Report of the NorTick 2014 Conference, held in Stavanger 5-6 February 2014.

Approx 70 people, mostly Norwegians but a few from Sweden, Denmark, Finland and Germany. 2 from the UK.

ID consultants, neurologists, microbiologists, paediatricians, GPs, public health, researchers (microbiology, biology, ticks & ecology) and 3 patients, gathered to share knowledge on tick-borne diseases.

Pål Iden, County medical of Rogaland Welcome to Stavanger and the opening of NorTick 2014.

• Crossing borders in our landscapes and our minds
• We need to assess what we do know and what we don’t
• Think how we can put our knowledge into action

Harald Reiso, MD, PhD, GP, Arendal municipality, Norway: An example case history.

• Illness started July 2012 IgG neg, IgM positive.
• Doxy; relapse; doxy; relapse
• NCB (Norway Centre of Borreliosis) suggested course of Artemesia
• Doxy + amoxi improved
• normal neurology exam. Then extended F response & degenerative changes
• Positive ANA; normal MRI head. Dyspnoea
• CK 470 (50-400) ? myositis; cardiology OK
• Oct/Nov 2013 gradually improving
• Jan 14 back at work but still some chronic ?neurodegenerative change in muscles of lower extremities

Left the question hanging – what was this?

Susan O`Connell, MD, UK How to diagnose Lyme borreliosis?

Dr O’Connell said she was presenting her last talk on Lyme Borreliosis.

• early treatment trials tended to use sub-optimal agents eg erythromycin “I would not use this for any infection”
• need to reach out to other professional organisations “I myself have talked to consultant neurology colleagues over the years”
• What is LB? rash varies, only develops clear centre with time. “I used to see people coming back from the USA” with homogenous rashes.
• Emphasised the need for case definitions. Need them when writing papers to clarify what we are talking about. If researcher says “clinically diagnosed” (as ILADS) what does this mean?
• Need to define chronic LB and PLDS
• Discussed lab tests and briefly said Scandinavia uses 2 tier system less because of high specificity of Dako Oxoid.
• Problems with IgM specificity including blots
• B afzelii slow evolution of symptoms “time and time again I have seen diagnosis of cellulitis and sub optimal antibiotics – ending up with grumbling infection”
• Now UK & USA use LP less frequently for MS; more MRI. So LNB can get missed.
• Chronic LB needs a definition. She would rather use “Late Lyme” as the word chronic means different things. “If we get rid of their infection, what damage is left?”
• Discussed post LB. “Patients are poorly – need to help them”
• Patients with EM post treatment have similar symptoms to control groups
• Good outcome of treatment in early LB
• Then a slide listing Scandinavian papers – which showed poor outcomes. Bit of a mixed message
• Possible mechanisms for continuing symptoms?
• “Something has altered that patient’s perception of pain. They are not crazy.”

Ram Dessau, MD, Clinical Microbiology, Region Sjaelland ,Denmark: Scandinavian biobank for Borrelia-serology

• Need well characterised samples for the biobank but “have to include some problem patients”
• discussed EFNS case definitions
• will use all CSF samples with pleocytosis, whether antibody index positive or not
• will use some CSF samples without pleocytosis.

2 reviewers will be selecting samples, with a third to resolve disagreement.

Unn Ljøstad, MD, professor, neurological department, Kristiansand, Norway: “Chronic Lyme”; diagnostic and therapeutic challenges.

Naming: has chosen “Chronic Lyme” as persistent and ongoing infection with Bb and symptoms> 6 months.

Prevalence:

• does it exist? Yes.
• is it widespread? No; not judging from Norwegian studies

Criteria for chronic LB

1.  > 6 months duration
2.  objective findings – eg nervous system deficits
3.  lab findings of Bb antibodies in serum/CSF or +ve PCR
4.  other diagnoses excluded

Pia Forsberg, MD, professor, department of infectious diseases, Linköping: Incidence of Borrelia infection after a tick bite in parts of Northern Sweden and Åland Islands, Finland, a prospective study 2008-2009

TBD STING study. Prevalence & diversity of microbes in ticks which have bitten humans. Not yet published.

• questionnaire on health status etc at 0 and 3 months
• blood sample examined for immune response and serology – 2 ELISAs + line blot at 0 and 3 months
• tick submitted to PCR & measurements to determine length of feeding

Dag Tveitnes, MD, PhD, paediatric department, Stavanger, Norway: Impact of gender in childhood neuroborreliosis

• Facial palsy more common in girls and they were younger
• Headache and/or stiff neck as single symptom more common in boys
• Boys sicker for longer before diagnosis
• CSF inflammation may be related to gender.

Knut Erik Eliassen, MD, GP, Oslo, Norway: Laboratory diagnostics of Lyme disease from the GPs view

• Reckons that in Norway, if you include EM, there are 5-10,000 cases /year
• Went through guidance available to Norwegian GPs. Included BMJ best Practice

Randi Eikeland, MD, PhD, neurological department, Arendal, Norway: National Advisory Unit for Tick-borne Diseases at Sørlandet Hospital

She has 10 years as a neurologist of treating TBDs. Mentioned the Lyme Wars and need to find cause of long term complaints.

The new national unit has just been established to be a National Advisory Unit on TBDs. Funding is approx. £220,000 pa. The aims are:

• To develop and increase knowledge & distribute it
• Cooperate with medical colleagues and patients
• Control & development of guidelines and knowledge

Purpose is to decentralise knowledge & skills, so they will not be needed at the end of the project. The unit will organise symposia and courses for health professionals.

They see the need for a 2nd opinion service, but have no funds – will try to make it happen.

Reidar Hjetland, MD, Clinical microbiologist, Førde, Norway: Antibodies to Borrelia, Anaplasma phagocytophilum and TBEV in blood donors in Sogn and Fjordane

• Survey W Norway. 65% population has had tick bites, 30% in last year. See Hjetland et al 2013. The over 60s 26.4% seropositive. About 10% positive both HGA and LB
• Overall females 5.5% IgG positive, Males 13.0% +ve
• Anaplasma not rare. (paper published separately)

Snorre Stuen, professor, NMBU, campus Sandnes, Norway: Anaplasma phagocytophilum and human infection

Looked at serology in sheep. Cofeeding ticks I ricinus and I trianguliceps. In W Norway 94% flock on I ricinus pastures seropositive HGA, but v few human cases recorded in Europe. HGA underreported – why?

• many examples on horses & dogs
• lack of awareness , lack of labs
• vague clinical signs
• ruminant variants – non virulent
• not many suitable hosts – eg hedgehogs

Katrine Paulsen, master student Oslo, Norway: TBEV and Louping ill-virus (LIV) in Southern Norway

• TBE & LIV closely related. LIV neuro disease in sheep, can affect humans, mainly farmers.
• LIV UK, Norway, Ireland and Spain, Greece & Turkey

Åshild Andreassen, Senior Scientist, Norwegian Institute of Public Health,Oslo, Norway: Serological studies of TBE in Norway & Kirsti Vainio, Senior Scientist, NIPH, Oslo, Norway

• TBE in Norway 1994-2013 94 cases; 2013 4 domestic, 2 overseas cases.
• LIV analysed by reference lab in Scotland.

Susanne G Dudman, Assistent director NIPH, Oslo, Norway: TBE vaccination on Åland

Per-Eric Lindgren, professor, clinical microbiologist, Linkøping, Sweden: TBE vaccination recommendations in Norway based on data from MSIS and ScandTick.

Åslaug Rudjord Lorentzen, MD, PhD, neurological department ,Kristiansand, Norway Ongoing post doc projects:

1.Fatigue in Lyme neuroborreliosis – genetic and other risk factors. About to conduct a study looking for genetic markers. 600 patients LNB from 2002-2012

2. Detection of Borrelia species in cerebrospinal fluid – a pilot study of PCR as a new diagnostic tool.

 Bjørn Barstad, MD, paediatric department, Stavanger, Norway: The BOB-study

To investigate clinical characteristics & new diagnostic markers.

• CXCL13 in CSF
• clinical presentation in different genotypes
• ECG with LNB as indicator of simultaneous Lyme carditis

Inclusion finished 31.12.13 240 samples – LNB, aseptic meningitis & non meningitis

Åse Mygland, professor, University of Bergen, Norway: Planned PhD project: Tick-borne infections and chronic subjective health complaints; a health survey in Vest-Agder (TickVA)

She talked about a new study to look at exposure in tick-rich areas. Are auto-immune disorders more common?

Olaf Kahl, Scientist, Editor, Berlin, Germany: How to estimate the risk of tick infestation and how to minimize it?

Overview of biology & tick feeding. larva feed for 2-4 days, nymphs 5-6 and adults 3-10. Temperature <-10 degC critical but snow cover helps survival.

Solveig Jore, VI Epidemiology, Asker, Norway: Climate and environmental change drives Ixodes ricinus geographical expansion at the northern range margin

Used presence of antibodies v Anaplasma in sheep serum as indicator of I ricinus

Lars Korslund, Associate professor, Ecology, Kristiansand, Norway Abundance of ticks and host over an altitudinal gradient in southern Norway. Ixodes ricinus more prevalent in coastal areas, I trianguliceps more prevalent in inland areas.

Per-Eric Lindgren, professor, clinical microbiologist, Linkøping, Sweden: Ixodes ricinus in Sweden and Finland: Seasonal pattern of ticks biting humans, attachment sites and duration of feeding

Older people removed ticks later – longer attachment.

Rikke Rollum, master student, Molecular biology, Kristiansand, Norway: “Comparison of tick DNA extraction methods”

Phenol-chloroform & DNEasy kit may be best for extracting DNA from ticks.

Snorre Stuen, professor, NMBU, campus Sandnes, Norway: A tick-sheep model for experimental infection

Small containers stuck on to shaved sheep skin with copydex. Worked well. One chamber with adults of unknown infection and another with lab reared nymphs to check transmission.

In the chamber with adult ticks left to engorgement, 41% of the adults died, 59% engorged. 5 were infected with Bb and they were all dead, unengorged. Nymph chamber – 90% engorged.

Gerd Marit Berge, chair of Norsk Lyme Borreliose-Forening: One year with “Flått dialog”, where are we now?

Gerd described the joint project between the NLBF and Sørlandet Hospital. They have achieved continuing two-way communication and an improved understanding. A popular science article describing LB diagnostics was produced for the website at www.lyme.no

Gerd described the world as patients see it, many with persisting symptoms. Specialists, on the other hand, tend to see just the early LB cases. The NLBF questions the two tenets held by specialists:

1. patients with late LB will always be seropositive
2. the recommended treatment will always kill the bacteria

NLBF focus on long term illness because that is where there is least knowledge and least help. She emphasised that mutual respect is important – and that the “strong£ party has a particular responsibility here. Patients should be taken seriously and allowed to relate their experiences. The “complicated” patients must not be “defined away” from help.

Stella Huyshe-Shires Lyme Disease Action UK: Shared priorities for research – The top 10 priorities.

Stella related how awareness of Lyme LB and experience of treating it is very low amongst UK doctors. The Department of Health and the main laboratory maintained that Lyme disease was easy to diagnose and cure and failed to listen to patients. LDA therefore used an official organisation in a patient funded project to prove that uncertainties exist in diagnosis and treatment.

Stella described the process from survey through literature search leading to 81 distinct questions of which 7 had a known answer, 5 were subject of a current trial and 69 were true uncertainties requiring further research. She listed the top 10 priorities as decided by a group of doctors and patients.

Atle Mysterud, professor, ecology, Oslo, Norway: Linking ticks and hosts: TickDeer and ZEWS project

Lise Grøva, PhD, Animal science, Tingvoll, Norway: TICKLESS; Reduced ticks and tick-borne diseases in sheep by integrated management.

Preliminary results. www.tickless.no Project had some funding from James Hutton Institute. Tick load may be an indicator of robustness (of constitution).

Vivian Kjelland, PhD, Scientist, Molecular biology, Kristiansand, Norway: ScandTick

This project is tying the Scandinavian region together: Shared knowledge, improved diagnostics, risk assessment, research dissemination.

Bb, TBE, Anaplasma, Babesia, LIV, Francisella tularensis, Rickettsia, Bartonella, Coxiella