Lyme disease and new molecular biological detection methods

Document Type : Review


1 Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran

2 Department of Biology, Payame Noor University (PNU), Tehran, Iran

3 Molecular Biology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran

4 Department of Biochemistry and Biophysics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran


Molecular biology is a crucial tool for understanding the structures, functions, and internal controls within cells. Its applications span from diagnosing diseases to developing new medicines and improving our understanding of cellular physiology. However, diagnosing Lyme disease presents unique challenges as the bacteria responsible for the disease are difficult to observe directly in body tissues and are slow-growing in laboratory environments. Lyme disease can affect multiple body systems and exhibit a range of non-specific symptoms, which can complicate diagnosis. Common laboratory diagnostics also have high rates of false positives in contaminated areas. To overcome these limitations, scientists have focused on developing fast and accurate diagnostic methods using molecular biology. Researchers have identified Borrelia burgdorferi, a type of gram-negative spirochete bacteria, as the primary cause of Lyme disease, but other species can also cause the disease. Accurate molecular tests have been designed to identify specific strains of Borrelia with precision. This study reviewed 131 related articles from Scopus, ISI, and PubMed databases and reported methods for creating accurate molecular tests to detect disease agents. These developments represent a significant step towards a more effective diagnosis and treatment of Lyme disease. The study analyzed the varied approaches and techniques outlined in the literature to create a cohesive understanding of the most effective methods for designing molecular tests. Ultimately, the study reported on the optimal methods for designing and implementing accurate molecular tests to diagnose and isolate disease agents.


  1. Dubrey SW, Bhatia A, Woodham S, Rakowicz W. Lyme disease in the United Kingdom. Postgrad Med J. 2014;90(1059):33-42. doi:10.1136/postgradmedj-2012-131522
  2. Dobson AD, Taylor JL, Randolph SE. Tick (Ixodes ricinus) abundance and seasonality at recreational sites in the UK: hazards in relation to fine-scale habitat types revealed by complementary sampling methods. Ticks Tick Borne Dis. 2011; 2(2):67-74. doi:10.1016/j.ttbdis.2011.03.002
  3. Sorouri R, Ramazani A, Karami A, Ranjbar R, Guy EC. Isolation and characterization of Borrelia burgdorferi strains from Ixodes ricinus ticks in the southern England. BioImpacts: BI. 2015; 5(2):71. doi:10.15171/bi.2015.08
  4. Zhang K, He J, Catalano C, Guo Y, Liu J, Li C. FlhF regulates the number and configuration of periplasmic flagella in Borrelia burgdorferi. Mol Microbiol. 2020;113(6):1122-39. doi:10.1111/mmi.14482
  5. Carroll BL, Liu J. Structural conservation and adaptation of the bacterial flagella motor. Biomolecules. 2020;10 (11): 1492. doi:10.3390/biom10111492
  6. Kraiczy P. Identification and characterization of Borrelia burgdorferi complement-binding proteins. Borrelia burgdorferi: Springer; 2018. p. 95-103. doi:10.1007/978-1-4939-7383-5_8
  7. Trevisan G, Cinco M, Ruscio M, Forgione P, BonoLyme disease i VLN. Borrelia Lyme Group. J Dermatol Res Rev Rep SRC/JDMRS-151. 2022;142.
  8. Barbour AG, Heiland RA, Howe TR. Heterogeneity of major proteins in Lyme disease borreliae: a molecular analysis of North American and European isolates. J Infect Dis. 1985;152(3):478-84. doi:10.1093/infdis/152.3.478
  9. Brisson D, Drecktrah D, Eggers CH, Samuels DS. Genetics of Borrelia burgdorferi. Ann Rev Genet. 2012; 46. doi:10.1146/annurev-genet-011112-112140
  10. Ivanova LB, Tomova A, González‐Acuña D, Murúa R, Moreno CX, Hernández C, et al. Borrelia chilensis, a new member of the Borrelia burgdorferi sensu lato complex that extends the range of this genospecies in the S outhern H emisphere. Environ Microbiol. 2014; 16 (4):1069-80. doi:10.1111/1462-2920.12310
  11. de Lemos JA, McGuire DK, Drazner MH. B-type natriuretic peptide in cardiovascular disease. The Lancet. 2003; 362 (9380): 316-22. doi:10.1016/S0140-6736(03)13976-1
  12. Casjens SR, Mongodin EF, Qiu W-G, Luft BJ, Schutzer SE, Gilcrease EB, et al. Genome stability of Lyme disease spirochetes: comparative genomics of Borrelia burgdorferi plasmids. PloS one. 2012;7(3):e33280. doi:10.1371/journal.pone.0033280
  13. Chaconas G, Castellanos M, Verhey TB. Changing of the guard: How the Lyme disease spirochete subverts the host immune response. J Biol Chem. 2020;295(2):301-13. doi:10.1074/jbc.REV119.008583
  14. Ojaimi C, Davidson BE, Saint Girons I, OLyme disease IG. Conservation of gene arrangement and an unusual organization of rRNA genes in the linear chromosomes of the Lyme disease spirochaetes Borrelia burgdorferi, B. gariniiand B. Microbiology. 1994;140(11):2931-40. doi:10.1099/13500872-140-11-2931
  15. Skuballa J, Petney T, Pfäffle M, Oehme R, Hartelt K, Fingerle V, et al. Occurrence of different Borrelia burgdorferi sensu lato genospecies including B. afzelii, B. bavariensis, and B. spielmanii in hedgehogs (Erinaceus spp.) in Europe. Ticks Tick Borne Dis. 2012;3(1):8-13. doi:10.1016/j.ttbdis.2011.09.008
  16. Paulauskas A, Ambrasiene D, Radzijevskaja J, Rosef O, Turcinaviciene J. Diversity in prevalence and genospecies of Borrelia burgdorferi sensu lato in Ixodes ricinus ticks and rodents in Lithuania and Norway. Int J Med Microbiol. 2008;298:180-7. doi:10.1016/j.ijmm.2008.04.003
  17. Margos G, Vollmer SA, Ogden NH, Fish D. Population genetics, taxonomy, phylogeny and evolution of Borrelia burgdorferi sensu lato. Infect Genet Evol. 2011;11(7):1545-63. doi:10.1016/j.meegid.2011.07.022
  18. Wang G, Van Dam AP, Schwartz I, Dankert J. Molecular typing of Borrelia burgdorferi sensu lato: taxonomic, epidemiological, and clinical implications. Clin Microbiol Rev. 1999;12(4):633-53. doi:10.1128/CMR.12.4.633
  19. Önder Ö, Humphrey PT, McOmber B, Korobova F, Francella N, Greenbaum DC, et al. OspC is potent plasminogen receptor on surface of Borrelia burgdorferi. J Biol Chem. 2012;287(20): 16860-8. doi:10.1074/jbc.M111.290775
  20. Schwan TG, Piesman J. Vector interactions and molecular adaptations of Lyme disease and relapsing fever spirochetes associated with transmission by ticks. Emerg Infect Dis. 2002; 8 (2):115. doi:10.3201/eid0802.010198
  21. Finlay BB, Falkow S. Common themes in microbial pathogenicity. Microbiol Rev. 1989;53(2):210-30. doi:10.1128/mr.53.2.210-230.1989
  22. Charon NW, GoLyme disease stein SF. Genetics of motility and chemotaxis of a fascinating group of bacteria: the spirochetes. Ann Rev Genet. 2002;36:47. doi:10.1146/annurev.genet.36.041602.134359
  23. GoLyme disease stein SF, Li C, Liu J, Miller M, Motaleb MA, Norris SJ, et al. The chic motility and chemotaxis of Borrelia burgdorferi. Borrelia: molecular biology, host interaction and pathogenesis. 2010:167-88.
  24. Guo BP, Norris SJ, Rosenberg LC, Höök M. Adherence of Borrelia burgdorferi to the proteoglycan decorin. Infect Immun. 1995;63(9):3467-72. doi:10.1128/iai.63.9.3467-3472.1995
  25. Coburn J, Cugini C. Targeted mutation of the outer membrane protein P66 disrupts attachment of the Lyme disease agent, Borrelia burgdorferi, to integrin αvβ Proc Natl Acad Sci. 2003; 100 (12):7301-6. doi:10.1073/pnas.1131117100         
  26. Brissette CA, Bykowski T, Cooley AE, Bowman A, Stevenson B. Borrelia burgdorferi RevA antigen binds host fibronectin. Infect Immun. 2009;77(7):2802-12. doi:10.1128/IAI.00227-09
  27. Verma A, Brissette CA, Bowman A, Stevenson B. Borrelia burgdorferi BmpA is a laminin-binding protein. Infect Immun. 2009;77(11):4940-6. doi:10.1128/IAI.01420-08
  28. Eisen L, Lane RS. Vectors of Borrelia burgdorferi sensu lato. Lyme borreliosis: biol, epidemiol control. 2002:91-115. doi:10.1079/9780851996325.0091
  29. Ružić-Sabljić E, Zore A, Strle F. Characterization of Borrelia burgdorferi sensu lato isolates by pulsed-fieLyme disease gel electrophoresis after MluI restriction of genomic DNA. Res Microbiol. 2008;159(6):441-8. doi:10.1016/j.resmic.2008.05.005
  30. Busch U, Hizo-Teufel C, Böhmer R, Fingerle V, RöbZler D, Wilske B, et al. Borrelia burgdorferi sensu lato strains isolated from cutaneous Lyme borreliosis biopsies differentiated by pulsed-fieLyme disease gel electrophoresis. Scand J Infect Dis. 1996; 28(6):583-9. doi:10.3109/00365549609037965
  31. Busch U, Teufel CH, Boehmer R, Wilske B, Preac‐Mursic V. Molecular characterization of Borrelia burgdorferi sensu lato strains by pulsed‐fieLyme disease gel electrophoresis. Electrophoresis. 1995;16(1):744-7. doi:10.1002/elps.11501601122
  32. Ruzić-Sabljić E, Maraspin V, Lotric-Furlan S, Jurca T, Logar M, Pikelj-Pecnik A, et al. Characterization of Borrelia burgdorferi sensu lato strains isolated from human material in Slovenia. Wiener klinische Wochenschrift. 2002; 114(13-14):544-50.
  33. Ružić‐Sabljić E, Lotrič‐Furlan S, Maraspin V, Cimperman J, Pleterski‐Rigler D, Strle F. Analysis of Borrelia burgdorferi sensu lato isolated from cerebrospinal fluid Note. Apmis. 2001; 109 (10):707-13. doi:10.1034/j.1600-0463.2001.d01-136.x
  34. Arnež M, Ružic-Sabljic E, Ahcan J, Radšel-Medvešcek A, Pleterski-Rigler D, Strle F. Isolation of Borrelia burgdorferi sensu lato from blood of chiLyme disease ren with solitary erythema migrans. Pediatr Infect Dis J. 2001;20(3):251-5. doi:10.1097/00006454-200103000-00007
  35. Ružić-Sabljić E, Arnež M, Lotrič-Furlan S, Maraspin V, Cimperman J, Strle F. Genotypic and phenotypic characterisation of Borrelia burgdorferi sensu lato strains isolated from human blood. J Med Microbiol. 2001;50(10):896-901. doi:10.1099/0022-1317-50-10-896
  36. Xu Y, Johnson RC. Analysis and comparison of plasmid profiles of Borrelia burgdorferi sensu lato strains. J Clin Microbiol. 1995; 33(10):2679-85. doi:10.1128/jcm.33.10.2679-2685.1995
  37. Biškup UG, Strle F, Ružić-Sabljić Loss of plasmids of Borrelia burgdorferi sensu lato during prolonged in vitro cultivation. Plasmid. 2011;66(1):1-6. doi:10.1016/j.plasmid.2011.02.006
  38. Marconi RT, Casjens S, Munderloh UG, Samuels DS. Analysis of linear plasmid dimers in Borrelia burgdorferi sensu lato isolates: implications concerning the potential mechanism of linear plasmid replication. J Bacteriol. 1996;178(11):3357-61. doi:10.1128/jb.178.11.3357-3361.1996
  39. Iyer R, Kalu O, Purser J, Norris S, Stevenson B, Schwartz I. Linear and circular plasmid content in Borrelia burgdorferi clinical isolates. Infect Immun. 2003; 71(7):3699-706. doi:10.1128/IAI.71.7.3699-3706.2003
  40. Wyres KL, Conway TC, Garg S, Queiroz C, Reumann M, Holt K, 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):437-58. doi:10.3390/pathogens3020437
  41. Troy EB, Lin T, Gao L, Lazinski DW, Camilli A, Norris SJ, et al. Understanding barriers to Borrelia burgdorferi dissemination during infection using massively parallel sequencing. Infect Immun. 2013;81(7):2347-57. doi:10.1128/IAI.00266-13
  42. Assous MV, Grimont PA. Diversity of Borrelia burgdorfeii Sensu Lato Evidenced by Restriction Fragment Length Polymorphism of rrf. Int J Syst Bacteriol. 1994:743-52. doi:10.1099/00207713-44-4-743
  43. Liveris D, Gazumyan A, Schwartz I. Molecular typing of Borrelia burgdorferi sensu lato by PCR-restriction fragment length polymorphism analysis. J Clin Microbiol. 1995;33(3):589-95. doi:10.1128/jcm.33.3.589-595.1995
  44. Wolcott KA, Margos G, Fingerle V, Becker NS. Host association of Borrelia burgdorferi sensu lato: A review. Ticks Tick Borne Dis. 2021;12(5):101766. doi:10.1016/j.ttbdis.2021.101766
  45. Cerar T, Ružić-Sabljić E, Glinšek U, Zore A, Strle F. Comparison of PCR methods and culture for the detection of Borrelia spp. in patients with erythema migrans. Clin Microbiol Infect. 2008; 14 (7): 653-8. doi:10.1111/j.1469-0691.2008.02013.x
  46. Liveris D, Varde S, Iyer R, Koenig S, Bittker S, Cooper D, et al. Genetic diversity of Borrelia burgdorferi in Lyme disease patients as determined by culture versus direct PCR with clinical specimens. J Clin Microbiol. 1999;37(3):565-9. doi:10.1128/JCM.37.3.565-569.1999
  47. Wang G, Ojaimi C, Iyer R, Saksenberg V, McClain SA, Wormser GP, et al. Impact of genotypic variation of Borrelia burgdorferi sensu stricto on kinetics of dissemination and severity of disease in C3H/HeJ mice. Infect Immun. 2001;69(7):4303-12. doi:10.1128/IAI.69.7.4303-4312.2001
  48. Wang G, Ojaimi C, Wu H, Saksenberg V, Iyer R, Liveris D, et al. Disease severity in a murine model of Lyme borreliosis is associated with the genotype of the infecting Borrelia burgdorferi sensu stricto strain. J Infect Dis. 2002;186(6):782-91. doi:10.1086/343043
  49. Wormser GP, Liveris D, Nowakowski J, Nadelman RB, Cavaliere LF, McKenna D, et al. Association of specific subtypes of Borrelia burgdorferi with hematogenous dissemination in early Lyme disease. J Infect Dis. 1999;180(3):720-5. doi:10.1086/314922
  50. Wormser GP, Brisson D, Liveris D, Hanincová K, Sandigursky S, Nowakowski J, et al. Borrelia burgdorferi genotype predicts the capacity for hematogenous dissemination during early Lyme disease. J Infect Dis. 2008;198(9):1358-64. doi:10.1086/592279
  51. Eisen L. Vector competence studies with hard ticks and Borrelia burgdorferi sensu lato spirochetes: A review. Ticks Tick Borne Dis. 2020;11(3):101359. doi:10.1016/j.ttbdis.2019.101359
  52. Samuels DS, Drecktrah D, Hall LS. Genetic transformation and complementation. Borrelia burgdorferi: Springer; 2018. p. 183-200. doi:10.1007/978-1-4939-7383-5_15
  53. OspC VF. Delineating the Requirement for the. Infect Immun. 2006;74(6):3547. doi:10.1128/IAI.00158-06
  54. Tilly K, Bestor A, Jewett MW, Rosa P. Rapid clearance of Lyme disease spirochetes lacking OspC from skin. Infect Immun. 2007; 75(3):1517-9. doi:10.1128/IAI.01725-06
  55. Aguero-RosenfeLyme disease ME, Wang G, Schwartz I, Wormser GP. Diagnosis of Lyme borreliosis. Clin Microbiol Rev. 2005;18(3):484-509. doi:10.1128/CMR.18.3.484-509.2005
  56. Wang I-N, Dykhuizen DE, Qiu W, Dunn JJ, Bosler EM, Luft BJ. Genetic diversity of ospC in a local population of Borrelia burgdorferi sensu stricto. Genetics. 1999;151 (1): 15-30. doi:10.1093/genetics/151.1.15
  57. Jones KL, Glickstein LJ, Damle N, Sikand VK, McHugh G, Steere AC. Borrelia burgdorferi genetic markers and disseminated disease in patients with early Lyme disease. J Clin Microbiol. 2006; 44(12):4407-13. doi:10.1128/JCM.01077-06
  58. Strle K, Jones KL, Drouin EE, Li X, Steere AC. Borrelia burgdorferi RST1 (OspC type A) genotype is associated with greater inflammation and more severe Lyme disease. Am J Pathol. 2011;178(6):2726-39. doi:10.1016/j.ajpath.2011.02.018
  59. Lagal V, Portnoï D, Faure G, Postic D, Baranton G. Borrelia burgdorferi sensu stricto invasiveness is correlated with OspC-plasminogen affinity. Microbes Infect. 2006; 8(3):645-52. doi:10.1016/j.micinf.2005.08.017
  60. Lagal V, Postic D, Ruzic-Sabljic E, Baranton G. 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): 5059-65. doi:10.1128/JCM.41.11.5059-5065.2003
  61. Berry O, Sarre SD. Gel‐free species identification using melt‐curve analysis. Mol Ecol Notes. 2007;7(1):1-4. doi:10.1111/j.1471-8286.2006.01541.x
  62. Lyon E, Wittwer CT. LightCycler technology in molecular diagnostics. J Mol Diagn. 2009; 11 (2):93-101. doi:10.2353/jmoldx.2009.080094
  63. Portnoï D, Sertour N, Ferquel E, Garnier M, Baranton G, Postic D. 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. doi:10.1111/j.1574-6968.2006.00249.x
  64. Mommert S, Gutzmer R, Kapp A, Werfel T. Sensitive detection of Borrelia burgdorferi sensu lato DNA and differentiation of Borrelia species by LightCycler PCR. J Clin Microbiol. 2001; 39 (7):2663-7. doi:10.1128/JCM.39.7.2663-2667.2001
  65. Rauter C, Oehme R, Diterich I, Engele M, Hartung T. 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. doi:10.1128/JCM.40.1.36-43.2002
  66. Schoen RT. Lyme disease: diagnosis and treatment. Curr Opin Rheumatol. 2020;32(3):247-54. doi:10.1097/BOR.0000000000000698
  67. Fraser CM, Casjens S, Huang WM, Sutton GG, Clayton R, Lathigra R, et al. Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi. Nature. 1997; 390 (6660): 580-6. doi:10.1038/37551
  68. Michalik J, Wodecka B, Liberska J, Dabert M, Postawa T, Piksa K, et al. Diversity of Borrelia burgdorferi sensu lato species in Ixodes ticks (Acari: Ixodidae) associated with cave-dwelling bats from Poland and Romania. Ticks Tick Borne Dis. 2020; 11 (1): 101300. doi:10.1016/j.ttbdis.2019.101300
  69. Jaulhac B, Heller R, Limbach F, Hansmann Y, Lipsker D, Monteil H, 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):1895-900. doi:10.1128/JCM.38.5.1895-1900.2000
  70. Urwin R, Maiden MC. Multi-locus sequence typing: a tool for global epidemiology. Trends Microbiol. 2003; 11 (10):479-87. doi:10.1016/j.tim.2003.08.006
  71. Struelens M. Molecular typing: a key tool for the surveillance and control of nosocomial infection. Curr Opin Infect Dis. 2002; 15 (4):383-5. doi:10.1097/00001432-200208000-00005
  72. Okeyo M, Hepner S, Rollins RE, Hartberger C, Straubinger RK, Marosevic D, et al. Longitudinal study of prevalence and spatio‐temporal distribution of Borrelia burgdorferi sensu lato in ticks from three defined habitats in Latvia, 1999-2010. Environ Microbiol. 2020;22(12):5033-47. doi:10.1111/1462-2920.15100
  73. Geebelen L, Lernout T, Devleesschauwer B, Kabamba-Mukadi B, Saegeman V, Belkhir L, et al. Non-specific symptoms and post-treatment Lyme disease syndrome in patients with Lyme borreliosis: a prospective cohort study in Belgium (2016-2020). BMC Infect Dis. 2022;22(1):1-14. doi:10.1186/s12879-022-07686-8
  74. BransfieLyme disease RC, Aidlen DM, Cook MJ, Javia S, editors. A clinical diagnostic system for late-stage neuropsychiatric Lyme Borreliosis based upon an analysis of 100 patients. Healthcare; 2020: Multidisciplinary Digital Publishing Institute. doi:10.3390/healthcare8010013
  75. Kullberg BJ, Vrijmoeth HD, van de Schoor F, Hovius JW. Lyme borreliosis: diagnosis and management. BMJ. 2020;369. doi:10.1136/bmj.m1041
  76. Stanek G, Strle F. Lyme borreliosis-from tick bite to diagnosis and treatment. FEMS Microbiol Rev. 2018;42(3):233-58. doi:10.1093/femsre/fux047
  77. Steere AC. Borrelia burgdorferi (Lyme disease, Lyme borreliosis). Mandell, Douglas, and Bennett's Principles and practice of infectious diseases. 2010:3071-81. doi:10.1016/B978-0-443-06839-3.00242-3
  78. Michalski MM, Kubiak K, Szczotko M, Chajęcka M, Dmitryjuk M. Molecular detection of Borrelia burgdorferi sensu lato and Anaplasma phagocytophilum in ticks collected from dogs in urban areas of North-Eastern Poland. Pathogens. 2020;9(6):455. doi:10.3390/pathogens9060455
  79. Trevisan G, Bonin S, Ruscio M. A practical approach to the diagnosis of lyme borreliosis: from clinical heterogeneity to laboratory methods. Front Med. 2020:265. doi:10.3389/fmed.2020.00265
  80. Schmidt B. PCR in laboratory diagnosis of human Borrelia burgdorferi infections. Clin Microbiol Rev. 1997;10(1): 185-201. doi:10.1128/CMR.10.1.185
  81. Brandt ME, Padhye AA, Mayer LW, Holloway BP. Utility of random amplified polymorphic DNA PCR and TaqMan automated detection in molecular identification of Aspergillus fumigatus. J Clin Microbiol. 1998;36(7):2057-62. doi:10.1128/JCM.36.7.2057-2062.1998
  82. Seo M-G, Kwon O-D, Kwak D. Molecular identification of Borrelia afzelii from ticks parasitizing domestic and wiLyme disease animals in South Korea. Microorganisms. 2020;8(5):649. doi:10.3390/microorganisms8050649
  83. Qiu B, Brunner M, Zhang G, Sigal L, Stein S. Selection of continuous epitope sequences and their incorporation into poly (ethylene glycol)-peptide conjugates for use in serodiagnostic immunoassays: Application to Lyme disease. Pept Sci. 2000; 55 (4):319-33. doi:10.1002/1097-0282(2000)55:4<319::AID-BIP1005>3.0.CO;2-W
  84. Pavia CS, Wormser GP, Bittker S, Cooper D. An indirect hemagglutination antibody test to detect antibodies to Borrelia burgdorferi in patients with Lyme disease. J Microbiol Method. 2000;40(2):163-73. doi:10.1016/S0167-7012(00)00119-6
  85. Gomes-Solecki MJ, Wormser GP, Schriefer M, Neuman G, Hannafey L, Glass JD, et al. Recombinant assay for serodiagnosis of Lyme disease regardless of OspA vaccination status. J Clin Microbiol. 2002;40(1):193-7. doi:10.1128/JCM.40.1.193-197.2002
  86. Fawcett PT, Rosé CD, Gibney KM, Doughty RA. Comparison of immunodot and Western blot assays for diagnosing Lyme borreliosis. Clin Diagn Lab Immunol. 1998;5(4):503-6. doi:10.1128/CDLI.5.4.503-506.1998
  87. Ledue TB, Collins MF, Young J, Schriefer ME. Evaluation of the recombinant VlsE-based liaison chemiluminescence immunoassay for detection of Borrelia burgdorferi and diagnosis of Lyme disease. Clin Vaccine Immunol. 2008;15(12):1796-804. doi:10.1128/CVI.00195-08
  88. Jobe DA, Lovrich SD, Asp KE, Mathiason MA, Albrecht SE, Schell RF, et al. Significantly improved accuracy of diagnosis of early Lyme disease by peptide enzyme-linked immunosorbent assay based on the borreliacidal antibody epitope of Borrelia burgdorferi OspC. Clin Vaccine Immunol. 2008;15(6):981-5. doi:10.1128/CVI.00079-08
  89. Trevejo R, Krause P, Sikand V, Schriefer M, Ryan R, Lepore T, et al. Evaluation of two-test serodiagnostic method for early Lyme disease in clinical practice. J Infect Dis. 1999;179(4):931-8. doi:10.1086/314663
  90. Mogilyansky E, Loa CC, Adelson ME, Mordechai E, Tilton RC. Comparison of Western immunoblotting and the C6 Lyme antibody test for laboratory detection of Lyme disease. Clin Vaccin Immunol. 2004;11(5):924-9. doi:10.1128/CDLI.11.5.924-929.2004
  91. Tilton RC, Sand MN, Manak M. The Western immunoblot for Lyme disease: determination of sensitivity, specificity, and interpretive criteria with use of commercially available performance panels. Clin Infect Dis. 1997;25(Supplement_1): S31-S4. doi:10.1086/516173
  92. Brissette CA, Rossmann E, Bowman A, Cooley AE, Riley SP, HunfeLyme disease K-P, et al. The borrelial fibronectin-binding protein RevA is an early antigen of human Lyme disease. Clin Vaccine Immunol. 2010;17(2):274-80. doi:10.1128/CVI.00437-09
  93. Sapi E, Pabbati N, Datar A, Davies EM, Rattelle A, Kuo BA. Improved culture conditions for the growth and detection of Borrelia from human serum. Int J Med Sci. 2013;10(4):362. doi:10.7150/ijms.5698
  94. Liveris D, Schwartz I, Bittker S, Cooper D, Iyer R, Cox ME, et al. Improving the yieLyme disease of blood cultures from patients with early Lyme disease. J Clin Microbiol. 2011;49(6):2166-8. doi:10.1128/JCM.00350-11
  95. Liveris D, Schwartz I, McKenna D, Nowakowski J, Nadelman R, DeMarco J, 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):243-5. doi:10.1016/j.diagmicrobio.2012.03.026
  96. Gomes-Solecki MJ, Wormser GP, Persing DH, Berger BW, Glass JD, Yang X, et al. A first-tier rapid assay for the serodiagnosis of Borrelia burgdorferi infection. Arch Intern Med. 2001; 161 (16): 2015-20. doi:10.1001/archinte.161.16.2015
  97. Hammer B, Moter A, Kahl O, Alberti G, Göbel UB. Visualization of Borrelia burgdorferi sensu lato by fluorescence in situ hybridization (FISH) on whole-body sections of Ixodes ricinus ticks and gerbil skin biopsies. Microbiology. 2001;147(6):1425-36. doi:10.1099/00221287-147-6-1425
  98. Nocton JJ, Bloom BJ, Rutledge BJ, Persing DH, Logigian EL, Schmid CH, et al. Detection of Borrelia burgdorferi DNA by polymerase chain reaction in cerebrospinal fluid in Lyme neuroborreliosis. J Infect Dis. 1996;174(3):623-7. doi:10.1093/infdis/174.3.623
  99. Kleshchenko YY, Moody TN, Furtak VA, Ochieng J, Lima MF, Villalta F. Human galectin-3 promotes Trypanosoma cruzi adhesion to human coronary artery smooth muscle cells. Infect Immun. 2004; 72 (11): 6717-21. doi:10.1128/IAI.72.11.6717-6721.2004
  100. Namekar M, Ellis EM, O'Connell M, Elm J, Gurary A, Park SY, et al. Evaluation of a new commercially available immunoglobulin M capture enzyme-linked immunosorbent assay for diagnosis of dengue virus infection. J Clin Microbiol. 2013; 51(9):3102-6. doi:10.1128/JCM.00351-13
  101. Phillips S, Mattman L, Hulinska D, Moayad H. A proposal for the reliable culture ofBorrelia burgdorferi from patients with chronic lyme disease, even from those previously aggressively treated. Infection. 1998;26(6):364-7. doi:10.1007/BF02770837
  102. Tilton RC, Barden D, Sand M. Culture of Borrelia burgdorferi. J Clin Microbiol. 2001; 39 (7): 2747 doi:10.1128/JCM.39.7.2747.2001
  103. Marques AR, Stock F, Gill V. Evaluation of a new culture medium for Borrelia burgdorferi. J Clin microbiol. 2000; 38 (11): 4239-41. doi:10.1128/JCM.38.11.4239-4241.2000
  104. Eshoo MW, Crowder CC, Rebman AW, Rounds MA, Matthews HE, Picuri JM, 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. doi:10.1371/journal.pone.0036825