Tick-transmitted co-infections among erythema migrans patients in a general practice setting in Norway: a clinical and laboratory follow-up study

Knut Eirik Eliassen,Lukas Frans Ocias,Morten Lindbak,Karen A Krogfelt,Åshild Andreassen,Per-Eric Lindgren,Susanne Gjeruldsen Dudman,Peter Wilhelmsson

doi:10.1186/s12879-021-06755-8

Abstract

BackgroundErythema migrans (EM) is the most common manifestation of Lyme borreliosis. Here, we examined EM patients in Norwegian general practice to find the proportion exposed to tick-transmitted microorganisms other than Borrelia, and the impact of co-infection on the clinical manifestations and disease duration.MethodsSkin biopsies from 139/188 EM patients were analyzed using PCR for Neoehrlichia mikurensis, Rickettsia spp., Anaplasma phagocytophilum and Babesia spp. Follow-up sera from 135/188 patients were analyzed for spotted fever group (SFG) Rickettsia, A. phagocytophilum and Babesia microti antibodies, and tested with PCR if positive. Day 0 sera from patients with fever (8/188) or EM duration of ≥ 21 days (69/188) were analyzed, using PCR, for A. phagocytophilum, Rickettsia spp., Babesia spp. and N. mikurensis. Day 14 sera were tested for TBEV IgG.ResultsWe detected no microorganisms in the skin biopsies nor in the sera of patients with fever or prolonged EM duration. Serological signs of exposure against SFG Rickettsia and A. phagocytophilum were detected in 11/135 and 8/135, respectively. Three patients exhibited both SFG Rickettsia and A. phagocytophilum antibodies, albeit negative PCR. No antibodies were detected against B. microti. 2/187 had TBEV antibodies without prior immunization. There was no significant increase in clinical symptoms or disease duration in patients with possible co-infection.ConclusionsCo-infection with N. mikurensis, A. phagocytophilum, SFG Rickettsia, Babesia spp. and TBEV is uncommon in Norwegian EM patients. Despite detecting antibodies against SFG Rickettsia and A. phagocytophilum in some patients, no clinical implications could be demonstrated.

Highlights

Erythema migrans (EM) is the most common manifestation of Lyme borreliosis
We examined EM-patients from Norway using molecular and serological methods to determine (1) the proportion exposed to tick-transmitted microorganisms other than Borrelia burgdorferi sensu lato (Bbsl), and (2) the impact of co-infection on the clinical manifestations and disease duration of these patients
Additional real-time Polymerase chain reaction (PCR) analysis on the inclusion samples of patients displaying at least a fourfold rise in anti-Rickettsia IgG compared to baseline revealed no detectable Rickettsia DNA

Summary

Introduction

Erythema migrans (EM) is the most common manifestation of Lyme borreliosis. Here, we examined EM patients in Norwegian general practice to find the proportion exposed to tick-transmitted microorganisms other than Borrelia, and the impact of co-infection on the clinical manifestations and disease duration. Lyme borreliosis (LB) is the most common tick-transmitted infection in the Nordic countries and often presents clinically as a slowly expanding, erythematous skin lesion, Eliassen et al BMC Infect Dis (2021) 21:1044. Erythematous skin lesions, similar to those seen in EM, have been associated with or attributed to N. mikurensis [12,13,14,15]. This relationship has, never been studied in a larger population sample and no causality has been established. It is important to determine the clinical significance of such co-infection and the possibility of skin lesions, similar to EM, being caused by tick-transmitted microorganisms other than Bbsl

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