The threat of Lyme disease Dr Roger Evans Consultant Clinical Scientist National Lyme Borreliosis Testing Laboratory What is Lyme disease? • Also known as Lyme borreliosis • An infection caused by Borrelia burgdorferi sensu lato, a gram negative spirochaete bacterium • Transmitted through the bite of an infected tick (Ixodes ricinus in the UK) – a tick needs to be attached to the skin for around 24 hours to transmit Borrelia sp. to a person. • Recognised clinical presentations: early localized, early disseminated and late Lyme disease • There are large gaps in our clinical understanding of Lyme disease, particularly for ‘Post Treatment Lyme Disease Syndrome ‘ Picture credit: James Gathany Ixodes ricinus (tick) ecology/ life cycle Adapted from Manelli et al. 2011 Laboratory samples and cases of LB in Scotland 1996 to 2016 500 7000 450 6000 400 350 5000 300 4000 250 3000 200 Number of cases Number of samples 150 2000 100 1000 50 0 0 Cases Seroneg EM Year Samples GP study (2010-2012) • Three GP practices in NHS Highland region: Nairn, Culloden, Fort William • Number of laboratory cases compared to number of cases treated for Lyme disease without testing • About 2 x number of cases diagnosed by GP without lab testing compared to those that were tested • 2010-2011 • 1440 blood donors • Screened by EIA • EIA positive or equivocal samples confirmed by immunoblot (IB) • 60/1440 (4.2%) IB positive Munro et al (2015) Transfusion Medicine. Letter to the Editor doi: 10.1111/tme.12197 What does it cost? • Netherlands study (2010) – 5 health outcomes: tick bite + no infection, tick bite + asymptomatic infection, erythema migrans (EM), late Lyme borreliosis (LB), Post Treatment Lyme Disease Syndrome (PTLDS) – Annual cost of 19.3M euros for population of 16.6M – 1748 Disability Adjusted Life Years Van den Wijngaard et al 2017 ‘The cost of Lyme borreliosis’ Eur J Public Health 27(3): 538-547 • USA study (2015) – Retrospective study 2006-2010 – Medical health claims data for 52 795 LD cases <65y compared to 264 000 controls with no LD exposure – $2 968 per person more for LD – Total cost in USA is $712M to $1.3B each year Adrion E et al 2015. Health care costs, utilization and patterns of care following Lyme disease. PLoS ONE 10(2): e0116767. doi:10.137/journal.pone.0116767 Patient case: NLBTL tests • June 2012 presented with lethargy, joint pain, tick bite • EIA negative, No evidence of Borrelia burgdorferi infection • March 2016 presented with chronic fatigue, cyclical illness, muscle pain • EIA negative, No evidence of Borrelia burgdorferi infection • September 2017 presented with fatigue, neurological symptoms after tick bite 2012 • EIA negative, No evidence of Borrelia burgdorferi infection Patient case: private tests • Report back from German private laboratory • February 2017 for comment – Lymphocyte transformation test positive • Results indicate current cellular activity against ‘Borrelia burgdorferi’ – Borrelia IgG serospot: negative – Borrelia IgM serospot: negative • Indicates no humoral immune response against Borrelia burgdorferi – Also tested for Ehrlichia, Bartonella, Babesia, Chlamydia pneumoniae, Mycoplasma pneumoniae, Yersinia, EBV, HSV 1/2, CMV, VZV, Coxsackie virus A7, B1 and HHV6 Lymphocyte transformation test (LTT) • Information presented about the LTT • Reflecting the current T-cellular activity of Lyme disease: Indication for a currently active Borrelia burgdorferi infection in cases of furthermore positive EliSpot after the end of therapies • T-Cell-Spot/IGRA has been approved by the FDA in May 2011 for M. tuberculosis: "… A positive result suggests that an infection is likely, a negative result suggests that an infection is unlikely…” “…Results can be available within 24 hours…” Meeting the ISO 15189 standard? • ‘Having acquired a broad range of expertise, Dr. Schwarzbach recognized the problem of insensitivities and lacking standardization with regard to Borrelia burgdorferi antibody ELISA and immunoblot tests. He accomplished this by comparing these test results with the patients’ typical symptoms for Lyme disease.’ Indirect threats of Lyme disease • Scientific method is being ignored; tests introduced with no, little or poor evidence base • Patients are paying large sums of monies for tests which may not be beneficial – harmful? • Patients may be mis-diagnosed and have inappropriate management What are we doing? • National Lyme disease sub group – Strategic planning and coordinate activity to reduce morbidity of Lyme disease in Scotland – Educational resources • Reference laboratory – Currently applying for reference lab status – Provide better epidemiological data in humans and ticks and improve research into different tests eg. LTT Questions? .