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Infectious Disease Epidemiology BMTRY 713 (A. Selassie, DrPH) Lecture 21 Lyme Disease Learning Objectives 1. Describe the agent and vector of Lyme Disease 2. Identify the geographic and temporal patterns of Lyme Disease 3. Identify the risk factors and prevention of Lyme Disease Lyme disease Overview Tick-borne zoonosis Most common vector-borne illness in US In 2011, 33,097 cases were reported Multisystem, multistage disease Early diagnosis and treatment important to prevent future complications Currently vaccines available Lyme disease Historical 1975 first identified by mothers 12 children diagnosed with juvenile rheumatoid arthritis Sudden onset of pain and swelling of joint, flu like symptoms Some following a unique skin lesion described as erythema migrans (EM), possibly from a tick bite Selassie AW (DPHS, MUSC) 1

Initial Investigation EM skin rash Occurred primarily in the summer Suggesting a seasonal disease Consistent with the tick bite hypothesis 2.8 cases/1,000 East side of the CT river and 0.1/1,000 on the West (East 28x higher) Patients more likely to have animals Deer tick (Ixodes scapularis) more abundant on the East than in the West Life Cycle of Ixodes scapularis Complicated lifecycle; 2 years to complete Progression through stages Egg Six legged Larval or seed tick Eight legged immature nymph Eight legged mature adult tick A blood meal is required at each stage Ticks do not fly, hop, or jump, they quest Life Cycle Eggs are laid in the spring. After hatching in larvae, they feed once White footed mouse is primary host Other small animals and birds are possible host Can be infected with Borrelia burgdorferi (a spirochete) Species name designated to the discoverer, Willy Burgdorfer Selassie AW (DPHS, MUSC) 2

Terminology Reservoir species Are species commonly infected with an organism and remain infectious to a vector for a prolonged period of time Vector competence The inherent ability of an arthropod to become infected with an organism subsequently to transmit the infectious agent to a new vertebrate host Life Cycle of Ixodes Ticks Adult Female Ixodes scapularis Selassie AW (DPHS, MUSC) 3

3 Feeds & Patterns of Transmission Larvae (infection free, can acquire it at first feeding, feed on mice) Nymph (usually feed on white-footed mice) Adult (usually feed on white-tailed deer) Vertical transmission is rare Importance is order of feeding If Nymph feed before larvae hatches higher prevalence of infection, NE US Northeast US Prev. (50%) Southeast US reversed feeding Prev. (1%) Another factor in SE is bridge vector ticks that feed on lizards Borrelia burgdorferi Spirochetes noted in midgut of most ticks Also identified in people with Lyme disease but not those without Bacteria, maintained in zoonotic cycles Reservoir hosts are hosts commonly infected and remain infectious for prolonged periods of time White footed mouse is preferred reservoir host White tailed Deer is responsible for maintenance of the vector Selassie AW (DPHS, MUSC) 4

Giemsa stain of blood with B. burgdorferi Immuno Florescence B. burgdorferi Two well known examples of spirochetes are, a) Borrelia burgdorferi b) Treponema pallidum Clinical Stages of Lyme Disease Early disease Characteristic skin lesion (Erythema cutaneous migrans) Warm, not painful or pruritic Flu-like symptoms Resolve within 3-4 weeks Secondary disease 1-6 months after exposure Neurologic disease, including meningitis Carditis, Disseminated lesions Erythema Cutaneous Migrans (ECM) skin lesion Selassie AW (DPHS, MUSC) 5

Lyme Disease (2) Late disease Occurs weeks to months after infection Most common is arthritis, severe joint pain Attacks last weeks to months Can be recurrent Characteristic skin eruption Additional EM rashes Chronic skin disease Neurological and musculoskeletal sx Bell s palsy Multiple sclerosis Nerve pain, Polymorphic symptoms Difficult to diagnose Post-treatment Lyme Disease Syndrome (PTLDS) Symptoms of Lyme Disease lasting >6 months after completing 2-4 wks. course of antibiotics Sometimes called Chronic Lyme Disease The lingering symptoms are the result of residual damage to tissues and the immune system that occurred during the infection These lingering symptoms might be due to autoimmune responses as noted in other infections like Campylobacter (Guillain-Barre syndrome), Chlamydia (Reiter's syndrome), and Strep throat (rheumatic heart disease) Longer course of antibiotics reduces risk of PTLDS Clinical Course of Lyme Disease Selassie AW (DPHS, MUSC) 6

Diagnosis Early phase on signs and symptoms Based upon characteristic clinical presentation, history of tick exposure Secondary phase Combination of meningitis and neuropathy Culturing organism, takes days to weeks Antibody may be present but not always Treatment Primary disease Doxycycline in adults Amoxicillin in pregnant and lactating women, in children More severe disease Intravenous antibiotics Epidemiology of Lyme disease Endemic in several areas in US and Russia US Northeast, upper Midwest, northern regions of the Pacific coast Number of cases fluctuates yearly, depending upon acorn production Worldwide Russia, north and central Europe Variation in strains of borrelia Selassie AW (DPHS, MUSC) 7

Distribution of Lyme Disease, US Temporal Patterns of Lyme Disease Reported Cases of Lyme Disease by Year, United States, 2003-2012 Content source: Centers for Disease Control and Prevention National Center for Emerging and Zoonotic Infectious Diseases (NCEZID) Division of Vector-Borne Diseases (DVBD) Selassie AW (DPHS, MUSC) 8

Confirmed Lyme disease cases by month of onset United States, 2001-2010 Risk Factors Living, working, or vacationing in a woodsy, rural environment Probability of contracting disease in an endemic area 0.012-0.05 Transmission is dependent upon how long the tic is attached (at least 36 hours) Control measures Control mice (reservoir species) Control deer (maintenance of vector) Control ticks (vector) Prevent exposure to vector Immunization against infection Selassie AW (DPHS, MUSC) 9

Vaccine LYMErix vaccination A Lyme disease vaccine is no longer available due to insufficient consumer 3 dose IM, initial, one month, 12 months Should be timed so 2 nd and 3 rd doses are administered weeks before transmission season Vaccine protection diminishes over time. Persons age15-70 Safety Local reaction, no serious adverse reactions Efficacy Intent to treat Against infection 2 doses 49%, 3 doses 76% Against disease 2 doses 83%, 3 doses 100% Vaccine (2) Decision to administer based upon the risk Density of vector ticks in environment Prevalence of B. burgdorferi in vector ticks Extent of person-tick contact Based upon geographic location and personal activities Vaccine (3) Vaccination recommendations Persons who reside, work, or recreate in areas of high or moderate risk Frequent exposure yes Moderate exposure possible Low exposure no Persons who reside, work, or recreate in areas of low risk- no Persons who travel to areas of high or moderate risk- possible Future recommendations Determine the safety and efficacy of the vaccine in children, individuals over 70 Identify the need for booster doses Selassie AW (DPHS, MUSC) 10