What s All the Fuss About Lyme Disease?

Transcription

1 What s All the Fuss About Lyme Disease? David M. Mushatt, MD, MPH&TM, FIDSA Chief, Tulane Adult ID Section Director, Tulane Adult ID Fellowship Training Program

2 Agent/Epidemiology Borrelia burgdorferi, a spirochete Vector: Ixodes ticks (I. scapularis, etc.) Ixodes nymphs quest during late spring, early summer, feeding on humans Mice predominant host, deer also important Humans come in contact with ticks along edges of fields adjacent to wooded areas

3 Incidence annual incidence is 107 cases/100, ,000 LD cases occur annually 10x the number reported Incidence of clinician-diagnosed Lyme disease, United States, Emerg Infect Dis, 2015 Aug.

4 Reported Cases of Lyme Disease by Year, United States,

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6 Life Cycle of Blacklegged Ticks that Can Transmit Anaplasmosis, Babesiosis, and Lyme Disease

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8 CLINICAL ASPECTS

9 Timeline of Stages of Lyme

10 Early Localized Stage (3 to 30 days post-tick bite) Red, expanding rash called erythema migrans (EM) Fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes

11 Shapiro ED. N Engl J Med 2014;370:

12 Early Disseminated Stage (days to weeks post-tick bite) Untreated, the infection may spread from the site of the bite to other parts of the body, producing an array of specific symptoms that may come and go, including: Additional EM rashes on other areas of the body Facial or Bell's palsy Severe headaches and neck stiffness due to meningitis Pain and swelling in the large joints (such as knees) Shooting pains that may interfere with sleep Heart palpitations and dizziness due to changes in heartbeat (Lyme carditis)

13 Bell s Palsy

14 Late Disseminated Stage (months to years post-tick bite) Approximately 60% of patients with untreated infection may begin to have intermittent bouts of arthritis Large joints are most often affected, particularly the knees Up to 5% of untreated patients may develop chronic neurological complaints Shooting pains, numbness, or tingling in the hands or feet, and problems with short-term memory

15 DIAGNOSIS

16 Clinical Diagnosis Erythema migrans (EM) + exposure risk = Lyme disease Serology (EIA, IgM) may be negative in early stage 1

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18 Pitfalls in Diagnosis EIA frequent false positives false negative in up to 65%, IgM peaks in 3-6 weeks Western blot (WB) confirmatory test IgM false positives common Positive IgM > 2 bands 1 out of 3 bands is not weakly or borderline positive Positive IgG > 5 bands 3 out of 5 bands is not partially positive! DO NOT ORDER WB UNLESS EIA + C6 Peptide Antibody assay

19 Post-treatment Lyme Disease Syndrome PTLDS Approximately 10-20% of patients with Lyme disease have symptoms that last months to years after treatment with antibiotics muscle and joint pains, cognitive difficulties, sleep disturbances, or fatigue

20 THE CONTROVERSY

21 The Evil Axis Clinical Infectious Diseases 2006; 43:

22 The Controversy To date, there is no convincing biologic evidence for the existence of symptomatic chronic B. burgdorferi infection among patients after receipt of recommended treatment regimens for Lyme disease. Antibiotic therapy has not proven to be useful and is not recommended for patients with chronic (> 6 months) subjective symptoms after administration of recommended treatment regimens for Lyme disease.

23 Attorney General Richard Blumenthal today announced that his antitrust investigation has uncovered serious flaws in the Infectious Diseases Society of America s (IDSA) process for writing its 2006 Lyme disease guidelines and the IDSA has agreed to reassess them with the assistance of an outside arbiter

24 Clinical Infectious Diseases, 2010;51:1-5

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28 Post-Treatment Lyme Disease Syndrome (PTLDS) Chronic Lyme disease Lingering symptoms of fatigue, pain, or joint and muscle aches Result of residual damage to tissues and the immune system that occurred during the infection? Similar complications and "auto immune" responses: Campylobacter (Guillain-Barre syndrome) Chlamydia (Reiter's syndrome) Strep throat (rheumatic heart disease)

29 100 subjects Mean duration of follow-up was 15.4 years Severe fatigue was found in 9 patients (9%) with cultureconfirmed early Lyme disease at 11 to 20 years after presentation, but was due to causes other than Lyme disease Fatigue of lesser severity, possibly due to Lyme disease, was found in 3% of the patients The American Journal of Medicine 2015;128:

30 PTLDS Some healthcare providers tell patients that these symptoms reflect persistent infection with Borrelia burgdorferi Is this supported by the data?

31 Borrelia burgdorferi antigens, but not infectious spirochetes, can remain adjacent to cartilage for extended periods after antibiotic treatment B. burgdorferi was not recovered by culture or xenodiagnosis with ticks after antibiotic treatment of WT mice

32 Rhesus macaques were infected with B. burgdorferi and a portion received aggressive antibiotic therapy 4 6 months later Testing for residual organisms: PCR, culture, IF, xenodiagnosis B. burgdorferi was recovered by xenodiagnosis in 2/3 animals PLoS ONE, 2012;7:e29914

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34 HHS Working Group on Lyme and Other Tickborne Diseases: Special Webinar on Lyme Disease and Borrelia Persistence

35 Research into Prolonged Treatment for Lyme Disease

36 129 patients had well-documented, previously treated Lyme Persistent musculoskeletal pain, neurocognitive symptoms, or dysesthesia, often associated with fatigue 78 sero+ pts Ceftriaxone 2 g IV QD x 30d then doxycycline 200 mg QD x 60d 51 sero- pts Matching IV/po placebos NEJM, 2001;345:85-92

37 Primary outcome measures: improvement on the physical- and mental-health component summary scales of the SF-36 Health Survey (health-related quality of life) on day 180 of the study Results considerable impairment of health-related quality of life among patients with persistent symptoms despite previous antibiotic treatment for acute Lyme disease no improvement in symptoms after 90 d of ABX

38 55 pts with Lyme, > 6 mos fatigue after ABX Ceftriaxone IV x 28d vs. placebo Neurology 2003;60:

39 Results CTX Placebo

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41 A Randomized, Placebo-controlled Trial of Repeated IV Antibiotic Therapy for Lyme Encephalopathy Fallon BA, et al. 37 pts previously treated for at least 3 weeks with IV AB All had objective memory impairment Randomized to ceftriaxone IV vs placebo x 10 weeks ABX group had greater cognitive improvement at 12 weeks Gains were lost at 24 weeks Adverse events: from either the study medication or the PICC 6 of 23 (26.1%) patients given IV ceftriaxone 1 of 14 (7.1%) patients given IV placebo Neurology 2008;70:

42 Lagniappe

43 Pontial Coinfections. Shapiro ED. N Engl J Med 2014;370:

44 Shapiro ED. N Engl J Med 2014;370:

45 Treatment Shapiro ED. N Engl J Med 2014;370:

46 Shapiro ED. N Engl J Med 2014;370:

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48 And when all else fails