Recommendations for research
- 1 Core outcome set for studies of management of Lyme disease
- 2 Clinical epidemiology of Lyme disease in the UK
- 3 Seroprevalence of Lyme disease-specific antibodies and other tick-borne infections in the UK population
- 4 Antimicrobial management of Lyme disease
- 5 Laboratory tests to diagnose initial and ongoing infection and determine re‑infection in the different presentations of Lyme disease in the UK
The guideline committee has made the following recommendations for research.
Can a core outcome set be developed for clinical trials of management of Lyme disease?
Antibiotic treatment is the mainstay of management for Lyme disease. The studies published on the management of Lyme disease use differing outcomes, which are often poorly defined. The development of a core outcome set has been identified as a high priority because it would allow comparison across trials and allow appropriate meta-analysis to strengthen results. The methods used should be patient-focused and include patient input on priority outcomes and how they should be measured.
What are the incidence, presenting features, management and outcome of Lyme disease in the UK?
There is a lack of robust epidemiological data on Lyme disease in the UK population. A large clinico-epidemiological study to collect data on incidence, presenting clinical features, management and outcome of Lyme disease in community and hospital settings in the UK would generate population-based statistics. These statistics would enable interventions such as antibiotic treatment and service improvements to be assessed properly and for services to be tailored so they best serve people with Lyme disease; this was felt to be of high priority. There is no current requirement to notify cases of Lyme disease; therefore, current data are likely to underestimate the number of cases.
3 Seroprevalence of Lyme disease-specific antibodies and other tick-borne infections in the UK population
What is the current seroprevalence of Lyme disease-specific antibodies and other tick-borne infections in people in the UK?
This information is not currently available and is of high priority. Without understanding the underlying population's seroprevalence of Lyme disease-specific antibodies in the UK, it is impossible to interpret incidence data accurately or to understand fully the epidemiology of Lyme disease in the UK. The available data suggest there are areas of higher and lower prevalence in the UK but there are many gaps in knowledge. This study is needed to act as a basis for future studies. The information may also help interpret serology of individuals living in endemic areas where positive serological results may be more common and may not always indicate an acute or recent infection.
Data now may also act as a baseline to help determine whether Lyme disease is spreading and becoming more common. This will be of benefit to patients affected by Lyme disease and healthcare workers treating it in the UK. Many people are concerned about the possible presence of co‑infections transmitted by ticks; these are thought to be rare in the UK (compared with other parts of the world) but there are insufficient data to confirm or refute this. Better evidence may improve diagnostic and treatment decisions.
What are the most clinically and cost-effective treatment options for different clinical presentations of Lyme disease in the UK?
The evidence on the effectiveness of antimicrobial treatment regimens used in different presentations of Lyme diseases is of poor quality, out-dated and often based on small studies. No relevant cost-effectiveness evidence was identified. A series of prospective multicentre studies is needed to compare the clinical and cost effectiveness of different dosages and length of treatments needed and the clinical and cost effectiveness of oral compared with intravenous treatments for different presentations of Lyme disease. This is felt to be of high priority because it has enormous implications for people with Lyme disease and for NHS costs.
There is currently insufficient quality evidence on the most effective drug and dose, and the effectiveness of extended treatment or retreatment regimens in those with continuing symptoms remains uncertain, leading to multiple referrals in search of alternative diagnoses. Clarification could improve outcomes, reduce costs and may minimise unnecessary treatment.
5 Laboratory tests to diagnose initial and ongoing infection and determine re‑infection in the different presentations of Lyme disease in the UK
What is the most clinically and cost-effective serological antibody-based test, biomarker or other test for diagnosing Lyme disease in the UK at all stages, including re‑infection?
Determining the most clinically and cost-effective diagnostic tests for Lyme disease will improve patient care and is a high priority. The clinical presentation of Lyme disease is variable with the diagnosis of all presentations, except erythema migrans, relying in part on laboratory testing. Current literature suggests that a combined IgG/IgM enzyme-linked immunosorbent assay (ELISA) based on the IR6 peptide and immunoblot are useful; however, published evidence is of either low or very low quality and is not UK based. There is evidence of variation in the IR6 peptide between the principal Borrelia genospecies in UK ticks and a combination of ELISAs may improve sensitivity.
A 'test of cure' for Lyme disease does not exist and, consistent with most other infectious diseases, serology is likely to remain positive for some time following successful treatment of infection in most patients. However, little is known about the evolution of antibody titres over time in those who have been treated successfully and in those who have ongoing symptoms.
It is frequently stated that early antibiotic treatment of Lyme disease abrogates the immune response, so that serology remains or becomes negative. This is not a common occurrence in other infections but there are inadequate prospective data on whether it occurs in people with Lyme disease. Observational studies to clarify this would be helpful. In addition, understanding the natural course of Lyme disease serology, and non-serological tests over time, may assist in the interpretation of test results in patients who remain symptomatic and in those who are high risk for re‑infection, such as those with occupational exposure.
In particular, further research into the value of novel biomarkers (for example, CXCL13 and others) and other types of tests may be helpful to support the current low-quality evidence. The examples of tests included in this research recommendation reflect those included in this guideline. However, other novel biomarkers are likely to be developed and require similar assessment.