Lyme and Other Tick-Borne Diseases: Science Bridging the Gap:
Lyme Disease Association 16th Annual Conference, November 14 & 15 2015, Rhode Island, USA
Report from Dr Sandra Pearson, Lyme Disease Action’s Medical Director, who attended the conference.
The conference was opened by Patricia Smith, President of the Lyme Disease Association, who gave an overview of the spread of Lyme disease and increase in tick-borne diseases in the USA. Pat detailed the work of the Lyme Disease Association in raising awareness and the significant support and fund-raising undertaken for important research projects.
Leading researchers in Lyme disease and tick-borne infections presented their work to a mixed audience of patients and their representatives, treating clinicians, researchers and the CDC.
William Robinson, Associate Professor of Medicine at Stanford presented the Keynote Speech ‘Next Generation Diagnostics for Lyme Disease’ describing the development of a new multi-antigen assay for earlier, accurate diagnosis of Lyme disease. Furthermore, detailed investigations into the nature of the human immune response to Borrelia reveal an emerging picture of complex T cell and B cell repertoires in acute Lyme and Post treatment Lyme Disease. These may potentially form the basis of future improved Lyme diagnostics.
Dr Charles Chiu, Associate Professor UCSF, described his work using genomics and proteomics to develop new assays and tests for diagnosis of Lyme disease. These may also be used to identify patients whose genes and gene expression (transcriptome) may put them at risk of persistent symptoms and excessive inflammation in response to Lyme disease.
The role of inflammation in Lyme neuroborreliosis was covered by Geeta Ramesh PhD, from Tulane National Primate Research Centre. Nervous tissue is highly sensitive to the inflammation associated with acute neurological infection, leading to a vicious circle of demyelination, damage to neural networks and degeneration of nerve cells. Further complexity arises as the immune cells of the central nervous system and some neurones possess particular receptors (TLR 2 receptors) that enable them to interact directly with bacterial cells without the need for inflammatory mediators.
The host immune response to infection with Borrelia was presented by Dr Klemen Strle from Harvard Medical School who presented evidence for the hypothesis that early and late manifestations of Lyme disease depend on the interaction between the particular strain of Borrelia and the genetic predisposition of the host towards inflammatory processes.
The phenomenon of Borrelia persister cells and their eradication in vitro was covered by Dr Kim Lewis and Professor Ying Zhang. Both researchers are commencing in vivo research on the use drug combinations or pulsed dosing of antibiotics in animal models of Lyme disease, with a view to commencing treatment trials in humans in the not too distant future.
Professor Richard Marconi described the use of advanced technology to build chimeric proteins or ‘chimeritopes’ to develop an effective protective human vaccine for Lyme disease, which is in the early stages of development. The potential exists for future versions to target not only European genospecies and strains but to include dominant proteins of major coinfections such as Anaplasma and Babesia. This technology may also form the basis of novel tests.
Dr Tim Brooks, Head of the Rare and Imported Pathogens Laboratory (RIPL), Public Health England gave an overview of the situation in England, which is experiencing a rising incidence of Lyme disease, often in areas previously not recognised as ‘hot-spots’. The UK has different tick vectors, including the sheep tick Ixodes ricinus and hedgehog tick Ixodes hexagonus, which may inhabit urban parks and gardens. As with the rest of Europe, the UK has a range of genospecies and a number of different strains of Borrelia, with Borrelia garinii being responsible for the majority of UK infections. The establishment of a network of dedicated clinicians, development of better tests (including large volume PCR and metabolomics), Lyme disease becoming a notifiable disease and the plan for NICE guidelines were covered. Given the lack of a robust evidence base in late stage Lyme disease and limited UK clinical experience, I asked whether treating clinicians from outside the UK might contribute in some way to the NICE Guidelines development process. I learned that a number of experienced clinicians had indicated they would be agreeable to do so.
Dr Hassan Minhas from Yale School of Medicine presented a case of repeated attempted suicide by a 40 year old male patient with Lyme neuroborreliosis and no previous psychiatric history. This man described ‘feeling in a fog’ and had great difficulty identifying his feelings (known in psychiatry as alexithymia). He did not appear depressed and didn’t respond to standard antidepressant treatment. Recovery occurred when he was diagnosed with Lyme neuroborreliosis, with drastic improvement one week after commencing a 28 day course of IV ceftriaxone. Following recovery, he had difficulty accounting for his suicidal behaviour.
Continuing on the theme of psychiatry, Professor Brian Fallon of Columbia University Medical Centre, addressed the latest developments in post-infectious psychiatric disorders, focussing on PANDAS (occurring after Streptococcal infection in children) and PANS (occurring after other infectious triggers such as Borrelia infection), together with an exploration of possible biomarkers of neurological Lyme disease.
William Padula, Director of the Padula Institute of Visual Rehabilitation presented his ongoing research into the effects on vision and the very debilitating visual processing problems that may occur after tick-borne diseases. This may result in a range of symptoms such as headaches, double vision, blurred vision, photophobia, problems with posture and balance, as well as dizziness and motion sickness. He explained that symptoms develop as a result of a mismatch in the way the brain processes two main types of visual signals. Test such as Visual Evoked Potentials help to evaluate this problem and a video was shown demonstrating the use of special corrective lenses called ‘base-in prisms’ to alleviate problems with posture and balance that occurred due to problems in visual processing.
Philip Molloy, Assistant Clinical Professor at Tufts University School of Medicine gave an interesting account of the first US cases of Borrelia miyamotoi which is a relapsing fever Borrelia carried by hard-bodied ticks, published in Annals Int Med, July 23 2015. He described seeing “short, fat, highly motile spirochaetes” in CSF under the microscope. The challenge of developing and ordering diagnostic tests was emphasised. There appears to be a brief phase of PCR positivity in blood with most patients only becoming seropositive, with measurable antibody levels, during convalescence. Clinical symptoms include high fever, chills, marked headache, and myalgia or arthralgia and 24% patients were hospitalized. Elevated liver enzyme levels, neutropenia, and thrombocytopenia were common.
Dr Edward Breitschwerdt highlighted the impact of Bartonella as an emerging zoonotic infection. Over 30 species have been identified so far, of which 17 have been associated with an expanding spectrum of human and animal diseases. Tick-borne viruses emerging in the USA, such as Heartland, Powassan and Colorado Tick Fever virus were covered by Nicholas Komar from the CDC’s Division of Vector-Borne Diseases. Alpha-Gal Meat allergy which may be triggered by the bite of the lone star tick, Amblyomma americanum was presented by Erin McGintee, NY Southampton Hospital, which may happen, particularly after ingestion of fattier red meats. Richard Ostfeldt from the Cary Institute of Ecosystem Studies explained how habitat fragmentation and loss of biodiversity favoured the abundance of small mammals which appear particularly efficient at transmitting Borrelia, Babesia and Anaplasma to larval ticks and thus supporting the enzootic life-cycle of all three pathogens. This in turn increases the risk of human exposure to ticks carrying multiple diseases.
Professor John Aucott of Johns Hopkins University presented his ground-breaking work on the SLICE study involving prospective follow-up and examining the impact of Lyme disease on long-term health outcomes and immune function. An extensive biorepository of samples and data enables detailed studies on a range of serum cytokine and chemokine biomarkers on an increasing and significant population of Lyme disease patients. Profound and persistent elevation of biomarkers may be associated with ongoing symptoms and inflammation after standard antibiotic therapy. This may prove useful in monitoring response to therapy and identifying people who are at risk of developing chronic symptoms and who may require more extensive treatment. The SLICE study is ongoing and promises to yield much useful information and data about Lyme disease.
The highlight of the second day was the comprehensive debate on sexual transmission of Lyme disease between Raphael Stricker (For) and Sam Donta (Against). Evidence from epidemiology as well as a limited number of studies in animals, ticks and humans was explored in a frank head to head public exchange. The conclusion highlighted the limitations of the available evidence base and the need for further well-conducted research to help resolve this important question.
This conference provided a safe space for open discussion of ideas and debate about the complexities and uncertainties that pose such a challenge for all those involved with or affected by Lyme and other tick-borne diseases. It was very encouraging to see patients, their support groups, researchers and treating clinicians not only coming together to hear about cutting edge research but also promoting and leading the research agenda.