Our common understanding of Lyme disease is that a tick bite is followed by the development of a classic rash pattern (erythema migrans). When treated early with a relatively short course of antibiotics, most patients have good outcomes.6 But the standard two tier testing for Lyme disease is inaccurate in the early stages, and many patients and doctors fail to recognise the rash.7 Patients who present with the later stages of the disease can also be easily dismissed because the two tier testing lacks sensitivity and cannot distinguish between current and past infection. At the same time, the evidence remains limited on the reasons for treatment failure and unresolved systemic symptoms in patients with or without serological evidence of the disease. Most patients will present to family physicians, who often have few subsequent resources when the initial treatment proves unsuccessful.
Recently, the medical community has been collectively forced out of its comfort zone on Lyme disease by increasing evidence of the complexity of this multisystem disease.8 To further complicate matters, some patients develop long term symptoms. The complexities are essentially related to either a lack of understanding of the disease or conflicting evidence. Many questions await full answers (box).9 Evidence that answers these questions, and especially that highlights the inter-relatedness of the different components, could underpin the necessary rethinking around this condition.
Tick box: research agenda
Range of clinical presentations, including between sexes
Diagnostic criteria and tools
Treatments and their efficacy
Transmission modes and vectors
Role of coinfections
Uncertainty over clinical definition of chronic Lyme disease and whether detection of active infection is essential
Whether and for how long the pathogen can persist
Role of psychoneuroimmunology, host-pathogen interactions, and autoimmunity to residual or persisting antigens
Role of toxins or other bacterial products in symptoms and signs
Contribution of environmental factors
Recent evidence shedding light on how spirochaetes of the Borrelia genus evade host immune defences and survive antibiotic challenge10 11 12 13 14 15 threaten current beliefs about the persistence of infection, one of the largest points of contention in the medical community. The possibility of persistent infection has important implications for diagnosis, treatment, and doctor-patient interactions.16