Lyme Persistence Studies

Persistence of Lyme Disease

The following references for persistence of Lyme disease (Lyme borreliosis) are listed alphabetically and chronologically:


1.          Aalto A, Sjowall J, Davidsson L, Forsberg P, Smedby O. Brain magnetic resonance imaging does not contribute to the diagnosis of chronic neuroborreliosis. Acta Radiol 2007; 48: 755-762. [white matter hyperintensities or basal ganglia lesions].

2.          Abele DC and Anders KH. The many faces and phases of borreliosis. J Am Acad Dermotol 1990; 23:401-410. [chronic Lyme borreliosis].

3.          Aberer E and Klade H. Cutaneous manifestations of Lyme borreliosis. Infection 1991; 19: 284-286. [chronic Lyme borreliosis].

4.          Aberer E, Breier F, Stanek G, and Schmidt B.  Success and failure in the treatment of acrodermatitis chronica atrophicans skin rash. Infection 1996; 24: 85-87.

5.          Aberer E, Kersten A, Klade H, Poitschek C, Jurecka W. Heterogeneity of Borrelia burgdorferi in the skin. Am J Dermatopathol 1996; 18(6): 571-519.

6.          Akin E, McHugh Gl, Flavell RA, Fikrig E, Steere AC. The immunoglobulin (IgG) antibody response to OspA and OspB correlates with severe and prolonged Lyme arthritis and the IgG response to P35 with mild and brief arthritis. Infect Immun 1999; 67: 173-181.

7.          Albert S, Schulze J, Riegel H, Brade V. Lyme arthritis in a 12-year-old patient after a latency period of 5 years. Infection 1999; 27(4-5): 286-288.

8.          Al-Robaiy S, Dihazi H, Kacza J, et al. Metamorphosis of Borrelia burgdorferi organisms―RNA, lipid and protein composition in context with the spirochete’s shape. J Basic Microbiol 2010, 50 Suppl 1, S5-17.

9.          Appel MJG, Allan S, Jacobson RH, Lauderdale TL, Chang YF, Shin SJ, Thomford JW, Todhunter RJ, and Summers BA. Experimental Lyme disease in dogs produces arthritis and persistent infection. J Inf Dis 1993; 167: 651-664.

10.      Åsbrink E, Hovmark A. Successful cultivation of spirochetes from skin lesions of patients with erythema chronicum migrans, Afzelius and acrodermatis chronica atrophicans. Acta Pathol Microbiol Immunol Sect B 1985; 93: 161-163.

11.      Åsbrink E, Hovmark A, and Olsson I. Clinical manifestations of acrodermatitis chronica atrophicans in 50 Swedish patients. Zentralbl Bakteriol Mikrobiol Hyg A 1986; 26: 253-261. [chronic Lyme borreliosis].

12.      Asch ES, Bujak DI, Weiss M, Peterson MGE, and Weinstein A. Lyme Disease: an infectious and postinfectious syndrome. J Rheumatol 1994; 21 (3): 451-461.

13.      Bankhead T and Chaconas G. The role of VlsE antigenic variation in the Lyme disease spirochete: persistence through a mechanism that differs from other pathogens. Molecular Microbiology 2007; 65: 1547-1558.

14.      Barthold SW, Persing DH, Armstrong AL, and Peeples RA. Kinetics of Borrelia burgdorferi dissemination and evolution of disease following intradermal inoculation of mice. Am J Pathol 1991; 139: 263-273. [in mice]

15.      Barthold SW, deSouza MS, Janotka JL, Smith AL, and Persing DH. Chronic Lyme borreliosis in laboratory mouse. Am J Pathol 1993; 143: 951-971. [in mice]

16.      Barthold S. Lyme Borreliosis. Chapter 14, In Persistent Bacterial Infections. Edited by J.P. Nataro, M.J. Blaser, and S. Cunningham-Rundles, pp 281-304. ASM Press, Washington, D.C.

17.      Barthold SW, Hodzic E, Imai DM, Feng S, Yang X, and Luft BJ. Ineffectiveness of tigecycline against persistent Borrelia burgdorferi. Antimicrob Agents Chemother 2010; 54(2): 643-651. [Persistence is listed for many reservoir-competent hosts: mice, rats, Peromyscus leucopus, hamsters, gerbils, rabbits, dogs, nonhuman primates, and humans]

18.      Battafarano DF, Combs JA, Enzenauer RJ, Fitzpatrick JE. Chronic septic arthritis caused by Borrelia burgdorferi. Clin Orthop 1993; 297: 238-241. [Patients with chronic septic Lyme arthritis of the knee for seven years, despite multiple antibiotic trials and synovectomies. Bb documented in synovium and synovial fluid.]

19.      Bayer ME, Zhang L, Bayer MH. Borrelia burgdorferi DNA in the urine of treated patients with chronic Lyme disease symptoms. A PCR study of 97 cases. Infection 1996; 24: 347-353. [97 patients who had been treated with antibiotics for extended periods of time and had symptoms of chronic Lyme were PCR-positive.]

20.      Benjamin J and J Luft. Chronic Lyme disease; an evolving syndrome. 9th Annual International Scientific Conference on Lyme Disease & Other Tick-Borne Disorders. 1996.

21.      Berglund J, Stjernberg L, Ornstein K, Tykesson-Joelsson K, Walter H. 5-y follow-up study of patients with neuroborreliosis. Scand. J. Infect. Dis. 2002; 34(6): 421-425.

22.      Bloom BJ, Wyckoff PM, Meissner HC, and Steere AC. Neurocognitive abnormalities in children after classic manifestations of Lyme disease. Pediatric Infect. Dis. J. 1998; 17(3): 189-196.

23.      Bradley JF, Johnson RC, Goodman JL.  The persistence of spirochetal nucleic acids in active Lyme arthritis. Ann Intern Med 1994; 120: 487.

24.      Bransfield R, Brand S, and Sherr V. Treatment of patients with persistent symptoms and a history of Lyme disease. N Engl Med 2001; 345: 1424-5.

25.      Breier F, Khanakah G, Stanek G, Aberer E, Schmidt B, and Tappeiner G.  Isolation and polymerase chain reaction typing of Borrelia afzelii from a skin lesion in a seronegative patient with generalized ulcerating bullous lichen sclerosus et atrophicus. Br J Dermatol 2001; 144: 387-392. [Borrelia afzelii, ulcerating lichen sclerosus et atrophicus]. [Despite treatment with four courses of ceftriaxone, “[s’pirochetes were isolated from skin cultures obtained from enlarging LSA lesion…[S]erology …was repeatedly negative.]

26.      Bockenstedt LK, J Mao, E Hodzic, SW Barthold, and D Fish. Detection of attenuated, noninfectious spirochetes in Borrelia burgdorferi-infected mice after antibiotic treatment. J Infect Dis 2002; 186: 1430-1437. [in mice]

27.      Brorson O and Brorson S-H. Transformation of cystic forms of Borrelia burgdorferi to normal mobile spirochetes. Infection. 1997; 25: 240-246. [change in physical characteristics; change of spirochetes to other pleomorphic forms, i.e., cell wall deficient forms, namely cysts.]

28.      Brorson O and Brorson S. In vitro conversion of Borrelia burgdorferi to cystic forms in spinal fluid, and transformation to mobile spirochetes by incubation in BSK-H medium. Infection. 1998; 26: 144-150. [change in physical characteristics; change of spirochetes to other pleomorphic forms, i.e., cell wall deficient forms, namely cysts.]

29.      Brorson O and Brorson S-H. An in vitro study of the susceptibility of mobile and cystic forms of Borrelia burgdorferi to tinidazole. International Microbiol 2004; 7: 139-142.

30.      Brown JP, Zachary JF, Teuscher C, Weis JJ, and Wooten M. Dual role of interleukin-10 in murine Lyme disease: regulation of arthritis severity and host defense. Infect Immun 1999; 67: 5142-5150. [suppression of harmful immune responses: defense stratagem of B. burgdorferi]

31.      Burrascano J.  Failure of aggressive antibiotic therapy to protect the placenta from invasion by B. burgdorferi in a pregnant patient with Lyme borreliosis.  6th Annual International Science Conference on Lyme Disease and other Tick-borne Diseases.1993.

32.      Cabello FC, Godfrey HP, and Newman SA. Hidden in plain sight: Borrelia burgdorferi and the extracellular matrix. Trends in Microbiology 2007; 15: 350-354. [sequestration]

33.      Cadavid D, O’Neill T, Schaefer H, and Pachner AR. Localization of Borrelia burgdorferi in the nervous system and organs in a nonhuman primate model of Lyme disease. Lab Invest 2000; 80: 1043-1054.

34.      Cadavid D, Y Bai, E Hodzic, K Narayan, SW Barthold, and Pachner AR. Cardiac involvement in non-human primates infected with the Lyme disease spirochete Borrelia burgdorferi. Lab Invest 2004; 84: 1439-1450. [in monkeys]

35.      Cameron D, Gaito A, Harris N et al. Evidence-based guidelines for the management of Lyme disease. Expert Rev Anti-Infect. Ther 2004; 2 (Suppl. 1), S1-S13.

36.      Cameron D. Results from Lyme disease treatment trial. Columbia University/LDA Conference, Lyme & Other Tick-Borne Diseases: Emerging Tick-Borne Diseases. October 28, 2005; Philadelphia, Pennsylvania.

37.      Cameron DJ. Generalizability in two clinic trials of Lyme disease. Perspectives and Innovation 2006; 3(12). [].

38.      Cameron D. Severity of Lyme disease with persistent symptoms. Insights from a double-blind placebo-controlled clinical trial. Minerva Med 2008; 99: 489-496.

39.      Cameron DJ. Insufficient evidence to deny antibiotic treatment to chronic Lyme disease patients. Med Hypotheses (2009), doi:10.1016i/j.mehy.2009.01.017

40.      Cameron DJ. Proof that Lyme disease exists. 2010. [].

41.      Cameron DJ. Proof that chronic Lyme disease exists. Interdisciplinary Perspect Infect Dis 2010. doi:10.1155/2010/876450.

42.      Cimmino MA, Azzolini A, Tobia F, Pesce CM. Spirochetes in the spleen of a patient with chronic Lyme disease. Am J Clin Pathol 1989; 91(1): 95-97.

43.      Chary-Valckenaere I, Jaulhac B, Champigneulle J, Piement Y, Mainard D, and Pourel J. Ultrastructural demonstration of intracellular localization of Borrelia burgdorferi in Lyme arthritis. Br J Rheumatol 1998; 37: 468-470.

44.      Chmielewski T, Tylewlska-Wierzhanowska S. Inhibition of fibroblast apoptosis by Borrelia afzelii, Coxiella burnetii and Bartonella henselae. Poll Microbiol 2011; 60(3); 269-272.

45.      Clarke AE, Esdaile JM, Bloch DA, Lacaille D, Danoff, and Fries JF. A Canadian study of the total medical costs for patients with systemic lupus erythema and the predictors of costs. Arthrit. Rheum. 1993; 36(11): 1548-1593.

46.      Cleveland CP, Dennler PS, Duray PH.  Recurrence of Lyme disease presenting as a chest wall mass:   Borrelia burgdorferi was present despite five months of IV ceftriaxone 2 g, and three months of oral cefixime 400 mg BID. The presence of Borrelia burgdorferi confirmed by biopsy and culture.  Poster presentation at V Lyme Disease Foundation International Scientific Conference. Stamford, CT, April 10-11, 1992.

47.      Cleveland CP, and Dennler S. Case history: recurrence of Lyme disease as a chest wall mass. Abstract presented at the 1993 LDF International Conference on Lyme Disease.

48.      Coyle P. Lyme Disease. Mosby Year Book, pp. 235, 1993. St Louis, Mo. [seclusion into immune privileged sites: defense strategem of B. burgdorferi]

49.      Dattwyler RJ, Volkman DJ, Luft BJ, Halperin JJ, Thomas J, and Golightly MG. Seronegative Lyme disease. Dissociation of specific T- and B-lymphocyte response to Borrelia burgdorferi. N Engl J Med 1988; 319(22): 1441-1446.

50.      Dejmková H, D Hulinska, D Tegzová, K Pavelka, J Gatterová, and P Vavřik. Seronegative Lyme arthritis caused by Borrelia garinii. Clin Rheumatol 2002; 21:330-334.

51.      DeLong AK, Blossom B, Maloney E, and Phillips SE. Antibiotic retreatment of Lyme disease in patients with persistent symptoms: A biostatistical review of randomized, placebo-controlled, clinical trials. Contemp Clin Trials 2012; epub ahead of print. [refutes Klempers {2001} conjecture that long-term antibiotics don’t work]

52.      de Koning J, et al. Demonstration of spirochetes in cardiac biopsies of patients with Lyme disease.  J. Infect. Dis. 1989; 160: 150-153. [intracellar sanctuaries of Bb]

53.      Demaershalck I, Messaoud AB, de Kesel M, Hoyois B, Lobet Y, Hoet P, Bigaignon G, Bollen A, and Godfroid E.  Simultaneous presence of different Borrelia burgdorferi genospecies in biological fluids of Lyme disease patients. J Clin Microbiol 1995: 33; 602-608.

54.      Diringer MN, Halperin JJ, and Dattwyler RJ. Lyme meningoencephalitis―report of a severe, penicillin resistant case. Arthritis Rheum 1987; 30: 705-708.

55.      Diterich I, Rauter C, Kirschning CJ, and Hartung T. Borrelia burgdorferi-induced tolerance as a model of persistence via immunosuppression. Infect Immun 2003; 71(7):3979-3987.

56.      Donta ST. Tetracycline therapy for chronic Lyme disease. Clin Inf Dis 1997; 25 (Suppl 1);S52-56.

57.      Donta ST. The existence of chronic Lyme disease. Curr Treat Op Infect Dis 2001; 3: 261-262.

58.      Donta ST. Late and chronic Lyme disease. Med Clin North Am 2002; 86: 341-349.

59.      Donta ST. Macrolide therapy of chronic Lyme disease. Med Sci Monit 2003; 9: 136-142.

60.      Dorward DW, Fischer ER, and Brooks DM. Invasion and cytopathic killing of human lymphocytes by spirochetes causing Lyme disease. Clin. Infect. Dis. 1997. 25 Suppl 1: S2-8. [intracellular sanctuaries of Bb]

61.      Dunham-Ems SM, Caimano MJ, Pal U, et al. Live imaging reveals a biphasic mode of dissemination of Borrelia burgdorferi within ticks. J. Clin Invest. 2009; 119: 3652-3665. [biofilms consist of a colony of spirochetes and cysts coated by a gelatinous, protective membrane]

62.      Duray PH. 1987. The surgical pathology of human Lyme disease. An enlarging picture. Am J Surg Pathol S1: 47-60. [Bb in brain]

63.      Duray PH and Steere AC. Clinical pathologic correlations of Lyme disease by stage. Ann N Y Acad Sci 1988; 539: 65-79.

64.      Duray PH, et al. Invasion of human tissue ex vivo by Borrelia burgdorferi.  J. Infect. Dis. 2005. 191(10): 1747-1754.

65.      Durovska J, Bazovska S, Ondrisova M, and Pancak J. 2010. Our experience with examination of antibodies against antigens of Borrelia burgdorferi in patients with suspected Lyme disease. Bratist. Lek. Listy 2010; 111(3): 153-155.

66.      Dvorakova J, and Celer V. [Pharmacological aspects of Lyme borreliosis] Seska Slov Farm. 2004(Jul); 53(4): 159-164.

67.      Ebel GD, Campbell EN, Goethert HK, Spielman A, and Telford SR. Enzootic transmission of deer tick virus in New England and Wisconsin sites. Am. J. Trop. Med. Hyg. 2000; 63(1-2): 36-42.

68.      Ekdahl KN, Henningsson AJ, Sandholm K, Forsberg P, Ernerudh J, Ekerfelt C; Immunity in borreliosis with special emphasis on the role of complement. Adv Exp Med Biol 2007; 598: 198-213.

69.      Embers ME, SW Barthold, JT Borda, L Bowers, L Doyle, E Hodzic, MB Jacobs, NR Hasenkampf, DS Martin, S. Narasimhan, KM Phillippi-Falkenstein, JE Purcell, MS Ratterree, and MT Philipp. Persistence of Borrelia burgdorferi in rhesus macaques following antibiotic treatment of disseminated infection. PLoS ONE 7(1): e29914. doi:10.1371/journal.pone.0029914  (2012) [Bb was cultured from rhesus macques after antibiotic treatment and confirmed by PCR.]

70.      Fallon BA, Schwartzberg M, Bransfield R, Zimmerman B, Scotti A, Weber CA, and Liebowitz MR. Late-stage neuropsychiatric Lyme borreliosis. Case reports. Psychosomatics 1995; 36: 295-300.

71.      Fallon BA, Das S, Plutchok JJ, Tager F, Liegner K, Van Heertum R. Functional brain imaging and neuropsychological testing in Lyme disease. Clin Infect Dis 1997; 25 (suppl 1): S57-S63.

72.      Fallon BA, et al. Repeated antibiotic treatment in chronic Lyme disease. J Spir Tick Borne Dis. 1999; 6: 94-101.

73.      Fallon BA, Keilp J, Prohovnik I, Heertum RV, Mann JJ. Regional cerebral blood flow and cognitive deficits in chronic Lyme disease. J Neuropsychiatry Clin Neurosci 2003; 15: 326-332.

74.      Fallon BA, Keilp JG, Corbera KM, Petkova K, Britton CB, Dwyer E, et al. A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy. Neurology 2008; 70: 992-1003.

75.      Fallon BA, Lipkin RB,  Corbera KM, Yu S, Nobler MS, Keilp JG, Petkova E, Lisanby SH, Moeller JR, Slavov I, Van Heertum R, Mensh BD, and Sackeim HA. Regional cerebral blood flow and metabolic rate in persistent Lyme encephalopathy. Arch Gen Psychiatry 2009; 66: 554-563.

76.      Feder Jr., HM and Whitaker DL. Misdiagnosis of erythema migrans. Am. J. Med. 1995; 99: 412-419.

77.      Fein L, and Tilton RC. Bone marrow as a source for Borrelia burgdorferi DNA. J Spir Tick-borne Dis 1997; 4: 58-60.

78.      Ferris J, et al. Lyme borreliosis. [letter] Lancet 1995; 345: 1436-1437.

79.      Franz JK, O Fritze, M Rittig et al. Insights from a novel three-dimensional in vitro model of Lyme arthritis: standardized analysis of cellular and molecular interactions between Borrelia burgdorferi and synovial explants and fibroblasts. Arthritis Rheum 2001; 44: 151-162.

80.      Fraser DD, Kong LI, and Miller FW. Molecular detection of persistent Borrelia burgdorferi in a man with dermatomyositis. Clinical and Experimental Rheumatology 1992; 10: 387-390.

81.      Frey M, Jaulhac B, Piemont Y, Marcellin L, Boohs PM, Vautravers P, Jesel M, Kuntz JL, Monteil H, and Sibilia J. Detection of Borrelia burgdorferi DNA in muscle of patients with chronic myalgia related to Lyme disease. Am J Med 1988; 104: 591-594.

82.      Fried MD, Duray P. Gastrointestinal disease in children with persistent Lyme disease: spirochetes isolated form the G.I. tract. IX Lyme Disease Foundation International Scientific Conference, Boston, MA, April 19-20, 1996.

83.      Garcia-Monco JC, Benach JL. The pathogenesis of Lyme disease. Rheum Dis Clin North Am 1989; 15: 711-726.

84.      Georgilis K, Peacocke M, and Klempner MS. Fibroblasts protect the Lyme disease spirochete, Borrelia burgdorferi, from ceftriaxone in vitro. J Infect Dis 1992; 166: 440-444.

85.      Giambartolomei GH, Dennis VA, and Philipp MT. Borrelia burgdorferi stimulates the production of interleukin-10 in peripheral blood mononuclear cells from uninfected humans and rhesus monkeys. Infect Immun 1998; 66: 2691-2697. [suppression of harmful immune responses: defense stratagem of B. burgdorferi]

86.      Girschick HJ, Huppertz HI, Rüssmann H, Krenn V, and Karch H. Intracellular persistence of Borrelia burgdorferi in human synovial cells. Rheumatol Int 1996; 16: 125-132. [intracellar sanctuaries of Bb]

87.      Goodman JL, Jurkovich P, Kodner C, and Johnson RC. Persistent cardiac and urinary tract infections with Borrelia burgdorferi in experimentally infected Syrian hamsters. J Clin Microbiol 1991; 29: 894-896.

88.      Grignolo MC, Buffrini L, Monteforte P, and Rovetta G. Reliability of a polymerase chain reaction (PCR) technique in the diagnosis of Lyme borreliosis. Minerva Med 2001; 92(1): 29-33. [Article in Italian]

89.      Gruntar I, et al. Conversion of Borrelia garinii cystic forms to motile spirochetes in vivo. APMIS 2001; 109(5): 383-388. [Persistence occurs when spirochetes change physical characteristics by converting to dormant cysts, and vis versa.]

90.      Halperin JJ,, Luft BJ, Anand AK, Roque CT, Alvarez O, Volkman DJ, Dattwyler RJ. Lyme neuroborreliosis: central nervous system manifestations. Neurology 1989; 39: 753-759. [hyperintensities persist after treatment]

91.      Halperin JJ. Prolonged Lyme disease treatment: enough is enough. Neurology 2008; 70(13): 986-987.

92.      Harvey WT and Salvato P. ‘Lyme disease’: ancient engine of an unrecognized borreliosis pandemic? Med Hypotheses 2003; 60: 742-759.

93.      Hassett AL, Radvanski DC, Buyske S, Savage SV, and Sigal LH. Psychiatric comorbidity and psychological factor in patients with “chronic Lyme disease.” Am. J. Med. 2009; 122(9): 843-850.

94.      Hassler D, Riedel K, Zorn J and Preac-Mursic V. Pulsed high-dose cefotaxime therapy in refractory Lyme borreliosis (letter). Lancet 1991; 338: 193.

95.      Häupl T, Hahn G, Rittig M, Krause A, Schoerner C, Schonherr U, Kalden JR, and Burmester GR. Persistence of Borrelia burgdorferi in ligamentous tissue from a patient with chronic Lyme borreliosis. Arthritis Rheum 1993; 36(11): 1621-1626. [Repeated antibiotic treatment necessary to stop the progession of disease but did not completely eliminate Bb from all sites of infection. Bb cultured from ligament sample; intracellar sanctuaries for Bb]

96.      Henneberg JP, and Neubert U.  Borrelia burgdorferi group: in vitro antibiotic sensitivity. Orv Hetil 2002; 143: 1195-1198.

97.      Hilton E, Tramontano A, DeVoti J, and Sood SK. Temporal study of immunoglobulin M seroreactivity to Borrelia burgdorferi in patients treated for Lyme borreliosis. J Clin Microbiol 1997; 35(3): 774-776.

98.      Hodzic E, Feng S, and Barthold SW. Stability of Borrelia burgdorferi outer surface protein C under immune selection pressure. J Infect Dis 2000; 181: 750-753.

99.      Hodzic E, Feng S, Holden K, Freet KJ, and Barthold SW. Persistence of Borrelia burgdorferi following antibiotic treatment in mice. Antimicrob Agents Chemother 2008; 52: 1728-1736. [in mice: following antibiotic treatment; mice remained infected with infectious spirochetes.]

100.   Holl-Weiden A, Suerbaum S, and Girschick HJ. Seronegative Lyme arthritis. Rheumatology International 2007; 11: 1091-1093.

101.   Honegr K, Hulinska D, Dostal V, Gebousky P, Hankova E, Horacek J, Vyslouzil L, and Havlasova J.  Persistence of Borrelia burgdorferi sensu lato in patients with Lyme borreliosis. Epidemiol Mikrobiol Immunol. 2001; 50: 10-16.

102.   Horowitz R. Chronic persistent Lyme borreliosis: PCR evidence of chronic infection despite extended antibiotic therapy – a retrospective review. 13th International Scientific Conference on Lyme Disease and Other Tick-Borne Disorders. CT, USA, 24-26 March 2000.

103.   Hudson BJ, Stewart M, Lennox VA, Fukunaga M, Yabuki M, Macorison H, Kitchener-Smith J. Culture-positive Lyme borreliosis. Med J Aust 1998; 168(10): 500-502.

104.   Hulínská D, Krausova M, Janovská D, Rohácová H, Hancil J, Mailer H. Electron microscopy and the polymerase chain reaction of spirochetes from the blood of patients with Lyme disease. Cent Eur J Public Health 1993; 1(2): 81-85.

105.   Hulinska D, Votypka J, and Valesova M. Persistence of Borrelia garinii and Borrelia afzelii in patients with Lyme arthritis. Int J Med Microbiol Virol Parasitol Infecdt Dis 1999; 289(3): 301-318.

106.   Hunfeld KP, Ruzic-Sabljic E, Norris DE, Kraiczy P, and Strle F. In vitro susceptibility testing of Borrelia burgdorferi sensu lato isolates cultured from patients with erythema migrans before and after antimicrobial chemotherapy. Antimicro Agents Chemother 2005; 49: 1294-1301.

107.   International Lyme and Associated Diseases Society (ILADS).  Evaluation of antibiotic treatment in patients with persistent symptoms of Lyme disease.

108.   James FM, JB Engiles, and J Beech. Meningitis, cranial neuritis, and radiculoneuritis associated with Borrelia burgdorferi infection in a horse. Journal of American Veterinary Medical Association 2010; 237: 1180-1185. [Horse was seropositive for Bb, and PCR assay of CSF for B. burgdorferi DNA was positive; horse was treated with doxycycline, responded well, then relapsed, treated with oxytetracycline and later died; diagnosis consistent with neuroborreliosis.]

109.   Johnson L and Stricker JB. Treatment of Lyme disease: a medicolegal assessment. Expert Rev Anti-Infect Ther 2004. 2: 533-557.

110.   Kaiser R. Clinical courses of acute and chronic neuroborreliosis following treatment with ceftriaxone. Nervenarzt. 2004(June); 75(6): 553-557.

111.   Kalish RA, Leong JM, and AC Steere. Association of treatment-resistant chronic Lyme arthritis with HLA-DR4 and antibody reactivity to OspA and OspB of Borrelia burgdorferi. Infect Immun 1993; 61: 2774-2779.

112.   Karma A, Stenborg T, Summanen P, Immonen I, Mikkila H, and Seppala I.  Long-term follow-up of chronic Lyme neuroretinitis. Retina 1996; 16: 505-509.

113.   Keat AC, and Hughes R.  Infectious agents in reactive arthritis. Curr Opin Rheumatol 1993; 5: 414-419.

114.   Keller TL, Halperin JJ, and Whitman M.  PCR detection of Borrelia burgdorferi DNA in cerebrospinal fluid of Lyme neuroborreliosis patients. Neurology 1992; 43: 32-42.

115.   Kersten A, Poitschek C, Rauch S, and Aberer E.  Effects of penicillin, ceftriaxone, and doxycycline on morphology of Borrelia burgdorferi. Antimicrob Agents Chemother 1995; 39: 1127-1133.

116.   Keszler K, and Tilton RC.  Persistent PCR positivity in a patient being treated for Lyme disease.  Journal of Spirochetal and Tick-Borne Diseases 1995; 2: 57-58.

117.   Kirsch M,, Ruben FL, Steere AC, Duray PH, Norden CW, Winkelstein A. Fatal adult respiratory distress syndrome in a patient with Lyme disease. JAMA 1988; 259(18) 2737-2739.

118.   Klempner MS, Noring R, and Rogers RA.  Invasion of human skin fibroblasts by the Lyme disease spirochetes, Borrelia burgdorferi. J Inf Dis 1993; 167: 1074-81.

119.   Kraiczy P, Hellwage J, Skerka C, Becker H, Kirschfink M,, Simon MM, et al. Complement resistance of Borrelia burgdorferi correlates with the expression of BbCRASP-1, a novel linear plasmid-encoded surface protein that interacts with human factor H and FHL-1 and is unrelated to Erp proteins. J Biol Chem 2004; 279: 2421-2429.

120.   Krupp LB, Masur D, Schwartz J, Coyle PK, Langenback IJ, and Fernquist SK. Cognitive functioning in late Lyme borreliosis. Arch Neurol 1999; 48: 1125-1129.

121.   Krupp LB, Hyman LG, Grimson R, Coyle PK, Melville P, Ahnn S, et al. Study and treatment of post Lyme disease (STOP-LD): a randomized double masked clinical trial. Neurology 2003; 60: 1923-1930.

122.   Krüger H, Helm E, Schuknecht B, and Scholz S. Acute and chronic neuroborreliosis with and without CNS involvement: a clinical, MRI, and HLA study of 27 cases. J Neurol 1991; 238: 271-280.

123.   Kullberg BJ, Berende A, van der Meer JW. The challenge of Lyme disease: tired of the Lyme wars. Neth J Med 2011; 69: 98-100. [refutes Klempers {2001} conjecture that long-term antibiotics don’t work]

124.   Latov N, Wu AT, Chin RL, Sander HW, Alaedini A, and Brannagran TH. Neuropathy and cognitive impairment following vaccination with the OspA protein of Borrelia burgdorferi. J Peripher Nerv Syst 2004; 9: 165-167.

125.   Lavoie PE. Failure of published antibiotic regimens in Lyme borreliosis: observations on prolonged oral therapy. Abstract. Lyme Borreliosis International Conference, Sweden, 1990.

126.   Lavoie PE.  Protocol from Rakel’s: explains persistence of infection despite “standard” courses of antibiotics. Lyme Times, Lyme Disease Resource Center, 1992; 2: 25-27. Reprinted from Conn’s Current Therapy, 1991.

127.   Lawrence C, Lipton RB, Lowy RD, and Coyle PK.  Seronegative chronic relapsing neuroborreliosis. Eur Neurol 1995; 35(2): 113-117. [Patient’s CSF was positive for complex anti-Bb antibodies, B. burgdorferi nucleic acids and free antigen despite aggressive antibiotic therapy.]

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247.   Stricker RB, Lautin A, and Burrascano JJ. Lyme disease: point/counterpoint. Expert Rev Anti-Infect Ther 2005: 3: 155-165.

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249.   Stricker RB, Green CL, Savely VR, Chamallas SN, and Johnson L. Benefit of intravenous antibiotic therapy in patients referred for treatment of neurologic Lyme disease. Int J Gen Med 2011; 4: 639-646. [refutes Klempers {2001} conjecture that long-term antibiotics don’t work]

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252.   Strle F, Cheng Y, Cimperman J, Maraspin V, Lotric-Furlan S, Nelson JA, Picken MM, Ruzic-Sabljic E, and Picken R.  Persistence of Borrelia burgdorferi sensu lato in resolved erythema migrans lesions.  Clin Inf Dis 1995; 23: 380-389.

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254.   Summers BA, Straubinger AF, Jacobson RH, Chang YF, Appel MJG, and Straubinger RK. Histopathological studies of experimental Lyme disease in the dog. J Comparative Pathol 2005; 133: 1-13.

255.   Sung SY, McDowell JV, Carlyon JA, and Marconi RT. Mutation and recombination in the upstream homology box-flanked ospE-related genes of the Lyme disease spirochetes result in the development of new antigenic variants during infection. Infect Immun 2000; 68; 1319-1327.

256.   Valesová M, et al. Detection of Borrelia in the synovial tissue from a patient with Lyme borreliosis by electron microscopy.  J. Rheumatol. 1989;16(11): 1502-1505. [intracellar sanctuaries of Bb]

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259.   Vázquez M, Sparrow SS, and Shapiro ED. Long-term neuropsychologic and health outcomes of children with facial nerve palsy attributable to Lyme disease. Pediatrics 2003; 112(2): e93-e97.

260.   Walberg P, Granlund H, Nyman D, Panelius J, and Seppälä I.  Treatment of late Lyme borreliosis. J Infection 1994; 29: 255-261.

261.   Waniek C, Prohovnik I, Kaufman MA, and Dwork AJ.  Rapid progressive frontal-type dementia associated with Lyme disease.  J Neuropsychiatry Clin Neurosci 1995; 7: 345-347. (B. burgdorferi detected at autopsy).

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264.   Weis JJ, Yang L, Seiler KP, and Silver RM.  Pathological manifestations in murine Lyme disease: association with tissue invasion and spirochete persistence.  Clin Infect Dis 1997 Suppl 1: S18-24.

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269.   Yrjänäinen H, Hytönen J, Söderström KO, Oksi J, Hartiala K, Viljanen MK. Persistent joint swelling and borrelia-specific antibodies in Borrelia garinii-infected mice after eradication of vegetative spirochetes with antibiotic treatment. Micr Infect 2006; 8: 2044-2051. [persistence if Bb in mice]

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271.   Yrjänäinen H, Hytönen J, Hartiala P, Oksi J, Viljanen MK. APMIS 2010;118(9): 665-673. [Borrelia burgdorferi DNA in joints and tissue adjacent to the joint is the niche of persisting B. burgdorferi in ceftriaxone-treated mice.]

272.   Zhang JR, Hardham JM, Barbour AG, and Norris SJ. Antigenic variation in Lyme disease Borreliae by promiscuous recombination of VMP-like sequence cassettes. Cell 1997; 89: 275-285. [antigenic variation: a defense stratagem of B. burgdorferi]

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Compiled by: John D. Scott, Research Division                                                       

April 2013

Lyme Disease Association of Ontario