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. 1997 Jan;10(1):185–201. doi: 10.1128/cmr.10.1.185

PCR in laboratory diagnosis of human Borrelia burgdorferi infections.

B L Schmidt 1
PMCID: PMC172948  PMID: 8993863

Abstract

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.

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Selected References

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  1. Aberer E., Breier F., Stanek G., Schmidt B. Success and failure in the treatment of acrodermatitis chronica atrophicans. Infection. 1996 Jan-Feb;24(1):85–87. doi: 10.1007/BF01780666. [DOI] [PubMed] [Google Scholar]
  2. Aberer E., Klade H., Stanek G., Gebhart W. Borrelia burgdorferi and different types of morphea. Dermatologica. 1991;182(3):145–154. [PubMed] [Google Scholar]
  3. Aberer E., Stanek G. Histological evidence for spirochetal origin of morphea and lichen sclerosus et atrophicans. Am J Dermatopathol. 1987 Oct;9(5):374–379. doi: 10.1097/00000372-198710000-00002. [DOI] [PubMed] [Google Scholar]
  4. Adam T., Gassmann G. S., Rasiah C., Göbel U. B. Phenotypic and genotypic analysis of Borrelia burgdorferi isolates from various sources. Infect Immun. 1991 Aug;59(8):2579–2585. doi: 10.1128/iai.59.8.2579-2585.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Amouriaux P., Assous M., Margarita D., Baranton G., Saint Girons I. 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 Mar-Apr;144(3):211–219. doi: 10.1016/0923-2508(93)90046-5. [DOI] [PubMed] [Google Scholar]
  6. Anderson J. F., Flavell R. A., Magnarelli L. A., Barthold S. W., Kantor F. S., Wallich R., Persing D. H., Mathiesen D., Fikrig E. Novel Borrelia burgdorferi isolates from Ixodes scapularis and Ixodes dentatus ticks feeding on humans. J Clin Microbiol. 1996 Mar;34(3):524–529. doi: 10.1128/jcm.34.3.524-529.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Anthonissen F. M., De Kesel M., Hoet P. P., Bigaignon G. H. Evidence for the involvement of different genospecies of Borrelia in the clinical outcome of Lyme disease in Belgium. Res Microbiol. 1994 May;145(4):327–331. doi: 10.1016/0923-2508(94)90187-2. [DOI] [PubMed] [Google Scholar]
  8. Appel M. J., Allan S., Jacobson R. H., Lauderdale T. L., Chang Y. F., Shin S. J., Thomford J. W., Todhunter R. J., Summers B. A. Experimental Lyme disease in dogs produces arthritis and persistent infection. J Infect Dis. 1993 Mar;167(3):651–664. doi: 10.1093/infdis/167.3.651. [DOI] [PubMed] [Google Scholar]
  9. Asbrink E., Hovmark A. Successful cultivation of spirochetes from skin lesions of patients with erythema chronicum migrans Afzelius and acrodermatitis chronica atrophicans. Acta Pathol Microbiol Immunol Scand B. 1985 Apr;93(2):161–163. doi: 10.1111/j.1699-0463.1985.tb02870.x. [DOI] [PubMed] [Google Scholar]
  10. Balmelli T., Piffaretti J. C. Association between different clinical manifestations of Lyme disease and different species of Borrelia burgdorferi sensu lato. Res Microbiol. 1995 May;146(4):329–340. doi: 10.1016/0923-2508(96)81056-4. [DOI] [PubMed] [Google Scholar]
  11. Barbour A. G., Maupin G. O., Teltow G. J., Carter C. J., Piesman J. Identification of an uncultivable Borrelia species in the hard tick Amblyomma americanum: possible agent of a Lyme disease-like illness. J Infect Dis. 1996 Feb;173(2):403–409. doi: 10.1093/infdis/173.2.403. [DOI] [PubMed] [Google Scholar]
  12. Barthold S. W., Fikrig E., Bockenstedt L. K., Persing D. H. Circumvention of outer surface protein A immunity by host-adapted Borrelia burgdorferi. Infect Immun. 1995 Jun;63(6):2255–2261. doi: 10.1128/iai.63.6.2255-2261.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Barthold S. W., Persing D. H., Armstrong A. L., Peeples R. A. Kinetics of Borrelia burgdorferi dissemination and evolution of disease after intradermal inoculation of mice. Am J Pathol. 1991 Aug;139(2):263–273. [PMC free article] [PubMed] [Google Scholar]
  14. Bassam B. J., Caetano-Anollés G. Automated "hot start" PCR using mineral oil and paraffin wax. Biotechniques. 1993 Jan;14(1):30–34. [PubMed] [Google Scholar]
  15. Battafarano D. F., Combs J. A., Enzenauer R. J., Fitzpatrick J. E. Chronic septic arthritis caused by Borrelia burgdorferi. Clin Orthop Relat Res. 1993 Dec;(297):238–241. [PubMed] [Google Scholar]
  16. Boom R., Sol C. J., Salimans M. M., Jansen C. L., Wertheim-van Dillen P. M., van der Noordaa J. Rapid and simple method for purification of nucleic acids. J Clin Microbiol. 1990 Mar;28(3):495–503. doi: 10.1128/jcm.28.3.495-503.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Bradley J. F., Johnson R. C., Goodman J. L. The persistence of spirochetal nucleic acids in active Lyme arthritis. Ann Intern Med. 1994 Mar 15;120(6):487–489. doi: 10.7326/0003-4819-120-6-199403150-00007. [DOI] [PubMed] [Google Scholar]
  18. Brunet L. R., Spielman A., Telford S. R., 3rd Short report: density of Lyme disease spirochetes within deer ticks collected from zoonotic sites. Am J Trop Med Hyg. 1995 Sep;53(3):300–302. doi: 10.4269/ajtmh.1995.53.300. [DOI] [PubMed] [Google Scholar]
  19. Burgess E. C., Wachal M. D., Cleven T. D. Borrelia burgdorferi infection in dairy cows, rodents, and birds from four Wisconsin dairy farms. Vet Microbiol. 1993 May;35(1-2):61–77. doi: 10.1016/0378-1135(93)90116-o. [DOI] [PubMed] [Google Scholar]
  20. Busch U., Hizo-Teufel C., Boehmer R., Fingerle V., Nitschko H., Wilske B., Preac-Mursic V. Three species of Borrelia burgdorferi sensu lato (B. burgdorferi sensu stricto, B afzelii, and B. garinii) identified from cerebrospinal fluid isolates by pulsed-field gel electrophoresis and PCR. J Clin Microbiol. 1996 May;34(5):1072–1078. doi: 10.1128/jcm.34.5.1072-1078.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Christen H. J., Eiffert H., Ohlenbusch A., Hanefeld F. 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 May;154(5):374–377. doi: 10.1007/BF02072106. [DOI] [PubMed] [Google Scholar]
  22. Coburn J., Leong J. M., Erban J. K. Integrin alpha IIb beta 3 mediates binding of the Lyme disease agent Borrelia burgdorferi to human platelets. Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7059–7063. doi: 10.1073/pnas.90.15.7059. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Cogswell F. B., Bantar C. E., Hughes T. G., Gu Y., Philipp M. T. Host DNA can interfere with detection of Borrelia burgdorferi in skin biopsy specimens by PCR. J Clin Microbiol. 1996 Apr;34(4):980–982. doi: 10.1128/jcm.34.4.980-982.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Cooke W. D., Bartenhagen N. H. Seroreactivity to Borrelia burgdorferi antigens in the absence of Lyme disease. J Rheumatol. 1994 Jan;21(1):126–131. [PubMed] [Google Scholar]
  25. Craft J. E., Grodzicki R. L., Steere A. C. Antibody response in Lyme disease: evaluation of diagnostic tests. J Infect Dis. 1984 May;149(5):789–795. doi: 10.1093/infdis/149.5.789. [DOI] [PubMed] [Google Scholar]
  26. Debue M., Gautier P., Hackel C., Van Elsen A., Herzog A., Bigaignon G., Bollen A. Detection of Borrelia burgdorferi in biological samples using the polymerase chain reaction assay. Res Microbiol. 1991 Jun;142(5):565–572. doi: 10.1016/0923-2508(91)90189-h. [DOI] [PubMed] [Google Scholar]
  27. Demaerschalck I., Ben Messaoud A., De Kesel M., Hoyois B., Lobet Y., Hoet P., Bigaignon G., Bollen A., Godfroid E. Simultaneous presence of different Borrelia burgdorferi genospecies in biological fluids of Lyme disease patients. J Clin Microbiol. 1995 Mar;33(3):602–608. doi: 10.1128/jcm.33.3.602-608.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Dieffenbach C. W., Lowe T. M., Dveksler G. S. General concepts for PCR primer design. PCR Methods Appl. 1993 Dec;3(3):S30–S37. doi: 10.1101/gr.3.3.s30. [DOI] [PubMed] [Google Scholar]
  29. Dillon W. I., Saed G. M., Fivenson D. P. Borrelia burgdorferi DNA is undetectable by polymerase chain reaction in skin lesions of morphea, scleroderma, or lichen sclerosus et atrophicus of patients from North America. J Am Acad Dermatol. 1995 Oct;33(4):617–620. doi: 10.1016/0190-9622(95)91281-9. [DOI] [PubMed] [Google Scholar]
  30. Dorward D. W., Schwan T. G., Garon C. F. Immune capture and detection of Borrelia burgdorferi antigens in urine, blood, or tissues from infected ticks, mice, dogs, and humans. J Clin Microbiol. 1991 Jun;29(6):1162–1170. doi: 10.1128/jcm.29.6.1162-1170.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Eiffert H., Ohlenbusch A., Christen H. J., Thomssen R., Spielman A., Matuschka F. R. Nondifferentiation between Lyme disease spirochetes from vector ticks and human cerebrospinal fluid. J Infect Dis. 1995 Feb;171(2):476–479. doi: 10.1093/infdis/171.2.476. [DOI] [PubMed] [Google Scholar]
  32. Erlich H. A., Gelfand D., Sninsky J. J. Recent advances in the polymerase chain reaction. Science. 1991 Jun 21;252(5013):1643–1651. doi: 10.1126/science.2047872. [DOI] [PubMed] [Google Scholar]
  33. Espy M. J., Smith T. F., Persing D. H. Dependence of polymerase chain reaction product inactivation protocols on amplicon length and sequence composition. J Clin Microbiol. 1993 Sep;31(9):2361–2365. doi: 10.1128/jcm.31.9.2361-2365.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Fan W., Leonardi C. L., Penneys N. S. Absence of Borrelia burgdorferi in patients with localized scleroderma (morphea). J Am Acad Dermatol. 1995 Oct;33(4):682–684. doi: 10.1016/0190-9622(95)91311-4. [DOI] [PubMed] [Google Scholar]
  35. Feder H. M., Jr, Gerber M. A., Luger S. W., Ryan R. W. Persistence of serum antibodies to Borrelia burgdorferi in patients treated for Lyme disease. Clin Infect Dis. 1992 Nov;15(5):788–793. doi: 10.1093/clind/15.5.788. [DOI] [PubMed] [Google Scholar]
  36. Feder H. M., Jr, Hunt M. S. Pitfalls in the diagnosis and treatment of Lyme disease in children. JAMA. 1995 Jul 5;274(1):66–68. [PubMed] [Google Scholar]
  37. Fitzgerald T. J., Johnson R. C., Miller J. N., Sykes J. A. Characterization of the attachment of Treponema pallidum (Nichols strain) to cultured mammalian cells and the potential relationship of attachment to pathogenicity. Infect Immun. 1977 Nov;18(2):467–478. doi: 10.1128/iai.18.2.467-478.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Fraser D. D., Kong L. I., Miller F. W. Molecular detection of persistent Borrelia burgdorferi in a man with dermatomyositis. Clin Exp Rheumatol. 1992 Jul-Aug;10(4):387–390. [PubMed] [Google Scholar]
  39. Gassmann G. S., Kramer M., Göbel U. B., Wallich R. Nucleotide sequence of a gene encoding the Borrelia burgdorferi flagellin. Nucleic Acids Res. 1989 May 11;17(9):3590–3590. doi: 10.1093/nar/17.9.3590. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Georgilis K., Peacocke M., Klempner M. S. Fibroblasts protect the Lyme disease spirochete, Borrelia burgdorferi, from ceftriaxone in vitro. J Infect Dis. 1992 Aug;166(2):440–444. doi: 10.1093/infdis/166.2.440. [DOI] [PubMed] [Google Scholar]
  41. Goldberg N. S., Forseter G., Nadelman R. B., Schwartz I., Jorde U., McKenna D., Holmgren D., Bittker S., Montecalvo M., Wormser G. P. Vesicular erythema migrans. Arch Dermatol. 1992 Nov;128(11):1495–1498. [PubMed] [Google Scholar]
  42. Goodman J. L., Bradley J. F., Ross A. E., Goellner P., Lagus A., Vitale B., Berger B. W., Luger S., Johnson R. C. Bloodstream invasion in early Lyme disease: results from a prospective, controlled, blinded study using the polymerase chain reaction. Am J Med. 1995 Jul;99(1):6–12. doi: 10.1016/s0002-9343(99)80097-7. [DOI] [PubMed] [Google Scholar]
  43. Goodman J. L., Jurkovich P., Kramber J. M., Johnson R. C. Molecular detection of persistent Borrelia burgdorferi in the urine of patients with active Lyme disease. Infect Immun. 1991 Jan;59(1):269–278. doi: 10.1128/iai.59.1.269-278.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Granter S. R., Barnhill R. L., Hewins M. E., Duray P. H. Identification of Borrelia burgdorferi in diffuse fasciitis with peripheral eosinophilia: borrelial fasciitis. JAMA. 1994 Oct 26;272(16):1283–1285. [PubMed] [Google Scholar]
  45. Grimprel E., Sanchez P. J., Wendel G. D., Burstain J. M., McCracken G. H., Jr, Radolf J. D., Norgard M. V. Use of polymerase chain reaction and rabbit infectivity testing to detect Treponema pallidum in amniotic fluid, fetal and neonatal sera, and cerebrospinal fluid. J Clin Microbiol. 1991 Aug;29(8):1711–1718. doi: 10.1128/jcm.29.8.1711-1718.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Guy E. C., Stanek G. Detection of Borrelia burgdorferi in patients with Lyme disease by the polymerase chain reaction. J Clin Pathol. 1991 Jul;44(7):610–611. doi: 10.1136/jcp.44.7.610. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Haff L. A. Improved quantitative PCR using nested primers. PCR Methods Appl. 1994 Jun;3(6):332–337. doi: 10.1101/gr.3.6.332. [DOI] [PubMed] [Google Scholar]
  48. Hashimoto Y., Takahashi H., Matsuo S., Hirai K., Takemori N., Nakao M., Miyamoto K., Iizuka H. Polymerase chain reaction of Borrelia burgdorferi flagellin gene in Shulman syndrome. Dermatology. 1996;192(2):136–139. doi: 10.1159/000246339. [DOI] [PubMed] [Google Scholar]
  49. Hay P. E., Clarke J. R., Strugnell R. A., Taylor-Robinson D., Goldmeier D. Use of the polymerase chain reaction to detect DNA sequences specific to pathogenic treponemes in cerebrospinal fluid. FEMS Microbiol Lett. 1990 Mar 15;56(3):233–238. doi: 10.1111/j.1574-6968.1990.tb13943.x. [DOI] [PubMed] [Google Scholar]
  50. He Q., Marjamäki M., Soini H., Mertsola J., Viljanen M. K. Primers are decisive for sensitivity of PCR. Biotechniques. 1994 Jul;17(1):82, 84, 86-7. [PubMed] [Google Scholar]
  51. Hoffmann J. C., Stichtenoth D. O., Zeidler H., Follmann M., Brandis A., Stanek G., Wollenhaupt J. Lyme disease in a 74-year-old forest owner with symptoms of dermatomyositis. Arthritis Rheum. 1995 Aug;38(8):1157–1160. doi: 10.1002/art.1780380820. [DOI] [PubMed] [Google Scholar]
  52. Hofmeister E. K., Markham R. B., Childs J. E., Arthur R. R. Comparison of polymerase chain reaction and culture for detection of Borrelia burgdorferi in naturally infected Peromyscus leucopus and experimentally infected C.B-17 scid/scid mice. J Clin Microbiol. 1992 Oct;30(10):2625–2631. doi: 10.1128/jcm.30.10.2625-2631.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Horneff G., Huppertz H. I., Müller K., Voit T., Karch H. Demonstration of Borrelia burgdorferi infection in a child with Guillain-Barré syndrome. Eur J Pediatr. 1993 Oct;152(10):810–812. doi: 10.1007/BF02073376. [DOI] [PubMed] [Google Scholar]
  54. Horowitz H. W., Sanghera K., Goldberg N., Pechman D., Kamer R., Duray P., Weinstein A. Dermatomyositis associated with Lyme disease: case report and review of Lyme myositis. Clin Infect Dis. 1994 Feb;18(2):166–171. doi: 10.1093/clinids/18.2.166. [DOI] [PubMed] [Google Scholar]
  55. Huppertz H. I., 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 May;152(5):414–417. doi: 10.1007/BF01955900. [DOI] [PubMed] [Google Scholar]
  56. Hyde F. W., Johnson R. C. Genetic relationship of lyme disease spirochetes to Borrelia, Treponema, and Leptospira spp. J Clin Microbiol. 1984 Aug;20(2):151–154. doi: 10.1128/jcm.20.2.151-154.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Hyde F. W., Johnson R. C., White T. J., Shelburne C. E. Detection of antigens in urine of mice and humans infected with Borrelia burgdorferi, etiologic agent of Lyme disease. J Clin Microbiol. 1989 Jan;27(1):58–61. doi: 10.1128/jcm.27.1.58-61.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Häupl T., Hahn G., Rittig M., Krause A., Schoerner C., Schönherr U., Kalden J. R., Burmester G. R. Persistence of Borrelia burgdorferi in ligamentous tissue from a patient with chronic Lyme borreliosis. Arthritis Rheum. 1993 Nov;36(11):1621–1626. doi: 10.1002/art.1780361118. [DOI] [PubMed] [Google Scholar]
  59. Jaulhac B., Chary-Valckenaere I., Sibilia J., Javier R. M., Piémont Y., Kuntz J. L., Monteil H., Pourel J. Detection of Borrelia burgdorferi by DNA amplification in synovial tissue samples from patients with Lyme arthritis. Arthritis Rheum. 1996 May;39(5):736–745. doi: 10.1002/art.1780390505. [DOI] [PubMed] [Google Scholar]
  60. Jaulhac B., Nicolini P., Piemont Y., Monteil H. Detection of Borrelia burgdorferi in cerebrospinal fluid of patients with Lyme borreliosis. N Engl J Med. 1991 May 16;324(20):1440–1440. [PubMed] [Google Scholar]
  61. Johnson B. J., Happ C. M., Mayer L. W., Piesman J. Detection of Borrelia burgdorferi in ticks by species-specific amplification of the flagellin gene. Am J Trop Med Hyg. 1992 Dec;47(6):730–741. doi: 10.4269/ajtmh.1992.47.730. [DOI] [PubMed] [Google Scholar]
  62. Johnston Y. E., Duray P. H., Steere A. C., Kashgarian M., Buza J., Malawista S. E., Askenase P. W. Lyme arthritis. Spirochetes found in synovial microangiopathic lesions. Am J Pathol. 1985 Jan;118(1):26–34. [PMC free article] [PubMed] [Google Scholar]
  63. Karch H., Huppertz H. I., Böhme M., Schmidt H., Wiebecke D., Schwarzkopf A. Demonstration of Borrelia burgdorferi DNA in urine samples from healthy humans whose sera contain B. burgdorferi-specific antibodies. J Clin Microbiol. 1994 Sep;32(9):2312–2314. doi: 10.1128/jcm.32.9.2312-2314.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Karch H., Huppertz H. I. Repeated detection of Borrelia burgdorferi DNA in synovial fluid of a child with Lyme arthritis. Rheumatol Int. 1993;12(6):227–229. doi: 10.1007/BF00301006. [DOI] [PubMed] [Google Scholar]
  65. Karlsson M., Hovind-Hougen K., Svenungsson B., Stiernstedt G. Cultivation and characterization of spirochetes from cerebrospinal fluid of patients with Lyme borreliosis. J Clin Microbiol. 1990 Mar;28(3):473–479. doi: 10.1128/jcm.28.3.473-479.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Karma A., Pirttilä T. A., Viljanen M. K., Lähde Y. E., Raitta C. M. Secondary retinitis pigmentosa and cerebral demyelination in Lyme borreliosis. Br J Ophthalmol. 1993 Feb;77(2):120–122. doi: 10.1136/bjo.77.2.120. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Kawabata H., Tashibu H., Yamada K., Masuzawa T., Yanagihara Y. Polymerase chain reaction analysis of Borrelia species isolated in Japan. Microbiol Immunol. 1994;38(8):591–598. doi: 10.1111/j.1348-0421.1994.tb01828.x. [DOI] [PubMed] [Google Scholar]
  68. Keller T. L., Halperin J. J., Whitman M. PCR detection of Borrelia burgdorferi DNA in cerebrospinal fluid of Lyme neuroborreliosis patients. Neurology. 1992 Jan;42(1):32–42. doi: 10.1212/wnl.42.1.32. [DOI] [PubMed] [Google Scholar]
  69. Klempner M. S., Noring R., Rogers R. A. Invasion of human skin fibroblasts by the Lyme disease spirochete, Borrelia burgdorferi. J Infect Dis. 1993 May;167(5):1074–1081. doi: 10.1093/infdis/167.5.1074. [DOI] [PubMed] [Google Scholar]
  70. Knoop C., Andrien M., Defleur V., Antonine M., de Francquen P., Goldman M., Estenne M. Detection of blood chimerism after lung and heart-lung transplantation. The superiority of nested as compared with standard polymerase chain reaction amplification. Transplantation. 1994 Dec 27;58(12):1335–1338. [PubMed] [Google Scholar]
  71. Krüger W. H., Pulz M. Detection of Borrelia burgdorferi in cerebrospinal fluid by the polymerase chain reaction. J Med Microbiol. 1991 Aug;35(2):98–102. doi: 10.1099/00222615-35-2-98. [DOI] [PubMed] [Google Scholar]
  72. Kuiper H., van Dam A. P., Spanjaard L., de Jongh B. M., Widjojokusumo A., Ramselaar T. C., Cairo I., Vos K., Dankert J. Isolation of Borrelia burgdorferi from biopsy specimens taken from healthy-looking skin of patients with Lyme borreliosis. J Clin Microbiol. 1994 Mar;32(3):715–720. doi: 10.1128/jcm.32.3.715-720.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Kwok S., Higuchi R. Avoiding false positives with PCR. Nature. 1989 May 18;339(6221):237–238. doi: 10.1038/339237a0. [DOI] [PubMed] [Google Scholar]
  74. Lazar J. G. Advanced methods in PCR product detection. PCR Methods Appl. 1994 Aug;4(1):S1–14. doi: 10.1101/gr.4.1.s1. [DOI] [PubMed] [Google Scholar]
  75. Lebech A. M., Clemmensen O., Hansen K. Comparison of in vitro culture, immunohistochemical staining, and PCR for detection of Borrelia burgdorferi in tissue from experimentally infected animals. J Clin Microbiol. 1995 Sep;33(9):2328–2333. doi: 10.1128/jcm.33.9.2328-2333.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  76. Lebech A. M., 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 Jul;30(7):1646–1653. doi: 10.1128/jcm.30.7.1646-1653.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  77. Lebech A. M., Hindersson P., Vuust J., Hansen K. Comparison of in vitro culture and polymerase chain reaction for detection of Borrelia burgdorferi in tissue from experimentally infected animals. J Clin Microbiol. 1991 Apr;29(4):731–737. doi: 10.1128/jcm.29.4.731-737.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Lesser R. L. Ocular manifestations of Lyme disease. Am J Med. 1995 Apr 24;98(4A):60S–62S. doi: 10.1016/s0002-9343(99)80045-x. [DOI] [PubMed] [Google Scholar]
  79. Liebling M. R., Nishio M. J., Rodriguez A., Sigal L. H., Jin T., Louie J. S. The polymerase chain reaction for the detection of Borrelia burgdorferi in human body fluids. Arthritis Rheum. 1993 May;36(5):665–675. doi: 10.1002/art.1780360514. [DOI] [PubMed] [Google Scholar]
  80. Liedtke W., Opalka B., Zimmermann C. W., Schmid E. Different methods of sample preparation influence sensitivity of Mycobacterium tuberculosis and Borrelia burgdorferi PCR. PCR Methods Appl. 1994 Apr;3(5):301–304. doi: 10.1101/gr.3.5.301. [DOI] [PubMed] [Google Scholar]
  81. Liegner K. B. Lyme disease: the sensible pursuit of answers. J Clin Microbiol. 1993 Aug;31(8):1961–1963. doi: 10.1128/jcm.31.8.1961-1963.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  82. Liegner K. B., Shapiro J. R., Ramsay D., Halperin A. J., Hogrefe W., Kong L. Recurrent erythema migrans despite extended antibiotic treatment with minocycline in a patient with persisting Borrelia burgdorferi infection. J Am Acad Dermatol. 1993 Feb;28(2 Pt 2):312–314. doi: 10.1016/0190-9622(93)70043-s. [DOI] [PubMed] [Google Scholar]
  83. Loewy Z. G., Mecca J., Diaco R. Enhancement of Borrelia burgdorferi PCR by uracil N-glycosylase. J Clin Microbiol. 1994 Jan;32(1):135–138. doi: 10.1128/jcm.32.1.135-138.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  84. Luft B. J., Steinman C. R., Neimark H. C., Muralidhar B., Rush T., Finkel M. F., Kunkel M., Dattwyler R. J. Invasion of the central nervous system by Borrelia burgdorferi in acute disseminated infection. JAMA. 1992 Mar 11;267(10):1364–1367. [PubMed] [Google Scholar]
  85. Magnarelli L. A., Anderson J. F., Stafford K. C., 3rd Detection of Borrelia burgdorferi in urine of Peromyscus leucopus by inhibition enzyme-linked immunosorbent assay. J Clin Microbiol. 1994 Mar;32(3):777–782. doi: 10.1128/jcm.32.3.777-782.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  86. Magnarelli L. A. Current status of laboratory diagnosis for Lyme disease. Am J Med. 1995 Apr 24;98(4A):10S–14S. doi: 10.1016/s0002-9343(99)80039-4. [DOI] [PubMed] [Google Scholar]
  87. Magnarelli L. A., Miller J. N., Anderson J. F., Riviere G. R. Cross-reactivity of nonspecific treponemal antibody in serologic tests for Lyme disease. J Clin Microbiol. 1990 Jun;28(6):1276–1279. doi: 10.1128/jcm.28.6.1276-1279.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  88. Maiwald M., Stockinger C., Hassler D., von Knebel Doeberitz M., Sonntag H. G. Evaluation of the detection of Borrelia burgdorferi DNA in urine samples by polymerase chain reaction. Infection. 1995 May-Jun;23(3):173–179. doi: 10.1007/BF01793860. [DOI] [PubMed] [Google Scholar]
  89. Malane M. S., Grant-Kels J. M., Feder H. M., Jr, Luger S. W. Diagnosis of Lyme disease based on dermatologic manifestations. Ann Intern Med. 1991 Mar 15;114(6):490–498. doi: 10.7326/0003-4819-114-6-490. [DOI] [PubMed] [Google Scholar]
  90. Malawista S. E., Schoen R. T., Moore T. L., Dodge D. E., White T. J., Persing D. H. Failure of multitarget detection of Borrelia burgdorferi-associated DNA sequences in synovial fluids of patients with juvenile rheumatoid arthritis: a cautionary note. Arthritis Rheum. 1992 Feb;35(2):246–247. doi: 10.1002/art.1780350220. [DOI] [PubMed] [Google Scholar]
  91. Malloy D. C., Nauman R. K., Paxton H. Detection of Borrelia burgdorferi using the polymerase chain reaction. J Clin Microbiol. 1990 Jun;28(6):1089–1093. doi: 10.1128/jcm.28.6.1089-1093.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  92. Mansy F., Hoyois B., De Vos M. J., Van Elsen A., Bollen A., Godfroid E. Colorimetric solid-phase capture hybridization assay for detection of amplified Borrelia burgdorferi DNA. Biotechniques. 1996 Jul;21(1):122–125. doi: 10.2144/96211rr03. [DOI] [PubMed] [Google Scholar]
  93. Marconi R. T., Garon C. F. Development of polymerase chain reaction primer sets for diagnosis of Lyme disease and for species-specific identification of Lyme disease isolates by 16S rRNA signature nucleotide analysis. J Clin Microbiol. 1992 Nov;30(11):2830–2834. doi: 10.1128/jcm.30.11.2830-2834.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  94. McGuire B. S., Chandler F. W., Felz M. W., Huey L. O., Field R. S. Detection of Borrelia burgdorferi in human blood and urine using the polymerase chain reaction. Pathobiology. 1992;60(3):163–167. doi: 10.1159/000163717. [DOI] [PubMed] [Google Scholar]
  95. Meis J. F., Koopman R., van Bergen B., Pool G., Melchers W. No evidence for a relation between Borrelia burgdorferi infection and old lesions of localized scleroderma (morphea) Arch Dermatol. 1993 Mar;129(3):386–387. [PubMed] [Google Scholar]
  96. Melchers W., Meis J., Rosa P., Claas E., Nohlmans L., Koopman R., Horrevorts A., Galama J. Amplification of Borrelia burgdorferi DNA in skin biopsies from patients with Lyme disease. J Clin Microbiol. 1991 Nov;29(11):2401–2406. doi: 10.1128/jcm.29.11.2401-2406.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  97. Merki H., Witzel L., Hüttemann W., Ansari A., Panijel M., Harre K., Heim J., Wolbergs E., Neumann H. J., Röhmel J. Early evening ranitidine administration promotes faster duodenal ulcer healing. Am J Gastroenterol. 1988 Apr;83(4):362–364. [PubMed] [Google Scholar]
  98. Montgomery R. R., Nathanson M. H., Malawista S. E. The fate of Borrelia burgdorferi, the agent for Lyme disease, in mouse macrophages. Destruction, survival, recovery. J Immunol. 1993 Feb 1;150(3):909–915. [PubMed] [Google Scholar]
  99. Moter S. E., Hofmann H., Wallich R., Simon M. M., Kramer M. D. 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 Dec;32(12):2980–2988. doi: 10.1128/jcm.32.12.2980-2988.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  100. Mouritsen C. L., Wittwer C. T., Litwin C. M., Yang L., Weis J. J., Martins T. B., Jaskowski T. D., Hill H. R. Polymerase chain reaction detection of Lyme disease: correlation with clinical manifestations and serologic responses. Am J Clin Pathol. 1996 May;105(5):647–654. doi: 10.1093/ajcp/105.5.647. [DOI] [PubMed] [Google Scholar]
  101. Muellegger R. R., Zoechling N., Soyer H. P., Hoedl S., Wienecke R., Volkenandt M., Kerl H. No detection of Borrelia burgdorferi-specific DNA in erythema migrans lesions after minocycline treatment. Arch Dermatol. 1995 Jun;131(6):678–682. [PubMed] [Google Scholar]
  102. Mullis K., Faloona F., Scharf S., Saiki R., Horn G., Erlich H. Specific enzymatic amplification of DNA in vitro: the polymerase chain reaction. Cold Spring Harb Symp Quant Biol. 1986;51(Pt 1):263–273. doi: 10.1101/sqb.1986.051.01.032. [DOI] [PubMed] [Google Scholar]
  103. Müller D. E., Itin P. H., Büchner S. A., Rufli T. Acrodermatitis chronica atrophicans involving the face. Evidence for Borrelia burgdorferi infection confirmed by DNA amplification. Dermatology. 1994;189(4):430–431. doi: 10.1159/000246901. [DOI] [PubMed] [Google Scholar]
  104. Nakao M., Miyamoto K., Fukunaga M., Hashimoto Y., Takahashi H. Comparative studies on Borrelia afzelii isolated from a patient of Lyme disease, Ixodes persulcatus ticks, and Apodemus speciosus rodents in Japan. Microbiol Immunol. 1994;38(6):413–420. doi: 10.1111/j.1348-0421.1994.tb01801.x. [DOI] [PubMed] [Google Scholar]
  105. Nielsen S. L., Young K. K., Barbour A. G. Detection of Borrelia burgdorferi DNA by the polymerase chain reaction. Mol Cell Probes. 1990 Feb;4(1):73–79. doi: 10.1016/0890-8508(90)90041-w. [DOI] [PubMed] [Google Scholar]
  106. Nocton J. J., Dressler F., Rutledge B. J., Rys P. N., Persing D. H., Steere A. C. Detection of Borrelia burgdorferi DNA by polymerase chain reaction in synovial fluid from patients with Lyme arthritis. N Engl J Med. 1994 Jan 27;330(4):229–234. doi: 10.1056/NEJM199401273300401. [DOI] [PubMed] [Google Scholar]
  107. Noordhoek G. T., Wolters E. C., de Jonge M. E., van Embden J. D. Detection by polymerase chain reaction of Treponema pallidum DNA in cerebrospinal fluid from neurosyphilis patients before and after antibiotic treatment. J Clin Microbiol. 1991 Sep;29(9):1976–1984. doi: 10.1128/jcm.29.9.1976-1984.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  108. Ohlenbusch A., Matuschka F. R., Richter D., Christen H. J., Thomssen R., Spielman A., Eiffert H. Etiology of the acrodermatitis chronica atrophicans lesion in Lyme disease. J Infect Dis. 1996 Aug;174(2):421–423. doi: 10.1093/infdis/174.2.421. [DOI] [PubMed] [Google Scholar]
  109. Oksi J., Mertsola J., Reunanen M., Marjamäki M., Viljanen M. K. Subacute multiple-site osteomyelitis caused by Borrelia burgdorferi. Clin Infect Dis. 1994 Nov;19(5):891–896. doi: 10.1093/clinids/19.5.891. [DOI] [PubMed] [Google Scholar]
  110. Orou A., Fechner B., Menzel H. J., Utermann G. Automatic separation of two PCRs in one tube by annealing temperature. Trends Genet. 1995 Apr;11(4):127–128. doi: 10.1016/s0168-9525(00)89021-6. [DOI] [PubMed] [Google Scholar]
  111. Pachner A. R., Delaney E., O'Neill T., Major E. Inoculation of nonhuman primates with the N40 strain of Borrelia burgdorferi leads to a model of Lyme neuroborreliosis faithful to the human disease. Neurology. 1995 Jan;45(1):165–172. doi: 10.1212/wnl.45.1.165. [DOI] [PubMed] [Google Scholar]
  112. Pachner A. R., Delaney E. The polymerase chain reaction in the diagnosis of Lyme neuroborreliosis. Ann Neurol. 1993 Oct;34(4):544–550. doi: 10.1002/ana.410340407. [DOI] [PubMed] [Google Scholar]
  113. Panaccio M., Good R. T., Reed M. B. A road map for PCR from clinical material. J Clin Lab Anal. 1994;8(5):315–322. doi: 10.1002/jcla.1860080510. [DOI] [PubMed] [Google Scholar]
  114. Pecharatana S., Pickett M. A., Watt P. J., Ward M. E. Genotyping ocular strains of Chlamydia trachomatis by single-tube nested PCR. PCR Methods Appl. 1993 Dec;3(3):200–204. doi: 10.1101/gr.3.3.200. [DOI] [PubMed] [Google Scholar]
  115. Persing D. H. Polymerase chain reaction: trenches to benches. J Clin Microbiol. 1991 Jul;29(7):1281–1285. doi: 10.1128/jcm.29.7.1281-1285.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  116. Persing D. H., Rutledge B. J., Rys P. N., Podzorski D. S., Mitchell P. D., Reed K. D., Liu B., Fikrig E., Malawista S. E. Target imbalance: disparity of Borrelia burgdorferi genetic material in synovial fluid from Lyme arthritis patients. J Infect Dis. 1994 Mar;169(3):668–672. doi: 10.1093/infdis/169.3.668. [DOI] [PubMed] [Google Scholar]
  117. Persing D. H., Telford S. R., 3rd, Rys P. N., Dodge D. E., White T. J., Malawista S. E., Spielman A. Detection of Borrelia burgdorferi DNA in museum specimens of Ixodes dammini ticks. Science. 1990 Sep 21;249(4975):1420–1423. doi: 10.1126/science.2402635. [DOI] [PubMed] [Google Scholar]
  118. Persing D. H., Telford S. R., 3rd, Spielman A., Barthold S. W. Detection of Borrelia burgdorferi infection in Ixodes dammini ticks with the polymerase chain reaction. J Clin Microbiol. 1990 Mar;28(3):566–572. doi: 10.1128/jcm.28.3.566-572.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  119. Picken M. M., Picken R. N., Han D., Cheng Y., Strle F. Single-tube nested polymerase chain reaction assay based on Flagellin gene sequences for detection of Borrelia burgdorferi sensu lato. Eur J Clin Microbiol Infect Dis. 1996 Jun;15(6):489–498. doi: 10.1007/BF01691317. [DOI] [PubMed] [Google Scholar]
  120. Picken R. N. 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 Jan;30(1):99–114. doi: 10.1128/jcm.30.1.99-114.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  121. Probert W. S., Allsup K. M., LeFebvre R. B. Identification and characterization of a surface-exposed, 66-kilodalton protein from Borrelia burgdorferi. Infect Immun. 1995 May;63(5):1933–1939. doi: 10.1128/iai.63.5.1933-1939.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  122. Rabb D. C., Lesher J. L., Jr, Chandler F. W. Polymerase chain reaction confirmation of Borrelia burgdorferi in benign lymphocytic infiltrate of dermis. J Am Acad Dermatol. 1992 Feb;26(2 Pt 1):267–268. doi: 10.1016/s0190-9622(08)80309-x. [DOI] [PubMed] [Google Scholar]
  123. Ranki A., Aavik E., Peterson P., Schauman K., Nurmilaakso P. Successful amplification of DNA specific for Finnish Borrelia burgdorferi isolates in erythema chronicum migrans but not in circumscribed scleroderma lesions. J Invest Dermatol. 1994 Mar;102(3):339–345. doi: 10.1111/1523-1747.ep12371793. [DOI] [PubMed] [Google Scholar]
  124. Roberts E. D., Bohm R. P., Jr, Cogswell F. B., Lanners H. N., Lowrie R. C., Jr, Povinelli L., Piesman J., Philipp M. T. Chronic lyme disease in the rhesus monkey. Lab Invest. 1995 Feb;72(2):146–160. [PubMed] [Google Scholar]
  125. Rosa P. A., Hogan D., Schwan T. G. Polymerase chain reaction analyses identify two distinct classes of Borrelia burgdorferi. J Clin Microbiol. 1991 Mar;29(3):524–532. doi: 10.1128/jcm.29.3.524-532.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  126. Rosa P. A., Schwan T. G. A specific and sensitive assay for the Lyme disease spirochete Borrelia burgdorferi using the polymerase chain reaction. J Infect Dis. 1989 Dec;160(6):1018–1029. doi: 10.1093/infdis/160.6.1018. [DOI] [PubMed] [Google Scholar]
  127. Ross S. A., Sánchez J. L., Taboas J. O. Spirochetal forms in the dermal lesions of morphea and lichen sclerosus et atrophicus. Am J Dermatopathol. 1990 Aug;12(4):357–362. doi: 10.1097/00000372-199008000-00005. [DOI] [PubMed] [Google Scholar]
  128. Rychlik W. Priming efficiency in PCR. Biotechniques. 1995 Jan;18(1):84-6, 88-90. [PubMed] [Google Scholar]
  129. Rys P. N., Persing D. H. Preventing false positives: quantitative evaluation of three protocols for inactivation of polymerase chain reaction amplification products. J Clin Microbiol. 1993 Sep;31(9):2356–2360. doi: 10.1128/jcm.31.9.2356-2360.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  130. Schempp C., Bocklage H., Lange R., Kölmel H. W., Orfanos C. E., Gollnick H. Further evidence for Borrelia burgdorferi infection in morphea and lichen sclerosus et atrophicus confirmed by DNA amplification. J Invest Dermatol. 1993 May;100(5):717–720. doi: 10.1111/1523-1747.ep12472369. [DOI] [PubMed] [Google Scholar]
  131. Schempp C., Bocklage H., Owsianowski M., Lange R., Orfanos C. E., Gollnick H. In-vivo- und In-vitro-Nachweis einer Borreliennfektion bei einer morpheaähnlichen Hautveränderung mit negativer Borrelien-Serologie. Hautarzt. 1993 Jan;44(1):14–18. [PubMed] [Google Scholar]
  132. Schmidli J., Hunziker T., Moesli P., Schaad U. B. Cultivation of Borrelia burgdorferi from joint fluid three months after treatment of facial palsy due to Lyme borreliosis. J Infect Dis. 1988 Oct;158(4):905–906. doi: 10.1093/infdis/158.4.905. [DOI] [PubMed] [Google Scholar]
  133. Schmidt B. L., Aberer E., Stockenhuber C., Klade H., Breier F., Luger A. Detection of Borrelia burgdorferi DNA by polymerase chain reaction in the urine and breast milk of patients with Lyme borreliosis. Diagn Microbiol Infect Dis. 1995 Mar;21(3):121–128. doi: 10.1016/0732-8893(95)00027-8. [DOI] [PubMed] [Google Scholar]
  134. Schmidt B., Muellegger R. R., Stockenhuber C., Soyer H. P., Hoedl S., Luger A., Kerl H. Detection of Borrelia burgdorferi-specific DNA in urine specimens from patients with erythema migrans before and after antibiotic therapy. J Clin Microbiol. 1996 Jun;34(6):1359–1363. doi: 10.1128/jcm.34.6.1359-1363.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  135. Schwartz I., Bittker S., Bowen S. L., Cooper D., Pavia C., Wormser G. P. Polymerase chain reaction amplification of culture supernatants for rapid detection of Borrelia burgdorferi. Eur J Clin Microbiol Infect Dis. 1993 Nov;12(11):879–882. doi: 10.1007/BF02000415. [DOI] [PubMed] [Google Scholar]
  136. Schwartz I., Wormser G. P., Schwartz J. J., Cooper D., Weissensee P., Gazumyan A., Zimmermann E., Goldberg N. S., Bittker S., Campbell G. L. Diagnosis of early Lyme disease by polymerase chain reaction amplification and culture of skin biopsies from erythema migrans lesions. J Clin Microbiol. 1992 Dec;30(12):3082–3088. doi: 10.1128/jcm.30.12.3082-3088.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  137. Siebert P. D., Larrick J. W. PCR MIMICS: competitive DNA fragments for use as internal standards in quantitative PCR. Biotechniques. 1993 Feb;14(2):244–249. [PubMed] [Google Scholar]
  138. Sigal L. H. Persisting symptoms of Lyme disease--possible explanations and implications for treatment. J Rheumatol. 1994 Apr;21(4):593–595. [PubMed] [Google Scholar]
  139. Sigal L. H. The polymerase chain reaction assay for Borrelia burgdorferi in the diagnosis of Lyme disease. Ann Intern Med. 1994 Mar 15;120(6):520–521. doi: 10.7326/0003-4819-120-6-199403150-00013. [DOI] [PubMed] [Google Scholar]
  140. Snydman D. R., Schenkein D. P., Berardi V. P., Lastavica C. C., Pariser K. M. Borrelia burgdorferi in joint fluid in chronic Lyme arthritis. Ann Intern Med. 1986 Jun;104(6):798–800. doi: 10.7326/0003-4819-104-6-798. [DOI] [PubMed] [Google Scholar]
  141. Stanek G., Pletschette M., Flamm H., Hirschl A. M., Aberer E., Kristoferitsch W., Schmutzhard E. European Lyme borreliosis. Ann N Y Acad Sci. 1988;539:274–282. doi: 10.1111/j.1749-6632.1988.tb31861.x. [DOI] [PubMed] [Google Scholar]
  142. Steere A. C., Gibofsky A., Patarroyo M. E., Winchester R. J., Hardin J. A., Malawista S. E. Chronic Lyme arthritis. Clinical and immunogenetic differentiation from rheumatoid arthritis. Ann Intern Med. 1979 Jun;90(6):896–901. doi: 10.7326/0003-4819-90-6-896. [DOI] [PubMed] [Google Scholar]
  143. Steere A. C., Grodzicki R. L., Kornblatt A. N., Craft J. E., Barbour A. G., Burgdorfer W., Schmid G. P., Johnson E., Malawista S. E. The spirochetal etiology of Lyme disease. N Engl J Med. 1983 Mar 31;308(13):733–740. doi: 10.1056/NEJM198303313081301. [DOI] [PubMed] [Google Scholar]
  144. Steere A. C. Lyme disease. N Engl J Med. 1989 Aug 31;321(9):586–596. doi: 10.1056/NEJM198908313210906. [DOI] [PubMed] [Google Scholar]
  145. Steere A. C., Schoen R. T., Taylor E. The clinical evolution of Lyme arthritis. Ann Intern Med. 1987 Nov;107(5):725–731. doi: 10.7326/0003-4819-107-5-725. [DOI] [PubMed] [Google Scholar]
  146. Strle F., Cheng Y., Cimperman J., Maraspin V., Lotric-Furlan S., Nelson J. A., Picken M. M., Ruzic-Sabljic E., Picken R. N. Persistence of Borrelia burgdorferi sensu lato in resolved erythema migrans lesions. Clin Infect Dis. 1995 Aug;21(2):380–389. doi: 10.1093/clinids/21.2.380. [DOI] [PubMed] [Google Scholar]
  147. Strle F., Preac-Mursic V., Ruzic E., Wilske B., Cimperman J. Isolation of Borrelia burgdorferi from a skin lesion in a patient with granuloma annulare. Infection. 1991 Sep-Oct;19(5):351–352. doi: 10.1007/BF01645368. [DOI] [PubMed] [Google Scholar]
  148. Tilston P., Corbitt G. A single tube nested PCR for the detection of hepatitis C virus RNA. J Virol Methods. 1995 May;53(1):121–129. doi: 10.1016/0166-0934(95)00006-g. [DOI] [PubMed] [Google Scholar]
  149. Valsangiacomo C., Balmelli T., Piffaretti J. C. A nested polymerase chain reaction for the detection of Borrelia burgdorferi sensu lato based on a multiple sequence analysis of the hbb gene. FEMS Microbiol Lett. 1996 Feb 1;136(1):25–29. doi: 10.1016/0378-1097(95)00477-7. [DOI] [PubMed] [Google Scholar]
  150. Wallach F. R., Forni A. L., Hariprashad J., Stoeckle M. Y., Steinberg C. R., Fisher L., Malawista S. E., Murray H. W. Circulating Borrelia burgdorferi in patients with acute Lyme disease: results of blood cultures and serum DNA analysis. J Infect Dis. 1993 Dec;168(6):1541–1543. doi: 10.1093/infdis/168.6.1541. [DOI] [PubMed] [Google Scholar]
  151. Wallich R., Moter S. E., Simon M. M., Ebnet K., Heiberger A., Kramer M. D. The Borrelia burgdorferi flagellum-associated 41-kilodalton antigen (flagellin): molecular cloning, expression, and amplification of the gene. Infect Immun. 1990 Jun;58(6):1711–1719. doi: 10.1128/iai.58.6.1711-1719.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  152. Walsh P. S., Metzger D. A., Higuchi R. Chelex 100 as a medium for simple extraction of DNA for PCR-based typing from forensic material. Biotechniques. 1991 Apr;10(4):506–513. [PubMed] [Google Scholar]
  153. Weidenthaler B., Roux M., Moter S. E., Schulze H. J., Kramer M. D. Sklerodermiforme Hautveränderungen bei Borrelia-burgdorferi-Infektion. Diagnostischer Einsatz der Polymerase-Kettenreaktion. Hautarzt. 1994 Mar;45(3):171–175. doi: 10.1007/s001050050058. [DOI] [PubMed] [Google Scholar]
  154. Wienecke R., Neubert U., Volkenandt M. Molecular detection of Borrelia burgdorferi in formalin-fixed, paraffin-embedded lesions of Lyme disease. J Cutan Pathol. 1993 Oct;20(5):385–388. doi: 10.1111/j.1600-0560.1993.tb00658.x. [DOI] [PubMed] [Google Scholar]
  155. Wienecke R., Schlüpen E. M., Zöchling N., Neubert U., Meurer M., Volkenandt M. No evidence for Borrelia burgdorferi-specific DNA in lesions of localized scleroderma. J Invest Dermatol. 1995 Jan;104(1):23–26. doi: 10.1111/1523-1747.ep12613456. [DOI] [PubMed] [Google Scholar]
  156. Wienecke R., Zöchling N., Neubert U., Schlüpen E. M., Meurer M., Volkenandt M. Molecular subtyping of Borrelia burgdorferi in erythema migrans and acrodermatitis chronica atrophicans. J Invest Dermatol. 1994 Jul;103(1):19–22. doi: 10.1111/1523-1747.ep12388947. [DOI] [PubMed] [Google Scholar]
  157. Wilke W. W., Jones R. N., Sutton L. D. Automation of polymerase chain reaction tests. Reduction of human errors leading to contamination. Diagn Microbiol Infect Dis. 1995 Apr;21(4):181–185. doi: 10.1016/0732-8893(95)00041-8. [DOI] [PubMed] [Google Scholar]
  158. Williams W. V., Callegari P., Freundlich B., Keenan G., Eldridge D., Shin H., Kreitman M., McCallus D., Weiner D. B. Molecular diagnosis of Borrelia burgdorferi infection (Lyme disease). DNA Cell Biol. 1992 Apr;11(3):207–213. doi: 10.1089/dna.1992.11.207. [DOI] [PubMed] [Google Scholar]
  159. Williams W. V., Callegari P., Freundlich B., Keenan G., Eldridge D., Shin H., Kreitman M., McCallus D., Weiner D. B. Molecular diagnosis of Borrelia burgdorferi infection (Lyme disease). DNA Cell Biol. 1994 Apr;13(4):447–447. doi: 10.1089/dna.1994.13.447. [DOI] [PubMed] [Google Scholar]
  160. Wilske B., Barbour A. G., Bergström S., Burman N., Restrepo B. I., Rosa P. A., Schwan T., Soutschek E., Wallich R. Antigenic variation and strain heterogeneity in Borrelia spp. Res Microbiol. 1992 Jul-Aug;143(6):583–596. doi: 10.1016/0923-2508(92)90116-6. [DOI] [PubMed] [Google Scholar]
  161. Wilson S. M., McNerney R., Nye P. M., Godfrey-Faussett P. D., Stoker N. G., Voller A. Progress toward a simplified polymerase chain reaction and its application to diagnosis of tuberculosis. J Clin Microbiol. 1993 Apr;31(4):776–782. doi: 10.1128/jcm.31.4.776-782.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  162. Wise D. J., Weaver T. L. Detection of the Lyme disease bacterium, Borrelia burgdorferi, by using the polymerase chain reaction and a nonradioisotopic gene probe. J Clin Microbiol. 1991 Jul;29(7):1523–1526. doi: 10.1128/jcm.29.7.1523-1526.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  163. Yssel H., Shanafelt M. C., Soderberg C., Schneider P. V., Anzola J., Peltz G. Borrelia burgdorferi activates a T helper type 1-like T cell subset in Lyme arthritis. J Exp Med. 1991 Sep 1;174(3):593–601. doi: 10.1084/jem.174.3.593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  164. Zbinden R., Goldenberger D., Lucchini G. M., Altwegg M. Comparison of two methods for detecting intrathecal synthesis of Borrelia burgdorferi-specific antibodies and PCR for diagnosis of Lyme neuroborreliosis. J Clin Microbiol. 1994 Jul;32(7):1795–1798. doi: 10.1128/jcm.32.7.1795-1798.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  165. van Dam A. P., Kuiper H., Vos K., Widjojokusumo A., de Jongh B. M., Spanjaard L., Ramselaar A. C., Kramer M. D., Dankert J. Different genospecies of Borrelia burgdorferi are associated with distinct clinical manifestations of Lyme borreliosis. Clin Infect Dis. 1993 Oct;17(4):708–717. doi: 10.1093/clinids/17.4.708. [DOI] [PubMed] [Google Scholar]
  166. von Stedingk L. V., Olsson I., Hanson H. S., Asbrink E., Hovmark A. 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 Jan;14(1):1–5. doi: 10.1007/BF02112610. [DOI] [PubMed] [Google Scholar]

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