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Vector Borne Diseases 2015 Agricultural Medicine Course October 14, 2015 Vector Borne Illnesses in the Northeast • Lyme disease and others • West Nile Virus infection • Eastern Equine Encephalitis • Powassan virus Encephalitis Christopher Grace, MD, FIDSA Jeffrey Heath, RN Director, Infectious Diseases Unit Vermont Department of Health University of Vermont Medical Center In the US Lyme Disease is Caused by Borrelia burgdoferi • Cork screw shaped motile bacterium (Spirochete) • Able to change the outer surface proteins (OSP) • Fastidious and difficult to culture • Inflammatory symptoms due to host immune response Lyme Diseases is a Worldwide Infection Borrelia burgdoferi B. afzelii; and B. garinii www.thelancet.com Vol 379 February 4, 2012 Two Year Cycle of Black- Legged Tick (Ixodes scapularis) MEAL 1 EGGS LARVAE • Mouse • Bird NYMPHS MEAL 2 (peak feeding Nymphs Eggs laid, time May-mid July) molt into adults die • Person adults • Mouse • Dog MEAL 3 * For adults SPRING SUMMER Larvae molt that did not into nymph feed in fall WINTER FALL stage • Person • Deer • Dog ADULTS MEAL 3 • Person • Deer • Dog Nymphs dormant Relative abundance of the three major tick stages Connecticut Tick Management Handbook Lyme Transmission • Nymphs account for most human cases: – Only 1 prior blood meal (only 1 chance to acquire B. burgdorferi, while adults have had 2) – Often unrecognized so allowed to feed >24 hours (adults usually removed sooner) Vermont Cases of Lyme Disease by Month of Onset and Status: 2008 - 2011 600 500 400 300 Probable Confirmed Number Casesof Reported Number 200 100 0 Jan Feb Mar Apr May June July Aug Sept Oct Nov Dec Month of Onset Vermont Ticks and Pathogens • Deer tick – Lyme disease, anaplasmosis, babesiosis, deer tick virus (Powassan-type virus) • Dog tick – Rocky Mountain spotted fever, tularemia • Woodchuck tick – Powassan virus • Lone star tick – Ehrlichiosis, STARI (southern tick-associated rash illness)) Tick Surveillance Project • Began in 2013 • Surveillance at 12 sites around state – 6 on either side of state • Collect ticks in spring and fall – at least once per site • Test deer ticks for pathogens: – B.burgdorferi, A. phagocytophilum, B. microti • Study leader: Lyndon State College Tick Surveillance – 2013/2014 Vermont Lyme Cases, 2002 – 2014 900 800 700 600 500 400 300 200 100 Number Cases of Number 0 Indigenous - Confirmed Imported/Unknown - Confirmed Indigenous - Probable Imported/Unknown - Probable U.S. Distribution of Lyme Disease 2001 - 2013 Age Distribution Untreated Lyme Disease Often Evolves Through Stages Days Weeks Months Years Early localized • skin • constitutional Early disseminated • skin Symptoms resolve • cardiac Late disease • neurologic • arthritis • neurologic Symptoms resolve Symptoms resolve Early Localized Disease is Characterized by Erythema Migrans • At tick bite site – after 7-14 days – range 3 to 32 days • Occurs in 80% of patients with Lyme • Slowly expanding over days to weeks . homogenous in 59% . central clearing in 9% Tick bite . > 5 cm, up to 20 cm lesion < 5 cm Jones KL. CID.2008;46:85 Mayo Clin Proc 2008;83:566 Erythema Migrans Can Take Many Forms Jones KL. CID.2008;46:85 Mayo Clin Proc 2008;83:566 Early Localized Disease Nonspecific Symptoms • Incubation: 3 to 30 days after tick bite • Constitutional symptoms: – Fatigue 54% – Anorexia 26% – Headache 42% – Neck stiffness 35% – Myalgia 44% – Arthralgia 44% – Regional lymphadenopathy 23% – Fever 16% • Laboratory: – Elevated LFTs 37% – Leukocytosis 5% – Leukopenia 4% Nadelman RB et al. Am J Med 1996:100;502 Early Disseminated Lyme Multiple Erythema Migrans Lesions Early Disseminated Lyme Facial Palsy • lower motor neuron lesion • weakness of both the lower face and forehead • 25% bilateral • HSV, VZV, CMV, EBV • Mycoplasma • HIV • syphilis • stroke • injury Can last for many months • ear disease Early Disseminated Lyme Meningitis • “Aseptic” or viral meningitis-like presentation • Headache, stiff neck, photophobia • Head CT or MRI most often “normal” • Enterovirus • Lumbar puncture: • HSV-2 • lymphocytic pleocytosis • VZV • Mean ~ 160 cells • HIV • elevated protein • Syphilis • Usually < 200- 300 mg% • normal glucose • RMSF • (+) Lyme antibody • Ehrlichia • may be local or from blood • may be long lasting – PCR • low sensitivity Early Disseminated Lyme Radiculopathy • Inflammation at or near the • Can mimic mechanical spinal nerve root radiculopathy • No injury • Imaging studies are usually not revealing • Motor and sensory abnormalities • Pain, numbness, weakness along the dermatones or myotomes • Pain may be on the side of the tick bite Early Disseminated Lyme Cardiac Manifestations • Atrioventricular block • Lyme disease in 875 patients: • 1-2 months (<1 to 28 weeks) • Cardiac manifestations (10%) after the onset of infection • 20% hospitalized • Can occur alone or with • Palpitations, 6.6% erythema migrans, neurologic • Conduction block, 1.8% symptoms • Myocarditis, 0.9 % • Lightheadedness, syncope, shortness of breath, • LV failure, 0.5 % palpitations, and/or chest • Pericarditis, 0.2% pain Late Disease Lyme Disease Rheumatologic and/or Neurologic • Arthritis – knee > shoulder, ankle, elbow, TMJ, wrist – begins abruptly and lasts from several weeks to months – not particularly painful, except from a tensely swollen joint – affected joints are usually very swollen and warm – synovial fluid ~ 24,000 WBC • Neurologic – encephalomyelitis (rare in US, but more common in Europe) – peripheral neuropathy – radiculopathy Lyme Disease is Treatable • Early localized and early disseminated – oral therapy for 14-21 days – doxycycline, amoxicillin, cefuroxime axetil – heart block • ceftriaxone 2g q24h oral x 14-21 days • temporary pacer, if necessary • Arthritis – doxycycline or amoxicillin for 28 days • Meningitis or radiculopathy – ceftriaxone or penicillin x 14-28 days – doxycycline may be adequate • Encephalomyelitis – ceftriaxone for 4 weeks Recovery Is Not always Straight Forward • Complete recovery in majority within ~ 3 wks • Jarisch-Herxheimer reaction in ~ 15% • Improvement may be slow 1,2,3: – more common in disseminated or severe illness – ongoing symptoms in 10 - 15% for > 6 months • fatigue • difficulties with concentration • musculoskeletal pain • no objective findings • no evidence of spirochete replication 1Ann Int Med 2003;138:697, 2Am J Med. 2003;115:91, 3The Lancet 2012;379:46 • Can get re-infected4 4N Engl J Med 2012;367:1883-90 Antibodies to Borrelia Infection Develop and Can be Tested For Acute Infection Chronic Infection IgG False (-) Antibody Titer IgM False (+) • weak bands • increased binding 0 1 2 3 4 5 6 7 8 Weeks Years Antibodies are Detected by Two Tier Testing ELISA • FDA • NIH Whole cell • Council of State and Sonicate Sensitive Territorial Epidemiologists • Association of Public Health Laboratories Western Blot • Clinical Laboratory Standards Institute • Canadian Public Health Specific Laboratory Network IgG (+): 5 of 10 bands • IDSA IgM (+): 2 bands BJB Johnson. Lyme Diseases: Evidence Based Approach. Ed Halperin. 2011 How Good is the Two Tier Test? (+) indeterminate (-) The sensitivity of 2-tier testing in patients with later manifestations of Lyme disease was 100% and the specificity was 99% Steere et al CID 2008:47 (15 July). Chronic Symptoms are often Incorrectly Attributed to Ongoing Active Infection Persistent Lyme disease Treatment symptoms • Fatigue • Pain • Cognitive Post Lyme Treatment Syndrome impairment • How common are these symptoms post treatment? • Are the spirochetes still alive ? This is not “chronic” active • Do prolonged courses of antibiotics help? Borrelia • If not due to infection, then what? infection Are Spirochetes Still Alive After Treatment? • Animal studies have shown that antibiotics cure B. burgdorferi infection even those that are highly immunocompromised1,2,3 • In humans, B. burgdorferi can be cultured from skin lesions prior to treatment but not afterwards4 • In none of the 843 specimens of blood or CSF, tested by culture or PCR, from the 129 patients enrolled in two of the controlled treatment trials could B. burgdorferi be detected5,6 National Institute of Allergy and Infectious Diseases7 Despite extensive study, no clear evidence has emerged to support the contention that post treatment Lyme syndrome results from persistent spirochete infection. N Engl J Med 2007;357:1422-30 4Am J Med 1993;94:583 1 Antimicrob Agents Chemother 1996; 40:2632–6. 5 N Engl J Med 2001;345:85-92 2 Antimicrob Agents Chemother 2002; 46:132–4 6 Vector Borne Zoonotic Dis 2002;2(4):255-63 3 Antimicrob Agents Chemother 1994; 38:1567–72 7 www3.niaid.nih.gov/topics/lymeDisease/understanding/chronic.htm Are Post Treatment Symptoms due to Immune Dysregulation? During the first visit, prior to antibiotic therapy A subset of patients with EM may have immune dysregulation reflected by the persistently elevated levels of IL-23, resulting in post-Lyme disease symptoms. Levels during the first year post therapy Strle et al. CID 2014:58 Do Prolonged Antibiotics Improve Symptoms? All participants had clinically documented Lyme: • Treated • 3 courses, 2 months • Randomized • Persistent symptoms > 6 m • Double blind • 4.6 years • Placebo controlled No iv ceftriaxone x 1 month doxycycline x 2 months 107 difference iv placebo x 1 month placebo pill x 2 months between groups Interfered with functioning • musculoskeletal pain Medical Outcome 36 item General Health Survey • cognitive impairment • fatigue Adverse effects in 25% of antibiotic group: • pulmonary embolism • fever, anemia, GI bleed Klemper et al. • rash, diarrhea,
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