2/5/19. Lyme Disease: It s Complicated! Lyme Disease is Worldwide. Lyme Disease: An Immune Response initiated by Borrelia burgdoferi

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1 Lyme Disease: It s Complicated! Mark J. Soloski, Ph.D. Professor of Medicine Department of Medicine, Division of Rheumatology Co-Director for Basic Research, Lyme Disease Research Center Johns Hopkins University School of Medicine Baltimore, Maryland USA Lyme Disease: An Immune Response initiated by Borrelia burgdoferi + Lyme Disease is Worldwide Steere, A. C. et al. (2016) Lyme borreliosis Nat. Rev. Dis. Primers doi: /nrdp

2 Lyme disease is an Ancient Disease Present in Europe 5,300 year ago! Why was Italian Ice Man killed by his pursuer? Medicinal tattooing over knee was used a treatment for arthritis DNA analysis identified B. burgdorferi the bacterial agent of Lyme disease. During the early 20 th Century Lyme Disease not common! The Ecology Needed to Support Transmission Vanished Deer were Almost Hunted to Extinction in the 1800s Farmland Replaced Forest 2

3 Lyme disease re-emerged by different names over the last hundred years: Erythema chronicum migrans & Bannwarth s Syndrome in Europe Montauk knee and Lyme Disease in the United States Lyme Connecticut Montauk NY European skin/nerve disease described 1975 Lyme, CT cluster of arthritis cases Geographic disease 3 major initial foci in the United States Northeast Upper Midwest Pacific First 512 Cases of Lyme disease in the United States: Locations correlated with distribution of Deer Ticks Annals of Internal Medicine 1979;91:730 Geographic Spread of Lyme Disease 30,000 cases/yr 3

4 300,000+/yr Yikes!!!!! Ticks are small! 4

5 Ticks are small! Ticks Carry Many Infectious Agents Ixodes scapularis Black Legged Tick Borrelia burgdorferi Borrelia miyamotoi Borrelia mayonii Anaplasmosis Babesiosis (protozoan) Powassan disease (virus) Other Tick-Borne Infections Ehrlichiosis Rocky Mountain spotted fever (RMSF) Colorado tick fever Heartland Virus Rickettsia parkeri rickettsiosis STARI Southern tick-associated rash illness Tickborne relapsing fever (TBRF) Tularemia U.S.364D rickettsiosis 5

6 Tick Landscape is Changing! Asian Ticks (Mysteriously) Turned Up On A New Jersey Sheep! Haemaphysalis longicornis. Severe Fever with Thrombocytopenia Syndrome Virus in China Recently Found in Virginia!!!! 2-Year Life cycle of the Dear Tick (Ixodes scapularis) The White Footed Mouse (Peromyscus leucopus): A major Reservoir of Borrelia Up to 95% of mice are infected with B. burgdorferi in high endemic areas Bb persists in mice for several years, seemingly without effect! 6

7 Why so Much Lyme Disease Now? Reforestation, Forest Fragmentation and Human Residential Patterns create the Perfect Environment for Lyme Disease Transmission Potential Reasons for the Increase in Lyme Disease Climate change induced changes in tick distribution Populations of deer, raccoon, opossum, birds, and other wildlife have rapidly expanded in the last few years due to reduced hunting activities Suburban development has encroached on woodlands = forest fragmentation = increased habitat and exposure. Migratory birds may partially account for the spread of this disease since larval and nymph black-legged ticks often feed on ground-feeding birds. Lyme Disease: An Immune Response initiated by Borrelia burgdoferi + 7

8 Natural History of Untreated Lyme Disease Clinical Landscape of Diagnosed and Treated Lyme Disease Early disease Late disease T R E A T M E N T Recovery 80-90% 10-20% Return to Health Post-Treatment Lyme Disease Syndrome Lyme Disease and the Human System The Human Person The Pathogen/Vector Genes and Genomics Immune Elements 8

9 Molecules Tissues Cells Immune System Immune System has a Big Task: Sense Danger! Schistosoma mansoni Pneumocystis carinii Trypanosoma brucei Staphylococcus aureus Listeria monocytogenes Influenza virus Parham, 2000 The Solution Physical barriers Skin mucous membranes Innate Immunity Complement phagocytic cells Acquired Immunity B lymphocytes T lymphocytes B Antigen/ Pathogen Keep m out T Rapid Response Clear them out & Remember Team 9

10 The Immune Response Pathogen Enters! Innate Immunity Rapid (hours) General Adaptive Immunity Slow (days/week) Specific Infection Return to Health Immune System Active Immune System Quiet 80-90% 10-20% Acute Lyme Infection Immune System Active Return to Health Immune System Quiet Persistent Disease Immune System Still Active 10

11 Study of Lyme Disease Immunology and Clinical Events (SLICE) The SLICE study is a prospective, controlled study of acute Lyme focused on long term health outcomes 1-year prospective cohort study. Data are collected from a cohort of Lyme patients and a cohort of non-lyme controls Uniform population at enrollment All patients have documented Lyme EM rash and no confounding symptoms Skin Lesions all documented with photographs Microbial validation by PCR and serology Uniform Entry Point Allows Study of Early Events in Infection and Immediately Post Treatment and Over Time Lyme cases Clinical evaluation, Surveys PBMC isolation, Serum archival Skin Biopsy Skin Biopsy Neurocognitive Neurocognitive * * v1 v2 v3.5 v5 v6 treatment -3 weeks 0 2 months 6 months 1 year v1 * v2 v3 * v4 Neurocognitive Neurocognitive Controls Clinical evaluation, Surveys PBMC isolation, Serum archival Clinical outcomes of antibiotic treated early Lyme Patients (n=127) 35% 55% 10% Returned to pre-lyme health s tatus Post-Treatment Lyme disease syndrome Persistent symptoms with normal functioning 11

12 Definition of PTLDS 1. Well documented Lyme disease with standard of care treatment. 2. Symptoms at 6-12 months following diagnosis. 3. The presence of at least one of: fatigue musculoskeletal pain cognitive complaints of difficulty finding words, focusing or concentrating or memory impairment. 4. Impact in daily life functioning. Personalized Brain Mapping: PET Imaging To identify regional neuroinflammation existing in an individual patient based on a TSPO brain atlas utspo (mitichondrial translocator protein) uupregulated in activated microglia ureflecting dynamic and complex nature of microglial activation Brain PET Imaging Shows Increased Inflammation in Patients with Chronic Post-treatment Lyme Disease Syndrome Lyme PTLDS TSPO Genotype: C/C Healthy Control TSPO Genotype: C/C 1 VT 6 12

13 80-90% 10-20% Acute Lyme Infection Immune System Active Return to Health Immune System Quiet Persistent Disease Immune System Still Active Prevention: What to Do? Vaccination? Human Vaccine (Lymerix) 80% effective licensed in 98 Removed from market in 2002 due to alleged side effects New vaccines may be more effective for all strains worldwide, but are not yet in testing phase. Animals and Lyme Disease Horses and dogs primarily affected Causes arthritis and systemic illness 13

14 Personal Protection Avoidance of high risk environment Proper clothing Permethrin treatment of clothing Deet treatment of skin The EPA has an online tool to help you select the repellent that is best for you and your family. Tick checks Showering Pets in bedroom? Environmental Control Peridomestic environment Fencing Clearing brush Wood chip barriers Deer Control Four poster stations Mouse reservoir Vaccination Permethrin Environmental Control Peridomestic environment Fencing Clearing brush Wood chip barriers Deer Control Four poster stations Mouse reservoir Vaccination Permethrin 14

15 Cutting Edge Next-Gen strategies Chickens as a weapon against ticks? CNY village considers proposal Cutting Edge Next-Gen strategies Virginia Military Institute engineers develop Tick-killing robot May 26, 2015 North Carolina, Uncover California... a tick killing robot that could eradicate the pesky arachnids from your property... dubbed Robo-Tic has the potential to lessen cases of Lyme disease in North Carolina and across the United States... Cutting Edge Next-Gen strategies 15

16 Thank you! QUESTIONS? 16