442
Views
29
CrossRef citations to date
0
Altmetric
Review

Progress in the molecular diagnosis of Lyme disease

&
Pages 19-30 | Received 24 Aug 2016, Accepted 07 Oct 2016, Published online: 28 Nov 2016

References

  • Margos G, Vollmer SA, Ogden NH, et al. Population genetics, taxonomy, phylogeny and evolution of Borrelia burgdorferi sensu lato. Infect Genet Evol. 2011;11(7):1545–1563.
  • Stanek G, Reiter M. The expanding Lyme Borrelia complex–clinical significance of genomic species? Clin Microbiol Infect. 2011;17(4):487–493.
  • Leydet BF Jr, Liang FT. Similarities in murine infection and immune response to Borrelia bissettii and Borrelia burgdorferi sensu stricto. Microbiology (Reading, England). 2015;161(12):2352–2360.
  • Pritt BS, Respicio-Kingry LB, Sloan LM, et al. Borrelia mayonii sp. nov., a member of the Borrelia burgdorferi sensu lato complex, detected in patients and ticks in the upper midwestern United States. Int J Syst Evol Microbiol. 2016;16:556–564.
  • Golovchenko M, Vancová M, Clark K, et al. A divergent spirochete strain isolated from a resident of the southeastern United States was identified by multilocus sequence typing as Borrelia bissettii. Parasit Vectors. 2016;9:68.
  • Adeolu M, Gupta RS. A phylogenomic and molecular marker based proposal for the division of the genus Borrelia into two genera: the emended genus Borrelia containing only the members of the relapsing fever Borrelia, and the genus Borreliella gen. nov. containing the members of the Lyme disease Borrelia (Borrelia burgdorferi sensu lato complex). Antonie Van Leeuwenhoek. 2014;105(6):1049–1072.
  • Mannelli A, Bertolotti L, Gern L, et al. Ecology of Borrelia burgdorferi sensu lato in Europe: transmission dynamics in multi-host systems, influence of molecular processes and effects of climate change. FEMS Microbiol Rev. 2012;36(4):837–861.
  • Eisen LLR. Vectors of Borrelia burgdorferi sensu lato. In: Gray JS, Kahl O, Lane RS, Stanek G, editors. Lyme borreliosis. Biology, epidemiology and control. Oxon: CABI Publishing; 2002. p. 91–116.
  • Stanek G, Wormser GP, Gray J, et al. Lyme borreliosis. Lancet. 2012;379(9814):461–473.
  • des Vignes F, Piesman J, Heffernan R, et al. Effect of tick removal on transmission of Borrelia burgdorferi and Ehrlichia phagocytophila by Ixodes scapularis nymphs. J Infect Dis. 2001;183(5):773–778.
  • Peavey CA, Lane RS. Transmission of Borrelia burgdorferi by Ixodes pacificus nymphs and reservoir competence of deer mice (Peromyscus maniculatus) infected by tick-bite. J Parasitol. 1995;81(2):175–178.
  • Cook MJ. Lyme borreliosis: a review of data on transmission time after tick attachment. Int J Gen Med. 2015;8:1–8.
  • Kurtenbach K, Dizij A, Seitz HM, et al. Differential immune responses to Borrelia burgdorferi in European wild rodent species influence spirochete transmission to Ixodes ricinus L. (Acari: Ixodidae). Infect Immun. 1994;62(12):5344–5352.
  • Tälleklint L, Jaenson TG, Mather TN. Seasonal variation in the capacity of the bank vole to infect larval ticks (Acari: ixodidae) with the Lyme disease spirochete, Borrelia burgdorferi. J Med Entomol. 1993;30(4):812–815.
  • Singh SK, Girschick HJ. Molecular survival strategies of the Lyme disease spirochete Borrelia burgdorferi. Lancet Infect Dis. 2004;4(9):575–583.
  • Comstedt P, Jakobsson T, Bergström S. Global ecology and epidemiology of Borrelia garinii spirochetes. Infect Ecol Epidemiol. 2011;1:9545.
  • Casjens SR, Mongodin EF, Qiu WG, et al. Genome stability of Lyme disease spirochetes: comparative genomics of Borrelia burgdorferi plasmids. Plos One. 2012;7(3):e33280.
  • Ojaimi C, Davidson BE, Saint Girons I, et al. Conservation of gene arrangement and an unusual organization of rRNA genes in the linear chromosomes of the Lyme disease spirochaetes Borrelia burgdorferi, B. garinii and B. afzelii. Microbiology. 1994;140(Pt 11):2931–2940.
  • Steere AC. Lyme borreliosis in 2005, 30 years after initial observations in Lyme Connecticut. Wien Klin Wochenschr. 2006;118(21–22):625–633.
  • Strle K, Jones KL, Drouin EE, et al. Borrelia burgdorferi RST1 (OspC type A) genotype is associated with greater inflammation and more severe Lyme disease. Am J Pathol. 2011;178(6):2726–2739.
  • Petzke M, Schwartz I. Borrelia burgdorferi pathogenesis and the immune response. Clin Lab Med. 2015;35(4):745–764.
  • Sykes RA, Makiello P. An estimate of Lyme borreliosis incidence in Western Europedagger. J Public Health (Bangkok). 2016:1–8.
  • NIJZ. Epidemiološko spremljanje nalezljivih bolezni v Sloveniji v letu 2014. Ljubljana: NIJZ; 2015.
  • Nelson CA, Saha S, Kugeler KJ, et al. Incidence of clinician-diagnosed lyme disease, United States, 2005-2010. Emerg Infect Dis. 2015;21(9):1625–1631.
  • Aguero-Rosenfeld ME, Wang G, Schwartz I, et al. Diagnosis of lyme borreliosis. Clin Microbiol Rev. 2005;18(3):484–509.
  • Cameron DJ, Johnson LB, Maloney EL. Evidence assessments and guideline recommendations in Lyme disease: the clinical management of known tick bites, erythema migrans rashes and persistent disease. Expert Rev Anti Infect Ther. 2014;12(9):1103–1135.
  • Marques AR. Laboratory diagnosis of Lyme disease: advances and challenges. Infect Dis Clin North Am. 2015;29(2):295–307.
  • Leeflang MM, Ang CW, Berkhout J, et al. The diagnostic accuracy of serological tests for Lyme borreliosis in Europe: a systematic review and meta-analysis. BMC Infect Dis. 2016;16:140.
  • Ružić-Sabljić E, Maraspin V, Cimperman J, et al. Comparison of isolation rate of Borrelia burgdorferi sensu lato in two different culture media, MKP and BSK-H. Clin Microbiol Infect. 2014;20(7):636–641.
  • O’Rourke M, Traweger A, Lusa L, et al. Quantitative detection of Borrelia burgdorferi sensu lato in erythema migrans skin lesions using internally controlled duplex real time PCR. Plos One. 2013;8(5):e63968.
  • Ogrinc K, Lotrič-Furlan S, Maraspin V, et al. Suspected early Lyme neuroborreliosis in patients with erythema migrans. Clin Infect Dis. 2013;57(4):501–509.
  • Cerar T, Ogrinc K, Cimperman J, et al. Validation of cultivation and PCR methods for diagnosis of Lyme neuroborreliosis. J Clin Microbiol. 2008;46(10):3375–3379.
  • Wormser GP, Bittker S, Cooper D, et al. Comparison of the yields of blood cultures using serum or plasma from patients with early Lyme disease. J Clin Microbiol. 2000;38(4):1648–1650.
  • Wormser GP, Bittker S, Cooper D, et al. Yield of large-volume blood cultures in patients with early Lyme disease. J Infect Dis. 2001;184(8):1070–1072.
  • Coipan EC, Jahfari S, Fonville M, et al. Imbalanced presence of Borrelia burgdorferi s.l. multilocus sequence types in clinical manifestations of Lyme borreliosis. Infect Genet Evol. 2016;42:66–76.
  • Dunaj J, Moniuszko A, Zajkowska J, et al. The role of PCR in diagnostics of Lyme borreliosis. Przegl Epidemiol. 2013;67(1):35–39, 119–123.
  • Thoendel M, Jeraldo PR, Greenwood-Quaintance KE, et al. Comparison of microbial DNA enrichment tools for metagenomic whole genome sequencing. J Microbiol Methods. 2016;127:141–145.
  • Horz HP, Scheer S, Vianna ME, et al. New methods for selective isolation of bacterial DNA from human clinical specimens. Anaerobe. 2010;16(1):47–53.
  • Feehery GR, Yigit E, Oyola SO, et al. A method for selectively enriching microbial DNA from contaminating vertebrate host DNA. Plos One. 2013;8(10):e76096.
  • Zhou L, Pollard AJ. A novel method of selective removal of human DNA improves PCR sensitivity for detection of Salmonella Typhi in blood samples. BMC Infect Dis. 2012;12:164-170.
  • Dundas N, Leos NK, Mitui M, et al. Comparison of automated nucleic acid extraction methods with manual extraction. J Mol Diagn. 2008;10(4):311–316.
  • Thatcher SA. DNA/RNA preparation for molecular detection. Clin Chem. 2015;61(1):89–99.
  • Schmidt BL. PCR in laboratory diagnosis of human Borrelia burgdorferi infections. Clin Microbiol Rev. 1997;10(1):185–201.
  • van Dam AP. Molecular diagnosis of Borrelia bacteria for the diagnosis of Lyme disease. Expert Opin Med Diagn. 2011;5(2):135–149.
  • Schwartz JJ, Gazumyan A, Schwartz I. rRNA gene organization in the Lyme disease spirochete, Borrelia burgdorferi. J Bacteriol. 1992;174(11):3757–3765.
  • Wilske B, Barbour AG, Bergstrom S, et al. Antigenic variation and strain heterogeneity in Borrelia spp. Res Microbiol. 1992;143(6):583–596.
  • Wang IN, Dykhuizen DE, Qiu W, et al. Genetic diversity of ospC in a local population of Borrelia burgdorferi sensu stricto. Genetics. 1999;151(1):15–30.
  • Ferdin J, Cerar T, Strle F, et al. Evaluation of real-time PCR targeting hbb gene for Borrelia species identification. J Microbiol Methods. 2010;82(2):115–119.
  • Ruzić-Sabljić E, Zore A, Strle F. Characterization of Borrelia burgdorferi sensu lato isolates by pulsed-field gel electrophoresis after MluI restriction of genomic DNA. Res Microbiol. 2008;159(6):441–448.
  • Wang G, van Dam AP, Schwartz I, et al. Molecular typing of Borrelia burgdorferi sensu lato: taxonomic, epidemiological, and clinical implications. Clin Microbiol Rev. 1999;12(4):633–653.
  • Postic D, Assous MV, Grimont PA, et al. Diversity of Borrelia burgdorferi sensu lato evidenced by restriction fragment length polymorphism of rrf (5S)-rrl (23S) intergenic spacer amplicons. Int J Syst Bacteriol. 1994;44(4):743–752.
  • de Leeuw BH, Maraha B, Hollemans L, et al. Evaluation of Borrelia real time PCR DNA targeting OspA, FlaB and 5S-23S IGS and Borrelia 16S rRNA RT-qPCR. J Microbiol Methods. 2014;107:41–46.
  • Eshoo MW, Crowder CC, Rebman AW, et al. Direct molecular detection and genotyping of Borrelia burgdorferi from whole blood of patients with early Lyme disease. Plos One. 2012;7(5):e36825.
  • Yang S, Rothman RE. PCR-based diagnostics for infectious diseases: uses, limitations, and future applications in acute-care settings. Lancet Infect Dis. 2004;4(6):337–348.
  • Singh C, Roy-Chowdhuri S. Quantitative real-time PCR: recent advances. Methods Mol Biol. 2016;1392:161–176.
  • Stupica D, Lusa L, Maraspin V, et al. Correlation of culture positivity, PCR positivity, and burden of Borrelia burgdorferi sensu lato in skin samples of erythema migrans patients with clinical findings. Plos One. 2015;10(9):e0136600.
  • Liveris D, Wang G, Girao G, et al. Quantitative detection of Borrelia burgdorferi in 2-millimeter skin samples of erythema migrans lesions: correlation of results with clinical and laboratory findings. J Clin Microbiol. 2002;40(4):1249–1253.
  • Wilhelmsson P, Fryland L, Börjesson S, et al. Prevalence and diversity of Borrelia species in ticks that have bitten humans in Sweden. J Clin Microbiol. 2010;48(11):4169–4176.
  • Buckwalter SP, Sloan LM, Cunningham SA, et al. Inhibition controls for qualitative real-time PCR assays: are they necessary for all specimen matrices? J Clin Microbiol. 2014;52(6):2139–2143.
  • Schrader C, Schielke A, Ellerbroek L, et al. PCR inhibitors - occurrence, properties and removal. J Appl Microbiol. 2012;113(5):1014–1026.
  • Portnoï D, Sertour N, Ferquel E, et al. A single-run, real-time PCR for detection and identification of Borrelia burgdorferi sensu lato species, based on the hbb gene sequence. FEMS Microbiol Lett. 2006;259(1):35–40.
  • Mommert S, Gutzmer R, Kapp A, et al. Sensitive detection of Borrelia burgdorferi sensu lato DNA and differentiation of Borrelia species by LightCycler PCR. J Clin Microbiol. 2001;39(7):2663–2667.
  • Rauter C, Oehme R, Diterich I, et al. Distribution of clinically relevant Borrelia genospecies in ticks assessed by a novel, single-run, real-time PCR. J Clin Microbiol. 2002;40(1):36–43.
  • Urwin R, Maiden MC. Multi-locus sequence typing: a tool for global epidemiology. Trends Microbiol. 2003;11(10):479–487.
  • Margos G, Vollmer SA, Cornet M, et al. A new Borrelia species defined by multilocus sequence analysis of housekeeping genes. Appl Environ Microbiol. 2009;75(16):5410–5416.
  • Wang G, Liveris D, Mukherjee P, et al. Molecular Typing of Borrelia burgdorferi. Curr Protoc Microbiol. 2014;34:12C 15 11–31.
  • Wang G, Aguero-Rosenfeld M, Wormser G, et al. Detection of Borrelia burgdorferi. In: Samuels DSRJ, editor. Borrelia: molecular biology, host interaction and pathogenesis. Norfolk: Caister Academic Press; 2010. p. 443–466.
  • Gern L, Humair F. Ecology of Borrelia burgdorferi sensu lato in Europe. In: Gray J, Kahl O, Lane RS, et al., editor. Lyme borreliosis: biology, epidemiology and control. Oxon: CAB International; 2002. p. 149–174.
  • Cerar T, Korva M, Avšič-Županc T, et al. Detection, identification and genotyping of Borrellia spp. in rodents in Slovenia by PCR and culture. BMC Vet Res. 2015;11:188.
  • Barthold SW, de Souza MS, Janotka JL, et al. Chronic Lyme borreliosis in the laboratory mouse. Am J Pathol. 1993;143(3):959–971.
  • Khanakah G, Kocianová E, Vyrosteková V, et al. Seasonal variations in detecting Borrelia burgdorferi sensu lato in rodents from north eastern Austria. Wien Klin Wochenschr. 2006;118(23–24):754–758.
  • Qiu WG, Dykhuizen DE, Acosta MS, et al. Geographic uniformity of the Lyme disease spirochete (Borrelia burgdorferi) and its shared history with tick vector (Ixodes scapularis) in the Northeastern United States. Genetics. 2002;160(3):833–849.
  • Barbour AG, Travinsky B. Evolution and distribution of the ospC Gene, a transferable serotype determinant of Borrelia burgdorferi. mBio. 2010;1(4):e00153–e00110.
  • Mukhacheva TA, Kovalev SY. Borrelia spirochetes in Russia: Genospecies differentiation by real-time PCR. Ticks Tick Borne Dis. 2014;5(6):722–726.
  • Takano A, Nakao M, Masuzawa T, et al. Multilocus sequence typing implicates rodents as the main reservoir host of human-pathogenic Borrelia garinii in Japan. J Clin Microbiol. 2011;49(5):2035–2039.
  • Moutailler S, Valiente Moro C, Vaumourin E, et al. Co-infection of ticks: the rule rather than the exception. Plos Negl Trop Dis. 2016;10(3):e0004539.
  • Brettschneider S, Bruckbauer H, Klugbauer N, et al. Diagnostic value of PCR for detection of Borrelia burgdorferi in skin biopsy and urine samples from patients with skin borreliosis. J Clin Microbiol. 1998;36(9):2658–2665.
  • Cerar T, Ruzić-Sabljić E, Glinsek U, et al. Comparison of PCR methods and culture for the detection of Borrelia spp. in patients with erythema migrans. Clin Microbiol Infect. 2008;14(7):653–658.
  • Floris R, Menardi G, Bressan R, et al. Evaluation of a genotyping method based on the ospA gene to detect Borrelia burgdorferi sensu lato in multiple samples of lyme borreliosis patients. New Microbiol. 2007;30(4):399–410.
  • Lebech AM, Hansen K, Brandrup F, et al. Diagnostic value of PCR for detection of Borrelia burgdorferi DNA in clinical specimens from patients with erythema migrans and Lyme neuroborreliosis. Mol Diag: J Devoted Underst Hum Dis through Clin Appl Mol Biol. 2000;5(2):139–150.
  • Melchers W, Meis J, Rosa P, et al. Amplification of Borrelia burgdorferi DNA in skin biopsies from patients with Lyme disease. J Clin Microbiol. 1991;29(11):2401–2406.
  • Moter SE, Hofmann H, Wallich R, et al. Detection of Borrelia burgdorferi sensu lato in lesional skin of patients with erythema migrans and acrodermatitis chronica atrophicans by ospA-specific PCR. J Clin Microbiol. 1994;32(12):2980–2988.
  • Muellegger RR, Zoechling N, Soyer HP, et al. No detection of Borrelia burgdorferi-specific DNA in erythema migrans lesions after minocycline treatment. Arch Dermatol. 1995;131(6):678–682.
  • Muellegger R, Zoechling N, Schluepen EM, et al. Polymerase chain reaction control of antibiotic treatment in dermatoborreliosis. Infection. 1996;24(1):76–79.
  • Oksi J, Marttila H, Soini H, et al. Early dissemination of Borrelia burgdorferi without generalized symptoms in patients with erythema migrans. APMIS. 2001;109(9):581–588.
  • Picken MM, Picken RN, Han D, et al. A two year prospective study to compare culture and polymerase chain reaction amplification for the detection and diagnosis of Lyme borreliosis. Mol Pathol. 1997;50(4):186–193.
  • Ranki A, Aavik E, Peterson P, et al. Successful amplification of DNA specific for Finnish Borrelia burgdorferi isolates in erythema chronicum migrans but not in circumscribed scleroderma lesions. J Invest Dermatol. 1994;102(3):339–345.
  • Rijpkema SG, Tazelaar DJ, Molkenboer MJ, et al. Detection of Borrelia afzelii, Borrelia burgdorferi sensu stricto, Borrelia garinii and group VS116 by PCR in skin biopsies of patients with erythema migrans and acrodermatitis chronica atrophicans. Clin Microbiol Infect. 1997;3(1):109–116.
  • Eisendle K, Grabner T, Zelger B. Focus floating microscopy: “gold standard” for cutaneous borreliosis? Am J Clin Pathol. 2007;127(2):213–222.
  • Brandt FC, Ertas B, Falk TM, et al. Genotyping of Borrelia from formalin-fixed paraffin-embedded skin biopsies of cutaneous borreliosis and tick bite reactions by assays targeting the intergenic spacer region, ospA and ospC genes. Br J Dermatol. 2014;171(3):528–543.
  • Wienecke R, Schlüpen EM, Zöchling N, et al. No evidence for Borrelia burgdorferi-specific DNA in lesions of localized scleroderma. J Invest Dermatol. 1995;104(1):23–26.
  • Wienecke R, Neubert U, Volkenandt M. Molecular detection of Borrelia burgdorferi in formalin-fixed, paraffin-embedded lesions of Lyme disease. J Cutan Pathol. 1993;20(5):385–388.
  • Moniuszko A, Dunaj J, Zajkowska J, et al. Comparison of detection of Borrelia burgdorferi DNA and anti-Borrelia burgdorferi antibodies in patients with erythema migrans in north-eastern Poland. Postepy Dermatologii I Alergologii. 2015;32(1):11–14.
  • Wormser GP, Masters E, Liveris D, et al. Microbiologic evaluation of patients from Missouri with erythema migrans. Clin Infect Dis. 2005;40(3):423–428.
  • Liveris D, Schwartz I, McKenna D, et al. Comparison of five diagnostic modalities for direct detection of Borrelia burgdorferi in patients with early Lyme disease. Diagn Microbiol Infect Dis. 2012;73(3):243–245.
  • Nowakowski J, Schwartz I, Liveris D, et al. Laboratory diagnostic techniques for patients with early Lyme disease associated with erythema migrans: a comparison of different techniques. Clin Infect Dis. 2001;33(12):2023–2027.
  • Cyr TL, Jenkins MC, Hall RD, et al. Improving the specificity of 16S rDNA-based polymerase chain reaction for detecting Borrelia burgdorferi sensu lato-causative agents of human Lyme disease. J Appl Microbiol. 2005;98(4):962–970.
  • Steere AC, Sikand VK, Meurice F, et al. Vaccination against Lyme disease with recombinant Borrelia burgdorferi outer-surface lipoprotein A with adjuvant. Lyme Disease Vaccine Study Group. N Engl J Med. 1998;339(4):209–215.
  • Coulter P, Lema C, Flayhart D, et al. Two-year evaluation of Borrelia burgdorferi culture and supplemental tests for definitive diagnosis of Lyme disease. J Clin Microbiol. 2005;43(10):5080–5084.
  • Schwartz I, Bittker S, Bowen SL, et al. Polymerase chain reaction amplification of culture supernatants for rapid detection of Borrelia burgdorferi. Eur J Clin Microbiol Infect Dis. 1993;12(11):879–882.
  • Schwartz I, Wormser GP, Schwartz JJ, et al. Diagnosis of early Lyme disease by polymerase chain reaction amplification and culture of skin biopsies from erythema migrans lesions. J Clin Microbiol. 1992;30(12):3082–3088.
  • Schaarschmidt D, Oehme R, Kimmig P, et al. Detection and molecular typing of Borrelia burgdorferi sensu lato in Ixodes ricinus ticks and in different patient samples from southwest Germany. Eur J Epidemiol. 2001;17(12):1067–1074.
  • Moreno C, Kutzner H, Palmedo G, et al. Interstitial granulomatous dermatitis with histiocytic pseudorosettes: a new histopathologic pattern in cutaneous borreliosis. Detection of Borrelia burgdorferi DNA sequences by a highly sensitive PCR-ELISA. J Am Acad Dermatol. 2003;48(3):376–384.
  • Lenormand C, Jaulhac B, Debarbieux S, et al. Expanding the clinicopathological spectrum of late cutaneous Lyme borreliosis (acrodermatitis chronica atrophicans [ACA]): A prospective study of 20 culture- and/or polymerase chain reaction (PCR)-documented cases. J Am Acad Dermatol. 2016;74(4):685–692.
  • von Stedingk LV, Olsson I, Hanson HS, et al. Polymerase chain reaction for detection of Borrelia burgdorferi DNA in skin lesions of early and late Lyme borreliosis. Eur J Clin Microbiol Infect Dis. 1995;14(1):1–5.
  • Kempf W, Kazakov DV, Hübscher E, et al. Cutaneous borreliosis associated with T cell-predominant infiltrates: a diagnostic challenge. J Am Acad Dermatol. 2015;72(4):683–689.
  • Roux F, Boyer E, Jaulhac B, et al. Lyme meningoradiculitis: prospective evaluation of biological diagnosis methods. Eur J Clin Microbiol Infect Dis. 2007;26(10):685–693.
  • Zbinden R, Goldenberger D, Lucchini GM, et al. Comparison of two methods for detecting intrathecal synthesis of Borrelia burgdorferi-specific antibodies and PCR for diagnosis of Lyme neuroborreliosis. J Clin Microbiol. 1994;32(7):1795–1798.
  • Huppertz HI, Schmidt H, Karch H. Detection of Borrelia burgdorferi by nested polymerase chain reaction in cerebrospinal fluid and urine of children with neuroborreliosis. Eur J Pediatr. 1993;152(5):414–417.
  • Debue M, Gautier P, Hackel C, et al. Detection of Borrelia burgdorferi in biological samples using the polymerase chain reaction assay. Res Microbiol. 1991;142(5):565–572.
  • Christen HJ, Eiffert H, Ohlenbusch A, et al. Evaluation of the polymerase chain reaction for the detection of Borrelia burgdorferi in cerebrospinal fluid of children with acute peripheral facial palsy. Eur J Pediatr. 1995;154(5):374–377.
  • Eiffert H, Ohlenbusch A, Christen HJ, et al. Nondifferentiation between Lyme disease spirochetes from vector ticks and human cerebrospinal fluid. J Infect Dis. 1995;171(2):476–479.
  • Amouriaux P, Assous M, Margarita D, et al. Polymerase chain reaction with the 30-kb circular plasmid of Borrelia burgdorferi B31 as a target for detection of the Lyme borreliosis agents in cerebrospinal fluid. Res Microbiol. 1993;144(3):211–219.
  • Priem S, Rittig MG, Kamradt T, et al. An optimized PCR leads to rapid and highly sensitive detection of Borrelia burgdorferi in patients with Lyme borreliosis. J Clin Microbiol. 1997;35(3):685–690.
  • Gooskens J, Templeton KE, Claas EC, et al. Evaluation of an internally controlled real-time PCR targeting the ospA gene for detection of Borrelia burgdorferi sensu lato DNA in cerebrospinal fluid. Clin Microbiol Infect. 2006;12(9):894–900.
  • Lebech AM. Polymerase chain reaction in diagnosis of Borrelia burgdorferi infections and studies on taxonomic classification. APMIS Suppl. 2002;105:1–40.
  • Lebech AM, Hansen K. Detection of Borrelia burgdorferi DNA in urine samples and cerebrospinal fluid samples from patients with early and late Lyme neuroborreliosis by polymerase chain reaction. J Clin Microbiol. 1992;30(7):1646–1653.
  • Chmielewski T, Fiett J, Gniadkowski M, et al. Improvement in the laboratory recognition of lyme borreliosis with the combination of culture and PCR methods. Mol Diag: J Devoted Underst Hum Dis through Clin Appl Mol Biol. 2003;7(3–4):155–162.
  • Pachner AR, Delaney E. The polymerase chain reaction in the diagnosis of Lyme neuroborreliosis. Ann Neurol. 1993;34(4):544–550.
  • Nocton JJ, Bloom BJ, Rutledge BJ, et al. Detection of Borrelia burgdorferi DNA by polymerase chain reaction in cerebrospinal fluid in Lyme neuroborreliosis. J Infect Dis. 1996;174(3):623–627.
  • Luft BJ, Steinman CR, Neimark HC, et al. Invasion of the central nervous system by Borrelia burgdorferi in acute disseminated infection. JAMA. 1992;267(10):1364–1367.
  • Keller TL, Halperin JJ, Whitman M. PCR detection of Borrelia burgdorferi DNA in cerebrospinal fluid of Lyme neuroborreliosis patients. Neurology. 1992;42(1):32–42.
  • Avery RA, Frank G, Eppes SC. Diagnostic utility of Borrelia burgdorferi cerebrospinal fluid polymerase chain reaction in children with Lyme meningitis. Pediatr Infect Dis J. 2005;24(8):705–708.
  • Liebling MR, Nishio MJ, Rodriguez A, et al. The polymerase chain reaction for the detection of Borrelia burgdorferi in human body fluids. Arthritis Rheum. 1993;36(5):665–675.
  • Vasiliu V, Herzer P, Rössler D, et al. Heterogeneity of Borrelia burgdorferi sensu lato demonstrated by an ospA-type-specific PCR in synovial fluid from patients with Lyme arthritis. Med Microbiol Immunol. 1998;187(2):97–102.
  • Priem S, Burmester GR, Kamradt T, et al. Detection of Borrelia burgdorferi by polymerase chain reaction in synovial membrane, but not in synovial fluid from patients with persisting Lyme arthritis after antibiotic therapy. Ann Rheum Dis. 1998;57(2):118–121.
  • Jaulhac B, Chary-Valckenaere I, Sibilia J, et al. Detection of Borrelia burgdorferi by DNA amplification in synovial tissue samples from patients with Lyme arthritis. Arthritis Rheum. 1996;39(5):736–745.
  • van der Heijden IM, Wilbrink B, Rijpkema SG, et al. Detection of Borrelia burgdorferi sensu stricto by reverse line blot in the joints of Dutch patients with Lyme arthritis. Arthritis Rheum. 1999;42(7):1473–1480.
  • Eiffert H, Karsten A, Thomssen R, et al. Characterization of Borrelia burgdorferi strains in Lyme arthritis. Scand J Infect Dis. 1998;30(3):265–268.
  • Schnarr S, Putschky N, Jendro MC, et al. Chlamydia and Borrelia DNA in synovial fluid of patients with early undifferentiated oligoarthritis: results of a prospective study. Arthritis Rheum. 2001;44(11):2679–2685.
  • Jones KL, McHugh GA, Glickstein LJ, et al. Analysis of Borrelia burgdorferi genotypes in patients with Lyme arthritis: High frequency of ribosomal RNA intergenic spacer type 1 strains in antibiotic-refractory arthritis. Arthritis Rheum. 2009;60(7):2174–2182.
  • Bradley JF, Johnson RC, Goodman JL. The persistence of spirochetal nucleic acids in active Lyme arthritis. Ann Intern Med. 1994;120(6):487–489.
  • Persing DH, Rutledge BJ, Rys PN, et al. Target imbalance: disparity of Borrelia burgdorferi genetic material in synovial fluid from Lyme arthritis patients. J Infect Dis. 1994;169(3):668–672.
  • Demaerschalck I, Ben Messaoud A, De Kesel M, et al. Simultaneous presence of different Borrelia burgdorferi genospecies in biological fluids of Lyme disease patients. J Clin Microbiol. 1995;33(3):602–608.
  • Santino I, Berlutti F, Pantanella F, et al. Detection of Borrelia burgdorferi sensu lato DNA by PCR in serum of patients with clinical symptoms of Lyme borreliosis. FEMS Microbiol Lett. 2008;283(1):30–35.
  • Bil-Lula I, Matuszek P, Pfeiffer T, et al. Lyme borreliosis–the utility of improved real-time PCR Assay in the detection of borrelia burgdorferi infections. Adv Clin Exp Med: off Organ Wroclaw Med Univ. 2015;24(4):663–670.
  • Oksi J, Marjamäki M, Nikoskelainen J, et al. Borrelia burgdorferi detected by culture and PCR in clinical relapse of disseminated Lyme borreliosis. Ann Med. 1999;31(3):225–232.
  • Wallach FR, Forni AL, Hariprashad J, et al. Circulating Borrelia burgdorferi in patients with acute Lyme disease: results of blood cultures and serum DNA analysis. J Infect Dis. 1993;168(6):1541–1543.
  • Goodman JL, Bradley JF, Ross AE, et al. Bloodstream invasion in early Lyme disease: results from a prospective, controlled, blinded study using the polymerase chain reaction. Am J Med. 1995;99(1):6–12.
  • Mouritsen CL, Wittwer CT, Litwin CM, et al. Polymerase chain reaction detection of Lyme disease: correlation with clinical manifestations and serologic responses. Am J Clin Pathol. 1996;105(5):647–654.
  • Lee SH, Vigliotti JS, Vigliotti VS, et al. Detection of borreliae in archived sera from patients with clinically suspect Lyme disease. Int J Mol Sci. 2014;15(3):4284–4298.
  • Busch U, Hizo Teufel C, Boehmer R, et al. Differentiation of Borrelia burgdorferi sensu lato strains isolated from skin biopsies and tick by pulsed-field gel electrophoresis. Rocz Akad Med Bialymst. 1996;41(1):51–58.
  • Belfaiza J, Postic D, Bellenger E, et al. Genomic fingerprinting of Borrelia burgdorferi sensu lato by pulsed-field gel electrophoresis. J Clin Microbiol. 1993;31(11):2873–2877.
  • Picken RN, Cheng Y, Strle F, et al. Molecular characterization of Borrelia burgdorferi sensu lato from Slovenia revealing significant differences between tick and human isolates. Eur J Clin Microbiol Infect Dis. 1996;15(4):313–323.
  • Busch U, Teufel CH, Boehmer R, et al. Molecular characterization of Borrelia burgdorferi sensu lato strains by pulsed-field gel electrophoresis. Electrophoresis. 1995;16(5):744–747.
  • Ruzić-Sabljić E, Maraspin V, Lotric-Furlan S, et al. Characterization of Borrelia burgdorferi sensu lato strains isolated from human material in Slovenia. Wien Klin Wochenschr. 2002;114(13–14):544–550.
  • Ruzić-Sabljić E, Lotric-Furlan S, Maraspin V, et al. Analysis of Borrelia burgdorferi sensu lato isolated from cerebrospinal fluid. APMIS. 2001;109(10):707–713.
  • Ruzić-Sabljić E, Strle F, Cimperman J, et al. Characterisation of Borrelia burgdorferi sensu lato strains isolated from patients with skin manifestations of Lyme borreliosis residing in Slovenia. J Med Microbiol. 2000;49(1):47–53.
  • Xu Y, Johnson RC. Analysis and comparison of plasmid profiles of Borrelia burgdorferi sensu lato strains. J Clin Microbiol. 1995;33(10):2679–2685.
  • Bustamante C, Gurrieri S, Smith SB. Towards a molecular description of pulsed-field gel electrophoresis. Trends Biotechnol. 1993;11(1):23–30.
  • Cirulli ET, Goldstein DB. Uncovering the roles of rare variants in common disease through whole-genome sequencing. Nature reviews. Genetics. 2010;11(6):415–425.
  • Goodwin S, McPherson JD, McCombie WR. Coming of age: ten years of next-generation sequencing technologies. Nature reviews. Genetics. 2016;17(6):333–351.
  • Wyres KL, Conway TC, Garg S, et al. WGS Analysis and interpretation in clinical and public health microbiology laboratories: what are the requirements and how do existing tools compare? Pathogens. 2014;3(2):437–458.
  • Troy EB, Lin T, Gao L, et al. Understanding barriers to Borrelia burgdorferi dissemination during infection using massively parallel sequencing. Infect Immun. 2013;81(7):2347–2357.
  • Carpi G, Cagnacci F, Wittekindt NE, et al. Metagenomic profile of the bacterial communities associated with Ixodes ricinus ticks. Plos One. 2011;6(10):e25604.
  • Leichty AR, Brisson D. Selective whole genome amplification for resequencing target microbial species from complex natural samples. Genetics. 2014;198(2):473–481.
  • Carpi G, Walter KS, Bent SJ, et al. Whole genome capture of vector-borne pathogens from mixed DNA samples: a case study of Borrelia burgdorferi. BMC Genomics. 2015;16:434.
  • Margos G, Gatewood AG, Aanensen DM, et al. MLST of housekeeping genes captures geographic population structure and suggests a European origin of Borrelia burgdorferi. Proc Natl Acad Sci U S A. 2008;105(25):8730–8735.
  • Lagal V, Postic D, Ruzic-Sabljic E, et al. Genetic diversity among Borrelia strains determined by single-strand conformation polymorphism analysis of the ospC gene and its association with invasiveness. J Clin Microbiol. 2003;41(11):5059–5065.
  • Wormser GP, Brisson D, Liveris D, et al. Borrelia burgdorferi genotype predicts the capacity for hematogenous dissemination during early Lyme disease. J Infect Dis. 2008;198(9):1358–1364.
  • Wormser GP, Liveris D, Nowakowski J, et al. Association of specific subtypes of Borrelia burgdorferi with hematogenous dissemination in early Lyme disease. J Infect Dis. 1999;180(3):720–725.
  • Cerar T, Strle F, Stupica D, et al. Differences in genotype, clinical features, and inflammatory potential of Borrelia burgdorferi sensu stricto strains from Europe and the United States. Emerg Infect Dis. 2016;22(5):818–827.
  • Rudenko N, Golovchenko M, Grubhoffer L, et al. The rare ospC allele L of Borrelia burgdorferi sensu stricto, commonly found among samples collected in a coastal plain area of the southeastern United States, is associated with ixodes affinis ticks and local rodent hosts Peromyscus gossypinus and Sigmodon hispidus. Appl Environ Microbiol. 2013;79(4):1403–1406.
  • Rudenko N, Golovchenko M, Hönig V, et al. 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. Appl Environ Microbiol. 2013;79(5):1444–1453.
  • Wilske B, Jauris-Heipke S, Lobentanzer R, et al. Phenotypic analysis of outer surface protein C (OspC) of Borrelia burgdorferi sensu lato by monoclonal antibodies: relationship to genospecies and OspA serotype. J Clin Microbiol. 1995;33(1):103–109.
  • Brisson D, Dykhuizen DE. ospC diversity in Borrelia burgdorferi: different hosts are different niches. Genetics. 2004;168(2):713–722.
  • Fukunaga M, Okada K, Nakao M, et al. Phylogenetic analysis of Borrelia species based on flagellin gene sequences and its application for molecular typing of Lyme disease borreliae. Int J Syst Bacteriol. 1996;46(4):898–905.
  • Picken RN. Polymerase chain reaction primers and probes derived from flagellin gene sequences for specific detection of the agents of Lyme disease and North American relapsing fever. J Clin Microbiol. 1992;30(1):99–114.
  • Jaulhac B, Heller R, Limbach FX, et al. Direct molecular typing of Borrelia burgdorferi sensu lato species in synovial samples from patients with lyme arthritis. J Clin Microbiol. 2000;38(5):1895–1900.
  • Berry O, Sarre SD. Gel-free species identification using melt-curve analysis. Mol Ecol Notes. 2007;7(1):1–4.
  • Lyon E, Wittwer CT. LightCycler technology in molecular diagnostics. J Mol Diagn. 2009;11(2):93–101.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.