25/05/2014 Personal details Medical Director: Lyme Disease Action - PDF document

25/05/2014 Personal details • Medical Director: Lyme Disease Action since 2010. Academic and consultancy role. sandra.pearson@lymediseaseaction.org.uk • Lived experience: Husband developed Lyme neuroborreliosis in 2008. My role as carer and advocate. • Consultant Psychiatrist: Honorary contract Devon Partnership NHS Trust, Member of Royal College of Psychiatrists. CCST Lyme Disease: Now you See it, Now General Adult Psychiatry. you Don’t • Member of ESCMID: European Society for Microbiology & Infectious Diseases. Dr Sandra Pearson, Medical Director LDA • Social media: Twitter @PearsLDA Lyme Disease Action Introduction A charity founded by a group of scientists in 2003. • • Lyme disease 100% funded by voluntary contributions. – Cause Serving patients, clinicians and researchers. • – Epidemiology & risk Factors – Clinical presentation Striving for the prevention and treatment of Lyme disease • – Laboratory tests and other tick borne diseases. – Diagnosis Web-site: http://www.lymediseaseaction.org.uk/ • – Treatment Accredited to NHS Information Standard. – Prevention Facebook: https://www.facebook.com/pages/Lyme- • Disease-Action/122058224483868 • Uncertainties • Twitter: @LymeAction • Way forward Ticks What is Lyme Disease? Hard bodied ticks: Ixodes ricinus An infectious disease caused by • Ixodes hexagonus the bacterium Borrelia burgdorferi • Ixodes canisuga – a spirochaete Discovered in 1981 • CDC Public Health Image Obligate parasite • Library Zoonosis • Transmitted to humans by the bite Endemic throughout UK • of an infected tick LDA Image Library 1

25/05/2014 Ticks and Borrelia: Tick Feeding 1 Zoonotic Life-cycle Risk zones: • Woods • Long grass • Undergrowth • Moors & Heathland Across the UK: Town and Country! Tick bites are painless and can go unnoticed Ticks carry & transmit other pathogens eg Anaplasma, Rickettsiae, LDA Image Library Viruses etc. ( Radolf JD , et al ‘Of Ticks, Mice and Men’. Nature reviews. 2012 Microbiology , 10 (2), 87 – 99 ) Tick Feeding 3 Tick Feeding 2 Chelicerae Hypostome LDA Image Library Borrelia burgdorferi Borrelia: survivability • Immunosuppressant properties of Tick saliva. The pathogen responsible for Lyme disease: a spirochaete: • Borrelia: Variation outer surface proteins/antigenic corkscrew shaped bacterium. expression. VlsE protein. Most common vector-borne • Slowing the rate of replication – sacrificing virulence for Disease in N Hemisphere. persistence. Dormancy. Borrelia burgdorferi sensu lato: • Protein binding - immune evasion, dissemination, tissue • B garinii tropism, binding to extra-cellular matrix. - Europe CDC Public Health Image Library B afzelii • - Europe B burgdorferi • Sequestration in immune privileged sites eg. beyond BBB. • - Europe, N America B spielmanii • - Europe • Immune dysfunction: Dissociation of T & B cell responses. Different species may account for varying disease profiles. • Immune modulation – Th1/Th2 responses>Tolerance. 2

25/05/2014 Epidemiology- UK Epidemiology – Europe 1 Number of Lyme disease cases in Europe as reported to WHO Centralized information system for infectious Diseases (CisiD) • M=F • Occurs any age • 45-64 year-old • Southern counties • Scottish Highlands March – • September Bimodal • distribution Occurs throughout the UK • Approximately 10-15% acquired abroad • Under-reported • True incidence (x10-20?) Lyme Borreliosis in Europe: http://www.ecdc.europa.eu/en/healthtopics/vectors/world-health-day- 2014/Documents/factsheet-lyme-borreliosis.pdf Epidemiology – Europe 2 Increasing incidence Country per 100,000 population 10 year average Climate change. • Slovenia 155 Austria 130 Probable Changes in land management. • Sweden (south) 80 under-reporting Netherlands 43 Changes in biodiversity. • USA high prevalence states 31 Switzerland 30 • Changes in human interaction with nature eg. Germany 25 outdoor leisure activities. 2009 France 17 E & W 1.8 • Increasing awareness. Norway 3 Scotland - 11 United Kingdom 0.7 Erythema migrans Clinical features • Multi-system disorder. • Pathognomonic Bull’s eye rash • Borrelia: Tropism, collagen-rich tissues. • 3-30 days after the • Skin, nervous system, joints heart and bite eyes. • May not be circular • May affect any organ of the body. • May be multiple • 20-30% European cases: Lyme neuroborreliosis. • May not be at bite site • USA: Arthritis more common than in • 1 in 3 recall tick-bite Europe. • 65% notice EM rash 3

25/05/2014 The New Great Imitator What are the symptoms? Acute Disseminated Late Disseminated (>4-6 • Amyotrophic Lateral Sclerosis • Migraine (days/weeks) months) (ALS) • Motor Neurone Disease (MND) • Anxiety • Multiple Sclerosis (MS) • Neurological:15 - 20% • Feeling unwell or ‘ flu-like • Arthritis • Myalgic Encephalomyelitis (ME) Bannwarth’s syndrome • • Profound fatigue/malaise Autoimmune conditions • Parkinson’s disease • • Rheumatological: Arthritis B12 Deficiency • Headache, stiff neck • Polymyalgia Rheumatica (PMR) • Bell's Palsy • Fleeting myalgia/arthralgia • Dermatological: • Poliomyelitis-like syndrome • Acrodermatitis Chronicum Chronic Fatigue Syndrome • Seizures • Sound/ Light sensitivity Atrophicans, (CFS) • Stroke • Early neuro symptoms: Lymphocytoma • Dementia • Tendonitis Facial palsy, diplopia • Delirium • Cardiac • Tension Headache • Heart Block due to Lyme • Depression • Opthalmic: uveitis • Thyroid Disease carditis • Diabetes • Vasculitis • Fibromyalgia • Guillain-Barré syndrome Stanek G et al (2011) European Society of Clinical Microbiology & Infectious Diseases , 17(1)69 – 79 Clinical Diagnosis Laboratory diagnostics 1 Evaluation of risk factors and clinical presentation: No gold standard test in routine clinical use. • No marker of disease activity. • 1. Exposure to ticks No test of cure. • 2. Tick bite: only 1/3 recall this 3. EM rash: 65% No test to reliably exclude Lyme disease. • 4. Pattern of symptoms & signs. 5. Seasonal Pattern Direct Tests: 6. Outdoor pursuits Culture difficult : Borrelia is a fastidious, slow-growing 7. Occupational groups organism. 8. Companion animals Molecular diagnostics: PCR insensitive due to low numbers 9. Evaluation of test results of Borrelia in body fluids & tissues. Same for microscopy. Treatment Laboratory diagnostics 2 • Treatment is with antibiotics Indirect tests measuring antibody response: 2-tier serology. • Early treatment is more likely to be successful 1. ELISA/ C6 EIA screening test. • Erythema migrans should be treated without waiting for a 2. Immunoblot (Virastripe). blood test (which may be negative) Early diagnosis • Typically official view is 2-3 weeks of antibiotics False positives: Cross reactions: IgM, p41 flagellar protein. • • usually complete recovery False negatives: Testing too early. • Late diagnosis Early antibiotics → abrogated immune response. • Longer term treatment may be necessary (controversial). Heterogeneity of European strains. • Re-treatment may be necessary. • 15-25% Residual symptoms ?cause. Commercial tests: Lack standardisation. • Recovery may take time. Antigenic variation by Borrelia eg. VlsE. Jarisch-Herxheimer reaction may complicate treatment. Borrelia evades & disrupts immune response. 4