Diagnosis Of Lyme Disease

If you think you have any of the above symptoms of Lyme Disease, please see a physician immediately. The EM rash, which may appear in up to 90 % of cases (in the US) is a specific feature of Lyme Disease and treatment should begin immediately (American Lyme Disease Foundation).

Even in the absence of the EM rash, diagnosis of early-stage Lyme Disease can be made on the basis of symptoms and evidence of a tick bite. Typically, blood tests are not useful in the first month after initial infection as they can give false results. However they are more reliable later in the course of the infection.

If you have travelled to a Lyme endemic area, and/or have symptoms consistent with early Lyme disease and suspect exposure to a tick (you have recently done some outdoor activities such as gardening, bushwalking, horseriding, mountain-biking or so on), present your suspicions to your GP so that they may make a more informed diagnosis.

If your early symptoms go undetected or ignored you may go on to develop more severe later stage symptoms several weeks, months, or even years after the initial infection. If this is the case, the US CDC recommends using the FDA approved two-step or “two-tier“: 1st step “EIA” (enzyme immunoassay) or rarely, an “IFA” (indirect immunofluorescence assay) and 2nd step Western-blot blood tests to determine whether you are infected. These tests, as mentioned above are more accurate when performed at least one month after initial infection but are not 100% accurate.

There is some disagreement in the medical literature about the sensitivity and specificity of the ELISA/Western Blot two-tiered testing approach. However, the phase of the illness when testing is done is crucial to the sensitivity and specificity. Combined with various clinical manifestations in early disseminating phase sensitivity ranged from 43 to 100 %, while specificity was uniformly excellent (99 %) in all disease settings (DeBiasi, 2014, Steere et al., 2008). In the latter study by Steere et al. the sensitivity of 2-tier testing in patients with later manifestations of Lyme disease was 100 %, and the specificity was 99 %. Please see The American Lyme Disease Foundation’s downloadable page on the Limitations of Antibody-Based Diagnostic Tests for Lyme Disease (here is the local pdf).

The two-tier testing for Lyme Disease is often criticised by some and as being low in sensitivity (ILADS: 65 %) and is in fact “no better than a coin toss“. However these people are being either incompetent or deliberately misleading. The test results they quote were from patients in the EM or early phase of Lyme Disease, when the immune response was just beginning and the antibody levels are very low. It is expected that the sensitivity at this stage would be quite low and has been reported by several researchers (Aguero-Rosenfeld et al., 1993, Aguero-Rosenfeld et al., 1996, Wormser et al., 2008). It is for this reason the CDC does not recommend testing in the early phase of the disease. Usually the EM rash (if present) is enough evidence to start on a course of antibiotics.

Diagnosis is not by serology alone. A diagnosis of Lyme disease can only be made in the presence of well defined objective clinical symptoms associated with Lyme disease.

If you have the neurological symptoms or swollen joints mentioned above your GP may recommend, in addition, a PCR (Polymerase Chain Reaction) test via a spinal tap or withdrawal of synovial fluid from an affected joint. This test amplifies the DNA of the spirochete and will usually indicate its presence (American Lyme Disease Foundation, Aguero-Rosenfeld et al., 2005).

The Australian Department of Health has guidelines for healthcare providers for the diagnosis of overseas acquired Lyme disease/borreliosis.

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Websites And Links

Centers for Disease Control and Prevention (CDC) page on Lyme Disease

American Lyme Disease Foundation

Infectious Diseases Society of America

University of Sydney’s Tick Borne Diseases Unit

US National Institute of Health

US National Institute of Allergy and Infectious Diseases (Lyme Disease Page)

Books

Institute of Medicine (US) Committee on Lyme Disease and Other Tick-Borne Diseases: The State of the Science. Critical Needs and Gaps in Understanding Prevention, Amelioration, and Resolution of Lyme and Other Tick-Borne Diseases: The Short-Term and Long-Term Outcomes: Workshop Report. Washington (DC): National Academies Press (US); 2011. Available from: http://www.ncbi.nlm.nih.gov/books/NBK57020/

Lyme Disease: the Great Controversy Halperin, J.J., Baker, P., and Wormser, G.P. In, “Lyme Disease: An Evidence-based Approach”(American Lyme Disease Foundation) (Link to Chapter 17 pdf)

Wang, G. (2015). Chapter 104 – Borrelia burgdorferi and other Borrelia species, Molecular Medical Microbiology (Second Edition), Pages 1867–1909, Elsevier Ltd.

Radolf, J. D., et al. (2010). Lyme disease in humans, Caister Academic Press.

Journal Articles

Halperin, J. J. “Nervous system Lyme disease, chronic Lyme disease, and none of the above.” Acta Neurol Belg, 2016, 116(1): 1-6.

Lantos, P. M. “Chronic Lyme disease.” Infect Dis Clin North Am, 2015, 29(2): 325-340.

Aucott, J. N. “Posttreatment Lyme disease syndrome.” Infect Dis Clin North Am, 2015, 29(2): 309-323.

Mayne, P. J. “Clinical determinants of Lyme borreliosis, babesiosis, bartonellosis, anaplasmosis, and ehrlichiosis in an Australian cohort.” Int J Gen Med, 2015, 8: 15-26.

Gofton, A. W., et al. “Inhibition of the endosymbiont “Candidatus Midichloria mitochondrii” during 16S rRNA gene profiling reveals potential pathogens in Ixodes ticks from Australia.” Parasit Vectors, 2015, 8: 345.

Gofton, A. W., et al. “Bacterial profiling reveals novel “Ca. Neoehrlichia”, Ehrlichia, and Anaplasma species in Australian human-biting ticks.” PLoS One, 2015, 10(12): e0145449/0145441-e0145449/0145416.

Patrick, D. M., et al. “Lyme Disease Diagnosed by Alternative Methods: A Phenotype Similar to That of Chronic Fatigue Syndrome.” Clin Infect Dis, 2015.

Ostfeld, R. S. and J. L. Brunner. “Climate change and Ixodes tick-borne diseases of humans.” Philos Trans R Soc Lond B Biol Sci, 2015, 370(1665).

Aguero-Rosenfeld, M. E. and G. P. Wormser. “Lyme disease: diagnostic issues and controversies.” Expert Rev. Mol. Diagn., 2015, 15(1): 1-4.

Halperin, J. J. “Chronic Lyme disease: misconceptions and challenges for patient management.” Infect Drug Resist, 2015, 8: 119-128.

Borchers, A. T., et al. “Lyme disease: a rigorous review of diagnostic criteria and treatment.” J Autoimmun, 2015, 57: 82-115.

Mayne, P., et al. “Evidence for Ixodes holocyclus (Acarina: Ixodidae) as a Vector for Human Lyme Borreliosis Infection in Australia.” J Insect Sci, 2014, 14(1).

Lantos, P. M. and G. P. Wormser. “Chronic coinfections in patients diagnosed with chronic lyme disease: a systematic review.” Am J Med, 2014, 127(11): 1105-1110.

DeBiasi, R. L. “A concise critical analysis of serologic testing for the diagnosis of lyme disease.” Curr Infect Dis Rep, 2014, 16(12): 450.

Brissette, C. A. and R. A. Gaultney. “That’s my story, and I’m sticking to it–an update on B. burgdorferi adhesins.” Front Cell Infect Microbiol, 2014, 4: 41.

Groshong, A. M. and J. S. Blevins. “Insights into the biology of Borrelia burgdorferi gained through the application of molecular genetics.” Adv. Appl. Microbiol., 2014, 86: 41-143.

Lantos, P. M., et al. “A systematic review of Borrelia burgdorferi morphologic variants does not support a role in chronic Lyme disease.” Clin Infect Dis, 2014, 58(5): 663-671.

Pavia, C. S. and G. P. Wormser. “Culture of the entire mouse to determine whether cultivable Borrelia burgdorferi persists in infected mice treated with a five-day course of ceftriaxone.” Antimicrob. Agents Chemother., 2014, 58(11): 6701-6703, 6704 pp.

O’Day, D. H. and A. Catalano. “A lack of correlation between the incidence of lyme disease and deaths due to Alzheimer’s disease.” J Alzheimers Dis, 2014, 42(1): 115-118.

Strle, K., et al. “Elevated Levels of IL-23 in a Subset of Patients With Post-Lyme Disease Symptoms Following Erythema Migrans.” Clin. Infect. Dis., 2014, 58(3): 372-380.

Halperin, J. J., et al. “Common misconceptions about Lyme disease.” Am J Med, 2013, 126(3): 264.e261-267.

Klempner, M. S., et al. “Treatment trials for post-Lyme disease symptoms revisited.” Am J Med, 2013, 126(8): 665-669.

Kobayashi, Y., et al. “A novel macrolide solithromycin exerts superior anti-inflammatory effect via NF-κB inhibition.” J Pharmacol Exp Ther, 2013, 345(1): 76-84.

Ajamian, M., et al. “Serologic markers of lyme disease in children with autism.” JAMA, J. Am. Med. Assoc., 2013, 309(17): 1771-1772.

Burbelo, P. D., et al. “Lack of serum antibodies against Borrelia burgdorferi in children with autism.” Clin. Vaccine Immunol., 2013, 20(7): 1092-1093.

Krut, J. J., et al. “Cerebrospinal fluid Alzheimer’s biomarker profiles in CNS infections.” J. Neurol., 2013, 260(2): 620-626.

Barbour, A. “Remains of infection.J. Clin. Invest., 2012, 122(7): 2344-2346.

Bockenstedt, L. K., et al. “Spirochete antigens persist near cartilage after murine Lyme borreliosis therapy.J. Clin. Invest., 2012, 122(7): 2652-2660.

Embers, M. E., et al. “Persistence of Borrelia burgdorferi in rhesus macaques following antibiotic treatment of disseminated infection.PLoS One, 2012, 7(1): e29914.

Huyshe-Shires, S. “Lyme disease antiscience.” Lancet Infect Dis, 2012, 12(5): 361; author reply 362-363.

Perronne, C. “Lyme disease antiscience.” Lancet Infect Dis, 2012, 12(5): 361-362; author reply 362-363.

Tuttle, C. “Lyme disease antiscience.” Lancet Infect Dis, 2012, 12(5): 362; author reply 362-363.

Auwaerter, P. G., et al. “Lyme disease antiscience – Authors’ reply.” Lancet Infect Dis, 2012, 12(5): 362-363.

Bastos, L. F. S., et al. “Tetracyclines and pain.” Naunyn-Schmiedeberg’s Arch. Pharmacol., 2012, 385(3): 225-241.

Auwaerter, P. G., et al. “Antiscience and ethical concerns associated with advocacy of Lyme disease.” Lancet Infect Dis, 2011, 11(9): 713-719.

Chandra, A., et al. “Anti-Borrelia burgdorferi antibody profile in post-Lyme disease syndrome.” Clin. Vaccine Immunol., 2011, 18(5): 767-771.

Stricker, R. B. and L. Johnson. ““Lyme literacy” and physicians in Connecticut.” J Pediatr, 2011, 158(3): 518-519; author reply 519-520.

Lantos, P. M. “Chronic Lyme disease: the controversies and the science.” Expert Rev Anti Infect Ther, 2011, 9(7): 787-797.

Halperin, J. J. “Nervous system lyme disease: is there a controversy?” Semin Neurol, 2011, 31(3): 317-324.

Schutzer, S. E., et al. “Distinct cerebrospinal fluid proteomes differentiate Post-Treatment Lyme disease from Chronic Fatigue syndrome.” PLoS One, 2011, 6(2): e17287.

Kanjwal, K., et al. “Postural orthostatic tachycardia syndrome following Lyme disease.” Cardiol J, 2011, 18(1): 63-66.

Alvarez, J. I., et al. “Disruption of central nervous system barriers in multiple sclerosis.” Biochim. Biophys. Acta, Mol. Basis Dis., 2011, 1812(2): 252-264.

Johnson, M. and H. M. Feder, Jr. “Chronic Lyme disease: a survey of Connecticut primary care physicians.” J Pediatr, 2010, 157(6): 1025-1029.e1021-1022.

Holzbauer, S. M., et al. “Death due to community-associated Clostridium difficile in a woman receiving prolonged antibiotic therapy for suspected lyme disease.” Clin Infect Dis, 2010, 51(3): 369-370.

Feder, H. M., Jr. “Reply.” J Pediatr, 2010, 158(3): 519-520.

Berende, A., et al. “Activation of innate host defense mechanisms by Borrelia.” Eur. Cytokine Network, 2010, 21(1): 7-18.

Nau, R., et al. “Lyme disease–current state of knowledge.” Dtsch Arztebl Int, 2009, 106(5): 72-81.

Wormser, G. P. and E. D. Shapiro. “Implications of gender in chronic Lyme disease.” J Womens Health (Larchmt), 2009, 18(6): 831-834.

Wahlberg, P. and D. Nyman. “Chronic Lyme borreliosis–fact or fiction?” Duodecim, 2009, 125(12): 1269-1276.

Qureshi, M., et al. “Lyme disease serology in amyotrophic lateral sclerosis.” Muscle Nerve, 2009, 40(4): 626-628.

ALSUntangled update 1: investigating a bug (Lyme Disease) and a drug (Iplex) on behalf of people with ALS.” Amyotrophic Lateral Sclerosis, 2009, 10: 248-250.

Allan, E. J., et al. “Bacterial L-forms.” Adv. Appl. Microbiol., 2009, 68: 1-39.

Wormser, G. P. and I. Schwartz. “Antibiotic treatment of animals infected with Borrelia burgdorferi.” Clin. Microbiol. Rev., 2009, 22(3): 387-395.

Wormser, G. P., et al. “Impact of clinical variables on Borrelia burgdorferi-specific antibody seropositivity in acute-phase sera from patients in North America with culture-confirmed early lyme disease.” Clin. Vaccine Immunol., 2008, 15(10): 1519-1522.

Marques, A. “Chronic Lyme disease: a review.” Infect Dis Clin North Am, 2008, 22(2): 341-360, vii-viii.

Dandache, P. and R. B. Nadelman. “Erythema migrans.” Infect Dis Clin North Am, 2008, 22(2): 235-260, vi.

Steere, A. C., et al. “Prospective study of serologic tests for lyme disease.” Clin Infect Dis, 2008, 47(2): 188-195.

Fallon, B. A., et al. “A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy.” Neurology, 2008, 70(13, Pt. 1): 992-1003.

Hodzic, E., et al. “Persistence of Borrelia burgdorferi following antibiotic treatment in mice.” Antimicrob. Agents Chemother., 2008, 52(5): 1728-1736.

Wilske, B., et al. “Microbiological and serological diagnosis of Lyme borreliosis.” FEMS Immunol. Med. Microbiol., 2007, 49(1): 13-21.

Feder, H. M., Jr., et al. “A critical appraisal of “chronic Lyme disease”.” N. Engl. J. Med., 2007, 357(14): 1422-1430.

Auwaerter, P. G. “Point: antibiotic therapy is not the answer for patients with persisting symptoms attributable to lyme disease.” Clin. Infect. Dis., 2007, 45(2): 143-148.

Stricker, R. B. “Counterpoint: long-term antibiotic therapy improves persistent symptoms associated with lyme disease.” Clin. Infect. Dis., 2007, 45(2): 149-157.

Wormser, G. P. “Clinical practice. Early Lyme disease.” N Engl J Med, 2006, 354(26): 2794-2801.

Wormser, G. P., et al. “The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America.” Clin Infect Dis, 2006, 43(9): 1089-1134.

Steere, A. C. and S. M. Angelis. “Therapy for Lyme arthritis.” Arthritis Rheum., 2006, 54(10): 3079-3086.

Ivetic Tkalcevic, V., et al. “Anti-inflammatory activity of azithromycin attenuates the effects of lipopolysaccharide administration in mice.” Eur. J. Pharmacol., 2006, 539(1-2): 131-138.

Aguero-Rosenfeld, M. E., et al. “Diagnosis of Lyme borreliosis.” Clin. Microbiol. Rev., 2005, 18(3): 484-509.

Bratton, R. L. and R. Corey. “Tick-borne disease.” Am Fam Physician, 2005, 71(12): 2323-2330.

Rothstein, J. D., et al. “β-Lactam antibiotics offer neuroprotection by increasing glutamate transporter expression.” Nature, 2005, 433(7021): 73-77.

Sanz, M.-J., et al. “Erythromycin exerts in vivo anti-inflammatory activity downregulating cell adhesion molecule expression.” Br J Pharmacol, 2005, 144(2): 190-201.

Cameron, D., et al. “Evidence-based guidelines for the management of Lyme disease.” Expert Rev Anti Infect Ther, 2004, 2(1 Suppl): S1-13.

Steere, A. C., et al. “The emergence of Lyme disease.” J. Clin. Invest., 2004, 113(8): 1093-1101.

Auwaerter, P. G., et al. “Lyme borreliosis (Lyme disease): molecular and cellular pathobiology and prospects for prevention, diagnosis and treatment.” Expert Rev Mol Med, 2004, 6(2): 1-22.

Domercq, M. and C. Matute. “Neuroprotection by tetracyclines.” Trends Pharmacol. Sci., 2004, 25(12): 609-612.

Tamaoki, J., et al. “Clinical implications of the immunomodulatory effects of macrolides.” Am. J. Med., 2004, 117(Suppl. 9A): 5S-11S.

Brownstein, J. S., et al. “A climate-based model predicts the spatial distribution of the Lyme disease vector Ixodes scapularis in the United States.” Environ Health Perspect, 2003, 111(9): 1152-1157

Krupp, L. B., et al. “Study and treatment of post Lyme disease (STOP-LD): a randomized double masked clinical trial.” Neurology, 2003, 60(12): 1923-1930.

Kaplan, R. F., et al. “Cognitive function in post-treatment Lyme disease. Do additional antibiotics help?” Neurology, 2003, 60(12): 1916-1922.

Sood, S. K. “Effective retrieval of Lyme disease information on the Web.” Clin Infect Dis, 2002, 35(4): 451-464.

Donta, S. T. “Late and chronic Lyme disease.” Med Clin North Am, 2002, 86(2): 341-349, vii.

Collignon, P. J. “11 Antibiotic resistance.” Med J Aust, 2002, 177(6): 325-329.

Alexopoulou, L., et al. “Hyporesponsiveness to vaccination with Borrelia burgdorferi OspA in humans and in TLR1- and TLR2-deficient mice.” Nat. Med., 2002, 8(8): 878-884.

Bockenstedt, L. K., et al. “Detection of attenuated, noninfectious spirochetes in Borrelia burgdorferi-infected mice after antibiotic treatment.” J Infect Dis, 2002, 186(10): 1430-1437.

Schmutzhard, E. “Multiple sclerosis and Lyme borreliosis.” Wien. Klin. Wochenschr., 2002, 114(13-14): 539-543.

Klempner, M. S., et al. “Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease.” N. Engl. J. Med., 2001, 345(2): 85-92.

Wooten, R. M. and J. J. Weis. “Host-pathogen interactions promoting inflammatory Lyme arthritis: Use of mouse models for dissection of disease processes.” Curr. Opin. Microbiol., 2001, 4(3): 274-279.

Steere, A. C. “Lyme disease.” N Engl J Med, 2001, 345(2): 115-125.

Lindgren, E. and R. Gustafson. “Tick-borne encephalitis in Sweden and climate change.” The Lancet, 2001, 358(9275): 16-18.

Gayle, A. and E. Ringdahl. “Tick-borne diseases.” Am Fam Physician, 2001, 64(3): 461-466.

Patel, R., et al. “Death from Inappropriate Therapy for Lyme Disease.” Clin. Infect. Dis., 2000, 31(4): 1107-1109.

Ozinsky, A., et al. “The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between toll-like receptors.” Proc Natl Acad Sci U S A, 2000, 97(25): 13766-13771.

Marques, A. R., et al. “Lack of evidence of Borrelia involvement in Alzheimer’s disease.” J Infect Dis, 2000, 182(3): 1006-1007.

Hirschfeld, M., et al. “Cutting edge: Inflammatory signaling by Borrelia burgdorferi lipoproteins is mediated by toll-like receptor 2.” J. Immunol., 1999, 163(5): 2382-2386.

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