Nordic Consensus on the Management of Tick-borne Diseases

Infektionsveckan & Mikrobiologiskt vårmöte Jønkøping mai 2019

On behalf of the Nordic Consensus working group on the Management of Tick-borne Diseases

Randi Eikeland, MD, PhD, neurologist and Medical director of the Norwegian National Advisory Unit on Tick-borne Diseases, Sørlandet Hospital

Anna J Henningsson, MD, PhD, Medical director, Clinical Microbiology and the National Reference Laboratory for Borreliosis, Region Jönköping County and Assoc. Prof, Department of Clinical and Experimental Medicine, Linköping University

Sweden Anna J HenningssonPia Forsberg, professor in meritus, MD infect.dis., Linköping UniversityBjörn Olsen, professor, MD infect. dis., Uppsala UniversityKatharina Ornstein, PhD, MD infect.dis., Region SkåneBarbro Hedin Skogman, PhD, MD pediatric, Landstinget i DalarnaMats Reimer, MD pediatric, Mölnlycke vårdcentral, Västra GötalandThomas Åkerlund, Chief of Department, Folkhälsomyndigheten Christian Franke, Medical advisor, SocialstyrelsenDenmark Sigurdur Skarphedinsson, PhD, MD infect.dis., Odense Univ. HospitalAnne-Mette Lebech PhD,DMSc, MD infect. Dis., RigshospitaletRam Dessau, PhD, MD, microb., Slagelse Hospital, Ålborg UniversityKaren Angeliki Krogfeld, professor, Statens Serum InstituttThøger Gorm Jensen, PhD, MD, clin. micr., Odense Univ. HospitalFinland Marika Nordberg PhD, MD infec.dis., Åland borrelia groupJukka Hytönen PhD, MD, Turku University Mari Kanerva MD infect. dis. Helsinki UniversityDag Nyman professor, MD, Åland borrela group Olli Vapalahti professor Helsinki UniversityJarmo Oksi, Professor, MD inf.dis., Turku Univ. hospitalNorway Ingeborg Aaberge PhD, MD immunology mikrobiol., Norwegian Institute of Public HealthAudun Aase PhD MD microb., Norwegian Institute of Public Health Harald Reiso PhD, GP, senior advisor Norwegian National Advisory Unit on Tick-borne Diseases Sølvi Noraas MD Microbiol. Leader of Norwegian reference lab. on borrelia, Sørlandet HospitalRandi Eikeland PhD, MD neurology, Medical director Norwegian National Advisory Unit on Tick-borne Diseases Svein H Henrichsen MD GP, senior advisor the Norwegian Directorate of Health Tone Synnestvedt Norsk Lyme borreliose foreningYvonne Kerlefsen managing director Medical director Norwegian Advisory Unit on Tick-borne Diseases Knut Erik Eliassen PhD, GP, Vossavangen legesenterInger Johanne Wedding Hansen MD rheumatology, Sørlandet hospital Kjersti Widding medical doctor in physical medicine and rehabilitation, Sørlandet rehabiliteringDag Tveitnes PhD, MD Pediatric Stavanger University Hospital Pascal Brügger-Synnes MD infect. Dis. ÅlesundSvein Erik Valle Prinz Physioterap. Lister Oddgeir Tjomsland advisor Norwegian Labour and Welfare Administration

BeLivTicks

Why do we need a Nordic consensus group?

• Tick-borne diseases (TBD) emerging in the Nordic countries/Europe• Tests improving, but still need for better tests• New pathogens in ticks• Disagreement on long-term complaints • Lack of knowledge (public, health workers, policy makers)• Patients feeling abandoned/lack of trust in the healthcare system• Alternative non-scientific pathways flourish• Huge costs for the patients and the society, including use of antibiotic

treatment in humans and animals

October 2015: Nordic prepatory meeting. A Nordic Consensus on the diagnosis & treatment of

Tick-borne diseases Kristiansand, Norway

Agreement 2016

There is no need for new Nordic guidelines on the treatment of acute borreliosis and TBE Knowledge and diagnostics of new emerging TBD such as anaplasmosis, rickettsiosis, bartonellosis, babesiosis, neoehrlichiosis is lackingRecommendations of assessment and follow-up of patients with chronic complaints after TBD, or suspected TBD – without laboratory confirmation -are lacking

The Norwegian Directorate of Health Mandate: a Nordic consensus for medical assessment

and follow-up of patients with suspected TBDClarification and recommendations for care of persons where TBD are suspected, but where no active TBD are found Assessment, treatment and follow-up of persons with tick-borne diseasesThe patient's organizations and Norwegian Institute of Public Health must be included in the Nordic consensus working group

Consensus conference

WG 2:Develop, present & publish a Nordic patients’ pathway

WG 1: Provide systematic scientific literature to support Working Groups 2, 3 & 4

WG 3:Develop, present & publish

a Nordic diagnostic pathway

WG 4:Develop, present & publish

a Nordic rehabilitationpathway

Nordic consensus for medical assessment and follow-up of persons with suspected tick-borne diseases (TBD)

• Assessment, treatment and follow-up of persons with TBDs• Clarification and recommendations for care of persons where TBDs are suspected, but where no TBDs are found

Including persons with persistent complaints after suspected TBDs

Publish inpeer reviewed journals

Consensus document

Nordic consensus congressPersistent symptoms in patiens with

suspected tick-borne diseases15.-16. oktober 2018, Hotell Continental, Oslo

Norwegian referencecenter for Borrelia

The results presented here:

• literature grading• mandate protocol • algorithm currently under revision by the working groups and the editor group

Patients TBD pathway-what do we want

• Find the right patients and receive a good referral from primary care

• Find the best individual patient diagnostic pathway• Examine for the relevance of TBD and other differential

diagnosis• Rule inn TBD as an explanation for the patients

complaints• Rule out TBD as an explanation for the patients

complaints• Find other explanations for the complaints• Treat complaints at the right specialty and level of care• Recommend rehabilitation paths when desirable

TBD diagnostics - what to do

1. Gather diagnostic pathways/flow charts from specialist centres concerning TBD and long-term complaints

2. Gather ”laboratory pathways” for other relevant diseases (such as ME/CFS)

3. Systemic literature-review of diagnostic for new TBD4. Publish review methods & diagnostic

recommendations

Literature review

3916 references new TBD excluded: TBE / acute

borreliosis

1221 possible relevant

562 included for sorting and grading

Screening by two independent persons using Covidence

More accurate screening

Sort by kind of infection

DiagnosticsTBDMicroorganism Current diagnostics Diagnostic recommendations

Serology PCR Other First choice test When acute infection is suspected

Confirmational test

A. phagocytophilum Yes Yes Microscopy Serology PCR; Whole blood PCR

Ca. Neoehrlichiamikurensis

No Yes PCR/Whole blood PCR; Whole blood/Skin biopsies

SequencingFollow-up test

Babesia spp. Yes Yes Microscopy Serology PCR; Whole blood PCR

Rickettsia helvetica Yes* Yes Serology PCR; Whole blood, skin biopsies, CSF

PCR, sequencing

Borrelia miyamotoi Yes** Yes (Serology) PCR; Whole blood, CSF PCR, sequencing

Differencial-diagnostic tests

– Hb, HbA1c, SR, leuk., tromb., fe, transferrin, transferrinsaturation, transferrin receptor, ferritin, Na, k, Ca, P, Mg, Glu, Alb, CRP, ASAT, ALAT, GT, bil., ALP, LD, kreat., CK, vit. B12, folat, vit. D, fri T4, TSH og Cortisol

– Optionally Immunological tests

– Optionally other infections

References: Odense, Uppsala, Amsterdam, Åland, CFS/ME Diagnostic pathway Norway

Contact patient - primary carephysician

1. Acute/Late Lymeborreliosis

2. Persistent symptoms >6 months after treatment ofLyme borreliosis (PTLBS)

3. Persistent symptoms >6 months of unknownorigin, with suspicion oftick-borne infection. Persistent

symptoms ofunknownorigin

Checklist

Dedicated unit for examinationand treatment of tick-borneinfection.

Additional diagnostics:Blood samplesLumbar punctureClinical examinationJoint affection:- Arthrocentesis and synovial biopsy

Relevant diagnostic

tests(Checklist of

symptoms vs. suspected

infection to test for

Persistent symptoms > 6 mos. aftertreatment(PTLBS)

Checklist

Suspectedlate Lymeborreliosis* or other tick -borne disease

Checklist

Other relevant examinationsand/or referral to other relevant specialty clinic, according to patient’s symptoms and objectivefindings.

Referral to rehabilitation

National advisoryunit for diagnosisand treatment oftick-borneinfections.

Diagnosis late borreliosis/ othertick-borne disease:

Treatmentaccordingto guidelines

No findingsindicative of Lymeborreliosis or othertick-borne infection

Referral inclusioncriteria ≥ 3/6

Diagnosis and treatmentof not tick-borne disease

Persistent non-spesificsymptoms withoutsuspicion of tick-borneorigin

X

Investigation flowchart for patients withpersistent symptoms, suspected to be fromtick-borne infection

*) Suspected late LB should be diagnosed more locallywhen thought of. Make sure all relevant testing has beendone and reconsider need of referral: Antibodies. lumbarpuncture, MRI of CNS, ECG, joint- and skin evaluation.

Reevaluation of

primarydiagnostics

and treatment

Reconsider

referralafter

relevant primary

diagnostics

DD?

Referral• GP starts the investigation and decides if the patients

should be referred to a specialist center • Other sources of fatigue/ chronic complaints easily

diagnosed / needed to be seen by other specialist checked out first

• No minor testing for TBD before referral• Gather information on symptoms/ previous diagnosis/

treatments • Encourage the patient to write down their symptoms

and what they think are the causes of their complaints• Patient should give permission to gather further

relevant medical information

General recommendation independent of long-term complaints

• Post infectious medical control at 3 months, and if necessary 6 months, after treated disseminated borreliosis

• Check for sequela, post infectious complaints to avoid chronification and reduce the possibility of interpretation of the symptoms as chronic borreliosis

• Think need for second opinion/rehabilitation

Check list

Investigation steps tailored for the individual patient

The referral First meeting

InterviewPhysical examinationRelevant blood samples Spinal puncture? Supplementary joint examination? Referral to other dedicated specialist

Second meetingInformationResults, both laboratory, and any results from relevant referral.Treatment?Multidisciplinary discussion

Follow upProgression/Effect of treatment, or status quo?

Rehabilitation?

Rehabilitation of persistent complaints after TBD

• Huge variation in prevalence, symptoms and function loss• Most common causes of functional disturbances are pain,

fatigue, cognition deficits, reduced ability to work• Rehabilitation of persistent complaints after TBD in the

Nordic countries are unorganized, scarce and not concrete (exception: Odense)

• No specific rehabilitation recommendations for persisting complaints after TBD exist

• Recommendations follow common rehabilitation principles

Questions?