Prevalence and determinants of persistent symptoms after treatment for Lyme borreliosis: study protocol for an observational, prospective cohort study (LymeProspect)

BMC Infect Dis. 2019 Apr 15;19(1):324. doi: 10.1186/s12879-019-3949-8.


Background: After antibiotic treatment of Lyme borreliosis, a subset of patients report persistent symptoms, also referred to as post-treatment Lyme disease syndrome. The reported prevalence of persistent symptoms varies considerably, and its pathophysiology is under debate. The LymeProspect study has been designed to investigate the prevalence, severity, and a wide range of hypotheses on the etiology of persistent symptoms among patients treated for Lyme borreliosis in the Netherlands.

Methods: LymeProspect is a prospective, observational cohort study among adults with proven or probable Lyme borreliosis, either erythema migrans or disseminated manifestations, included at the start of antibiotic treatment. During one year of follow-up, participants are subjected to questionnaires every three months and blood is collected repeatedly during the first three months. The primary outcome is the prevalence of persistent symptoms after treatment, assessed by questionnaires online focusing on fatigue (CIS, subscale fatigue severity), pain (SF-36, subscale pain) and neurocognitive dysfunction (CFQ). Potential microbiological, immunological, genetic, epidemiological and cognitive-behavioral determinants for persistent symptoms are secondary outcome measures. Control cohorts include patients with long-lasting symptoms and unconfirmed Lyme disease, population controls, and subjects having reported a tick bite not followed by Lyme borreliosis.

Discussion: This article describes the background and design of the LymeProspect study protocol. This study is characterized by a prospective, explorative and multifaceted design. The results of this study will provide insights into the prevalence and determinants of persistent symptoms after treatment for Lyme borreliosis, and may provide a rationale for preventive and treatment recommendations.

Trial registration: NTR4998 (Netherlands Trial Register). Date of registration: 13 February 2015.

Keywords: Borrelia; Borreliosis; Erythema Migrans; Lyme disease; Persistent symptoms; Post-treatment Lyme disease syndrome; Study protocol.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Anti-Bacterial Agents / therapeutic use
  • Bites and Stings / complications
  • Clinical Protocols
  • Cohort Studies
  • Erythema Chronicum Migrans / drug therapy
  • Erythema Chronicum Migrans / epidemiology
  • Erythema Chronicum Migrans / etiology
  • Fatigue / etiology
  • Humans
  • Lyme Disease / drug therapy*
  • Lyme Disease / epidemiology*
  • Lyme Disease / etiology
  • Middle Aged
  • Netherlands / epidemiology
  • Prevalence
  • Prospective Studies
  • Surveys and Questionnaires
  • Ticks


  • Anti-Bacterial Agents