review article discusses the importance of birds in the ecology and epidemiology of B. garinii spirochetes. PMID:22957111

  19. Large Scale Spatial Risk and Comparative Prevalence of Borrelia miyamotoi and Borrelia burgdorferi Sensu Lato in Ixodes pacificus

    PubMed Central

    Padgett, Kerry; Bonilla, Denise; Kjemtrup, Anne; Vilcins, Inger-Marie; Yoshimizu, Melissa Hardstone; Hui, Lucia; Sola, Milagros; Quintana, Miguel; Kramer, Vicki

    2014-01-01

    Borrelia miyamotoi is a newly described emerging pathogen transmitted to people by Ixodes species ticks and found in temperate regions of North America, Europe, and Asia. There is limited understanding of large scale entomological risk patterns of B. miyamotoi and of Borreila burgdorferi sensu stricto (ss), the agent of Lyme disease, in western North America. In this study, B. miyamotoi, a relapsing fever spirochete, was detected in adult (n = 70) and nymphal (n = 36) Ixodes pacificus ticks collected from 24 of 48 California counties that were surveyed over a 13 year period. Statewide prevalence of B. burgdorferi sensu lato (sl), which includes B. burgdorferi ss, and B. miyamotoi were similar in adult I. pacificus (0.6% and 0.8%, respectively). In contrast, the prevalence of B. burgdorferi sl was almost 2.5 times higher than B. miyamotoi in nymphal I. pacificus (3.2% versus 1.4%). These results suggest similar risk of exposure to B. burgdorferi sl and B. miyamotoi from adult I. pacificus tick bites in California, but a higher risk of contracting B. burgdorferi sl than B. miyamotoi from nymphal tick bites. While regional risk of exposure to these two spirochetes varies, the highest risk for both species is found in north and central coastal California and the Sierra Nevada foothill region, and the lowest risk is in southern California; nevertheless, tick-bite avoidance measures should be implemented in all regions of California. This is the first study to comprehensively evaluate entomologic risk for B. miyamotoi and B. burgdorferi for both adult and nymphal I. pacificus, an important human biting tick in western North America. PMID:25333277

  20. Purified human C1-esterase inhibitor is safe in acute relapses of neuromyelitis optica

    PubMed Central

    Levy, Michael

    2014-01-01

    Objective: To minimize complement-mediated damage in acute relapses of neuromyelitis optica (NMO) by adding treatment with a complement inhibitor, purified C1-esterase inhibitor, to the current standard of care (high-dose glucocorticoids). Method: We conducted an open-label phase 1b safety and proof-of-concept trial in 10 patients with NMO–immunoglobulin G seropositive NMO or NMO spectrum disease (NMOSD) who presented with acute transverse myelitis and/or optic neuritis. In addition to treating with 1 g of daily IV methylprednisolone, we infused 2,000 units of C1-esterase inhibitor daily for 3 days, beginning on day 1 of hospitalization. The primary outcome measure was safety, and the secondary efficacy measure was change in Expanded Disability Status Scale (EDSS) scores. Results: Ten patients with NMO/NMOSD were enrolled, 7 of whom presented with acute transverse myelitis and 3 with acute optic neuritis. C1-esterase inhibitor proved to be safe in all 10 patients, with no serious adverse events recorded. There were no thromboembolic events or related lab abnormalities in any of the subjects. EDSS scores dropped from a median of 4.5 on admission to 4.0 on discharge and then down to 2.5 on 30-day follow-up. All but 1 patient returned to preattack EDSS or better and only 2 patients required escalation to plasmapheresis. Conclusions: C1-esterase inhibitor is a safe add-on therapy for patients with NMO/NMOSD presenting with acute transverse myelitis and optic neuritis. Preliminary evidence suggests a promising benefit with C1-esterase inhibitor in reducing neurologic damage and improving outcomes. A placebo-controlled trial is necessary to confirm these findings. Classification of evidence: This study provides Class IV evidence that for patients with NMO with acute transverse myelitis or optic neuritis, C1-esterase inhibitor is safe and improves disability. PMID:25340061

  1. Sequence Analysis and Serological Responses against Borrelia turicatae BipA, a Putative Species-Specific Antigen

    PubMed Central

    Lopez, Job E.; Wilder, Hannah K.; Boyle, William; Drumheller, L. Brock; Thornton, Justin A.; Willeford, Bridget; Morgan, Timothy W.; Varela-Stokes, Andrea

    2013-01-01

    Background Relapsing fever spirochetes are global yet neglected pathogens causing recurrent febrile episodes, chills, nausea, vomiting, and pregnancy complications. Given these nonspecific clinical manifestations, improving diagnostic assays for relapsing fever spirochetes will allow for identification of endemic foci and expedite proper treatment. Previously, an antigen designated the Borrelia immunogenic protein A (BipA) was identified in the North American species Borrelia hermsii. Thus far, BipA appears unique to relapsing fever spirochetes. The antigen remains unidentified outside of these pathogens, while interspecies amino acid identity for BipA in relapsing fever spirochetes is only 24–36%. The current study investigated the immunogenicity of BipA in Borrelia turicatae, a species distributed in the southern United States and Latin America. Methodology/Principal Findings bipA was amplified from six isolates of Borrelia turicatae, and sequence analysis demonstrated that the gene is conserved among isolates. A tick transmission system was developed for B. turicatae in mice and a canine, two likely vertebrate hosts, which enabled the evaluation of serological responses against recombinant BipA (rBipA). These studies indicated that BipA is antigenic in both animal systems after infection by tick bite, yet serum antibodies failed to bind to B. hermsii rBipA at a detectable level. Moreover, mice continued to generate an antibody response against BipA one year after the initial infection, further demonstrating the protein's potential toward identifying endemic foci for B. turicatae. Conclusions/Significance These initial studies support the hypothesis that BipA is a spirochete antigen unique to a relapsing fever Borrelia species, and could be used to improve efforts for identifying B. turicatae endemic regions. PMID:24069498

  2. Borrelia burgdorferi Infections in the United States

    PubMed Central

    Heymann, Warren R.

    2012-01-01

    It is becoming increasingly evident that the clinical presentation of infection with Borrelia burgdorferi varies greatly between different parts of the world. A growing number of European and Asian isolates of Lyme borreliae, differing from the American strain of Borrelia burgdorferi, have been identified in several different disorders. In light of the increasing number of reports describing an association between various cutaneous disorders and infection with Borrelia burgdorferi and the controversy that still remains over where Borrelia burgdorferi is truly pathogenic in these diseases, this review of the literature assesses the significance of these reports in substantiating these hypotheses, as such associations are important both diagnostically and therapeutically. PMID:22916311

  3. Borrelia infection in Ixodes pararicinus ticks (Acari: Ixodidae) from northwestern Argentina.

    PubMed

    Nava, Santiago; Barbieri, Amalia M; Maya, Leticia; Colina, Rodney; Mangold, Atilio J; Labruna, Marcelo B; Venzal, José M

    2014-11-01

    The aim of this work was to describe for the first time the presence of Borrelia burgdorferi sensu lato infecting ticks in Argentina. Unfed specimens of Ixodes pararicinus collected from vegetation in Jujuy Province were tested for Borrelia infection by PCR targeting the gene flagellin (fla), the rrfA-rrlB intergenic spacer region (IGS) and the 16S rDNA (rrs) gene. One male and one female of I. pararicinus collected in Jujuy were found to be positive to Borrelia infection with the three molecular markers tested. Phylogenetically, the Borrelia found in I. pararicinus from Jujuy belongs to the B. burgdorferi s.l complex, and it was similar to one of the genospecies detected in I. aragaoi from Uruguay. Also, this genospecies is closely related to two genospecies known from USA, Borrelia americana and the Borrelia sp. genospecies 1. The epidemiological risk that implies the infection with Borrelia in I. paracinus ticks from Argentina appears to be low because the genospecies detected is not suspected of having clinical relevance and there are no records of Ixodes ticks biting humans in the southern cone of South America. Further studies are needed to assess accurately if there is risk of borreliosis transmitted by ticks in South America. PMID:24979685

  4. Prevalence of Borrelia burgdorferi s. l. in Ixodes ricinus ticks from four localities in Bavaria, Germany.

    PubMed

    Vögerl, Maria; Zubriková, Dana; Pfister, Kurt

    2012-01-01

    As a part of a larger survey a total of 599 Ixodes ricinus ticks collected from four locations (Neustadt an der Waldnaab, Amberg, Poppenricht and Lintach) in the north of the Upper Palatinate in Bavaria were investigated for infection with Borrelia burgdorferi sensu lato (s. l.) species using the 5S-23S intergenic spacer of rRNA gene as a target in a nested PCR (Rijpkema et al., 1995) and a sequencing method. Overall, 15.8% ticks were infected with B. burgdorferi s. I. Borrelia afzelii (43.1%) was the predominant genospecies, followed by Borrelia valaisiana (14.7%), Borrelia garinii (13.7%) and Borrelia burgdorferi sensu stricto (6.3%). Also Borrelia spielmanii was found (1.1%). Of the infected ticks, 21.1% harbored multiple infections with B. burgdorferi s. I. The highest number of infected ticks was found in Amberg (22.5%) and the lowest number in Neustadt an der Waldnaab (11.9%). In Poppenricht and Lintach, the numbers of infected ticks were 12% and 18.7%, respectively. Human pathogenic Borrelia species were found to be prevalent at each study site thus representing the potential risk for people living and visiting these areas. PMID:23045802

  5. Mapping human risk of infection with Borrelia burgdorferi sensu lato, the agent of Lyme borreliosis, in a periurban forest in France.

    PubMed

    Vourc'h, G; Abrial, D; Bord, S; Jacquot, M; Masséglia, S; Poux, V; Pisanu, B; Bailly, X; Chapuis, J-L

    2016-07-01

    Lyme borreliosis is a major zoonosis in Europe, with estimates of over 26,000 cases per year in France alone. The etiological agents are spirochete bacteria that belong to the Borrelia burgdorferi sensu lato (s. l.) complex and are transmitted by hard ticks among a large range of vertebrate hosts. In Europe, the tick Ixodes ricinus is the main vector. In the absence of a vaccine and given the current difficulties to diagnose and treat chronic Lyme syndromes, there is urgent need for prevention. In this context, accurate information on the spatial patterns of risk of exposure to ticks is of prime importance for public health. The objective of our study was to provide a snapshot map of the risk of human infection with B. burgdorferi s. l. pathogens in a periurban forest at a high resolution, and to analyze the factors that contribute to variation in this risk. Field monitoring took place over three weeks in May 2011 in the suburban Sénart forest (3,200ha; southeast of Paris), which receives over 3 million people annually. We sampled ticks over the entire forest area (from 220 forest stands with a total area of 35,200m(2)) and quantified the density of questing nymphs (DON), the prevalence of infection among nymphs (NIP), and the density of infected nymphs (DIN), which is the most important predictor of the human risk of Lyme borreliosis. For each of these response variables, we explored the relative roles of weather (saturation deficit), hosts (abundance indices of ungulates and Tamias sibiricus, an introduced rodent species), vegetation and forest cover, superficial soil composition, and the distance to forest roads. In total, 19,546 questing nymphs were collected and the presence of B. burgdorferi s. l. was tested in 3,903 nymphs by qPCR. The mean DON was 5.6 nymphs per 10m(2) (standard deviation=10.4) with an average NIP of 10.1% (standard deviation=0.11). The highest DIN was 8.9 infected nymphs per 10m(2), with a mean of 0.59 (standard deviation=0.6). Our

  6. TLR1/TLR2 heterodimers play an important role in the recognition of Borrelia spirochetes.

    PubMed

    Oosting, Marije; Ter Hofstede, Hadewych; Sturm, Patrick; Adema, Gosse J; Kullberg, Bart-Jan; van der Meer, Jos W M; Netea, Mihai G; Joosten, Leo A B

    2011-01-01

    After infection with Borrelia species, the risk for developing Lyme disease varies significantly between individuals. Recognition of Borrelia by the immune system is mediated by pattern recognition receptors (PRRs), such as TLRs. While TLR2 is the main recognition receptor for Borrelia spp., little is known about the role of TLR1 and TLR6, which both can form functionally active heterodimers with TLR2. Here we investigated the recognition of Borrelia by both murine and human TLR1 and TLR6. Peritoneal macrophages from TLR1- and TLR6- gene deficient mice were isolated and exposed to Borrelia. Human PBMCs were stimulated with Borrelia with or without specific TLR1 and TLR6 blocking using specific antibodies. Finally, the functional consequences of TLR polymorphisms on Borrelia-induced cytokine production were assessed. Splenocytes isolated from both TLR1-/- and TLR6-/- mice displayed a distorted Th1/Th2 cytokine balance after stimulation with B.burgdorferi, while no differences in pro-inflammatory cytokine production were observed. In contrast, blockade of TLR1 with specific neutralizing antibodies led to decreased cytokine production by human PBMCs after exposure to B.burgdorferi. Blockade of human TLR6 did not lead to suppression of cytokine production. When PBMCs from healthy individuals bearing polymorphisms in TLR1 were exposed to B.burgdorferi, a remarkably decreased in vitro cytokine production was observed in comparison to wild-type controls. TLR6 polymorphisms lead to a minor modified cytokine production. This study indicates a dominant role for TLR1/TLR2 heterodimers in the induction of the early inflammatory response by Borrelia spirochetes in humans. PMID:21998742

  7. Borrelia-induced cytokine production is mediated by spleen tyrosine kinase (Syk) but is Dectin-1 and Dectin-2 independent.

    PubMed

    Oosting, Marije; Buffen, Kathrin; Cheng, Shih-Chin; Verschueren, Ineke C; Koentgen, Frank; van de Veerdonk, Frank L; Netea, Mihai G; Joosten, Leo A B

    2015-12-01

    Although it is known that Borrelia species express sugar-like structures on their outer surface, not much is known about the role of these structures in immune recognition by host cells. Fungi, like Candida albicans, are mainly recognized by C-type lectin receptors, in specific Dectin-1 and Dectin-2. In this study we assessed the role of Dectin-1 and Dectin-2 in the recognition process of Borrelia spirochetes. Using specific inhibitors against these receptors on human cells did not influenced cytokine production. Individuals carrying a SNP leading to an early stop codon in the DECTIN-1 gene also did not lead to differential induction of Borrelia-dependent cytokines. After injection of live Borrelia into knee joints of Dectin-2 deficient mice a trend towards lower inflammation was observed. Inhibition of Syk in human cells resulted in lower cytokine production after Borrelia stimulation. In conclusion, Dectin-1 and Dectin-2 seem not to play a major role in Borrelia recognition or Borrelia-induced inflammation. However, Syk seems to be involved in Borrelia-induced cytokine production. PMID:26297607

  8. Tickborne Relapsing Fever, Bitterroot Valley, Montana, USA

    PubMed Central

    Christensen, Joshua; Fischer, Robert J.; McCoy, Brandi N.; Raffel, Sandra J.

    2015-01-01

    In July 2013, a resident of the Bitterroot Valley in western Montana, USA, contracted tickborne relapsing fever caused by an infection with the spirochete Borrelia hermsii. The patient’s travel history and activities before onset of illness indicated a possible exposure on his residential property on the eastern side of the valley. An onsite investigation of the potential exposure site found the vector, Ornithodoros hermsi ticks, and 1 chipmunk infected with spirochetes, which on the basis of multilocus sequence typing were identical to the spirochete isolated from the patient. Field studies in other locations found additional serologic evidence and an infected tick that demonstrated a wider distribution of spirochetes circulating among the small mammal populations. Our study demonstrates that this area of Montana represents a previously unrecognized focus of relapsing fever and poses a risk for persons of acquiring this tickborne disease. PMID:25625502

  9. A Novel Surface Antigen of Relapsing Fever Spirochetes Can Discriminate between Relapsing Fever and Lyme Borreliosis▿ † ‡

    PubMed Central

    Lopez, Job E.; Schrumpf, Merry E.; Nagarajan, Vijayaraj; Raffel, Sandra J.; McCoy, Brandi N.; Schwan, Tom G.

    2010-01-01

    In a previous immunoproteome analysis of Borrelia hermsii, candidate antigens that bound IgM antibodies from mice and patients infected with relapsing fever spirochetes were identified. One candidate that was identified is a hypothetical protein with a molecular mass of 57 kDa that we have designated Borrelia immunogenic protein A (BipA). This protein was further investigated as a potential diagnostic antigen for B. hermsii given that it is absent from the Borrelia burgdorferi genome. The bipA locus was amplified and sequenced from 39 isolates of B. hermsii that had been acquired from western North America. bipA was also expressed as a recombinant fusion protein. Serum samples from mice and patients infected with B. hermsii or B. burgdorferi were used to confirm the immunogenicity of the recombinant protein in patients infected with relapsing fever spirochetes. Lastly, in silico and experimental analysis indicated that BipA is a surface-exposed lipoprotein in B. hermsii. These findings enhance the capabilities of diagnosing infection with relapsing fever spirochetes. PMID:20147497

  10. Louse-borne relapsing fever in a refugee from Somalia arriving in Belgium.

    PubMed

    Darcis, Gilles; Hayette, Marie-Pierre; Bontems, Sebastien; Sauvage, Anne-Sophie; Meuris, Christelle; Van Esbroeck, Marjan; Leonard, Philippe

    2016-03-01

    We report a case of louse-borne relapsing fever (LBRF) in a refugee from Somalia who had arrived in Belgium a few days earlier. He complained of myalgia and secondarily presented fever. Blood smears revealed spirochetes later identified as Borrelia recurrentis. LBRF should be considered in countries hosting refugees, particularly those who transit through endemic regions. PMID:27356309

  11. Recombinant constructs of Borrelia burgdorferi

    DOEpatents

    Dattwyler, Raymond J.; Gomes-Solecki, Maria J. C.; Luft, Benjamin J.; Dunn, John J.

    2007-02-20

    Novel chimeric nucleic acids, encoding chimeric Borrelia proteins comprising OspC or an antigenic fragment thereof and OspA or an antigenic fragment thereof, are disclosed. Chimeric proteins encoded by the nucleic acid sequences are also disclosed. The chimeric proteins are useful as vaccine immunogens against Lyme borreliosis, as well as for immunodiagnostic reagents.

  12. Transmission Dynamics of Borrelia turicatae from the Arthropod Vector

    PubMed Central

    Boyle, William K.; Wilder, Hannah K.; Lawrence, Amanda M.; Lopez, Job E.

    2014-01-01

    Background With the global distribution, morbidity, and mortality associated with tick and louse-borne relapsing fever spirochetes, it is important to understand the dynamics of vector colonization by the bacteria and transmission to the host. Tick-borne relapsing fever spirochetes are blood-borne pathogens transmitted through the saliva of soft ticks, yet little is known about the transmission capability of these pathogens during the relatively short bloodmeal. This study was therefore initiated to understand the transmission dynamics of the relapsing fever spirochete Borrelia turicatae from the vector Ornithodoros turicata, and the subsequent dissemination of the bacteria upon entry into murine blood. Methodology/Principal Findings To determine the minimum number of ticks required to transmit spirochetes, one to three infected O. turicata were allowed to feed to repletion on individual mice. Murine infection and dissemination of the spirochetes was evaluated by dark field microscopy of blood, quantitative PCR, and immunoblotting against B. turicatae protein lysates and a recombinant antigen, the Borrelia immunogenic protein A. Transmission frequencies were also determined by interrupting the bloodmeal 15 seconds after tick attachment. Scanning electron microscopy (SEM) was performed on infected salivary glands to detect spirochetes within acini lumen and excretory ducts. Furthermore, spirochete colonization and dissemination from the bite site was investigated by feeding infected O. turicata on the ears of mice, removing the attachment site after engorment, and evaluating murine infection. Conclusion/Significance Our findings demonstrated that three ticks provided a sufficient infectious dose to infect nearly all animals, and B. turicatae was transmitted within seconds of tick attachment. Spirochetes were also detected in acini lumen of salivary glands by SEM. Upon host entry, B. turicatae did not require colonization of the bite site to establish murine

  13. Sylvatic maintenance of Borrelia burgdorferi (Spirochaetales) in Northern California: untangling the web of transmission.

    PubMed

    Brown, R N; Peot, M A; Lane, R S

    2006-07-01

    Lyme borreliosis is associated with several genospecies of Borrelia burgdorferi sensu lato (s.l.) (Spirochaetales), but human disease has been associated only with Borrelia burgdorferi sensu stricto (s.s.) Johnson, Schmid, Hyde, Steigerwalt & Brenner in the western United States. Restriction fragment length polymorphism (RFLP) analysis of rrf-rrl amplicons from 124 tick and mammalian isolates from various habitats yielded 13 RFLP patterns. Of these patterns, six were patterns previously associated either with Borrelia bissettii Postic, Marti Ras, Lane, Hendson & Baranton or Borrelia burgdorferi s.s., and the remaining seven patterns belonged to diverse and previously uncharacterized Borrelia spp. Uncharacterized Borrelia spp. were cultured most frequently from Ixodes spinipalpis Hadwen & Nuttall and California kangaroo rats, Dipodomys californicus Merriam, inhabiting grasslands, and B. bissettii from I. spinipalpis and dusky-footed woodrats, Neotoma fuscipes Baird, associated with oak woodlands or chaparral. B. burgdorferi s.s. typically was isolated from host-seeking Ixodes pacificus Cooley & Kohls collected in dense oak woodlands, woodland-grass, or redwood forests. Although some isolates of B. burgdorferi s.s. were cultured from woodrats, there was no clear association of this human pathogen with any vertebrate host. These findings, along with recent evidence indicating that the western gray squirrel, Sciurus griseus Ord, may be an important reservoir of B. burgdorferi s.s. in Californian oak woodlands, suggest that our earlier hypothesis implicating an enzootic cycle involving woodrats and I. spinipalpis is insufficient to account for observed patterns of infection in nature. PMID:16892634

  14. "Candidatus Borrelia kalaharica" Detected from a Febrile Traveller Returning to Germany from Vacation in Southern Africa

    PubMed Central

    Wächtler, Martin; Margos, Gabriele; Ruske, Sabine; Jung, Jette; Löscher, Thomas; Wendtner, Clemens; Wieser, Andreas

    2016-01-01

    A 26 year-old female patient presented to the Tropical Medicine outpatient unit of the Ludwig Maximilians-University in Munich with febrile illness after returning from Southern Africa, where she contracted a bite by a large mite-like arthropod, most likely a soft-tick. Spirochetes were detected in Giemsa stained blood smears and treatment was started with doxycycline for suspected tick-borne relapsing fever. The patient eventually recovered after developing a slight Jarisch-Herxheimer reaction during therapy. PCR reactions performed from EDTA-blood revealed a 16S rRNA sequence with 99.4% similarity to both, Borrelia duttonii, and B. parkeri. Further sequences obtained from the flagellin gene (flaB) demonstrated genetic distances of 0.066 and 0.097 to B. parkeri and B. duttonii, respectively. Fragments of the uvrA gene revealed genetic distance of 0.086 to B. hermsii in genetic analysis and only distant relations with classic Old World relapsing fever species. This revealed the presence of a novel species of tick-borne relapsing fever spirochetes that we propose to name “Candidatus Borrelia kalaharica”, as it was contracted from an arthropod bite in the Kalahari Desert belonging to both, Botswana and Namibia, a region where to our knowledge no relapsing fever has been described so far. Interestingly, the novel species shows more homology to New World relapsing fever Borrelia such as B. parkeri or B. hermsii than to known Old World species such as B. duttonii or B. crocidurae. PMID:27031729

  15. "Candidatus Borrelia kalaharica" Detected from a Febrile Traveller Returning to Germany from Vacation in Southern Africa.

    PubMed

    Fingerle, Volker; Pritsch, Michael; Wächtler, Martin; Margos, Gabriele; Ruske, Sabine; Jung, Jette; Löscher, Thomas; Wendtner, Clemens; Wieser, Andreas

    2016-03-01

    A 26 year-old female patient presented to the Tropical Medicine outpatient unit of the Ludwig Maximilians-University in Munich with febrile illness after returning from Southern Africa, where she contracted a bite by a large mite-like arthropod, most likely a soft-tick. Spirochetes were detected in Giemsa stained blood smears and treatment was started with doxycycline for suspected tick-borne relapsing fever. The patient eventually recovered after developing a slight Jarisch-Herxheimer reaction during therapy. PCR reactions performed from EDTA-blood revealed a 16S rRNA sequence with 99.4% similarity to both, Borrelia duttonii, and B. parkeri. Further sequences obtained from the flagellin gene (flaB) demonstrated genetic distances of 0.066 and 0.097 to B. parkeri and B. duttonii, respectively. Fragments of the uvrA gene revealed genetic distance of 0.086 to B. hermsii in genetic analysis and only distant relations with classic Old World relapsing fever species. This revealed the presence of a novel species of tick-borne relapsing fever spirochetes that we propose to name "Candidatus Borrelia kalaharica", as it was contracted from an arthropod bite in the Kalahari Desert belonging to both, Botswana and Namibia, a region where to our knowledge no relapsing fever has been described so far. Interestingly, the novel species shows more homology to New World relapsing fever Borrelia such as B. parkeri or B. hermsii than to known Old World species such as B. duttonii or B. crocidurae. PMID:27031729

  16. Comparison of Growth of Borrelia afzelii, Borrelia garinii, and Borrelia burgdorferi Sensu Stricto at Five Different Temperatures

    PubMed Central

    Veinović, Gorana; Ružić-Sabljić, Eva; Strle, Franc; Cerar, Tjaša

    2016-01-01

    Lyme borreliosis is caused by the spirochete Borrelia burgdorferi sensu lato, a fastidious bacterium that replicates slowly and requires special conditions to grow in the laboratory. Borrelia isolation from clinical material is a golden standard for microbiological diagnosis of borrelial infection. Important factors that affect in vitro borrelia growth are temperature of incubation and number of borrelia cells in the sample. The aim of the study was to assess the influence of temperature on borrelia growth and survival by evaluation and comparison of growth of 31 different borrelia strains at five different temperatures and to determine the influence of different inoculums on borrelia growth at different temperatures. Borreliae were cultured in the MKP medium; the initial and final number of spirochetes was determined by dark field microscopy using Neubauer counting chamber. The growth of borrelia was defined as final number of cells/mL after three days of incubation. For all three Borrelia species, the best growth was found at 33°C, followed by 37, 28, and 23°C, while no growth was detected at 4°C (P<0.05). The growth of B. afzelii species was weaker in comparison to the other two species at 23, 28, 33 and 37°C (P<0.05), respectively. There was no statistically significant difference between the growth of B. garinii and B. burgdorferi sensu stricto at 28, 33, and 37°C (P>0.05), respectively. Inoculum had statistically significant influence on growth of all three Borrelia species at all tested temperatures except at 4°C. PMID:27310556

  17. Comparison of Growth of Borrelia afzelii, Borrelia garinii, and Borrelia burgdorferi Sensu Stricto at Five Different Temperatures.

    PubMed

    Veinović, Gorana; Ružić-Sabljić, Eva; Strle, Franc; Cerar, Tjaša

    2016-01-01

    Lyme borreliosis is caused by the spirochete Borrelia burgdorferi sensu lato, a fastidious bacterium that replicates slowly and requires special conditions to grow in the laboratory. Borrelia isolation from clinical material is a golden standard for microbiological diagnosis of borrelial infection. Important factors that affect in vitro borrelia growth are temperature of incubation and number of borrelia cells in the sample. The aim of the study was to assess the influence of temperature on borrelia growth and survival by evaluation and comparison of growth of 31 different borrelia strains at five different temperatures and to determine the influence of different inoculums on borrelia growth at different temperatures. Borreliae were cultured in the MKP medium; the initial and final number of spirochetes was determined by dark field microscopy using Neubauer counting chamber. The growth of borrelia was defined as final number of cells/mL after three days of incubation. For all three Borrelia species, the best growth was found at 33°C, followed by 37, 28, and 23°C, while no growth was detected at 4°C (P<0.05). The growth of B. afzelii species was weaker in comparison to the other two species at 23, 28, 33 and 37°C (P<0.05), respectively. There was no statistically significant difference between the growth of B. garinii and B. burgdorferi sensu stricto at 28, 33, and 37°C (P>0.05), respectively. Inoculum had statistically significant influence on growth of all three Borrelia species at all tested temperatures except at 4°C. PMID:27310556

  18. Serologic Evidence for Borrelia hermsii Infection in Rodents on Federally Owned Recreational Areas in California

    PubMed Central

    Payne, Jessica R.; Schwan, Tom G.

    2013-01-01

    Abstract Tick-borne relapsing fever (TBRF) is endemic in mountainous regions of the western United States. In California, the principal agent is the spirochete Borrelia hermsii, which is transmitted by the argasid tick Ornithodoros hermsi. Humans are at risk of TBRF when infected ticks leave an abandoned rodent nest in quest of a blood meal. Rodents are the primary vertebrate hosts for B. hermsii. Sciurid rodents were collected from 23 sites in California between August, 2006, and September, 2008, and tested for serum antibodies to B. hermsii by immunoblot using a whole-cell sonicate and a specific antigen, glycerophosphodiester phosphodiesterase (GlpQ). Antibodies were detected in 20% of rodents; seroprevalence was highest (36%) in chipmunks (Tamias spp). Seroprevalence in chipmunks was highest in the Sierra Nevada (41%) and Mono (43%) ecoregions and between 1900 and 2300 meters elevation (43%). The serological studies described here are effective in implicating the primary vertebrate hosts involved in the maintenance of the ticks and spirochetes in regions endemic for TBRF. PMID:23488454

  19. Delayed Invasion of the Kidney and Brain by Borrelia crocidurae in Plasminogen-Deficient Mice

    PubMed Central

    Nordstrand, Annika; Shamaei-Tousi, Alireza; Ny, Annelii; Bergström, Sven

    2001-01-01

    Borrelia crocidurae is an etiologic agent of relapsing fever in Africa and is transmitted to humans by the bite of soft ticks of the genus Ornithodoros. The role of the plasminogen (Plg) activation system for the pathogenicity of B. crocidurae was investigated by infection of Plg-deficient (plg−/−) and Plg wild-type (plg+/+) mice. No differences in spirochetemia were observed between the plg−/− and plg+/+ mice. However, signs indicative of brain invasion, such as neurological symptoms and/or histopathological changes, were more common in plg+/+ mice. Quantitative immunohistochemical analysis demonstrated infection of spirochetes in kidney interstitium and brain as soon as 2 days postinoculation. Lower numbers of extravascular spirochetes in plg−/− mice during the first days of infection suggested a less efficient invasion mechanism in these mice than in the plg+/+ mice. The invasion of the kidneys in plg−/− mice produced no significant inflammation, as seen by quantitative immunohistochemistry of the CD45 common leukocyte marker. However, significant kidney inflammation was observed with infection in the plg+/+ mice. In brain, inflammation was more severe in plg+/+ mice than in plg−/− mice, and the numbers of CD45+ cells increased significantly with duration of infection in the plg+/+ mice. The results show that invasion of brain and kidney occurs as early as 2 days after inoculation. Also, Plg is not required for establishment of spirochetemia by the organism, whereas it is involved in the invasion of organs. PMID:11500461

  20. Serologic evidence for Borrelia hermsii infection in rodents on federally owned recreational areas in California.

    PubMed

    Fritz, Curtis L; Payne, Jessica R; Schwan, Tom G

    2013-06-01

    Tick-borne relapsing fever (TBRF) is endemic in mountainous regions of the western United States. In California, the principal agent is the spirochete Borrelia hermsii, which is transmitted by the argasid tick Ornithodoros hermsi. Humans are at risk of TBRF when infected ticks leave an abandoned rodent nest in quest of a blood meal. Rodents are the primary vertebrate hosts for B. hermsii. Sciurid rodents were collected from 23 sites in California between August, 2006, and September, 2008, and tested for serum antibodies to B. hermsii by immunoblot using a whole-cell sonicate and a specific antigen, glycerophosphodiester phosphodiesterase (GlpQ). Antibodies were detected in 20% of rodents; seroprevalence was highest (36%) in chipmunks (Tamias spp). Seroprevalence in chipmunks was highest in the Sierra Nevada (41%) and Mono (43%) ecoregions and between 1900 and 2300 meters elevation (43%). The serological studies described here are effective in implicating the primary vertebrate hosts involved in the maintenance of the ticks and spirochetes in regions endemic for TBRF. PMID:23488454

  1. Tick-Borne Relapsing Fever Outbreak Among a High School Football Team at an Outdoor Education Camping Trip, Arizona, 2014.

    PubMed

    Jones, Jefferson M; Hranac, Carter R; Schumacher, Mare; Horn, Kim; Lee, Darlene M; Terriquez, Joel; Engelthaler, David M; Peoples, Marie; Corrigan, Jennifer; Replogle, Adam; Souders, Nina; Komatsu, Kenneth K; Nieto, Nathan C

    2016-09-01

    During August 2014, five high school students who had attended an outdoor education camp were hospitalized with a febrile illness, prompting further investigation. Ten total cases of tick-borne relapsing fever (TBRF) were identified-six cases confirmed by culture or visualization of spirochetes on blood smear and four probable cases with compatible symptoms (attack rate: 23%). All patients had slept in the campsite's only cabin. Before the camp, a professional pest control company had rodent proofed the cabin, but no acaricides had been applied. Cabin inspection after the camp found rodents and Ornithodoros ticks, the vector of TBRF. Blood samples from a chipmunk trapped near the cabin and from patients contained Borrelia hermsii with identical gene sequences (100% over 630 base pairs). Health departments in TBRF endemic areas should consider educating cabin owners and pest control companies to apply acaricides during or following rodent proofing, because ticks that lack rodents for a blood meal might feed on humans. PMID:27430539

  2. Chemotherapy and recombinant human granulocyte colony-stimulating factor primed donor leukocyte infusion for treatment of relapse after allogeneic bone marrow transplantation.

    PubMed

    Sica, S; Di Mario, A; Salutari, P; Rutella, S; Chiusolo, P; Rumi, C; Menichella, G; D'Onofrio, G; Leone, G

    1995-09-01

    Two patients affected by acute leukemia relapsed 10 and 12 months respectively after allogeneic bone marrow transplantation. They were treated with aggressive chemotherapy and then infused with HLA-identical donor leukocytes (DLI) collected after recombinant human granulocyte colony-stimulating factor (rhG-CSF) administration. A total of 5.6 and 6.3 x 10(6)/kg CD34+ cells, 2.7 and 3.0 x 10(4)/kg CFU-GM, 4.7 and 4.4 x 10(8)/kg MNC, 4.6 and 3.9 x 10(9)/kg PMN respectively were infused. Both patients achieved complete remission (CR) and complete chimerism was re-established. One patient developed grade IV acute graft-versus-host disease of the liver requiring immunosuppression and he died in CR from disseminated aspergillosis, 7 months after chemotherapy; one patient is alive in relapse 12 months after treatment. PMID:8535325

  3. Discovery and Targeted Proteomics on Cutaneous Biopsies Infected by Borrelia to Investigate Lyme Disease*

    PubMed Central

    Schnell, Gilles; Boeuf, Amandine; Westermann, Benoît; Jaulhac, Benoît; Lipsker, Dan; Carapito, Christine; Boulanger, Nathalie; Ehret-Sabatier, Laurence

    2015-01-01

    Lyme disease is the most important vector-borne disease in the Northern hemisphere and represents a major public health challenge with insufficient means of reliable diagnosis. Skin is rarely investigated in proteomics but constitutes in the case of Lyme disease the key interface where the pathogens can enter, persist, and multiply. Therefore, we investigated proteomics on skin samples to detect Borrelia proteins directly in cutaneous biopsies in a robust and specific way. We first set up a discovery gel prefractionation-LC-MS/MS approach on a murine model infected by Borrelia burgdorferi sensu stricto that allowed the identification of 25 Borrelia proteins among more than 1300 mouse proteins. Then we developed a targeted gel prefractionation-LC-selected reaction monitoring (SRM) assay to detect 9/33 Borrelia proteins/peptides in mouse skin tissue samples using heavy labeled synthetic peptides. We successfully transferred this assay from the mouse model to human skin biopsies (naturally infected by Borrelia), and we were able to detect two Borrelia proteins: OspC and flagellin. Considering the extreme variability of OspC, we developed an extended SRM assay to target a large set of variants. This assay afforded the detection of nine peptides belonging to either OspC or flagellin in human skin biopsies. We further shortened the sample preparation and showed that Borrelia is detectable in mouse and human skin biopsies by directly using a liquid digestion followed by LC-SRM analysis without any prefractionation. This study thus shows that a targeted SRM approach is a promising tool for the early direct diagnosis of Lyme disease with high sensitivity (<10 fmol of OspC/mg of human skin biopsy). PMID:25713121

  4. Interaction between Borrelia burgdorferi and endothelium in vitro.

    PubMed

    Szczepanski, A; Furie, M B; Benach, J L; Lane, B P; Fleit, H B

    1990-05-01

    During the pathogenesis of Lyme disease, Borrelia burgdorferi spreads hematogenously from the site of a tick bite to several tissues throughout the body. The specific mechanism of spirochete emigration is presently unknown. Using cultured human umbilical vein endothelial cells, we found that Borrelia burgdorferi bound to the endothelial cells and to the subendothelial matrix. Low passage isolates adhered 22-30-fold greater than a strain maintained in culture continuously. Spirochete binding to subendothelial matrix was inhibited 48-63% by pretreatment of the matrix with anti-fibronectin antiserum. Spirochete migration across endothelial monolayers cultured on amniotic membrane was increased when the monolayers were damaged by chemical or physical means. Electron microscopic examination of spirochete-endothelial interactions demonstrated the presence of spirochetes in the intercellular junctions between endothelial cells as well as beneath the monolayers. Scanning electron microscopy identified a mechanism of transendothelial migration whereby spirochetes pass between cells into the amniotic membrane at areas where subendothelium is exposed. PMID:2332509

  5. Imbalanced presence of Borrelia burgdorferi s.l. multilocus sequence types in clinical manifestations of Lyme borreliosis.

    PubMed

    Coipan, E Claudia; Jahfari, Setareh; Fonville, Manoj; Oei, G Anneke; Spanjaard, Lodewijk; Takumi, Katsuhisa; Hovius, Joppe W R; Sprong, Hein

    2016-08-01

    In this study we used typing based on the eight multilocus sequence typing scheme housekeeping genes (MLST) and 5S-23S rDNA intergenic spacer (IGS) to explore the population structure of Borrelia burgdorferi sensu lato isolates from patients with Lyme borreliosis (LB) and to test the association between the B. burgdorferi s.l. sequence types (ST) and the clinical manifestations they cause in humans. Isolates of B. burgdorferi from 183 LB cases across Europe, with distinct clinical manifestations, and 257 Ixodes ricinus lysates from The Netherlands, were analyzed for this study alone. For completeness, we incorporated in our analysis also 335 European B. burgdorferi s.l. MLST profiles retrieved from literature. Borrelia afzelii and Borrelia bavariensis were associated with human cases of LB while Borrelia garinii, Borrelia lusitaniae and Borrelia valaisiana were associated with questing I. ricinus ticks. B. afzelii was associated with acrodermatitis chronica atrophicans, while B. garinii and B. bavariensis were associated with neuroborreliosis. The samples in our study belonged to 251 different STs, of which 94 are newly described, adding to the overall picture of the genetic diversity of Borrelia genospecies. The fraction of STs that were isolated from human samples was significantly higher for the genospecies that are known to be maintained in enzootic cycles by mammals (B. afzelii, B. bavariensis, and Borrelia spielmanii) than for genospecies that are maintained by birds (B. garinii and B. valaisiana) or lizards (B. lusitaniae). We found six multilocus sequence types that were significantly associated to clinical manifestations in humans and five IGS haplotypes that were associated with the human LB cases. While IGS could perform just as well as the housekeeping genes in the MLST scheme for predicting the infectivity of B. burgdorferi s.l., the advantage of MLST is that it can also capture the differential invasiveness of the various STs. PMID:27125686

  6. Activation of human monocytic cells by Treponema pallidum and Borrelia burgdorferi lipoproteins and synthetic lipopeptides proceeds via a pathway distinct from that of lipopolysaccharide but involves the transcriptional activator NF-kappa B.

    PubMed Central

    Norgard, M V; Arndt, L L; Akins, D R; Curetty, L L; Harrich, D A; Radolf, J D

    1996-01-01

    There is increasing evidence that lipoproteins of Treponema pallidum and Borrelia burgdorferi are key inflammatory mediators during syphilis and Lyme disease. A principal objective of the present study was to identify more precisely similarities and divergences among lipopolysaccharide (LPS)- and lipoprotein-lipopeptide-induced immune cell signaling events. Like LPS, purified native B. burgdorferi OspA and synthetic analogs of OspA, OspB, and two T. pallidum lipoproteins (Tpp47 and Tpp17) all induced NF-kappa B translocation in THP-1 human monocytoid cells. Acylation of OspA and the synthetic peptides was requisite for cell activation. Polymyxin B abrogated only the response to LPS. By using 70Z/3-derived pre-B-cell lines either lacking or expressing human CD14 (the LPS receptor), it was observed that expression of human CD14 imparted responsiveness to LPS but not to OspA or spirochetal lipopeptides (assessed by induction of NF-kappa B and expression of surface immunoglobulin M). Finally, the biological relevance of the observation that T. pallidum lipoproteins-lipopeptides induce both NF-kappa B and cytokine production in monocytes was supported by the ability of the synthetic analogs to promote human immunodeficiency virus replication in chronically infected U1 monocytoid cells; these observations also suggest a potential mechanism whereby a syphilitic chancre can serve as a cofactor for human immunodeficiency virus transmission. The combined data lend additional support to the proposal that spirochetal lipoproteins and LPS initiate monocyte activation via different cell surface events but that the signaling pathways ultimately converge to produce qualitatively similar cellular responses. PMID:8751937

  7. Columbian black-tailed deer (Odocoileus hemionus columbianus) as hosts for Borrelia spp. in northern California.

    PubMed

    Lane, Robert S; Mun, Jeomhee; Parker, John M; White, Marshall

    2005-01-01

    The prevalence of infection of Columbian black-tailed deer (Odocoileus hemionus columbianus) with Borrelia spp. was evaluated in an area of northwestern California (USA) where Lyme disease is endemic and the relapsing-fever group spirochete Borrelia coriaceae is enzootic, and in a far-removed comparison area having a disparate climate and lower density of vector ticks. Blood samples collected from both deer herds in 1987, 1988, and from 2000-02 were assayed for borrelial infection with microscopic and molecular methods. Serum specimens from two (5%) of 39 deer from the Dye Creek Preserve in Tehama County versus 13 (20%) of 64 animals from the Hopland Research and Extension Center (HREC) in Mendocino County, California were polymerase chain reaction (PCR) test positive for B. burgdorferi sensu lato. DNA sequencing analyses revealed that eight animals were infected with B. bissettii, six with three unclassified genotypes, and one with B. burgdorferi sensu stricto. One serum sample (2%) from HREC was positive for a relapsing-fever group spirochete that had a 16S rRNA sequence homology of 99% with the C053 type strain of B. coriaceae. Spirochetes undetermined to geno-species were detected in thick-blood drops prepared from three (8%) of 36 deer from the HREC by direct immunofluorescence. Adults of the hippoboscid flies Lipoptena depressa (n=73) and Neolipoptena ferrisi (n=24), the Pacific Coast tick (Dermacentor occidentalis) (n=22), and the western black-legged tick (Ixodes pacificus) (n=1) that had been removed from deer from both study areas in 2002 were PCR test negative for borreliae. The occurrence of diverse borreliae in deer from northern California confounds and, consequently, reduces the utility of borrelial serosurveys for detecting specific genospecies, unless they are complemented by more specific assays (e.g., immunoblotting, PCR/sequencing analysis). PMID:15827217

  8. Challenging complications of treatment – human herpes virus 6 encephalitis and pneumonitis in a patient undergoing autologous stem cell transplantation for relapsed Hodgkin's disease: a case report

    PubMed Central

    Bommer, Martin; Pauls, Sandra; Greiner, Jochen

    2009-01-01

    Background Reactivation of human herpesvirus 6 (HHV-6) occurs frequently in patients after allogeneic stem cell transplantation and is associated with bone-marrow suppression, enteritis, pneumonitis, pericarditis and also encephalitis. After autologous stem cell transplantation or intensive polychemotherapy HHV-6 reactivation is rarely reported. Case report This case demonstrates a severe symptomatic HHV-6 infection with encephalitis and pneumonitis after autologous stem cell transplantation of a patient with relapsed Hodgkin's disease. Conclusion Careful diagnostic work up in patients with severe complications after autologous stem cell transplantation is mandatory to identify uncommon infections. PMID:19619326

  9. Variation in Human Cytochrome P-450 Drug-Metabolism Genes: A Gateway to the Understanding of Plasmodium vivax Relapses

    PubMed Central

    Silvino, Ana Carolina Rios; Costa, Gabriel Luiz; de Araújo, Flávia Carolina Faustino; Ascher, David Benjamin; Pires, Douglas Eduardo Valente; Fontes, Cor Jesus Fernandes; Carvalho, Luzia Helena; de Brito, Cristiana Ferreira Alves; Sousa, Tais Nobrega

    2016-01-01

    Although Plasmodium vivax relapses are classically associated with hypnozoite activation, it has been proposed that a proportion of these cases are due to primaquine (PQ) treatment failure caused by polymorphisms in cytochrome P-450 2D6 (CYP2D6). Here, we present evidence that CYP2D6 polymorphisms are implicated in PQ failure, which was reinforced by findings in genetically similar parasites, and may explain a number of vivax relapses. Using a computational approach, these polymorphisms were predicted to affect the activity of CYP2D6 through changes in the structural stability that could lead to disruption of the PQ-enzyme interactions. Furthermore, because PQ is co-administered with chloroquine (CQ), we investigated whether CQ-impaired metabolism by cytochrome P-450 2C8 (CYP2C8) could also contribute to vivax recurrences. Our results show that CYP2C8-mutated patients frequently relapsed early (<42 days) and had a higher proportion of genetically similar parasites, suggesting the possibility of recrudescence due to CQ therapeutic failure. These results highlight the importance of pharmacogenetic studies as a tool to monitor the efficacy of antimalarial therapy. PMID:27467145

  10. Activation of Human Monocytes by Live Borrelia burgdorferi Generates TLR2-Dependent and -Independent Responses Which Include Induction of IFN-β

    PubMed Central

    Salazar, Juan C.; Duhnam-Ems, Star; La Vake, Carson; Cruz, Adriana R.; Moore, Meagan W.; Caimano, Melissa J.; Velez-Climent, Leonor; Shupe, Jonathan; Krueger, Winfried; Radolf, Justin D.

    2009-01-01

    It is widely believed that innate immune responses to Borrelia burgdorferi (Bb) are primarily triggered by the spirochete's outer membrane lipoproteins signaling through cell surface TLR1/2. We recently challenged this notion by demonstrating that phagocytosis of live Bb by peripheral blood mononuclear cells (PBMCs) elicited greater production of proinflammatory cytokines than did equivalent bacterial lysates. Using whole genome microarrays, we show herein that, compared to lysates, live spirochetes elicited a more intense and much broader transcriptional response involving genes associated with diverse cellular processes; among these were IFN-β and a number of interferon-stimulated genes (ISGs), which are not known to result from TLR2 signaling. Using isolated monocytes, we demonstrated that cell activation signals elicited by live Bb result from cell surface interactions and uptake and degradation of organisms within phagosomes. As with PBCMs, live Bb induced markedly greater transcription and secretion of TNF-α, IL-6, IL-10 and IL-1β in monocytes than did lysates. Secreted IL-18, which, like IL-1β, also requires cleavage by activated caspase-1, was generated only in response to live Bb. Pro-inflammatory cytokine production by TLR2-deficient murine macrophages was only moderately diminished in response to live Bb but was drastically impaired against lysates; TLR2 deficiency had no significant effect on uptake and degradation of spirochetes. As with PBMCs, live Bb was a much more potent inducer of IFN-β and ISGs in isolated monocytes than were lysates or a synthetic TLR2 agonist. Collectively, our results indicate that the enhanced innate immune responses of monocytes following phagocytosis of live Bb have both TLR2-dependent and -independent components and that the latter induce transcription of type I IFNs and ISGs. PMID:19461888

  11. Diversity of Ixodes-borne Borrelia species--clinical, pathogenetic, and diagnostic implications and impact on vaccine development.

    PubMed

    van Dam, Alje P

    2002-01-01

    Among Borrelia spirochetes carried by hard ticks belonging to the various Ixodes species, at least 10 species can be distinguished. Of these, Borrelia burgdorferi sensu stricto is involved in human Lyme borreliosis in North America and Europe, and Borrelia garinii and Borrelia afzelii in human disease in Europe and Asia. The pathogenetic significance of the other species is uncertain. Although some of the Borrelia species are restricted to certain tick species, Ixodes ricinus, the vector of Lyme borreliosis in Europe, can be infested by at least five different species, including all three pathogenic species. There is evidence that different Borrelia species are preferentially found in different hosts: In Europe, B. afzelii is frequently found in small mammals, whereas B. garinii and Borrelia valaisiana are often found in birds. This could very well be related to differential sensitivity of these species to complement-mediated bactericidal activity of different hosts. Borrelial complement regulator acquiring proteins, among them OspE or Erp proteins, bind to host factor H and related proteins, and this binding protects against activation of complement by the spirochetal surface. The binding is different for proteins originating from different species and is also depending on the host origin of factor H. In Europe, B. garinii is mainly found in neuroborreliosis, whereas in skin disease B. afzelii is more frequently found. The reason is unclear. The majority of human sera cross-react between proteins of different Borrelia species, but some sera react only with proteins from one of the species. This holds especially for reactivity with OspC. A vaccine against B. burgdorferi sensu stricto has been licensed, but was recently redrawn from the market because of commercial reasons. A vaccine protecting against all three pathogenic species is not yet available. PMID:12804166

  12. Anti-relapse medications: Preclinical models for drug addiction treatment

    PubMed Central

    Yahyavi-Firouz-Abadi, Noushin; See, Ronald E.

    2009-01-01

    Addiction is a chronic relapsing brain disease and treatment of relapse to drug-seeking is considered the most challenging part of treating addictive disorders. Relapse can be modeled in laboratory animals using reinstatement paradigms, whereby behavioral responding for a drug is extinguished and then reinstated by different trigger factors, such as environmental cues or stress. In this review, we first describe currently used animal models of relapse, different relapse triggering factors, and the validity of this model to assess relapse in humans. We further summarize the growing body of pharmacological interventions that have shown some promise in treating relapse to psychostimulant addiction. Moreover, we present an overview on the drugs tested in cocaine or methamphetamine addicts and examine the overlap of existing preclinical and clinical data. Finally, based on recent advances in our understanding of the neurobiology of relapse and published preclinical data, we highlight the most promising areas for future anti-relapse medication development. PMID:19683019

  13. Molecular detection of Rickettsia, Borrelia, and Babesia species in Ixodes ricinus sampled in northeastern, central, and insular areas of Italy.

    PubMed

    Castro, Lyda R; Gabrielli, Simona; Iori, Albertina; Cancrini, Gabriella

    2015-07-01

    The aim of the present study was to provide insight into the diversity of tick-borne pathogens circulating in Italy, carried/transmitted by Ixodes ricinus, one of the most abundant tick species in the country. A total of 447 specimens sampled in five areas of northeastern, central and insular Italy were analysed by polymerase chain reaction and sequencing for the presence of rickettsiae, borreliae and babesiae. Several rickettsial species of the spotted fever group of zoonotic concern and other zoonotic pathogens were found, such as Borrelia burgdorferi s.s., Borrelia afzelii, Borrelia garinii, and Babesia venatorum. These findings confirm a wide distribution of tick-borne bacterial and protozoan species in Italy, and highlight the sanitary importance of I. ricinus, often recorded as feeding on humans. PMID:25784072

  14. Maternal mortality in a rural Tanzanian hospital: fatal Jarisch-Herxheimer reaction in a case of relapsing fever in pregnancy.

    PubMed

    Rustenhoven-Spaan, Ilona; Melkert, Peter; Nelissen, Ellen; van Roosmalen, Jos; Stekelenburg, Jelle

    2013-10-01

    Relapsing fever is a disease caused by one of the species of Borrelia. It is often misdiagnosed as malaria and can have fatal complications such as the Jarisch-Herxheimer reaction (JHR) after the commencement of treatment with antibiotics. A 19-year-old Tanzanian woman was admitted after a term home delivery that day. She presented with a 2 day history of fever, headache, general body malaise and vomiting. She was misdiagnosed as having severe malaria and was treated with quinine. The blood slide showed Borrelia duttoni. The patient continued treatment with procaine penicillin fortified for relapsing fever. Several hours later the woman died, probably due to JHR. This case of a patient with relapsing fever who died from a JHR stresses the importance of adequate diagnosis and treatment which should include careful monitoring, especially for the first hours after starting antibiotics. PMID:23976777

  15. Borrelia bavariensis sp. nov. is widely distributed in Europe and Asia.

    PubMed

    Margos, Gabriele; Wilske, Bettina; Sing, Andreas; Hizo-Teufel, Cecilia; Cao, Wu-Chun; Chu, Chenyi; Scholz, Holger; Straubinger, Reinhard K; Fingerle, Volker

    2013-11-01

    Since the original description of Borrelia bavariensis sp. nov. in 2009, additional samples available from humans and ticks from Europe and Mongolia, respectively, have been used to further characterize Borrelia strains belonging to this group of spirochaetes that utilize rodents as reservoir hosts. These investigations suggested the presence of related strains in Europe and Asia and confirmed their status as representing a distinct species. Furthermore, samples that were investigated by researchers from China and Japan confirm the ecological relationship of members of this proposed species with rodents and suggest that it has a wide distribution in Eurasia. Here, we use phylogenetic and genetic distance analyses to validate B. bavariensis sp. nov. as a species within the Borrelia burgdorferi sensu lato species complex. The type strain is PBi(T) ( = DSM 23469(T) = BAA-2496(T)). PMID:23838444

  16. Multilocus sequence analysis of Borrelia bissettii strains from North America reveals a new Borrelia species, Borrelia kurtenbachii

    PubMed Central

    Margos, Gabriele; Hojgaard, Andrias; Lane, Robert S.; Cornet, Muriel; Fingerle, Volker; Rudenko, Nataliia; Ogden, Nicholas; Aanensen, David M.; Fish, Durland; Piesman, Joseph

    2010-01-01

    Using multilocus sequence analyses (MLSA), we investigated the phylogenetic relationship of spirochaete strains from North America previously assigned to the genospecies Borrelia bissettii. We amplified internal fragments of 8 housekeeping genes (clpA, clpX, nifS, pepX, pyrG, recG, rplB, and uvrA) located on the main linear chromosome by polymerase chain reaction. Phylogenetic analysis of concatenated sequences of the 8 loci showed that the B. bissettii clade consisted of 4 closely related clusters which included strains from California (including the type strain DN127-Cl9-2/p7) and Colorado that were isolated from Ixodes pacificus, I. spinipalpis, or infected reservoir hosts. Several strains isolated from I. scapularis clustered distantly from B. bissettii. Genetic distance analyses confirmed that these strains are more distant to B. bissettii than they are to B. carolinensis, a recently described Borrelia species, which suggests that they constitute a new Borrelia genospecies. We propose that it be named Borrelia kurtenbachii sp. nov. in honour of the late Klaus Kurtenbach. The data suggest that ecological differences between B. bissettii and the new Borrelia genospecies reflect different transmission cycles. In view of these findings, the distinct vertebrate host-tick vector associations and the distributions of B. bissettii and B. kurtenbachii require further investigation. PMID:21157575

  17. [Borrelia burgdorferi sensu lato in ixodid ticks from Ostrava slag heaps].

    PubMed

    Jarosová, V; Rudolf, I; Halouzka, J; Hubálek, Z

    2009-04-01

    In 2005 and 2006, Ixodes ricinus ticks were collected on two slag (waste rock) heaps from coal mines in the Ostrava area (North Moravia/Silesia, Czech Republic), Oskar (site A) and Emma (site B), partially covered by vegetation including trees, and at a control forest site near Hlucín (site C). The mean numbers of L. ricinus nymphs and imagoes flagged per person-hour were high: 35.3 nymphs and 12.7 imagoes, at site A, 23.3 and 26.0, respectively, at site B, and 25.4 and 16.8, respectively, at control site C. Using dark-field microscopy, 100 nymphs and 100 imagoes (50 females and 50 males) from each site were examined for borreliae. The mean prevalence rates of Borrelia burgdorferi sensu lato in nymphs and imagoes were 10.0% and 12.0%, respectively, at site A, 10.0% and 24.0%, respectively, at site B, and 13.0% and 17.0%, respectively, at site C. Differences in the prevalence of borreliae in nymphal and adult ticks from the slag heaps and control site were insignificant, but adult ticks from site B compared to site A contained borreliae significantly more frequently. The mean numbers of nymphs and imagoes infected with borreliae flagged per person-hour were 3.3 and 1.2, respectively at site A, 1.5 and 2.9, respectively, at site B, and 3.1 and 2.6, respectively, at site C. Isolation experiments for borreliae were carried out only in 16 ticks containing higher numbers of borreliae, with eight of these being culture-positive. The cultured borreliae were identified by PCR-RFLP as B. garinii (3 isolates: two from site B, one from site C), B. afzelii (4 isolates: one from site A, three from site B) and B. burgdorferi s.s. (one isolate from site A). Surprisingly, the results suggest that slag heaps, when covered by woody vegetation and frequented by humans, could theoretically pose roughly the same LB transmission risk to humans as common forest biotopes. PMID:19526923

  18. Characterization of a DNA Adenine Methyltransferase Gene of Borrelia hermsii and Its Dispensability for Murine Infection and Persistence

    PubMed Central

    James, Allison E.; Rogovskyy, Artem S.; Crowley, Michael A.; Bankhead, Troy

    2016-01-01

    DNA methyltransferases have been implicated in the regulation of virulence genes in a number of pathogens. Relapsing fever Borrelia species harbor a conserved, putative DNA methyltransferase gene on their chromosome, while no such ortholog can be found in the annotated genome of the Lyme disease agent, Borrelia burgdorferi. In the relapsing fever species Borrelia hermsii, the locus bh0463A encodes this putative DNA adenine methyltransferase (dam). To verify the function of the BH0463A protein product as a Dam, the gene was cloned into a Dam-deficient strain of Escherichia coli. Restriction fragment analysis subsequently demonstrated that complementation of this E. coli mutant with bh0463A restored adenine methylation, verifying bh0463A as a Dam. The requirement of bh0463A for B. hermsii viability, infectivity, and persistence was then investigated by genetically disrupting the gene. The dam- mutant was capable of infecting immunocompetent mice, and the mean level of spirochetemia in immunocompetent mice was not significantly different from wild type B. hermsii. Collectively, the data indicate that dam is dispensable for B. hermsii viability, infectivity, and persistence. PMID:27195796

  19. Detection of Borrelia lonestari, putative agent of southern tick-associated rash illness, in white-tailed deer (Odocoileus virginianus) from the southeastern United States.

    PubMed

    Moore, Victor A; Varela, Andrea S; Yabsley, Michael J; Davidson, William R; Little, Susan E

    2003-01-01

    To determine if white-tailed deer may serve as a reservoir host for Borrelia lonestari, we used a nested PCR for the Borrelia flagellin gene to evaluate blood samples collected from deer from eight southeastern states. Seven of 80 deer (8.7%) from 5 of 17 sites (29.4%) had sequence-confirmed evidence of a B. lonestari flagellin gene by PCR, indicating that deer are infected with B. lonestari or another closely related Borrelia species. Our findings expand the known geographic range of B. lonestari and provide the first evidence of this organism in a vertebrate other than humans. PMID:12517884

  20. First report of Borrelia burgdorferi sensu lato in two threatened carnivores: the Marbled polecat, Vormela peregusna and the European mink, Mustela lutreola (Mammalia: Mustelidae)

    PubMed Central

    2012-01-01

    Background Lyme disease is a widespread cosmopolitan zoonosis caused by species belonging to the genus Borrelia. It is transmitted from animal reservoir hosts to humans through hard - ticks of genus Ixodes which are vectors of the disease. Case presentation Borrelia burgdorferi sensu lato infection was identified in a marbled polecat, Vormela peregusna, and two European minks, Mustela lutreola, from Romania, by PCR. RFLP revealed the presence of a single genospecies, Borrelia burgdorferi sensu stricto. Conclusions This is the first report of the Lyme disease spirochetes in the two mentioned hosts. PMID:22901862

  1. Borrelia burgdorferi tissue morphologies and imaging methodologies.

    PubMed

    MacDonald, A B

    2013-08-01

    This manuscript offers an image presentation of diverse forms of Borrelia burgdorferi spirochetes which are not spiral or corkscrew shaped. Explanations are offered to justify the legitimacy of tissue forms of Borrelia which may confuse the inexperienced microscopic examiner and which may lead to the misdiagnosis of non-spiral forms as artifacts. Images from the author's personal collection of Borrelia burgdorferi images and a few select images of Borrelia burgdorferi from the peer-reviewed published literature are presented. A commentary justifying each of the image profiles and a survey of the imaging modalities utilized provides the reader with a frame of reference. Regularly spiraled Borrelia are rarely seen in solid tissues. A variety of straightened, undulating, and clipped-off profiles are demonstrated, and the structural basis for each image is explained. Tissue examination is a diagnostic tool and a quality control for judging the eradication or the persistence of borreliosis following attempts to eradicate the infection with antibiotic therapy. The presence or absence of chronic Lyme borreliosis may be objectively adjudicated by tissue examinations which demonstrate or which fail to show pathogenic microbes in patients who have received a full course of antibiotics. PMID:23479042

  2. Crystal Structure of Neurotropism-Associated Variable Surface Protein 1 (VSP1) of Borrelia Turicatae

    SciTech Connect

    Lawson,C.; Yung, B.; Barbour, A.; Zuckert, W.

    2006-01-01

    Vsp surface lipoproteins are serotype-defining antigens of relapsing fever spirochetes that undergo multiphasic antigenic variation to allow bacterial persistence in spite of an immune response. Two isogenic serotypes of Borrelia turicatae strain Oz1 differ in their Vsp sequences and in disease manifestations in infected mice: Vsp1 is associated with the selection of a neurological niche, while Vsp2 is associated with blood and skin infection. We report here crystal structures of the Vsp1 dimer at 2.7 and 2.2 Angstroms. The structures confirm that relapsing fever Vsp proteins share a common helical fold with OspCs of Lyme disease-causing Borrelia. The fold features an inner stem formed by highly conserved N and C termini and an outer 'dome' formed by the variable central residues. Both Vsp1 and OspC structures possess small water-filled cavities, or pockets, that are lined largely by variable residues and are thus highly variable in shape. These features appear to signify tolerance of the Vsp-OspC fold for imperfect packing of residues at its antigenic surface. Structural comparison of Vsp1 with a homology model for Vsp2 suggests that observed differences in disease manifestation may arise in part from distinct differences in electrostatic surface properties; additional predicted positively charged surface patches on Vsp2 compared to Vsp1 may be sufficient to explain the relative propensity of Vsp2 to bind to acidic glycosaminoglycans.

  3. Hemolytic activity of Borrelia burgdorferi.

    PubMed Central

    Williams, L R; Austin, F E

    1992-01-01

    Zones of beta-hemolysis occurred around colonies of Borrelia burgdorferi grown on Barbour-Stoenner-Kelly medium containing agarose and horse blood. Blood plates were inoculated with either the infective strain Sh-2-82 or noninfective strain B-31 in an overlay and incubated in a candle jar. Both strains of B. burgdorferi displayed beta-hemolysis after 1 to 2 weeks of incubation. The hemolytic activity diffused out from the borrelial colonies, eventually resulting in lysis of the entire blood plate. Hemolysis was most pronounced with horse blood and was less intense with bovine, sheep, and rabbit blood. Hemolysis was enhanced by hot-cold incubation, which is typical of phospholipase-like activities in other bacteria. Further characterization of the borrelial hemolysin by using a spectrophotometric assay revealed its presence in the supernatant fluids of stationary-phase cultures. Detection of the borrelial hemolytic activity was dependent on activation of the hemolysin by the reducing agent cysteine. This study provides the first evidence of hemolytic activity associated with B. burgdorferi. Images PMID:1639493

  4. [Relapsing fever: an almost forgotten disease in focus again].

    PubMed

    Wieser, Andreas; Löscher, Thomas; Schunk, Mirjam; Seilmaier, Michael; Balzer, Lukas; Margos, Gabriele; von Both, Ulrich; Schulzki, Thomas; Kopf, Sabine; Hoch, Martin; Sing, Andreas; Fingerle, Volker

    2016-07-01

    Introduction | Relapsing fevers, transmitted by arthropods, are rarely encountered in Germany, thus they are often not considered as differential diagnosis in febrile patients. In the last months, more than fourty cases of louse-borne relapsing fever were diagnosed in asylum seekers in Germany. Some of the patients had to be admitted to intensive care units, one patient died despite therapy. Pathogen, disease and diagnosis | The causative agents are spirochetes of the genus borrelia, which can reach high densities in patient blood. Depending on the vector and the region, different species are prevalent worldwide. For diagnosis, appropriate techniques include direct detection by microscopy or PCR from EDTA-blood. Ordering such tests should not be delayed when there is suspicion for relapsing fever. Besides, malaria can also be excluded with microscopy of blood smears. Therapy | First-line antibiotics include tetracyclines and penicillin, acquired resistance has not yet been observed. Frequently patients develop a Jarisch-Herxheimer reaction shortly after initiation of therapy, requiring hospitalization or intensive care treatment. Managing the treatment exclusively in an outpatient setting is not recommended. Especially in migrants with febrile illness, relapsing fever is an important differential diagnosis. PMID:27404930

  5. Differential associations of Borrelia species with European badgers (Meles meles) and raccoon dogs (Nyctereutes procyonoides) in western Poland.

    PubMed

    Wodecka, Beata; Michalik, Jerzy; Lane, Robert S; Nowak-Chmura, Magdalena; Wierzbicka, Anna

    2016-07-01

    European badgers and raccoon dogs and their associated ticks and lice were assayed for the presence of Lyme borreliosis and relapsing fever-group spirochete DNA in western Poland. Analyses of blood, ear-biopsy and liver samples revealed that 25% of 28 raccoon dogs and 12% of 34 badgers were PCR positive for borreliae. Borrelia garinii was the dominant species in raccoon dogs (62.5%), followed by B. afzelii (25%) and B. valaisiana (12.5%). PCR-positive badgers were infected only with B. afzelii. A total of 351 attached ticks was recovered from 23 (82%) of the raccoon dogs and 13 (38%) of the badgers. Using a nested PCR targeting the ITS2 fragments of Ixodes DNA, four Ixodes species were identified: I. ricinus, I. canisuga, I. hexagonus, and one provisionally named I. cf. kaiseri. Ixodes canisuga and I. ricinus prevailed on both host species. The highest infection prevalence was detected in I. ricinus, followed by I. canisuga and I. cf. kaiseri. Borrelia garinii and B. afzelii accounted for 61.6% and 30.1% of the infections detected in all PCR-positive ticks, respectively. Four other Borrelia species (B. burgdorferi sensu stricto, B. valaisiana, B. lusitaniae and B. miyamotoi) were detected only in I. ricinus from raccoon dogs. Moreover, Borrelia DNA, mostly B. garinii, was detected in 57 (81.4%) of 70 Trichodectes melis lice derived from 12 badgers. The detection of B. afzelii in one-half of PCR-positive biopsies reconfirms previous associations of this species with mammalian hosts, whereas the high prevalence of B. garinii in feeding lice and I. ricinus ticks (including larvae) demonstrates that both carnivores serve as hosts for B. garinii. The lack of B. garinii DNA in the tissues of badgers versus its prevalence in raccoon-dog biopsies, however, incriminates only the latter carnivore as a potential reservoir host. PMID:27263838

  6. Isolation of Lyme disease Borrelia from puffins (Fratercula arctica) and seabird ticks (Ixodes uriae) on the Faeroe Islands.

    PubMed

    Gylfe; Olsen, B; Strasevicius, D; Marti Ras, N; Weihe, P; Noppa, L; Ostberg, Y; Baranton, G; Bergström, S

    1999-04-01

    This is the first report on the isolation of Lyme disease Borrelia from seabirds on the Faeroe Islands and the characteristics of its enzootic cycle. The major components of the Borrelia cycle include the puffin (Fratercula arctica) as the reservoir and Ixodes uriae as the vector. The importance of this cycle and its impact on the spread of human Lyme borreliosis have not yet been established. Borrelia spirochetes isolated from 2 of 102 sampled puffins were compared to the borreliae previously obtained from seabird ticks, I. uriae. The rrf-rrl intergenic spacer and the rrs and the ospC genes were sequenced and a series of phylogenetic trees were constructed. Sequence data and restriction fragment length polymorphism analysis grouped the strains together with Borrelia garinii. In a seroepidemiological survey performed with residents involved in puffin hunting on the Faeroe Islands, 3 of 81 serum samples were found to be positive by two commonly used clinical tests: a flagellin-based enzyme-linked immunosorbent assay (ELISA) and Western blotting. These three positive serum samples also had high optical density values in a whole-cell ELISA. The finding of seropositive Faeroe Islanders who are regularly exposed to I. uriae indicate that there may be a transfer of B. garinii by this tick species to humans. PMID:10074497

  7. Notes from the Field: Tickborne Relapsing Fever Outbreak at an Outdoor Education Camp - Arizona, 2014.

    PubMed

    Jones, Jefferson M; Schumacher, Mare; Peoples, Marie; Souders, Nina; Horn, Kimberly; Fox, Lisa; Scott, Michele; Brady, Shane; Weiss, Joli; Komatsu, Ken; Nieto, Nathan

    2015-06-19

    Tickborne relapsing fever (TBRF) is a bacterial infection characterized by recurring episodes of fever, headache, muscle and joint aches, and nausea. In North America, TBRF primarily is caused by Borrelia hermsii spirochetes transmitted by Ornithodoros hermsii ticks. Once infected, these soft ticks are infectious for life and transmit the spirochete to sleeping humans quickly (possibly within 30 seconds) during short feeds (15-90 minutes). On August 10, 2014, the Coconino County Public Health Services District in Arizona was notified by a local hospital that five high school students who attended the same outdoor education camp had been hospitalized with fever, headache, and myalgias. Hantavirus infection initially was suspected because of reported exposure to rodent droppings, but after detecting spirochetes on peripheral blood smears from all five hospitalized students, TBRF was diagnosed. The camp was instructed to close immediately, and the health department, in collaboration with local university experts, investigated to identify additional cases, determine the cause, and prevent further infections. A total of 11 cases (six confirmed and five probable) were identified. PMID:26086637

  8. Animal models of fear relapse.

    PubMed

    Goode, Travis D; Maren, Stephen

    2014-01-01

    Whereas fear memories are rapidly acquired and enduring over time, extinction memories are slow to form and are susceptible to disruption. Consequently, behavioral therapies that involve extinction learning (e.g., exposure therapy) often produce only temporary suppression of fear and anxiety. This review focuses on the factors that are known to influence the relapse of extinguished fear. Several phenomena associated with the return of fear after extinction are discussed, including renewal, spontaneous recovery, reacquisition, and reinstatement. Additionally, this review describes recent work, which has focused on the role of psychological stress in the relapse of extinguished fear. Recent developments in behavioral and pharmacological research are examined in light of treatment of pathological fear in humans. PMID:25225304

  9. [Relapse: causes and consequences].

    PubMed

    Thomas, P

    2013-09-01

    Relapse after a first episode of schizophrenia is the recurrence of acute symptoms after a period of partial or complete remission. Due to its variable aspects, there is no operational definition of relapse able to modelise the outcome of schizophrenia and measure how the treatment modifies the disease. Follow-up studies based on proxys such as hospital admission revealed that 7 of 10 patients relapsed after a first episode of schizophrenia. The effectiveness of antipsychotic medications on relapse prevention has been widely demonstrated. Recent studies claim for the advantages of atypical over first generation antipsychotic medication. Non-adherence to antipsychotic represents with addictions the main causes of relapse long before some non-consensual factors such as premorbid functioning, duration of untreated psychosis and associated personality disorders. The consequences of relapse are multiple, psychological, biological and social. Pharmaco-clinical studies have demonstrated that the treatment response decreases with each relapse. Relapse, even the first one, will contribute to worsen the outcome of the disease and reduce the capacity in general functionning. Accepting the idea of continuing treatment is a complex decision in which the psychiatrist plays a central role besides patients and their families. The development of integrated actions on modifiable risk factors such as psychosocial support, addictive comorbidities, access to care and the therapeutic alliance should be promoted. Relapse prevention is a major goal of the treatment of first-episode schizophrenia. It is based on adherence to the maintenance treatment, identification of prodromes, family active information and patient therapeutical education. PMID:24084426

  10. Bird-feeding ticks transstadially transmit Borrelia burgdorferi that infect Syrian hamsters.

    PubMed

    Anderson, J F; Magnarelli, L A; Stafford, K C

    1990-01-01

    Bird-feeding Ixodes dammini ticks were documented for the first time to successfully molt and transstadially pass Borrelia burgdorferi spirochetes that were indistinguishable by sodium dodecyl sulfate-polyacrylamide gel electrophoresis from the type B31 strain. Forty-six of 73 blood-engorged larvae and 50 of 66 fully-fed nymphs, removed from wild-caught birds, successfully molted. Borreliae were isolated from 21 of 78 partially- and fully-fed larvae off birds, including six specimens that molted. Spirochete-positive cultures also were obtained from 35 of 60 partially- and fully-fed nymphs that had fed from birds, including 20 nymphs that molted into adult ticks. Transstadially passed borreliae by bird-feeding larval and nymphal I. dammini were infectious to hamsters, leading us to suggest that these ticks are capable of subsequently transmitting infectious spirochetes to mammals, including humans. An isolated of B. burgdorferi, recovered from a bird-feeding larval Ixodes dentatus, was indistinguishable by sodium dodecyl sulfate-polyacrylamide gel electrophoresis from the B31 strain. This isolate, unlike another from I. dentatus off a cottontail rabbit (Sylvilagus floridanus), had a protein band with a molecular weight of approximately 31,000 that reacted with murine monoclonal antibodies H3TS and H5332 in western blot analysis. Thus, closely related borreliae are present in both I. dentatus and I. dammini. PMID:2304189

  11. Recent developments in animal models of drug relapse.

    PubMed

    Marchant, Nathan J; Li, Xuan; Shaham, Yavin

    2013-08-01

    Drug craving and relapse to drug use during abstinence are defining features of addiction. Evidence indicates that drug craving and relapse in humans are often provoked by acute exposure to the self-administered drug, drug-associated cues, or stress. During the last two decades, this clinical scenario has been primarily studied at the preclinical level using the classical reinstatement model. However, a single preclinical model cannot capture the complicated nature of human drug relapse. Therefore, more recently, we and others have developed several other models to study different facets of human drug relapse. In this review, we introduce and discuss recent findings from these other relapse models, including incubation of drug craving, reacquisition and resurgence models, and punishment-based and conflict-based relapse models. PMID:23374536

  12. The dynamic proteome of Lyme disease Borrelia.

    PubMed

    Norris, Steven J

    2006-01-01

    The proteome of the spirochete bacterium Borrelia burgdorferi, the tick-borne agent of Lyme disease, has been characterized by two different approaches using mass spectrometry, providing a launching point for future studies on the dramatic changes in protein expression that occur during transmission of the bacterium between ticks and mammals. PMID:16563176

  13. Genotypic Variation and Mixtures of Lyme Borrelia in Ixodes Ticks from North America and Europe

    PubMed Central

    Crowder, Chris D.; Matthews, Heather E.; Schutzer, Steven; Rounds, Megan A.; Luft, Benjamin J.; Nolte, Oliver; Campbell, Scott R.; Phillipson, Curtis A.; Li, Feng; Sampath, Ranga; Ecker, David J.; Eshoo, Mark W.

    2010-01-01

    Background Lyme disease, caused by various species of Borrelia, is transmitted by Ixodes ticks in North America and Europe. Studies have shown the genotype of Borrelia burgdorferi sensu stricto (s.s.) or the species of B. burgdorferi sensu lato (s.l.) affects the ability of the bacteria to cause local or disseminated infection in humans. Methodology/Principal Findings We used a multilocus PCR electrospray mass spectrometry assay to determine the species and genotype Borrelia from ticks collected in New York, Connecticut, Indiana, Southern Germany, and California and characterized isolates from parts of the United States and Europe. These analyses identified 53 distinct genotypes of B. burgdorferi sensu stricto with higher resolution than ospC typing. Genotypes of other members of the B. burgdorferi sensu lato complex were also identified and genotyped including B. afzelii, B. garinii, B. lusitaniae, B. spielmanii, and B. valaisiana. While each site in North America had genotypes unique to that location, we found genotypes shared between individual regions and two genotypes found across the United States. Significant B. burgdorferi s.s. genotypic diversity was observed between North America and Europe: only 6.6% of US genotypes (3 of 45) were found in Europe and 27% of the European genotypes (3 of 11) were observed in the US. Interestingly, 39% of adult Ixodes scapularis ticks from North America were infected with more than one genotype of B. burgdorferi s.s. and 22.2% of Ixodes ricinus ticks from Germany were infected with more than one genotype of B. burgdorferi s.l. Conclusions/Significance The presence of multiple Borrelia genotypes in ticks increases the probability that a person will be infected with more than one genotype of B. burgdorferi, potentially increasing the risks of disseminated Lyme disease. Our study indicates that the genotypic diversity of Borrelia in ticks in both North America and Europe is higher then previously reported and can have

  14. Natural foci of Borrelia lusitaniae in a mountain region of Central Europe.

    PubMed

    Tarageľová, Veronika Rusňáková; Mahríková, Lenka; Selyemová, Diana; Václav, Radovan; Derdáková, Markéta

    2016-03-01

    Lyme borreliosis is the most prevalent tick-borne disease in Europe. It is caused by spirochaetes of the Borrelia burgdorferi sensu lato (s.l.) complex and transmitted to humans by ticks of the genus Ixodes. Borrelia afzelii, Borrelia garinii, and Borrelia valaisiana are the most common genospecies in Central Europe. In contrast, Borrelia lusitaniae predominates in Mediterranean countries such as Portugal, Morocco, and Tunisia. In Slovakia, its prevalence is low and restricted to only a few sites. The aim of our research was to study the expansion of ticks into higher altitudes in the ecosystem of the Malá Fatra mountains (north Slovakia) and their infection with B. burgdorferi s.l. pathogens. Questing ticks were collected by flagging in seven years (2004, 2006-2011) at three different altitudes: low (630-660 m above sea level (ASL)), intermediate (720-750 m ASL), and high (1040-1070 m ASL). Tick abundance was highest at the lowest altitude and lowest at the highest altitude. The average infection prevalence of B. burgdorferi s.l. in nymphs and adults was 16.8% and 36.2%, respectively. The number of infected ticks decreased from 38.5% at the lowest altitude to 4.4% at the highest altitude. B. lusitaniae was the most frequently found genospecies (>60% of the ticks found positive for B. burgdorferi s.l.) in all sites in all the studied years with the exception of 2008 when B. afzelii predominated (62%). Our study confirms the spread of Ixodes ricinus ticks to higher altitudes in Slovakia. The discovery that our mountain study sites were a natural foci of B. lusitaniae was unexpected because this genospecies is usually associated with lizards and xerothermic habitats. PMID:26711673

  15. Immunity against Ixodes scapularis Salivary Proteins Expressed within 24 Hours of Attachment Thwarts Tick Feeding and Impairs Borrelia Transmission

    PubMed Central

    Narasimhan, Sukanya; DePonte, Kathleen; Marcantonio, Nancy; Liang, Xianping; Royce, Thomas E.; Nelson, Kenneth F.; Booth, Carmen J.; Koski, Benjamin; Anderson, John F.; Kantor, Fred; Fikrig, Erol

    2007-01-01

    In North America, the black-legged tick, Ixodes scapularis, an obligate haematophagus arthropod, is a vector of several human pathogens including Borrelia burgdorferi, the Lyme disease agent. In this report, we show that the tick salivary gland transcriptome and proteome is dynamic and changes during the process of engorgement. We demonstrate, using a guinea pig model of I. scapularis feeding and B. burgdorferi transmission, that immunity directed against salivary proteins expressed in the first 24 h of tick attachment — and not later — is sufficient to evoke all the hallmarks of acquired tick-immunity, to thwart tick feeding and also to impair Borrelia transmission. Defining this subset of proteins will promote a mechanistic understanding of novel I. scapularis proteins critical for the initiation of tick feeding and for Borrelia transmission. PMID:17505544

  16. Virulence of recurrent infestations with Borrelia-infected ticks in a Borrelia-amplifying bird

    PubMed Central

    Heylen, Dieter J. A.; Müller, Wendt; Vermeulen, Anke; Sprong, Hein; Matthysen, Erik

    2015-01-01

    Lyme disease cases caused by Borrelia burgdorferi s.l. bacteria is increasing steadily in Europe, in part due to the expansion of the vector, Ixodes ricinus. Wild reservoir hosts are typically recurrently infested. Understanding the impact of these cumulative parasite exposures on the host’s health is, therefore, central to predict the distribution of tick populations and their pathogens. Here, we have experimentally investigated the symptoms of disease caused by recurrent infestations in a common songbird (Parus major). Birds were exposed three times in succession to ticks collected in a Borrelia endemic area. Health and immune measures were analyzed in order to investigate changes in response to tick infestation and Borrelia infection rate. Nitric oxide levels increased with the Borrelia infection rate, but this effect was increasingly counteracted by mounting tick infestation rates. Tick infestations equally reduced haematocrit during each cycle. But birds overcompensated in their response to tick feeding, having higher haematocrit values during tick-free periods depending on the number of ticks they had been previously exposed to. Body condition showed a similar overshooting response in function of the severity of the Borrelia infection. The observed overcompensation increases the bird’s energetic needs, which may result in an increase in transmission events. PMID:26553505

  17. Virulence of recurrent infestations with Borrelia-infected ticks in a Borrelia-amplifying bird

    NASA Astrophysics Data System (ADS)

    Heylen, Dieter J. A.; Müller, Wendt; Vermeulen, Anke; Sprong, Hein; Matthysen, Erik

    2015-11-01

    Lyme disease cases caused by Borrelia burgdorferi s.l. bacteria is increasing steadily in Europe, in part due to the expansion of the vector, Ixodes ricinus. Wild reservoir hosts are typically recurrently infested. Understanding the impact of these cumulative parasite exposures on the host’s health is, therefore, central to predict the distribution of tick populations and their pathogens. Here, we have experimentally investigated the symptoms of disease caused by recurrent infestations in a common songbird (Parus major). Birds were exposed three times in succession to ticks collected in a Borrelia endemic area. Health and immune measures were analyzed in order to investigate changes in response to tick infestation and Borrelia infection rate. Nitric oxide levels increased with the Borrelia infection rate, but this effect was increasingly counteracted by mounting tick infestation rates. Tick infestations equally reduced haematocrit during each cycle. But birds overcompensated in their response to tick feeding, having higher haematocrit values during tick-free periods depending on the number of ticks they had been previously exposed to. Body condition showed a similar overshooting response in function of the severity of the Borrelia infection. The observed overcompensation increases the bird’s energetic needs, which may result in an increase in transmission events.

  18. Effects of Fatty Acid Amide Hydrolase (FAAH) Inhibitors in Non-Human Primate Models of Nicotine Reward and Relapse.

    PubMed

    Justinova, Zuzana; Panlilio, Leigh V; Moreno-Sanz, Guillermo; Redhi, Godfrey H; Auber, Alessia; Secci, Maria E; Mascia, Paola; Bandiera, Tiziano; Armirotti, Andrea; Bertorelli, Rosalia; Chefer, Svetlana I; Barnes, Chanel; Yasar, Sevil; Piomelli, Daniele; Goldberg, Steven R

    2015-08-01

    Inhibition of the enzyme fatty acid amide hydrolase (FAAH) counteracts reward-related effects of nicotine in rats, but it has not been tested for this purpose in non-human primates. Therefore, we studied the effects of the first- and second-generation O-arylcarbamate-based FAAH inhibitors, URB597 (cyclohexyl carbamic acid 3'-carbamoyl-3-yl ester) and URB694 (6-hydroxy-[1,1'-biphenyl]-3-yl-cyclohexylcarbamate), in squirrel monkeys. Both FAAH inhibitors: (1) blocked FAAH activity in brain and liver, increasing levels of endogenous ligands for cannabinoid and α-type peroxisome proliferator-activated (PPAR-α) receptors; (2) shifted nicotine self-administration dose-response functions in a manner consistent with reduced nicotine reward; (3) blocked reinstatement of nicotine seeking induced by reexposure to either nicotine priming or nicotine-associated cues; and (4) had no effect on cocaine or food self-administration. The effects of FAAH inhibition on nicotine self-administration and nicotine priming-induced reinstatement were reversed by the PPAR-α antagonist, MK886. Unlike URB597, which was not self-administered by monkeys in an earlier study, URB694 was self-administered at a moderate rate. URB694 self-administration was blocked by pretreatment with an antagonist for either PPAR-α (MK886) or cannabinoid CB1 receptors (rimonabant). In additional experiments in rats, URB694 was devoid of THC-like or nicotine-like interoceptive effects under drug-discrimination procedures, and neither of the FAAH inhibitors induced dopamine release in the nucleus accumbens shell--consistent with their lack of robust reinforcing effects in monkeys. Overall, both URB597 and URB694 show promise for the initialization and maintenance of smoking cessation because of their ability to block the rewarding effects of nicotine and prevent nicotine priming-induced and cue-induced reinstatement. PMID:25754762

  19. Effects of Fatty Acid Amide Hydrolase (FAAH) Inhibitors in Non-Human Primate Models of Nicotine Reward and Relapse

    PubMed Central

    Justinova, Zuzana; Panlilio, Leigh V; Moreno-Sanz, Guillermo; Redhi, Godfrey H; Auber, Alessia; Secci, Maria E; Mascia, Paola; Bandiera, Tiziano; Armirotti, Andrea; Bertorelli, Rosalia; Chefer, Svetlana I; Barnes, Chanel; Yasar, Sevil; Piomelli, Daniele; Goldberg, Steven R

    2015-01-01

    Inhibition of the enzyme fatty acid amide hydrolase (FAAH) counteracts reward-related effects of nicotine in rats, but it has not been tested for this purpose in non-human primates. Therefore, we studied the effects of the first- and second-generation O-arylcarbamate-based FAAH inhibitors, URB597 (cyclohexyl carbamic acid 3'-carbamoyl-3-yl ester) and URB694 (6-hydroxy-[1,1'-biphenyl]-3-yl-cyclohexylcarbamate), in squirrel monkeys. Both FAAH inhibitors: (1) blocked FAAH activity in brain and liver, increasing levels of endogenous ligands for cannabinoid and α-type peroxisome proliferator-activated (PPAR-α) receptors; (2) shifted nicotine self-administration dose–response functions in a manner consistent with reduced nicotine reward; (3) blocked reinstatement of nicotine seeking induced by reexposure to either nicotine priming or nicotine-associated cues; and (4) had no effect on cocaine or food self-administration. The effects of FAAH inhibition on nicotine self-administration and nicotine priming-induced reinstatement were reversed by the PPAR-α antagonist, MK886. Unlike URB597, which was not self-administered by monkeys in an earlier study, URB694 was self-administered at a moderate rate. URB694 self-administration was blocked by pretreatment with an antagonist for either PPAR-α (MK886) or cannabinoid CB1 receptors (rimonabant). In additional experiments in rats, URB694 was devoid of THC-like or nicotine-like interoceptive effects under drug-discrimination procedures, and neither of the FAAH inhibitors induced dopamine release in the nucleus accumbens shell—consistent with their lack of robust reinforcing effects in monkeys. Overall, both URB597 and URB694 show promise for the initialization and maintenance of smoking cessation because of their ability to block the rewarding effects of nicotine and prevent nicotine priming-induced and cue-induced reinstatement. PMID:25754762

  20. Nanoscopic Localization of Surface-Exposed Antigens of Borrelia burgdorferi.

    PubMed

    Lemgruber, Leandro; Sant'Anna, Celso; Griffths, Caron; Abud, Yuri; Mhlanga, Musa; Wallich, Reinhard; Frischknecht, Friedrich

    2015-06-01

    Borrelia burgdorferi sensu lato, the causative agent of Lyme disease, is transmitted to humans through the bite of infected Ixodes spp. ticks. Successful infection of vertebrate hosts necessitates sophisticated means of the pathogen to escape the vertebrates' immune system. One strategy employed by Lyme disease spirochetes to evade adaptive immunity involves a highly coordinated regulation of the expression of outer surface proteins that is vital for infection, dissemination, and persistence. Here we characterized the expression pattern of bacterial surface antigens using different microscopy techniques, from fluorescent wide field to super-resolution and immunogold-scanning electron microscopy. A fluorescent strain of B. burgdorferi spirochetes was labeled with monoclonal antibodies directed against various bacterial surface antigens. Our results indicate that OspA is more evenly distributed over the surface than OspB and OspC that were present as punctate areas. PMID:25739645

  1. Evaluation of Soluble Human Leukocyte Antigen-G (sHLA-G) Isoforms and Regulatory T Cells in Relapsing-Remitting Multiple Sclerosis.

    PubMed

    Alsahebfosoul, Fereshteh; Zavaran Hosseini, Ahmad; Salehi, Rasoul; Etemadifar, Masood; Esmaeil, Nafiseh; Jamshidian, Azam

    2015-06-01

    Soluble forms of nonclassical human leukocyte antigen (HLA)-G have recently been suggested as immunomodulatory factors in multiple sclerosis (MS). HLA-G inhibits the effecter function of T cells and natural killer (NK) cells. Also regulatory T cells (Treg) are considered as pivotal players in MS pathogenesis. Thus, we aimed to evaluate the presence of HLA-G molecules and Treg cells in Relapsing-Remitting Multiple Sclerosis (RRMS) patients and compare it to healthy controls. Patients with RRMS (n=205, mean age=31.32±8.53) and healthy subjects (n=205, mean age=32.2±7.48) were studied. The patients subgrouped to untreated and treated with Interferon beta. Then sHLA-G levels (sHLA-G1 and sHLA-G5) were measured using ELISA method. Treg (CD4+ CD25+ Foxp3+) cells in patients who had sHLA-G>10 U/ml were characterized by using flow cytometry. Our data showed that there was no significant differences between RRMS patients and healthy controls in sHLA-G concentration (p>0.05). Treg cell frequencies were higher in the patients who had sHLA-G >10 U/ml compared to healthy subjects (p<0.05). Collectively, there was significant correlation between sHLA-G and frequency of Treg cells in treated RRMS patients and healthy individuals. It seems that high level sHLA-G has been instrumental in raising frequency of Treg cells in treated patients and could be associated with remission of MS disease. PMID:26546899

  2. Is Localized Scleroderma Caused by Borrelia burgdorferi?

    PubMed

    Zinchuk, Alexander N; Kalyuzhna, Lidiya D; Pasichna, Iryna A

    2016-09-01

    Despite considerable achievements in the study of localized scleroderma, the etiology of the disease has not been investigated completely. Borrelia burgdorferi-the agent of Lyme disease-is suggested to be one of the possible etiological factors of localized scleroderma. However, among scientists, this hypothesis is quite controversial. We have conducted investigations of the level of IgM and IgG class antibodies to B. burgdorferi in the serum of patients with localized scleroderma. To rationally substantiate the role of B. burgdorferi in the occurrence of localized scleroderma, thirty-two patients with localized scleroderma treated at an in-patient department were examined. The level of anti-Borrelia antibodies was determined in ELISA. Diagnostic levels of IgM and/or IgG were detected in 18.8% of patients with localized scleroderma, which is more than in the population (p < 0.01). Positive levels of anti-Borrelia antibodies in patients with localized scleroderma confirm the borreliosis nature of the disease, requiring conduction of complex antimicrobial treatment. PMID:27387068

  3. Tickborne Relapsing Fever Diagnosis Obscured by Malaria, Togo

    PubMed Central

    Nordstrand, Annika; Bunikis, Ignas; Larsson, Christer; Tsogbe, Kodjo; Schwan, Tom G.; Nilsson, Mikael

    2007-01-01

    Given the prevalence of relapsing fever (RF) in Senegal, this disease may cause illness and death in other areas of West Africa. We performed a cross-sectional, clinic-based study to investigate the presence of RF in Togo during 2002–2004. Blood samples from patients with fever were examined for RF spirochetes by microscopy, PCR, and DNA sequencing of amplicons and for antibodies to the glycerophosphodiester phosphodiesterase antigen. Although no spirochetes were seen in blood smears, ≈10% of the patients were positive by PCR and ≈13% were seropositive for spirochetes. DNA sequencing demonstrated that Borrelia crocidurae and B. duttonii were present. Most patients were treated for malaria whether or not plasmodia were observed. Thus, many RF patients originally had a misdiagnosis of malaria, which resulted in ineffective treatment. The inability of microscopic analysis to detect spirochetes compared with PCR demonstrates the need for tests with greater sensitivity. PMID:17370524

  4. Relapsing Fever Spirochetes Retain Infectivity After Prolonged in vitro Cultivation

    PubMed Central

    Schrumpf, Merry E.; Raffel, Sandra J.; Policastro, Paul F.; Porcella, Stephen F.; Schwan, Tom G.

    2008-01-01

    Abstract Borrelia hermsii and Borrelia burgdorferi, two closely related spirochetes, are the etiological agents of tick-borne relapsing fever and Lyme disease, respectively. Previous studies have shown the loss of infectivity of B. burgdorferi is associated with in vitro cultivation. This diminished infectivity of B. burgdorferi has occurred as early as three in vitro passages, and the loss of plasmids have been observed with these less virulent to noninfective cultures. The effects of long-term in vitro cultivation on B. hermsii have not been investigated. However, understanding the degree of genomic degradation during in vitro cultivation is important for investigating pathogenic mechanisms of spirochetes. In this study, we analyzed the effects of continuous in vitro cultivation on the genomic composition and infectivity of B. hermsii and B. turicatae. We report that all seven isolates of B. hermsii and the one isolate of B. turicatae examined retained infectivity in mice after 1 year of continuous in vitro cultivation. Furthermore, there were few apparent differences in the plasmid profiles after long-term cultivation. Two isolates of B. hermsii remained infective after high passage despite losing a portion of the 200-kb linear plasmid containing the fhbA gene encoding the factor H binding protein. Also, sequence analysis of multiple B. hermsii isolates demonstrated two types of fhbA with complete congruence with the two genomic groups of B. hermsii spirochetes. Therefore, these results suggest that relapsing fever spirochetes are genetically stable during in vitro cultivation, and the fhbA-containing segment of DNA that is lost during cultivation is not required for infection. PMID:18637723

  5. Borrelia garinii in Seabird Ticks (Ixodes uriae), Atlantic Coast, North America

    PubMed Central

    Muzaffar, Sabir Bin; Lavers, Jennifer; Lacombe, Eleanor H.; Cahill, Bruce K.; Lubelczyk, Charles B.; Kinsler, Allen; Mathers, Amy J.; Rand, Peter W.

    2006-01-01

    Borrelia garinii is the most neurotropic of the genospecies of B. burgdorferi sensu lato that cause Lyme disease in Europe, where it is transmitted to avian and mammalian reservoir hosts and to humans by Ixodes ricinus. B. garinii is also maintained in an enzootic cycle in seabirds by I. uriae, a tick found at high latitudes in both the Northern and Southern Hemispheres. To determine whether B. garinii is present in seabird ticks on the Atlantic Coast of North America, we examined 261 I. uriae ticks by polyclonal antiborrelial fluorescent antibody. Ten of 61 ticks from Gull Island, Newfoundland, were positive for borreliae by this screen. Amplicons of DNA obtained by PCR that targeted the B. garinii rrs-rrla intergenic spacer were sequenced and matched to GenBank sequences for B. garinii. The potential for introduction of this agent into the North American Lyme disease enzootic is unknown. PMID:17326943

  6. Antibodies to Borrelia burgdorferi in rodents in the eastern and southern United States.

    PubMed Central

    Magnarelli, L A; Oliver, J H; Hutcheson, H J; Boone, J L; Anderson, J F

    1992-01-01

    Serologic studies were conducted to determine whether white-footed mice (Peromyscus leucopus) and cotton mice (Peromyscus gossypinus) contained serum antibodies to Borrelia burgdorferi, the causative agent of Lyme borreliosis. Enzyme-linked immunosorbent assays detected antibodies to this spirochete in 35.7 and 27.3% of 56 P. leucopus and 535 P. gossypinus serum samples, respectively, collected in Connecticut, North Carolina, South Carolina, Georgia, Florida, Alabama, and Mississippi. Antibody titers ranged from 1:160 to greater than or equal to 1:40,960. On the basis of adsorption tests, the antibodies detected appeared to be specific to Borrelia spirochetes. Seropositive rodents in the eastern and southern United States, areas where human cases of Lyme borreliosis have been reported, indicate a widespread geographic distribution of B. burgdorferi or a closely related spirochete. PMID:1624561

  7. Effectiveness of Stevia Rebaudiana Whole Leaf Extract Against the Various Morphological Forms of Borrelia Burgdorferi in Vitro.

    PubMed

    Theophilus, P A S; Victoria, M J; Socarras, K M; Filush, K R; Gupta, K; Luecke, D F; Sapi, E

    2015-12-01

    Lyme disease is a tick-borne multisystemic disease caused by Borrelia burgdorferi. Administering antibiotics is the primary treatment for this disease; however, relapse often occurs when antibiotic treatment is discontinued. The reason for relapse remains unknown, but recent studies suggested the possibilities of the presence of antibiotic resistant Borrelia persister cells and biofilms. In this study, we evaluated the effectiveness of whole leaf Stevia extract against B. burgdorferi spirochetes, persisters, and biofilm forms in vitro. The susceptibility of the different forms was evaluated by various quantitative techniques in addition to different microscopy methods. The effectiveness of Stevia was compared to doxycycline, cefoperazone, daptomycin, and their combinations. Our results demonstrated that Stevia had significant effect in eliminating B. burgdorferi spirochetes and persisters. Subculture experiments with Stevia and antibiotics treated cells were established for 7 and 14 days yielding, no and 10% viable cells, respectively compared to the above-mentioned antibiotics and antibiotic combination. When Stevia and the three antibiotics were tested against attached biofilms, Stevia significantly reduced B. burgdorferi forms. Results from this study suggest that a natural product such as Stevia leaf extract could be considered as an effective agent against B. burgdorferi. PMID:26716015

  8. Effectiveness of Stevia Rebaudiana Whole Leaf Extract Against the Various Morphological Forms of Borrelia Burgdorferi in Vitro

    PubMed Central

    Theophilus, P. A. S.; Victoria, M. J.; Socarras, K. M.; Filush, K. R.; Gupta, K.; Luecke, D. F.; Sapi, E.

    2015-01-01

    Lyme disease is a tick-borne multisystemic disease caused by Borrelia burgdorferi. Administering antibiotics is the primary treatment for this disease; however, relapse often occurs when antibiotic treatment is discontinued. The reason for relapse remains unknown, but recent studies suggested the possibilities of the presence of antibiotic resistant Borrelia persister cells and biofilms. In this study, we evaluated the effectiveness of whole leaf Stevia extract against B. burgdorferi spirochetes, persisters, and biofilm forms in vitro. The susceptibility of the different forms was evaluated by various quantitative techniques in addition to different microscopy methods. The effectiveness of Stevia was compared to doxycycline, cefoperazone, daptomycin, and their combinations. Our results demonstrated that Stevia had significant effect in eliminating B. burgdorferi spirochetes and persisters. Subculture experiments with Stevia and antibiotics treated cells were established for 7 and 14 days yielding, no and 10% viable cells, respectively compared to the above-mentioned antibiotics and antibiotic combination. When Stevia and the three antibiotics were tested against attached biofilms, Stevia significantly reduced B. burgdorferi forms. Results from this study suggest that a natural product such as Stevia leaf extract could be considered as an effective agent against B. burgdorferi. PMID:26716015

  9. Persisting atypical and cystic forms of Borrelia burgdorferi and local inflammation in Lyme neuroborreliosis

    PubMed Central

    Miklossy, Judith; Kasas, Sandor; Zurn, Anne D; McCall, Sherman; Yu, Sheng; McGeer, Patrick L

    2008-01-01

    Background The long latent stage seen in syphilis, followed by chronic central nervous system infection and inflammation, can be explained by the persistence of atypical cystic and granular forms of Treponema pallidum. We investigated whether a similar situation may occur in Lyme neuroborreliosis. Method Atypical forms of Borrelia burgdorferi spirochetes were induced exposing cultures of Borrelia burgdorferi (strains B31 and ADB1) to such unfavorable conditions as osmotic and heat shock, and exposure to the binding agents Thioflavin S and Congo red. We also analyzed whether these forms may be induced in vitro, following infection of primary chicken and rat neurons, as well as rat and human astrocytes. We further analyzed whether atypical forms similar to those induced in vitro may also occur in vivo, in brains of three patients with Lyme neuroborreliosis. We used immunohistochemical methods to detect evidence of neuroinflammation in the form of reactive microglia and astrocytes. Results Under these conditions we observed atypical cystic, rolled and granular forms of these spirochetes. We characterized these abnormal forms by histochemical, immunohistochemical, dark field and atomic force microscopy (AFM) methods. The atypical and cystic forms found in the brains of three patients with neuropathologically confirmed Lyme neuroborreliosis were identical to those induced in vitro. We also observed nuclear fragmentation of the infected astrocytes using the TUNEL method. Abundant HLA-DR positive microglia and GFAP positive reactive astrocytes were present in the cerebral cortex. Conclusion The results indicate that atypical extra- and intracellular pleomorphic and cystic forms of Borrelia burgdorferi and local neuroinflammation occur in the brain in chronic Lyme neuroborreliosis. The persistence of these more resistant spirochete forms, and their intracellular location in neurons and glial cells, may explain the long latent stage and persistence of Borrelia infection

  10. Antigenically variable Borrelia burgdorferi isolated from cottontail rabbits and Ixodes dentatus in rural and urban areas.

    PubMed Central

    Anderson, J F; Magnarelli, L A; LeFebvre, R B; Andreadis, T G; McAninch, J B; Perng, G C; Johnson, R C

    1989-01-01

    Spirochetes were isolated from 71 subadult Ixodes dentatus removed from cottontail rabbits captured in Millbrook, N.Y., and in New York, N.Y. Spirochetes were also cultured from kidney tissues of six rabbits. While all isolates reacted with monoclonal antibody H9724, which identifies the spirochetes as borreliae, more than half did not bind with antibody H5332 and even fewer reacted with H3TS, both of which were produced to outer surface protein A of Borrelia burgdorferi. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis protein profiles of three isolates differed from one another and from all previously characterized B. burgdorferi strains from humans, ticks, and wildlife in North America. The 12 periplasmic flagella that originated subterminally from each pointed end of a rabbit Borellia isolate contrasted with the 11 or fewer flagella for B. burgdorferi reported previously from North America. Although DNA homology and restriction endonuclease analysis also revealed differences among a rabbit kidney isolate, an I. dentatus isolate, and B. burgdorferi B31, similarities were sufficient to lead us to conclude that the borreliae in rabbits and I. dentatus are B. burgdorferi. Enzyme-linked immunosorbent assay titers of sera from humans with diagnosed Lyme disease to rabbit tick B. burgdorferi were often similar to one another and to those recorded for a reference B. burgdorferi strain. Images PMID:2913024

  11. Thwarting the Renewal (Relapse) of Conditioned Fear with the Explicitly Unpaired Procedure: Possible Interpretations and Implications for Treating Human Fears and Phobias

    ERIC Educational Resources Information Center

    Thomas, Brian L.; Longo, Craig L.; Ayres, John J. B.

    2005-01-01

    In three experiments using the barpress conditioned suppression task with albino rats, we studied the renewal (relapse) of conditioned fear in an ABA fear-renewal paradigm. We found that explicitly unpaired (EU) deliveries of conditioned stimuli (CSs) and unconditioned stimuli (USs) in Context B thwarted fear renewal in Context A. Evidence…

  12. Borrelia burgdorferi mutant lacking Osp: biological and immunological characterization.

    PubMed Central

    Sadziene, A; Thomas, D D; Barbour, A G

    1995-01-01

    All Borrelia burgdorferi sensu lato isolates characterized to date have one or a combination of several major outer surface proteins (Osps). Mutants of B. burgdorferi lacking Osps were selected with polyclonal or monoclonal antibodies at a frequency of 10(-6) to 10(-5). One mutant that lacked OspA, -B, -C, and -D was further characterized. It was distinguished from the OspA+B+ cells by its (i) autoaggregation and slower growth rate, (ii) decreased plating efficiency on solid medium, (iii) serum and complement sensitivity, and (iv) diminished capacity to adhere to human umbilical vein endothelial cells. The Osp-less mutant was unable to evoke a detectable immune response after intradermal live cell immunization even though mutant survived in mouse skin for the same duration as wild-type cells. Polyclonal mouse serum raised against Osp-less cells inhibited growth of the mutant but not of wild-type cells, an indication that other antigens are present on the surface of the Osp-less mutant. Two types of monoclonal antibodies (MAbs) with growth-inhibiting properties for mutant cells were identified. The first type bound to a 13-kDa surface protein of B. burgdorferi sensu stricto and of B. afzelii. The MIC of the Fab fragment of one MAb of this type was 0.2 micrograms/ml. The second type of MAb to the Osp-less mutant did not bind to B. burgdorferi components by Western blotting (immunoblotting) but did not bind to unfixed, viable cells in immunofluorescence and growth inhibition assays. These studies revealed possible functions Osp proteins in borrelias, specifically serum resistance, and indicated that in the absence of Osp proteins, other antigens are expressed or become accessible at the cell surface. PMID:7890424

  13. Complement Evasion by Borrelia burgdorferi: Serum-Resistant Strains Promote C3b Inactivation

    PubMed Central

    Alitalo, Antti; Meri, Taru; Rämö, Lasse; Jokiranta, T. Sakari; Heikkilä, Tero; Seppälä, Ilkka J. T.; Oksi, Jarmo; Viljanen, Matti; Meri, Seppo

    2001-01-01

    The most characteristic features of the Lyme disease pathogens, the Borrelia burgdorferi sensu lato (s.l.) group, are their ability to invade tissues and to circumvent the immune defenses of the host for extended periods of time, despite elevated levels of borrelia-specific antibodies in serum and other body fluids. Our aim in the present study was to determine whether B. burgdorferi is able to interfere with complement (C) at the level of C3 by accelerating C3b inactivation and thus to inhibit the amplification of the C cascade. Strains belonging to different genospecies (Borrelia garinii, B. burgdorferi sensu stricto, and Borrelia afzelii) were compared for their sensitivities to normal human serum and abilities to promote factor I-mediated C3b degradation. B. burgdorferi sensu stricto and B. afzelii strains were found to be serum resistant. When the spirochetes were incubated with radiolabeled C3b, factor I-mediated degradation of C3b was observed in the presence of C-resistant B. afzelii (n = 3) and B. burgdorferi sensu stricto (n = 1) strains but not in the presence of C-sensitive B. garinii (n = 7) strains or control bacteria (Escherichia coli, Staphylococcus aureus, and Enterococcus faecalis). Immunoblotting and radioligand binding analyses showed that the C-resistant strains had the capacity to acquire the C inhibitors factor H and factor H-like protein 1 (FHL-1) from growth medium and human serum. A novel surface protein with an apparent molecular mass of 35 kDa was found to preferentially bind to the N terminus region of factor H. Thus, the serum-resistant B. burgdorferi s.l. strains can circumvent C attack by binding the C inhibitors factor H and FHL-1 to their surfaces and promoting factor I-mediated C3b degradation. PMID:11349031

  14. A Case of Relapsing-Remitting Neuroborreliosis? Challenges in the Differential Diagnosis of Recurrent Myelitis

    PubMed Central

    Albrecht, P.; Henke, N.; Lehmann, H.C.; Macht, S.; Hefter, H.; Goebels, N.; Mackenzie, C.; Rupprecht, T.A.; Fingerle, V.; Hartung, H.P.; Methner, A.

    2012-01-01

    We report the case of a 31-year-old woman with 4 episodes of myelitis with pleocytosis, a positive Borrelia burgdorferi serology with positive antibody indices, and full recovery each time after antibiotic and steroid treatment, suggesting neuroborreliosis. We nevertheless believe that recurrent neuroborreliosis is improbable based on the levels of the chemokine CXCL13 in cerebrospinal fluid and favor the diagnosis of post-infectious autoimmune-mediated transverse myelitis possibly triggered by an initial neuroborreliosis as the cause of the relapses observed in our patient. We demonstrate the diagnostic steps and procedures which were important in the differential diagnosis of this unusual and challenging case. PMID:22649342

  15. Multiplex 5′ Nuclease-Quantitative PCR for Diagnosis of Relapsing Fever in a Large Tanzanian Cohort ▿

    PubMed Central

    Reller, Megan E.; Clemens, Emily G.; Schachterle, Steve E.; Mtove, George A.; Sullivan, David J.; Dumler, J. Stephen

    2011-01-01

    Relapsing fever (RF) is caused by tick- and louse-borne Borrelia spp., is characterized by recurrent fever, and is often misdiagnosed as malaria. Because of submicroscopic bacteremia, microscopy can be insensitive between febrile bouts. We designed a multiplex quantitative PCR (qPCR) assay to distinguish RF Borrelia from Plasmodium falciparum and P. vivax. The assay specifically (100%) amplified pathogenic RF Borrelia (1 copy/reaction). We then tested blood from participants within a Tanzanian cohort assessed at scheduled intervals and with fever. Among 8,617 blood samples from 2,057 participants surveyed routinely, 7 (0.08%) samples and 7 (0.3%) participants had RF DNA (median, 4.4 × 103 copies/ml). Of 382 samples from 310 febrile persons, 15 (3.9%) samples from 13 (4.2%) participants had RF DNA (median, 7.9 × 102 copies/ml). Five (1.3%) samples from 4 (1.3%) participants were found to harbor Borrelia by microscopy. We conclude that multiplex qPCR holds promise for improved clinical diagnosis and epidemiologic assessment of RF. PMID:21775542

  16. Genomic Characteristics of Chinese Borrelia burgdorferi Isolates

    PubMed Central

    Hou, Xuexia; Zhang, Lin; Zhang, Yuanyuan; Liu, Huixin; Liu, Wei; Chen, Chen; Wan, Kanglin

    2016-01-01

    In China, B. burgdorferi, B.garinii, B. afzelii and B. yangtze sp. nov have been reported; B.garinii and B. afzelii are the main pathogenic genotypes. But until now only one Chinese strain was reported with whole genome sequence. In order to further understand the genomic characteristics and diversity of Chinese Borrelia strains, 5 isolates from China were sequenced and compared with the whole genome sequences of strains in other areas. The results showed a high degree of conservation within the linear chromosome of Chinese strains, whereas plasmid showed a much larger diversity according to the majority genomic information of plasmids. The genome sequences of the five Chinese strains were compared with the corresponding reference strains, respectively, according to the genospecies. Pairwise analysis demonstrates that there are only 70 SNPs between the genomes of CS4 and B31. However, there are many more SNPs between the genomes of QX-S13 and VS116, PD91 and PBi, FP1 and PKo, R9 and Pko, respectively. Gene comparison showed some important different genes. OspA was one of the important different genes. Comparative genomic studies have found that OspA gene sequences of PD91 and R9 had great differences compared with the sequence of B31. OspA gene sequence of R9 had a 96bp deletion; OspA gene of PD91 had two deletions: 9bp and 10 bp. To conclude, we showed the genomic characteristics of four genotype Chinese B. burgdorferi strains. The genomic sequence of B. yangtze sp. nov and differences from B. valaisiana were first reported. Comparative analysis of Chinese strains with the different Borrelia species from other areas will help us to understand evolution and pathogenesis of Chinese Borrelia burgdorferi strains. PMID:27093540

  17. Insomnia, alcoholism and relapse.

    PubMed

    Brower, Kirk J

    2003-12-01

    Insomnia and alcoholism are significantly associated in community surveys and patient samples. Insomnia occurs in 36-72% of alcoholic patients and may last for weeks to months after initiating abstinence from alcohol. Some correlates of insomnia in alcoholic patients are identical to those observed in non-alcoholic insomniacs, including anxiety and depression, tobacco smoking, and the use of alcohol to aid sleep. Other studies suggest that as the severity of alcoholism increases, so does the likelihood of insomnia in alcoholic patients. In the sleep laboratory, alcoholic patients who complain of insomnia have disrupted sleep continuity when compared to alcoholic patients without insomnia complaints. Recently sober alcoholics are also more likely than non-alcoholics to have sleep-disordered breathing and increased periodic leg movements, which might contribute to insomnia in some alcoholic patients. The co-occurrence of insomnia and alcoholism is clinically significant because alcoholism can exacerbate the adverse consequences of insomnia (e.g. mood changes and performance decrements) and because insomnia among patients entering treatment for alcoholism has been significantly associated with subsequent alcoholic relapse. Baseline polysomnographic correlates of subsequent relapse include prolonged sleep latency, decreased sleep efficiency and total sleep time, increased rapid eye movement sleep pressure, and decreased slow wave sleep. Whether treatment of insomnia in alcoholic patients reduces relapse rates is unknown, but preliminary treatment guidelines that accommodate the special characteristics of alcoholic patients are provided, with a goal to reduce daytime impairment and psychological distress. PMID:15018094

  18. Borrelia infection and risk of non-Hodgkin lymphoma

    PubMed Central

    Melbye, Mads; Munksgaard, Lars; Smedby, Karin Ekström; Rostgaard, Klaus; Glimelius, Bengt; Chang, Ellen T.; Roos, Göran; Hansen, Mads; Adami, Hans-Olov; Hjalgrim, Henrik

    2008-01-01

    Reports of the presence of Borrelia burgdorferi DNA in malignant lymphomas have raised the hypothesis that infection with B burgdorferi may be causally related to non-Hodgkin lymphoma (NHL) development. We conducted a Danish-Swedish case-control study including 3055 NHL patients and 3187 population controls. History of tick bite or Borrelia infection was ascertained through structured telephone interviews and through enzyme-linked immunosorbent assay serum analyses for antibodies against B burgdorferi in a subset of 1579 patients and 1358 controls. Statistical associations with risk of NHL, including histologic subtypes, were assessed by logistic regression. Overall risk of NHL was not associated with self-reported history of tick bite (odds ratio [OR] = 1.0; 95% confidence interval: 0.9-1.1), Borrelia infection (OR = 1.3 [0.96-1.8]) or the presence of anti-Borrelia antibodies (OR = 1.3 [0.9-2.0]). However, in analyses of NHL subtypes, self-reported history of B burgdorferi infection (OR = 2.5 [1.2-5.1]) and seropositivity for anti-Borrelia antibodies (OR = 3.6 [1.8-7.4]) were both associated with risk of mantle cell lymphoma. Notably, this specific association was also observed in persons who did not recall Borrelia infection yet tested positive for anti-Borrelia antibodies (OR = 4.2 [2.0-8.9]). Our observations suggest a previously unreported association between B burgdorferi infection and risk of mantle cell lymphoma. PMID:18424667

  19. First isolation and cultivation of Borrelia burgdorferi sensu lato from Missouri.

    PubMed

    Oliver, J H; Kollars, T M; Chandler, F W; James, A M; Masters, E J; Lane, R S; Huey, L O

    1998-01-01

    Five Borrelia burgdorferi sensu lato isolates from Missouri are described. This represents the first report and characterization of such isolates from that state. The isolates were obtained from either Ixodes dentatus or Amblyomma americanum ticks that had been feeding on cottontail rabbits (Sylvilagus floridanus) from a farm in Bollinger County, Mo., where a human case of Lyme disease had been reported. All isolates were screened immunologically by indirect immunofluorescence by using monoclonal antibodies to B. burgdorferi-specific outer surface protein A (OspA) (antibodies H3TS and H5332), B. burgdorferi-specific OspB (antibody H6831), Borrelia (genus)-specific antiflagellin (antibody H9724), and Borrelia hermsii-specific antibody (antibody H9826). Analysis of the isolates also involved a comparison of their protein profiles by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Finally, the isolates were analyzed by PCR with six pairs of primers known to amplify selected DNA target sequences specifically found in the reference strain B. burgdorferi B-31. Although some genetic variability was detected among the five isolates as well as between them and the B-31 strain, enough similarities were found to classify them as B. burgdorferi sensu lato. PMID:9431909

  20. Colony formation and morphology in Borrelia burgdorferi.

    PubMed

    Kurtti, T J; Munderloh, U G; Johnson, R C; Ahlstrand, G G

    1987-11-01

    Two strains of Borrelia burgdorferi, B31 and 297, formed colonies when plated onto Barbour-Stoenner-Kelly medium solidified with agarose (1.3%) and incubated in a candle jar at 34 degrees C. Colonies differing in morphology were observed in both strains after 2 to 3 weeks of incubation. Strain B31 colonies were either compact, round (mean diameter, 0.43 mm), and restricted to the surface of the agarose medium or diffuse (mean diameter, 1.80 mm) and penetrating into the solid medium. Strain 297 colonies (mean diameter, 1.43 mm) either showed a raised center surrounded by a diffuse ring of spirochetes or consisted of numerous small spirochetal aggregates. Both colony types expanded into the agarose medium. Scanning electron and light microscopy confirmed that the colonies were formed by spirochetes. Twisted tangles of intertwined spirochetes were visible on the surface, with numerous spherical bodies among them, especially in the central regions. At the periphery, the borreliae were more loosely packed, and individual coils were discernible. PMID:3693538

  1. Borrelia burgdorferi bind to epithelial cell proteoglycans.

    PubMed Central

    Isaacs, R D

    1994-01-01

    Borrelia burgdorferi adhere to mammalian cells in vitro but neither the ligand(s) nor the receptor(s) has (have) been clearly established. Using an in vitro attachment-inhibition assay, a B. burgdorferi attachment mechanism has been identified. Heparin, heparan sulfate, and dermatan sulfate reduced the attachment of virulent B. burgdorferi strain 297 to HeLa cells by approximately 60%. In addition, virulent, but not avirulent, B. burgdorferi strains B31, N40, and HB19 demonstrated heparin attachment-inhibition. Attachment to Chinese hamster ovary cells deficient in heparan sulfate proteoglycans was reduced by 68% compared to attachment to wild-type cells and was identical to attachment at maximum heparin inhibition to the wild-type cells. Pretreatment of HeLa cell monolayers with heparitinase, heparinase, and chondroitinase ABC, but not with chondroitinase AC, reduced borrelial attachment by approximately 50%. A moderately high affinity, low copy number, promiscuous B. burgdorferi glycosaminoglycan receptor was demonstrated by equilibrium binding studies. A 39-kD polypeptide, purified by heparin affinity chromatography from Triton X-100 extracts derived from virulent borrelia, was a candidate for this receptor. These studies indicate that one mode of B. burgdorferi attachment to eukaryotic cells is mediated by a borrelial glycosaminoglycan receptor attaching to surface-exposed proteoglycans on mammalian cells. Images PMID:8113413

  2. Tickborne relapsing fever in a mother and newborn child--Colorado, 2011.

    PubMed

    2012-03-16

    Tickborne relapsing fever (TBRF) is a bacterial infection caused by certain species of Borrelia spirochetes and transmitted through the bite of Ornithodoros ticks. Clinical illness is characterized by relapsing fever, myalgias, and malaise. On May 10, 2011, CDC and the Colorado Department of Public Health and Environment were notified of two patients with TBRF: a young woman and her newborn child. This report summarizes the clinical course of these patients and emphasizes the importance of considering a diagnosis of TBRF among patients with compatible clinical symptoms and residence or travel in a TBRF-endemic area. Pregnant women and neonates are at increased risk for TBRF-associated complications and require prompt diagnosis and treatment for optimal clinical outcomes. Public health follow-up of reported TBRF cases should include a search for persons sharing an exposure with the patient and environmental investigation with remediation measures to prevent additional infections. PMID:22419050

  3. [Relapse prevention in drug addicts].

    PubMed

    Rácz, József

    2013-12-01

    The literature review deals with methods of relapse prevention. Relapse prevention is the key in the treatment of clients with drug addictions according to the transtheoretical model of change. If relapse prevention is more effective then not only the relapse would be prevented, but the client would leave the circulus vitiosus of relapses. Among psychotherapies cognitive behavioural methods are proven effective. Shorter forms of cognitive therapies are also available: for example, cognitive bias modification. Pharmacotherapy partly decreases craving of the clients or ceases the effects of psychoactive substances. Specific pharmacotherapeutic methods prevent relapses in a non-abstinent treatment design. Here the goal is not the abstinence in a short time, but the reduction of harms associated with drug use. In this way, a new target group of drug users can be involved in treatment. PMID:24380964

  4. The Heterogeneity, Distribution, and Environmental Associations of Borrelia burgdorferi Sensu Lato, the Agent of Lyme Borreliosis, in Scotland

    PubMed Central

    James, Marianne C.; Gilbert, Lucy; Bowman, Alan S.; Forbes, Ken J.

    2014-01-01

    Lyme borreliosis is an emerging infectious human disease caused by the Borrelia burgdorferi sensu lato complex of bacteria with reported cases increasing in many areas of Europe and North America. To understand the drivers of disease risk and the distribution of symptoms, which may improve mitigation and diagnostics, here we characterize the genetics, distribution, and environmental associations of B. burgdorferi s.l. genospecies across Scotland. In Scotland, reported Lyme borreliosis cases have increased almost 10-fold since 2000 but the distribution of B. burgdorferi s.l. is so far unstudied. Using a large survey of over 2200 Ixodes ricinus tick samples collected from birds, mammals, and vegetation across 25 sites we identified four genospecies: Borrelia afzelii (48%), Borrelia garinii (36%), Borrelia valaisiana (8%), and B. burgdorferi sensu stricto (7%), and one mixed genospecies infection. Surprisingly, 90% of the sequence types were novel and, importantly, up to 14% of samples were mixed intra-genospecies co-infections, suggesting tick co-feeding, feeding on multiple hosts, or multiple infections in hosts. B. garinii (hosted by birds) was considerably more genetically diverse than B. afzelii (hosted by small mammals), as predicted since there are more species of birds than small mammals and birds can import strains from mainland Europe. Higher proportions of samples contained B. garinii and B. valaisiana in the west, while B. afzelii and B. garinii were significantly more associated with mixed/deciduous than with coniferous woodlands. This may relate to the abundance of transmission hosts in different regions and habitats. These data on the genetic heterogeneity within and between Borrelia genospecies are a first step to understand pathogen spread and could help explain the distribution of patient symptoms, which may aid local diagnosis. Understanding the environmental associations of the pathogens is critical for rational policy making for disease risk

  5. Biomechanics of Borrelia burgdorferi Vascular Interactions.

    PubMed

    Ebady, Rhodaba; Niddam, Alexandra F; Boczula, Anna E; Kim, Yae Ram; Gupta, Nupur; Tang, Tian Tian; Odisho, Tanya; Zhi, Hui; Simmons, Craig A; Skare, Jon T; Moriarty, Tara J

    2016-09-01

    Systemic dissemination of microbes is critical for progression of many infectious diseases and is associated with most mortality due to bacterial infection. The physical mechanisms mediating a key dissemination step, bacterial association with vascular endothelia in blood vessels, remain unknown. Here, we show that endothelial interactions of the Lyme disease spirochete Borrelia burgdorferi under physiological shear stress mechanistically resemble selectin-dependent leukocyte rolling. Specifically, these interactions are mediated by transfer of mechanical load along a series of adhesion complexes and are stabilized by tethers and catch bond properties of the bacterial adhesin BBK32. Furthermore, we found that the forces imposed on adhesive bonds under flow may be small enough to permit active migration driven by bacterial flagellar motors. These findings provide insight into the biomechanics of bacterial-vascular interactions and demonstrate that disseminating bacteria and circulating host immune cells share widely conserved mechanisms for interacting with endothelia under physiological shear stress. PMID:27568563

  6. Immunologic and genetic analyses of VmpA of a neurotropic strain of Borrelia turicatae.

    PubMed Central

    Cadavid, D; Pennington, P M; Kerentseva, T A; Bergström, S; Barbour, A G

    1997-01-01

    In mice infected with serotype A but not serotype B of the relapsing fever spirochete Borrelia turicatae, early invasion of the brain occurs. Serotypes A and B are further distinguished by the abundant surface protein they produce: VmpA and VmpB, respectively. Western blotting with monoclonal antibodies, one-dimensional peptide mapping, and partial amino acid sequencing demonstrated regions of the VmpA protein that differed from VmpB. Oligonucleotide primers based on the partial amino acid sequences of unique regions were used to amplify a portion of the VmpA gene (vmpA) by PCR, and the product was used as a probe in Southern blot and Northern blot analyses. These experiments showed that (i) expression of the vmpA sequence was determined at the level of transcription and (ii) the vmpA sequence was in two locations in serotype A and one location in serotype B. The vmpA gene at the expression-linked locus of serotype A was cloned and sequenced. An open reading frame would encode a polypeptide of 214 amino acids. The polypeptide expressed by Escherichia coli was bound by VmA-specific but not VmpB-specific antibody. Primer extension analysis identified a consensus sigma70-type promoter for vmpA at the expression locus. Phylogenetic analysis revealed that VmpA is homologous to small Vmp (Vsp) proteins of B. hermsii and to OspC proteins of B. burgdorferi. These findings indicate that a function of the Vsp-OspC family of proteins of Borrelia spp. may be differential localization in organs, including the brain, during infection. PMID:9234797

  7. Tick-borne Relapsing Fever in the Pacific Northwest: An Underdiagnosed Illness?

    PubMed Central

    Fihn, Stephan; Larson, Eric B.

    1980-01-01

    Some 30 cases of tick-borne relapsing fever due to Borrelia are known to have occurred between 1965 and 1978 in the Pacific Northwest. This disease was found more frequently in young men with a history of wilderness exposure during the summer months. Recurrent fever was the most common symptom with temperatures reaching higher than 39.5° C (103.1° F) in all cases, and many patients had three or more febrile episodes. Splenomegaly was the second most common finding reported. Diagnosis of relapsing fever was made in 20 cases by identifying spirochetes on peripheral blood smears. In ten remaining cases the diagnosis was made on clinical and epidemiologic grounds. Information regarding therapy was available in 21 cases. Ten patients received a tetracycline drug and all had a prompt response without relapse. Two of the patients died, a 68-year-old woman with possible myocardial involvement and a newborn infant with infection acquired in utero and meningeal involvement. The diagnosis was often delayed in spite of outpatient evaluation and admittance to hospital, probably because borreliosis was not considered in the differential diagnosis. Because tick-borne relapsing fever is eventually a self-limited disease in most patients, it is probably not recognized often enough. Awareness of this disease and examination of the peripheral blood smear for spirochetes will lead to earlier diagnosis. Prompt initiation of tetracycline therapy should reduce morbidity associated with borreliosis. ImagesFigure 3. PMID:7415171

  8. Distribution of Borrelia burgdorferi in host mice in Pennsylvania.

    PubMed Central

    Lord, R D; Lord, V R; Humphreys, J G; McLean, R G

    1994-01-01

    Host mice (Peromyscus leucopus and Peromyscus maniculatus) were sampled throughout the state of Pennsylvania to determine the geographical and ecological distribution of the Lyme disease spirochete Borrelia burgdorferi. All 67 counties of the state were sampled. A total of 1,619 mice were captured from a total of 157 sites during the period 1990 to 1993 for an overall capture rate of 29.69%. A total of 112 (6.92%) isolations of B. burgdorferi were made. The distribution of isolations revealed the reason for the correlated distribution of human cases of Lyme disease in the state. Significantly more mice were captured and significantly more isolations were made from hemlock (Tsuga canadensis) habitat than from deciduous species forest. Nevertheless, high isolation rates from counties of the southeastern corner of the state illustrate well that hemlock habitat is not essential. Evidence suggests that in some areas, transmission between mice is occurring in some way other than through ticks as vectors. Host mice proved useful for determining the geographical and ecological distribution of B. burgdorferi. PMID:7814489

  9. Linear and Circular Plasmid Content in Borrelia burgdorferi Clinical Isolates

    PubMed Central

    Iyer, Radha; Kalu, Ogori; Purser, Joye; Norris, Steven; Stevenson, Brian; Schwartz, Ira

    2003-01-01

    The genome of Borrelia burgdorferi, the etiologic agent of Lyme disease, is composed of a linear chromosome and more than 20 linear and circular plasmids. Typically, plasmid content analysis has been carried out by pulsed-field gel electrophoresis and confirmed by Southern hybridization. However, multiple plasmids of virtually identical sizes (e.g., lp28 and cp32) complicate the interpretation of such data. The present study was undertaken to investigate the complete plasmid complements of B. burgdorferi clinical isolates cultivated from patients from a single region where early Lyme disease is endemic. A total of 21 isolates obtained from the skin biopsy or blood samples of Lyme disease patients were examined for their complete plasmid complements by Southern hybridization and plasmid-specific PCR analysis. All clinical isolates harbored at least six of the nine previously characterized cp32s. Fourteen isolates harbored all B31-like linear plasmids, and seven isolates simultaneously lacked lp56, lp38, and some segments of lp28-1. The distinctive plasmid profile observed in these seven isolates was specific to organisms that had ribosomal spacer type 2 and pulsed-field gel type A, which implies a clonal origin for this genotype. The presence of nearly identical complements of multiple linear and circular plasmids in all of the human isolates suggests that these plasmids may be particularly necessary for infection, adaptation, and/or maintenance in the infected host. PMID:12819050

  10. Morphological and biochemical features of Borrelia burgdorferi pleomorphic forms

    PubMed Central

    Herranen, Anni; Schwarzbach, Armin; Gilbert, Leona

    2015-01-01

    The spirochaete bacterium Borrelia burgdorferi sensu lato is the causative agent of Lyme disease, the most common tick-borne infection in the northern hemisphere. There is a long-standing debate regarding the role of pleomorphic forms in Lyme disease pathogenesis, while very little is known about the characteristics of these morphological variants. Here, we present a comprehensive analysis of B. burgdorferi pleomorphic formation in different culturing conditions at physiological temperature. Interestingly, human serum induced the bacterium to change its morphology to round bodies (RBs). In addition, biofilm-like colonies in suspension were found to be part of B. burgdorferi’s normal in vitro growth. Further studies provided evidence that spherical RBs had an intact and flexible cell envelope, demonstrating that they are not cell wall deficient, or degenerative as previously implied. However, the RBs displayed lower metabolic activity compared with spirochaetes. Furthermore, our results indicated that the different pleomorphic variants were distinguishable by having unique biochemical signatures. Consequently, pleomorphic B. burgdorferi should be taken into consideration as being clinically relevant and influence the development of novel diagnostics and treatment protocols. PMID:25564498

  11. Extinction, Relapse, and Behavioral Momentum

    PubMed Central

    Podlesnik, Christopher A.; Shahan, Timothy A.

    2010-01-01

    Previous experiments on behavioral momentum have shown that relative resistance to extinction of operant behavior in the presence of a discriminative stimulus depends upon the baseline rate or magnitude of reinforcement associated with that stimulus (i.e., the Pavlovian stimulus-reinforcer relation). Recently, we have shown that relapse of operant behavior in reinstatement, resurgence, and context renewal preparations also is a function of baseline stimulus-reinforcer relations. In this paper we present new data examining the role of baseline stimulus-reinforcer relations on resistance to extinction and relapse using a variety of baseline training conditions and relapse operations. Furthermore, we evaluate the adequacy of a behavioral-momentum based model in accounting for the results. The model suggests that relapse occurs as a result of a decrease in the disruptive impact of extinction precipitated by a change in circumstances associated with extinction, and that the degree of relapse is a function of the pre-extinction baseline Pavlovian stimulus-reinforcer relation. Across experiments, relative resistance to extinction and relapse were greater in the presence of stimuli associated with more favorable conditions of reinforcement and were positively related to one another. In addition, the model did a good job in accounting for these effects. Thus, behavioral momentum theory may provide a useful quantitative approach for characterizing how differential reinforcement conditions contribute to relapse of operant behavior. PMID:20152889

  12. Extinction, relapse, and behavioral momentum.

    PubMed

    Podlesnik, Christopher A; Shahan, Timothy A

    2010-05-01

    Previous experiments on behavioral momentum have shown that relative resistance to extinction of operant behavior in the presence of a discriminative stimulus depends upon the baseline rate or magnitude of reinforcement associated with that stimulus (i.e., the Pavlovian stimulus-reinforcer relation). Recently, we have shown that relapse of operant behavior in reinstatement, resurgence, and context renewal preparations also is a function of baseline stimulus-reinforcer relations. In this paper we present new data examining the role of baseline stimulus-reinforcer relations on resistance to extinction and relapse using a variety of baseline training conditions and relapse operations. Furthermore, we evaluate the adequacy of a behavioral momentum based model in accounting for the results. The model suggests that relapse occurs as a result of a decrease in the disruptive impact of extinction precipitated by a change in circumstances associated with extinction, and that the degree of relapse is a function of the pre-extinction baseline Pavlovian stimulus-reinforcer relation. Across experiments, relative resistance to extinction and relapse were greater in the presence of stimuli associated with more favorable conditions of reinforcement and were positively related to one another. In addition, the model did a good job in accounting for these effects. Thus, behavioral momentum theory may provide a useful quantitative approach for characterizing how differential reinforcement conditions contribute to relapse of operant behavior. PMID:20152889

  13. Short-term stability of Borrelia garinii in cerebrospinal fluid.

    PubMed

    Berenová, Dagmar; Krsek, Daniel; Šípková, Lenka; Lukavská, Alena; Malý, Marek; Kurzová, Zuzana; Hořejší, Jan; Kodym, Petr

    2016-01-01

    The aim of our study was to find out the optimal conditions for short-term storage of cerebrospinal fluid (CSF) samples for direct diagnosis of Lyme disease. A mixture of Borrelia-negative CSFs spiked with a defined amount of cultured Borrelia garinii was used. Borrelia stability was investigated over 7 days at four different temperatures [room temperature (RT), +4, -20 and -70 °C]. Quantitative changes in CSF Borrelia were measured by quantitative PCR (qPCR), and morphological changes in the spirochetes were observed by transmission electron microscopy (TEM). These qPCR results were statistically evaluated. We found +4 °C to be an optimal temperature for short-term storage of CSF samples intended for TEM observation. There was no significant difference between the temperatures tested in the average quantity of Borrelia measured by qPCR. On the contrary, electron optical diagnosis of frozen samples and samples stored at RT showed destructive morphological changes and decreased spirochete counts. Our results show that optimal conditions for the pre-analytical phase of investigation of one type of material can differ depending on the diagnostic method employed. PMID:26104540

  14. Transstadial transmission of Borrelia turcica in Hyalomma aegyptium ticks.

    PubMed

    Kalmár, Zsuzsa; Cozma, Vasile; Sprong, Hein; Jahfari, Setareh; D'Amico, Gianluca; Mărcuțan, Daniel I; Ionică, Angela M; Magdaş, Cristian; Modrý, David; Mihalca, Andrei D

    2015-01-01

    Borrelia turcica comprises the third major group of arthropod-transmitted borreliae and is phylogenetically divergent from other Borrelia groups. The novel group of Borrelia was initially isolated from Hyalomma aegyptium ticks in Turkey and it was recently found in blood and multiple organs of tortoises exported from Jordan to Japan. However, the ecology of these spirochetes and their development in ticks or the vertebrate hosts were not investigated in detail; our aims were to isolate the pathogen and to evaluate the possibility of transstadial transmission of Borrelia turcica by H. aegyptium ticks. Ticks were collected from Testudo graeca tortoises during the summer of 2013 from southeastern Romania. Engorged nymphs were successfully molted to the adult stage. Alive B. turcica was isolated from molted ticks by using Barbour-Stoenner-Kelly (BSK) II medium. Four pure cultures of spirochetes were obtained and analyzed by PCR and sequencing. Sequence analysis of glpQ, gyrB and flaB revealed 98%-100% similarities with B. turcica. H. aegyptium ticks collected from T. graeca tortoises were able to pass the infection with B. turcica via transstadial route, suggesting its vectorial capacity. PMID:25695663

  15. Transstadial Transmission of Borrelia turcica in Hyalomma aegyptium Ticks

    PubMed Central

    Kalmár, Zsuzsa; Cozma, Vasile; Sprong, Hein; Jahfari, Setareh; D’Amico, Gianluca; Mărcuțan, Daniel I.; Ionică, Angela M.; Magdaş, Cristian; Modrý, David; Mihalca, Andrei D.

    2015-01-01

    Borrelia turcica comprises the third major group of arthropod-transmitted borreliae and is phylogenetically divergent from other Borrelia groups. The novel group of Borrelia was initially isolated from Hyalomma aegyptium ticks in Turkey and it was recently found in blood and multiple organs of tortoises exported from Jordan to Japan. However, the ecology of these spirochetes and their development in ticks or the vertebrate hosts were not investigated in detail; our aims were to isolate the pathogen and to evaluate the possibility of transstadial transmission of Borrelia turcica by H. aegyptium ticks. Ticks were collected from Testudo graeca tortoises during the summer of 2013 from southeastern Romania. Engorged nymphs were successfully molted to the adult stage. Alive B. turcica was isolated from molted ticks by using Barbour-Stoenner-Kelly (BSK) II medium. Four pure cultures of spirochetes were obtained and analyzed by PCR and sequencing. Sequence analysis of glpQ, gyrB and flaB revealed 98%–100% similarities with B. turcica. H. aegyptium ticks collected from T. graeca tortoises were able to pass the infection with B. turcica via transstadial route, suggesting its vectorial capacity. PMID:25695663

  16. Molecular and Pathogenic Characterization of Borrelia burgdorferi Sensu Lato Isolates from Spain

    PubMed Central

    Escudero, Raquel; Barral, Marta; Pérez, Azucena; Vitutia, M. Mar; García-Pérez, Ana L.; Jiménez, Santos; Sellek, Ricela E.; Anda, Pedro

    2000-01-01

    Fifteen Borrelia burgdorferi sensu lato isolates from questing ticks and skin biopsy specimens from erythema migrans patients in three different areas of Spain were characterized. Four different genospecies were found (nine Borrelia garinii, including the two human isolates, three B. burgdorferi sensu stricto, two B. valaisiana, and one B. lusitaniae), showing a diverse spectrum of B. burgdorferi sensu lato species. B. garinii isolates were highly variable in terms of pulsed-field gel electrophoresis pattern and OspA serotype, with four of the seven serotypes described. One of the human isolates was OspA serotype 5, the same found in four of seven tick isolates. The second human isolate was OspA serotype 3, which was not present in ticks from the same area. Seven B. garinii isolates were able to disseminate through the skin of C3H/HeN mice and to cause severe inflammation of joints. One of the two B. valaisiana isolates also caused disease in mice. Only one B. burgdorferi sensu stricto isolate was recovered from the urinary bladder. One isolate each of B. valaisiana and B. lusitaniae were not able to disseminate through the skin of mice or to infect internal organs. In summary, there is substantial diversity in the species and in the pathogenicity of B. burgdorferi sensu lato in areas in northern Spain where Lyme disease is endemic. PMID:11060064

  17. [Relapse prevention in anorexia nervosa].

    PubMed

    Giel, Katrin; Leehr, Elisabeth; Becker, Sandra; Startup, Helen; Zipfel, Stephan; Schmidt, Ulrike

    2013-07-01

    Anorexia nervosa is characterised by high relapse rates and thus there is a need for strategies that reduce reoccurrence of illness. One way of achieving this is to integrate relapse prevention into treatment, but clearly this requires identification of risk and maintenance factors. The Maudsley Model of Anorexia Nervosa Treatment in Adults (MANTRA) by Schmidt & Treasure has 5 major treatment stages. These include an initial stage of motivation and dialogue about change, an individual relapse formulation, improvement of cognitive and socio-emotional skills, work on the patient's identity and eventually a final stage of ending and parting. These treatment stages are derived from a maintenance model of AN by Schmidt & Treasure and on evidence from recovered patients and part of their objective is to prevent relapse. PMID:23592490

  18. Progressive-Relapsing MS (PRMS)

    MedlinePlus

    ... the disease process in MS and in MRI technology. Individuals who were previously diagnosed with progressive-relapsing MS would now be ... The National MS Society is Here to Help Need More Information? We ...

  19. Serological survey of Borrelia infection of dogs in Sapporo, Japan, where Borrelia garinii infection was previously detected

    PubMed Central

    UESAKA, Karin; MAEZAWA, Masaki; INOKUMA, Hisashi

    2015-01-01

    A serological survey of Borrelia infection of dogs was performed in Sapporo, Japan, where Borrelia garinii infection in dogs was detected in 2011. A total of 314 serum samples were collected from dogs that visited three animal hospitals in Sapporo from 2012 to 2014. The two-step evaluation method, involving screening ELISA followed by Western blot analysis, was used to detect antibodies against Borrelia species. A total of 34 samples were positive by ELISA. Among those 34 samples, 32 were positive for Borrelia spp. by Western blot. These findings suggest that the 32 dogs (10.2%) generated antibodies against Borrelia burgdorferi sensu lato, such as B. garinii or B. afzelii. Antibody positivity was 7.6% and 13.3% for dogs living in urban and rural areas, respectively. Dogs with a history of tick infestation showed a positive rate of 16.7%, which was higher, although not significantly, than the 6.7% among dogs without a history. PMID:26522809

  20. Serological survey of Borrelia infection of dogs in Sapporo, Japan, where Borrelia garinii infection was previously detected.

    PubMed

    Uesaka, Karin; Maezawa, Masaki; Inokuma, Hisashi

    2016-04-01

    A serological survey of Borrelia infection of dogs was performed in Sapporo, Japan, where Borrelia garinii infection in dogs was detected in 2011. A total of 314 serum samples were collected from dogs that visited three animal hospitals in Sapporo from 2012 to 2014. The two-step evaluation method, involving screening ELISA followed by Western blot analysis, was used to detect antibodies against Borrelia species. A total of 34 samples were positive by ELISA. Among those 34 samples, 32 were positive for Borrelia spp. by Western blot. These findings suggest that the 32 dogs (10.2%) generated antibodies against Borrelia burgdorferi sensu lato, such as B. garinii or B. afzelii. Antibody positivity was 7.6% and 13.3% for dogs living in urban and rural areas, respectively. Dogs with a history of tick infestation showed a positive rate of 16.7%, which was higher, although not significantly, than the 6.7% among dogs without a history. PMID:26522809

  1. Intrauterine transmission of Borrelia burgdorferi in dogs.

    PubMed

    Gustafson, J M; Burgess, E C; Wachal, M D; Steinberg, H

    1993-06-01

    To determine whether intrauterine transmission of Borrelia burgdorferi could exist in dogs, 10 female Beagles were inoculated intradermally with approximately 1,000 B burgdorferi on day 1 of proestrus; inoculation was repeated every 2 weeks during the gestation period. Ten female control Beagles were similarly inoculated with phosphate-buffered saline solution. Prior to the start of the study, all females and 3 males used for breeding were seronegative for B burgdorferi on the basis of results of the indirect fluorescent antibody test and immunoblot (western analysis. Similarly, results of culture of blood for B burgdorferi were negative. All 20 of the females were bred naturally. Blood samples were collected weekly for serologic testing and culture. Blood samples were obtained from live pups on day 1 of life, then weekly until pups were 6 weeks old when they were euthanatized. Tissues were obtained for culture and testing by use of polymerase chain reaction (PCR). Of 10 spirochete-inoculated (SI) females, 8 became infected with B burgdorferi as evidenced by spirochete culture results and/or PCR-detected B burgdorferi DNA in the tissues of females or their pups. Of the 10 SI females, 8 delivered litters (3 to 7 pups) that had at least 1 neonatal or 6-week-old pup with B burgdorferi DNA-positive tissues (by PCR), and spirochetes were cultured from tissues from pups of 2 litters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8323057

  2. Rickettsiae and Borrelia burgdorferi in ixodid ticks.

    PubMed Central

    Magnarelli, L A; Andreadis, T G; Stafford, K C; Holland, C J

    1991-01-01

    Nymphs and adults of hard-bodied ticks were collected in Connecticut and tested by direct and indirect immunofluorescence staining methods for rickettsiae and Borrelia burgdorferi. Of the 609 Ixodes dammini ticks examined, 59 (9.7%) harbored rickettsialike microorganisms in hemocytes (blood cells). These bacteria reacted with fluorescein-conjugated antiserum to Ehrlichia canis, the etiologic agent of with fluorescein-conjugated antiserum to Ehrlichia canis, the etiologic agent of canine ehrlichiosis. Prevalence of infection ranged from 6.8 to 12.7% for males and females, respectively. Although the specific identities of the hemocytic rickettsialike organisms are unknown, they share antigens with ehrlichiae. Electron microscopy revealed rickettsiae in ovarian tissues of I. dammini that also had infected hemocytes. Rickettsialike organisms were also observed in the hemocytes of 5 (6.9%) of 73 Dermacentor variabilis ticks. In analyses for B. burgdorferi, 146 (23.7%) of 617 I. dammini ticks harbored these spirochetes in midguts. Hemocytic rickettsialike microorganisms coexisted with B. burgdorferi in 36 (6.7%) of the 537 nymphs and adults of I. dammini examined. I. dammini, with its broad host range, has the potential to acquire multiple microorganisms. Images PMID:1757551

  3. Adherence of Borrelia burgdorferi to granulocytes of different animal species.

    PubMed

    Grassmann, B; Kopp, P A; Schmitt, M; Blobel, H

    1997-04-01

    Adherence of 4 Borrelia (B.) burgdorferi strains (z7/22, z7/27, z7/41, PBi) to polymorphonuclear granulocytes from different domestic animals (horses, cattle, sheep, dogs) was investigated. All 4 strains adhered to the granulocytes. Binding assays indicated that the adherence occurred between structures on the surface of the borreliae ("binding-sites") and on the membranes of the granulocytes ("receptors"). The "receptors" consisted of 4 fractions (A, B, C, and D) with components differing in molecular weight (MW) and binding activity for proteins on the surface of B. burgdorferi. Fraction A (MW 80000) had the highest binding activity for B. burgdorferi. PMID:9144911

  4. Renal lesions associated with Borrelia burgdorferi infection in a dog.

    PubMed

    Grauer, G F; Burgess, E C; Cooley, A J; Hagee, J H

    1988-07-15

    Borrelia burgdorferi infection was diagnosed serologically in a dog with lethargy, stiffness, and anorexia. Treatment with ampicillin and chloramphenicol did not alleviate the signs. Azotemia, proteinuria, cylindruria, pyuria, and hematuria developed over a 3-month period. Antibody titer for B burgdorferi remained high (1:8,192) during this time. Renal histopathologic findings included severe, chronic, diffuse, membranoproliferative glomerulonephritis and moderate chronic, multifocal, interstitial nephritis. Borrelia burgdorferi organisms were identified in renal tissue and in urine by results of immunofluorescent studies and bacteriologic culture, respectively. PMID:3403355

  5. Blackbirds Turdus merula as competent reservoirs for Borrelia turdi and Borrelia valaisiana in Portugal: evidence from a xenodiagnostic experiment.

    PubMed

    Norte, Ana C; Lopes de Carvalho, Isabel; Núncio, Maria S; Ramos, Jaime A; Gern, Lise

    2013-08-01

    To confirm that thrushes, such as blackbirds Turdus merula, play a role as reservoir for some Borrelia genospecies, we performed a xenodiagnostic experiment with blackbirds captured in a mixed wood located in Western Portugal where Borrelia turdi, an uncommon genospecies in Europe, was the most prevalent genospecies associated with birds. Two out of five birds harboured B. turdi infected Ixodes frontalis at the time of capture. Four out of five birds transmitted spirochaetes to Ixodes ricinus xenodiagnostic ticks: two birds transmitted Borrelia valaisiana to 25.7% and 10.5% of ticks, and two transmitted B. turdi to 6.4% and 5.4% of ticks. Our results showed that blackbirds transmit B. valaisiana and B. turdi to I. ricinus feeding larvae, acting as reservoir hosts for these genospecies in nature. PMID:23864576

  6. Modeling Relapsing Disease Dynamics in a Host-Vector Community

    PubMed Central

    Stone, Emily F.

    2016-01-01

    Vector-borne diseases represent a threat to human and wildlife populations and mathematical models provide a means to understand and control epidemics involved in complex host-vector systems. The disease model studied here is a host-vector system with a relapsing class of host individuals, used to investigate tick-borne relapsing fever (TBRF). Equilibrium analysis is performed for models with increasing numbers of relapses and multiple hosts and the disease reproduction number, R0, is generalized to establish relationships with parameters that would result in the elimination of the disease. We show that host relapses in a single competent host-vector system is needed to maintain an endemic state. We show that the addition of an incompetent second host with no relapses increases the number of relapses needed for maintaining the pathogen in the first competent host system. Further, coupling of the system with hosts of differing competencies will always reduce R0, making it more difficult for the system to reach an endemic state. PMID:26910884

  7. The reinstatement model and relapse prevention: a clinical perspective

    PubMed Central

    Preston, Kenzie L

    2005-01-01

    Objectives This commentary assesses the degree to which the reinstatement model is homologous to the human experience of relapse. Results A review of the literature suggests that the relationship is less clear than is often assumed, largely due to a lack of prospective data on the precipitants and process of relapse (especially relapse to heroin or cocaine abuse). However, reinstatement does not need to resemble relapse to have immediate clinical value; predictive validity as a medication screen would be sufficient. Whether the model has predictive validity is unknown, because, to date, very few clinical trials have tested medications that are effective in the reinstatement model, and even fewer have used designs comparable to those of reinstatement experiments. A clinical trial comparable to a reinstatement experiment would enroll participants who are already abstinent, and its main outcome measure would be propensity to undergo a specific type of relapse (e.g., relapse induced by stress or cues). Conclusions Until clinical and preclinical work are more comparable, criticisms of the reinstatement model’s presumed shortcomings are premature. PMID:12721778

  8. Modeling Relapsing Disease Dynamics in a Host-Vector Community.

    PubMed

    Johnson, Tammi L; Landguth, Erin L; Stone, Emily F

    2016-02-01

    Vector-borne diseases represent a threat to human and wildlife populations and mathematical models provide a means to understand and control epidemics involved in complex host-vector systems. The disease model studied here is a host-vector system with a relapsing class of host individuals, used to investigate tick-borne relapsing fever (TBRF). Equilibrium analysis is performed for models with increasing numbers of relapses and multiple hosts and the disease reproduction number, R0, is generalized to establish relationships with parameters that would result in the elimination of the disease. We show that host relapses in a single competent host-vector system is needed to maintain an endemic state. We show that the addition of an incompetent second host with no relapses increases the number of relapses needed for maintaining the pathogen in the first competent host system. Further, coupling of the system with hosts of differing competencies will always reduce R0, making it more difficult for the system to reach an endemic state. PMID:26910884

  9. [Louse-borne-relapsing-fever in refugees from the Horn of Africa; a case series of 25 patients].

    PubMed

    Seilmaier, M; Guggemos, W; Wieser, A; Fingerle, V; Balzer, L; Fenzl, T; Hoch, M; von Both, U; Schmidt, H U; Wendtner, C M; Strobel, E

    2016-07-01

    Background | Relapsing fever is divided into tick borne relapsing fever (TBRF) and louse borne relapsing fever (LBRF). This report describes 25 refugees from East Africa who were diagnosed to suffer from LBRF within a period of 6 month only at a single hospital in Munich / Germany. Material & Methods | The aim was to point out common clinical features as well as laboratory findings and clinical symptoms before and after initiation of treatment in 25 patients with louse borne relapsing fever (LBRF) who were diagnosed and treated at Klinikum München Schwabing from August 2015 to January 2016. To the best of our knowledge this is the largest case series of LBRF in the western world for decades. Main focus of the investigation was put on clinical aspects. Results | All 25 patients suffered from acute onset of high fever with chills, headache and severe prostration. Laboratory analysis showed high CRP and a marked thrombocytopenia. A Giemsa blood stain was procured immediately in order to look for malaria. In the blood smear spirochetes with typical shape and aspect of borrelia species could be detected.The further PCR analysis confirmed infection with Borrelia recurrentis. Treatment with Doxycycline was started forthwith. The condition improved already on the second day after treatment was started and all were restored to health in less than a week. Apart from a mild to moderate Jarisch-Herxheimer-reaction we didn`t see any side effects of the therapy. Conclusion | LBRF has to be taken into account in feverish patients who come as refugees from East-Africa. It seems that our patients belong to a cluster which probably has its origin in Libya and more patients are to be expected in the near future. As LBRF might cause outbreaks in refugee camps it is pivotal to be aware of this emerging infectious disease in refugees from East-Africa. PMID:27404939

  10. Late relapsing childhood lymphoblastic leukemia.

    PubMed

    Vora, A; Frost, L; Goodeve, A; Wilson, G; Ireland, R M; Lilleyman, J; Eden, T; Peake, I; Richards, S

    1998-10-01

    Childhood lymphoblastic leukemia (ALL) is usually assumed to have been permanently eradicated in patients in long-term remission, but occasionally can recur after many years. To learn more about the problem, we studied a group of children whose leukemia had been in remission for 10 or more years before relapse and tried to determine whether they had true recurrences or second malignancies. We studied children treated on Medical Research Council ALL protocols between 1970 and 1984 and followed up by the Clinical Trial Service Unit in Oxford. Detailed clinical and laboratory data was collected from the centers concerned on all who were reported to have had a recurrence of their leukemia after 10 or more years from the time of achieving first complete remission (CR1). To prove that the relapse was a true recurrence rather than a second or secondary leukemia, DNA extracted from archived marrow smears was subjected to polymerase chain reaction (PCR) analysis for the presence of an identical Ig heavy chain (IgH) or T-cell receptor (TCR) gene rearrangement at initial diagnosis and subsequent relapse. A total of 1,134 of 2,746 children had survived 10 years or more (range, 10 to 24 years) in CR1 and of those, 12 (approximately 1%) had subsequently relapsed. Relapse blast cells were shown to express the common ALL antigen (CD 10) in all cases and an identical clonal IgH or TCR gene rearrangement was found on PCR analysis of DNA from diagnosis and relapse in all eight cases where DNA extraction was successful. A further program of therapy was successful in inducing a second CR in all patients, four of whom have succumbed to a second relapse after 12 to 27 months. The remaining eight are in continuing CR2 at a follow-up of 12 to 108 months (median, 52) from relapse. Although the risk of relapse of childhood ALL after 10 years in remission appears to be small (around 1%), it persists. This raises questions about how blasts can survive quiescent for so long and when we can

  11. A case of canine borreliosis in Iran caused by Borrelia persica.

    PubMed

    Shirani, Darush; Rakhshanpoor, Alaleh; Cutler, Sally Jane; Ghazinezhad, Behnaz; Naddaf, Saied Reza

    2016-04-01

    Tick-borne relapsing fever is an endemic disease in Iran, with most cases attributed to infection by Borrelia persica, which is transmitted by Ornithodoros tholozani soft ticks. Here, we report spirochetemia in blood of a puppy residing in Tehran, Iran. The causative species was identified by use of highly discriminative IGS sequencing; the 489 bp IGS sequence obtained in our study showed 99% identity (100% coverage) when compared with B. persica sequences derived from clinical cases or from O. tholozani ticks. Our IGS sequence also showed 99% similarity over 414 bp (85% coverage) with a strain from a domestic dog, and 96% over 328 bp (69% coverage) with a strain from a domestic cat. Pet-keeping in cosmopolitan cities like Tehran has become increasingly popular in recent years. Animals are often transported into the city in cages or cardboard boxes that might also harbor minute tick larvae and/or early stages of the nymphs bringing them into the urban environment. This may pose a threat to household members who buy and keep these puppies and as a result may come into close contact with infected ticks. PMID:26776536

  12. Relapse prevention for addictive behaviors

    PubMed Central

    2011-01-01

    The Relapse Prevention (RP) model has been a mainstay of addictions theory and treatment since its introduction three decades ago. This paper provides an overview and update of RP for addictive behaviors with a focus on developments over the last decade (2000-2010). Major treatment outcome studies and meta-analyses are summarized, as are selected empirical findings relevant to the tenets of the RP model. Notable advances in RP in the last decade include the introduction of a reformulated cognitive-behavioral model of relapse, the application of advanced statistical methods to model relapse in large randomized trials, and the development of mindfulness-based relapse prevention. We also review the emergent literature on genetic correlates of relapse following pharmacological and behavioral treatments. The continued influence of RP is evidenced by its integration in most cognitive-behavioral substance use interventions. However, the tendency to subsume RP within other treatment modalities has posed a barrier to systematic evaluation of the RP model. Overall, RP remains an influential cognitive-behavioral framework that can inform both theoretical and clinical approaches to understanding and facilitating behavior change. PMID:21771314

  13. BBA70 of Borrelia burgdorferi Is a Novel Plasminogen-binding Protein*

    PubMed Central

    Koenigs, Arno; Hammerschmidt, Claudia; Jutras, Brandon L.; Pogoryelov, Denys; Barthel, Diana; Skerka, Christine; Kugelstadt, Dominik; Wallich, Reinhard; Stevenson, Brian; Zipfel, Peter F.; Kraiczy, Peter

    2013-01-01

    The Lyme disease spirochete Borrelia burgdorferi lacks endogenous, surface-exposed proteases. In order to efficiently disseminate throughout the host and penetrate tissue barriers, borreliae rely on recruitment of host proteases, such as plasmin(ogen). Here we report the identification of a novel plasminogen-binding protein, BBA70. Binding of plasminogen is dose-dependent and is affected by ionic strength. The BBA70-plasminogen interaction is mediated by lysine residues, primarily located in a putative C-terminal α-helix of BBA70. These lysine residues appear to interact with the lysine-binding sites in plasminogen kringle domain 4 because a deletion mutant of plasminogen lacking that domain was unable to bind to BBA70. Bound to BBA70, plasminogen activated by urokinase-type plasminogen activator was able to degrade both a synthetic chromogenic substrate and the natural substrate fibrinogen. Furthermore, BBA70-bound plasmin was able to degrade the central complement proteins C3b and C5 and inhibited the bacteriolytic effects of complement. Consistent with these functional activities, BBA70 is located on the borrelial outer surface. Additionally, serological evidence demonstrated that BBA70 is produced during mammalian infection. Taken together, recruitment and activation of plasminogen could play a beneficial role in dissemination of B. burgdorferi in the human host and may possibly aid the spirochete in escaping the defense mechanisms of innate immunity. PMID:23861404

  14. Geographic Differences in Genetic Locus Linkages for Borrelia burgdorferi

    PubMed Central

    Travinsky, Bridgit; Bunikis, Jonas

    2010-01-01

    Borrelia burdorferi genotype in the northeastern United States is associated with Lyme borreliosis severity. Analysis of DNA sequences of the outer surface protein C gene and rrs-rrlA intergenic spacer from extracts of Ixodes spp. ticks in 3 US regions showed linkage disequilibrium between the 2 loci within a region but not consistently between regions. PMID:20587192

  15. Borrelia burgdorferi Infection and Cutaneous Lyme Disease, Mexico

    PubMed Central

    Gordillo-Pérez, Guadalupe; Torres, Javier; Solórzano-Santos, Fortino; de Martino, Sylvie; Lipsker, Dan; Velázquez, Edmundo; Ramon, Guillermo; Onofre, Muñoz; Jaulhac, Benoit

    2007-01-01

    Four patients who had received tick bites while visiting forests in Mexico had skin lesions that met the case definition of erythema migrans, or borrelial lymphocytoma. Clinical diagnosis was supported with histologic, serologic, and molecular tests. This study suggests the Borrelia burgdorferi infection is in Mexico. PMID:18258006

  16. Borrelia burgdorferi visualized in Ixodes scapularis tick excrement by immunofluorescence.

    PubMed

    Patton, Toni G; Brandt, Kevin S; Gilmore, Robert D

    2012-11-01

    The enzootic cycle of Borrelia burgdorferi, the etiologic agent of Lyme disease, involves Ixodes spp. ticks and vertebrates. Resident tick Borrelia, harbored inside the midgut, are eventually expelled with the tick's saliva into the vertebrate host when a tick consumes a blood meal. During this 4- to 5-day feeding period I. scapularis will defecate onto the host's skin. Previously we detected borrelial DNA in tick feces throughout engorgement. In this study we report the microscopic examination for B. burgdorferi in nymphal excrement. Using immunofluorescence assays, we observed Borrelia in all mouse skin and capsule fecal swabs tested, although we could not culture the spirochetes. These results update our previous analysis by revealing that spirochetes can also be visualized in tick excrement. Furthermore, the results emphasize that borrelial contamination by defecation is a possibility, and that caution should be exercised by researchers investigating pathogen/host/vector interactions. The biological significance of the presence of non-culturable Borrelia in tick feces during engorgement is unclear. PMID:22651382

  17. Relapsed Hodgkin Lymphoma: Management Strategies

    PubMed Central

    Montanari, Francesca; Diefenbach, Catherine

    2016-01-01

    Although Hodgkin lymphoma (HL) is largely curable with first-line therapy, approximately one-third of patients will not have a complete response to frontline treatment or will subsequently relapse. Only 50 % of these patients will be effectively salvaged with conventional therapies. The prognosis is particularly poor for those patients with chemotherapy refractory disease, who are unable to obtain even transient disease control, and for patients who relapse following high dose chemotherapy and autologous stem cell transplant. In this review, we summarize the most recent updates on the management of patients with relapsed HL, the role of novel therapies such as brentuximab vedotin, and an overview of promising new agents currently under investigation. We also discuss the role of consolidation strategies such as high-dose chemotherapy and autologous stem cell transplant, and reduced-intensity allogeneic hematopoietic stem cell transplant, and the need for new strategies in the elderly patient population. PMID:24942298

  18. Novel therapies for relapsed myeloma.

    PubMed

    Stewart, A Keith

    2009-01-01

    Treatment of myeloma relapse needs to be individualized to reflect the effectiveness and toxicities of prior therapies, with consideration given to pragmatic issues such as the tempo of relapse, age of the patient, access to drugs and patient preference. In general, combination therapies have been associated with higher response rates and improved progression-free survival and may be preferable when a rapid response is required. Nevertheless, in a slower-tempo relapse it is unclear at this juncture whether sequencing of drugs or multi-agent combinations offer superior overall survival results. Fortunately, active novel agents that offer further possibilities for some myeloma patients have become available in clinical trials. In this review we will describe the various classes of novel drugs being tested and the pros and cons of preclinical testing, and will particularly focus on two agents with single-agent activity in myeloma: carfilzomib, a proteasome inhibitor, and pomalidomide, a member of the immunomodulatory class of drugs. PMID:20008242

  19. Preventing Relapse Following Smoking Cessation

    PubMed Central

    Collins, Susan E.; Witkiewitz, Katie; Kirouac, Megan; Marlatt, G. Alan

    2012-01-01

    Cigarette smoking is the leading cause of preventable deaths worldwide. Long-term smoking cessation can drastically reduce people’s risk for developing smoking-related disease. The research literature points to a need for clearer operationalization and differentiation between smoking cessation and relapse prevention interventions and outcomes. That said, extensive meta-analyses and research studies have indicated that there are various efficacious smoking interventions that can both support smoking cessation and relapse prevention efforts. Specifically, behavioral treatments, relapse prevention psychotherapy, pharmacologic interventions, motivational enhancement, smoking reduction to quit, brief advice, alternative intervention modes (telephone, Internet, computer), self-help, and tailored treatments can help prepare smokers for longer-term abstinence. Although these methods vary on reach, they are relatively efficacious, particularly in combined formats. PMID:26550097

  20. Transcriptional Profiling the 150 kb Linear Megaplasmid of Borrelia turicatae Suggests a Role in Vector Colonization and Initiating Mammalian Infection

    PubMed Central

    Wilder, Hannah K.; Raffel, Sandra J.; Barbour, Alan G.; Porcella, Stephen F.; Sturdevant, Daniel E.; Vaisvil, Benjamin; Kapatral, Vinayak; Schmitt, Daniel P.; Schwan, Tom G.; Lopez, Job E.

    2016-01-01

    Adaptation is key for survival as vector-borne pathogens transmit between the arthropod and vertebrate, and temperature change is an environmental signal inducing alterations in gene expression of tick-borne spirochetes. While plasmids are often associated with adaptation, complex genomes of relapsing fever spirochetes have hindered progress in understanding the mechanisms of vector colonization and transmission. We utilized recent advances in genome sequencing to generate the most complete version of the Borrelia turicatae 150 kb linear megaplasmid (lp150). Additionally, a transcriptional analysis of open reading frames (ORFs) in lp150 was conducted and identified regions that were up-regulated during in vitro cultivation at tick-like growth temperatures (22°C), relative to bacteria grown at 35°C and infected murine blood. Evaluation of the 3’ end of lp150 identified a cluster of ORFs that code for putative surface lipoproteins. With a microbe’s surface proteome serving important roles in pathogenesis, we confirmed the ORFs expression in vitro and in the tick compared to spirochetes infecting murine blood. Transcriptional evaluation of lp150 indicates the plasmid likely has essential roles in vector colonization and/or initiating mammalian infection. These results also provide a much needed transcriptional framework to delineate the molecular mechanisms utilized by relapsing fever spirochetes during their enzootic cycle. PMID:26845332

  1. Transcriptional Profiling the 150 kb Linear Megaplasmid of Borrelia turicatae Suggests a Role in Vector Colonization and Initiating Mammalian Infection.

    PubMed

    Wilder, Hannah K; Raffel, Sandra J; Barbour, Alan G; Porcella, Stephen F; Sturdevant, Daniel E; Vaisvil, Benjamin; Kapatral, Vinayak; Schmitt, Daniel P; Schwan, Tom G; Lopez, Job E

    2016-01-01

    Adaptation is key for survival as vector-borne pathogens transmit between the arthropod and vertebrate, and temperature change is an environmental signal inducing alterations in gene expression of tick-borne spirochetes. While plasmids are often associated with adaptation, complex genomes of relapsing fever spirochetes have hindered progress in understanding the mechanisms of vector colonization and transmission. We utilized recent advances in genome sequencing to generate the most complete version of the Borrelia turicatae 150 kb linear megaplasmid (lp150). Additionally, a transcriptional analysis of open reading frames (ORFs) in lp150 was conducted and identified regions that were up-regulated during in vitro cultivation at tick-like growth temperatures (22°C), relative to bacteria grown at 35°C and infected murine blood. Evaluation of the 3' end of lp150 identified a cluster of ORFs that code for putative surface lipoproteins. With a microbe's surface proteome serving important roles in pathogenesis, we confirmed the ORFs expression in vitro and in the tick compared to spirochetes infecting murine blood. Transcriptional evaluation of lp150 indicates the plasmid likely has essential roles in vector colonization and/or initiating mammalian infection. These results also provide a much needed transcriptional framework to delineate the molecular mechanisms utilized by relapsing fever spirochetes during their enzootic cycle. PMID:26845332

  2. Ménage à trois: Borrelia, dendritic cells, and tick saliva interactions.

    PubMed

    Mason, Lauren M K; Veerman, Christiaan C; Geijtenbeek, Teunis B H; Hovius, Joppe W R

    2014-02-01

    Borrelia burgdorferi sensu lato, the causative agent of Lyme borreliosis, is inoculated into the skin during an Ixodes tick bite where it is recognised and captured by dendritic cells (DCs). However, considering the propensity of Borrelia to disseminate, it would appear that DCs fall short in mounting a robust immune response against it. Many aspects of the DC-driven immune response to Borrelia have been examined. Recently, components of tick saliva have been identified that sabotage DC responses and aid Borrelia infection. In this review, we summarise what is currently known about the immune response of DCs to Borrelia and explore the mechanisms by which Borrelia manages to circumvent this immune response, with or without the help of tick salivary proteins. PMID:24388562

  3. Reservoir Targeted Vaccine Against Borrelia burgdorferi: A New Strategy to Prevent Lyme Disease Transmission

    PubMed Central

    Richer, Luciana Meirelles; Brisson, Dustin; Melo, Rita; Ostfeld, Richard S.; Zeidner, Nordin; Gomes-Solecki, Maria

    2014-01-01

    A high prevalence of infection with Borrelia burgdorferi in ixodid ticks is correlated with a high incidence of Lyme disease. The transmission of B. burgdorferi to humans can be disrupted by targeting 2 key elements in its enzootic cycle: the reservoir host and the tick vector. In a prospective 5-year field trial, we show that oral vaccination of wild white-footed mice resulted in outer surface protein A–specific seropositivity that led to reductions of 23% and 76% in the nymphal infection prevalence in a cumulative, time-dependent manner (2 and 5 years, respectively), whereas the proportion of infected ticks recovered from control plots varied randomly over time. Significant decreases in tick infection prevalence were observed within 3 years of vaccine deployment. Implementation of such a long-term public health measure could substantially reduce the risk of human exposure to Lyme disease. PMID:24523510

  4. A MODEST MODEL EXPLAINS THE DISTRIBUTION AND ABUNDANCE OF BORRELIA BURGDORFERI STRAINS

    PubMed Central

    BRISSON, DUSTIN; DYKHUIZEN, DANIEL E.

    2006-01-01

    The distribution and abundance of Borrelia burgdorferi, including human Lyme disease strains, is a function of its interactions with vertebrate species. We present a mathematical model describing important ecologic interactions affecting the distribution and abundance of B. burgdorferi strains, marked by the allele at the outer surface protein C locus, in Ixodes scapularis ticks, the principal vector. The frequency of each strain in ticks can be explained by the vertebrate species composition, the density of each vertebrate species, the number of ticks that feed on individuals of each species, and the rate at which those ticks acquire different strain. The model results are consistent with empirical data collected in a major Lyme disease focus in New England. An applicable extension of these results would be to predict the proportion of ticks carrying human infectious strains of B. burgdorferi from disease host densities and thus predict the local risk of contracting Lyme disease. PMID:16606995

  5. Survival After Relapse of Medulloblastoma.

    PubMed

    Koschmann, Carl; Bloom, Karina; Upadhyaya, Santhosh; Geyer, J Russell; Leary, Sarah E S

    2016-05-01

    Survival after recurrence of medulloblastoma has not been reported in an unselected cohort of patients in the contemporary era. We reviewed 55 patients diagnosed with medulloblastoma between 2000 and 2010, and treated at Seattle Children's Hospital to evaluate patterns of relapse treatment and survival. Fourteen of 47 patients (30%) over the age of 3 experienced recurrent or progressive medulloblastoma after standard therapy. The median time from diagnosis to recurrence was 18.0 months (range, 3.6 to 62.6 mo), and site of recurrence was metastatic in 86%. The median survival after relapse was 10.3 months (range, 1.3 to 80.5 mo); 3-year survival after relapse was 18%. There were trend associations between longer survival and having received additional chemotherapy (median survival 12.8 vs. 1.3 mo, P=0.16) and radiation therapy (15.4 vs. 5.9 mo, P=0.20). Isolated local relapse was significantly associated with shorter survival (1.3 vs. 12.8 mo, P=0.009). Recurrence of medulloblastoma is more likely to be metastatic than reported in previous eras. Within the limits of our small sample, our data suggest a potential survival benefit from retreatment with cytotoxic chemotherapy and radiation even in heavily pretreated patients. This report serves as a baseline against which to evaluate novel therapy combinations. PMID:26907655

  6. Western gray squirrel (Rodentia: Sciuridae): a primary reservoir host of Borrelia burgdorferi in Californian oak woodlands?

    PubMed

    Lane, Robert S; Mun, Jeomhee; Eisen, Rebecca J; Eisen, Lars

    2005-05-01

    In California, dense woodlands have been recognized as important biotopes where humans are exposed to the nymphal stage of the western blacklegged tick, Ixodes pacificus Cooley & Kohls, the primary vector of the Lyme disease spirochete Borrelia burgdorferi sensu stricto (s.s.), in the far-western United States. To identify the principal reservoir host(s) of this spirochete, and of closely related spirochetes in the B. burgdorferi sensu lato (s.l.) complex, in dense woodlands in Mendocino County, California, approximately 50 species of birds and mammals, including wood rats and kangaroo rats, were evaluated as potential hosts for vector ticks and borreliae in 2002 and 2003. Although polymerase chain reaction (PCR) and sequencing analyses revealed that many vertebrate species had been exposed to one or more members of the B. burgdorferi s.l. spirochetal complex, only the western gray squirrel, Sciurus griseus, fulfilled the major criteria for a reservoir host of B. burgdorferi s.s. Ear-punch biopsies from eight of 10 squirrels collected from five separate woodlands were PCR-positive for B. burgdorferi s.s., 47% of I. pacificus larvae (n = 64) and 31% of nymphs (n = 49) removed from squirrels contained B. burgdorferi s.l., and the engorgement status of I. pacificus larvae was associated positively with acquisition of spirochetes. Overall, 83 and 100% of the amplicons sequenced from PCR-positive I. pacificus larvae and nymphs, respectively, were identified as B. burgdorferi s.s, Among the five remaining positive I. pacificus larvae, three contained B. bissettii and two had uncharacterized B. burgdorferi s.l. Borrelia burgdorferi s.s. was detected in one of five larvae and zero of two nymphs of the Pacific Coast tick, Dermacentor occidentalis Marx, that likewise had been removed from squirrels. The rickettsial agent of human anaplasmosis, Anaplasma phagocytophilum, was detected in the blood or ear biopsies of two squirrels and in one (1.6%) of 64 I. pacificus larvae and

  7. Determinants of Relapse Following Smoking Cessation.

    ERIC Educational Resources Information Center

    Shiffman, Saul M.

    Although research has been conducted on who will relapse after having quit smoking in clinics, little has been done to determine the immediate precipitants of recidivism. A telephone hotline, manned by four experienced interviewers, was set up to receive calls from ex-smokers who had relapsed or who felt at high risk for relapse. A structured…

  8. Influence of arthritis-related protein (BBF01) on infectivity of Borrelia burgdorferi B31

    PubMed Central

    2013-01-01

    Background Lyme borreliosis, caused by tick-borne Borrelia burgdorferi, is a multi-phasic, multi-system disease in humans. Similar to humans, C3H mice develop arthritis and carditis, with resolution and periodic bouts of recurrence over the course of persistent infection. Borrelia burgdorferi arthritis-related protein (Arp/BBF01), a highly conserved protein among B. burgdorferi s.s. isolates, has been shown to be antigenic in humans with Lyme borreliosis, and a target for antibody-mediated disease resolution in the mouse model. Results A mutant strain of B. burgdorferi s.s. deficient of the arp gene and a complemented version of that mutant were created and examined for phenotypic effects in mice compared to wild-type B. burgdorferi. Deletion of arp did not abolish infectivity, but did result in a higher infectious dose compared to wild-type B. burgdorferi, which was restored by complementation. Spirochete burdens in tissues of C3H-scid mice were lower when infected with the arp mutant, compared to wild-type, but arthritis was equally severe. Spirochete burdens were also lower in C3H mice infected with the arp mutant, but disease was markedly reduced. Ticks that fed upon infected C3H mice were able to acquire infection with both wild-type and arp mutant spirochetes. Arp mutant spirochetes were marginally able to be transmitted to naïve hosts by infected ticks. Conclusion These results indicated that deletion of BBF01/arp did not abrogate, but diminished infectivity and limited spirochete burdens in tissues of both immunocompetent and immunodeficient hosts, and attenuated, but did not abolish the ability of ticks to acquire or transmit infection. PMID:23651628

  9. The combination of milatuzumab, a humanized anti-CD74 antibody, and veltuzumab, a humanized anti-CD20 antibody, demonstrates activity in patients with relapsed and refractory B-cell non-Hodgkin lymphoma.

    PubMed

    Christian, Beth A; Poi, Ming; Jones, Jeffrey A; Porcu, Pierluigi; Maddocks, Kami; Flynn, Joseph M; Benson, Don M; Phelps, Mitch A; Wei, Lai; Byrd, John C; Wegener, William A; Goldenberg, David M; Baiocchi, Robert A; Blum, Kristie A

    2015-06-01

    As a result of the anti-tumour activity observed in vitro and in vivo with combined anti-CD20 and anti-CD74 antibodies, we initiated a phase I/II trial of veltuzumab and milatuzumab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL). Patients received an induction of veltuzumab 200 mg/m(2) weekly combined with escalating doses of milatuzumab at 8, 16 and 20 mg/kg weekly for 4 weeks. Patients without disease progression could receive an extended induction with treatment on weeks 12, 20, 28 and 36. A total of 35 patients enrolled on the study. Median age was 63 years, median number of prior therapies was 3, and 63% of patients were rituximab refractory. No dose-limiting toxicities were observed in the phase I study. Related grade 3-4 toxicities included lymphopenia, leucopenia, neutropenia, anaemia, infusion reactions, hyperglycaemia, fatigue and atrial tachycardia. Median weeks of therapy was 12 and 29% of patients completed all 36 weeks of therapy. The overall response rate was 24%, median duration of response was 12 months, and responses were observed at all dose levels and in 50% of patients refractory to rituximab. Combination therapy with veltuzumab and milatuzumab demonstrated activity in a population of heavily pre-treated patients with relapsed or refractory indolent NHL. PMID:25847298

  10. Late Relapse of Testicular Germ Cell Tumors.

    PubMed

    O'Shaughnessy, Matthew J; Feldman, Darren R; Carver, Brett S; Sheinfeld, Joel

    2015-08-01

    Germ cell tumors of the testis have an overall survival rate greater than 90% as a result of a successful multidisciplinary approach to management. Late relapse affects a subset of patients however, and tends to be chemorefractory and the overall prognosis is poor. Surgery is the mainstay in management of late relapse but salvage chemotherapy can be successful. In this review, the clinical presentation and detection of late relapse, clinical outcomes, and predictors of survival in late relapse and the importance of a multidisciplinary treatment approach for successful management of late relapse are discussed. PMID:26216823

  11. Borrelia burgdorferi and tick proteins supporting pathogen persistence in the vector

    PubMed Central

    Kung, Faith; Anguita, Juan; Pal, Utpal

    2013-01-01

    Borrelia burgdorferi, a pathogen transmitted by Ixodes ticks, is responsible for a prevalent illness known as Lyme disease, and a vaccine for human use is unavailable. Recently, genome sequences of several B. burgdorferi strains and Ixodes scapularis ticks have been determined. In addition, remarkable progress has been made in developing molecular genetic tools to study the pathogen and vector, including their intricate relationship. These developments are helping unravel the mechanisms by which Lyme disease pathogens survive in a complex enzootic infection cycle. Notable discoveries have already contributed to understanding the spirochete gene regulation accounting for the temporal and spatial expression of B. burgdorferi genes during distinct phases of the lifecycle. A number of pathogen and vector gene products have also been identified that contribute to microbial virulence and/or persistence. These research directions will enrich our knowledge of vector-borne infections and contribute towards the development of preventative strategies against Lyme disease. PMID:23252492

  12. Evolution and population genomics of the Lyme borreliosis pathogen, Borrelia burgdorferi

    PubMed Central

    Seifert, Stephanie N; Khatchikian, Camilo E.; Zhou, Wei

    2015-01-01

    Population genomic studies have the potential to address many unresolved questions about microbial pathogens by facilitating the identification of genes underlying ecologically important traits such as novel virulence factors and adaptations to humans or other host species. Additionally, this framework improves estimations of population demography and evolutionary history to accurately reconstruct recent epidemics and identify the molecular and environmental factors that resulted in the outbreak. The Lyme disease bacterium, Borrelia burgdorferi, exemplifies the power and promise of the application of population genomics to microbial pathogens. We discuss here the future of evolutionary studies in B.burgdorferi - focusing on the primary evolutionary forces of horizontal gene transfer, natural selection, and migration - as investigations transition from analyses of single genes to genomes. PMID:25765920

  13. Borrelia burgdorferi, Host-Derived Proteases, and the Blood-Brain Barrier

    PubMed Central

    Grab, Dennis J.; Perides, George; Dumler, J. Stephen; Kim, Kee Jun; Park, Jinho; Kim, Yuri V.; Nikolskaia, Olga; Choi, Kyoung Seong; Stins, Monique F.; Kim, Kwang Sik

    2005-01-01

    Neurological manifestations of Lyme disease in humans are attributed in part to penetration of the blood-brain barrier (BBB) and invasion of the central nervous system (CNS) by Borrelia burgdorferi. However, how the spirochetes cross the BBB remains an unresolved issue. We examined the traversal of B. burgdorferi across the human BBB and systemic endothelial cell barriers using in vitro model systems constructed of human brain microvascular endothelial cells (BMEC) and EA.hy 926, a human umbilical vein endothelial cell (HUVEC) line grown on Costar Transwell inserts. These studies showed that B. burgdorferi differentially crosses human BMEC and HUVEC and that the human BMEC form a barrier to traversal. During the transmigration by the spirochetes, it was found that the integrity of the endothelial cell monolayers was maintained, as assessed by transendothelial electrical resistance measurements at the end of the experimental period, and that B. burgdorferi appeared to bind human BMEC by their tips near or at cell borders, suggesting a paracellular route of transmigration. Importantly, traversal of B. burgdorferi across human BMEC induces the expression of plasminogen activators, plasminogen activator receptors, and matrix metalloproteinases. Thus, the fibrinolytic system linked by an activation cascade may lead to focal and transient degradation of tight junction proteins that allows B. burgdorferi to invade the CNS. PMID:15664945

  14. Endocannabinoid regulation of relapse mechanisms.

    PubMed

    Fattore, Liana; Fadda, Paola; Fratta, Walter

    2007-11-01

    Addiction involves a complex neuropharmacologic behavioural cycle, in which positive reinforcement exerted by the drug and the negative state of withdrawal drive the user to extremes to obtain the drug. Comprehensive studies have established that relapse is the most common outcome of recovery programs treating addictive behaviours. Several types of anticraving medication are available nowadays, such as naltrexone for the treatment of alcoholism, bupropion for nicotine, methadone or buprenorphine for heroin. This review focuses on recent behavioural data providing a rationale for an endocannabinoid mechanism underlying reinstatement of compulsive drug seeking. Studies supporting the contention that reinstatement of extinguished drug self-administration behaviour may be generated by cannabinoid CB1 receptor agonists and attenuated, if not blocked, by CB1 receptor antagonists, are here reviewed. In support to these findings, conditioned place preference studies substantiate the involvement of the endocannabinoid system in recidivism mechanisms by demonstrating that motivation to relapse can be triggered by CB1 receptor activation while blockade of such receptors may prevent reinstatement of place conditioning induced by either drug primings or drug-associated cues. Finally, biochemical studies evaluating changes in endocannabinoid levels, CB1 receptor density and CB1 mRNA expression during re-exposure to drug following extinction are also examined. Taken together, the evidence available has important implications in the understanding and treatment of relapsing episodes in patients undergoing detoxification. PMID:17936008

  15. [Diagnostic aspects of Borrelia-infections in dogs].

    PubMed

    Hovius, K E; Houwers, D J

    2007-08-15

    This paper discusses the problem of diagnosing borreliosis (Lyme disease) in dogs. A prospective cohort study in the Kempen district, a known Borrelia focus in The Netherlands, showed that dogs with the presumptive symptoms of borreliosis, episodic malaise and lameness, had significantly higher and longer lasting anti-Borrelia IgG titers than asymptomatic dogs. A small part of these dogs also had antibodies directed against the IR6 (C6) antigen which indicates persistent active Borrelia infection. A few typical case histories are presented. Dogs with episodic malaise and lameness with persistent high IgG titers are suspect of suffering from borreliosis. IR6 antibodies make this diagnosis likely. Initially, such patients should be treated with doxycyclin (10 mg/kg 1dd) for 10 days. If the symptoms recurr within a few months, a longer treatment (eg 6 weeks) should be considered. Bernese mountain dogs were strongly over-represented among the borreliosis patients in the cohort study and most high titered samples among those submitted for--diagnostic--serology appear to come from this breed, which suggests that these dogs have difficulties with clearing this tick-borne infection. PMID:17849909

  16. Development of Genetic System to Inactivate a Borrelia turicatae Surface Protein Selectively Produced within the Salivary Glands of the Arthropod Vector

    PubMed Central

    Lopez, Job E.; Wilder, Hannah K.; Hargrove, Reid; Brooks, Christopher P.; Peterson, Karin E.; Beare, Paul A.; Sturdevant, Daniel E.; Nagarajan, Vijayaraj; Raffel, Sandra J.; Schwan, Tom G.

    2013-01-01

    Background Borrelia turicatae, an agent of tick-borne relapsing fever, is an example of a pathogen that can adapt to disparate conditions found when colonizing the mammalian host and arthropod vector. However, little is known about the genetic factors necessary during the tick-mammalian infectious cycle, therefore we developed a genetic system to transform this species of spirochete. We also identified a plasmid gene that was up-regulated in vitro when B. turicatae was grown in conditions mimicking the tick environment. This 40 kilodalton protein was predicted to be surface localized and designated the Borrelia repeat protein A (brpA) due to the redundancy of the amino acid motif Gln-Gly-Asn-Val-Glu. Methodology/Principal Findings Quantitative reverse-transcriptase polymerase chain reaction using RNA from B. turicatae infected ticks and mice indicated differential regulation of brpA during the tick-mammalian infectious cycle. The surface localization was determined, and production of the protein within the salivary glands of the tick was demonstrated. We then applied a novel genetic system for B. turicatae to inactivate brpA and examined the role of the gene product for vector colonization and the ability to establish murine infection. Conclusions/Significance These results demonstrate the complexity of protein production in a population of spirochetes within the tick. Additionally, the development of a genetic system is important for future studies to evaluate the requirement of specific B. turicatae genes for vector colonization and transmission. PMID:24205425

  17. Use of T7 RNA polymerase to direct expression of outer Surface Protein A (OspA) from the Lyme disease Spirochete, Borrelia burgdorferi

    NASA Technical Reports Server (NTRS)

    Dunn, John J.; Lade, Barbara N.

    1991-01-01

    The OspA gene from a North American strain of the Lyme disease Spirochete, Borrelia burgdorferi, was cloned under the control of transciption and translation signals from bacteriophage T7. Full-length OspA protein, a 273 amino acid (31kD) lipoprotein, is expressed poorly in Escherichia coli and is associated with the insoluble membrane fraction. In contrast, a truncated form of OspA lacking the amino-terminal signal sequence which normally would direct localization of the protein to the outer membrane is expressed at very high levels (less than or equal to 100 mg/liter) and is soluble. The truncated protein was purified to homogeneity and is being tested to see if it will be useful as an immunogen in a vaccine against Lyme disease. Circular dichroism and fluorescence spectroscopy was used to characterize the secondary structure and study conformational changes in the protein. Studies underway with other surface proteins from B burgdorferi and a related spirochete, B. hermsii, which causes relapsing fever, leads us to conclude that a strategy similar to that used to express the truncated OspA can provide a facile method for producing variations of Borrelia lipoproteins which are highly expressed in E. coli and soluble without exposure to detergents.

  18. Detection of Borrelia burgdorferi sensu stricto and Borrelia garinii DNAs in patient with Hyperkeratosis lenticularis perstans (Flegel disease).

    PubMed

    Schwarzova, Katarina; Kozub, Peter; Szep, Zoltan; Golovchenko, Marina; Rudenko, Natasha

    2016-09-01

    Determination of the causative agent of erythema-like skin lesions in case of nonspecific superficial perivascular dermatitis was supported by histological examination and led to the latter diagnosis of Hyperkeratosis lenticularis perstans (Flegel disease) in patient. The presence of antibodies against Borrelia burgdorferi in patient serum was confirmed by a routine ELISA method and verified by Western blot technique. Skin biopsy and blood specimens were analyzed by PCR and multilocus sequence analysis (MLSA). Western blot method revealed IgG antibody response against two specific antigens, 17 and 83 kDa proteins. The recombinant test detected IgG antibody response against p100 and p41 antigens. The sequence analysis of amplicons from the selected genomic loci obtained from skin biopsy and serum samples revealed the presence of two species from B. burgdorferi sensu lato complex as a co-infection in this patient-B. burgdorferi sensu stricto (s.s.) and Borrelia garinii. PMID:26769152

  19. Cooperation of Doxycycline with Phytochemicals and Micronutrients Against Active and Persistent Forms of Borrelia sp

    PubMed Central

    Goc, Anna; Niedzwiecki, Alexandra; Rath, Matthias

    2016-01-01

    Phytochemicals and micronutrients represent a growing theme in antimicrobial defense; however, little is known about their anti-borreliae effects of reciprocal cooperation with antibiotics. A better understanding of this aspect could advance our knowledge and help improve the efficacy of current approaches towards Borrelia sp. In this study, phytochemicals and micronutrients such as baicalein, luteolin, 10-HAD, iodine, rosmarinic acid, and monolaurin, as well as, vitamins D3 and C were tested in a combinations with doxycycline for their in vitro effectiveness against vegetative (spirochetes) and latent (rounded bodies, biofilm) forms of Borrelia burgdorferi and Borrelia garinii. Anti-borreliae effects were evaluated according to checkerboard assays and supported by statistical analysis. The results showed that combination of doxycycline with flavones such as baicalein and luteolin exhibited additive effects against all morphological forms of studied Borrelia sp. Doxycycline combined with iodine demonstrated additive effects against spirochetes and biofilm, whereas with fatty acids such as monolaurin and 10-HAD it produced FICIs of indifference. Additive anti-spirochetal effects were also observed when doxycycline was used with rosmarinic acid and both vitamins D3 and C. Antagonism was not observed in any of the cases. This data revealed the intrinsic anti-borreliae activity of doxycycline with tested phytochemicals and micronutrients indicating that their addition may enhance efficacy of this antibiotic in combating Borrelia sp. Especially the addition of flavones balcalein and luteolin to a doxycycline regimen could be explored further in defining more effective treatments against these bacteria. PMID:27570483

  20. A boy with a tight skin: Borrelia-associated early-onset morphea.

    PubMed

    Verberkt, Roos M; Janssen, Matthijs; Wesseling, Judit

    2014-01-01

    We present a case of a 16-year-old boy with morphea caused by Borrelia burgdorferi. We re-emphasise an immunohistochemical method, focus floating microscopy (FFM), to detect Borrelia burgdorferi spirochetes in tissue sections. Focus floating microscopy (FFM) proved to be more sensitive than polymerase chain reaction (PCR) and nearly equally specific. PMID:24093617

  1. Genome Sequence of Borrelia chilensis VA1, a South American Member of the Lyme Borreliosis Group

    PubMed Central

    Huang, Weihua; Ojaimi, Caroline; Fallon, John T.; Travisany, Dante; Maass, Alejandro; Ivanova, Larisa; Tomova, Alexandra; González-Acuña, Daniel; Cabello, Felipe C.

    2015-01-01

    Borrelia chilensis strain VA1 is a recently described South American member of the Borrelia burgdorferi sensu lato complex from Chile. Whole-genome sequencing analysis determined its linear chromosome and plasmids lp54 and cp26, confirmed its membership in the Lyme borreliosis group, and will open new research avenues regarding its pathogenic potential. PMID:25676758

  2. Variable exposure and immunological response to Lyme disease Borrelia among North Atlantic seabird species

    PubMed Central

    Staszewski, V; McCoy, K.D; Boulinier, T

    2008-01-01

    Colonial seabirds often breed in large aggregations. These individuals can be exposed to parasitism by the tick Ixodes uriae, but little is known about the circulation of pathogens carried by this ectoparasite, including Lyme disease Borrelia. Here we investigated the prevalence of antibodies (Ab) against Borrelia burgdorferi sensu lato in seabird species sampled at eight locations across the North Atlantic. Using enzyme-linked immunosorbent assay tests, we found that the prevalence of anti-Borrelia Ab in adult seabirds was 39.6% on average (over 444 individuals), but that it varied among colonies and species. Common guillemots showed higher seroprevalence (77.1%±5.9) than black-legged kittiwakes (18.6%±6.7) and Atlantic puffins (22.6%±6.3). Immunoblot-banding patterns of positive individuals, reflecting the variability of Borrelia antigens against which Ab were produced, also differed among locations and species, and did not tightly match the prevalence of Borrelia phylogroups previously identified in ticks collected from the same host individuals. These results represent the first report of the widespread prevalence of Ab against Borrelia within an assemblage of seabird species and demonstrate that Borrelia is an integrated aspect in the interaction between seabirds and ticks. More detailed studies on the dynamics of Borrelia within and among seabird species at different spatial scales will now be required to better understand the implications of this interaction for seabird ecology and the epidemiology of Lyme disease. PMID:18577503

  3. Cooperation of Doxycycline with Phytochemicals and Micronutrients Against Active and Persistent Forms of Borrelia sp.

    PubMed

    Goc, Anna; Niedzwiecki, Alexandra; Rath, Matthias

    2016-01-01

    Phytochemicals and micronutrients represent a growing theme in antimicrobial defense; however, little is known about their anti-borreliae effects of reciprocal cooperation with antibiotics. A better understanding of this aspect could advance our knowledge and help improve the efficacy of current approaches towards Borrelia sp. In this study, phytochemicals and micronutrients such as baicalein, luteolin, 10-HAD, iodine, rosmarinic acid, and monolaurin, as well as, vitamins D3 and C were tested in a combinations with doxycycline for their in vitro effectiveness against vegetative (spirochetes) and latent (rounded bodies, biofilm) forms of Borrelia burgdorferi and Borrelia garinii. Anti-borreliae effects were evaluated according to checkerboard assays and supported by statistical analysis. The results showed that combination of doxycycline with flavones such as baicalein and luteolin exhibited additive effects against all morphological forms of studied Borrelia sp. Doxycycline combined with iodine demonstrated additive effects against spirochetes and biofilm, whereas with fatty acids such as monolaurin and 10-HAD it produced FICIs of indifference. Additive anti-spirochetal effects were also observed when doxycycline was used with rosmarinic acid and both vitamins D3 and C. Antagonism was not observed in any of the cases. This data revealed the intrinsic anti-borreliae activity of doxycycline with tested phytochemicals and micronutrients indicating that their addition may enhance efficacy of this antibiotic in combating Borrelia sp. Especially the addition of flavones balcalein and luteolin to a doxycycline regimen could be explored further in defining more effective treatments against these bacteria. PMID:27570483

  4. Mathematical Models of Tuberculosis Reactivation and Relapse

    PubMed Central

    Wallis, Robert S.

    2016-01-01

    The natural history of human infection with Mycobacterium tuberculosis (Mtb) is highly variable, as is the response to treatment of active tuberculosis. There is presently no direct means to identify individuals in whom Mtb infection has been eradicated, whether by a bactericidal immune response or sterilizing antimicrobial chemotherapy. Mathematical models can assist in such circumstances by measuring or predicting events that cannot be directly observed. The 3 models discussed in this review illustrate instances in which mathematical models were used to identify individuals with innate resistance to Mtb infection, determine the etiologic mechanism of tuberculosis in patients treated with tumor necrosis factor blockers, and predict the risk of relapse in persons undergoing tuberculosis treatment. These examples illustrate the power of various types of mathematic models to increase knowledge and thereby inform interventions in the present global tuberculosis epidemic. PMID:27242697

  5. Why do patients with ulcerative colitis relapse?

    PubMed

    Riley, S A; Mani, V; Goodman, M J; Lucas, S

    1990-02-01

    To determine the factors responsible for ulcerative colitis relapse a cohort of 92 patients (18 to 78 years, 50 men) with clinically inactive disease have been followed for over 48 weeks. At 12 weekly intervals patients were asked, by means of standardised questionnaires, about infections, compliance with maintenance medication, new drug treatment, dietary changes, episodes of non-bloody diarrhoea, life stresses, and feelings of anxiety and depression. Thirty five patients (38%) relapsed (median interval 17 weeks, range three to 46 weeks). Patients who relapsed had a higher previous relapse rate than non-relapsers (p less than 0.001) and a shorter time from previous relapse to trial entry (p less than 0.05). Other clinical characteristics were equally matched in the two groups. Between and within group comparisons revealed that upper respiratory tract symptoms, antibiotic ingestion, analgesic intake, diarrhoeal episodes and stressful life events were no more common in the four weeks before relapse than before routine attendance. Anxiety and depression ratings were also similar in the two groups. The timing of ulcerative colitis relapse showed a clear seasonal pattern with 26 patients relapsing from August to January and only nine from January to July (p less than 0.001). In addition, a retrospective case note analysis revealed significant seasonality of onset of ulcerative colitis. We conclude that seasonal factors may contribute to both onset and relapse of ulcerative colitis. PMID:2311975

  6. Genome Stability of Lyme Disease Spirochetes: Comparative Genomics of Borrelia burgdorferi Plasmids

    PubMed Central

    Casjens, Sherwood R.; Mongodin, Emmanuel F.; Qiu, Wei-Gang; Luft, Benjamin J.; Schutzer, Steven E.; Gilcrease, Eddie B.; Huang, Wai Mun; Vujadinovic, Marija; Aron, John K.; Vargas, Levy C.; Freeman, Sam; Radune, Diana; Weidman, Janice F.; Dimitrov, George I.; Khouri, Hoda M.; Sosa, Julia E.; Halpin, Rebecca A.; Dunn, John J.; Fraser, Claire M.

    2012-01-01

    Lyme disease is the most common tick-borne human illness in North America. In order to understand the molecular pathogenesis, natural diversity, population structure and epizootic spread of the North American Lyme agent, Borrelia burgdorferi sensu stricto, a much better understanding of the natural diversity of its genome will be required. Towards this end we present a comparative analysis of the nucleotide sequences of the numerous plasmids of B. burgdorferi isolates B31, N40, JD1 and 297. These strains were chosen because they include the three most commonly studied laboratory strains, and because they represent different major genetic lineages and so are informative regarding the genetic diversity and evolution of this organism. A unique feature of Borrelia genomes is that they carry a large number of linear and circular plasmids, and this work shows that strains N40, JD1, 297 and B31 carry related but non-identical sets of 16, 20, 19 and 21 plasmids, respectively, that comprise 33–40% of their genomes. We deduce that there are at least 28 plasmid compatibility types among the four strains. The B. burgdorferi ∼900 Kbp linear chromosomes are evolutionarily exceptionally stable, except for a short ≤20 Kbp plasmid-like section at the right end. A few of the plasmids, including the linear lp54 and circular cp26, are also very stable. We show here that the other plasmids, especially the linear ones, are considerably more variable. Nearly all of the linear plasmids have undergone one or more substantial inter-plasmid rearrangements since their last common ancestor. In spite of these rearrangements and differences in plasmid contents, the overall gene complement of the different isolates has remained relatively constant. PMID:22432010

  7. Genome Stability of Lyme Disease Spirochetes: Comparative Genomics of Borrelia burgdorferi Plasmids

    SciTech Connect

    Casjens S. R.; Dunn J.; Mongodin, E. F.; Qiu, W.-G.; Luft, B. J.; Schutzer, S. E.; Gilcrease, E. B.; Huang, W. M.; Vujadinovic, M.; Aron, J. K.; Vargas, L. C.; Freeman, S.; Radune, D.; Weidman, J. F.; Dimitrov, G. I.; Khouri, H. M.; Sosa, J. E.; Halpin, R. A.; Fraser, C. M.

    2012-03-14

    Lyme disease is the most common tick-borne human illness in North America. In order to understand the molecular pathogenesis, natural diversity, population structure and epizootic spread of the North American Lyme agent, Borrelia burgdorferi sensu stricto, a much better understanding of the natural diversity of its genome will be required. Towards this end we present a comparative analysis of the nucleotide sequences of the numerous plasmids of B. burgdorferi isolates B31, N40, JD1 and 297. These strains were chosen because they include the three most commonly studied laboratory strains, and because they represent different major genetic lineages and so are informative regarding the genetic diversity and evolution of this organism. A unique feature of Borrelia genomes is that they carry a large number of linear and circular plasmids, and this work shows that strains N40, JD1, 297 and B31 carry related but non-identical sets of 16, 20, 19 and 21 plasmids, respectively, that comprise 33-40% of their genomes. We deduce that there are at least 28 plasmid compatibility types among the four strains. The B. burgdorferi {approx}900 Kbp linear chromosomes are evolutionarily exceptionally stable, except for a short {le}20 Kbp plasmid-like section at the right end. A few of the plasmids, including the linear lp54 and circular cp26, are also very stable. We show here that the other plasmids, especially the linear ones, are considerably more variable. Nearly all of the linear plasmids have undergone one or more substantial inter-plasmid rearrangements since their last common ancestor. In spite of these rearrangements and differences in plasmid contents, the overall gene complement of the different isolates has remained relatively constant.

  8. Lymphoma relapse presenting as neurolymphomatosis

    PubMed Central

    Pham, My; Awad, Mohammed

    2016-01-01

    Neurolymphomatosis (NL) is a rare neurological manifestation of lymphoma characterized by malignant lymphoma cells infiltrating cranial or peripheral nerve, or their roots. We present the first reported Australian case of a patient whose initial presentation of relapsed mantle cell lymphoma was NL. Our case highlights that clinical and imaging findings of NL often mimic other neuropathies, and hence presents unique challenges that may lead to delayed diagnosis and management. We emphasize the importance of considering NL in the differential diagnosis and combining imaging with other diagnostic modalities such as lumbar puncture (LP) to aid in the diagnosis of NL particularly where there is acute neurological deterioration. PMID:26889293

  9. Disease Risk & Landscape Attributes of Tick-Borne Borrelia Pathogens in the San Francisco Bay Area, California

    PubMed Central

    Carbajales-Dale, Patricia; Carbajales-Dale, Michael; Cinkovich, Stephanie S.; Lambin, Eric F.

    2015-01-01

    Habitat heterogeneity influences pathogen ecology by affecting vector abundance and the reservoir host communities. We investigated spatial patterns of disease risk for two human pathogens in the Borrelia genus–B. burgdorferi and B. miyamotoi–that are transmitted by the western black-legged tick, Ixodes pacificus. We collected ticks (349 nymphs, 273 adults) at 20 sites in the San Francisco Bay Area, California, USA. Tick abundance, pathogen prevalence and density of infected nymphs varied widely across sites and habitat type, though nymphal western black-legged ticks were more frequently found, and were more abundant in coast live oak forest and desert/semi-desert scrub (dominated by California sagebrush) habitats. We observed Borrelia infections in ticks at all sites where we able to collect >10 ticks. The recently recognized human pathogen, B. miyamotoi, was observed at a higher prevalence (13/349 nymphs = 3.7%, 95% CI = 2.0–6.3; 5/273 adults = 1.8%, 95% CI = 0.6–4.2) than recent studies from nearby locations (Alameda County, east of the San Francisco Bay), demonstrating that tick-borne disease risk and ecology can vary substantially at small geographic scales, with consequences for public health and disease diagnosis. PMID:26288371

  10. Disease Risk & Landscape Attributes of Tick-Borne Borrelia Pathogens in the San Francisco Bay Area, California.

    PubMed

    Salkeld, Daniel J; Nieto, Nathan C; Carbajales-Dale, Patricia; Carbajales-Dale, Michael; Cinkovich, Stephanie S; Lambin, Eric F

    2015-01-01

    Habitat heterogeneity influences pathogen ecology by affecting vector abundance and the reservoir host communities. We investigated spatial patterns of disease risk for two human pathogens in the Borrelia genus-B. burgdorferi and B. miyamotoi-that are transmitted by the western black-legged tick, Ixodes pacificus. We collected ticks (349 nymphs, 273 adults) at 20 sites in the San Francisco Bay Area, California, USA. Tick abundance, pathogen prevalence and density of infected nymphs varied widely across sites and habitat type, though nymphal western black-legged ticks were more frequently found, and were more abundant in coast live oak forest and desert/semi-desert scrub (dominated by California sagebrush) habitats. We observed Borrelia infections in ticks at all sites where we able to collect >10 ticks. The recently recognized human pathogen, B. miyamotoi, was observed at a higher prevalence (13/349 nymphs = 3.7%, 95% CI = 2.0-6.3; 5/273 adults = 1.8%, 95% CI = 0.6-4.2) than recent studies from nearby locations (Alameda County, east of the San Francisco Bay), demonstrating that tick-borne disease risk and ecology can vary substantially at small geographic scales, with consequences for public health and disease diagnosis. PMID:26288371

  11. Blocking pathogen transmission at the source: reservoir targeted OspA-based vaccines against Borrelia burgdorferi

    PubMed Central

    Gomes-Solecki, Maria

    2014-01-01

    Control strategies are especially challenging for microbial diseases caused by pathogens that persist in wildlife reservoirs and use arthropod vectors to cycle amongst those species. One of the most relevant illnesses that pose a direct human health risk is Lyme disease; in the US, the Centers for Disease Control and Prevention recently revised the probable number of cases by 10-fold, to 300,000 cases per year. Caused by Borrelia burgdorferi, Lyme disease can affect the nervous system, joints and heart. No human vaccine is approved by the Food and Drug Administration. In addition to novel human vaccines, new strategies for prevention of Lyme disease consist of pest management interventions, vector-targeted vaccines and reservoir-targeted vaccines. However, even human vaccines can not prevent Lyme disease expansion into other geographical areas. The other strategies aim at reducing tick density and at disrupting the transmission of B. burgdorferi by targeting one or more key elements that maintain the enzootic cycle: the reservoir host and/or the tick vector. Here, I provide a brief overview of the application of an OspA-based wildlife reservoir targeted vaccine aimed at reducing transmission of B. burgdorferi and present it as a strategy for reducing Lyme disease risk to humans. PMID:25309883

  12. Multi-trophic interactions driving the transmission cycle of Borrelia afzelii between Ixodes ricinus and rodents: a review.

    PubMed

    van Duijvendijk, Gilian; Sprong, Hein; Takken, Willem

    2015-01-01

    The tick Ixodes ricinus is the main vector of the spirochaete Borrelia burgdorferi sensu lato, the causal agent of Lyme borreliosis, in the western Palearctic. Rodents are the reservoir host of B. afzelii, which can be transmitted to I. ricinus larvae during a blood meal. The infected engorged larvae moult into infected nymphs, which can transmit the spirochaetes to rodents and humans. Interestingly, even though only about 1% of the larvae develop into a borreliae-infected nymph, the enzootic borreliae lifecycle can persist. The development from larva to infected nymph is a key aspect in this lifecycle, influencing the density of infected nymphs and thereby Lyme borreliosis risk. The density of infected nymphs varies temporally and geographically and is influenced by multi-trophic (tick-host-borreliae) interactions. For example, blood feeding success of ticks and spirochaete transmission success differ between rodent species and host-finding success appears to be affected by a B. afzelii infection in both the rodent and the tick. In this paper, we review the major interactions between I. ricinus, rodents and B. afzelii that influence this development, with the aim to elucidate the critical factors that determine the epidemiological risk of Lyme borreliosis. The effects of the tick, rodent and B. afzelii on larval host finding, larval blood feeding, spirochaete transmission from rodent to larva and development from larva to nymph are discussed. Nymphal host finding, nymphal blood feeding and spirochaete transmission from nymph to rodent are the final steps to complete the enzootic B. afzelii lifecycle and are included in the review. It is concluded that rodent density, rodent infection prevalence, and tick burden are the major factors affecting the development from larva to infected nymph and that these interact with each other. We suggest that the B. afzelii lifecycle is dependent on the aggregation of ticks among rodents, which is manipulated by the pathogen

  13. Prevalence of Borrelia burgdorferi sensu lato in ticks from eastern China.

    PubMed

    Hou, Juan; Ling, Feng; Chai, Chengliang; Lu, Ye; Yu, Xianghua; Lin, Junfen; Sun, Jimin; Chang, Yue; Ye, Xiaodong; Gu, Shiping; Pang, Weilong; Wang, Chengwei; Zheng, Xiaohua; Jiang, Jianmin; Chen, Zhiping; Gong, Zhenyu

    2015-02-01

    To explore the tick distribution and prevalence of Borrelia in Zhejiang Province, we performed a survey in nine sites. A total of 447 adult ticks of 11 species were captured and the dominant tick species were Haemaphysalis longicornis and Ixodes sinensis and the abundance of tick species in different areas varied significantly. Overall, 4.70% of the ticks were polymerase chain reaction (PCR) positive for Borrelia. The average PCR positive rates were 5.19% for H. longicornis, 3.45% for Amblyomma testudinarium, 1.06% for I. sinensis, 5.00% for Rhipicephalus (Boophilus) microplus, and 19.44% for Ixodes granulatus, respectively. No Borrelia DNA was detected in Rhiphicephalus haemaphysaloides, Haemaphysalis yeni, Dermacentor taiwanensis, Haemaphysalis hystricis, Hyalomna asiaticum, and Ixodes ovatus. The prevalence of Borrelia was significantly different among tick species and the prevalence in I. granulatus was significantly higher than that in other tick species. Of note, experimentally confirmed vectors for B. burgdorferi s.l. including I. sinensis and I. granulatus were found in Zhejiang Province. Two species of B. burgdorferi s.l. exist in Zhejiang Province of which 12 sequences were most similar to the sequence of Borrelia garinii and nine sequences were most similar to the sequence of Borrelia valaisiana or Borrelia yangtze sp. nov. PMID:25548382

  14. Whole-Genome Sequences of Thirteen Isolates of Borrelia burgdorferi

    SciTech Connect

    Schutzer S. E.; Dunn J.; Fraser-Liggett, C. M.; Casjens, S. R.; Qiu, W.-G.; Mongodin, E. F.; Luft, B. J.

    2011-02-01

    Borrelia burgdorferi is a causative agent of Lyme disease in North America and Eurasia. The first complete genome sequence of B. burgdorferi strain 31, available for more than a decade, has assisted research on the pathogenesis of Lyme disease. Because a single genome sequence is not sufficient to understand the relationship between genotypic and geographic variation and disease phenotype, we determined the whole-genome sequences of 13 additional B. burgdorferi isolates that span the range of natural variation. These sequences should allow improved understanding of pathogenesis and provide a foundation for novel detection, diagnosis, and prevention strategies.

  15. Molecular cloning and characterization of nlpH, encoding a novel, surface-exposed, polymorphic, plasmid-encoded 33-kilodalton lipoprotein of Borrelia afzelii.

    PubMed Central

    Theisen, M

    1996-01-01

    Borrelia burgdorferi sensu lato organisms, comprising B. burgdorferi sensu stricto, Borrelia afzelii, and Borrelia garinii, are tick-borne pathogens causing Lyme borreliosis in humans. To identify putative virulence determinants, a B. afzelii DNA library was screened for Congo red dye binding, a property associated with virulence in pathogenic bacteria. One clone was found to carry a 663-nucleotide-long open reading frame encoding a Congo red dye-binding protein with a calculated molecular mass of 25,660 Da. The amino acid sequence deduced from its nucleotide sequence was found to include a consensus bacterial lipidation site present at residues 15 to 18 (Leu-Ser-Gly-Cys). The lipoprotein nature was demonstrated by incorporation of radioactive palmitate; hence, this protein has been termed NlpH, for new lipoprotein H. NlpH is located on the surface of B. afzelii, and the nlpH gene is found on a circular plasmid. The nlpH gene is also found in B. burgdorferi sensu stricto and B. garinii. Immediately upstream of nlpH is located a smaller reading frame encoding a polypeptide containing the casein kinase II phosphorylation recognition sequence, (Ser/Thr)-X-Y-(Glu/Asp), repeated 10 times. PMID:8932298

  16. Polysynovitis in a horse due to Borrelia burgdorferi sensu lato infection--Case study.

    PubMed

    Passamonti, Fabrizio; Veronesi, Fabrizia; Cappelli, Katia; Capomaccio, Stefano; Reginato, Alice; Miglio, Arianna; Vardi, Doron M; Stefanetti, Valentina; Coletti, Mauro; Bazzica, Chiara; Pepe, Marco

    2015-01-01

    Lyme borreliosis (LB) is a multi-systemic tick-borne disease affecting both humans and animals, including horses, and is caused by a group of interrelated spirochetes classified within the Borrelia burgdorferi sensu lato (s.l.) complex. Despite the high reported seroprevalence in the European equine population for B. burgdorferi s.l., to-date no documented clinical cases have been described. A 6-year-old Paint gelding was referred with a history of three weeks of fever, intermittent lameness and digital flexor tendon sheath effusion of the right hind limb. Based on a strict diagnostic protocol, which included serological tests for infectious diseases and molecular investigations, a final diagnosis was made of polysynovitis due to B. burgdorferi s.l. infection. An unreported aspect observed in this case was the absence of the pathogen DNA in two of the affected joints. To the authors' knowledge, the case described represents the first documented clinical case of equine LB in Italy. Moreover, the absence of pathogen DNA in two of the affected joints observed in this case revealed a possible similarity with the same condition described in humans, where an immunomediated pathogenesis for arthropathy due to B. burgdorferi s.l. infection is suspected. Since humans and horses share the same habitat, this report supports the role of the horse as potential sentinel for human biological risk. PMID:26094517

  17. Early Cytokine Release in Response to Live Borrelia burgdorferi Sensu Lato Spirochetes Is Largely Complement Independent

    PubMed Central

    Säve, Susanne; Bergström, Sven; Forsberg, Pia; Jonsson, Nina; Ernerudh, Jan; Ekdahl, Kristina N.

    2014-01-01

    Aim Here we investigated the role of complement activation in phagocytosis and the release of cytokines and chemokines in response to two clinical isolates: Borrelia afzelii K78, which is resistant to complement-mediated lysis, and Borrelia garinii LU59, which is complement-sensitive. Methods Borrelia spirochetes were incubated in hirudin plasma, or hirudin-anticoagulated whole blood. Complement activation was measured as the generation of C3a and sC5b-9. Binding of the complement components C3, factor H, C4, and C4BP to the bacterial surfaces was analyzed. The importance of complement activation on phagocytosis, and on the release of cytokines and chemokines, was investigated using inhibitors acting at different levels of the complement cascade. Results 1) Borrelia garinii LU59 induced significantly higher complement activation than did Borrelia afzelii K78. 2) Borrelia afzelii K78 recruited higher amounts of factor H resulting in significantly lower C3 binding. 3) Both Borrelia strains were efficiently phagocytized by granulocytes and monocytes, with substantial inhibition by complement blockade at the levels of C3 and C5. 4) The release of the pro-inflammatory cytokines and chemokines IL-1β, IL-6, TNF, CCL20, and CXCL8, together with the anti-inflammatory IL-10, were increased the most (by>10-fold after exposure to Borrelia). 5) Both strains induced a similar release of cytokines and chemokines, which in contrast to the phagocytosis, was almost totally unaffected by complement blockade. Conclusions Our results show that complement activation plays an important role in the process of phagocytosis but not in the subsequent cytokine release in response to live Borrelia spirochetes. PMID:25265036

  18. A case of hemifacial paresis in a patient with Lyme neuroborreliosis treated with antibiotics in whom Borrelia meningitis developed.

    PubMed

    Shimizu, Hisao; Haratani, Koji; Miyazaki, Masayuki; Kakehi, Yoshiaki; Nagami, Shuhei; Katanami, Yuichi; Kawabata, Hiroki; Takahashi, Nobuyuki

    2016-07-28

    A 38-year-old man visited our hospital because of hemifacial paresis that developed 2 months after being bit by a tick. We diagnosed idiopathic peripheral facial palsy and gave the patient oral prednisolone and valacyclovir. Although the symptoms completely resolved in about 2 weeks, there was a risk of Lyme neuroborreliosis. The patient therefore received doxycycline (100 mg twice daily) and amoxicillin (1,000 mg 3 times daily) for 14 days. Two months later, he had symptoms of meningitis such as headache and fever accompanied by lymphocytic cerebrospinal fluid pleocytosis. Viral meningitis was diagnosed and treated with parenteral acyclovir. The symptoms of meningitis improved. Tests for serum IgG antibodies against borrelia were positive. We gave the patient a diagnosis of Lyme neuroborreliosis. The patient received intravenous ceftriaxone and had no relapse. It is a rare for meningitis to develop in a patient with cranial neuropathy who received doxycycline. Lyme neuroborreliosis is a rare disease in Japan. Care should therefore be exercised in the diagnosis of Lyme neuroborreliosis and evaluation of the response to treatment. PMID:27356734

  19. Acylated Cholesteryl Galactosides Are Specific Antigens of Borrelia Causing Lyme Disease and Frequently Induce Antibodies in Late Stages of Disease

    PubMed Central

    Stübs, Gunthard; Fingerle, Volker; Wilske, Bettina; Göbel, Ulf B.; Zähringer, Ulrich; Schumann, Ralf R.; Schröder, Nicolas W. J.

    2009-01-01

    Borrelia burgdorferi sensu lato is the causative agent of Lyme disease (LD), an infectious disease occurring in North America, Europe, and Asia in different clinical stages. B. burgdorferi sensu lato encompasses at least 12 species, with B. burgdorferi sensu stricto, B. garinii, and B. afzelii being of highest clinical importance. Immunologic testing for LD as well as recent vaccination strategies exclusively refer to proteinaceous antigens. However, B. burgdorferi sensu stricto exhibits glycolipid antigens, including 6-O-acylated cholesteryl β-d-galactopyranoside (ACGal), and first the data indicated that this compound may act as an immunogen. Here we investigated whether B. garinii and B. afzelii also possess this antigen, and whether antibodies directed against these compounds are abundant among patients suffering from different stages of LD. Gas-liquid chromatography/mass spectroscopy and NMR spectroscopy showed that both B. garinii and B. afzelii exhibit ACGal in high quantities. In contrast, B. hermsii causing relapsing fever features 6-O-acylated cholesteryl β-d-glucopyranoside (ACGlc). Sera derived from patients diagnosed for LD contained antibodies against ACGal, with 80% of patients suffering from late stage disease exhibiting this feature. Antibodies reacted with ACGal from all three B. burgdorferi species tested, but not with ACGlc from B. hermsii. These data show that ACGal is present in all clinically important B. burgdorferi species, and that specific antibodies against this compound are frequently found during LD. ACGal may thus be an interesting tool for improving diagnostics as well as for novel vaccination strategies. PMID:19307181

  20. Prodromal Signs and Symptoms of Schizophrenic Relapse.

    ERIC Educational Resources Information Center

    Subotnik, Kenneth L.; Nuechterlein, Keith H.

    Increasing evidence that decompensation into acute psychosis by schizophrenics can often be avoided with active pharmacological and psychosocial intervention at the early signs of relapse has stimulated research into the signs and symptoms prodromal to acute psychosis. In this study, 6-week periods prior to 17 psychotic relapses and to 11 relapses…

  1. Adjuvant steroids and relapse of typhoid fever.

    PubMed

    Cooles, P

    1986-10-01

    In a retrospective study, relapse after non-severe acute typhoid fever was highly significantly related to the use of adjuvant steroid in the initial illness. The steroid was given late and in small doses when compared with other studies. Caution should be observed when using steroids in this way as relapse though often mild may be a severe illness. PMID:3795323

  2. Relapse Crises and Coping among Dieters.

    ERIC Educational Resources Information Center

    Grilo, Carlos M.; And Others

    1989-01-01

    Examined situational antecedents of dieting relapse crises and dieters'attempts to cope with temptations to overeat among obese type II diabetics (N=57). Found three categories of relapse crises: mealtime, low-arousal, and emotional upset situations. Found upset situations most frequently produced negative outcome while strong cognitive and…

  3. Preventing Adolescent Relapse: Concepts, Theories and Techniques.

    ERIC Educational Resources Information Center

    Mishra, Shitala P.; Ressler, Robert A.

    This chapter discusses adolescent drug abuse relapse prevention. It presents the following four conclusions regarding the efficacy of prevention programs. First, more controlled studies are needed to evaluate the long-term effectiveness of relapse prevention strategies with adolescents in reducing factors such as cravings and increasing their…

  4. Infection of Ixodes ricinus (Acari: Ixodidae) by Borrelia burgdorferi sensu lato in North Africa

    USGS Publications Warehouse

    Zhioua, E.; Bouattour, A.; Hu, C.M.; Gharbi, M.; Aeschliman, A.; Ginsberg, H.S.; Gern, L.

    1999-01-01

    Free-living adult Ixodes ricinus L. were collected in Amdoun, situated in the Kroumiry mountains in northwestern Tunisia (North Africa). Using direct fluorescence antibody assay, the infection rate of field-collected I. ricinus by Borrelia burgdorferi sensu lato was 30.5% (n = 72). No difference in infection rate was observed between male and female ticks. Spirochetes that had been isolated from I. ricinus from Ain Drahim (Kroumiry Mountains) in 1988 were identified as Borrelia lusitaniae (formerly genospecies PotiB2). This is the first identification of a genospecies of Borrelia burgdorferi sensu lato from the continent of Africa.

  5. Relapsing polychondritis: A clinical update.

    PubMed

    Longo, Lucia; Greco, Antonio; Rea, Andrea; Lo Vasco, Vincenza Rita; De Virgilio, Armando; De Vincentiis, Marco

    2016-06-01

    Relapsing polychondritis (RP) is a rare connective tissue disease in which recurrent bouts of inflammation, involve the cartilage of the ears, nose, larynx, tracheobronchial tree and cardiovascular system. RP is generally observed in the fourth and fifth decades of life and occurs with equal frequency in both sexes. The cause of RP is still unknown. It is considered an immune-mediated disease, as there is an overlap between well documented RP with other rheumatic and autoimmune diseases. There is a significant association of RP with the antigen HLA-DR4. RP includes loss of basophilic staining of cartilage matrix perichondral accompanied by inflammation of the cartilage. Cells are present perivascular mononuclear and polymorphonuclear cells infiltrated. The chondrocytes become vacuolated and necrotic and are replaced by fibrous tissue. Common symptoms are often absent in the early stages of the disease in almost half the cases, resulting in delay in diagnosis. The development of chondrite allows the diagnosis of RP in patients initially evaluated for joint abnormalities, ocular, cutaneous, or audio-vestibular. Diagnostic criteria for RP are based on characteristic clinical manifestations. According to Damiani and Levine, the diagnosis can be considered final when one or more of the clinical features are present in conjunction with biopsy confirmation. The course of symptoms for patients with relapsing polychondritis is often unpredictable. Patients with mild signs of acute inflammation are usually treated with non-steroidal anti-inflammatory drugs and small doses of prednisone. Patients with severe manifestations, such as airway compromise may require high doses of prednisone or even intravenous pulse methyl-prednisone. PMID:26876384

  6. Modelling intervention effects after cancer relapses

    PubMed Central

    González, Juan R.; Peña, Edsel A.; Slate, Elizabeth H.

    2014-01-01

    Summary This article addresses the problem of incorporating information regarding the effects of treatments or interventions into models for repeated cancer relapses. In contrast to many existing models, our approach permits the impact of interventions to differ after each relapse. We adopt the general model for recurrent events proposed by Peña and Hollander, in which the effect of interventions is represented by an effective age process acting on the baseline hazard rate function. To accommodate the situation of cancer relapse, we propose an effective age function that encodes three possible therapeutic responses: complete remission, partial remission, and null response. The proposed model also incorporates the effect of covariates, the impact of previous relapses, and heterogeneity among individuals. We use our model to analyse the times to relapse for 63 patients with a particular subtype of indolent lymphoma and compare the results to those obtained using existing methods. PMID:16320269

  7. Trans-Atlantic exchanges have shaped the population structure of the Lyme disease agent Borrelia burgdorferi sensu stricto

    PubMed Central

    Castillo-Ramírez, S.; Fingerle, V.; Jungnick, S.; Straubinger, R. K.; Krebs, S.; Blum, H.; Meinel, D. M.; Hofmann, H.; Guertler, P.; Sing, A.; Margos, G.

    2016-01-01

    The origin and population structure of Borrelia burgdorferi sensu stricto (s.s.), the agent of Lyme disease, remain obscure. This tick-transmitted bacterial species occurs in both North America and Europe. We sequenced 17 European isolates (representing the most frequently found sequence types in Europe) and compared these with 17 North American strains. We show that trans-Atlantic exchanges have occurred in the evolutionary history of this species and that a European origin of B. burgdorferi s.s. is marginally more likely than a USA origin. The data further suggest that some European human patients may have acquired their infection in North America. We found three distinct genetically differentiated groups: i) the outgroup species Borrelia bissettii, ii) two divergent strains from Europe, and iii) a group composed of strains from both the USA and Europe. Phylogenetic analysis indicated that different genotypes were likely to have been introduced several times into the same area. Our results demonstrate that irrespective of whether B. burgdorferi s.s. originated in Europe or the USA, later trans-Atlantic exchange(s) have occurred and have shaped the population structure of this genospecies. This study clearly shows the utility of next generation sequencing to obtain a better understanding of the phylogeography of this bacterial species. PMID:26955886

  8. Trans-Atlantic exchanges have shaped the population structure of the Lyme disease agent Borrelia burgdorferi sensu stricto.

    PubMed

    Castillo-Ramírez, S; Fingerle, V; Jungnick, S; Straubinger, R K; Krebs, S; Blum, H; Meinel, D M; Hofmann, H; Guertler, P; Sing, A; Margos, G

    2016-01-01

    The origin and population structure of Borrelia burgdorferi sensu stricto (s.s.), the agent of Lyme disease, remain obscure. This tick-transmitted bacterial species occurs in both North America and Europe. We sequenced 17 European isolates (representing the most frequently found sequence types in Europe) and compared these with 17 North American strains. We show that trans-Atlantic exchanges have occurred in the evolutionary history of this species and that a European origin of B. burgdorferi s.s. is marginally more likely than a USA origin. The data further suggest that some European human patients may have acquired their infection in North America. We found three distinct genetically differentiated groups: i) the outgroup species Borrelia bissettii, ii) two divergent strains from Europe, and iii) a group composed of strains from both the USA and Europe. Phylogenetic analysis indicated that different genotypes were likely to have been introduced several times into the same area. Our results demonstrate that irrespective of whether B. burgdorferi s.s. originated in Europe or the USA, later trans-Atlantic exchange(s) have occurred and have shaped the population structure of this genospecies. This study clearly shows the utility of next generation sequencing to obtain a better understanding of the phylogeography of this bacterial species. PMID:26955886

  9. Isolation of live Borrelia burgdorferi sensu lato spirochaetes from patients with undefined disorders and symptoms not typical for Lyme borreliosis.

    PubMed

    Rudenko, N; Golovchenko, M; Vancova, M; Clark, K; Grubhoffer, L; Oliver, J H

    2016-03-01

    Lyme borreliosis is a multisystem disorder with a diverse spectrum of clinical manifestations, caused by spirochaetes of the Borrelia burgdorferi sensu lato complex. It is an infectious disease that can be successfully cured by antibiotic therapy in the early stages; however, the possibility of the appearance of persistent signs and symptoms of disease following antibiotic treatment is recognized. It is known that Lyme borreliosis mimics multiple diseases that were never proven to have a spirochaete aetiology. Using complete modified Kelly-Pettenkofer medium we succeeded in cultivating live B. burgdorferi sensu lato spirochaetes from samples taken from people who suffered from undefined disorders, had symptoms not typical for Lyme borreliosis, but who had undergone antibiotic treatment due to a suspicion of having Lyme disease even though they were seronegative. We report the first recovery of live B. burgdorferi sensu stricto from residents of southeastern USA and the first successful cultivation of live Borrelia bissettii-like strain from residents of North America. Our results support the fact that B. bissettii is responsible for human Lyme borreliosis worldwide along with B. burgdorferi s.s. The involvement of new spirochaete species in Lyme borreliosis changes the understanding and recognition of clinical manifestations of this disease. PMID:26673735

  10. Mammal Diversity and Infection Prevalence in the Maintenance of Enzootic Borrelia burgdorferi along the Western Coastal Plains of Maryland

    PubMed Central

    ANDERSON, JENNIFER M.; SWANSON, KATHERINE I.; SCHWARTZ, TIMOTHY R.; GLASS, GREGORY E.; NORRIS, DOUGLAS E.

    2014-01-01

    The primary vector of Borrelia burgdorferi in North America, Ixodes scapularis, feeds on various mammalian, avian, and reptilian hosts. Several small mammal hosts; Peromyscus leucopus, Tamias striatus, Microtus pennsylvanicus, and Blarina spp. can serve as reservoirs in an enzootic cycle of Lyme disease. The primary reservoir in the northeast United States is the white-footed mouse, P. leucopus. The infection prevalence of this reservoir as well as the roles of potential secondary reservoirs has not been established in southern Maryland, a region of low to moderate Borrelia infection in humans. Intensive trapping at 96 locations throughout the western Coastal Plains of Maryland was conducted and we found that 31.6% of P. leucopus were infected with B. burgdorferi. Sequence and phylogenetic analysis revealed that only B. burgdorferi sensu stricto circulated in southern Maryland. Feral house mice and voles also were infected and may serve as secondary hosts. Peromyscus gender, age and month of capture were significantly associated with infection status. Larval I. scapularis were the dominant ectoparasite collected from captured rodents even though host seeking A. americanum and D. variabilis were collected in greater numbers across the sampling region. Our findings illustrate that the enzootic cycle of LD is maintained in the western Coastal Plains region of southern Maryland between I. scapularis and P. leucopus as the dominant reservoir. PMID:17187577

  11. [Case of Borrelia brainstem encephalitis presenting with severe dysphagia].

    PubMed

    Kawano, Yuji; Shigeto, Hiroshi; Shiraishi, Yoshimasa; Ohyagi, Yasumasa; Kira, Jun-Ichi

    2010-04-01

    We report the case of a 30-year-old man who developed severe dysphagia owing to neuroborreliosis. He showed dysphagia, diplopia, hiccups, and walking difficulty Neurological examination revealed mild disturbance of consciousness, diplopia on left lateral gaze, left-side-dominant blephaloptosis, gaze-evoked horizontal nystagmus on left lateral gaze, mild bilateral muscle weakness, palatoplegia, dysphagia, dysarthria, and truncal ataxia An increased pharyngeal reflex caused dysphagia in this patient. An EEG revealed intermittent high amplitude slow wave activity. However, head MRI, blood count, serum chemistry, and cerebrospinal fluid examination showed no abnormality. Initially, brainstem encephalitis with unknown etiology was diagnosed. The hiccups, diplopia, and ptosis were improved by corticosteroid therapy, but other symptoms were refractory to corticosteroid therapy and IVIg. After these immunotherapies, anti-Borrelia IgG and IgM antibodies were found to be positive, and symptoms, including dysphagia, were improved by doxycycline and cefotaxime. Because the clinical symptoms of Borrelia infection are widely variable, neuroborreliosis should be considered in patients with brainstem encephalitis refractory to conventional immunotherapies. PMID:20411811

  12. Case Report: Bilateral diaphragmatic dysfunction due to Borrelia Burgdorferi

    PubMed Central

    Basunaid, Suhail; van der Grinten, Chris; Cobben, Nicole; Otte, Astrid; Sprooten, Roy; Gernot, Rohde

    2014-01-01

    Summary: In this case report we describe a rare case of bilateral diaphragmatic dysfunction due to Lyme disease. Case report: A 62-years-old male presented to the hospital because of flu-like symptoms. During initial evaluation a bilateral diaphragmatic weakness with orthopnea and nocturnal hypoventilation was observed, without a known aetiology. Bilateral diaphragmatic paralysis was confirmed by fluoroscopy with a positive sniff test. The patient was referred to our centre for chronic non-invasive nocturnal ventilation (cNPPV). Subsequent investigations revealed evidence of anti- Borrelia seroactivity in EIA-IgG and IgG-blot, suggesting a recent infection with Lyme disease, and resulted in a 4-week treatment with oral doxycycline. The symptoms of nocturnal hypoventilation were successfully improved with cNPPV. However, our patient still shows impaired diaphragmatic function but he is no longer fully dependent on nocturnal ventilatory support.     Conclusion: Lyme disease should be considered in the differential diagnosis of diaphragmatic dysfunction. It is a tick-borne illness caused by one of the three pathogenic species of the spirochete Borrelia burgdorferi, present in Europe. A delay in recognizing the symptoms can negatively affect the success of treatment. Non-invasive mechanical ventilation (NIV) is considered a treatment option for patients with diaphragmatic paralysis. PMID:25671085

  13. The distribution of canine exposure to Borrelia burgdorferi in a Lyme-Disease endemic area.

    PubMed Central

    Falco, R C; Smith, H A; Fish, D; Mojica, B A; Bellinger, M A; Harris, H L; Hechemy, K E

    1993-01-01

    OBJECTIVES. A serosurvey of canine exposure to Borrelia burgdorferi, the causative agent of human Lyme disease, was conducted in Westchester County, New York, to determine the distribution of exposure in an area endemic for Lyme disease. METHODS. A total of 1446 blood samples was collected from resident dogs and tested by modified enzyme-linked immunosorbent assay. Equivocal samples were further tested by immunoblot. A mean number of 57.8 samples was collected from each of 25 towns and cities. RESULTS. Seroprevalence rates for municipalities ranged from 6.5% to 85.2%. County seroprevalence was 49.2%. There was a significant difference among the rates for the northern (67.3%), central (45.2%), and southern (17.3%) regions. Multiple range analysis indicated homogeneity between the southern and central regions and the central and northern regions. CONCLUSIONS. Canine exposure to B burgdorferi increases in a south to north gradient within the county. Intensity of exposure, measured by enzyme-linked immunosorbent assay titers, indicates a similar pattern. The close association between dogs and humans suggests that human risk of acquiring Lyme disease within Westchester County is equally disparate and is inversely related to the degree of urbanization. PMID:8363007

  14. Seasonal prevalence of Borrelia burgdorferi in natural populations of white-footed mice, Peromyscus leucopus.

    PubMed

    Anderson, J F; Johnson, R C; Magnarelli, L A

    1987-08-01

    Borrelia burgdorferi, the etiologic agent of Lyme disease, was isolated from 111 of 237 Peromyscus leucopus captured during all seasons of the year. Borreliae were cultured from tissues of the spleen (101 mice), left kidney (76 mice), and right kidney (73 mice), from blood (12 mice), and from one fetus. Mice were infected during the winter, when immature Ixodes dammini were inactive. The prevalence of infection during the winter (less than or equal to 33%) was more than twofold lower than that during the summer (ca. 75%), a time when nymphal ticks are abundant. Overwintering, infected mice are reservoir hosts for subadult ticks that begin feeding in early spring. Twenty white-footed mice from which B. burgdorferi was isolated from tissues of spleen or kidney but not from blood were parasitized by larval I. dammini or Dermacentor variabilis which harbored borreliae. We conclude that these mice were infectious to feeding ticks, even though borreliae were not isolated from blood. PMID:3624451

  15. A New Borrelia Species Defined by Multilocus Sequence Analysis of Housekeeping Genes▿ †

    PubMed Central

    Margos, Gabriele; Vollmer, Stephanie A.; Cornet, Muriel; Garnier, Martine; Fingerle, Volker; Wilske, Bettina; Bormane, Antra; Vitorino, Liliana; Collares-Pereira, Margarida; Drancourt, Michel; Kurtenbach, Klaus

    2009-01-01

    Analysis of Lyme borreliosis (LB) spirochetes, using a novel multilocus sequence analysis scheme, revealed that OspA serotype 4 strains (a rodent-associated ecotype) of Borrelia garinii were sufficiently genetically distinct from bird-associated B. garinii strains to deserve species status. We suggest that OspA serotype 4 strains be raised to species status and named Borrelia bavariensis sp. nov. The rooted phylogenetic trees provide novel insights into the evolutionary history of LB spirochetes. PMID:19542332

  16. Improving reporting of multiple sclerosis relapse.

    PubMed

    Roberts, Megan; Lush, Tessa; Pohorely, John

    Many people with multiple sclerosis do not report a relapse. When it is reported, it is not always recorded in their notes. This can mean patients do not always have the most appropriate treatment. This article reviews some of the reasons why relapse reports are lacking and how the problem could be addressed. As a result, the decision was made to develop an app that patients could use to record their symptoms and wellbeing over time, to help identify and record relapses. Information could then be passed to their health professional via email, if desired. PMID:26775329

  17. Management of relapsed ovarian cancer: a review.

    PubMed

    Giornelli, Gonzalo H

    2016-01-01

    Around 70 % of ovarian cancer patients relapse after primary cytoreductive surgery and standard first-line chemotherapy. The biology of relapse remains unclear, but cancer stem cells seem to play an important role. There are still some areas of controversy on how to manage these relapses and or progressions that occur almost unavoidably in the course of this disease with shorter intervals between them as the natural history of this disease develops. The goal of treatments investigated in this neoplasm has shifted to maintenance therapy, trying to extend the progression free intervals in a disease that is becoming more and more protracted. PMID:27516935

  18. Synanthropic birds influence the distribution of Borrelia species: analysis of Ixodes ricinus ticks feeding on passerine birds.

    PubMed

    Dubska, Lenka; Literak, Ivan; Kocianova, Elena; Taragelova, Veronika; Sverakova, Veronika; Sychra, Oldrich; Hromadko, Miloslav

    2011-02-01

    Ixodes ricinus ticks collected from 835 birds and from vegetation in the Czech Republic were analyzed. Host-seeking ticks (n = 427) were infected predominantly by Borrelia afzelii (25%). Ticks (n = 1,012) from songbirds (Passeriformes) were infected commonly by Borrelia garinii (12.1%) and Borrelia valaisiana (13.4%). Juveniles of synanthropic birds, Eurasian blackbirds (Turdus merula) and song thrushes (Turdus philomelos), were major reservoir hosts of B. garinii. PMID:21148704

  19. Recognition of Borrelia burgdorferi by NOD2 is central for the induction of an inflammatory reaction.

    PubMed

    Oosting, Marije; Berende, Anneleen; Sturm, Patrick; Ter Hofstede, Hadewych J M; de Jong, Dirk J; Kanneganti, Thirumala-Devi; van der Meer, Jos W M; Kullberg, Bart-Jan; Netea, Mihai G; Joosten, Leo A B

    2010-06-15

    Toll-like receptor 2 (TLR2) plays an important role in the recognition of Borrelia bacteria, the causative agent of Lyme disease, but the existence and importance of additional receptors in this process has been hypothesized. In the present study, we confirmed the role played by TLR2 in the recognition of Borrelia bacteria but also demonstrated a crucial role for the intracellular peptidoglycan receptor NOD2 for sensing the spirochete. Cells from individuals who were homozygous for the loss-of-function mutation 3020insC in the NOD2 gene were defective with respect to cytokine release after stimulation with Borrelia species, and this was confirmed in peritoneal macrophages from mice lacking RICK, the adaptor molecule used by NOD2. In contrast, NOD1 played no major role in the recognition of Borrelia spirochetes. This raises the intriguing possibility that recognition of Borrelia spirochetes is exerted by TLR2 in combination with NOD2 and that both receptors are necessary for an effective induction of cytokines by Borrelia species. The interplay between TLR2 and NOD2 might not only be necessary for the induction of a proper immune response but may also contribute to inflammatory-induced pathology. PMID:20441518

  20. Evidence for Host-Genotype Associations of Borrelia burgdorferi Sensu Stricto

    PubMed Central

    Mechai, Samir; Margos, Gabriele; Feil, Edward J.; Barairo, Nicole; Lindsay, L. Robbin; Michel, Pascal; Ogden, Nicholas H.

    2016-01-01

    Different genotypes of the agent of Lyme disease in North America, Borrelia burgdorferi sensu stricto, show varying degrees of pathogenicity in humans. This variation in pathogenicity correlates with phylogeny and we have hypothesized that the different phylogenetic lineages in North America reflect adaptation to different host species. In this study, evidence for host species associations of B. burgdorferi genotypes was investigated using 41 B. burgdorferi-positive samples from five mammal species and 50 samples from host-seeking ticks collected during the course of field studies in four regions of Canada: Manitoba, northwestern Ontario, Quebec, and the Maritimes. The B. burgdorferi genotypes in the samples were characterized using three established molecular markers (multi-locus sequence typing [MLST], 16S-23S rrs-rrlA intergenic spacer, and outer surface protein C sequence [ospC] major groups). Correspondence analysis and generalized linear mixed effect models revealed significant associations between B. burgdorferi genotypes and host species (in particular chipmunks, and white-footed mice and deer mice), supporting the hypotheses that host adaptation contributes to the phylogenetic structure and possibly the observed variation in pathogenicity in humans. PMID:26901761

  1. GENETIC AND IMMUNOLOGICAL EVIDENCES OF BORRELIA BURGDORFERI IN DOG IN THAILAND.

    PubMed

    Sthitmatee, Nattawooti; Jinawan, Wanna; Jaisan, Nawaporn; Tangjitjaroen, Weerapongse; Chailangkarn, Sasisophin; Sodarat, Chollada; Ekgatat, Monaya; Padungtod, Pawin

    2016-01-01

    Lyme disease is a tick-borne zoonotic disease caused by spirochete Borrelia burgdorferi. It is transmitted from animals to humans by the bite of infected ticks of the genus Ixodes. Although Lyme disease has been reported in China and Japan, the disease has never been reported in Thailand. Blood samples and ticks were collected from 402 dogs from 7 and 3 animal clinics in Chiang Mai and Phuket Provinces, Thailand, respectively. Blood samples were tested for antibodies against B. burgdorferi, Anaplasma spp, Ehrlichia spp and Dirofilaria immitis using a commercial kit, and positive blood samples were subjected to nested PCR assay for B. burgdorferi fla, ospA and ospC, amplicons of which also were sequenced. Only one dog (from Chiang Mai) was positive for B. burgdorferi, with 97% to 100% genetic identity, depending on the sequences used for comparison, with strains from United State of America. All 376 ticks collected were Rhipicephalus sanguineus, but no tick was found on the infected dog. Further investigations of the infection source and vector are needed to understand potential risks of Lyme disease to dogs and humans in Thailand. PMID:27086427

  2. Vectors as Epidemiological Sentinels: Patterns of Within-Tick Borrelia burgdorferi Diversity

    PubMed Central

    Walter, Katharine S.; Carpi, Giovanna; Evans, Benjamin R.; Caccone, Adalgisa; Diuk-Wasser, Maria A.

    2016-01-01

    Hosts including humans, other vertebrates, and arthropods, are frequently infected with heterogeneous populations of pathogens. Within-host pathogen diversity has major implications for human health, epidemiology, and pathogen evolution. However, pathogen diversity within-hosts is difficult to characterize and little is known about the levels and sources of within-host diversity maintained in natural populations of disease vectors. Here, we examine genomic variation of the Lyme disease bacteria, Borrelia burgdorferi (Bb), in 98 individual field-collected tick vectors as a model for study of within-host processes. Deep population sequencing reveals extensive and previously undocumented levels of Bb variation: the majority (~70%) of ticks harbor mixed strain infections, which we define as levels Bb diversity pre-existing in a diverse inoculum. Within-tick diversity is thus a sample of the variation present within vertebrate hosts. Within individual ticks, we detect signatures of positive selection. Genes most commonly under positive selection across ticks include those involved in dissemination in vertebrate hosts and evasion of the vertebrate immune complement. By focusing on tick-borne Bb, we show that vectors can serve as epidemiological and evolutionary sentinels: within-vector pathogen diversity can be a useful and unbiased way to survey circulating pathogen diversity and identify evolutionary processes occurring in natural transmission cycles. PMID:27414806

  3. Vectors as Epidemiological Sentinels: Patterns of Within-Tick Borrelia burgdorferi Diversity.

    PubMed

    Walter, Katharine S; Carpi, Giovanna; Evans, Benjamin R; Caccone, Adalgisa; Diuk-Wasser, Maria A

    2016-07-01

    Hosts including humans, other vertebrates, and arthropods, are frequently infected with heterogeneous populations of pathogens. Within-host pathogen diversity has major implications for human health, epidemiology, and pathogen evolution. However, pathogen diversity within-hosts is difficult to characterize and little is known about the levels and sources of within-host diversity maintained in natural populations of disease vectors. Here, we examine genomic variation of the Lyme disease bacteria, Borrelia burgdorferi (Bb), in 98 individual field-collected tick vectors as a model for study of within-host processes. Deep population sequencing reveals extensive and previously undocumented levels of Bb variation: the majority (~70%) of ticks harbor mixed strain infections, which we define as levels Bb diversity pre-existing in a diverse inoculum. Within-tick diversity is thus a sample of the variation present within vertebrate hosts. Within individual ticks, we detect signatures of positive selection. Genes most commonly under positive selection across ticks include those involved in dissemination in vertebrate hosts and evasion of the vertebrate immune complement. By focusing on tick-borne Bb, we show that vectors can serve as epidemiological and evolutionary sentinels: within-vector pathogen diversity can be a useful and unbiased way to survey circulating pathogen diversity and identify evolutionary processes occurring in natural transmission cycles. PMID:27414806

  4. Relapse from safer sex: the next challenge for AIDS prevention efforts.

    PubMed

    Stall, R; Ekstrand, M; Pollack, L; McKusick, L; Coates, T J

    1990-01-01

    Prevention campaigns to reduce sexual transmission of human immunodeficiency virus (HIV) typically emphasize the initial adoption of safer sex techniques. We present data from a 5-year prospective study to show that the vast majority of resident gay men in San Francisco have made these initial risk reductions. Rather, relapse from safer sex techniques is now the predominant predominant kind of high-risk sex, accounting for approximately two thirds of all prevalent high-risk sex in the 1988 wave of data collection. Predictors of relapse from safer sex are identified, and these are discussed in terms of their implications for preventing relapse from the exclusive practice of safe sex. In communities that have already manifested widespread behavioral risk reductions and in which HIV infection is highly prevalent, finding ways to prevent relapse of behavioral risk reductions will be the next important challenge in the fight against acquired immune deficiency syndrome. PMID:2243318

  5. Quantitative Detection of Borrelia burgdorferi sensu lato in Erythema Migrans Skin Lesions Using Internally Controlled Duplex Real Time PCR

    PubMed Central

    Lusa, Lara; Stupica, Dasa; Maraspin, Vera; Barrett, P. Noel; Strle, Franc; Livey, Ian

    2013-01-01

    B. burgdorferi sensu stricto, B. afzelii, B. garinii and B. bavariensis are the principal species which account for Lyme borreliosis (LB) globally. We have developed an internally controlled duplex quantitative real time PCR assay targeting the Borrelia 16S rRNA and the human RNAseP genes. This assay is well-suited for laboratory confirmation of suspected cases of LB and will be used to assess the efficacy of a vaccine against LB in clinical trials. The assay is highly specific, successfully detecting DNA extracted from 83 diverse B. burgdorferi sensu lato strains representing all major species causing LB, while 21 unrelated microbial species and human genomic DNA tested negative. The assay was highly reproducible and sensitive, with a lower limit of detection of 6 copies per PCR reaction. Together with culture, the assay was used to evaluate paired 3 mm skin biopsy samples taken from 121 patients presenting with solitary erythema migrans (EM) lesion. PCR testing identified more positive biopsy samples than culture (77.7% PCR positive versus 55.1% culture positive) and correctly identified all specimens scored as culture positive. OspA-based typing identified the majority of isolates as B. afzelii (96.8%) and the bacterial load was significantly higher in culture positive biopsies than in culture negative biopsies (P<0.001). The quantitative data also enabled relationships between Borrelia burden and patient symptoms to be evaluated. The bacterial load was significantly higher among patients with systemic symptoms than without (P = 0.02) and was significantly higher for biopsies retrieved from patients with EM lesions with central clearing (P<0.001). 16S copy numbers were moderately lower in samples from patients reporting a history of LB (P = 0.10). This is the first quantitative PCR study of human skin biopsies predominantly infected with B. afzelii and the first study to demonstrate a clear relationship between clinical symptoms in B. afzelii

  6. Prevalence of Ehrlichia, Borrelia, and Rickettsial agents in Amblyomma americanum (Acari : Ixodidae) collected from nine states

    USGS Publications Warehouse

    Mixson, T.R.; Campbell, S.R.; Gill, J.S.; Ginsberg, H.S.; Reichard, M.V.; Schultz, T.L.; Dasch, G.A.

    2006-01-01

    Ambyomma antericanum (L.) (Acari: Ixodidae) is an aggressive tick that feeds on humans during all postembryonic life stages. In many regions of the United States, it is the tick most commonly found attached to humans. Public health interest has grown recently, due to the recognition of new human pathogens transmitted by A. antericanum and the expanding distribution of the tick. A. americanum is a vector of several bacteria pathogenic to humans. Ehrlichia chaffeensis and Ehrlichia ewingii cause moderate-to-severe febrile illness. 'Rickettsia amblyommii,' a member of the spotted fever group Rickettsia, also has recently been implicated as a possible human pathogen based on serologic evidence from persons recovering from illness after a tick bite. We have determined the prevalence of infection of Ehrlichia chaffeensis, E. ewingii, 'Borrelia lonestari,' and R. amblyommii within A. americanum ticks from 29 sites in nine states. Overall infection prevalences were 4.7% for E. chaffeensis (range, 0-27%), 3.5% for E. ewingii (range, 0-18.6%), 2.5% for B. lonestari (range, 0-12.2%), and 41.2% for R. amblyommii (range, 0-84.0%). In addition, 87 ticks (4.3%) were infected with two or more bacteria. This report documents new distribution records for E. ewingii, B. lonestari, and R. amblyommii and underscores the nonhomogeneous distribution of pathogen foci of infection. Additional surveillance throughout the range of A. antericanum is warranted to increase physician and public awareness of the risk of disease to humans from exposure to the agents transmitted by this tick.

  7. Bullying Borrelia: when the culture of science is under attack.

    PubMed

    Auwaerter, Paul G; Melia, Michael T

    2012-01-01

    Although Lyme disease responds to short courses of antibiotics, tick-borne Borrelia burgdorferi has been advanced by some as a frequent explanation for medically unexplained symptoms such as continual fatigue, musculoskeletal pains, and subjective neurocognitive dysfunction. Often called "chronic Lyme disease" by adherents of this philosophy, it is loosely defined, and practitioners liberally prescribe nostrums, including prolonged antimicrobial therapies, in a belief that this eradicates suspected infection. Perhaps due to the lack of supportive data, proponents of this theory have developed their own meetings, literature, activist groups, and substantial internet activities to advance their views. Forces motivating this movement are explored, as are tactics used to advance non-scientific ideas that have included legal action and garnering legislative endorsement. While neither logical nor evidence-based, "chronic Lyme disease" harnesses corrosive energies that taint modern medicine and society. PMID:23303970

  8. Susceptibility of selected rodent species from Colorado to Borrelia burgdorferi.

    PubMed

    Ubico, S R; McLean, R G; Cooksey, L M

    1996-04-01

    To determine the susceptibility of some common Colorado (USA) rodent species to Borrelia burgdorferi, pregnant Peromyscus maniculatus, Tamias minimus, and Spermophilus lateralis were trapped in May 1990 and kept in quarantine until their young were old enough to be used in the experiment. Six to eight 8-wk-old individuals of each of the Colorado species and, for comparison, eight laboratory raised P. leucopus were subcutaneously inoculated with > or = 10(5) spirochetes in 0.1 ml in July 1990. Tissue specimens were collected for isolation from these animals through April 1991. Spirochetes were isolated from blood, ear, bladder, kidney, spleen, liver, and eye in Barbour-Stoener-Kelly (BSK) medium from P. maniculatus, P. leucopus and T. minimus. Spirochetes were isolated from at least one tissue from all of these animals and no isolations were obtained from any of the S. lateralis. Thus, three of the four rodent species tested are susceptible to, and could harbor, B. burgdorferi. PMID:8722268

  9. Persister Development by Borrelia burgdorferi Populations In Vitro.

    PubMed

    Caskey, John R; Embers, Monica E

    2015-10-01

    Doxycycline is an antibiotic commonly used to treat Lyme disease and other bacterial infections. The MIC and minimum bactericidal concentration (MBC) for Borrelia burgdorferi have been investigated by different groups but were experimentally established in this study as a function of input cell density. We demonstrated that B. burgdorferi treated in the stationary phase has a higher probability of regrowth following removal of antibiotic. In addition, we determined experimentally and mathematically that the spirochetes which persist posttreatment do not have a longer lag phase but exhibit a lower growth rate than untreated spirochetes. Finally, we found that treating the spirochetes by pulse-dosing did not eliminate growth or reduce the persister population in vitro. From these data, we propose that B. burgdorferi persister development is stochastic and driven by slowed growth. PMID:26248368

  10. Lipid Exchange between Borrelia burgdorferi and Host Cells

    PubMed Central

    Crowley, Jameson T.; Toledo, Alvaro M.; LaRocca, Timothy J.; Coleman, James L.; London, Erwin; Benach, Jorge L.

    2013-01-01

    Borrelia burgdorferi, the agent of Lyme disease, has cholesterol and cholesterol-glycolipids that are essential for bacterial fitness, are antigenic, and could be important in mediating interactions with cells of the eukaryotic host. We show that the spirochetes can acquire cholesterol from plasma membranes of epithelial cells. In addition, through fluorescent and confocal microscopy combined with biochemical approaches, we demonstrated that B. burgdorferi labeled with the fluorescent cholesterol analog BODIPY-cholesterol or 3H-labeled cholesterol transfer both cholesterol and cholesterol-glycolipids to HeLa cells. The transfer occurs through two different mechanisms, by direct contact between the bacteria and eukaryotic cell and/or through release of outer membrane vesicles. Thus, two-way lipid exchange between spirochetes and host cells can occur. This lipid exchange could be an important process that contributes to the pathogenesis of Lyme disease. PMID:23326230

  11. Borrelia burgdorferi infection and Lyme disease in children.

    PubMed

    Esposito, Susanna; Bosis, Samantha; Sabatini, Caterina; Tagliaferri, Laura; Principi, Nicola

    2013-03-01

    Lyme disease is a multisystem disease that frequently affects children. It is caused by a group of related spirochetes, Borrelia burgdorferi sensu lato, that are transmitted by ticks belonging to species of the genus Ixodes. The clinical characteristics of Lyme disease in pediatrics resemble those observed in adults, although the symptoms may last for a shorter time and the outcome may be better. However, identifying Lyme disease in children can be significantly more difficult because some of its signs and symptoms can be similar to those of other common pediatric clinical manifestations. Finally, the diagnostic and therapeutic approach to childhood Lyme disease is frequently not codified, and guidelines specifically prepared for adults are used for children without having been validated. This review of the currently available data will evaluate what may be the best approach to the diagnosis and treatment of B. burgdorferi infection and disease in the pediatric population. PMID:23141587

  12. Bullying Borrelia: When the Culture of Science is Under Attack

    PubMed Central

    Auwaerter, Paul G.; Melia, Michael T.

    2012-01-01

    Although Lyme disease responds to short courses of antibiotics, tick-borne Borrelia burgdorferi has been advanced by some as a frequent explanation for medically unexplained symptoms such as continual fatigue, musculoskeletal pains, and subjective neurocognitive dysfunction. Often called “chronic Lyme disease” by adherents of this philosophy, it is loosely defined, and practitioners liberally prescribe nostrums, including prolonged antimicrobial therapies, in a belief that this eradicates suspected infection. Perhaps due to the lack of supportive data, proponents of this theory have developed their own meetings, literature, activist groups, and substantial internet activities to advance their views. Forces motivating this movement are explored, as are tactics used to advance non-scientific ideas that have included legal action and garnering legislative endorsement. While neither logical nor evidence-based, “chronic Lyme disease” harnesses corrosive energies that taint modern medicine and society. PMID:23303970

  13. Enhancement of Borrelia burgdorferi PCR by uracil N-glycosylase.

    PubMed Central

    Loewy, Z G; Mecca, J; Diaco, R

    1994-01-01

    Uracil DNA glycosylases are DNA repair enzymes present in virtually every organism. These enzymes function by excising from DNA uracil residues resulting from either misincorporation of dUMP residues by a DNA polymerase or deamination of cytosine. Recently, the enzyme has been exploited in PCRs as a means for controlling carryover contamination from previously amplified DNA. When the enzyme is used in amplifications of Borrelia burgdorferi target sequences, we have observed an enhancement in signal detected by a microwell plate DNA hybridization assay. This increase in signal is dependent upon the length of the target, is titratable with enzyme concentration, and has been observed with amplifications performed with both symmetric and asymmetric PCR profiles. The enhancement is shown to occur at the level of the target genomic DNA. PMID:8126168

  14. Late relapses in acute promyelocytic leukaemia.

    PubMed

    Latagliata, Roberto; Carmosino, Ida; Breccia, Massimo; Minni, Antonio; Testi, Anna; Iorio, Nicol; Lo-Coco, Francesco; Avvisati, Giuseppe; Petti, Maria Concetta; Mandelli, Franco; Cimino, Giuseppe

    2007-01-01

    From January 1988 to December 1997, among 53 acute promyelocytic leukaemia patients in 1st complete remission (CR) after 5 years from diagnosis, we observed 5 late relapses (9.4%) after 60, 61, 71, 101 and 155 months from diagnosis; 3 of those late relapses (7.7%) occurred among 39 patients previously treated with all-trans-retinoic acid. An involvement of the mastoid occurred in 3/5 patients (60%), compared with 2/32 patients (6.3%) at an early relapse (p < 0.02). As to the treatment of the late relapse, 1 patient received all-trans-retinoic acid alone followed by allogeneic transplantation and 4 patients were treated according to the GIMEMA 0191 protocol. All patients achieved a 2nd CR and are still alive: 4 in the 2nd molecular CR after 6, 33, 34 and 115 months; 1 relapsed after 15 months and is now in the 3rd CR. In conclusion, a late relapse occurred in a sizeable fraction of acute promyelocytic leukaemia patients: the high rate of ear involvement might be explained considering the ear as a 'disease sanctuary'. PMID:17135723

  15. Relapse Prevention with Substance Abusers: Clinical Issues and Myths.

    ERIC Educational Resources Information Center

    Daley, Dennis C.

    1987-01-01

    Discusses the problems of relapse with alcoholics and other drug abusers from three perspectives: client-related variables, common erroneous beliefs and myths held by professionals regarding relapse, and treatment system problems that may contribute to relapse. Offers proposed solutions and describes a relapse prevention model. (Author/ABB)

  16. Perivascular M2 Macrophages Stimulate Tumor Relapse after Chemotherapy

    PubMed Central

    Hughes, Russell; Qian, Bin-Zhi; Rowan, Charlotte; Muthana, Munitta; Keklikoglou, Ioanna; Olson, Oakley C.; Tazzyman, Simon; Danson, Sarah; Addison, Christina; Clemons, Mark; Gonzalez-Angulo, Ana Maria; Joyce, Johanna A.; De Palma, Michele; Pollard, Jeffrey W.; Lewis, Claire E.

    2016-01-01

    Tumor relapse after chemotherapy-induced regression is a major clinical problem, because it often involves inoperable metastatic disease. Tumor-associated macrophages (TAM) are known to limit the cytotoxic effects of chemotherapy in preclinical models of cancer. Here, we report that an alternatively activated (M2) subpopulation of TAMs (MRC1+TIE2HiCXCR4Hi) accumulate around blood vessels in tumors after chemotherapy, where they promote tumor revascularization and relapse, in part, via VEGF-A release. A similar perivascular, M2-related TAM subset was present in human breast carcinomas and bone metastases after chemotherapy. Although a small proportion of M2 TAMs were also present in hypoxic tumor areas, when we genetically ablated their ability to respond to hypoxia via hypoxia-inducible factors 1 and 2, tumor relapse was unaffected. TAMs were the predominant cells expressing immunoreactive CXCR4 in chemotherapy-treated mouse tumors, with the highest levels expressed by MRC1+ TAMs clustering around the tumor vasculature. Furthermore, the primary CXCR4 ligand, CXCL12, was upregulated in these perivascular sites after chemotherapy, where it was selectively chemotactic for MRC1+ TAMs. Interestingly, HMOX-1, a marker of oxidative stress, was also upregulated in perivascular areas after chemotherapy. This enzyme generates carbon monoxide from the breakdown of heme, a gas known to upregulate CXCL12. Finally, pharmacologic blockade of CXCR4 selectively reduced M2-related TAMs after chemotherapy, especially those in direct contact with blood vessels, thereby reducing tumor revascularization and regrowth. Our studies rationalize a strategy to leverage chemotherapeutic efficacy by selectively targeting this perivascular, relapse-promoting M2-related TAM cell population. PMID:26269531

  17. Allopurinol Resistance in Leishmania infantum from Dogs with Disease Relapse

    PubMed Central

    Yasur-Landau, Daniel; Jaffe, Charles L.; David, Lior; Baneth, Gad

    2016-01-01

    Background Visceral leishmaniasis caused by the protozoan Leishmania infantum is a zoonotic, life threatening parasitic disease. Domestic dogs are the main peridomestic reservoir, and allopurinol is the most frequently used drug for the control of infection, alone or in combination with other drugs. Resistance of Leishmania strains from dogs to allopurinol has not been described before in clinical studies. Methodology/Principal Findings Following our observation of clinical disease relapse in dogs under allopurinol treatment, we tested susceptibility to allopurinol of L. infantum isolated from groups of dogs pre-treatment, treated in remission, and with disease relapse during treatment. Promastigote isolates obtained from four treated relapsed dogs (TR group) showed an average half maximal inhibitory concentration (IC50) of 996 μg/mL. A significantly lower IC50 (P = 0.01) was found for isolates from ten dogs before treatment (NT group, 200 μg/mL), as well as for five isolates obtained from treated dogs in remission (TA group, 268 μg/mL). Axenic amastigotes produced from isolates of the TR group also showed significantly higher (P = 0.002) IC50 compared to the NT group (1678 and 671 μg/mL, respectively). The lower sensitivity of intracellular amastigotes from the TR group relative to those from the NT group (P = 0.002) was confirmed using an infected macrophage model (6.3% and 20% growth inhibition, respectively at 300 μg/mL allopurinol). Conclusions This is the first study to demonstrate allopurinol resistance in L. infantum and to associate it with disease relapse in the canine host. These findings are of concern as allopurinol is the main drug used for long term control of the disease in dogs, and resistant L. infantum strains may enhance uncontrolled transmission to humans and to other dogs. PMID:26735519

  18. BB0323 function is essential for Borrelia burgdorferi virulence and persistence through tick-rodent transmission cycle

    PubMed Central

    Zhang, Xinyue; Yang, Xiuli; Kumar, Manish; Pal, Utpal

    2010-01-01

    Borrelia burgdorferi bb0323 encodes an immunogenic protein in mammalian hosts including humans. An analysis of bb0323 expression in vivo showed variable transcription throughout the spirochete infection cycle, with elevated expression during tick-mouse transmission. Deletion of bb0323 in infectious B. burgdorferi did not affect microbial survival in vitro, despite significant alterations in growth kinetics and cell morphology. bb0323 mutants were unable to infect either mice or ticks, and were quickly eliminated from immunocompetent and immunodeficient hosts and the vector, within the first few days of inoculation. Chromosomal complementation of the mutant with native bb0323 and phenotypic analysis in vivo indicated the significant restoration of spirochete virulence and persistence throughout the mouse-tick infection cycle. BB0323 may serve an indispensable physiological function that is more pronounced during microbial persistence and transitions between the host and the vector in vivo. Strategies to interfere with BB0323 function may interrupt the infectious cycle of spirochetes. PMID:19754308

  19. Live imaging reveals a biphasic mode of dissemination of Borrelia burgdorferi within ticks

    PubMed Central

    Dunham-Ems, Star M.; Caimano, Melissa J.; Pal, Utpal; Wolgemuth, Charles W.; Eggers, Christian H.; Balic, Anamaria; Radolf, Justin D.

    2009-01-01

    Lyme disease is caused by transmission of the spirochete Borrelia burgdorferi from ticks to humans. Although much is known about B. burgdorferi replication, the routes and mechanisms by which it disseminates within the tick remain unclear. To better understand this process, we imaged live, infectious B. burgdorferi expressing a stably integrated, constitutively expressed GFP reporter. Using isolated tick midguts and salivary glands, we observed B. burgdorferi progress through the feeding tick via what we believe to be a novel, biphasic mode of dissemination. In the first phase, replicating spirochetes, positioned at varying depths throughout the midgut at the onset of feeding, formed networks of nonmotile organisms that advanced toward the basolateral surface of the epithelium while adhering to differentiating, hypertrophying, and detaching epithelial cells. In the second phase of dissemination, the nonmotile spirochetes transitioned into motile organisms that penetrated the basement membrane and entered the hemocoel, then migrated to and entered the salivary glands. We designated the first phase of dissemination “adherence-mediated migration” and provided evidence that it involves the inhibition of spirochete motility by one or more diffusible factors elaborated by the feeding tick midgut. Our studies, which we believe are the first to relate the transmission dynamics of spirochetes to the complex morphological and developmental changes that the midgut and salivary glands undergo during engorgement, challenge the conventional viewpoint that dissemination of Lyme disease–causing spirochetes within ticks is exclusively motility driven. PMID:19920352

  20. Borrelia burgdorferi BmpA Is a Laminin-Binding Protein▿

    PubMed Central

    Verma, Ashutosh; Brissette, Catherine A.; Bowman, Amy; Stevenson, Brian

    2009-01-01

    The Borrelia burgdorferi BmpA outer surface protein plays a significant role in mammalian infection by the Lyme disease spirochete and is an important antigen for the serodiagnosis of human infection. B. burgdorferi adheres to host extracellular matrix components, including laminin. The results of our studies indicate that BmpA and its three paralogous proteins, BmpB, BmpC, and BmpD, all bind to mammalian laminin. BmpA did not bind mammalian type I or type IV collagens or fibronectin. BmpA-directed antibodies significantly inhibited the adherence of live B. burgdorferi to laminin. The laminin-binding domain of BmpA was mapped to the carboxy-terminal 80 amino acids. Solubilized collagen inhibited BmpA-laminin binding, suggesting interactions through the collagen-binding domains of laminin. These results, together with previous data, indicate that BmpA and its paralogs are targets for the development of preventative and curative therapies for Lyme disease. PMID:19703983

  1. Autophagy Modulates Borrelia burgdorferi-induced Production of Interleukin-1β (IL-1β)*

    PubMed Central

    Buffen, Kathrin; Oosting, Marije; Mennens, Svenja; Anand, Paras K.; Plantinga, Theo S.; Sturm, Patrick; van de Veerdonk, Frank L.; van der Meer, Jos W. M.; Xavier, Ramnik J.; Kanneganti, Thirumala-Devi; Netea, Mihai G.; Joosten, Leo A. B.

    2013-01-01

    Borrelia burgdorferi sensu lato is the causative agent of Lyme disease. Recent studies have shown that recognition of the spirochete is mediated by TLR2 and NOD2. The latter receptor has been associated with the induction of the intracellular degradation process called autophagy. The present study demonstrated for the first time the induction of autophagy by exposure to B. burgdorferi and that autophagy modulates the B. burgdorferi-dependent cytokine production. Human peripheral blood mononuclear cells treated with autophagy inhibitors showed an increased IL-1β and IL-6 production in response to the exposure of the spirochete, whereas TNFα production was unchanged. Autophagy induction against B. burgdorferi was dependent on reactive oxygen species (ROS) because cells from patients with chronic granulomatous disease, which are defective in ROS production, also produced elevated IL-1β. Further, the enhanced production of the proinflammatory cytokines was because of the elevated mRNA expression in the absence of autophagy. Our results thus demonstrate the induction of autophagy, which, in turn, modulates cytokine production by B. burgdorferi for the first time. PMID:23386602

  2. The salt-sensitive structure and zinc inhibition of Borrelia burgdorferi protease BbHtrA.

    PubMed

    Russell, Theresa M; Tang, Xiaoling; Goldstein, Jason M; Bagarozzi, Dennis; Johnson, Barbara J B

    2016-02-01

    HtrA serine proteases are highly conserved and essential ATP-independent proteases with chaperone activity. Bacteria express a variable number of HtrA homologues that contribute to the virulence and pathogenicity of bacterial pathogens. Lyme disease spirochetes possess a single HtrA protease homologue, Borrelia burgdorferi HtrA (BbHtrA). Previous studies established that, like the human orthologue HtrA1, BbHtrA is proteolytically active against numerous extracellular proteins in vitro. In this study, we utilized size exclusion chromatography and blue native polyacrylamide gel electrophoresis (BN-PAGE) to demonstrate BbHtrA oligomeric structures that were substrate independent and salt sensitive. Examination of the influence of transition metals on the activity of BbHtrA revealed that this protease is inhibited by Zn(2+) > Cu(2+) > Mn(2+). Extending this analysis to two other HtrA proteases, E. coli DegP and HtrA1, revealed that all three HtrA proteases were reversibly inhibited by ZnCl2 at all micro molar concentrations examined. Commercial inhibitors for HtrA proteases are not available and physiologic HtrA inhibitors are unknown. Our observation of conserved zinc inhibition of HtrA proteases will facilitate structural and functional studies of additional members of this important class of proteases. PMID:26480895

  3. Persistence of antibodies to Borrelia burgdorferi in dogs of New York and Connecticut.

    PubMed

    Magnarelli, L A; Anderson, J F; Schreier, A B

    1990-04-01

    Multiple blood samples were obtained from privately owned dogs living in tick-infested areas of New York (Westchester County) and Connecticut, where Lyme disease in human beings has been reported. Of the 175 dogs examined, 127 (72.6%) had limb/joint disorder, whereas the remaining 48 dogs were considered healthy. Results of analysis of 419 serum samples revealed IgM antibody to Borrelia burgdorferi in healthy and lame dogs during all seasons. Prevalence of seropositivity was significantly (P less than 0.01) greater, using a polyvalent ELISA (89.5%) than using a class-specific ELISA for IGM antibody (57.8%). Mean antibody titers obtained by use of polyvalent ELISA were likewise higher than IgM titers. Analysis of paired serum samples from dogs with limb/joint disorder indicated that 118 (92.9%) remained positive for IgM or IgG antibodies when retested weeks or months after initial testing. In 48 dogs without history of joint involvement or other signs of disease, 43 (89.6%) had antibody to B burgdorferi 2 or more times. Serotest results also revealed little or no change in antibody titer for lame dogs given antibiotics or for healthy dogs 2 or more months after initial sample collection. PMID:2329074

  4. Seroprevalence of Borrelia burgdorferi antibodies in white-tailed deer from Texas.

    PubMed

    Adetunji, Shakirat A; Krecek, Rosina C; Castellanos, Gabrielle; Morrill, John C; Blue-McLendon, Alice; Cook, Walt E; Esteve-Gassent, Maria D

    2016-08-01

    Lyme Disease is caused by the bacterial pathogen Borrelia burgdorferi, and is transmitted by the tick-vector Ixodes scapularis. It is the most prevalent arthropod-borne disease in the United States. To determine the seroprevalence of B. burgdorferi antibodies in white-tailed deer (Odocoileus virginianus) from Texas, we analyzed serum samples (n = 1493) collected during the 2001-2015 hunting seasons, using indirect ELISA. Samples with higher sero-reactivity (0.803 and above) than the negative control group (0.662) were further tested using a more specific standardized western immunoblot assay to rule out false positives. Using ELISA, 4.7% of the samples were sero-reactive against B. burgdorferi, and these originated in two eco-regions in Texas (Edwards Plateau and South Texas Plains). However, only 0.5% of the total samples were sero-reactive by standardized western immunoblot assay. Additionally, both ELISA and standardized western immunoblot assay results correlated with an increased incidence in human Lyme Disease cases reported in Texas. This is the first longitudinal study to demonstrate fluctuation in sero-reactivity of white-tailed deer to B. burgdorferi sensu stricto antigens in southern United States. Future ecological and geographical studies are needed to assess the environmental factors governing the prevalence of Lyme Disease in non-endemic areas of the southern United States. PMID:27366674

  5. The BBA33 lipoprotein binds collagen and impacts Borrelia burgdorferi pathogenesis

    PubMed Central

    Zhi, Hui; Weening, Eric H.; Barbu, Elena Magda; Hyde, Jenny A.; Höök, Magnus; Skare, Jon T.

    2016-01-01

    Summary Borrelia burgdorferi , the etiologic agent of Lyme disease, adapts to the mammalian hosts by differentially expressing several genes in the BosR and Rrp2-RpoN-RpoS dependent pathways, resulting in a distinct protein profile relative to that seen for survival in the Ixodes spp. tick. Previous studies indicate that a putative lipoprotein, BBA33, is produced in an RpoS-dependent manner under conditions that mimic the mammalian component of the borrelial lifecycle. However, the significance and function for BBA33 is not known. Given its linkage to the BosR/Rrp2-RpoN-RpoS regulatory cascade, we hypothesized that BBA33 facilitates B. burgdorferi infection in the mammalian host. The deletion of bba33 eliminated B. burgdorferi infectivity in C3H mice, which was rescued by genetic complementation with intact bba33. With regard to function, a combinatorial peptide approach, coupled with subsequent in vitro binding assays, indicated that BBA33 binds to collagen type VI and, to a lesser extent, collagen type IV. Whole cell binding assays demonstrated BBA33-dependent binding to human collagen type VI. Taken together, these results suggest that BBA33 interacts with collagenous structures and may function as an adhesin in a process that is required to prevent bacterial clearance. PMID:25560615

  6. The BBA33 lipoprotein binds collagen and impacts Borrelia burgdorferi pathogenesis.

    PubMed

    Zhi, Hui; Weening, Eric H; Barbu, Elena Magda; Hyde, Jenny A; Höök, Magnus; Skare, Jon T

    2015-04-01

    Borrelia burgdorferi, the etiologic agent of Lyme disease, adapts to the mammalian hosts by differentially expressing several genes in the BosR and Rrp2-RpoN-RpoS dependent pathways, resulting in a distinct protein profile relative to that seen for survival in the Ixodes spp. tick. Previous studies indicate that a putative lipoprotein, BBA33, is produced in an RpoS-dependent manner under conditions that mimic the mammalian component of the borrelial lifecycle. However, the significance and function for BBA33 is not known. Given its linkage to the BosR/Rrp2-RpoN-RpoS regulatory cascade, we hypothesized that BBA33 facilitates B. burgdorferi infection in the mammalian host. The deletion of bba33 eliminated B. burgdorferi infectivity in C3H mice, which was rescued by genetic complementation with intact bba33. With regard to function, a combinatorial peptide approach, coupled with subsequent in vitro binding assays, indicated that BBA33 binds to collagen type VI and, to a lesser extent, collagen type IV. Whole cell binding assays demonstrated BBA33-dependent binding to human collagen type VI. Taken together, these results suggest that BBA33 interacts with collagenous structures and may function as an adhesin in a process that is required to prevent bacterial clearance. PMID:25560615

  7. Prevalence of Borrelia burgdorferi in white-footed mice and Ixodes dammini at Fort McCoy, Wis.

    PubMed Central

    Anderson, J F; Duray, P H; Magnarelli, L A

    1987-01-01

    Borrelia burgdorferi, the causative agent of Lyme disease, was isolated from 15 of 17 white-footed mice (Peromyscus leucopus) and 54 of 82 subadult Ixodes dammini from Fort McCoy, Wis. Of the 47 isolates tested, all reacted in indirect fluorescent-antibody tests with monoclonal antibodies directed against a surface protein of B. burgdorferi (approximate molecular weight, 31,000) and flagellins that are common to all Borrelia species. Indirect fluorescent-antibody reactions were variable when an antibody that binds to a surface protein with an approximate molecular weight of 34,000 was tested. The major proteins of isolates from ticks and mice had approximate molecular weights of 31,000, 34,000, and 41,000. Antibodies to B. burgdorferi were present (titer, greater than or equal to 1:64) in 16 of 97 white-tailed deer (Odocoileus virginianus). The mean number of subadult I. dammini on mice captured in June 1986 was 6.5, and the mean number of adult I. dammini on deer killed in November 1986 was 5.9. The presence of ticks and the high prevalence of I. dammini and mice infected with B. burgdorferi establish that Fort McCoy is an area in which the Lyme disease agent is highly endemic, even though there have been relatively few documented cases in humans. The low number of reported cases in humans may be a result of National Guard and reserve unit personnel returning home to civilian life and having symptoms expressed subsequently, or it could be due to misdiagnosis or nonreporting. Images PMID:3305566

  8. Cotransmission of Divergent Relapsing Fever Spirochetes by Artificially Infected Ornithodoros hermsi▿†

    PubMed Central

    Policastro, Paul F.; Raffel, Sandra J.; Schwan, Tom G.

    2011-01-01

    The soft tick Ornithodoros hermsi, which ranges in specific arboreal zones of western North America, acts as a vector for the relapsing fever spirochete Borrelia hermsii. Two genomic groups (genomic group I [GGI] and GGII) of B. hermsii are differentiated by multilocus sequence typing yet are codistributed in much of the vector's range. To test whether the tick vector can be infected via immersion, noninfected, colony-derived O. hermsi larvae were exposed to reduced-humidity conditions before immersion in culture suspensions of several GGI and GGII isolates. We tested for spirochetes in ticks by immunofluorescence microscopy and in mouse blood by quantitative PCR of the vtp locus to differentiate spirochete genotypes. The immersed larval ticks were capable of spirochete transmission to mice at the first nymphal feeding. Tick infection with mixed cultures of isolates DAH (vtp-6) (GGI) and MTW-2 (vtp-5) (GGII) resulted in ticks that caused spirochetemias in mice consisting of MTW-2 or both DAH and MTW-2. These findings show that this soft tick species can acquire B. hermsii by immersion in spirochete suspensions, that GGI and GGII isolates can coinfect the tick vector by this method, and that these spirochetes can be cotransmitted to a rodent host. PMID:21965393

  9. Tick infestation risk and Borrelia burgdorferi s.l. infection-induced increase in host-finding efficacy of female Ixodes ricinus under natural conditions.

    PubMed

    Faulde, Michael K; Robbins, Richard G

    2008-02-01

    An investigation of the risk of human tick infestation, together with the prevalence of Borrelia burgdorferi s.l. infection, was conducted in a sylvatic habitat in western Germany to provide data needed for future risk-benefit evaluations of acaricides used for clothing impregnation. Additionally, data were collected on behavioural changes in Borrelia burgdorferi s.l.-infected adult female I. ricinus ticks and the possible impact of such changes on host-finding efficacy. The risk of I. ricinus-infestation was determined by collecting from the protective clothing of volunteers and by dragging in known tick-infested sites in the Kühkopf Mountain area, Koblenz, Germany, from June through October 2006. The overall tick infestation rate per person per hour was 7.4+/-5.5, with the following sex- and stage-specific differences: males 0.32+/-0.37, females 1.1+/-1.2, nymphs 3.6+/-4.4, larvae 2.4+/-3.5. Concurrent dragging revealed an average 19.4+/-16.2 times higher infestation rate as well as a markedly lower infection rate with borreliae in adult I. ricinus ticks when compared to ticks collected from exposed human volunteers. Although the difference in infection rates was statistically significant (P<0.023) only in adult female ticks, our data indicate that B. burgdorferi s.l. infection may increase host-finding efficacy in adult I. ricinus. The overall exposure risk was 1.0 B. burgdorferi s.l.-infected ticks per person per hour of exposure, or 0.25 ticks per 100 m walking distance in the study area. PMID:18273686

  10. Risk of Ovarian Cancer Relapse Score

    PubMed Central

    Rizzuto, Ivana; Stavraka, Chara; Chatterjee, Jayanta; Borley, Jane; Hopkins, Thomas Glass; Gabra, Hani; Ghaem-Maghami, Sadaf; Huson, Les; Blagden, Sarah P.

    2015-01-01

    Objective The aim of this study was to construct a prognostic index that predicts risk of relapse in women who have completed first-line treatment for ovarian cancer (OC). Methods A database of OC cases from 2000 to 2010 was interrogated for International Federation of Gynecology and Obstetrics stage, grade and histological subtype of cancer, preoperative and posttreatment CA-125 level, presence or absence of residual disease after cytoreductive surgery and on postchemotherapy computed tomography scan, and time to progression and death. The strongest predictors of relapse were included into an algorithm, the Risk of Ovarian Cancer Relapse (ROVAR) score. Results Three hundred fifty-four cases of OC were analyzed to generate the ROVAR score. Factors selected were preoperative serum CA-125, International Federation of Gynecology and Obstetrics stage and grade of cancer, and presence of residual disease at posttreatment computed tomography scan. In the validation data set, the ROVAR score had a sensitivity and specificity of 94% and 61%, respectively. The concordance index for the validation data set was 0.91 (95% confidence interval, 0.85-0.96). The score allows patient stratification into low (<0.33), intermediate (0.34–0.67), and high (>0.67) probability of relapse. Conclusions The ROVAR score stratifies patients according to their risk of relapse following first-line treatment for OC. This can broadly facilitate the appropriate tailoring of posttreatment care and support. PMID:25647256

  11. Pathological gambling: understanding relapses and dropouts.

    PubMed

    Aragay, Núria; Jiménez-Murcia, Susana; Granero, Roser; Fernández-Aranda, Fernando; Ramos-Grille, Irene; Cardona, Sara; Garrido, Gemma; Anisul Islam, Mohammed; Menchón, José M; Vallès, Vicenç

    2015-02-01

    There is little available information on the factors that influence relapses and dropouts during therapy for pathological gambling (PG). The aim of this study was to determine socio-demographic, clinical, personality, and psychopathological predictors of relapse and dropout in a sample of pathological gamblers seeking treatment. A total of 566 consecutive outpatients diagnosed with PG according to DSM-IV-TR criteria were included. All patients underwent an individualized cognitive-behavioral treatment program. We analyzed predictors of relapse during 6months of treatment and during the subsequent 6months of follow-up, and predictors of dropout over the entire therapeutic program. Eighty patients (14.1%) experienced at least one relapse during the entire follow-up of the study: 50 (8.8%) within the treatment period and 12 (2.1%) during the subsequent 6-month follow-up period. The main predictors of relapse were single marital status, spending less than 100euros/week on gambling, active gambling behavior at treatment inclusion, and high scores on the TCI-R Harm Avoidance personality dimension. One hundred fifty-seven patients (27.8%) missed 3 or more therapeutic sessions over the entire therapeutic program. The main predictors of dropout were single marital status, younger age, and high scores on the TCI-R Novelty Seeking personality dimension. The presence of these factors at inclusion should be taken into account by physicians dealing with PG patients. PMID:25434846

  12. Relapse prevention with intellectually disabled sexual offenders.

    PubMed

    Keeling, Jenny A; Rose, John L

    2005-10-01

    The adaptation of relapse prevention theory to sexual offending (W. D. Pithers, J. K. Marques, C. C. Gibat, & G. A. Marlatt, 1983) has represented an important movement in cognitive-behavioural treatment for sexual offenders. However, this model of relapse prevention has been criticised for its limited view and oversimplification of the relapse prevention process (R. K. Hanson, 2000; T. Ward & S. M. Hudson, 1996). As a result, T. Ward and S. M. Hudson (2000a) have developed a multiple pathway model of the relapse prevention process based on self-regulation theory. Although this model continues to be empirically validated on sexual offenders (J. A. Bickley & A. R. Beech, 2002; T. Ward, S. M. Hudson, & J. C. McCormick, 1999), there has been no empirical research regarding the application of this theory to intellectually disabled sexual offenders. This paper discusses whether the characteristics of offenders in each of the relapse offence pathways, as described by T. Ward and S. M. Hudson (2000a), may be similar to the characteristics of intellectually disabled sexual offenders. From a review of the literature, it appears that the intellectually disabled sexual offender may be most likely to offend via the approach-automatic pathway or the avoidant-passive pathway. The potential treatment implications of the self-regulation model for intellectually disabled sexual offenders is discussed, as well as the need for empirical evaluation with regards to the application of this model to the intellectually disabled sexual offender population. PMID:16341602

  13. Occurrence of Borrelia burgdorferi s.l. in different genera of mosquitoes (Culicidae) in Central Europe.

    PubMed

    Melaun, Christian; Zotzmann, Sina; Santaella, Vanesa Garcia; Werblow, Antje; Zumkowski-Xylander, Helga; Kraiczy, Peter; Klimpel, Sven

    2016-03-01

    Lyme disease or Lyme borreliosis is a vector-borne infectious disease caused by spirochetes of the Borrelia burgdorferi sensu lato complex. Some stages of the borrelial transmission cycle in ticks (transstadial, feeding and co-feeding) can potentially occur also in insects, particularly in mosquitoes. In the present study, adult as well as larval mosquitoes were collected at 42 different geographical locations throughout Germany. This is the first study, in which German mosquitoes were analyzed for the presence of Borrelia spp. Targeting two specific borrelial genes, flaB and ospA encoding for the subunit B of flagellin and the outer surface protein A, the results show that DNA of Borrelia afzelii, Borrelia bavariensis and Borrelia garinii could be detected in ten Culicidae species comprising four distinct genera (Aedes, Culiseta, Culex, and Ochlerotatus). Positive samples also include adult specimens raised in the laboratory from wild-caught larvae indicating that transstadial and/or transovarial transmission might occur within a given mosquito population. PMID:26631488

  14. An Interpersonal Model of Addiction Relapse

    PubMed Central

    Leach, David; Kranzler, Henry R.

    2012-01-01

    In this article, we review the literature on interpersonal stress and rejection sensitivity and examine how these factors increase the risk of relapse in individuals with alcohol or drug dependence. We begin by considering the constructs of social pain and social threat, examining their evolutionary origins and their neuroanatomical, neuropsychological and neurophysiological dimensions. Together, these perspectives provide insight into the role of interpersonal stress as a powerful and oftentimes destructive factor that affects individuals in recovery from substance dependence. We then review the empirical evidence showing that intrapersonal traits and interpersonal environments interact to increase an addict’s risk of relapse. We conclude by proposing that substance-dependent individuals with high trait rejection sensitivity and a critical interpersonal environment are particularly vulnerable to relapse to substance use. PMID:24489485

  15. Coexistence of Borrelia burgdorferi s.l. genospecies within Ixodes ricinus ticks from central and eastern Poland.

    PubMed

    Sytykiewicz, Hubert; Karbowiak, Grzegorz; Chorostowska-Wynimko, Joanna; Szpechciński, Adam; Supergan-Marwicz, Marta; Horbowicz, Marcin; Szwed, Magdalena; Czerniewicz, Paweł; Sprawka, Iwona

    2015-12-01

    The purpose of the study was to assess the prevalence and coinfection rates of Borrelia burgdorferi sensu lato genotypes in Ixodes ricinus (L.) ticks sampled from diverse localities in central and eastern regions of Poland. In years 2009-2011, questing nymphs and adults of I. ricinus were collected using a flagging method at 18 localities representing distinct ecosystem types: urban green areas, suburban forests and rural woodlands. Molecular detection of B. burgdorferi s.l. genospecies was based on amplification of a fla gene using nested PCR technique, subsequent PCR-RFLP analysis and bidirectional sequencing. It was revealed that 45 samples (2.1%) harboured two different B. burgdorferi s.l. genospecies, whereas triple infections with various spirochetes was found in 11 (0.5%) individuals. Generally, the highest average coinfection rates were evidenced in arachnids gathered at rural woodlands, intermediate at suburban forests, while the lowest were recorded at urban green areas. Overall, single spirochete infections were noted in 16.3% (n = 352/2,153) ticks. Importantly, it is the first report evidencing the occurrence of Borrelia miyamotoi (0.3%, n = 7/2153) in I. ricinus populations within central Poland. Circumstantial variability of B. burgdorferi s.l. genospecies in the common tick individuals sampled at various habitat types in central and eastern Poland was displayed. The coexistence of two or three different spirochete genospecies in single adult ticks, as well as the presence of B. miyamotoi were demonstrated. Therefore, further studies uncovering the co-circulation of the tested bacteria and other human pathogens in I. ricinus ticks are required. PMID:26408587

  16. Vector competence of the blacklegged tick, Ixodes scapularis, for the recently recognized Lyme borreliosis spirochete Candidatus Borrelia mayonii.

    PubMed

    Dolan, Marc C; Hojgaard, Andrias; Hoxmeier, J Charles; Replogle, Adam J; Respicio-Kingry, Laurel B; Sexton, Christopher; Williams, Martin A; Pritt, Bobbi S; Schriefer, Martin E; Eisen, Lars

    2016-07-01

    A novel species within the Borrelia burgdorferi sensu lato complex, provisionally named Borrelia mayonii, was recently found to be associated with Lyme borreliosis in the Upper Midwest of the United States. Moreover, B. mayonii was detected from host-seeking Ixodes scapularis, the primary vector of B. burgdorferi sensu stricto in the eastern United States. We therefore conducted a study to confirm the experimental vector competence of I. scapularis for B. mayonii (strain MN14-1420), using colony ticks originating from adults collected in Connecticut and CD-1 white mice. Larvae fed on mice 10 weeks after needle-inoculation with B. mayonii acquired spirochetes and maintained infection through the nymphal stage at an average rate of 12.9%. In a transmission experiment, 40% of naïve mice exposed to a single infected nymph developed viable infections, as compared with 87% of mice fed upon by 2-3 infected nymphs. Transmission of B. mayonii by one or more feeding infected nymphs was uncommon up to 48h after attachment (one of six mice developed viable infection) but occurred frequently when nymphs were allowed to remain attached for 72-96h or feed to completion (11 of 16 mice developed viable infection). Mice infected via tick bite maintained viable infection with B. mayonii, as determined by ear biopsy culture, for at least 28 weeks. Our results demonstrate that I. scapularis is capable of serving as a vector of B. mayonii. This finding, together with data showing that field-collected I. scapularis are infected with B. mayonii, indicate that I. scapularis likely is a primary vector to humans of this recently recognized Lyme borreliosis spirochete. PMID:26922324

  17. Pathways to relapse: the neurobiology of drug- and stress-induced relapse to drug-taking.

    PubMed Central

    Stewart, J

    2000-01-01

    Relapse is a major characteristic of drug addiction, and remains the primary problem in treating drug abuse. Without an understanding of the factors that determine renewed drug-seeking, the urge to use drugs, and the persistent craving for them, it is unlikely that health care professionals can provide effective treatment. Using an animal model of relapse, the author and her team are studying factors that induce reinstatement of drug-taking behaviour after short and long periods of abstinence, and they are exploring the neurobiological basis of these effects. In their experiments, rats are trained to self-administer drugs intravenously by pressing 1 of 2 levers. During a subsequent period, the drug is no longer available, but the rats are free to try to obtain the drug (a period of "extinction training"). After extinction of responding, the investigators test for the ability of various events to reinitiate drug-seeking. On this background of renewed drug-seeking or relapse, the investigators search for pharmacological and neurochemical manipulations that might block or attenuate such behaviour. They have found that the 2 most effective events for reinstating responding after both short and long drug-free periods are re-exposure to the drug itself and exposure to a brief period of stress. The critical neurochemical pathways mediating drug-induced relapse are not identical to those mediating stress-induced relapse. Relapse induced by "priming" injections of heroin or cocaine involves activation of the mesolimbic dopaminergic pathways, whereas relapse induced by stress involves actions of corticotropin-releasing factor (CRF) in the brain, and of brain noradrenergic (NE) systems. In addition, evidence shows that CRF and NE may interact at the level of the bed nucleus of the stria terminalis in stress-induced relapse. By contrast, relapse induced by "priming" injections of drugs is relatively unaffected by manipulation of CRF and NE systems of the brain. PMID:10740986

  18. Enhanced Adhesion and OspC Protein Synthesis of the Lyme Disease Spirochete Borrelia Burgdorferi Cultivated in a Host-Derived Tissue Co-Culture System

    PubMed Central

    Şen, Ece; Sigal, Leonard H.

    2013-01-01

    Background: The adhesion process of Borrelia burgdorferi to susceptible host cell has not yet been completely understood regarding the function of OspA, OspB and OspC proteins and a conflict exists in the infection process. Aims: The adhesion rates of pathogenic (low BSK medium passaged or susceptible rat joint tissue co-cultivated) or non-pathogenic Borrelia burgdorferi (high BSK medium passaged) isolate (FNJ) to human umbilical vein endothelial cells (HUVEC) cultured on coverslips and the synthesis of OspA and OspC proteins were investigated to analyze the infection process of this bacterium. Study Design: In-vitro study. Methods: Spirochetes were cultured in BSK medium or in a LEW/N rat tibiotarsal joint tissue feeder layer supported co-culture system using ESG co-culture medium and labelled with 3H-adenine for 48 hours. SDS-PAGE, Western Blotting, Immunogold A labeling as well as radiolabeling experiments were used to compare pathogenic or non pathogenic spirochetes during the adhesion process. Results: Tissue co-cultured B. burgdorferi adhered about ten times faster than BSK-grown spirochetes. Trypsin inhibited attachment to HUVEC and co-culture of trypsinized spirochetes with tissues reversed the inhibition. Also, the synthesis of OspC protein by spirochetes was increased in abundance after tissue co-cultures, as determined by SDS-PAGE and by electron microscopy analysis of protein A-immunogold staining by anti-OspC antibodies. OspA protein was synthesized in similar quantities in all Borrelia cultures analyzed by the same techniques. Conclusion: Low BSK passaged or tissue co-cultured pathogenic Lyme disease spirochetes adhere to HUVEC faster than non-pathogenic high BSK passaged forms of this bacterium. Spirochetes synthesized OspC protein during host tissue-associated growth. However, we did not observe a reduction of OspA synthesis during host tissue co-cultivation in vitro. PMID:25207103

  19. [Suspected syphilis during pregnancy due to cross reactions in Borrelia infection].

    PubMed

    Enders, G; Biber, M; Baier, R; Hlobil, H; Wellensiek, H J

    1988-09-30

    A weakly positive titre (1:20) in the Treponema pallidum haemagglutination test and a highly positive titre (1:1280) in the fluorescence Treponema antibody absorption test, but negative result for IgM antibodies, were found in the serum of a 23-year-old pregnant woman. The cardiolipin microflocculation test was at first borderline positive, but negative on repeat. In the absence of a history of syphilis tests for Borrelia antibodies were performed. Those for antibodies against B. burgdorferi were highly positive in the ELISA test (550 units), in the indirect Borrelia immunofluorescence test 1:1280 for IgG antibodies and 1:160 for IgM antibodies. In the Borrelia-specific indirect haemagglutination test, which measures both IgG and IgM antibodies, the titres were 1:640 to 1:1280. These results confirmed the presence of an infection with B. burgdorferi and not with Treponema pallidum. PMID:3048959

  20. In vitro activities of faropenem, ertapenem, imipenem and meropenem against Borrelia burgdorferi s.l.

    PubMed

    Rödel, Rebecca; Freyer, Alexandra; Bittner, Thomas; Schäfer, Volker; Hunfeld, Klaus-Peter

    2007-07-01

    Little is known about the in vitro activity of penems and carbapenems against the spirochete Borrelia burgdorferi. Here, faropenem, ertapenem, imipenem and meropenem as well as the third-generation cephalosporin ceftriaxone and tobramycin were tested in vitro against 11 isolates of the B. burgdorferi sensu lato complex. On a microg/mL basis, ertapenem was the most potent carbapenem (minimal inhibitory concentration (MIC) range: 0.015-0.125 microg/mL), with in vitro activity comparable with that of ceftriaxone against Borrelia. These findings are supported by the results of time-kill experiments in a Borrelia afzelii skin isolate, demonstrating a >3 log10 unit (99.9%) reduction of the inoculum after 96 h of exposure to either drug at a concentration of three log2 unit dilutions above the respective MIC. PMID:17512703

  1. The anti-borreliae efficacy of phytochemicals and micronutrients: an update.

    PubMed

    Goc, Anna; Rath, Matthias

    2016-06-01

    Naturally occurring substances have been used for centuries to fight against various pathogens. They serve as a source for new chemical entities or provide options to already existing therapeutics. While there is an increasing interest in studying antimicrobial properties of naturally derived agents, little is known about their effects against Borrelia burgdorferi sensu lato, the causative pathogens of Lyme disease. A better understanding of this aspect could advance knowledge about pathophysiology of these bacteria and help improve the efficacy of current approaches against Lyme disease. Here, we review all naturally occurring substances scientifically evaluated to date, including plant extracts, their metabolites, and micronutrients, against vegetative (spirochetes) and latent (rounded bodies, biofilm) forms of Borrelia sp. This summary reveals the potent anti-borreliae activity of several of these natural compounds indicating their potential in enhancing the efficacy of current treatments for Lyme disease, and offering new options to already existing therapeutic regiments. PMID:27536352

  2. How do Lyme Borrelia Organisms Cause Disease? The Quest for Virulence Determinants#

    PubMed Central

    Norris, Steven J

    2012-01-01

    Lyme disease Borrelia are invasive, nontoxigenic, persistent pathogens, and little is known about their mechanisms of pathogenesis. In our laboratory, a signature-tagged mutagenesis (STM) library of over 4,000 Borrelia burgdorferi transposon mutants has been constructed and is being screened for infectivity in mice. In this manner, a global view of the virulence determinants (factors required for full infectivity) is being developed. Additionally, the mechanisms of immune evasion involving the VMP-like system (vls) are under analysis, and cryo-electron microscopy is providing a detailed view of the three-dimensional structure of B. burgdorferi. These approaches will contribute to the improved understanding of how Lyme disease Borrelia cause disease. PMID:23091573

  3. The anti-borreliae efficacy of phytochemicals and micronutrients: an update

    PubMed Central

    Goc, Anna; Rath, Matthias

    2016-01-01

    Naturally occurring substances have been used for centuries to fight against various pathogens. They serve as a source for new chemical entities or provide options to already existing therapeutics. While there is an increasing interest in studying antimicrobial properties of naturally derived agents, little is known about their effects against Borrelia burgdorferi sensu lato, the causative pathogens of Lyme disease. A better understanding of this aspect could advance knowledge about pathophysiology of these bacteria and help improve the efficacy of current approaches against Lyme disease. Here, we review all naturally occurring substances scientifically evaluated to date, including plant extracts, their metabolites, and micronutrients, against vegetative (spirochetes) and latent (rounded bodies, biofilm) forms of Borrelia sp. This summary reveals the potent anti-borreliae activity of several of these natural compounds indicating their potential in enhancing the efficacy of current treatments for Lyme disease, and offering new options to already existing therapeutic regiments. PMID:27536352

  4. Loss of Mismatched HLA on the Leukemic Blasts of Patients With Relapsed Lymphoid Malignancies Following Bone Marrow Transplantation From Related Donors With HLA Class II Mismatches in the Graft Versus Host Direction.

    PubMed

    Hirabayashi, Koichi; Kurata, Takashi; Horiuchi, Kazuki; Saito, Shoji; Shigemura, Tomonari; Tanaka, Miyuki; Yanagisawa, Ryu; Matsuda, Kazuyuki; Sakashita, Kazuo; Koike, Kenichi; Nakazawa, Yozo

    2016-04-01

    Mechanisms of relapse of acute lymphoblastic leukemia (ALL) after human leukocyte antigen (HLA) class II mismatched hematopoietic stem cell transplantation (HSCT) remain unclear. We report two children with relapsed ALL after HSCT from related donors with HLA-DRB1 and -DQB1 mismatches in the graft versus host direction. One lost HLA-DRB1, DQB1, and DPB1 alleles, and the other lost one HLA haplotype of the leukemic blasts at relapse. HLA class II loss may be a triggering event for ALL relapse after partially HLA-mismatched-related HSCT. In addition, HLA typing of relapsed leukemic blasts could be vital in the selection of retransplant donors. PMID:26544669

  5. Virulent strain associated outer membrane proteins of Borrelia burgdorferi.

    PubMed Central

    Skare, J T; Shang, E S; Foley, D M; Blanco, D R; Champion, C I; Mirzabekov, T; Sokolov, Y; Kagan, B L; Miller, J N; Lovett, M A

    1995-01-01

    We have isolated and purified outer membrane vesicles (OMV) from Borrelia burgdorferi strain B31 based on methods developed for isolation of Treponema pallidum OMV. Purified OMV exhibited distinct porin activities with conductances of 0.6 and 12.6 nano-Siemen and had no detectable beta-NADH oxidase activity indicating their outer membrane origin and their lack of inner membrane contamination, respectively. Hydrophobic proteins were identified by phase partitioning with Triton X-114. Most of these hydrophobic membrane proteins were not acylated, suggesting that they are outer membrane-spanning proteins. Identification of palmitate-labeled lipoproteins revealed that several were enriched in the OMV, several were enriched in the protoplasmic cylinder inner membrane fraction, and others were found exclusively associated with the inner membrane. The protein composition of OMV changed significantly with successive in vitro cultivation of strain B31. Using antiserum with specificity for virulent strain B31, we identified OMV antigens on the surface of the spirochete and identified proteins whose presence in OMV could be correlated with virulence and protective immunity in the rabbit Lyme disease model. These virulent strain associated outer membrane-spanning proteins may provide new insight into the pathogenesis of Lyme disease. Images PMID:7593626

  6. Serological Detection of Borrelia burgdorferi among Horses in Korea

    PubMed Central

    Lee, Seung-Hun; Yun, Sun-Hee; Choi, Eunsang; Park, Yong-Soo; Lee, Sang-Eun; Cho, Gil-Jae; Kwon, Oh-Deog; Kwak, Dongmi

    2016-01-01

    Lyme disease is a tick-borne zoonotic infectious disease caused by Borrelia burgdorferi. The present study assessed the infection status of B. burgdorferi among horses reared in Korea using ELISA and PCR. Between 2009 and 2013, blood samples were collected from 727 horses throughout Korea. Data for each animal including age, gender, breed, and region of sample collection were used for epidemiological analysis. Overall, 38 (5.2%; true prevalence: 5.5%) of 727 horses were seropositive by ELISA. There were statistically significant differences according to breed and region (P<0.001) whose differences might be attributed to the ecology of vector ticks and climate conditions. Using 2 nested PCR, none of the samples tested positive for B. burgdorferi. Thus, a positive ELISA result can indicate only that the tested horse was previously exposed to B. burgdorferi, with no certainty over the time of exposure. Since global warming is likely to increase the abundance of ticks in Korea, continuous monitoring of tick-borne diseases in Korean horses is needed. PMID:26951987

  7. Pleomorphic forms of Borrelia burgdorferi induce distinct immune responses.

    PubMed

    Meriläinen, Leena; Brander, Heini; Herranen, Anni; Schwarzbach, Armin; Gilbert, Leona

    2016-01-01

    Borrelia burgdorferi is the causative agent of tick-borne Lyme disease. As a response to environmental stress B. burgdorferi can change its morphology to a round body form. The role of B. burgdorferi pleomorphic forms in Lyme disease pathogenesis has long been debated and unclear. Here, we demonstrated that round bodies were processed differently in differentiated macrophages, consequently inducing distinct immune responses compared to spirochetes in vitro. Colocalization analysis indicated that the F-actin participates in internalization of both forms. However, round bodies end up less in macrophage lysosomes than spirochetes suggesting that there are differences in processing of these forms in phagocytic cells. Furthermore, round bodies stimulated distinct cytokine and chemokine production in these cells. We confirmed that spirochetes and round bodies present different protein profiles and antigenicity. In a Western blot analysis Lyme disease patients had more intense responses to round bodies when compared to spirochetes. These results suggest that round bodies have a role in Lyme disease pathogenesis. PMID:27139815

  8. The Elastic Basis for the Shape of Borrelia burgdorferi

    PubMed Central

    Dombrowski, Christopher; Kan, Wanxi; Motaleb, Md. Abdul; Charon, Nyles W.; Goldstein, Raymond E.; Wolgemuth, Charles W.

    2009-01-01

    The mechanisms that determine bacterial shape are in many ways poorly understood. A prime example is the Lyme disease spirochete, Borrelia burgdorferi (B. burgdorferi), which mechanically couples its motility organelles, helical flagella, to its rod-shaped cell body, producing a striking flat-wave morphology. A mathematical model is developed here that accounts for the elastic coupling of the flagella to the cell cylinder and shows that the flat-wave morphology is in fact a natural consequence of the geometrical and material properties of the components. Observations of purified periplasmic flagella show two flagellar conformations. The mathematical model suggests that the larger waveform flagellum is the more relevant for determining the shape of B. burgdorferi. Optical trapping experiments were used to measure directly the mechanical properties of these spirochetes. These results imply relative stiffnesses of the two components, which confirm the predictions of the model and show that the morphology of B. burgdorferi is completely determined by the elastic properties of the flagella and cell body. This approach is applicable to a variety of other structures in which the shape of the composite system is markedly different from that of the individual components, such as coiled-coil domains in proteins and the eukaryotic axoneme. PMID:19486665

  9. Membrane topology of Borrelia burgdorferi and Treponema pallidum lipoproteins.

    PubMed Central

    Jones, J D; Bourell, K W; Norgard, M V; Radolf, J D

    1995-01-01

    A critical issue regarding the molecular architectures of Treponema pallidum and Borrelia burgdorferi, the agents of venereal syphilis and Lyme disease, respectively, concerns the membrane topologies of their major lipoprotein immunogens. A related question is whether these lipid-modified membrane proteins form intramembranous particles during freeze fracture electron microscopy. To address these issues, native borrelial and treponemal lipoproteins were reconstituted into liposomes of diverse composition. The importance of the covalently associated lipids for membrane association of lipoproteins was revealed by the observation that nonlipidated recombinant forms of both B. burgdorferi OspA and the T. pallidum 47-kDa immunogen (Tpp47) showed very weak or no binding to model bilayer vesicles. In contrast to control liposomes reconstituted with bacteriorhodopsin or bovine rhodopsin, two well-characterized transmembrane proteins, none of the lipoprotein-liposomes contained particles when examined by freeze fracture electron microscopy. To extend these findings to prokaryotic lipoproteins with relatively amphiphilic polypeptides, similar experiments were conducted with a recombinant nonlipidated form of Escherichia coli TraT, a lipoprotein which has putative transmembrane domains. The nonlipidated TraT oligomers bound vesicles derived from E. coli lipids but, surprisingly, did not form particles in the freeze-fractured liposomes. These findings support (i) a proposed topology of spirochetal lipoproteins in which the polypeptide is extrinsic to the membrane surface and (ii) the contention that particles visualized in freeze-fractured spirochetal membranes represent poorly characterized transmembrane proteins. PMID:7790053

  10. aadA Confers Streptomycin Resistance in Borrelia burgdorferi

    PubMed Central

    Frank, Kristi L.; Bundle, Sharyl F.; Kresge, Michele E.; Eggers, Christian H.; Samuels, D. Scott

    2003-01-01

    To enhance genetic manipulation of the Lyme disease spirochete Borrelia burgdorferi, we assayed the aadA gene for the ability to confer resistance to the antibiotics spectinomycin and streptomycin. Using the previously described pBSV2 as a backbone, a shuttle vector, termed pKFSS1, which carries the aadA open reading frame fused to the B. burgdorferi flgB promoter was constructed. The hybrid flgB promoter-aadA cassette confers resistance to spectinomycin and streptomycin in both B. burgdorferi and Escherichia coli. pKFSS1 has a replication origin derived from the 9-kb circular plasmid and can be comaintained in B. burgdorferi with extant shuttle vector pCE320, which has a replication origin derived from a 32-kb circular plasmid, or pBSV2, despite the fact that pKFSS1 and pBSV2 have the same replication origin. Our results demonstrate the availability of a new selectable marker and shuttle vector for genetically dissecting B. burgdorferi at the molecular level. PMID:14594849

  11. Immunogenic integral membrane proteins of Borrelia burgdorferi are lipoproteins.

    PubMed

    Brandt, M E; Riley, B S; Radolf, J D; Norgard, M V

    1990-04-01

    The pathogenic spirochete Borrelia burgdorferi contains a set of integral membrane proteins which were selectively extracted into the detergent phase upon solubilization of intact B. burgdorferi with the nonionic detergent Triton X-114. Virtually all of these hydrophobic proteins were recognized by antibodies in pooled sera from patients with chronic Lyme arthritis, demonstrating that proteins partitioning into the detergent phase of Triton X-114 encompass the major B. burgdorferi immunogens. Furthermore, most of these immunogenic proteins, including the previously characterized OspA and OspB membrane antigens, could be biosynthetically labeled when B. burgdorferi was incubated in vitro with [3H]palmitate. The OspA and OspB antigens were radioimmunoprecipitated from [3H]palmitate-labeled detergent-phase proteins with monoclonal antibodies, and [3H]palmitate was recovered unaltered from these proteins after sequential alkaline and acid hydrolyses. The combined results provide formal confirmation that the major B. burgdorferi immunogens extracted by Triton X-114 are lipoproteins. The demonstration that B. burgdorferi integral membrane antigens are lipoproteins may explain the basis of their immunogenicity and may help to improve our understanding of the surface topology of B. burgdorferi. PMID:2318538

  12. Serological Detection of Borrelia burgdorferi among Horses in Korea.

    PubMed

    Lee, Seung-Hun; Yun, Sun-Hee; Choi, Eunsang; Park, Yong-Soo; Lee, Sang-Eun; Cho, Gil-Jae; Kwon, Oh-Deog; Kwak, Dongmi

    2016-02-01

    Lyme disease is a tick-borne zoonotic infectious disease caused by Borrelia burgdorferi. The present study assessed the infection status of B. burgdorferi among horses reared in Korea using ELISA and PCR. Between 2009 and 2013, blood samples were collected from 727 horses throughout Korea. Data for each animal including age, gender, breed, and region of sample collection were used for epidemiological analysis. Overall, 38 (5.2%; true prevalence: 5.5%) of 727 horses were seropositive by ELISA. There were statistically significant differences according to breed and region (P<0.001) whose differences might be attributed to the ecology of vector ticks and climate conditions. Using 2 nested PCR, none of the samples tested positive for B. burgdorferi. Thus, a positive ELISA result can indicate only that the tested horse was previously exposed to B. burgdorferi, with no certainty over the time of exposure. Since global warming is likely to increase the abundance of ticks in Korea, continuous monitoring of tick-borne diseases in Korean horses is needed. PMID:26951987

  13. Proteome Analysis of Borrelia burgdorferi Response to Environmental Change

    SciTech Connect

    Angel, Thomas E.; Luft, Benjamin J.; Yang, Xiaohua; Nicora, Carrie D.; Camp, David G.; Jacobs, Jon M.; Smith, Richard D.

    2010-11-02

    We examined global changes in protein expression in the B31 strain of Borrelia burgdorferi, in response to two environmental cues (pH and temperature) chosen for their reported similarity to those encountered at different stages of the organism’s life cycle. Multidimensional nano-liquid chromatographic separations coupled with tandem mass spectrometry were used to examine the array of proteins (i.e., the proteome) of B. burgdorferi for different pH and temperature culture conditions. Changes in pH and temperature elicited in vitro adaptations of this spirochete known to cause Lyme disease and led to alterations in protein expression that are associated with increased microbial pathogenesis. We identified 1031 proteins that represent 59% of the annotated genome of B. burgdorferi and elucidated a core proteome of 414 proteins that were present in all environmental conditions investigated. Observed changes in protein abundances indicated varied replicon usage, as well as proteome functional distributions between the in vitro cell culture conditions. Surprisingly, the pH and temperature conditions that mimicked B. burgdorferi residing in the gut of a fed tick showed a marked reduction in protein diversity. Additionally, the results provide us with leading candidates for exploring how B. burgdorferi adapts to and is able to survive in a wide variety of environmental conditions and lay a foundation for planned in situ studies of B. burgdorferi isolated from the tick midgut and infected animals.

  14. Diversity of Antibody Responses to Borrelia burgdorferi in Experimentally Infected Beagle Dogs

    PubMed Central

    Grosenbaugh, Deborah A.

    2014-01-01

    Lyme borreliosis (LB) is a common infection of domestic dogs in areas where there is enzootic transmission of the agent Borrelia burgdorferi. While immunoassays based on individual subunits have mostly supplanted the use of whole-cell preparations for canine serology, only a limited number of informative antigens have been identified. To more broadly characterize the antibody responses to B. burgdorferi infection and to assess the diversity of those responses in individual dogs, we examined sera from 32 adult colony-bred beagle dogs that had been experimentally infected with B. burgdorferi through tick bites and compared those sera in a protein microarray with sera from uninfected dogs in their antibody reactivities to various recombinant chromosome- and plasmid-encoded B. burgdorferi proteins, including 24 serotype-defining OspC proteins of North America. The profiles of immunogenic proteins for the dogs were largely similar to those for humans and natural-reservoir rodents; these proteins included the decorin-binding protein DbpB, BBA36, BBA57, BBA64, the fibronectin-binding protein BBK32, VlsE, FlaB and other flagellar structural proteins, Erp proteins, Bdr proteins, and all of the OspC proteins. In addition, the canine sera bound to the presumptive lipoproteins BBB14 and BB0844, which infrequently elicited antibodies in humans or rodents. Although the beagle, like most other domestic dog breeds, has a small effective population size and features extensive linkage disequilibrium, the group of animals studied here demonstrated diversity in antibody responses in measures of antibody levels and specificities for conserved proteins, such as DbpB, and polymorphic proteins, such as OspC. PMID:24695775

  15. Diverse Borrelia burgdorferi Strains in a Bird-Tick Cryptic Cycle ▿ †

    PubMed Central

    Hamer, Sarah A.; Hickling, Graham J.; Sidge, Jennifer L.; Rosen, Michelle E.; Walker, Edward D.; Tsao, Jean I.

    2011-01-01

    The blacklegged tick Ixodes scapularis is the primary vector of the most prevalent vector-borne zoonosis in North America, Lyme disease (LD). Enzootic maintenance of the pathogen Borrelia burgdorferi by I. scapularis and small mammals is well documented, whereas its “cryptic” maintenance by other specialist ticks and wildlife hosts remains largely unexplored because these ticks rarely bite humans. We quantified B. burgdorferi infection in a cryptic bird-rabbit-tick cycle. Furthermore, we explored the role of birds in maintaining and moving B. burgdorferi strains by comparing their genetic diversity in this cryptic cycle to that found in cycles vectored by I. scapularis. We examined birds, rabbits, and small mammals for ticks and infection over a 4-year period at a focal site in Michigan, 90 km east of a zone of I. scapularis invasion. We mist netted 19,631 birds that yielded 12,301 ticks, of which 86% were I. dentatus, a bird-rabbit specialist. No resident wildlife harbored I. scapularis, and yet 3.5% of bird-derived ticks, 3.6% of rabbit-derived ticks, and 20% of rabbit ear biopsy specimens were infected with B. burgdorferi. We identified 25 closely related B. burgdorferi strains using an rRNA gene intergenic spacer marker, the majority (68%) of which had not been reported previously. The presence of strains common to both cryptic and endemic cycles strongly implies bird-mediated dispersal. Given continued large-scale expansion of I. scapularis populations, we predict that its invasion into zones of cryptic transmission will allow for bridging of novel pathogen strains to humans and animals. PMID:21257811

  16. Seroprevalence of Borrelia burgdorferi in occupationally exposed persons in the Belgrade area, Serbia

    PubMed Central

    Jovanovic, Dragutin; Atanasievska, Sonja; Protic-Djokic, Vesna; Rakic, Uros; Lukac-Radoncic, Elvira; Ristanovic, Elizabeta

    2015-01-01

    Lyme disease (LD) is a natural focal zoonotic disease caused by Borrelia burgdorferi, which is mainly transmitted through infected Ixodes ricinus tick bites. The presence and abundance of ticks in various habitats, the infectivity rate, as well as prolonged human exposure to ticks are factors that may affect the infection risk as well as the incidence of LD. In recent years, 20% to 25% of ticks infected with different borrelial species, as well as about 5,300 citizens with LD, have been registered in the Belgrade area. Many of the patients reported tick bites in city’s grassy areas. The aim of this study was to assess the seroprevalence of B. burgdorferi in high-risk groups (forestry workers and soldiers) in the Belgrade area, and to compare the results with healthy blood donors. A two-step algorithm consisting of ELISA and Western blot tests was used in the study. Immunoreactivity profiles were also compared between the groups. The results obtained showed the seroprevalence to be 11.76% in the group of forestry workers, 17.14% in the group of soldiers infected by tick bites and 8.57% in the population of healthy blood donors. The highest IgM reactivity was detected against the OspC protein, while IgG antibodies showed high reactivity against VlsE, p19, p41, OspC, OspA and p17. Further investigations in this field are necessary in humans and animals in order to improve protective and preventive measures against LD. PMID:26413064

  17. Occurrence and transmission efficiencies of Borrelia burgdorferi ospC types in avian and mammalian wildlife

    PubMed Central

    Vuong, Holly B.; Canham, Charles D.; Fonseca, Dina M.; Brisson, Dustin; Morin, Peter J.; Smouse, Peter E.; Ostfeld, Richard S.

    2014-01-01

    Borrelia burgdorferi s.s., the bacterium that causes Lyme disease in North America, circulates among a suite of vertebrate hosts and their tick vector. The bacterium can be differentiated at the outer surface protein C (ospC) locus into 25 genotypes. Wildlife hosts can be infected with a suite of ospC types but knowledge on the transmission efficiencies of these naturally infected hosts to ticks is still lacking. To evaluate the occupancy and detection of ospC types in wildlife hosts, we adapted a likelihood-based species patch occupancy model to test for the occurrence probabilities (ψ – “occupancy”) and transmission efficiencies (ε – “detection”) of each ospC type. We detected differences in ospC occurrence and transmission efficiencies from the null models with HIS (human invasive strains) types A and K having the highest occurrence estimates, but both HIS and non-HIS types having high transmission efficiencies. We also examined ospC frequency patterns with respect to strains known to be invasive in humans across the host species and phylogenetic groups. We found that shrews and to a lesser extent, birds, were important host groups supporting relatively greater frequencies of HIS to non-HIS types. This novel method of simultaneously assessing occurrence and transmission of ospC types provides a powerful tool in assessing disease risk at the genotypic level in naturally infected wildlife hosts and offers the opportunity to examine disease risk at the community level. PMID:24382473

  18. Lyme Borreliosis: is there a preexisting (natural) variation in antimicrobial susceptibility among Borrelia burgdorferi strains?

    PubMed Central

    Hodzic, Emir

    2015-01-01

    The development of antibiotics changed the world of medicine and has saved countless human and animal lives. Bacterial resistance/tolerance to antibiotics have spread silently across the world and has emerged as a major public health concern. The recent emergence of pan-resistant bacteria can overcome virtually any antibiotic and poses a major problem for their successful control. Selection for antibiotic resistance may take place where an antibiotic is present in the skin, gut, and other tissues of humans and animals and in the environment. Borrelia burgdorferi, the etiological agents of Lyme borreliosis, evades host immunity and establishes persistent infections in its mammalian hosts. The persistent infection poses a challenge to the effective antibiotic treatment, as demonstrated in various animal models. An increasingly heterogeneous subpopulation of replicatively attenuated spirochetes arises following treatment, and these persistent antimicrobial tolerant/resistant spirochetes are non-cultivable. The non-cultivable spirochetes resurge in multiple tissues at 12 months after treatment, with B. burgdorferi-specific DNA copy levels nearly equivalent to those found in shame-treated experimental animals. These attenuated spirochetes remain viable, but divide slowly, thereby being tolerant to antibiotics. Despite the continued non-cultivable state, RNA transcription of multiple B. burgdorferi genes was detected in host tissues, spirochetes were acquired by xenodiagnostic ticks, and spirochetal forms could be visualized within ticks and mouse tissues. A number of host cytokines were up- or down-regulated in tissues of both shame- and antibiotic-treated mice in the absence of histopathology, indicating a lack of host response to the presence of antimicrobial tolerant/resistant spirochetes. PMID:26295288

  19. Statins Reduce the Risks of Relapse to Addiction in Rats.

    PubMed

    Chauvet, Claudia; Nicolas, Celine; Lafay-Chebassier, Claire; Jaber, Mohamed; Thiriet, Nathalie; Solinas, Marcello

    2016-05-01

    Statins are drugs that have been used for decades in humans for the treatment of hypercholesterolemia. More recently, several lines of evidence demonstrate that statins, in addition to their peripheral effects, produce a wide variety of effects in the brain and may be beneficial in neurological and psychiatric conditions. In this study, we allowed rats to self-administer cocaine for several weeks and, at the end of self-administration training, we treated them with low doses of statins daily for a 21-day period of abstinence. Chronic administration of brain-penetrating statins, simvastatin (1 mg/kg) and atorvastatin (1 mg/kg), reduced cocaine seeking compared with vehicle, whereas administration of pravastatin (2 mg/kg), a statin with low brain penetrability, did not. Importantly, the effects of brain-penetrating statins persisted even after discontinuation of the treatment and were specific for drug seeking because drug taking was not altered by simvastatin treatment. Finally, the effects of simvastatin were found to generalize to another drug of abuse such as nicotine, but not to food reward, and to reinstatement of cocaine seeking induced by stress. These results demonstrate that brain-penetrating statins can reduce risks of relapse to addiction. Given their well-known safety profile in humans, statins could be a novel effective treatment for relapse to cocaine and nicotine addiction and their use could be implemented in clinical settings without major health risks. PMID:26466819

  20. Resistance to Change and Relapse of Observing

    ERIC Educational Resources Information Center

    Thrailkill, Eric A.; Shahan, Timothy A.

    2012-01-01

    Four experiments examined relapse of extinguished observing behavior of pigeons using a two-component multiple schedule of observing-response procedures. In both components, unsignaled periods of variable-interval (VI) food reinforcement alternated with extinction and observing responses produced stimuli associated with the availability of the VI…

  1. The School Counselor's Role in Relapse Prevention.

    ERIC Educational Resources Information Center

    Fisher, Gary L.; Harrison, Thomas C.

    1993-01-01

    Notes that most individuals who receive treatment for alcohol or other drug problems fail to maintain abstinence. Sees it as essential that school counselors be aware of relapse prevention strategies and use these strategies proactively when adolescents complete treatment. Discusses strategies, adapted from work using cognitive-behavioral…

  2. Noncirrhotic hyperammonemia causing relapsing altered mental status

    PubMed Central

    Khatiwada, Binod; Holbrook, Christopher; Ekeh, Ifeoma Sylvia; Uzoka, Chukwuemeka; Ikwu, Isaac; Upadhyay, Bishwas

    2015-01-01

    Hyperammonemia is a recognized cause of encephalopathy. However, it is commonly seen in patients with liver disease. The clinical entity of noncirrhotic hyperammonemia is now being increasingly recognized. We report a man who presented to our hospital with relapsing altered mental status later diagnosed as noncirrhotic hyperammonemia. PMID:26424945

  3. Immunotoxin Therapy for Relapsed Hairy Cell Leukemia

    Cancer.gov

    In this trial, patients with hairy cell leukemia who have relapsed multiple times or not responded to prior chemotherapy will be treated with an experimental immunotoxin called moxetumomab pasudotox given intravenously on days 1, 3, and 5 of 28-day cycles

  4. Hypopyon uveitis (without scleritis) a manifestation symptom of relapsing polychondritis.

    PubMed

    Genevois, Olivier; Calenda, E; Nasser, Z; Benzerroug, M; Gardea, E; Muraine, M

    2009-01-01

    We report an atypical ocular symptom, hypopyon uveitis without scleritis encountered in relapsing polychondritis. Relapsing polychondritis should be considered in the differential diagnosis of sterile hypopyon uveitis. PMID:20214060

  5. Smoking Linked to Higher Relapse Risk After Surgery for Crohn's

    MedlinePlus

    ... html Smoking Linked to Higher Relapse Risk After Surgery for Crohn's Research supports immediate drug treatment after bowel surgery for ... Crohn's disease patients will have relapses after bowel surgery, new research suggests. The study included 240 Crohn's disease patients ...

  6. [Explanation and forecast: relapse of juvenile offenders].

    PubMed

    Giebel, S M

    2006-01-01

    On the basis of n=82 juvenile offenders from a prison for juvenile offenders in Rheinland Pfalz the model of the logistic regression is compared with a procedure from the family of the neural nets in its efficiency to explain and predict "relapse" in form of a renewed imprisonment or prosecution /police search after dismissal. The group which can be examined is limited by the population of the prison for juvenile offenders and the explaining variables for "relapse" as "addicted to drugs" present non-metric scaling. For the explanation only probabilities for "relapse" can be indicated in this connection. By means of this probability it is possible to classify the individual case. The forecast is simulated by coincidental dividing of the data: the first part of the data is used for the explanation, the second for the forecast. With the comparison of the logistic regression with the neural nets, the superiority of neural nets in the explanation of "relapse" can be shown, since the neural nets are able to consider dependence between the explaining variables and according to that they offer a differentiated explanation. Their efficiency to predict "relapse" depends on the comparability of the distribution in the two coincidentally provided samples, the training data record for determining the explanation and the test case for the use of the explanation regarding the forecast. For optimal explanation and forecast neural nets are to be preferred to the logistic regression, since in the model with the better explanation also includes the potential for a usable better forecast. Moreover the model of the logistic regression is in fact a special case of the neural net, with a reduced complexity of the net. PMID:17124800

  7. Neuronal Substrates of Relapse to Cocaine-Seeking Behavior: Role of Prefrontal Cortex

    ERIC Educational Resources Information Center

    Rebec, George V.; Sun, WenLin

    2005-01-01

    The return to drug seeking, even after prolonged periods of abstinence, is a defining feature of cocaine addiction. The neural circuitry underlying relapse has been identified in neuropharmacological studies of experimental animals, typically rats, and supported in brain imaging studies of human addicts. Although the nucleus accumbens (NAcc),…

  8. Antipsychotic withdrawal-induced relapse predicts future relapses in institutionalized adults with severe intellectual disability.

    PubMed

    Janowsky, David S; Barnhill, L Jarrett; Khalid, Abdul S; Davis, John M

    2008-08-01

    Severe intellectual and developmental disabilities are frequently associated with aggression toward self and others, destruction of property, and disruption. Antipsychotic medications are a mainstay of treatment of such behaviors. National and state guidelines suggest stopping these medications or decreasing their dosages when possible if patients have maintained stability. The current study evaluated the likelihood of future antipsychotic drug withdrawal-induced relapses in those individuals where such a relapse had occurred previously. Subjects were 57 institutionalized adults with severe or profound intellectual disability. Between 1990 and 2000, each had experienced an initial activation of maladaptive aggressive behaviors after an attempt at antipsychotic drug withdrawal and/or termination. Quarterly behavioral reports were evaluated to determine whether subsequent antipsychotic drug withdrawal attempts were also associated with future relapses. Initial relapse was followed by subsequent antipsychotic drug withdrawal attempts in 49 of the 57 individuals. Between 1990 and 2005, 28.6% of these 49 subjects had experienced 1, 38.7% had 2, 20.4% had 3, and 8.2% had 4 additional relapses. Two (4.1%) had not relapsed. Eight individuals remained on antipsychotic agents without a subsequent withdrawal attempt. By the end of 2005, only 4 (7%) of the 57 individuals had become antipsychotic drug free, 22.8% were receiving first-generation antipsychotic agents alone, 45.6% were receiving second-generation antipsychotic agents alone, and 24.6% were receiving a combination of first- and second-generation antipsychotic agents. Thus, if relapse occurs after an antipsychotic drug withdrawal attempt, subsequent attempts at withdrawal are also very likely to lead to further relapses. PMID:18626266

  9. Trait impulsive choice predicts resistance to extinction and propensity to relapse to cocaine seeking: a bidirectional investigation.

    PubMed

    Broos, Nienke; Diergaarde, Leontien; Schoffelmeer, Anton Nm; Pattij, Tommy; De Vries, Taco J

    2012-05-01

    Despite the strong association between impulsivity and addiction in humans, it is still a matter of debate whether impulsive choice predisposes to, or results from, drug dependence. Furthermore, it is unknown whether treating impulsivity can protect against relapse propensity. Therefore, this study explored the bidirectional relationship between impulsive choice and cocaine taking and seeking in rat behavioral models. In experiment 1, to determine whether impulsive choice predisposes to cocaine taking or seeking, rats were selected based on trait impulsivity in a delayed reward task and subsequently compared on various stages of cocaine self-administration (SA). To examine the consequence of cocaine intake on impulsive choice, impulsivity was monitored once a week throughout various stages of cocaine SA. To determine whether treating impulsive choice can protect against relapse propensity, in experiment 2, impulsive choice was manipulated by pharmacological interventions and cocaine-associated contextual cues. Trait impulsive choice as determined in experiment 1 predicted high extinction resistance and enhanced propensity to context-induced relapse in the cocaine SA model, whereas cocaine intake did not alter impulsive choice. Furthermore, acute changes in impulsive choice were not related to rates of context-induced relapse. Taken together, the current data indicate that trait impulsive choice predicts persistent cocaine seeking during extinction and enhanced propensity to relapse, whereas acute manipulations of impulsive choice had no favorable outcomes on relapse measures. These observations suggest that trait impulsivity can be used as a predictive factor for addiction liability, but treating this impulsivity does not necessarily protect against relapse. PMID:22318198

  10. Killing the hypnozoite – drug discovery approaches to prevent relapse in Plasmodium vivax

    PubMed Central

    Campo, Brice; Vandal, Omar; Wesche, David L.; Burrows, Jeremy N.

    2015-01-01

    The eradication of malaria will only be possible if effective, well-tolerated medicines kill hypnozoites in vivax and ovale malaria, and thus prevent relapses in patients. Despite progress in the 8-aminoquinoline series, with tafenoquine in Phase III showing clear benefits over primaquine, the drug discovery challenge to identify hypnozoiticidal or hypnozoite-activating compounds has been hampered by the dearth of biological tools and assays, which in turn has been limited by the immense scientific and logistical challenges associated with accessing relevant human tissue and sporozoites. This review summarises the existing drug discovery series and approaches concerning the goal to block relapse. PMID:25891812

  11. Analyzing diaries for analytical relapse prevention using natural induction: a method and preliminary results.

    PubMed

    Wojtusiak, Janusz; Michalski, Ryszard S

    2008-01-01

    This article briefly describes natural induction approach to knowledge discovery, and then applies it to the problem of bad habit relapse prevention by analyzing patients' diaries. Natural induction seeks patterns in data that are in forms easy to understand and interpret, because they resemble those in which humans represent knowledge, such as natural language descriptions and visual forms. The application of natural induction to the problem of bad habit relapse has produced patterns easy to understand, in some cases of surprising simplicity. PMID:18204380

  12. The role of neuroadaptations in relapse to drug seeking.

    PubMed

    Shaham, Yavin; Hope, Bruce T

    2005-11-01

    One of the most difficult problems in treating addiction is not withdrawing addicts from drugs, but preventing relapse. Persistent neuroadaptations are thought to underlie aspects of addiction, including relapse. This commentary assesses the degree to which these neuroadaptations, primarily identified in preclinical studies on cocaine, induce relapse. PMID:16251983

  13. Developing Cognitive Behavioral Therapy to Prevent Depressive Relapse in Youth

    ERIC Educational Resources Information Center

    Kennard, Betsy D.; Stewart, Sunita M.; Hughes, Jennifer L.; Jarrett, Robin B.; Emslie, Graham J.

    2008-01-01

    Relapse rates for children and adolescents with major depressive disorder (MDD) range from 30% to 40% within 1 to 2 years after acute treatment. Although relapse rates are high, there have been relatively few studies on the prevention of relapse in youth. While acute phase pharmacotherapy has been shown to reduce symptoms rapidly in depressed…

  14. Preventing Relapse to Cigarette Smoking by Behavioral Skill Training.

    ERIC Educational Resources Information Center

    Hall, Sharon M.; And Others

    1984-01-01

    Crossed two relapse prevention conditions (skills training-vs-discussion control) with two levels of aversive smoking in volunteer subjects (N=123). Results indicated that relapse-prevention skill training did prevent relapse among cigarette smokers. Lighter smokers were more favorably influenced. (LLL)

  15. Relapse Prevention Model of Behavioral Maintenance: Implications for Alcohol Education.

    ERIC Educational Resources Information Center

    Rose-Colley, Mary; Cinelli, Bethann

    1992-01-01

    Describes Relapse Prevention as therapeutic modality, based on Social Learning Theory, used to prevent relapse for individuals who have completed treatment for substance abuse behaviors. Outlines relapse prevention theory and suggests various components of model be incorporated into alcohol education curricula. Outlines teaching strategies to…

  16. HLA mismatching as a strategy to reduce relapse after alternative donor transplantation.

    PubMed

    Fleischhauer, Katharina; Beelen, Dietrich W

    2016-04-01

    Human leukocyte antigen (HLA) mismatches are targets of alloreactive T cells, mediators of graft-versus-leukemia (GvL) and graft-versus-host disease (GvHD) after alternative donor transplantation. Exploitation of HLA mismatching in order to reduce relapse is hampered by necessary interventions aimed at controlling GvHD on the one hand, and by the possibility of immune escape through selective loss of mismatched HLA in relapsing leukemia on the other. Retrospective studies reporting the impact of HLA mismatches on post-transplant relapse need to be interpreted with caution, due to many confounding factors, including disease and use of T-cell depletion, and to be constantly updated to the rapidly changing clinical protocols. Current evidence suggests similar relapse rates for 8/8, 7/8 HLA-matched unrelated, T-cell-replete haploidentical and umbilical cord blood transplantation; however, investigations of locus-specific effects are still scarce in the latter two settings. In unrelated transplantation, a specific role for mismatches at HLA-C and HLA-DPB1, and therein of permissive mismatches defined on the basis of T-cell alloreactivity and/or expression levels, in reducing relapse has been demonstrated in independent studies. This observation suggests new approaches to utilize HLA matching in unrelated donor searches, and the need for further research in the field. PMID:27000727

  17. Maladjusted host immune responses induce experimental cerebral malaria-like pathology in a murine Borrelia and Plasmodium co-infection model.

    PubMed

    Normark, Johan; Nelson, Maria; Engström, Patrik; Andersson, Marie; Björk, Rafael; Moritz, Thomas; Fahlgren, Anna; Bergström, Sven

    2014-01-01

    In the Plasmodium infected host, a balance between pro- and anti-inflammatory responses is required to clear the parasites without inducing major host pathology. Clinical reports suggest that bacterial infection in conjunction with malaria aggravates disease and raises both mortality and morbidity in these patients. In this study, we investigated the immune responses in BALB/c mice, co-infected with Plasmodium berghei NK65 parasites and the relapsing fever bacterium Borrelia duttonii. In contrast to single infections, we identified in the co-infected mice a reduction of L-Arginine levels in the serum. It indicated diminished bioavailability of NO, which argued for a dysfunctional endothelium. Consistent with this, we observed increased sequestration of CD8+ cells in the brain as well over expression of ICAM-1 and VCAM by brain endothelial cells. Co-infected mice further showed an increased inflammatory response through IL-1β and TNF-α, as well as inability to down regulate the same through IL-10. In addition we found loss of synchronicity of pro- and anti-inflammatory signals seen in dendritic cells and macrophages, as well as increased numbers of regulatory T-cells. Our study shows that a situation mimicking experimental cerebral malaria (ECM) is induced in co-infected mice due to loss of timing and control over regulatory mechanisms in antigen presenting cells. PMID:25075973

  18. Maladjusted Host Immune Responses Induce Experimental Cerebral Malaria-Like Pathology in a Murine Borrelia and Plasmodium Co-Infection Model

    PubMed Central

    Normark, Johan; Nelson, Maria; Engström, Patrik; Andersson, Marie; Björk, Rafael; Moritz, Thomas; Fahlgren, Anna; Bergström, Sven

    2014-01-01

    In the Plasmodium infected host, a balance between pro- and anti-inflammatory responses is required to clear the parasites without inducing major host pathology. Clinical reports suggest that bacterial infection in conjunction with malaria aggravates disease and raises both mortality and morbidity in these patients. In this study, we investigated the immune responses in BALB/c mice, co-infected with Plasmodium berghei NK65 parasites and the relapsing fever bacterium Borrelia duttonii. In contrast to single infections, we identified in the co-infected mice a reduction of L-Arginine levels in the serum. It indicated diminished bioavailability of NO, which argued for a dysfunctional endothelium. Consistent with this, we observed increased sequestration of CD8+ cells in the brain as well over expression of ICAM-1 and VCAM by brain endothelial cells. Co-infected mice further showed an increased inflammatory response through IL-1β and TNF-α, as well as inability to down regulate the same through IL-10. In addition we found loss of synchronicity of pro- and anti-inflammatory signals seen in dendritic cells and macrophages, as well as increased numbers of regulatory T-cells. Our study shows that a situation mimicking experimental cerebral malaria (ECM) is induced in co-infected mice due to loss of timing and control over regulatory mechanisms in antigen presenting cells. PMID:25075973

  19. Oral Immunization with OspC Does Not Prevent Tick-Borne Borrelia burgdorferi Infection

    PubMed Central

    Melo, Rita; Richer, Luciana; Johnson, Daniel L.; Gomes-Solecki, Maria

    2016-01-01

    Oral vaccination strategies are of interest to prevent transmission of Lyme disease as they can be used to deliver vaccines to humans, pets, and to natural wildlife reservoir hosts of Borrelia burgdorferi. We developed a number of oral vaccines based in E. coli expressing recombinant OspC type K, OspB, BBK32 from B. burgdorferi, and Salp25, Salp15 from Ixodes scapularis. Of the five immunogenic candidates only OspC induced significant levels of antigen-specific IgG and IgA when administered to mice via the oral route. Antibodies to OspC did not prevent dissemination of B. burgdorferi as determined by the presence of spirochetes in ear, heart and bladder tissues four weeks after challenge. Next generation sequencing of genomic DNA from ticks identified multiple phyletic types of B. burgdorferi OspC (A, D, E, F, I, J, K, M, Q, T, X) in nymphs that engorged on vaccinated mice. PCR amplification of OspC types A and K from flat and engorged nymphal ticks, and from heart and bladder tissues collected after challenge confirmed sequencing analysis. Quantification of spirochete growth in a borreliacidal assay shows that both types of spirochetes (A and K) survived in the presence of OspC-K specific serum whereas the spirochetes were killed by OspA specific serum. We show that oral vaccination of C3H-HeN mice with OspC-K induced significant levels of antigen-specific IgG. However, these serologic antibodies did not protect mice from infection with B. burgdorferi expressing homologous or heterologous types of OspC after tick challenge. PMID:26990760

  20. Oral Immunization with OspC Does Not Prevent Tick-Borne Borrelia burgdorferi Infection.

    PubMed

    Melo, Rita; Richer, Luciana; Johnson, Daniel L; Gomes-Solecki, Maria

    2016-01-01

    Oral vaccination strategies are of interest to prevent transmission of Lyme disease as they can be used to deliver vaccines to humans, pets, and to natural wildlife reservoir hosts of Borrelia burgdorferi. We developed a number of oral vaccines based in E. coli expressing recombinant OspC type K, OspB, BBK32 from B. burgdorferi, and Salp25, Salp15 from Ixodes scapularis. Of the five immunogenic candidates only OspC induced significant levels of antigen-specific IgG and IgA when administered to mice via the oral route. Antibodies to OspC did not prevent dissemination of B. burgdorferi as determined by the presence of spirochetes in ear, heart and bladder tissues four weeks after challenge. Next generation sequencing of genomic DNA from ticks identified multiple phyletic types of B. burgdorferi OspC (A, D, E, F, I, J, K, M, Q, T, X) in nymphs that engorged on vaccinated mice. PCR amplification of OspC types A and K from flat and engorged nymphal ticks, and from heart and bladder tissues collected after challenge confirmed sequencing analysis. Quantification of spirochete growth in a borreliacidal assay shows that both types of spirochetes (A and K) survived in the presence of OspC-K specific serum whereas the spirochetes were killed by OspA specific serum. We show that oral vaccination of C3H-HeN mice with OspC-K induced significant levels of antigen-specific IgG. However, these serologic antibodies did not protect mice from infection with B. burgdorferi expressing homologous or heterologous types of OspC after tick challenge. PMID:26990760

  1. Distribution and molecular analysis of Lyme disease spirochetes, Borrelia burgdorferi, isolated from ticks throughout California.

    PubMed Central

    Schwan, T G; Schrumpf, M E; Karstens, R H; Clover, J R; Wong, J; Daugherty, M; Struthers, M; Rosa, P A

    1993-01-01

    Previous studies describing the occurrence and molecular characteristics of Lyme disease spirochetes, Borrelia burgdorferi, from California have been restricted primarily to isolates obtained from the north coastal region of this large and ecologically diverse state. Our objective was to look for and examine B. burdorferi organisms isolated from Ixodes pacificus ticks collected from numerous regions spanning most parts of California where this tick is found. Thirty-one isolates of B. burgdorferi were examined from individual or pooled I. pacificus ticks collected from 25 counties throughout the state. One isolate was obtained from ticks collected at Wawona Campground in Yosemite National Park, documenting the occurrence of the Lyme disease spirochete in an area of intensive human recreational use. One isolate from an Ixodes neotomae tick from an additional county was also examined. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis, immunoblot analysis, agarose gel electrophoresis, Southern blot analysis, and the polymerase chain reaction were used to examine the molecular and genetic determinants of these uncloned, low-passage-number isolates. All of the isolates were identified as B. burgdorferi by their protein profiles and reactivities with monoclonal and polyclonal antibodies, and all the isolates were typed by the polymerase chain reaction as North American-type spirochetes (B. burgdorferi sensu stricto). Although products of the ospAB locus were identified in protein analyses in all of the isolates, several isolates contained deleted forms of this locus that would result in the expression of chimeric OspA-OspB proteins. The analysis of OspC demonstrated that this protein was widely conserved among the isolates but was also quite variable in its molecular mass and the amount of it that was expressed. Images PMID:8308101

  2. Borrelia burgdorferi intercepts host hormonal signals to regulate expression of outer surface protein A

    PubMed Central

    Scheckelhoff, Mark R.; Telford, Sam R.; Wesley, Mary; Hu, Linden T.

    2007-01-01

    The Borrelia burgdorferi infectious cycle requires that the organism adapt to vast differences in environmental conditions found in its tick and mammalian hosts. Previous studies have shown that B. burgdorferi accomplishes this accomodation in part by regulating expression of its surface proteins. Outer surface protein A (OspA) is a borrelial protein important in colonization of the tick midgut. OspA is up-regulated when the organism is in its tick host and down-regulated when it is in a mammalian host. However, little is known about how it is up-regulated again in a mammalian host in preparation for entry into a feeding tick. Here, we report that the host neuroendocrine stress hormones, epinephrine and norepinephrine, are specifically bound by B. burgdorferi and result in increased expression of OspA. This recognition is specific and blocked by competitive inhibitors of human adrenergic receptors. To determine whether recognition of catecholamines, which are likely to be present at the site of a tick bite, may play a role in preparing the organism for reentry into a tick from a mammalian host, we administered a β-adrenergic blocker, propranolol, to infected mice. Propranolol significantly reduced uptake of B. burgdorferi by feeding ticks and decreased expression of OspA in B. burgdorferi recovered from ticks that fed on propranolol-treated mice. Our studies suggest that B. burgdorferi may co-opt host neuroendocrine signals to inform the organism of local changes that predict the presence of its next host and allow it to prepare for transition to a new environment. PMID:17438273

  3. Population Bottlenecks during the Infectious Cycle of the Lyme Disease Spirochete Borrelia burgdorferi

    PubMed Central

    Rego, Ryan O. M.; Bestor, Aaron; Štefka, Jan; Rosa, Patricia A.

    2014-01-01

    Borrelia burgdorferi is a zoonotic pathogen whose maintenance in nature depends upon an infectious cycle that alternates between a tick vector and mammalian hosts. Lyme disease in humans results from transmission of B. burgdorferi by the bite of an infected tick. The population dynamics of B. burgdorferi throughout its natural infectious cycle are not well understood. We addressed this topic by assessing the colonization, dissemination and persistence of B. burgdorferi within and between the disparate mammalian and tick environments. To follow bacterial populations during infection, we generated seven isogenic but distinguishable B. burgdorferi clones, each with a unique sequence tag. These tags resulted in no phenotypic changes relative to wild type organisms, yet permitted highly sensitive and specific detection of individual clones by PCR. We followed the composition of the spirochete population throughout an experimental infectious cycle that was initiated with a mixed inoculum of all clones. We observed heterogeneity in the spirochete population disseminating within mice at very early time points, but all clones displayed the ability to colonize most mouse tissues by 3 weeks of infection. The complexity of clones subsequently declined as murine infection persisted. Larval ticks typically acquired a reduced and variable number of clones relative to what was present in infected mice at the time of tick feeding, and maintained the same spirochete population through the molt to nymphs. However, only a random subset of infectious spirochetes was transmitted to naïve mice when these ticks next fed. Our results clearly demonstrate that the spirochete population experiences stochastic bottlenecks during both acquisition and transmission by the tick vector, as well as during persistent infection of its murine host. The experimental system that we have developed can be used to further explore the forces that shape the population of this vector-borne bacterial pathogen

  4. Borrelia burgdorferi Promotes the Establishment of Babesia microti in the Northeastern United States

    PubMed Central

    Dunn, Jessica M.; Krause, Peter J.; Davis, Stephen; Vannier, Edouard G.; Fitzpatrick, Meagan C.; Rollend, Lindsay; Belperron, Alexia A.; States, Sarah L.; Stacey, Andrew; Bockenstedt, Linda K.; Fish, Durland; Diuk-Wasser, Maria A.

    2014-01-01

    Babesia microti and Borrelia burgdorferi, the respective causative agents of human babesiosis and Lyme disease, are maintained in their enzootic cycles by the blacklegged tick (Ixodes scapularis) and use the white-footed mouse (Peromyscus leucopus) as primary reservoir host. The geographic range of both pathogens has expanded in the United States, but the spread of babesiosis has lagged behind that of Lyme disease. Several studies have estimated the basic reproduction number (R0) for B. microti to be below the threshold for persistence (<1), a finding that is inconsistent with the persistence and geographic expansion of this pathogen. We tested the hypothesis that host coinfection with B. burgdorferi increases the likelihood of B. microti transmission and establishment in new areas. We fed I. scapularis larva on P. leucopus mice that had been infected in the laboratory with B. microti and/or B. burgdorferi. We observed that coinfection in mice increases the frequency of B. microti infected ticks. To identify the ecological variables that would increase the probability of B. microti establishment in the field, we integrated our laboratory data with field data on tick burden and feeding activity in an R0 model. Our model predicts that high prevalence of B. burgdorferi infected mice lowers the ecological threshold for B. microti establishment, especially at sites where larval burden on P. leucopus is lower and where larvae feed simultaneously or soon after nymphs infect mice, when most of the transmission enhancement due to coinfection occurs. Our studies suggest that B. burgdorferi contributes to the emergence and expansion of B. microti and provides a model to predict the ecological factors that are sufficient for emergence of B. microti in the wild. PMID:25545393

  5. Rituximab add-on therapy for breakthrough relapsing multiple sclerosis

    PubMed Central

    Naismith, R.T.; Piccio, L.; Lyons, J.A.; Lauber, J.; Tutlam, N.T.; Parks, B.J.; Trinkaus, K.; Song, S.K.; Cross, A.H.

    2010-01-01

    Objective: B cells and the humoral immune system have been implicated in the pathogenesis of multiple sclerosis (MS). This study sought to evaluate the efficacy, safety, and tolerability of add-on therapy with rituximab, a monoclonal antibody that depletes circulating B cells, in subjects with relapsing MS with breakthrough disease defined by clinical and MRI activity (Class III evidence). Methods: Thirty subjects with a relapse within the past 18 months despite use of an injectable disease-modifying agent, and with at least 1 gadolinium-enhancing (GdE) lesion on any of 3 pretreatment MRIs, received rituximab administered at 375 mg/m2 weekly × 4 doses. Three monthly posttreatment brain MRI scans were obtained beginning 12 weeks after the first infusion. Multiple Sclerosis Functional Composite (MSFC) and Expanded Disability Status Scale (EDSS) were obtained at baseline and throughout the posttreatment follow-up. Results: GdE lesions were reduced after treatment with rituximab, with 74% of posttreatment MRI scans being free of GdE activity compared with 26% free of GdE activity at baseline (p < 0.0001). Median GdE lesions were reduced from 1.0 to 0, and mean number was reduced from 2.81 per month to 0.33 after treatment (88% reduction). MSFC improved as well (p = 0.02). EDSS remained stable. Conclusion: Rituximab add-on therapy was effective based upon blinded radiologic endpoints in this phase II study. In combination with standard injectable therapies, rituximab was well-tolerated with no serious adverse events. B-cell–modulating therapy remains a potential option for treatment of patients with relapsing MS with an inadequate response to standard injectable therapies. Classification of evidence: This study provides Class III evidence that add-on rituximab reduces gadolinium-enhancing brain lesions in multiple sclerosis. GLOSSARY DMT = disease-modifying therapy; EDSS = Expanded Disability Status Scale; FOV = field of view; GdE = gadolinium-enhancing; HACA = human

  6. Two Boundaries Separate Borrelia burgdorferi Populations in North America

    PubMed Central

    Tsao, Jean I.; Castillo-Ramírez, Santiago; Girard, Yvette A.; Hamer, Sarah A.; Hoen, Anne Gatewood; Lane, Robert S.; Raper, Steve L.; Ogden, Nicholas H.

    2012-01-01

    Understanding the spread of infectious diseases is crucial for implementing effective control measures. For this, it is important to obtain information on the contemporary population structure of a disease agent and to infer the evolutionary processes that may have shaped it. Here, we investigate on a continental scale the population structure of Borrelia burgdorferi, the causative agent of Lyme borreliosis (LB), a tick-borne disease, in North America. We test the hypothesis that the observed population structure is congruent with recent population expansions and that these were preceded by bottlenecks mostly likely caused by the near extirpation in the 1900s of hosts required for sustaining tick populations. Multilocus sequence typing and complementary population analytical tools were used to evaluate B. burgdorferi samples collected in the Northeastern, Upper Midwestern, and Far-Western United States and Canada. The spatial distribution of sequence types (STs) and inferred population boundaries suggest that the current populations are geographically separated. One major population boundary separated western B. burgdorferi populations transmitted by Ixodes pacificus in California from Eastern populations transmitted by I. scapularis; the other divided Midwestern and Northeastern populations. However, populations from all three regions were genetically closely related. Together, our findings suggest that although the contemporary populations of North American B. burgdorferi now comprise three geographically separated subpopulations with no or limited gene flow among them, they arose from a common ancestral population. A comparative analysis of the B. burgdorferi outer surface protein C (ospC) gene revealed novel linkages and provides additional insights into the genetic characteristics of strains. PMID:22729536

  7. Differential Expression of Borrelia burgdorferi Proteins during Growth In Vitro

    PubMed Central

    Ramamoorthy, Ramesh; Philipp, Mario T.

    1998-01-01

    In an earlier paper we described the transcriptionally regulated differential levels of expression of two lipoproteins of Borrelia burgdorferi, P35 and P7.5, during growth of the spirochetes in culture from logarithmic phase to stationary phase (K. J. Indest, R. Ramamoorthy, M. Solé, R. D. Gilmore, B. J. B. Johnson, and M. T. Philipp, Infect. Immun. 65:1165–1171, 1997). Here we further assess this phenomenon by investigating whether the expression of other antigens of B. burgdorferi, including some well-characterized ones, are also regulated in a growth-phase-dependent manner in vitro. These studies revealed 13 additional antigens, including OspC, BmpD, and GroEL, that were upregulated 2- to 66-fold and a 28-kDa protein that was downregulated 2- to 10-fold, during the interval between the logarithmic- and stationary-growth phases. Unlike with these in vitro-regulated proteins, the levels of expression of OspA, OspB, P72, flagellin, and BmpA remained unchanged throughout growth of the spirochetes in culture. Furthermore, ospAB, bmpAB, groEL, and fla all exhibited similar mRNA profiles, which is consistent with the constitutive expression of these genes. By contrast, the mRNA and protein profiles of ospC and bmpD indicated regulated expression of these genes. While bmpD exhibited a spike in mRNA expression in early stationary phase, ospC maintained a relatively higher level of mRNA throughout culture. These findings demonstrate that there are additional genes besides P7.5 and P35 whose regulated expression can be investigated in vitro and which may thus serve as models to facilitate the study of regulatory mechanisms in an organism that cycles between an arthropod and a vertebrate host. PMID:9784512

  8. Borrelia hermsii Acquisition Order in Superinfected Ticks Determines Transmission Efficiency

    PubMed Central

    Raffel, Sandra J.; Schwan, Tom G.

    2013-01-01

    Multilocus sequence typing of Borrelia hermsii isolates reveals its divergence into two major genomic groups (GG), but no differences in transmission efficiency or host pathogenicity are associated with these genotypes. To compare GGI and GGII in the tick-host infection cycle, we first determined if spirochetes from the two groups could superinfect the tick vector Ornithodoros hermsi. We infected mice with isolates from each group and fed ticks sequentially on these mice. We then fed the infected ticks on naive mice and measured GGI and GGII spirochete densities in vector and host, using quantitative PCR of genotype-specific chromosomal DNA sequences. Sequential feedings resulted in dual tick infections, showing that GGI or GGII primary acquisition did not block superinfection by a secondary agent. On transmission to naive mice at short intervals after acquisition, ticks with primary GGI and secondary GGII spirochete infections caused mixed GGI and GGII infections in mice. However, ticks with primary GGII and secondary GGI spirochete infections caused only GGII infections with all isolate pairs examined. At longer intervals after acquisition, the exclusion of GGI by GGII spirochetes declined and cotransmission predominated. We then examined GGI and GGII spirochetemia in mice following single inoculation and coinoculation by needle and found that GGI spirochete densities were reduced on multiple days when coinoculated with GGII. These findings indicate that dual GGI-GGII spirochete infections can persist in ticks and that transmission to a vertebrate host is dependent on the order of tick acquisition and the interval between acquisition and transmission events. PMID:23716615

  9. Patterns and regulation of ribosomal RNA transcription in Borrelia burgdorferi

    PubMed Central

    2011-01-01

    Background Borrelia burgdorferi contains one 16S and two tandem sets of 23S-5S ribosomal (r) RNA genes whose patterns of transcription and regulation are unknown but are likely to be critical for survival and persistence in its hosts. Results RT-PCR of B. burgdorferi N40 and B31 revealed three rRNA region transcripts: 16S rRNA-alanine transfer RNA (tRNAAla); tRNAIle; and both sets of 23S-5S rRNA. At 34°C, there were no differences in growth rate or in accumulation of total protein, DNA and RNA in B31 cultured in Barbour-Stoenner-Kelly (BSK)-H whether rabbit serum was present or not. At 23°C, B31 grew more slowly in serum-containing BSK-H than at 34°C. DNA per cell was higher in cells in exponential as compared to stationary phase at either temperature; protein per cell was similar at both temperatures in both phases. Similar amounts of rRNA were produced in exponential phase at both temperatures, and rRNA was down-regulated in stationary phase at either temperature. Interestingly, a relBbu deletion mutant unable to generate (p)ppGpp did not down-regulate rRNA at transition to stationary phase in serum-containing BSK-H at 34°C, similar to the relaxed phenotype of E. coli relA mutants. Conclusions We conclude that rRNA transcription in B. burgdorferi is complex and regulated both by growth phase and by the stringent response but not by temperature-modulated growth rate. PMID:21251259

  10. Fatty acids of Treponema pallidum and Borrelia burgdorferi lipoproteins.

    PubMed Central

    Belisle, J T; Brandt, M E; Radolf, J D; Norgard, M V

    1994-01-01

    A fundamental ultrastructural feature shared by the spirochetal pathogens Treponema pallidum subsp. pallidum (T. pallidum) and Borrelia burgdorferi, the etiological agents of venereal syphilis and Lyme disease, respectively, is that their most abundant membrane proteins contain covalently attached fatty acids. In this study, we identified the fatty acids covalently bound to lipoproteins of B. burgdorferi and T. pallidum and examined potential acyl donors to these molecules. Palmitate was the predominant fatty acid of both B. burgdorferi and T. pallidum lipoproteins. T. pallidum lipoproteins also contained substantial amounts of stearate, a fatty acid not typically prevalent in prokaryotic lipoproteins. In both spirochetes, the fatty acids of cellular lipids differed from those of their respective lipoproteins. To characterize phospholipids in these organisms, spirochetes were metabolically labeled with [3H]palmitate or [3H]oleate; B. burgdorferi contained only phosphatidylglycerol and phosphatidylcholine, while T. pallidum contained phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, and cardiolipin. Although palmitate predominated in the lipoproteins, there were no apparent differences in the incorporation of these two fatty acids into phospholipids (putative acyl donors). Phospholipase A1 and A2 digestion of phosphatidylcholine from B. burgdorferi and T. pallidum labeled with either [3H]palmitate or [3H]oleate also revealed that neither fatty acid was incorporated preferentially into the 1 and 2 positions (potential acyl donor sites) of the glycerol backbone. The combined findings suggest that fatty acid utilization during lipoprotein synthesis is determined largely by the fatty acid specificities of the lipoprotein acyl transferases. These findings also provide the basis for ongoing efforts to elucidate the relationship between lipoprotein acylation and the physiological functions and inflammatory

  11. Acid ceramidase in prostate cancer radiation therapy resistance and relapse

    NASA Astrophysics Data System (ADS)

    Cheng, Joseph C.

    Prostate tumor cell escape from ionizing radiation (IR)-induced killing can lead to disease progression and relapse. Sphingolipids such as ceramide and sphingosine 1-phosphate influence signal transduction pathways that regulate stress response in cancer cells. In particular, metabolism of apoptotic ceramide constitutes an important survival adaptation. Assessments of enzyme activity, mRNA, and protein demonstrated preferential upregulation of the ceramide deacylating enzyme acid ceramidase (AC) in irradiated cancer cells. Promoter-reporter and ChIP-qPCR assays revealed AC transcription by activator protein 1 (AP-1) is sensitive to pharmacological inhibition of de novo ceramide biosynthesis, identifying a protective feedback mechanism that mitigates the effects of IR-induced ceramide. Deregulation of c-Jun, in particular, induced marked radiosensitization in vitro and in vivo, which was rescued by ectopic AC over-expression. AC over-expression in prostate cancer clonogens surviving 80 Gray fractionated irradiation was associated with increased radioresistance and proliferation, suggesting a role in radiotherapy failure and relapse. Indeed, immunohistochemical analysis of human prostate cancer tissues revealed higher levels of AC after radiotherapy failure than therapy-naive adenocarcinoma, PIN, or benign tissues. By genetically downregulating AC with small interfering RNA (siRNA), we observed radiosensitization of cells using clonogenic and cytotoxicity assays. Finally, treatment with lysosomotropic small molecule inhibitors of AC, LCL385 or LCL521, induced prostate cancer xenograft radiosensitization and long-term suppression, suggesting AC is a tractable target for adjuvant radiotherapy.

  12. Fourier transform infrared spectroscopy of DNA from Borrelia burgdorferi sensu lato and Ixodes ricinus ticks.

    PubMed

    Muntean, Cristina M; Stefan, Razvan; Bindea, Maria; Cozma, Vasile

    2013-06-01

    In this work we present a method for detection of motile and immotile Borrelia burgdorferi genomic DNA, in relation with infectious and noninfectious spirochetes. An FT-IR study of DNA isolated from B. burgdorferi sensu lato strains and from positive and negative Ixodes ricinus ticks, respectively, is reported. Motile bacterial cells from the species B. burgdorferi sensu stricto, Borrelia garinii and Borrelia afzelii were of interest. Also, FT-IR absorbance spectra of DNA from immotile spirochetes of B. burgdorferi sensu stricto, in the absence and presence of different antibiotics (doxycycline, erythromycin, gentamicin, penicillin V or phenoxymethylpenicillin, tetracycline, respectively) were investigated. FT-IR spectra, providing a high molecular structural information, have been analyzed in the wavenumber range 400-1800 cm(-1). FT-IR signatures, spectroscopic band assignments and structural interpretations of these DNAs are reported. Spectral differences between FT-IR absorbances of DNAs from motile bacterial cells and immotile spirochetes, respectively, have been found. Particularly, alterations of the sugar-phosphate B-form chain in the case of DNA from Borrelia immotile cells, as compared with DNA from B. burgdorferi sensu lato motile cells have been observed. Based on this work, specific B. burgdorferi sensu lato and I. ricinus DNA-ligand interactions, respectively, might be further investigated using Fourier transform infrared spectroscopy. PMID:23563637

  13. Treatment with Doxycycline of Generalized Annular Elastolytic Giant Cell Granuloma Associated with Borrelia burgdorferi Infection

    PubMed Central

    Tas, B; Caglar, A; Ozdemir, B

    2015-01-01

    ABSTRACT This is a case of generalized annular elastolytic giant cell granuloma (AEGCG) associated with borrelia infection and genes of p-30, p-31, p-39. A possible cross-mediated reaction from the T-cell type which might have induced the AEGCG is discussed from the concept of “heat-shock proteins (HSPs) and molecular mimicry”. PMID:26624605

  14. Lyme Borrelia positive serology associated with spontaneous abortion in an endemic Italian area.

    PubMed

    Carlomagno, G; Luksa, V; Candussi, G; Rizzi, G M; Trevisan, G

    1988-01-01

    Lyme borreliosis acquired during pregnancy may be associated with stillbirth and fetal malformations. This paper reports preliminary results of a study intended to evaluate the frequency of Borrelia burgdorferi infection associated with spontaneous abortion in an endemic Italian area. PMID:3252658

  15. Antibodies against Borrelia burgdorferi sensu lato among Adults, Germany, 2008–2011

    PubMed Central

    Fingerle, Volker; Klier, Christiane; Thamm, Michael; Stark, Klaus

    2015-01-01

    To assess Borrelia burgdorferi sensu lato (the cause of Lyme borreliosis) seropositivity in Germany, we tested serum samples from health survey (2008–2011) participants. Seroprevalence was 5.8% among women and 13.0% among men; infection risk was highest among persons >60 years of age. Public health interventions, including education about risk factors and preventive measures, are needed. PMID:25531140

  16. Antibodies against Borrelia burgdorferi sensu lato among Adults, Germany, 2008-2011.

    PubMed

    Wilking, Hendrik; Fingerle, Volker; Klier, Christiane; Thamm, Michael; Stark, Klaus

    2015-01-01

    To assess Borrelia burgdorferi sensu lato (the cause of Lyme borreliosis) seropositivity in Germany, we tested serum samples from health survey (2008-2011) participants. Seroprevalence was 5.8% among women and 13.0% among men; infection risk was highest among persons >60 years of age. Public health interventions, including education about risk factors and preventive measures, are needed. PMID:25531140

  17. The Lyme disease agent Borrelia burgdorferi requires BB0690, a Dps homologue, to persist within ticks.

    PubMed

    Li, Xin; Pal, Utpal; Ramamoorthi, Nandhini; Liu, Xianzhong; Desrosiers, Daniel C; Eggers, Christian H; Anderson, John F; Radolf, Justin D; Fikrig, Erol

    2007-02-01

    Borrelia burgdorferi survives in an enzootic cycle, and Dps proteins protect DNA against damage during starvation or oxidative stress. The role of a Dps homologue encoded by Borrelia in spirochaete survival was assessed. Dps-deficient spirochaetes were infectious in mice via needle-inoculation at the dose of 10(5) spirochaetes. Larval ticks successfully acquired Dps-deficient spirochaetes via a blood meal on mice. However, after extended periods within unfed nymphs, the Dps-deficient spirochaetes failed to be transmitted to a new host when nymphs fed. Our data suggest that Dps functions to protect the spirochaetes during dormancy in unfed ticks, and in its absence, the spirochaetes become susceptible during tick feeding. dps is differentially expressed in vivo- low in mice and high in ticks - but constitutively expressed in vitro, showing little change during growth or in response to oxidative stress. Borrelia Dps forms a dodecameric complex capable of sequestering iron. The Dps-deficient spirochaetes showed no defect in starvation and oxidative stress assays, perhaps due to the lack of iron in spirochaetes grown in vitro. Dps is critical for spirochaete persistence within ticks, and strategies to interfere with Dps could potentially reduce Borrelia populations in nature and thereby influence the incidence of Lyme disease. PMID:17181780

  18. Borrelia miyamotoi Infection in Patients from Upper Midwestern United States, 2014-2015.

    PubMed

    Jobe, Dean A; Lovrich, Steven D; Oldenburg, Darby G; Kowalski, Todd J; Callister, Steven M

    2016-08-01

    We confirmed Borrelia miyamotoi infection in 7 patients who had contracted an illness while near La Crosse, Wisconsin, USA, an area where Ixodes scapularis ticks are endemic. B. miyamatoi infection should now be considered among differential diagnoses for patients from the midwestern United States who have signs and symptoms suggestive of tickborne illness. PMID:27434048

  19. Proteomic Analysis of Lyme Disease: Global Protein Comparison of Three Strains of Borrelia burgdorferi

    SciTech Connect

    Jacobs, Jon M.; Yang, Xiaohua; Luft, Benjamin J.; Dunn, John J.; Camp, David G.; Smith, Richard D.

    2005-04-01

    The Borrelia burgdorferi spirochete is the causative agent of Lyme disease, the most common tick-borne disease in the United States. It has been studied extensively to help understand its pathogenicity of infection and how it can persist in different mammalian hosts. We report the proteomic analysis of the archetype B. burgdorferi B31 strain and two other strains (ND40, and JD-1) having different Borrelia pathotypes using strong cation exchange fractionation of proteolytic peptides followed by high-resolution, reversed phase capillary liquid chromatography coupled with ion trap tandem mass spectrometric (LC-MS/MS) analysis. Protein identification was facilitated by the availability of the complete B31 genome sequence. A total of 665 Borrelia proteins were identified representing ~38 % coverage of the theoretical B31 proteome. A significant overlap was observed between the identified proteins in direct comparisons between any two strains (>72%), but distinct differences were observed among identified hypothetical and outer membrane proteins of the three strains. Such a concurrent proteomic overview of three Borrelia strains based upon only the B31 genome sequence is shown to provide significant insights into the presence or absence of specific proteins and a broad overall comparison among strains.

  20. Fourier transform infrared spectroscopy of DNA from Borrelia burgdorferi sensu lato and Ixodes ricinus ticks

    NASA Astrophysics Data System (ADS)

    Muntean, Cristina M.; Stefan, Razvan; Bindea, Maria; Cozma, Vasile

    2013-06-01

    In this work we present a method for detection of motile and immotile Borrelia burgdorferi genomic DNA, in relation with infectious and noninfectious spirochetes. An FT-IR study of DNA isolated from B. burgdorferi sensu lato strains and from positive and negative Ixodes ricinus ticks, respectively, is reported. Motile bacterial cells from the species B. burgdorferi sensu stricto, Borrelia garinii and Borrelia afzelii were of interest. Also, FT-IR absorbance spectra of DNA from immotile spirochetes of B. burgdorferi sensu stricto, in the absence and presence of different antibiotics (doxycycline, erythromycin, gentamicin, penicillin V or phenoxymethylpenicillin, tetracycline, respectively) were investigated. FT-IR spectra, providing a high molecular structural information, have been analyzed in the wavenumber range 400-1800 cm-1. FT-IR signatures, spectroscopic band assignments and structural interpretations of these DNAs are reported. Spectral differences between FT-IR absorbances of DNAs from motile bacterial cells and immotile spirochetes, respectively, have been found. Particularly, alterations of the sugar-phosphate B-form chain in the case of DNA from Borrelia immotile cells, as compared with DNA from B. burgdorferi sensu lato motile cells have been observed. Based on this work, specific B. burgdorferi sensu lato and I. ricinus DNA-ligand interactions, respectively, might be further investigated using Fourier transform infrared spectroscopy.

  1. Borrelia miyamotoi Infection in Patients from Upper Midwestern United States, 2014–2015

    PubMed Central

    Jobe, Dean A.; Lovrich, Steven D.; Oldenburg, Darby G.; Kowalski, Todd J.

    2016-01-01

    We confirmed Borrelia miyamotoi infection in 7 patients who had contracted an illness while near La Crosse, Wisconsin, USA, an area where Ixodes scapularis ticks are endemic. B. miyamatoi infection should now be considered among differential diagnoses for patients from the midwestern United States who have signs and symptoms suggestive of tickborne illness. PMID:27434048

  2. Role of outer membrane architecture in immune evasion by Treponema pallidum and Borrelia burgdorferi.

    PubMed

    Radolf, J D

    1994-09-01

    Combined ultrastructural and molecular studies have revealed that the syphilis and Lyme-disease spirochetes, Treponema pallidum and Borrelia burgdorferi, have distinctive molecular architectures. Both organisms persist in their hosts and have strategies for immune evasion that include the use of rare, poorly immunogenic surface-exposed proteins as potential virulence determinants. PMID:7812663

  3. Combined MYC and P53 defects emerge at medulloblastoma relapse and define rapidly progressive, therapeutically targetable disease.

    PubMed

    Hill, Rebecca M; Kuijper, Sanne; Lindsey, Janet C; Petrie, Kevin; Schwalbe, Ed C; Barker, Karen; Boult, Jessica K R; Williamson, Daniel; Ahmad, Zai; Hallsworth, Albert; Ryan, Sarra L; Poon, Evon; Robinson, Simon P; Ruddle, Ruth; Raynaud, Florence I; Howell, Louise; Kwok, Colin; Joshi, Abhijit; Nicholson, Sarah Leigh; Crosier, Stephen; Ellison, David W; Wharton, Stephen B; Robson, Keith; Michalski, Antony; Hargrave, Darren; Jacques, Thomas S; Pizer, Barry; Bailey, Simon; Swartling, Fredrik J; Weiss, William A; Chesler, Louis; Clifford, Steven C

    2015-01-12

    We undertook a comprehensive clinical and biological investigation of serial medulloblastoma biopsies obtained at diagnosis and relapse. Combined MYC family amplifications and P53 pathway defects commonly emerged at relapse, and all patients in this group died of rapidly progressive disease postrelapse. To study this interaction, we investigated a transgenic model of MYCN-driven medulloblastoma and found spontaneous development of Trp53 inactivating mutations. Abrogation of p53 function in this model produced aggressive tumors that mimicked characteristics of relapsed human tumors with combined P53-MYC dysfunction. Restoration of p53 activity and genetic and therapeutic suppression of MYCN all reduced tumor growth and prolonged survival. Our findings identify P53-MYC interactions at medulloblastoma relapse as biomarkers of clinically aggressive disease that may be targeted therapeutically. PMID:25533335

  4. Combined MYC and P53 Defects Emerge at Medulloblastoma Relapse and Define Rapidly Progressive, Therapeutically Targetable Disease

    PubMed Central

    Hill, Rebecca M.; Kuijper, Sanne; Lindsey, Janet C.; Petrie, Kevin; Schwalbe, Ed C.; Barker, Karen; Boult, Jessica K.R.; Williamson, Daniel; Ahmad, Zai; Hallsworth, Albert; Ryan, Sarra L.; Poon, Evon; Robinson, Simon P.; Ruddle, Ruth; Raynaud, Florence I.; Howell, Louise; Kwok, Colin; Joshi, Abhijit; Nicholson, Sarah Leigh; Crosier, Stephen; Ellison, David W.; Wharton, Stephen B.; Robson, Keith; Michalski, Antony; Hargrave, Darren; Jacques, Thomas S.; Pizer, Barry; Bailey, Simon; Swartling, Fredrik J.; Weiss, William A.; Chesler, Louis; Clifford, Steven C.

    2015-01-01

    Summary We undertook a comprehensive clinical and biological investigation of serial medulloblastoma biopsies obtained at diagnosis and relapse. Combined MYC family amplifications and P53 pathway defects commonly emerged at relapse, and all patients in this group died of rapidly progressive disease postrelapse. To study this interaction, we investigated a transgenic model of MYCN-driven medulloblastoma and found spontaneous development of Trp53 inactivating mutations. Abrogation of p53 function in this model produced aggressive tumors that mimicked characteristics of relapsed human tumors with combined P53-MYC dysfunction. Restoration of p53 activity and genetic and therapeutic suppression of MYCN all reduced tumor growth and prolonged survival. Our findings identify P53-MYC interactions at medulloblastoma relapse as biomarkers of clinically aggressive disease that may be targeted therapeutically. PMID:25533335

  5. Novel Therapies for Relapsed Acute Lymphoblastic Leukemia

    PubMed Central

    Fullmer, Amber; O’Brien, Susan; Kantarjian, Hagop; Jabbour, Elias

    2015-01-01

    The outcome of salvage therapy for relapsed acute lymphoblastic leukemia (ALL) remains poor. Salvage therapy mimics regimens with activity in newly diagnosed ALL. Novel strategies under investigation as monotherapy or in combination with chemotherapy improve the treatment of relapsed disease. For some ALL subsets, specific therapies are indicated. The addition of targeted therapy in Philadelphia chromosome–positive ALL has improved responses in relapsed patients without resistance to available tyrosine kinase inhibitors. Nelarabine demonstrates activity as monotherapy in T-cell ALL and is approved by the US Food and Drug Administration. Clofarabine, a second-generation purine analogue approved in pediatric leukemia, has shown activity in adult acute leukemias including ALL and acute myeloid leukemia. The role of pegaspargase in adult ALL requires further investigation. The benefit of matched related-donor allogeneic stem cell transplantation is significant for standard-risk ALL but not for high-risk ALL. Development of new drugs and agents tailored to subset-specific cytogenetic-molecular characteristics remains vital to success in treating adult ALL. PMID:20425428

  6. Treatment of relapsed and refractory Hodgkin Lymphoma.

    PubMed

    von Tresckow, Bastian; Moskowitz, Craig H

    2016-07-01

    Despite the high first-line cure rates in patients with Hodgkin Lymphoma (HL) still 10%-20% of patients suffer from relapsed or refractory disease. High-dose chemotherapy (HDCT) followed by autologous stem cell transplant (ASCT) is standard of care for suitable patients with relapsed or refractory HL and allows for cure in approximately 50%. Due to the poor prognosis of high-risk patients even with HDCT and ASCT, consolidation strategies have been evaluated to improve the cure rates. For patients with recurrence after HDCT and ASCT, treatment is palliative in most cases. The anti-CD30 antibody-drug conjugate brentuximab vedotin (BV) has been shown to induce high response rates in these patients; however, durable responses were reported in a small percentage of patients only. For carefully selected patients with multiple relapses, dose-reduced allogeneic transplant (RICallo) is a potentially curative option. The role of RICallo will have to be re-evaluated in the era of anti-programmed death-1 (PD1) antibodies. PMID:27496309

  7. Craving and relapse measurement in alcoholism.

    PubMed

    Potgieter, A S; Deckers, F; Geerlings, P

    1999-01-01

    This paper attempts to summarize the measurement of craving with four different craving instruments and to relate this to definitions and measurement of relapse. The definitions of relapse may vary between studies and researchers, but are usually well defined. Five commonly used methods to measure relapse are: (1) quantity/frequency of drinking; (2) cumulative duration of abstinence (CDA); (3) post-withdrawal abstinent period; (4) stable recovery period; (5) the time line follow-back method. The definition of craving is much less clear and is mostly described as an emotional-motivational state or as obsessive-compulsive behaviour. Four self-rating instruments are briefly discussed and compared: the Obsessive-Compulsive Drinking Scale, OCDS, the Lübeck Craving Scale, LCRR, the Alcohol Craving Questionnaire, ACQ-Now-SF-R, and ordinal scales (e.g. visual analogue, Likert, or verbal descriptive scales). These instruments measure different aspects or dimensions of craving over different periods. The different dimensions measured suggest that there is still a need to conceptualize a standard interpretation of the word craving. There is a need also to measure an emotional-motivational dimension, a cognitive-behavioural dimension, expectancies, and effects on positive and negative reinforcement with different instruments or with one multidimensional instrument. It is suggested that different patients are expected to have different craving profiles. PMID:10344785

  8. [Tick infestation and the prevalence of Borrelia burgdorferi and Babesia divergens in cattle in Bavaria].

    PubMed

    Lengauer, Heidi; Just, Frank Thomas; Edelhofer, Renate; Pfister, Kurt

    2006-01-01

    During the grazing period 2002 319 cattle from 31 farms located in 6 districts of southern Bavaria were examined for the presence of ticks in 4- to 5-week intervals, and 287 serum samples were tested for the presence of antibodies against Borrelia burgdorferi and Babesia divergens. Ticks were detected in all 31 farms with a mean prevalence of 69%. 3218 out of 3453 collected ticks were Ixodes ricinus; 139 nymphs, 19 larvae and 77 damaged adult specimens could only be determined to the Genus level (Ixodes). The seasonal pattern revealed the highest frequencies of ticks in May/June and September. The intensity of tick infestation of positive animals was generally low. 76.5% of parasitized cattle had 1-6 ticks per day of investigation. Individual cattle showed up to 250 ticks per day. The percentage of infested animals in each herd varied within the period between 0-100%. The examination of serum samples by immunofluorescence technique (IFAT) revealed positive anti-Borrelia antibody titers (> or = 1:64) for 45.6% of the animals. The within-farm seroprevalence of borreliosis ranged from 20 to 100% in 27 of the 31 farms. A significant correlation could be detected between the number of ticks/cattle and the anti-Borrelia burgdorferi IgG-titer. By contrast, there was no significant correlation between the age of the animals and anti-Borrelia serum titers. For comparative reasons, 64 IFAT-positive serum samples were tested by Western blot techniques for the presence of antibodies cross-reacting with Borrelia garinii antigen. These analyses revealed that 69% of the samples reacted positively, 28% were unclear and 3% were negative. Examinations of the 287 serum samples for the presence of anti-Babesia divergens antibodies revealed one positive animal with a titer of 1:16. PMID:17009719

  9. Divergence of Borrelia burgdorferi sensu lato spirochetes could be driven by the host: diversity of Borrelia strains isolated from ticks feeding on a single bird

    PubMed Central

    2014-01-01

    Background The controversy surrounding the potential impact of birds in spirochete transmission dynamics and their capacity to serve as a reservoir has existed for a long time. The majority of analyzed bird species are able to infect larval ticks with Borrelia. Dispersal of infected ticks due to bird migration is a key to the establishment of new foci of Lyme borreliosis. The dynamics of infection in birds supports the mixing of different species, the horizontal exchange of genetic information, and appearance of recombinant genotypes. Methods Four Borrelia burgdorferi sensu lato strains were cultured from Ixodes minor larvae and four strains were isolated from Ixodes minor nymphs collected from a single Carolina Wren (Thryothorus ludovicianus). A multilocus sequence analysis that included 16S rRNA, a 5S-23S intergenic spacer region, a 16S-23S internal transcribed spacer, flagellin, p66, and ospC separated 8 strains into 3 distinct groups. Additional multilocus sequence typing of 8 housekeeping genes, clpA, clpX, nifS, pepX, pyrG, recG, rplB, and uvrA was used to resolve the taxonomic status of bird-associated strains. Results Results of analysis of 14 genes confirmed that the level of divergence among strains is significantly higher than what would be expected for strains within a single species. The presence of cross-species recombination was revealed: Borrelia burgdorferi sensu stricto housekeeping gene nifS was incorporated into homologous locus of strain, previously assigned to B. americana. Conclusions Genetically diverse Borrelia strains are often found within the same tick or same vertebrate host, presenting a wide opportunity for genetic exchange. We report the cross-species recombination that led to incorporation of a housekeeping gene from the B. burgdorferi sensu stricto strain into a homologous locus of another bird-associated strain. Our results support the hypothesis that recombination maintains a majority of sequence polymorphism within Borrelia

  10. Predictors of Relapse and Dropout During a 12-Week Relapse Prevention Program for Methamphetamine Users.

    PubMed

    Chen, Yi-Chih; Chen, Chih-Ken; Wang, Liang-Jen

    2015-01-01

    In this research, the possible neuropsychological predictors of relapse and dropout of group cognitive behavioral therapy (CBT) for methamphetamine (MA) users were explored. Participants were 42 MA users sentenced by the judicial system to take part in an out-patient relapse prevention program for MA abuse and dependence that employs a CBT model once a week over the course of 12 weeks. Baseline neuropsychological functions were evaluated with the Conners' Continuous Performance Test, Wisconsin Card Sorting Test, Iowa Gambling Task, and Barratt Impulsiveness Scale. All participants had to submit to urine drug tests every week. Of the 42 participants, 69.0% had a MA positive urine screening result at least once throughout the program (relapse), while 40.5% dropped out of the treatment program prior to its completion. Short duration of MA abstinence at baseline and poor attention predicted relapse. Predictors of dropout included being unmarried and having risky decision making. Findings may be helpful for clinicians, who can screen for the aforementioned risk factors and provide strategies for high-risk patients to help prevent relapse and dropout among MA users in treatment programs. PMID:26267045

  11. Symptomatic co-infection with Babesia microti and Borrelia burgdorferi in patient after international exposure; a challenging case in Poland.

    PubMed

    Jabłońska, Joanna; Żarnowska-Prymek, Hanna; Stańczak, Joanna; Kozłowska, Joanna; Wiercińska-Drapało, Alicja

    2016-06-01

    The report presents a well-documented case of symptomatic co-infection of Babesia microti and Borrelia burgdorferi in a Polish immunocompetent patient after travelling to Canada and the USA. PMID:27294655

  12. Functional outcomes in patients with Borrelia burgdorferi reinfection.

    PubMed

    Jares, Tyler M; Mathiason, Michelle A; Kowalski, Todd J

    2014-02-01

    When Lyme disease is treated with appropriate antibiotic therapy in the early stages, long-term outcomes are good. However, a few patients have persistent symptoms despite appropriate therapy. Whether these patients' symptoms are any different from those of patients with reinfection is unclear. Our objective was to compare long-term symptoms and functional outcomes of patients with Borrelia burgdorferi reinfection with those of patients with only 1 episode of infection and with no history of infection. We compared outcomes of Lyme reinfection patients, characterized by recurrent erythema migrans (EM) lesions, with those of patients with 1 episode of Lyme disease (Lyme control) and with no history of Lyme disease (non-Lyme control) by retrospective medical record review and a survey consisting of a 36-item Short-Form Health Survey (SF-36) and a 10-item symptom questionnaire. Analysis of variance (ANOVA) for continuous variables and χ(2) analysis for categorical variables were used. In cases of low cell counts, Fisher's exact tests were used. Bonferroni correction was used for multiple comparisons when ANOVA was significant. Reinfection was identified in 23/673 (3.4%) patients who had a diagnosis of Lyme disease in our health system during 2000-2004. Of the 23, 15 had long-term follow-up data and were age- and sex-matched to 45 Lyme control and 60 non-Lyme control group patients. Clinical characteristics were similar in the reinfection and Lyme control groups. SF-36 results were similar between groups for all domains except energy/vitality (VT). The SF-36 domain of VT was significantly different between groups: 63.0 vs. 54.5 vs. 64.5 in the reinfection, Lyme control, and non-Lyme control groups, respectively (p=0.047). Clinical features and long-term outcomes of patients with recurrent EM lesions were similar to those of the control groups and consistent with B. burgdorferi reinfection, not persistent infection. Patients with Lyme reinfection should be treated with

  13. Multiple Sclerosis Relapses: Epidemiology, Outcomes and Management. A Systematic Review.

    PubMed

    Kalincik, Tomas

    2015-01-01

    Relapses (episodic exacerbations of neurological signs or symptoms) are a defining feature of relapsing-remitting multiple sclerosis (MS), the most prevalent MS phenotype. While their diagnostic value relates predominantly to the definition of clinically definite MS, their prognostic value is determined by their relatively high associated risk of incomplete remission resulting in residual disability. The mechanisms governing a relapse incidence are unknown, but numerous modifiers of relapse risk have been described, including demographic and clinical characteristics, many of which represent opportunities for improved disease management. Also relapse phenotypes have been associated with patient and disease characteristics and an individual predisposition to certain phenotypic presentations may imply individual neuroanatomical disease patterns. While immunomodulatory therapies and corticosteroids represent the mainstay of relapse prevention and acute management, respectively, their effect has only been partial and further search for more efficient relapse therapies is warranted. Other areas of research include pathophysiology and determinants of relapse incidence, recurrence and phenotypes, including the characteristics of the relapsing and non-relapsing multiple sclerosis variants and their responsiveness to therapies. PMID:25997994

  14. New Findings on Biological Factors Predicting Addiction Relapse Vulnerability

    PubMed Central

    2013-01-01

    Relapse is a highly prevalent phenomenon in addiction. This paper examines the new research on identifying biological factors that contribute to addiction relapse risk. Prospective studies examining relapse risk are reviewed, and clinical, biological, and neural factors that predict relapse risk are identified. Clinical factors, patient-related factors, and subjective and behavioral measures such as depressive symptoms, stress, and drug craving all predict future relapse risk. Among biological measures, endocrine measures such as cortisol and cortisol/corticotropin (ACTH) ratio as a measure of adrenal sensitivity and serum brain-derived neurotrophic factor were also predictive of future relapse risk. Among neural measures, brain atrophy in the medial frontal regions and hyperreactivity of the anterior cingulate during withdrawal were identified as important in drug withdrawal and relapse risk. Caveats pertaining to specific drug abuse type and phase of addiction are discussed. Finally, significant implications of these findings for clinical practice are presented, with a specific focus on determining biological markers of relapse risk that may be used to identify those individuals who are most at risk of relapse in the clinic. Such markers may then be used to assess treatment response and develop specific treatments that will normalize these neural and biological sequelae so as to significantly improve relapse outcomes. PMID:21792580

  15. Drugs in development for relapsing multiple sclerosis.

    PubMed

    Ali, Rehiana; Nicholas, Richard St John; Muraro, Paolo Antonio

    2013-05-01

    drugs in development, and it is likely that BG-12 will be licensed this year. This has been licensed for psoriasis so there are good safety data in humans that may also hold true in MS; however, its three times daily dosage will probably impact on patient compliance. Laquinimod has lower efficacy than BG-12 but appears safe and could find a place as a first-line agent. Teriflunomide has just been licensed by the US FDA and may challenge the current injectable first-line therapies as it has a similar efficacy but the advantage of being taken orally. However, risk of teratogenicity may caution against its use in some women of child-bearing potential. This review will examine drugs that have been recently approved as well as those that are in late phase 2 or 3 development as treatment for relapsing MS, highlighting their mechanism of action as well as the clinical trial and safety data before discussing their potential for success in an increasingly florid and complex DMT armamentarium. PMID:23609782

  16. An Ixodes minor and Borrelia carolinensis enzootic cycle involving a critically endangered Mojave Desert rodent

    PubMed Central

    Foley, Janet; Ott-Conn, Caitlin; Worth, Joy; Poulsen, Amanda; Clifford, Deana

    2014-01-01

    Microtus californicus scirpensis is an endangered, isolated subspecies of California vole. It requires water pools and riparian bulrush (Schoenoplectus americanus) and occupies some of the rarest habitat of any North American mammal. The minimally vegetated, extremely arid desert surrounding the pools is essentially uninhabitable for Ixodes species ticks. We describe an enzootic cycle of Borrelia carolinensis in Ixodes minor ticks at a site 3500 km distant from the region in which I. minor is known to occur in Tecopa Host Springs, Inyo County, eastern Mojave Desert, California. Voles were live-trapped, and ticks and blood samples queried by PCR and DNA sequencing for identification and determination of the presence of Borrelia spp. Between 2011–2013, we found 21 Ixodes minor ticks (prevalence 4–8%) on Amargosa voles and Reithrodontomys megalotis. DNA sequencing of 16S rRNA from ticks yielded 99% identity to I. minor. There was 92% identity with I. minor in the calreticulin gene fragment. Three ticks (23.1%), 15 (24%) voles, three (27%) house mice, and one (7%) harvest mice were PCR positive for Borrelia spp. Sequencing of the 5S-23S intergenic spacer region and flagellin gene assigned Amargosa vole Borrelia strains to B. carolinensis. Ixodes minor, first described in 1902 from a single Guatemalan record, reportedly occurs only in the southeast American on small mammals and birds. The source of this tick in the Mojave Desert and time scale for introduction is not known but likely via migratory birds. Borrelia strains in the Amargosa ecosystem most closely resemble B. carolinensis. B. carolinensis occurs in a rodent-I. minor enzootic cycle in the southeast U.S. although its epidemiological significance for people or rodents is unknown. The presence of a tick and Borrelia spp. only known from southeast U.S. in this extremely isolated habitat on the other side of the continent is of serious concern because it suggests that the animals in the

  17. An Ixodes minor and Borrelia carolinensis enzootic cycle involving a critically endangered Mojave Desert rodent.

    PubMed

    Foley, Janet; Ott-Conn, Caitlin; Worth, Joy; Poulsen, Amanda; Clifford, Deana

    2014-03-01

    Microtus californicus scirpensis is an endangered, isolated subspecies of California vole. It requires water pools and riparian bulrush (Schoenoplectus americanus) and occupies some of the rarest habitat of any North American mammal. The minimally vegetated, extremely arid desert surrounding the pools is essentially uninhabitable for Ixodes species ticks. We describe an enzootic cycle of Borrelia carolinensis in Ixodes minor ticks at a site 3500 km distant from the region in which I. minor is known to occur in Tecopa Host Springs, Inyo County, eastern Mojave Desert, California. Voles were live-trapped, and ticks and blood samples queried by PCR and DNA sequencing for identification and determination of the presence of Borrelia spp. Between 2011-2013, we found 21 Ixodes minor ticks (prevalence 4-8%) on Amargosa voles and Reithrodontomys megalotis. DNA sequencing of 16S rRNA from ticks yielded 99% identity to I. minor. There was 92% identity with I. minor in the calreticulin gene fragment. Three ticks (23.1%), 15 (24%) voles, three (27%) house mice, and one (7%) harvest mice were PCR positive for Borrelia spp. Sequencing of the 5S-23S intergenic spacer region and flagellin gene assigned Amargosa vole Borrelia strains to B. carolinensis. Ixodes minor, first described in 1902 from a single Guatemalan record, reportedly occurs only in the southeast American on small mammals and birds. The source of this tick in the Mojave Desert and time scale for introduction is not known but likely via migratory birds. Borrelia strains in the Amargosa ecosystem most closely resemble B. carolinensis. B. carolinensis occurs in a rodent-I. minor enzootic cycle in the southeast U.S. although its epidemiological significance for people or rodents is unknown. The presence of a tick and Borrelia spp. only known from southeast U.S. in this extremely isolated habitat on the other side of the continent is of serious concern because it suggests that the animals in the ecosystem

  18. Complex Population Structure of Lyme Borreliosis Group Spirochete Borrelia garinii in Subarctic Eurasia

    PubMed Central

    Comstedt, Pär; Asokliene, Loreta; Eliasson, Ingvar; Olsen, Björn; Wallensten, Anders; Bunikis, Jonas; Bergström, Sven

    2009-01-01

    Borrelia garinii, a causative agent of Lyme borreliosis in Europe and Asia, is naturally maintained in marine and terrestrial enzootic cycles, which primarily involve birds, including seabirds and migratory passerines. These bird groups associate with, correspondingly, Ixodes uriae and Ixodes ricinus ticks, of which the latter species may bite and transmit the infection to humans. Studies of the overlap between these two natural cycles of B. garinii have been limited, in part due to the absence of representative collections of this spirochete's samples, as well as of the lack of reliable measure of the genetic heterogeneity of its strains. As a prerequisite for understanding the epidemiological correlates of the complex maintenance of B. garinii, the present study sought to assess the diversity and phylogenetic relationships of this species' strains from its natural hosts and patients with Lyme borreliosis from subarctic Eurasia. We used sequence typing of the partial rrs-rrl intergenic spacer (IGS) of archived and prospective samples of B. garinii from I. uriae ticks collected predominantly on Commander Islands in North Pacific, as well as on the islands in northern Sweden and arctic Norway. We also typed B. garinii samples from patients with Lyme borreliosis and I. ricinus ticks infesting migratory birds in southern Sweden, or found questing in selected sites on the islands in the Baltic Sea and Lithuania. Fifty-two (68%) of 77 B. garinii samples representing wide geographical range and associated with I. ricinus and infection of humans contributed 12 (60%) of total 20 identified IGS variants. In contrast, the remaining 25 (32%) samples recovered from I. uriae ticks from a few islands accounted for as many as 10 (50%) IGS types, suggesting greater local diversity of B. garinii maintained by seabirds and their ticks. Two IGS variants of the spirochete in common for both tick species were found in I. ricinus larvae from migratory birds, an indication that B

  19. The Alcohol Relapse Situation Appraisal Questionnaire: Development and Validation

    PubMed Central

    Martin, Rosemarie A.; MacKinnon, Selene M.; Johnson, Jennifer E.; Myers, Mark G.; Cook, Travis A. R.; Rohsenow, Damaris J.

    2011-01-01

    Background The role of cognitive appraisal of the threat of alcohol relapse has received little attention. A previous instrument, the Relapse Situation Appraisal Questionnaire (RSAQ), was developed to assess cocaine users’ primary appraisal of the threat of situations posing a high risk for cocaine relapse. The purpose of the present study was to modify the RSAQ in order to measure primary appraisal in situations involving a high risk for alcohol relapse. Methods The development and psychometric properties of this instrument, the Alcohol Relapse Situation Appraisal Questionnaire (A-RSAQ), were examined with two samples of abstinent adults with alcohol abuse or dependence. Factor structure and validity were examined in Study 1 (N=104). Confirmation of the factor structure and predictive validity were assessed in Study 2 (N=161). Results Results demonstrated construct, discriminant and predictive validity and reliability of the A-RSAQ. Discussion Results support the important role of primary appraisal of degree of risk in alcohol relapse situations. PMID:21237586

  20. Callosal Disconnection Syndrome Associated with Relapsing Polychondritis.

    PubMed

    Baba, Toru; Kanno, Shigenori; Shijo, Tomomi; Nishio, Yoshiyuki; Iizuka, Osamu; Kamimura, Naoto; Ishii, Tomonori; Mori, Etsuro

    2016-01-01

    Relapsing polychondritis (RP) is a rare inflammatory disorder of the cartilagenous structures, and it sometimes involves the central nervous system. Encephalitis associated with RP causes a wide variety of symptoms according to the affected sites. We herein report the first case of 72-year-old right-handed man who developed acute meningoencephalitis associated with RP involving the corpus callous. After immunosuppressive therapy, his symptoms dramatically improved, but difficulty in performing bimanual movements with occasional diagonistic dyspraxia in his right hand remained. Because callosal signs are easily missed, especially in acute settings, it would be useful to know that RP can sometimes cause callosal disconnection syndrome. PMID:27150878

  1. Co-Infection of Blacklegged Ticks with Babesia microti and Borrelia burgdorferi Is Higher than Expected and Acquired from Small Mammal Hosts

    PubMed Central

    Hersh, Michelle H.; Ostfeld, Richard S.; McHenry, Diana J.; Tibbetts, Michael; Brunner, Jesse L.; Killilea, Mary E.; LoGiudice, Kathleen; Schmidt, Kenneth A.; Keesing, Felicia

    2014-01-01

    Humans in the northeastern and midwestern United States are at increasing risk of acquiring tickborne diseases – not only Lyme disease, but also two emerging diseases, human granulocytic anaplasmosis and human babesiosis. Co-infection with two or more of these pathogens can increase the severity of health impacts. The risk of co-infection is intensified by the ecology of these three diseases because all three pathogens (Borrelia burgdorferi, Anaplasma phagocytophilum, and Babesia microti) are transmitted by the same vector, blacklegged ticks (Ixodes scapularis), and are carried by many of the same reservoir hosts. The risk of exposure to multiple pathogens from a single tick bite and the sources of co-infected ticks are not well understood. In this study, we quantify the risk of co-infection by measuring infection prevalence in 4,368 questing nymphs throughout an endemic region for all three diseases (Dutchess County, NY) to determine if co-infections occur at frequencies other than predicted by independent assortment of pathogens. Further, we identify sources of co-infection by quantifying rates of co-infection on 3,275 larval ticks fed on known hosts. We find significant deviations of levels of co-infection in questing nymphs, most notably 83% more co-infection with Babesia microti and Borrelia burgdorferi than predicted by chance alone. Further, this pattern of increased co-infection was observed in larval ticks that fed on small mammal hosts, but not on meso-mammal, sciurid, or avian hosts. Co-infections involving A. phagocytophilum were less common, and fewer co-infections of A. phagocytophilum and B. microti than predicted by chance were observed in both questing nymphs and larvae fed on small mammals. Medical practitioners should be aware of the elevated risk of B. microti/B. burgdorferi co-infection. PMID:24940999

  2. Differences in prevalence of Borrelia burgdorferi and Anaplasma spp. infection among host-seeking Dermacentor occidentalis, Ixodes pacificus, and Ornithodoros coriaceus ticks in northwestern California

    PubMed Central

    Lane, Robert S.; Mun, Jeomhee; Peribáñez, Miguel A.; Fedorova, Natalia

    2010-01-01

    Previous studies revealed that the Pacific Coast tick (Dermacentor occidentalis) is infected occasionally with the agents of Lyme disease (Borrelia burgdorferi) or human granulocytic anaplasmosis (Anaplasma phagocytophilum) and that it is an inefficient experimental vector of B. burgdorferi. The relationship of the pajahuello tick (Ornithodoros coriaceus) to each of these bacterial zoonotic agents has not been reported. The primary bridging vector of both bacterial zoonotic agents to humans is the western black-legged tick (Ixodes pacificus). Because of the spatial and temporal overlap of D. occidentalis and O. coriaceus populations with those of I. pacificus in natural foci of B. burgdorferi and A. phagocytophilum in northwestern California, we conducted field and laboratory studies to determine if the Pacific Coast tick or the pajahuello tick potentially may serve as secondary vectors of either bacterium. Our findings reconfirmed that wild-caught D. occidentalis ticks are infected infrequently with B. burgdorferi or A. phagocytophilum, but some adult ticks from dense woodlands or chaparral were found to contain 2 important veterinary pathogens for the first time (Anaplasma bovis, A. ovis). The high prevalence of A. bovis infection (4.3%, n=185 ticks) within chaparral-derived ticks suggests that D. occidentalis could be an efficient vector of this rickettsia. Experimental attempts to transmit borreliae or Anaplasma spp. that may have been present in >100 wild-caught D. occidentalis adults to naïve rabbits were unsuccessful. Anaplasma spp. were not detected in O. coriaceus, but one (4.3%) of 23 nymphs was infected with B. bissettii. This finding and an antecedent report of a B. burgdorferi-like spirochete from the same tick species demonstrate that O. coriaceus sometimes acquires and transstadially passes Lyme disease group spirochetes. I. pacificus nymphs inhabiting a woodland nidus of B. burgdorferi and A. phagocytophilum had a 5-fold higher prevalence of

  3. Understanding Recovery Barriers: Youth Perceptions About Substance Use Relapse

    PubMed Central

    Gonzales, Rachel; Anglin, M. Douglas; Beattie, Rebecca; Ong, Chris Angelo; Glik, Deborah C.

    2014-01-01

    Objective To qualitatively explore how treatment-involved youth retrospectively contextualize relapse from substance use. Methods Fourteen focus groups were conducted with 118 youth (78.3% male; 66.1% Latino) enrolled in participating substance abuse treatment programs (4 young adult and 10 adolescent) throughout Los Angeles County. Transcripts were analyzed for relapse perception themes. Results Dominant relapse themes include emotional reasons (90%), life stressors (85%), cognitive factors (75%), socialization processes (65%), and environmental issues (55%). Conclusions Youth perceptions about relapse during treatment should be used to better inform clinical approaches and shape early-intervention recovery agendas for substance-abusing youth. PMID:22584088

  4. Relapsing experimental allergic encephalomyelitis. An autoimmune model of multiple sclerosis.

    PubMed

    Lublin, F D

    1985-01-01

    R-EAE is a valuable model for human MS. Table 2 outlines the similarities between R-EAE and MS. The clinical course and pathologic changes seen in this model accurately reflect the pattern of MS. The immunologic changes seen in animals with R-EAE also are similar to those seen in MS. Therefore, the clinicopathologic features of MS can be duplicated with a purely autoimmune model. Although this is of considerable pathogenic significance in understanding MS, we do not know what the inciting event is in MS that would be the equivalent of immunizing an animal with neural antigen. Despite this, R-EAE has and should continue to provide experimental data of considerable importance to an understanding of the mechanisms involved in the evolution of inflammatory demyelination. Other important models of MS utilize viral-induced demyelination. Although the clinical picture of most of the chronic demyelinating viral infections does not show as clear a relapsing or remitting pattern as seen in R-EAE, viral etiologies better fit the epidemiology of MS [16]. Several studies have demonstrated development of an acute EAE-like disease with sensitization to neural antigens following viral infection [12, 30, 56]. Thus, one can hypothesize an initial viral illness causing sensitization of the host to a neural antigen (?MBP) with a subsequent immunopathogenic course similar to that seen in R-EAE. Whether this will in fact be the case remains unproven as yet. Our understanding of the immunopathogenic mechanisms underlying inflammatory demyelination has been enlarged through studies of R-EAE. It is now clear that the minimal myelin antigen necessary for production of the disease is MBP, although this may differ in some species. The relapsing nature of this disorder is mediated in part through lymphocytes, as demonstrated in transfer studies, and thus does not require persistent antigenic depots. There is a genetic susceptibility to development of the CNS autoimmune state, and we speculate

  5. Relapsing and refractory ulcerative colitis in children.

    PubMed

    Turner, Dan

    2014-01-01

    Approximately half of the children with ulcerative colitis (UC) have refractory, relapsing or steroid-dependent disease. UC in children is more extensive than in adults, presents more often with severe attacks and carries a more aggressive disease course. Therefore, although a step-up approach is usually recommended in UC, aggressive therapy will often be indicated in children since steroid dependency should never be tolerated. It is vital to ensure that in every resistant case, the symptoms are truly related to the inflammatory disease activity and not to other conditions such as poor adherence to treatment, infections, adverse reactions to drugs, irritable bowel syndrome, lactose intolerance, celiac disease and bacterial overgrowth. The clinician should be ready to escalate therapy in a timely manner but only after ensuring optimization of current treatments. Optimization may include, among others, appropriate dosage, utilization of assays that determine thiopurine, calcineurin inhibitors and anti-tumor necrosis factor levels, introduction of combination therapy when indicated (enemas and immunomodulators) and a long enough time for treatment to become effective. Colectomy is always a valid option and should be discussed before major treatment escalations. Experimental therapies can be considered when all else fails and the family prefers to avoid colectomy. The management of refractory and relapsing disease is particularly challenging in children, and this review summarizes the available evidence to guide treatment decisions in this setup. PMID:24969290

  6. Chronic myeloid leukemia relapsing ten years after allogenic bone marrow transplantation.

    PubMed

    Hino, Yutaro; Doki, Noriko; Yamamoto, Keita; Senoo, Yasushi; Sasajima, Satoshi; Sakaguchi, Masahiro; Hattori, Keiichiro; Kaito, Satoshi; Kurosawa, Shuhei; Harada, Kaito; Ikegawa, Shuntaro; Watanabe, Daisuke; Hagino, Takeshi; Yoshioka, Kosuke; Watakabe, Kyoko; Igarashi, Aiko; Najima, Yuho; Kobayashi, Takeshi; Kakihana, Kazuhiko; Sakamaki, Hisashi; Ohashi, Kazuteru

    2016-05-01

    A 58-year-old female was diagnosed with Philadelphia chromosome positive chronic myeloid leukemia (CML) in blast crisis (BC) in 2004. The patient received imatinib, which quickly induced molecular remission, and subsequently underwent bone marrow transplantation (BMT) from an unrelated human leukocyte antigen (HLA)-identical donor. The post-transplant clinical course was essentially uneventful. In 2014, ten years after the BMT, the patient was admitted to our hospital complaining of lymphadenopathy, and blasts were observed in peripheral blood. The patient was diagnosed as having a CML relapse in myeloid BC, with leukemic infiltration in lymph nodes, and was treated with dasatinib. Subsequently, pleural effusion developed and nilotinib was administered, which induced normal blood counts without blasts and partial cytogenetic remission, one month after administration. Six months after the relapse, this patient underwent a second BMT from an HLA-matched unrelated donor. Recent studies have demonstrated the cumulative incidence of CML relapse more than five years after allogeneic hematopoietic stem cell transplantation (allo-HSCT) to be higher than in acute myeloid leukemia. Although rare, the possibility of late relapse should be considered in patients diagnosed with CML after allo-HSCT. PMID:27263786

  7. Allogeneic hemopoietic stem cell transplants for patients with relapsed acute leukemia: long-term outcome.

    PubMed

    Bacigalupo, A; Lamparelli, T; Gualandi, F; Occhini, D; Bregante, S; Raiola, A M; Ibatici, A; di Grazia, C; Dominietto, A; Piaggio, G; Podesta, M; Bruno, B; Lombardi, A; Frassoni, F; Viscoli, C; Sacchi, N; Van Lint, M T

    2007-03-01

    We assessed the long-term outcome of patients with relapsed acute myeloid (n=86) or acute lymphoid leukemia (n=66), undergoing an allogeneic hemopoietic stem cell transplantation in our unit. The median blast count in the marrow was 30%. Conditioning regimen included total body irradiation (TBI) (10-12 Gy) in 115 patients. The donor was a matched donor (n=132) or a family mismatched donor (n=20). Twenty-two patients (15%) survive disease free, with a median follow-up of 14 years: 18 are off medications. The cumulative incidence of transplant related mortality is 40% and the cumulative incidence of relapse related death (RRD) is 45%. In multivariate analysis of survival, favorable predictors were chronic graft-versus-host disease (GvHD) (P=0.0003), donor other than family mismatched (P=0.02), donor age less than 34 years (P=0.02) and blast count less than 30% (P=0.07). Patients with all four favorable predictors had a 54% survival. In multivariate analysis of relapse, protective variables were the use of TBI (P=0.005) and cGvHD (P=0.01). This study confirms that a fraction of relapsed leukemias is cured with an allogeneic transplant: selection of patients with a blast count <30%, identification of young, human leukocyte antigen-matched donors and the use of total body radiation may significantly improve the outcome. PMID:17277788

  8. Transposon mutagenesis as an approach to improved understanding of Borrelia pathogenesis and biology

    PubMed Central

    Lin, Tao; Troy, Erin B.; Hu, Linden T.; Gao, Lihui; Norris, Steven J.

    2014-01-01

    Transposon insertion provides a method for near-random mutation of bacterial genomes, and has been utilized extensively for the study of bacterial pathogenesis and biology. This approach is particularly useful for organisms that are relatively refractory to genetic manipulation, including Lyme disease Borrelia. In this review, progress to date in the application of transposon mutagenesis to the study of Borrelia burgdorferi is reported. An effective Himar1-based transposon vector has been developed and used to acquire a sequence-defined library of nearly 4500 mutants in the infectious, moderately transformable B. burgdorferi B31 derivative 5A18NP1. Analysis of these transposon mutants using signature-tagged mutagenesis (STM) and Tn-seq approaches has begun to yield valuable information regarding the genes important in the pathogenesis and biology of this organism. PMID:24904839

  9. Biochemical and biophysical characterization of the major outer surface protein, OSP-A from North American and European isolates of Borrelia burgdorferi

    SciTech Connect

    McGrath, B.C.; Dunn, J.J.; France, L.L.; Jaing, W.; Polin, D.; Gorgone, G.; Luft, B.; Dykhuizen, D.

    1995-12-31

    Lyme borreliosis, caused by the spirochete Borrelia burgdorferi, is the most common vector-borne disease in North America and Western Europe. As the major delayed immune response in humans, a better understanding of the major outer surface lipoproteins OspA and OspB are of much interest. These proteins have been shown to exhibit three distinct phylogenetic genotypes based on their DNA sequences. This paper describes the cloning of genomic DNA for each variant and amplification of PCR. DNA sequence data was used to derive computer driven phylogenetic analysis and deduced amino acid sequences. Overproduction of variant OspAs was carried out in E. coli using a T7-based expression system. Circular dichroism and fluorescence studies was carried out on the recombinant B31 PspA yielding evidence supporting a B31 protein containing 11% alpha-helix, 34% antiparallel beta-sheet, 12% parallel beta sheet.

  10. ErpC, a member of the complement regulator-acquiring family of surface proteins from Borrelia burgdorferi, possesses an architecture previously unseen in this protein family

    PubMed Central

    Caesar, Joseph J. E.; Johnson, Steven; Kraiczy, Peter; Lea, Susan M.

    2013-01-01

    Borrelia burgdorferi is a spirochete responsible for Lyme disease, the most commonly occurring vector-borne disease in Europe and North America. The bacterium utilizes a set of proteins, termed complement regulator-acquiring surface proteins (CRASPs), to aid evasion of the human complement system by recruiting and presenting complement regulator factor H on its surface in a manner that mimics host cells. Presented here is the atomic resolution structure of a member of this protein family, ErpC. The structure provides new insights into the mechanism of recruitment of factor H and other factor H-related proteins by acting as a molecular mimic of host glycosaminoglycans. It also describes the architecture of other CRASP proteins belonging to the OspE/F-related paralogous protein family and suggests that they have evolved to bind specific complement proteins, aiding survival of the bacterium in different hosts. PMID:23722838

  11. Suppression of Long-Lived Humoral Immunity Following Borrelia burgdorferi Infection

    PubMed Central

    Elsner, Rebecca A.; Hastey, Christine J.; Olsen, Kimberly J.; Baumgarth, Nicole

    2015-01-01

    Lyme Disease caused by infection with Borrelia burgdorferi is an emerging infectious disease and already by far the most common vector-borne disease in the U.S. Similar to many other infections, infection with B. burgdorferi results in strong antibody response induction, which can be used clinically as a diagnostic measure of prior exposure. However, clinical studies have shown a sometimes-precipitous decline of such antibodies shortly following antibiotic treatment, revealing a potential deficit in the host’s ability to induce and/or maintain long-term protective antibodies. This is further supported by reports of frequent repeat infections with B. burgdorferi in endemic areas. The mechanisms underlying such a lack of long-term humoral immunity, however, remain unknown. We show here that B. burgdorferi infected mice show a similar rapid disappearance of Borrelia-specific antibodies after infection and subsequent antibiotic treatment. This failure was associated with development of only short-lived germinal centers, micro-anatomical locations from which long-lived immunity originates. These showed structural abnormalities and failed to induce memory B cells and long-lived plasma cells for months after the infection, rendering the mice susceptible to reinfection with the same strain of B. burgdorferi. The inability to induce long-lived immune responses was not due to the particular nature of the immunogenic antigens of B. burgdorferi, as antibodies to both T-dependent and T-independent Borrelia antigens lacked longevity and B cell memory induction. Furthermore, influenza immunization administered at the time of Borrelia infection also failed to induce robust antibody responses, dramatically reducing the protective antiviral capacity of the humoral response. Collectively, these studies show that B. burgdorferi-infection results in targeted and temporary immunosuppression of the host and bring new insight into the mechanisms underlying the failure to develop long

  12. High Prevalence of Borrelia miyamotoi among Adult Blacklegged Ticks from White-Tailed Deer

    PubMed Central

    Hickling, Graham J.; Tsao, Jean I.

    2016-01-01

    We compared the prevalence of Borrelia miyamotoi infection in questing and deer-associated adult Ixodes scapularis ticks in Wisconsin, USA. Prevalence among deer-associated ticks (4.5% overall, 7.1% in females) was significantly higher than among questing ticks (1.0% overall, 0.6% in females). Deer may be a sylvatic reservoir for this newly recognized zoonotic pathogen. PMID:26811985

  13. Lyme borreliosis caused by diverse genospecies of Borrelia burgdorferi sensu lato in northeastern China.

    PubMed

    Ni, X-B; Jia, N; Jiang, B-G; Sun, T; Zheng, Y-C; Huo, Q-B; Liu, K; Ma, L; Zhao, Q-M; Yang, H; Wang, X; Jiang, J-F; Cao, W-C

    2014-08-01

    The variety of Borrelia burgdorferi sensu lato (B. burgdorferi) genospecies leads to distinction in clinical manifestations of Lyme borreliosis (LB). There are reports of LB clinical characteristics in China, where the B. burgdorferi genospecies in ticks and animal hosts are different from those in Europe and North America. During May to September in 2010 and 2011, all patients who had erythema migrans (EM, more than 5 cm in diameter) after a recent tick-bite, and sought medical care at Mudanjiang Forestry Central Hospital, Heilongjiang Province of northeastern China, were enrolled in the study. Specific PCR was used to determine the B. burgdorferi genospecies in the disseminated patients. Of 265 EM patients, B. burgdorferi DNA was detected in blood specimens from 15 of 55 disseminated patients. Sequence analyses of 5S-23S rRNA, flagellin, ospC, 16S rRNA and ospA genes revealed that 11 patients were infected with Borrelia garinii, three with Borrelia afzelii and one with Borrelia valaisiana-related genospecies. Among 15 patients, 40%, 13.3% and 13.3% manifested pruritus, pain and ulceration, respectively. Systemic symptoms, arthralgia or a swollen joint and lymphadenopathy were observed in 26.7%, 13.3% and 6.7% patients, respectively. In northeastern China, three genospecies of LB patients were detected. The B. burgdorferi genospecies identified in this study was predominantly B. garinii. A case infected with B. valaisiana-related genospecies was reported for the first time. PMID:24438159

  14. Geographical differences in seroprevalence of Borrelia burgdorferi antibodies in Norway, 2011-2013.

    PubMed

    Vestrheim, Didrik F; White, Richard A; Aaberge, Ingeborg S; Aase, Audun

    2016-07-01

    Detection of specific antibodies against Borrelia burgdorferi sensu lato is a useful aid for the diagnosis of Lyme borreliosis. However, antibodies are present in the general population. The seroprevalence increase with age, and varies according to the prevalence of infected ticks. We performed a seroprevalence study of IgM and IgG antibody reactivity against B. burgdorferi sensu lato in Norway by age-groups and geography, in order to provide a reference set of seroprevalence to inform the interpretation of positive test results. We used two commercially available enzyme immuno assays (EIA) and a multiplexed bead assay to detect Borrelia IgG antibodies in a convenience sample of 3057 sera collected from clinical chemistry laboratories in 10 of 19 counties in Norway between December 2011 and January 2013. We estimated seroprevalence by age and county by a logistic regression model. IgM antibodies were detected by two commercially available EIAs and a multiplexed bead assay. The overall seroprevalence of Borrelia IgG was 4.0% (95% CI: 2.4-6.6%) and 4.2% (2.6-6.8%) by the two EIAs, respectively. The seroprevalence increased by age, and by geography from north to south. The IgG assays showed a good agreement for positive test results. All sera positive for IgG in the multiplexed bead assay reacted with the VlsE antigen, and also had high antibody levels by EIA. The Borrelia seroprevalence varied by geography and increased by age. The results indicate regional differences in pre-test probabilities for positive test results, and can inform the interpretation of laboratory results. PMID:26961275

  15. Few vertebrate species dominate the Borrelia burgdorferi s.l. life cycle

    NASA Astrophysics Data System (ADS)

    Hofmeester, T. R.; Coipan, E. C.; van Wieren, S. E.; Prins, H. H. T.; Takken, W.; Sprong, H.

    2016-04-01

    Background. In the northern hemisphere, ticks of the Ixodidae family are vectors of diseases such as Lyme borreliosis, Rocky Mountain spotted fever and tick-borne encephalitis. Most of these ticks are generalists and have a three-host life cycle for which they are dependent on three different hosts for their blood meal. Finding out which host species contribute most in maintaining ticks and the pathogens they transmit, is imperative in understanding the drivers behind the dynamics of a disease. Methods. We performed a systematic review to identify the most important vertebrate host species for Ixodes ricinus and Borrelia burgdorferi s.l. as a well-studied model system for tick-borne diseases. We analyzed data from 66 publications and quantified the relative contribution for 15 host species. Review results. We found a positive correlation between host body mass and tick burdens for the different stages of I. ricinus. We show that nymphal burdens of host species are positively correlated with infection prevalence with B. burgdorferi s.l., which is again positively correlated with the realized reservoir competence of a host species for B. burgdorferi s.l. Our quantification method suggests that only a few host species, which are amongst the most widespread species in the environment (rodents, thrushes and deer), feed the majority of I. ricinus individuals and that rodents infect the majority of I. ricinus larvae with B. burgdorferi s.l. Discussion. We argue that small mammal-transmitted Borrelia spp. are maintained due to the high density of their reservoir hosts, while bird-transmitted Borrelia spp. are maintained due to the high infection prevalence of their reservoir hosts. Our findings suggest that Ixodes ricinus and Borrelia burgdorferi s.l. populations are maintained by a few widespread host species. The increase in distribution and abundance of these species, could be the cause for the increase in Lyme borreliosis incidence in Europe in recent decades.

  16. Structural and functional analysis of BB0689 from Borrelia burgdorferi, a member of the bacterial CAP superfamily.

    PubMed

    Brangulis, Kalvis; Jaudzems, Kristaps; Petrovskis, Ivars; Akopjana, Inara; Kazaks, Andris; Tars, Kaspars

    2015-12-01

    Spirochete Borrelia burgdorferi is the causative agent of Lyme disease and is transmitted from infected Ixodes ticks to a mammalian host after a tick bite. The outer surface protein BB0689 from B. burgdorferi is up-regulated when the tick feeds, which indicates a potential role for BB0689 in Lyme disease pathogenesis. We have determined the crystal structure of BB0689, which revealed that the protein belongs to the CAP superfamily. Though the CAP domain is widespread in all three cellular domains of life, thus far the CAP domain has been studied only in eukaryotes, in which it is usually linked to certain other domains to form a multi-domain protein and is associated with the mammalian reproductive tract, the plant response to pathogens, venom allergens from insects and reptiles, and the growth of human brain tumors. Though the exact function of the isolated CAP domain remains ambiguous, several functions, including the binding of cholesterol, lipids and heparan sulfate, have been recently attributed to different CAP domain proteins. In this study, the bacterial CAP domain structure was analyzed and compared with the previously solved crystal structures of representative CAPs, and the function of BB0689 was examined. To determine the potential function of BB0689 and ascertain whether the functions that have been attributed to the CAP domain proteins are conserved, the binding of previously reported CAP domain interaction partners was analyzed, and the results suggested that BB0689 has a unique function that is yet to be discovered. PMID:26407658

  17. Allozyme polymorphism of Mdh and alpha-Gpdh in Ixodes ricinus populations: comparison of borreliae-infected and uninfected ticks.

    PubMed

    Radulović, Zeljko; Milutinović, Marija; Andelković, Marko; Vujcić, Zoran; Tomanović, Snezana; Bozić, Natasa; Marinković, Dragoslav

    2006-01-01

    Ixodes ricinus Linnaeus (Acari: Ixodidae) ticks are vectors of numerous infectious diseases in humans and animals. The allozyme variability of MDH and alpha-Gpdh was detected by native polyacrylamide gel electrophoresis in I. ricinus natural populations in three localities in Serbia. Four alleles of Mdh locus (MDH 1, MDH 2, MDH 3 and MDH X) and four alleles of alpha-Gpdh locus (VS, S, F and VF) were detected. Interpopulation differences in Mdh and alpha-Gpdh allele frequencies were statistically insignificant. Significant difference in alpha-Gpdh allele frequencies between males and females was recorded in the largest sample only. Differences in allele frequencies, detected between borreliae-infected and uninfected I. ricinus ticks, were close to the level of statistical significance, especially for alpha-Gpdh locus. Clear significant difference appeared in females when sexes were tested separatelly (P = 0.037). It is interesting that genotypes containing rarer alleles (MDH 1 and S) were infected in higher proportion in comparison to other genotypes. Our results point towards a possible role of Mdh and alpha-Gpdh loci in I. ricinus ticks in the determination of energy requirements for host seeking. Sex differences in alpha-Gpdh allele frequencies suggest that selective pressure, concerning efficiency of reserve materials utilisation, points to alpha-Gpdh rather than to Mdh locus. PMID:17072538

  18. BGA66 and BGA71 facilitate complement resistance of Borrelia bavariensis by inhibiting assembly of the membrane attack complex.

    PubMed

    Hammerschmidt, Claudia; Klevenhaus, Yvonne; Koenigs, Arno; Hallström, Teresia; Fingerle, Volker; Skerka, Christine; Pos, Klaas Martinus; Zipfel, Peter F; Wallich, Reinhard; Kraiczy, Peter

    2016-01-01

    Borrelia (B.) bavariensis exhibits a marked tropism for nervous tissues and frequently causes neurological manifestations in humans. The molecular mechanism by which B. bavariensis overcomes innate immunity, in particular, complement remains elusive. In contrast to other serum-resistant spirochetes, none of the B. bavariensis isolates investigated bound complement regulators of the alternative (AP) and classical pathway (CP) or proteolytically inactivated complement components. Focusing on outer surface proteins BGA66 and BGA71, we demonstrated that both molecules either inhibit AP, CP and terminal pathway (TP) activation, or block activation of the CP and TP respectively. Both molecules bind complement components C7, C8 and C9, and thereby prevent assembly of the terminal complement complex. This inhibitory activity was confirmed by the introduction of the BGA66 and BGA71 encoding genes into a serum-sensitive B. garinii strain. Transformed spirochetes producing either BGA66 or BGA71 overcome complement-mediated killing, thus indicating that both proteins independently facilitate serum resistance of B. bavariensis. The generation of C-terminally truncated proteins as well as a chimeric BGA71 protein lead to the localization of the complement-interacting binding site within the N-terminus. Collectively, our data reveal a novel immune evasion strategy of B. bavariensis that is directed against the activation of the TP. PMID:26434356

  19. Pervasive recombination and sympatric genome diversification driven by frequency-dependent selection in Borrelia burgdorferi, the Lyme disease bacterium.

    PubMed

    Haven, James; Vargas, Levy C; Mongodin, Emmanuel F; Xue, Vincent; Hernandez, Yozen; Pagan, Pedro; Fraser-Liggett, Claire M; Schutzer, Steven E; Luft, Benjamin J; Casjens, Sherwood R; Qiu, Wei-Gang

    2011-11-01

    How genomic diversity within bacterial populations originates and is maintained in the presence of frequent recombination is a central problem in understanding bacterial evolution. Natural populations of Borrelia burgdorferi, the bacterial agent of Lyme disease, consist of diverse genomic groups co-infecting single individual vertebrate hosts and tick vectors. To understand mechanisms of sympatric genome differentiation in B. burgdorferi, we sequenced and compared 23 genomes representing major genomic groups in North America and Europe. Linkage analysis of >13,500 single-nucleotide polymorphisms revealed pervasive horizontal DNA exchanges. Although three times more frequent than point mutation, recombination is localized and weakly affects genome-wide linkage disequilibrium. We show by computer simulations that, while enhancing population fitness, recombination constrains neutral and adaptive divergence among sympatric genomes through periodic selective sweeps. In contrast, simulations of frequency-dependent selection with recombination produced the observed pattern of a large number of sympatric genomic groups associated with major sequence variations at the selected locus. We conclude that negative frequency-dependent selection targeting a small number of surface-antigen loci (ospC in particular) sufficiently explains the maintenance of sympatric genome diversity in B. burgdorferi without adaptive divergence. We suggest that pervasive recombination makes it less likely for local B. burgdorferi genomic groups to achieve host specialization. B. burgdorferi genomic groups in the northeastern United States are thus best viewed as constituting a single bacterial species, whose generalist nature is a key to its rapid spread and human virulence. PMID:21890743

  20. Serologic survey of the wild boar (Sus scrofa) for Borrelia burgdorferi sensu lato.

    PubMed

    Juricová, Z; Hubálek, Z

    2009-10-01

    Sera of 642 wild boars (Sus scrofa) shot by hunters in ten administrative regions of the Czech Republic during 1995-2000, were tested by indirect hemagglutination assay (IHA) for the presence of anti-Borrelia IgG. Antibodies to Borrelia burgdorferi sensu lato (Bb) were detected in serum samples from all 10 regions, and overall seroprevalence rate was 12.8%. Titres of antibodies ranged from 1:80 to 1:640. Borrelia antibodies were most frequent in the animals from three administrative regions of the Czech Republic: Moravskoslezsky (25.0%), Pardubicky (25.0%) and Královehradecky (24.1%), followed by the regions Plzen sky (16.7%), Olomoucky (13.3%), Jihomoravsky (12.8%), Vysoc ina (11.1%), Jihoc esky (11.1%), Zlínsky (10.3%), and Liberecky (8.9%). Seasonal seroprevalence rate increased in March and April, the peak was in May. The results suggest frequent exposure of wild boars to ixodid ticks infected with Bb, predominantly in rural and forested regions. The study also reviews the importance of wild boar in Lyme borreliosis (LB) ecology. Wild boar serology may provide another means of surveillance of endemic areas of LB. PMID:18973452

  1. Serological reactivity to Borrelia burgdorferi sensu lato in dogs and horses from distinct areas in Romania.

    PubMed

    Kiss, Timea; Cadar, Daniel; Krupaci, Alexandra Florina; Bordeanu, Armela; Brudaşcă, Gheorghe Florinel; Mihalca, Andrei Daniel; Mircean, Viorica; Gliga, Lucia; Dumitrache, Mirabela Oana; Spînu, Marina

    2011-09-01

    Lyme disease is a perfect model of the complex relationship between host, vector, and the vector-borne bacteria. Both dogs and horses in Romania are exposed to infection. The aim of the present study was to assess the seroreactivity against Borrelia burgdorferi sensu lato in dogs and horses from different regions of Romania. 276 samples from dogs and 260 samples from horses located in different regions of Romania were analyzed by ELISA and IFA, respectively. The effect of several factors potentially affecting seroreactivity (location, age, gender, occupation, and vector exposition risk) was evaluated using Fisher's exact test (R 2.12.0). The overall prevalence of anti-Borrelia antibodies was 6.52% (18/276) in dogs, with a significantly higher positivity (46.15%, 6/13, p = 0.0005) recorded in a midcountry region. Seroreactivity was correlated with occupation, with working dogs being more exposed. The results may indicate that Lyme borreliosis foci are restricted to small areas, but further studies on Borrelia prevalence in tick populations are needed to confirm this hypothesis. In horses, a global seroprevalence of 11.92% (31/260) was observed. No correlations were found between positive results and age, sex, county, or occupation. This is the first serological survey on antibodies to B. burgdorferi sensu lato in Romanian dogs and horses. PMID:21612524

  2. Identification of Anaplasma phagocytophilum and Borrelia burgdorferi sensu lato in patients with erythema migrans.

    PubMed

    Hulínská, D; Votýpka, J; Vanousová, D; Hercogová, J; Hulínský, V; Drevová, H; Kurzová, Z; Uherková, L

    2009-01-01

    Anaplasma phagocytophilum has been first isolated from the blood of two Czech patients simultaneously with a cultivation of Borrelia burgdorferi sensu lato from their erythema migrans lesions. Cultivation of different Borrelia spp. from 12 erythema migrans biopsies, from 2 blood, one liquor and one placenta sample in BSK-H medium was successful. Adapted conventional methods targeting 16S rRNA and OspA genes for real-time polymerase chain reaction (PCR) and partial sequencing of these genes together with microscopical examinations of the blood smears provided a direct detection of the B. afzelii, B. burgdorferi, B. garinii, B. valaisiana and B. bissettii in the skin, B. garinii in the blood, placenta and liquor in 24 (36.3 %) patients, and A. phagocytophilum in 10 (15 %) patients with erythema migrans. Positive indirect IgM immunofluorescence against Anaplasma sp. was obtained in 7 cases, specific IgG antibodies were detected in 12 patients. Three women suffering from erythema migrans in the first trimester had positive PCR for Anaplasma and/or for Borrelia in the blood and two of them, later, in the placenta. Interpretation of laboratory data can bring important contribution to establishing the role of Anaplasma sp. in erythema migrans and forming the principle of precaution with laboratory diagnosis during pregnancy which always should be reflected in the resistance of Anaplasma sp. toward penicillins. PMID:19649743

  3. Laboratory diagnosis of Lyme neuroborreliosis: a comparison of three CSF anti-Borrelia antibody assays.

    PubMed

    Henningsson, A J; Christiansson, M; Tjernberg, I; Löfgren, S; Matussek, A

    2014-05-01

    The diagnosis of Lyme neuroborreliosis (LNB) requires the detection of intrathecal synthesis of Borrelia-specific antibodies, but in very early disease, the sensitivity may be low. We compared the performance of the second-generation IDEIA Lyme Neuroborreliosis test (Oxoid), based on purified native flagellum antigen, with two newly developed tests based on several recombinant antigens for the diagnosis of LNB. Patients investigated for LNB during 2003 through 2007 were included (n = 175); 52 with definite LNB, four with possible LNB and 119 non-LNB patients. Serum and cerebrospinal fluid (CSF) were analysed with the IDEIA Lyme Neuroborreliosis (Oxoid), VIDAS Lyme IgG (bioMérieux) and recomBead Borrelia IgM and IgG (Mikrogen) assays. Intrathecal antibody indices (AIs) were calculated according to the manufacturers' protocols. The IDEIA test performed with an overall sensitivity (IgM and IgG AIs taken together) of 88 % and a specificity of 99 %. The VIDAS test showed a sensitivity of 86 % and a specificity of 97 %. An overall sensitivity of 100 % and a specificity of 97 % were achieved by the recomBead test. We conclude that the three assays performed equally well regarding specificity, but our data suggest an improved diagnostic sensitivity with the recomBead Borrelia test. PMID:24263552

  4. Morphoea and Borrelia burgdorferi: results from the Scottish Highlands in the context of the world literature

    PubMed Central

    Goodlad, J R; Davidson, M M; Gordon, P; Billington, R; Ho-Yen, D O

    2002-01-01

    Aims: Previous studies investigating the link between infection with Borrelia burgdorferi and morphoea have produced conflicting results. Often, these studies have been undertaken in patients from different regions or countries, and using methods of varying sensitivity for detecting Borrelia burgdorferi infection. This study aimed to establish whether a relation could be demonstrated in the Highlands of Scotland, an area with endemic Lyme disease, with the use of a sensitive method for detecting the organism. Methods: The study was performed on biopsies of lesional skin taken from 16 patients from the Highlands of Scotland with typical clinical features of morphoea. After histological confirmation of the diagnosis, a nested polymerase chain reaction (PCR) using primers to a unique conserved region of the Borrelia burgdorferi flagellin gene was performed on DNA extracts from each biopsy. A literature search was also performed for comparable studies. Results: None of the 16 patients had documented clinical evidence of previous infection with B burgdorferi. DNA was successfully extracted from 14 of the 16 cases but all of these were negative using PCR for B burgdorferi specific DNA, despite successful amplification of appropriate positive controls in every test. The results were compared with those of other documented studies. Conclusions: Examination of the literature suggests that there is a strong geographical relation between B burgdorferi and morphoea. These results, in which no such association was found, indicate that morphoea may not be associated with the subspecies of B burgdorferi found in the Highlands of Scotland. PMID:12456775

  5. Induction of Type I and Type III Interferons by Borrelia burgdorferi Correlates with Pathogenesis and Requires Linear Plasmid 36

    PubMed Central

    Krupna-Gaylord, Michelle A.; Liveris, Dionysios; Love, Andrea C.; Wormser, Gary P.; Schwartz, Ira; Petzke, Mary M.

    2014-01-01

    The capacity for Borrelia burgdorferi to cause disseminated infection in humans or mice is associated with the genotype of the infecting strain. The cytokine profiles elicited by B. burgdorferi clinical isolates of different genotype (ribosomal spacer type) groups were assessed in a human PBMC co-incubation model. RST1 isolates, which are more frequently associated with disseminated Lyme disease in humans and mice, induced significantly higher levels of IFN-α and IFN-λ1/IL29 relative to RST3 isolates, which are less frequently associated with disseminated infection. No differences in the protein concentrations of IFN-γ, IL-1β, IL-6, IL-8, IL-10 or TNF-α were observed between isolates of differing genotype. The ability of B. burgdorferi to induce type I and type III IFNs was completely dependent on the presence of linear plasmid (lp) 36. An lp36-deficient B. burgdorferi mutant adhered to, and was internalized by, PBMCs and specific dendritic cell (DC) subsets less efficiently than its isogenic B31 parent strain. The association defect with mDC1s and pDCs could be restored by complementation of the mutant with the complete lp36. The RST1 clinical isolates studied were found to contain a 2.5-kB region, located in the distal one-third of lp36, which was not present in any of the RST3 isolates tested. This divergent region of lp36 may encode one or more factors required for optimal spirochetal recognition and the production of type I and type III IFNs by human DCs, thus suggesting a potential role for DCs in the pathogenesis of B. burgdorferi infection. PMID:24945497

  6. [Relapse prevention group therapy for paedophiles: French adaptation].

    PubMed

    Smith, J; Petibon, C

    2005-01-01

    changes often occur quite quickly in paedophiles when they are offered group therapy. The group makes it easier to confront paedophiles to the reality of their offence and of their sexual fantasies. These patients often express being very relieved after the first sessions, as the group therapy is generally their first opportunity to express their feelings, sexual fantasies and thoughts about paedophilia. Pithers' model, used within a group were patients are free to speak in a human, warm and confronting atmosphere, seems clinically accurate and effective in helping paedophiles in France. We now need studies to check therapy effectiveness on relapse and to understand which therapy factors are efficient on sex offenders. PMID:16598959

  7. Borrelia chilensis, a new member of the Borrelia burgdorferi sensu lato complex that extends the range of this genospecies in the Southern Hemisphere

    PubMed Central

    Ivanova, Larisa B.; Tomova, Alexandra; González-Acuña, Daniel; Murúa, Roberto; Moreno, Claudia X.; Hernández, Claudio; Cabello, Javier; Cabello, Carlos; Daniels, Thomas J.; Godfrey, Henry P.; Cabello, Felipe C.

    2014-01-01

    Summary Borrelia burgdorferi sensu lato (s.l.), transmitted by Ixodes spp. ticks, is the causative agent of Lyme disease. Although Ixodes spp. ticks are distributed in both Northern and Southern Hemispheres, evidence for the presence of B. burgdorferi s.l. in South America apart from Uruguay is lacking. We now report the presence of culturable spirochetes with flat-wave morphology and borrelial DNA in endemic Ixodes stilesi ticks collected in Chile from environmental vegetation and long-tailed rice rats (Oligoryzomys longicaudatus). Cultured spirochetes and borrelial DNA in ticks were characterized by multilocus sequence typing and by sequencing five other loci (16S and 23S ribosomal genes, 5S-23S intergenic spacer, flaB, ospC). Phylogenetic analysis placed this spirochete as a new genospecies within the Lyme borreliosis group. Its plasmid profile determined by PCR and pulsed-field gel electrophoresis differed from that of B. burgdorferi B31A3. We propose naming this new South American member of the Lyme borreliosis group Borrelia chilensis VA1, in honor of its country of origin. PMID:24148079

  8. Complement Receptor 3 Binds the Borrelia burgdorferi Outer Surface Proteins OspA and OspB in an iC3b-Independent Manner

    PubMed Central

    Garcia, Rodolfo C.; Murgia, Rossella; Cinco, Marina

    2005-01-01

    Persistence of borreliae within the vertebrate host depends on the fate of interactions between the spirochetes and target cells. The present work demonstrates the direct binding of the Borrelia burgdorferi outer surface proteins OspA and OspB to CR3 and that this binding is independent of iC3b. PMID:16113335

  9. Endogenous Task Shift Processes in Relapsing-Remitting Multiple Sclerosis

    ERIC Educational Resources Information Center

    Stablum, F.; Meligrana, L.; Sgaramella, T.; Bortolon, F.; Toso, V.

    2004-01-01

    This paper reports a study that was aimed to evaluate executive functions in relapsing-remitting multiple sclerosis patients. The groups tested comprised 22 relapsing-remitting multiple sclerosis patients, and 22 non-brain damaged controls. When one is engaged in two speeded tasks, not simultaneously but with some form of alternation, it is slower…

  10. Relapse Prevention Needs More Emphasis on Interpersonal Factors

    ERIC Educational Resources Information Center

    Stanton, Mark

    2005-01-01

    This article presents comments on "Relapse Prevention for Alcohol and Drug Problems: That Was Zen, This Is Tao," by Katie Witkiewitz and G.A. Marlatt. Stanton notes that the recent reconceptualization of relapse prevention by Witkiewitz and Marlatt enhances the model by "synthesizing recent empirical findings into a unified theory", but it does…

  11. Louseborne Relapsing Fever among East African Refugees, Italy, 2015

    PubMed Central

    Lipani, Filippo; Costa, Cecilia; Scarvaglieri, Mariaelisabetta; Balbiano, Rosanna; Carosella, Sinibaldo; Calcagno, Andrea; Audagnotto, Sabrina; Barbui, Anna Maria; Brossa, Silvia; Ghisetti, Valeria; Dal Conte, Ivano; Caramello, Pietro; Di Perri, Giovanni

    2016-01-01

    During June 9–September 30, 2015, five cases of louseborne relapsing fever were identified in Turin, Italy. All 5 cases were in young refugees from Somalia, 2 of whom had lived in Italy since 2011. Our report seems to confirm the possibility of local transmission of louse-borne relapsing fever. PMID:26812354

  12. Emphasis on Interpersonal Factors in a Dynamic Model of Relapse

    ERIC Educational Resources Information Center

    Witkiewitz, Katie; Marlatt, G. Alan

    2005-01-01

    This article presents comments on "Relapse Prevention Needs More Emphasis on Interpersonal Factors" by Stanton which is a comment on the original article "Relapse Prevention for Alcohol and Drug Problems: That Was Zen, This Is Tao" by Katie Witkiewitz and G. Alan Marlatt. In the current comment the authors of the original article respond to…

  13. Impact of Life Events on the Relapse of Schizophrenic Patients

    ERIC Educational Resources Information Center

    Hussein, Hassan Ali; Jacoob, Shirooq; Sharour, Loai Abu

    2016-01-01

    Objectives: To investigate the relationship between stressful life events at the time of relapse in schizophrenic patients at psychiatric hospitals in Baghdad city. Methodology: A purposive (non-probability) sampling of 50 schizophrenic patients who have relapsed was involved in the present study. Data were collected through the use of the…

  14. Polysubstance Use and Heroin Relapse among Adolescents following Residential Treatment

    ERIC Educational Resources Information Center

    Branson, Christopher E.; Clemmey, Philip; Harrell, Paul; Subramaniam, Geetha; Fishman, Marc

    2012-01-01

    This study examined posttreatment patterns of polysubstance use and heroin relapse in a sample of 43 adolescents (ages 14-20) entering short-term residential treatment for primary heroin use. At 12-month follow-up, youths that achieved heroin abstinence (N = 19) were significantly less likely than youths that relapsed to heroin (N = 24) to endorse…

  15. Power2: Relapse Management with Adolescents Who Stutter.

    ERIC Educational Resources Information Center

    Blood, Gordon W.

    1995-01-01

    This article describes a cognitive-behavioral treatment package for relapse management in adolescents who stutter. The package includes game-based training techniques in problem solving, communication skills, and assertiveness; coping responses for stuttering episodes; and realistic expectations for fluency and relapse. Follow-up results with…

  16. Effects of Nicotine Fading and Relapse Prevention on Smoking Cessation.

    ERIC Educational Resources Information Center

    Brown, Richard A.; And Others

    1984-01-01

    Conducted a pilot study which combined nicotine-fading and relapse prevention with smokers (N=30) and compared this program to conditions where subjects (N=46) received nicotine-fading or relapse prevention only. Results showed no difference among groups in abstinence or rate at any follow-up point. (LLL)

  17. Effects of Vocational Consultation on Relapse Rate and Hope among Drug Dependents in Bojnurd, Iran

    PubMed Central

    Hojjat, Seyed Kaveh; Raufpoor, Roghieh; Khalili, Mina Norozi; Hamidi, Mahin; Danesh, Mahsa; Ziarat, Hadiseh Monadi

    2016-01-01

    Introduction Drug addiction is one of the most flagrant social damages that can easily enervate the socio-cultural foundation of a country as well as endanger human dynamism. One of the prevalent problems among most addicted people is their low hope and relapse of drug dependence. The aim of this study was to assess the effect of vocational consultation (for training on problem-solving skills) on hope and relapse rate of patients treated in methadone maintenance clinics. Methods This experiment was conducted on 60 drug abusers treated in a methadone maintenance program in drug addiction centers in Bojnurd, Iran, in 2014. The patients were randomly and equally allocated into two study and control groups. All patients completed the Miller Hope Questionnaire before and after the intervention. Ten sessions of vocational consultation were held for the study group while the control group received no special treatment. Patients were followed up on for relapses for six months. Data were analyzed using SPSS (version 16) and the paired-samples t-test technique. Results The results indicated that the mean and standard deviation of hope on the pre-test in the study group increased on the post-test (from M=175.5, SD=31.8, to M=198.5, SD=20.4), while in the control group the mean of hope decreased from the pre-test to past-test stage (M=184.7, SD=27.7, to M=183.3, SD=26.1), showing a significant relationship, t(56)= 5.657, p<0.05. The relapse rate was not significantly different in the two groups. Conclusion The vocational consultation positively affects hope among drug dependents but did not affect their relapse rate during the six-month follow-up. Increasing the hope in these groups of patients may be effective in other aspects of treatment success in long-term follow-up. PMID:26955440

  18. Genetic Profiling to Determine Risk of Relapse Free Survival in High-risk Localized Prostate Cancer

    PubMed Central

    Barnett, Christine M.; Heinrich, Michael C.; Lim, Jeong; Nelson, Dylan; Beadling, Carol; Warrick, Andrea; Neff, Tanaya; Higano, Celestia S.; Garzotto, Mark; Qian, David; Corless, Christopher L.; Thomas, George V.; Beer, Tomasz M.

    2014-01-01

    Purpose The characterization of actionable mutations in human tumors is a prerequisite for the development of individualized, targeted therapy. We examined the prevalence of potentially therapeutically actionable mutations in patients with high risk clinically localized prostate cancer. Experimental Design 48 samples of formalin fixed paraffin embedded prostatectomy tissue from a neoadjuvant chemotherapy trial were analyzed. DNA extracted from microdissected tumor was analyzed for 643 common solid tumor mutations in 53 genes using mass spectroscopy based sequencing. In addition, PTEN loss and ERG translocations were examined using immunohistochemistry in associated tissue microarrays. Association with relapse during 5 years of follow-up was examined in exploratory analyses of the potential clinical relevance of the genetic alterations. Results Of the 40 tumors evaluable for mutations, 10% had point mutations in potentially actionable cancer genes. Of the 47 tumors evaluable for IHC, 36% had PTEN loss and 40% had ERG rearrangement. Individual mutations were not frequent enough to determine associations with relapse. Using Kaplan-Meier analysis with a log-rank test, the 16 patients who had PTEN loss had a significantly shorter median relapse free survival, 19 vs. 106 months (p = .01). Conclusions This study confirms that point mutations in the most common cancer regulatory genes in prostate cancer are rare. However, the PIK3CA/AKT pathway was mutated in 10% of our samples. While point mutations alone did not have a statistically significant association with relapse, PTEN loss was associated with an increased relapse in high risk prostate cancer treated with chemotherapy followed by surgery. PMID:24352642

  19. Relapsing Polychondritis: Inflamed Joints and Ears

    PubMed Central

    Melikoğlu, Meltem Alkan; Şenel, Kazım

    2015-01-01

    Background: Relapsing polychondritis (RP) is an episodic and progressive inflammatory disease of the cartilaginous structures, including elastic cartilage of the ear and nose, hyaline cartilage of the peripheral joints, fibrocartilage at axial sites, and cartilage of the tracheo-bronchial tree. The spectrum of its presentations may vary from intermittent mild episodes of chondritis to occasional organ involvement or even life-threatening manifestations. Case Report: We presented a 64 year-old male patient with bilaterally knee arthritis and discoloration of pinna. Conclusion: There is lack of awareness about this disease due to its rarity. With this case presentation, our goal was to draw attention to this disease, which could be delayed for the diagnosis. PMID:25759785

  20. Graves’ Ophthalmopathy Misdiagnosed as Relapsing Conjunctivitis

    PubMed Central

    Chatziralli, Irini P.; Kanonidou, Evgenia; Keryttopoulos, Petros; Papadopoulou, Dionyssia; Papazisis, Leonidas

    2010-01-01

    A 59-year-old female patient presented at the outpatients’ Department of Ophthalmology with epiphora, eyelid swelling, and a foreign body feeling in the right eye. The symptoms were present for 4 months, and the patient was treated as suffering from relapsing conjunctivitis. The slit lamp examination revealed keratitis due to exposure, related with the deficient closure of the eyelids. There was a 2 mm difference in the readings with the Hertel exophthalmometry examination between the eyes. Her medical history was clear, and she was referred for computed tomography of the orbits and brain and biochemical examinations (FT3, FT4, and TSH) to investigate the presence of an intraorbital mass. FT3 was significantly increased and TSH was accordingly low, indicating the diagnosis of Graves’ disease, which presented without other signs and symptoms apart from ophthalmopathy. Computed tomography scan excluded the diagnosis of an intraorbital mass. Therefore, it is important not to underestimate the ocular manifestations of systemic diseases. PMID:21060773

  1. Detection of Borrelia, Ehrlichia, and Rickettsia spp. in ticks in northeast Missouri.

    PubMed

    Hudman, D A; Sargentini, N J

    2016-07-01

    We evaluated Amblyomma americanum (lone star tick) and Dermacentor variabilis (American dog tick) in northeast Missouri for the presence of Borrelia, Ehrlichia, and Rickettsia bacteria. We collected actively questing ticks from four sites within Adair County, Missouri. A total of 15,162 ticks were collected, of which 13,980 were grouped in 308 pools (lone star ticks, 288 pools; American dog ticks, 20 pools) and tested for presence/absence of bacteria using polymerase chain reaction. Infection rates were calculated as the maximum likelihood estimation (MLE) with 95% confidence intervals (CI). Of the 308 pools tested, 229 (74.4%) were infected with bacteria and the overall MLE of the infection rate per 100 ticks was calculated as 2.9% (CI 2.61-3.21). Infection rates varied among life stages, 28.6% (CI 23.89-33.97) in adults, 7.0% (CI 5.10-9.86) in nymphs, and 1.0% (CI 0.75-1.20) in larvae. In the 116 adult lone star pools, infection rates were calculated for Borrelia lonestari (1.4%), Borrelia spp. (2.7%), Ehrlichia chaffeensis (6.1%), Ehrlichia ewingii (3.3%), Rickettsia amblyommii (18.3%), and Rickettsia montanensis (0.4%). Infection rates for the 52 nymphal lone star pools were calculated as B. lonestari (1.03%), Borrelia spp. (0.40%), E. chaffeensis (2.02%), E. ewingii (0.24%), and R. amblyommii (2.70%). In the 20 adult American dog tick pools, infection rates were determined as E. chaffeensis (9.47%), E. ewingii (5.47%), and R. montanensis (8.06%). Eight Borrelia samples were sequenced with five 99-100% identical to B. burgdorferi (s.l.) and three 99% identical to B. lonestari. Eight samples were sequenced for E. chaffeensis (all 99-100% identical) and one sample was sequenced for E. ewingii (99% identical). Seven samples were sequenced for Rickettsia and three were 99% identical to R. montanensis and four were 100% identical to R. amblyommii. This study demonstrates B. lonestari, E. chaffeensis, E. ewingii, R. amblyommii, and R. montanensis in northeast

  2. New pharmacological treatment strategies for relapse prevention.

    PubMed

    Spanagel, Rainer; Vengeliene, Valentina

    2013-01-01

    Here we discuss treatment strategies that are based on pharmacological interventions to reduce craving and relapse in alcohol-dependent patients. We will first provide a historical overview about relapse prevention strategies. We will then review the development of disulfiram, naltrexone, acamprosate, and nalmefene and discuss their neurobiological modes of action. Then the concept of convergent genomic analysis will be introduced for the discovery of new molecular treatment targets. Finally, we will provide convincing evidence for the use of N-methyl-D-aspartate (NMDA) receptor channel blockers as substitution drugs. Important conclusions of this review are: (i) learning from other addictive substances is very helpful-e.g., substitution therapies as applied to opiate addiction for decades could also be translated to alcoholics, (ii) the glutamate theory of alcohol addiction provides a convincing framework for the use of NMDA receptor antagonists as substitution drugs for alcohol-dependent patients, (iii) a combination of behavioral and pharmacological therapies may be the optimal approach for future treatment strategies-one promising example concerns the pharmacological disruption of reconsolidation processes of alcohol cue memories, (iv) given that many neurotransmitter systems are affected by chronic alcohol consumption, numerous druggable targets have been identified; consequently, a "cocktail" of different compounds will further improve the treatment situation, (v) in silico psychopharmacology, such as drug repurposing will yield new medications, and finally, (vi) the whole organism has to be taken into consideration to provide the best therapy for our patients. In summary, there is no other field in psychiatric research that has, in recent years, yielded so many novel, druggable targets and innovative treatment strategies than for alcohol addiction. However, it will still be several years before the majority of the "treatment-seeking population" will benefit

  3. Relapse Prevention and the Five Rules of Recovery

    PubMed Central

    Melemis, Steven M.

    2015-01-01

    There are four main ideas in relapse prevention. First, relapse is a gradual process with distinct stages. The goal of treatment is to help individuals recognize the early stages, in which the chances of success are greatest. Second, recovery is a process of personal growth with developmental milestones. Each stage of recovery has its own risks of relapse. Third, the main tools of relapse prevention are cognitive therapy and mind-body relaxation, which are used to develop healthy coping skills. Fourth, most relapses can be explained in terms of a few basic rules. Educating clients in these rules can help them focus on what is important: 1) change your life (recovery involves creating a new life where it is easier to not use); 2) be completely honest; 3) ask for help; 4) practice self-care; and 5) don’t bend the rules. PMID:26339217

  4. Studies on the Plasmodium vivax relapse pattern in Delhi, India.

    PubMed

    Adak, T; Sharma, V P; Orlov, V S

    1998-07-01

    A five-year epidemiologic study of patients attending a malaria clinic in Delhi was conducted to find the relapse rate of infections with Plasmodium vivax, its seasonal correlation between the primary infection and subsequent relapses, the duration of the incubation period, and the patterns of relapse. By our definition, the relapse rate ranged from 23% to 44% depending on the duration of follow-up. The relapse pattern observed in the study clearly suggests the existence of both tropical and temperate zone types of P. vivax in the population characterized by distinct incubation periods and the possible existence of P. vivax subpopulations characterized by primary long incubation periods. The implication of different incubating forms of P. vivax on the epidemiology and control of malaria is also discussed. PMID:9684649

  5. Borreliacidal activity of Borrelia metal transporter A (BmtA) binding small molecules by manganese transport inhibition.

    PubMed

    Wagh, Dhananjay; Pothineni, Venkata Raveendra; Inayathullah, Mohammed; Liu, Song; Kim, Kwang-Min; Rajadas, Jayakumar

    2015-01-01

    Borrelia burgdorferi, the causative agent of Lyme disease, utilizes manganese (Mn) for its various metabolic needs. We hypothesized that blocking Mn transporter could be a possible approach to inhibit metabolic activity of this pathogen and eliminate the infection. We used a combination of in silico protein structure prediction together with molecular docking to target the Borrelia metal transporter A (BmtA), a single known Mn transporter in Borrelia and screened libraries of FDA approved compounds that could potentially bind to the predicted BmtA structure with high affinity. Tricyclic antihistamines such as loratadine, desloratadine, and 3-hydroxydesloratadine as well as yohimbine and tadalafil demonstrated a tight binding to the in silico folded BmtA transporter. We, then, tested borreliacidal activity and dose response of the shortlisted compounds from this screen using a series of in vitro assays. Amongst the probed compounds, desloratadine exhibited potent borreliacidal activity in vitro at and above 78 μg/mL (250 μM). Borrelia treated with lethal doses of desloratadine exhibited a significant loss of intracellular Mn specifically and a severe structural damage to the bacterial cell wall. Our results support the possibility of developing a novel, targeted therapy to treat Lyme disease by targeting specific metabolic needs of Borrelia. PMID:25709405

  6. Determinants of relapse periodicity in Plasmodium vivax malaria

    PubMed Central

    2011-01-01

    Plasmodium vivax is a major cause of febrile illness in endemic areas of Asia, Central and South America, and the horn of Africa. Plasmodium vivax infections are characterized by relapses of malaria arising from persistent liver stages of the parasite (hypnozoites) which can be prevented only by 8-aminoquinoline anti-malarials. Tropical P. vivax relapses at three week intervals if rapidly eliminated anti-malarials are given for treatment, whereas in temperate regions and parts of the sub-tropics P. vivax infections are characterized either by a long incubation or a long-latency period between illness and relapse - in both cases approximating 8-10 months. The epidemiology of the different relapse phenotypes has not been defined adequately despite obvious relevance to malaria control and elimination. The number of sporozoites inoculated by the anopheline mosquito is an important determinant of both the timing and the number of relapses. The intervals between relapses display a remarkable periodicity which has not been explained. Evidence is presented that the proportion of patients who have successive relapses is relatively constant and that the factor which activates hypnozoites and leads to regular interval relapse in vivax malaria is the systemic febrile illness itself. It is proposed that in endemic areas a large proportion of the population harbours latent hypnozoites which can be activated by a systemic illness such as vivax or falciparum malaria. This explains the high rates of vivax following falciparum malaria, the high proportion of heterologous genotypes in relapses, the higher rates of relapse in people living in endemic areas compared with artificial infection studies, and, by facilitating recombination between different genotypes, contributes to P. vivax genetic diversity particularly in low transmission settings. Long-latency P. vivax phenotypes may be more widespread and more prevalent than currently thought. These observations have important

  7. A Surface-Exposed Region of a Novel Outer Membrane Protein (P66) of Borrelia spp. Is Variable in Size and Sequence

    PubMed Central

    Bunikis, Jonas; Luke, Catherine J.; Bunikiene, Elena; Bergström, Sven; Barbour, Alan G.

    1998-01-01

    A model of the 66-kDa outer membrane protein (P66) of Lyme disease Borrelia spp. predicts a surface-exposed loop near the C terminus. This region contains an antigen commonly recognized by sera from Lyme disease patients. In the present study, this region of P66 and homologous proteins of other Borrelia spp. were further investigated by using monoclonal antibodies, epitope mapping of P66 of Borrelia burgdorferi, and DNA sequencing. A monoclonal antibody specific for B. burgdorferi bound to the portion of P66 that was accessible to proteolysis in situ. The linear epitope for the antibody was mapped within a variable segment of the surface-exposed region. To further study this protein, the complete gene of Borrelia hermsii for a protein homologous to P66 was cloned. The deduced protein was 589 amino acids in length and 58% identical to P66 of B. burgdorferi. The B. hermsii P66 protein was predicted to have a surface-exposed region in the same location as that of B. burgdorferi’s P66 protein. With primers designed on the basis of conserved sequences and PCR, we identified and cloned the same regions of P66 proteins of Borrelia turicatae, Borrelia parkeri, Borrelia coriaceae, and Borrelia anserina. The deduced protein sequences from all species demonstrated two conserved hydrophobic regions flanking a surface-exposed loop. The loop sequences were highly variable between different Borrelia spp. in both sequence and size, varying between 35 and 45 amino acids. Although the actual function of P66 of Borrelia spp. is unknown, the results suggest that its surface-exposed region is subject to selective pressure. PMID:9537355

  8. mGlu5 Receptors and Relapse to Cocaine-Seeking: The Role of Receptor Trafficking in Postrelapse Extinction Learning Deficits

    PubMed Central

    Knackstedt, Lori A.

    2016-01-01

    We have previously demonstrated that MTEP, an allosteric antagonist of mGlu5, infused into the nucleus accumbens attenuates relapse after abstinence from cocaine self-administration. MTEP infused into the dorsolateral striatum (dlSTR) does not alter relapse but has long-lasting effects on subsequent extinction learning. Here we tested whether systemic MTEP would prevent relapse after abstinence or alter extinction learning. We also investigated the mechanism of action by which intra-dlSTR MTEP on test day alters extinction on subsequent days. Animals self-administered cocaine for 12 days followed by abstinence for 20-21 days. MTEP (0.5–5 mg/kg IP) was administered prior to placement into the operant chamber for a context-primed relapse test. A separate group of animals received intra-dlSTR MTEP prior to the relapse test and were sacrificed day later. Systemic administration of MTEP attenuated abstinent-relapse without significantly affecting extinction learning. Surface biotinylation analysis of protein expression in the dlSTR revealed that, in cocaine animals, intra-dlSTR MTEP administration decreased mGlu5 surface expression and prevented changes in Arc and GluA1/GluA2 observed in their vehicle counterparts. Thus, blockade of mGlu5 receptors may be utilized in future treatment strategies for relapse prevention in humans, although the effects of chronic blockade on extinction learning should be further evaluated. PMID:26881139

  9. Genetically Modified T-cell Immunotherapy in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-08-10

    Adult Acute Myeloid Leukemia in Remission; Donor; Early Relapse of Acute Myeloid Leukemia; Late Relapse of Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  10. Relapses in patients with Henoch–Schönlein purpura

    PubMed Central

    Calvo-Río, Vanesa; Hernández, José Luis; Ortiz-Sanjuán, Francisco; Loricera, Javier; Palmou-Fontana, Natalia; González-Vela, Maria C.; González-Lamuño, Domingo; González-López, Marcos A.; Armesto, Susana; Blanco, Ricardo; González-Gay, Miguel A.

    2016-01-01

    Abstract To further investigate into the relapses of Henoch–Schönlein purpura (HSP), we analyzed the frequency, clinical features, and predictors of relapses in series of 417 unselected patients from a single center. After a median follow-up of 12 (interquartile range [IQR]: 2–38) years, almost one-third of the 417 patients (n = 133; 32%; 85 men/48 women) had experienced at least 1 relapse. At the time of disease diagnosis, patients who later experienced relapses had less commonly infections than those who never suffered flares (30.8% vs 41.9%; P = 0.03). In contrast, patients who experienced relapses had a longer duration of the first episode of palpable purpura than those without relapses (palpable purpura lasting >7 days; 80.0% vs 68.1%; P = 0.04). Abdominal pain (72.3% vs 62.3%; P = 0.03) and joint manifestations (27.8% vs 15.5%; P = 0.005) were also more common in patients who later developed relapses. In contrast, patients who never suffered relapses had a slightly higher frequency of fever at the time of disease diagnosis (9.3% vs 3.8%; P = 0.06). At the time of disease diagnosis, corticosteroids were more frequently given to patients who later had relapses of the disease (44% vs 32% in nonrelapsing patients; P = 0.03). Relapses generally occurred soon after the first episode of vasculitis. The median time from the diagnosis of HSP to the first relapse was 1 (IQR: 1–2) month. The median number of relapses was 1 (IQR 1–3). The main clinical features at the time of the relapse were cutaneous (88.7%), gastrointestinal (27.1%), renal (24.8%), and joint (16.5%) manifestations. After a mean ± standard deviation follow-up of 18.9 ± 9.8 years, complete recovery was observed in 110 (82.7%) of the 133 patients who had relapses. Renal sequelae (persistent renal involvement) was found in 11 (8.3%) of the patients with relapses. The best predictive factors for relapse were joint and gastrointestinal manifestations at HSP diagnosis (odds ratio [OR]: 2

  11. Outcome following late marrow relapse in childhood acute lymphoblastic leukemia

    SciTech Connect

    Chessells, J.; Leiper, A.; Rogers, D.

    1984-10-01

    Thirty-four children with acute lymphoblastic leukemia, who developed bone marrow relapse after treatment was electively stopped, received reinduction, consolidation, continuing therapy, and intrathecal (IT) methotrexate (MTX). Sixteen children who relapsed within six months of stopping treatment had a median second-remission duration of 26 weeks; all next relapses occurred in the bone marrow. In 18 children who relapsed later, the median duration of second remission was in excess of two years, but after a minimum of four years follow-up, 16 patients have so far relapsed again (six in the CNS). CNS relapse occurred as a next event in four of 17 children who received five IT MTX injections only and in two of 14 children who received additional regular IT MTX. Although children with late marrow relapses may achieve long second remissions, their long-term out-look is poor, and regular IT MTX does not afford adequate CNS prophylaxis. It remains to be seen whether more intensive chemotherapy, including high-dose chemoradiotherapy and bone marrow transplantation, will improve the prognosis in this group of patients.

  12. Detection of Borrelia burgdorferi sensu lato and spotted fever group rickettsiae in hard ticks (Acari, Ixodidae) parasitizing bats in Poland.

    PubMed

    Piksa, Krzysztof; Stańczak, Joanna; Biernat, Beata; Górz, Andrzej; Nowak-Chmura, Magdalena; Siuda, Krzysztof

    2016-04-01

    A total of 491 Ixodes vespertilionis and 8 Ixodes ricinus collected from bats and cave walls in southern Poland between 2010 and 2012 were examined by the polymerase chain reaction for tick-transmitted pathogens. PCR analysis for Borrelia burgdorferi s.l., Rickettsia spp., and Anaplasma phagocytophilum yielded negative results for all I. vespertilionis. DNA of Rickettsia helvetica was detected in three specimens of I. ricinus attached to Rhinolophus hipposideros or Myotis myotis, while Borrelia garinii was found in one tick parasitizing Myotis daubentonii. These pathogens were recorded for the first time in hard ticks that parasitized bats. PMID:26833325

  13. [An experimental study of the capacity of the rat mite Ornithonyssus bacoti (Hirst, 1913) to ingest, maintain and transmit Borrelia].

    PubMed

    Lopatina, Iu V; Vasil'eva, I S; Gutova, V P; Ershova, A S; Burakova, O V; Naumov, R L; Petrova, A D

    1999-01-01

    For the first time a possibility of the gamasina mites' O. bacoti participation in Lyme disease spirochetes' circulation has been demonstrated. It has been experimentally shown that Borrelia burgdorferi s.l. are received by O. bacoti, survive in them for at least 21 days and are transmitted to white mice through mites' bites. Mice's infestation has occurred in 23% of cases. It is suggested that other bloodsucking gamasina mites inhabiting the Lyme borreliosis reservoir rodents nests may be capable of participating in borrelia circulation in the Lyme disease endemic areas. PMID:10703202

  14. Individualized relapse prediction: personality measures and striatal and insular activity during reward-processing robustly predict relapse*

    PubMed Central

    Gowin, Joshua L.; Ball, Tali M.; Wittmann, Marc; Tapert, Susan F.; Paulus, Martin P.

    2015-01-01

    Background Nearly half of individuals with substance use disorders relapse in the year after treatment. A diagnostic tool to help clinicians make decisions regarding treatment does not exist for psychiatric conditions. Identifying individuals with high risk for relapse to substance use following abstinence has profound clinical consequences. This study aimed to develop neuroimaging as a robust tool to predict relapse. Methods 68 methamphetamine-dependent adults (15 female) were recruited from 28-day inpatient treatment. During treatment, participants completed a functional MRI scan that examined brain activation during reward processing. Patients were followed 1 year later to assess abstinence. We examined brain activation during reward processing between relapsing and abstaining individuals and employed three random forest prediction models (clinical and personality measures, neuroimaging measures, a combined model) to generate predictions for each participant regarding their relapse likelihood. Results 18 individuals relapsed. There were significant group by reward-size interactions for neural activation in the left insula and right striatum for rewards. Abstaining individuals showed increased activation for large, risky relative to small, safe rewards, whereas relapsing individuals failed to show differential activation between reward types. All three random forest models yielded good test characteristics such that a positive test for relapse yielded a likelihood ratio 2.63, whereas a negative test had a likelihood ratio of 0.48. Conclusions These findings suggest that neuroimaging can be developed in combination with other measures as an instrument to predict relapse, advancing tools providers can use to make decisions about individualized treatment of substance use disorders. PMID:25977206

  15. Refractory and/or Relapsing Cryptococcosis Associated with Acquired Immune Deficiency Syndrome: Clinical Features, Genotype, and Virulence Factors of Cryptococcus spp. Isolates.

    PubMed

    Nascimento, Erika; Vitali, Lucia H; Tonani, Ludmilla; Kress, Marcia R Von Zeska; Takayanagui, Osvaldo M; Martinez, Roberto

    2016-05-01

    Refractory and relapsing crytocococcosis in acquired immune deficiency syndrome (AIDS) patients have a poor prognosis. The risk factors for this complicated infection course were evaluated by comparing refractory and/or relapsing cryptococcosis in human immunodeficiency virus-coinfected patients (cohort 1) with another group of AIDS patients who adequately responded to antifungals (cohort 2). Except for one isolate of Cryptococcus gattii from a cohort 2 case, all other isolates were identified as Cryptococcus neoformans var. grubii, sex type α, genotype VNI, including Cryptococcus reisolated from the relapse or in the refractory state. No differences were observed with respect to Cryptococcus capsule size and in the melanin and phospholipase production. The cohort 1 patients presented higher prevalence of cryptococcemia, cerebral dissemination, chronic liver disease, and leucopenia, and have increased death rate. Apparently, the refractory and/or relapsing cryptococcosis in the AIDS patients were more related to the host and the extent of the infection than to the fungal characteristics. PMID:26928832

  16. Complete Genome Sequence of Borrelia afzelii K78 and Comparative Genome Analysis

    PubMed Central

    Schüler, Wolfgang; Bunikis, Ignas; Weber-Lehman, Jacqueline; Comstedt, Pär; Kutschan-Bunikis, Sabrina; Stanek, Gerold; Huber, Jutta; Meinke, Andreas; Bergström, Sven; Lundberg, Urban

    2015-01-01

    The main Borrelia species causing Lyme borreliosis in Europe and Asia are Borrelia afzelii, B. garinii, B. burgdorferi and B. bavariensis. This is in contrast to the United States, where infections are exclusively caused by B. burgdorferi. Until to date the genome sequences of four B. afzelii strains, of which only two include the numerous plasmids, are available. In order to further assess the genetic diversity of B. afzelii, the most common species in Europe, responsible for the large variety of clinical manifestations of Lyme borreliosis, we have determined the full genome sequence of the B. afzelii strain K78, a clinical isolate from Austria. The K78 genome contains a linear chromosome (905,949 bp) and 13 plasmids (8 linear and 5 circular) together presenting 1,309 open reading frames of which 496 are located on plasmids. With the exception of lp28-8, all linear replicons in their full length including their telomeres have been sequenced. The comparison with the genomes of the four other B. afzelii strains, ACA-1, PKo, HLJ01 and Tom3107, as well as the one of B. burgdorferi strain B31, confirmed a high degree of conservation within the linear chromosome of B. afzelii, whereas plasmid encoded genes showed a much larger diversity. Since some plasmids present in B. burgdorferi are missing in the B. afzelii genomes, the corresponding virulence factors of B. burgdorferi are found in B. afzelii on other unrelated plasmids. In addition, we have identified a species specific region in the circular plasmid, cp26, which could be used for species determination. Different non-coding RNAs have been located on the B. afzelii K78 genome, which have not previously been annotated in any of the published Borrelia genomes. PMID:25798594

  17. Novel methods for surveying reservoir hosts and vectors of Borrelia burgdorferi in Northern Minnesota

    NASA Astrophysics Data System (ADS)

    Seifert, Veronica Aili

    Lyme disease is the most prevalent tick-borne disease in North America and presents challenges to clinicians, researchers and the public in diagnosis, treatment and prevention. Lyme disease is caused by the spirochete, Borrelia burgdorferi, which is a zoonotic pathogen obligate upon hematophagous arthropod vectors and propagates in small mammal reservoir hosts. Identifying factors governing zoonotic diseases within regions of high-risk provides local health and agricultural agencies with necessary information to formulate public policy and implement treatment protocols to abate the rise and expansion of infectious disease outbreaks. In the United States, the documented primary reservoir host of Lyme disease is the white-footed mouse, Peromyscus leucopus, and the arthropod vector is the deer tick, Ixodes scapularis. Reducing the impact of Lyme disease will need novel methods for identifying both the reservoir host and the tick vector. The reservoir host, Peromyscus leucopus is difficult to distinguish from the virtually identical Peromyscus maniculatus that also is present in Northern Minnesota, a region where Lyme disease is endemic. Collection of the Ixodes tick, the Lyme disease vector, is difficult as this is season dependent and differs from year to year. This study develops new strategies to assess the extent of Borrelia burgdorferi in the local environment of Northern Minnesota. A selective and precise method to identify Peromyscus species was developed. This assay provides a reliable and definitive method to identify the reservoir host, Peromyscus leucopus from a physically identical and sympatric Peromyscus species, Peromyscus maniculatus. A new strategy to collect ticks for measuring the disbursement of Borrelia was employed. Students from local high schools were recruited to collect ticks. This strategy increased the available manpower to cover greater terrain, provided students with valuable experience in research methodology, and highlighted the

  18. In vitro susceptibilities of Borrelia burgdorferi to five oral cephalosporins and ceftriaxone.

    PubMed

    Agger, W A; Callister, S M; Jobe, D A

    1992-08-01

    We determined the in vitro susceptibilities of eight Borrelia burgdorferi isolates to five oral cephalosporins. MICs for B. burgdorferi 297 were 23 micrograms/ml (cephalexin), 45 micrograms/ml (cefadroxil), 91 micrograms/ml (cefaclor), 0.13 microgram/ml (cefuroxime), 0.8 microgram/ml (cefixime), and 0.02 microgram/ml (ceftriaxone). When B. burgdorferi isolates were exposed to concentrations twice the MIC of cefuroxime, cefixime, or ceftriaxone, at least 72 h of incubation was required to kill 99% of the organisms. PMID:1416868

  19. Statistical analysis of the distribution of amino acids in Borrelia burgdorferi genome under different genetic codes

    NASA Astrophysics Data System (ADS)

    García, José A.; Alvarez, Samantha; Flores, Alejandro; Govezensky, Tzipe; Bobadilla, Juan R.; José, Marco V.

    2004-10-01

    The genetic code is considered to be universal. In order to test if some statistical properties of the coding bacterial genome were due to inherent properties of the genetic code, we compared the autocorrelation function, the scaling properties and the maximum entropy of the distribution of distances of amino acids in sequences obtained by translating protein-coding regions from the genome of Borrelia burgdorferi, under different genetic codes. Overall our results indicate that these properties are very stable to perturbations made by altering the genetic code. We also discuss the evolutionary likely implications of the present results.

  20. Treating Multiply Relapsed or Refractory Hairy Cell Leukemia

    Cancer.gov

    In this trial, patients with hairy cell leukemia who have not responded or relapsed after initial chemotherapy will be randomly assigned to receive rituximab combined with either pentostatin or bendamustine.

  1. Novel treatment strategies for patients with relapsed classical Hodgkin lymphoma

    PubMed Central

    Jona, Adam; Younes, Anas

    2011-01-01

    The treatment of patients with relapsed and refractory Hodgkin lymphoma (HL), especially those who relapse after autologous stem cell transplantation, remains challenging. Patients with HL whose disease relapses after stem cell transplantation are rarely cured with current treatment modalities, and have a median survival is less than 3 years. With no new drugs have been approved by the FDA for HL in more than three decades, there is a clear unmet medical need for drug development for this patients population. New treatment strategies that are based on targeting oncogenic signaling pathways are currently explored. This review will focus on emerging new treatment modalities that are currently under investigation for patients with relapsed classical HL. PMID:20828898

  2. Treatment of a relapsing facial pyoderma gangrenosum (malignant pyoderma).

    PubMed

    Mantovani, Lucia; Zauli, Stefania; Sarno, Oriele; Querzoli, Patrizia; Corazza, Monica; Virgili, Annarosa

    2013-06-01

    A case of rapidly relapsing pyoderma gangrenosum (PG) of the left preauricular area with no undermined borders is described. This might be considered a case of malignant pyoderma (PM), a rare variety of PG. Five months after complete healing obtained with systemic corticosteroids, the preauricular lesion of PG relapsed. As retreatment with oral methylprednisolone induced glucose intolerance and high arterial pressure, sulfa drugs were initially employed with a transitory recovery of the skin lesion. A successive prolonged course with minocycline induced a new complete resolution. To date, at six months' follow-up, the patient is relapse-free. This case confirms that sulfa drugs and minocycline may also be considered alternative therapies in PM. PM is a variety of PG characterized by specific morphological features, a higher tendency to relapse, and poor responsiveness to treatment. PMID:23330662

  3. Three-Drug Combination for Relapsed Multiple Myeloma

    Cancer.gov

    A summary of Interim results from an international, randomized phase III trial that suggest that adding carfilzomib (Kyprolis®) to a standard treatment improves outcomes for patients with multiple myeloma whose cancer has relapsed.

  4. Geographic uniformity of the Lyme disease spirochete (Borrelia burgdorferi) and its shared history with tick vector (Ixodes scapularis) in the Northeastern United States.

    PubMed

    Qiu, Wei-Gang; Dykhuizen, Daniel E; Acosta, Michael S; Luft, Benjamin J

    2002-03-01

    Over 80% of reported cases of Lyme disease in the United States occur in coastal regions of northeastern and mid-Atlantic states. The genetic structure of the Lyme disease spirochete (Borrelia burgdorferi) and its main tick vector (Ixodes scapularis) was studied concurrently and comparatively by sampling natural populations of I. scapularis ticks along the East Coast from 1996 to 1998. Borrelia is genetically highly diverse at the outer surface protein ospC. Since Borrelia is highly clonal, the ospC alleles can be used to define clones. A newly designed reverse line blotting (RLB) assay shows that up to 10 Borrelia clones can infect a single tick. The clone frequencies in Borrelia populations are the same across the Northeast. On the other hand, I. scapularis populations show strong regional divergence (among northeastern, mid-Atlantic, and southern states) as well as local differentiation. The high genetic diversity within Borrelia populations and the disparity in the genetic structure between Borrelia and its tick vector are likely consequences of strong balancing selection on local Borrelia clones. Demographically, both Borrelia and I. scapularis populations in the Northeast show the characteristics of a species that has recently expanded from a population bottleneck. Major geological and ecological events, such as the last glacial maximum (18,000 years ago) and the modern-day expansion of tick habitats, are likely causes of the observed "founder effects" for the two organisms in the Northeast. We therefore conclude that the genetic structure of B. burgdorferi has been intimately shaped by the natural history of its main vector, the northern lineage of I. scapularis ticks. PMID:11901105

  5. Geographic uniformity of the Lyme disease spirochete (Borrelia burgdorferi) and its shared history with tick vector (Ixodes scapularis) in the Northeastern United States.

    PubMed Central

    Qiu, Wei-Gang; Dykhuizen, Daniel E; Acosta, Michael S; Luft, Benjamin J

    2002-01-01

    Over 80% of reported cases of Lyme disease in the United States occur in coastal regions of northeastern and mid-Atlantic states. The genetic structure of the Lyme disease spirochete (Borrelia burgdorferi) and its main tick vector (Ixodes scapularis) was studied concurrently and comparatively by sampling natural populations of I. scapularis ticks along the East Coast from 1996 to 1998. Borrelia is genetically highly diverse at the outer surface protein ospC. Since Borrelia is highly clonal, the ospC alleles can be used to define clones. A newly designed reverse line blotting (RLB) assay shows that up to 10 Borrelia clones can infect a single tick. The clone frequencies in Borrelia populations are the same across the Northeast. On the other hand, I. scapularis populations show strong regional divergence (among northeastern, mid-Atlantic, and southern states) as well as local differentiation. The high genetic diversity within Borrelia populations and the disparity in the genetic structure between Borrelia and its tick vector are likely consequences of strong balancing selection on local Borrelia clones. Demographically, both Borrelia and I. scapularis populations in the Northeast show the characteristics of a species that has recently expanded from a population bottleneck. Major geological and ecological events, such as the last glacial maximum (18,000 years ago) and the modern-day expansion of tick habitats, are likely causes of the observed "founder effects" for the two organisms in the Northeast. We therefore conclude that the genetic structure of B. burgdorferi has been intimately shaped by the natural history of its main vector, the northern lineage of I. scapularis ticks. PMID:11901105

  6. Recrudescence and relapse of meningococcal meningitis and septicaemia.

    PubMed

    Nielsen, P E; Thelle, T; Tvede, M

    1995-03-01

    Three cases of recrudescence and relapse of Neisseria meningitidis group B meningitis and septicaemia are reported. The recrudescence and relapses could not be explained by infectious foci, increased bacterial penicillin resistance or immunological defects. As a supplement to antibiotic treatment, all three patients received corticosteroids for the initial 2 days of treatment, and this may have contributed to the unusual course of the disease in our patient. PMID:7780262

  7. Relapse and rehospitalization: comparing oral and depot antipsychotics.

    PubMed

    Schooler, Nina R

    2003-01-01

    A review of studies that compared conventional oral and depot antipsychotic medications highlighted the following points. Mirror-image studies in which patients served as their own controls provided evidence of substantial benefit for depot injectable medications. The randomized clinical trials did not, in general, support the findings of significant decrease in relapse rates between these 2 routes of administration. Across the studies reviewed, the 1-year relapse rate for long-acting depot medication was 27% compared with 42% for patients who received oral medication. The 27% risk of relapse in patients who received guaranteed depot medication suggests that relapse is not always driven by noncompliance. In the only study that lasted for 2 years, the risk of relapse decreased substantially in the depot-treated patients, suggesting that risk of noncompliance may be a more important factor in relapse over extended periods of time. A recent formal meta-analytic review of depot medications concluded that this route of administration resulted in clinical advantages in terms of global outcome. PMID:14680414

  8. Relapsed neuroblastomas show frequent RAS-MAPK pathway mutations.

    PubMed

    Eleveld, Thomas F; Oldridge, Derek A; Bernard, Virginie; Koster, Jan; Daage, Leo Colmet; Diskin, Sharon J; Schild, Linda; Bentahar, Nadia Bessoltane; Bellini, Angela; Chicard, Mathieu; Lapouble, Eve; Combaret, Valérie; Legoix-Né, Patricia; Michon, Jean; Pugh, Trevor J; Hart, Lori S; Rader, JulieAnn; Attiyeh, Edward F; Wei, Jun S; Zhang, Shile; Naranjo, Arlene; Gastier-Foster, Julie M; Hogarty, Michael D; Asgharzadeh, Shahab; Smith, Malcolm A; Guidry Auvil, Jaime M; Watkins, Thomas B K; Zwijnenburg, Danny A; Ebus, Marli E; van Sluis, Peter; Hakkert, Anne; van Wezel, Esther; van der Schoot, C Ellen; Westerhout, Ellen M; Schulte, Johannes H; Tytgat, Godelieve A; Dolman, M Emmy M; Janoueix-Lerosey, Isabelle; Gerhard, Daniela S; Caron, Huib N; Delattre, Olivier; Khan, Javed; Versteeg, Rogier; Schleiermacher, Gudrun; Molenaar, Jan J; Maris, John M

    2015-08-01

    The majority of patients with neuroblastoma have tumors that initially respond to chemotherapy, but a large proportion will experience therapy-resistant relapses. The molecular basis of this aggressive phenotype is unknown. Whole-genome sequencing of 23 paired diagnostic and relapse neuroblastomas showed clonal evolution from the diagnostic tumor, with a median of 29 somatic mutations unique to the relapse sample. Eighteen of the 23 relapse tumors (78%) showed mutations predicted to activate the RAS-MAPK pathway. Seven of these events were detected only in the relapse tumor, whereas the others showed clonal enrichment. In neuroblastoma cell lines, we also detected a high frequency of activating mutations in the RAS-MAPK pathway (11/18; 61%), and these lesions predicted sensitivity to MEK inhibition in vitro and in vivo. Our findings provide a rationale for genetic characterization of relapse neuroblastomas and show that RAS-MAPK pathway mutations may function as a biomarker for new therapeutic approaches to refractory disease. PMID:26121087

  9. Relapsed neuroblastomas show frequent RAS-MAPK pathway mutations

    PubMed Central

    Eleveld, Thomas F.; Oldridge, Derek A.; Bernard, Virginie; Koster, Jan; Daage, Leo Colmet; Diskin, Sharon J.; Schild, Linda; Bentahar, Nadia Bessoltane; Bellini, Angela; Chicard, Mathieu; Lapouble, Eve; Combaret, Valérie; Legoix-Né, Patricia; Michon, Jean; Pugh, Trevor J.; Hart, Lori S.; Rader, JulieAnn; Attiyeh, Edward F.; Wei, Jun S.; Zhang, Shile; Naranjo, Arlene; Gastier-Foster, Julie M.; Hogarty, Michael D.; Asgharzadeh, Shahab; Smith, Malcolm A.; Guidry Auvil, Jaime M.; Watkins, Thomas B. K.; Zwijnenburg, Danny A.; Ebus, Marli E.; van Sluis, Peter; Hakkert, Anne; van Wezel, Esther; van der Schoot, C. Ellen; Westerhout, Ellen M.; Schulte, Johannes H.; Tytgat, Godelieve A.; Dolman, M. Emmy M.; Janoueix-Lerosey, Isabelle; Gerhard, Daniela S.; Caron, Huib N.; Delattre, Olivier; Khan, Javed; Versteeg, Rogier; Schleiermacher, Gudrun; Molenaar, Jan J.; Maris, John M.

    2016-01-01

    The majority of neuroblastoma patients have tumors that initially respond to chemotherapy, but a large proportion of patients will experience therapy-resistant relapses. The molecular basis of this aggressive phenotype is unknown. Whole genome sequencing of 23 paired diagnostic and relapsed neuroblastomas showed clonal evolution from the diagnostic tumor with a median of 29 somatic mutations unique to the relapse sample. Eighteen of the 23 relapse tumors (78%) showed mutations predicted to activate the RAS-MAPK signaling pathway. Seven events were detected only in the relapse tumor while the others showed clonal enrichment. In neuroblastoma cell lines we also detected a high frequency of activating mutations in the RAS-MAPK pathway (11/18, 61%) and these lesions predicted for sensitivity to MEK inhibition in vitro and in vivo. Our findings provide the rationale for genetic characterization of relapse neuroblastoma and show that RAS-MAPK pathway mutations may function as a biomarker for new therapeutic approaches to refractory disease. PMID:26121087

  10. Aggressive chemotherapy for acute leukemia relapsed after transplantation.

    PubMed

    Sica, S; Salutari, P; Di Mario, A; D'Onofrio, G; Etuk, B; Leone, G

    1994-09-01

    Bone marrow transplantation procedure has emerged as an effective treatment for hematological malignancies. However, recurrence of leukemia is still the major cause of treatment failure. Subsequent treatment in this category of patients, generally considered incurable, has not been yet standardized. At our institution, 13 patients, 7 with acute non lymphoid leukemia (ANLL) and 6 with acute lymphoid leukemia (ALL), were treated at relapse after bone marrow transplantation either autologous or allogeneic (AuBMT 8, ABMT 4) performed in complete remission (CR). The interval between BMT and relapse was less than 9 months in 6 patients (2 ABMT and 4 AuBMT) and more than 9 months in 7 patients. Early relapsed patients showed no response to treatment and died at a median of 5.5 months (range 1-13) after relapse. Late relapse after BMT was characterized by a high percentage of response (5 CR and 1 PR), particularly after intensive chemotherapy and by a longer survival (median 14 months; range 2-36). Chemotherapy after transplantation should be carefully evaluated in patients relapsed after BMT in order to select a population that can achieve long term disease free survival. PMID:7858490

  11. Adoptive transfer of murine relapsing experimental allergic encephalomyelitis.

    PubMed

    Lublin, F D

    1985-02-01

    Relapsing experimental allergic encephalomyelitis (EAE), an autoimmune disorder resembling multiple sclerosis, has been produced by inoculating SJL/J mice with spinal cord or myelin basic protein in appropriate adjuvants. To determine whether initially sensitized lymphocytes or the persistence of antigen depots in the animal were responsible for the relapsing episodes of inflammatory demyelination, adoptive transfer studies were undertaken utilizing lymphocytes from relapsing EAE-immunized donors transferred directly or after in vitro culture. In direct-transfer studies donor lymphocytes produced clinical and pathological signs of relapsing EAE in 3 of 7 recipients of lymph node lymphocytes and 1 of 5 recipients of splenic lymphocytes. In vitro culture of lymphocytes in myelin basic protein or T cell growth factor prior to transfer increased both the incidence of disease and the number of animals having relapses, and allowed transfer with fewer lymphocytes. Because all animals had delayed onset of disease, this study demonstrates that the ability to develop relapsing inflammatory demyelination is transferable with lymphocytes and does not require the presence of antigen. PMID:3977301

  12. Radiation-induced acid ceramidase confers prostate cancer resistance and tumor relapse

    PubMed Central

    Cheng, Joseph C.; Bai, Aiping; Beckham, Thomas H.; Marrison, S. Tucker; Yount, Caroline L.; Young, Katherine; Lu, Ping; Bartlett, Anne M.; Wu, Bill X.; Keane, Barry J.; Armeson, Kent E.; Marshall, David T.; Keane, Thomas E.; Smith, Michael T.; Jones, E. Ellen; Drake, Richard R.; Bielawska, Alicja; Norris, James S.; Liu, Xiang

    2013-01-01

    Escape of prostate cancer (PCa) cells from ionizing radiation–induced (IR-induced) killing leads to disease progression and cancer relapse. The influence of sphingolipids, such as ceramide and its metabolite sphingosine 1-phosphate, on signal transduction pathways under cell stress is important to survival adaptation responses. In this study, we demonstrate that ceramide-deacylating enzyme acid ceramidase (AC) was preferentially upregulated in irradiated PCa cells. Radiation-induced AC gene transactivation by activator protein 1 (AP-1) binding on the proximal promoter was sensitive to inhibition of de novo ceramide biosynthesis, as demonstrated by promoter reporter and ChIP-qPCR analyses. Our data indicate that a protective feedback mechanism mitigates the apoptotic effect of IR-induced ceramide generation. We found that deregulation of c-Jun induced marked radiosensitization in vivo and in vitro, which was rescued by ectopic AC overexpression. AC overexpression in PCa clonogens that survived a fractionated 80-Gy IR course was associated with increased radioresistance and proliferation, suggesting a role for AC in radiotherapy failure and relapse. Immunohistochemical analysis of human PCa tissues revealed higher levels of AC after radiotherapy failure than those in therapy-naive PCa, prostatic intraepithelial neoplasia, or benign tissues. Addition of an AC inhibitor to an animal model of xenograft irradiation produced radiosensitization and prevention of relapse. These data indicate that AC is a potentially tractable target for adjuvant radiotherapy. PMID:24091326

  13. Radiation-induced acid ceramidase confers prostate cancer resistance and tumor relapse.

    PubMed

    Cheng, Joseph C; Bai, Aiping; Beckham, Thomas H; Marrison, S Tucker; Yount, Caroline L; Young, Katherine; Lu, Ping; Bartlett, Anne M; Wu, Bill X; Keane, Barry J; Armeson, Kent E; Marshall, David T; Keane, Thomas E; Smith, Michael T; Jones, E Ellen; Drake, Richard R; Bielawska, Alicja; Norris, James S; Liu, Xiang

    2013-10-01

    Escape of prostate cancer (PCa) cells from ionizing radiation-induced (IR-induced) killing leads to disease progression and cancer relapse. The influence of sphingolipids, such as ceramide and its metabolite sphingosine 1-phosphate, on signal transduction pathways under cell stress is important to survival adaptation responses. In this study, we demonstrate that ceramide-deacylating enzyme acid ceramidase (AC) was preferentially upregulated in irradiated PCa cells. Radiation-induced AC gene transactivation by activator protein 1 (AP-1) binding on the proximal promoter was sensitive to inhibition of de novo ceramide biosynthesis, as demonstrated by promoter reporter and ChIP-qPCR analyses. Our data indicate that a protective feedback mechanism mitigates the apoptotic effect of IR-induced ceramide generation. We found that deregulation of c-Jun induced marked radiosensitization in vivo and in vitro, which was rescued by ectopic AC overexpression. AC overexpression in PCa clonogens that survived a fractionated 80-Gy IR course was associated with increased radioresistance and proliferation, suggesting a role for AC in radiotherapy failure and relapse. Immunohistochemical analysis of human PCa tissues revealed higher levels of AC after radiotherapy failure than those in therapy-naive PCa, prostatic intraepithelial neoplasia, or benign tissues. Addition of an AC inhibitor to an animal model of xenograft irradiation produced radiosensitization and prevention of relapse. These data indicate that AC is a potentially tractable target for adjuvant radiotherapy. PMID:24091326

  14. Inter- and intra-specific pan-genomes of Borrelia burgdorferi sensu lato: genome stability and adaptive radiation

    PubMed Central

    2013-01-01

    Background Lyme disease is caused by spirochete bacteria from the Borrelia burgdorferi sensu lato (B. burgdorferi s.l.) species complex. To reconstruct the evolution of B. burgdorferi s.l. and identify the genomic basis of its human virulence, we compared the genomes of 23 B. burgdorferi s.l. isolates from Europe and the United States, including B. burgdorferi sensu stricto (B. burgdorferi s.s., 14 isolates), B. afzelii (2), B. garinii (2), B. “bavariensis” (1), B. spielmanii (1), B. valaisiana (1), B. bissettii (1), and B. “finlandensis” (1). Results Robust B. burgdorferi s.s. and B. burgdorferi s.l. phylogenies were obtained using genome-wide single-nucleotide polymorphisms, despite recombination. Phylogeny-based pan-genome analysis showed that the rate of gene acquisition was higher between species than within species, suggesting adaptive speciation. Strong positive natural selection drives the sequence evolution of lipoproteins, including chromosomally-encoded genes 0102 and 0404, cp26-encoded ospC and b08, and lp54-encoded dbpA, a07, a22, a33, a53, a65. Computer simulations predicted rapid adaptive radiation of genomic groups as population size increases. Conclusions Intra- and inter-specific pan-genome sizes of B. burgdorferi s.l. expand linearly with phylogenetic diversity. Yet gene-acquisition rates in B. burgdorferi s.l. are among the lowest in bacterial pathogens, resulting in high genome stability and few lineage-specific genes. Genome adaptation of B. burgdorferi s.l. is driven predominantly by copy-number and sequence variations of lipoprotein genes. New genomic groups are likely to emerge if the current trend of B. burgdorferi s.l. population expansion continues. PMID:24112474

  15. Canine infection with Dirofilaria immitis, Borrelia burgdorferi, Anaplasma spp., and Ehrlichia spp. in the United States, 2010–2012

    PubMed Central

    2014-01-01

    Background The geographic distribution of canine infection with vector-borne disease agents in the United States appears to be expanding. Methods To provide an updated assessment of geographic trends in canine infection with Dirofilaria immitis, Borrelia burgdorferi, Ehrlichia spp., and Anaplasma spp., we evaluated results from an average of 3,588,477 dogs tested annually by veterinarians throughout the United States from 2010 – 2012. Results As in an earlier summary report, the percent positive test results varied by agent and region, with antigen of D. immitis and antibody to Ehrlichia spp. most commonly identified in the Southeast (2.9% and 3.2%, respectively) and antibody to both B. burgdorferi and Anaplasma spp. most commonly identified in the Northeast (13.3% and 7.1%, respectively) and upper Midwest (4.4% and 3.9%, respectively). Percent positive test results for D. immitis antigen were lower in every region considered, including in the Southeast, than previously reported. Percent positive test results for antibodies to B. burgdorferi and Ehrlichia spp. were higher nationally than previously reported, and, for antibodies to Anaplasma spp., were higher in the Northeast but lower in the Midwest and West, than in the initial report. Annual reports of human cases of Lyme disease, ehrlichiosis, and anaplasmosis were associated with percent positive canine test results by state for each respective tick-borne disease agent (R2 = 0.701, 0.457, and 0.314, respectively). Within endemic areas, percent positive test results for all three tick-borne agents demonstrated evidence of geographic expansion. Conclusions Continued national monitoring of canine test results for vector-borne zoonotic agents is an important tool for accurately mapping the geographic distribution of these agents, and greatly aids our understanding of the veterinary and public health threats they pose. PMID:24886589

  16. Outer surface protein OspC is an antiphagocytic factor that protects Borrelia burgdorferi from phagocytosis by macrophages.

    PubMed

    Carrasco, Sebastian E; Troxell, Bryan; Yang, Youyun; Brandt, Stephanie L; Li, Hongxia; Sandusky, George E; Condon, Keith W; Serezani, C Henrique; Yang, X Frank

    2015-12-01

    Outer surface protein C (OspC) is one of the major lipoproteins expressed on the surface of Borrelia burgdorferi during tick feeding and the early phase of mammalian infection. OspC is required for B. burgdorferi to establish infection in both immunocompetent and SCID mice and has been proposed to facilitate evasion of innate immune defenses. However, the exact biological function of OspC remains elusive. In this study, we showed that the ospC-deficient spirochete could not establish infection in NOD-scid IL2rγ(null) mice that lack B cells, T cells, NK cells, and lytic complement. The ospC mutant also could not establish infection in anti-Ly6G-treated SCID and C3H/HeN mice (depletion of neutrophils). However, depletion of mononuclear phagocytes at the skin site of inoculation in SCID and C3H/HeN mice allowed the ospC mutant to establish infection in vivo. In phagocyte-depleted mice, the ospC mutant was able to colonize the joints and triggered neutrophilia during dissemination. Furthermore, we found that phagocytosis of green fluorescent protein (GFP)-expressing ospC mutant spirochetes by murine peritoneal macrophages and human THP-1 macrophage-like cells, but not in PMN-HL60, was significantly higher than parental wild-type B. burgdorferi strains, suggesting that OspC has an antiphagocytic property. In addition, overproduction of OspC in spirochetes also decreased the uptake of spirochetes by murine peritoneal macrophages. Together, our findings provide evidence that mononuclear phagocytes play a key role in clearance of the ospC mutant and that OspC promotes spirochetes' evasion of macrophages during early Lyme borreliosis. PMID:26438793

  17. In Vivo Imaging Demonstrates That Borrelia burgdorferi ospC Is Uniquely Expressed Temporally and Spatially throughout Experimental Infection.

    PubMed

    Skare, Jonathan T; Shaw, Dana K; Trzeciakowski, Jerome P; Hyde, Jenny A

    2016-01-01

    Borrelia burgdorferi is a spirochetal bacterium transmitted by the Ixodes tick that causes Lyme disease in humans due to its ability to evade the host immune response and disseminate to multiple immunoprotective tissues. The pathogen undergoes dynamic genetic alterations important for adaptation from the tick vector to the mammalian host, but little is known regarding the changes at the transcriptional level within the distal tissues they colonize. In this study, B. burgdorferi infection and gene expression of the essential virulence determinant ospC was quantitatively monitored in a spatial and temporal manner utilizing reporter bioluminescent borrelial strains with in vivo and ex vivo imaging. Although expressed from a shuttle vector, the PospC-luc construct exhibited a similar expression pattern relative to native ospC. Bacterial burden in skin, inguinal lymph node, heart, bladder and tibiotarsal joint varied between tissues and fluctuated over the course of infection possibly in response to unique cues of each microenvironment. Expression of ospC, when normalized for changes in bacterial load, presented unique profiles in murine tissues at different time points. The inguinal lymph node was infected with a significant B. burgdorferi burden, but showed minimal ospC expression. B. burgdorferi infected skin and heart induced expression of ospC early during infection while the bladder and tibiotarsal joint continued to display PospC driven luminescence throughout the 21 day time course. Localized skin borrelial burden increased dramatically in the first 96 hours following inoculation, which was not paralleled with an increase in ospC expression, despite the requirement of ospC for dermal colonization. Quantitation of bioluminescence representing ospC expression in individual tissues was validated by qRT-PCR of the native ospC transcript. Taken together, the temporal regulation of ospC expression in distal tissues suggests a role for this virulence determinant beyond

  18. Outer Surface Protein OspC Is an Antiphagocytic Factor That Protects Borrelia burgdorferi from Phagocytosis by Macrophages

    PubMed Central

    Carrasco, Sebastian E.; Troxell, Bryan; Yang, Youyun; Brandt, Stephanie L.; Li, Hongxia; Sandusky, George E.; Condon, Keith W.

    2015-01-01

    Outer surface protein C (OspC) is one of the major lipoproteins expressed on the surface of Borrelia burgdorferi during tick feeding and the early phase of mammalian infection. OspC is required for B. burgdorferi to establish infection in both immunocompetent and SCID mice and has been proposed to facilitate evasion of innate immune defenses. However, the exact biological function of OspC remains elusive. In this study, we showed that the ospC-deficient spirochete could not establish infection in NOD-scid IL2rγnull mice that lack B cells, T cells, NK cells, and lytic complement. The ospC mutant also could not establish infection in anti-Ly6G-treated SCID and C3H/HeN mice (depletion of neutrophils). However, depletion of mononuclear phagocytes at the skin site of inoculation in SCID and C3H/HeN mice allowed the ospC mutant to establish infection in vivo. In phagocyte-depleted mice, the ospC mutant was able to colonize the joints and triggered neutrophilia during dissemination. Furthermore, we found that phagocytosis of green fluorescent protein (GFP)-expressing ospC mutant spirochetes by murine peritoneal macrophages and human THP-1 macrophage-like cells, but not in PMN-HL60, was significantly higher than parental wild-type B. burgdorferi strains, suggesting that OspC has an antiphagocytic property. In addition, overproduction of OspC in spirochetes also decreased the uptake of spirochetes by murine peritoneal macrophages. Together, our findings provide evidence that mononuclear phagocytes play a key role in clearance of the ospC mutant and that OspC promotes spirochetes' evasion of macrophages during early Lyme borreliosis. PMID:26438793

  19. Prevalence of the Lyme Disease Spirochete, Borrelia burgdorferi, in Blacklegged Ticks, Ixodes scapularis at Hamilton-Wentworth, Ontario.

    PubMed

    Scott, John D; Anderson, John F; Durden, Lance A; Smith, Morgan L; Manord, Jodi M; Clark, Kerry L

    2016-01-01

    Lyme disease has emerged as a major health concern in Canada, where the etiological agent, Borrelia burgdorferi sensu lato (s.l.), a spirochetal bacterium, is typically spread by the bite of certain ticks. This study explores the presence of B. burgdorferi s.l. in blacklegged ticks, Ixodes scapularis, collected at Dundas, Ontario (a locality within the region of Hamilton-Wentworth). Using passive surveillance, veterinarians and pet groomers were asked to collect blacklegged ticks from dogs and cats with no history of travel. Additionally, I. scapularis specimens were submitted from local residents and collected by flagging. Overall, 12 (41%) of 29 blacklegged ticks were infected with B. burgdorferi s.l. Using polymerase chain reaction (PCR) and DNA sequencing, two borrelial amplicons were characterized as B. burgdorferi sensu stricto (s.s.), a genospecies pathogenic to humans and certain domestic animals. Notably, three different vertebrate hosts each had two engorged I. scapularis females removed on the same day and, likewise, one cat had three repeat occurrences of this tick species. These multiple infestations suggest that a population of I. scapularis may be established in this area. The local public health unit has been underreporting the presence of B. burgdorferi s.l.-infected I. scapularis in the area encompassing Dundas. Our findings raise concerns about the need to erect tick warning signs in parkland areas. Veterinarians, medical professionals, public health officials, and the general public must be vigilant that Lyme disease-carrying blacklegged ticks pose a public health risk in the Dundas area and the surrounding Hamilton-Wentworth region. PMID:27226771

  20. Prevalence of the Lyme Disease Spirochete, Borrelia burgdorferi, in Blacklegged Ticks, Ixodes scapularis at Hamilton-Wentworth, Ontario

    PubMed Central

    Scott, John D.; Anderson, John F.; Durden, Lance A.; Smith, Morgan L.; Manord, Jodi M.; Clark, Kerry L.

    2016-01-01

    Lyme disease has emerged as a major health concern in Canada, where the etiological agent, Borrelia burgdorferi sensu lato (s.l.), a spirochetal bacterium, is typically spread by the bite of certain ticks. This study explores the presence of B. burgdorferi s.l. in blacklegged ticks, Ixodes scapularis, collected at Dundas, Ontario (a locality within the region of Hamilton-Wentworth). Using passive surveillance, veterinarians and pet groomers were asked to collect blacklegged ticks from dogs and cats with no history of travel. Additionally, I. scapularis specimens were submitted from local residents and collected by flagging. Overall, 12 (41%) of 29 blacklegged ticks were infected with B. burgdorferi s.l. Using polymerase chain reaction (PCR) and DNA sequencing, two borrelial amplicons were characterized as B. burgdorferi sensu stricto (s.s.), a genospecies pathogenic to humans and certain domestic animals. Notably, three different vertebrate hosts each had two engorged I. scapularis females removed on the same day and, likewise, one cat had three repeat occurrences of this tick species. These multiple infestations suggest that a population of I. scapularis may be established in this area. The local public health unit has been underreporting the presence of B. burgdorferi s.l.-infected I. scapularis in the area encompassing Dundas. Our findings raise concerns about the need to erect tick warning signs in parkland areas. Veterinarians, medical professionals, public health officials, and the general public must be vigilant that Lyme disease-carrying blacklegged ticks pose a public health risk in the Dundas area and the surrounding Hamilton-Wentworth region. PMID:27226771