Neoehrlichia mikurensis in Sweden : An emerging tick-borne human pathogen

Abstract: Neoehrlichia mikurensis is an emerging tick-borne human pathogen, causing neoehrlichiosis in immunosuppressed and immunocompetent individuals. It targets the vascular endothelium, leading to thromboembolic and vascular events, but can also pass without symptoms. As symptoms easily are misinterpreted, immunosuppressive treatment or chemotherapy is often incorrectly initiated. Diagnostic delay can be considerable.The overall aim of this thesis was to gain a better understanding on N. mikurensis in Sweden, focusing on human infections and public health aspects. The prevalence of N. mikurensis in different populations was examined. The symptomatology of neoehrlichiosis and the risk of transfusion-mediated transmission was studied. N. mikurensis was observed in low prevalences in ticks collected from migratory birds, in tick-bitten individuals, in patients with persistent symptoms attributed to presumed tick-bite exposure, and in blood donors. Fourteen N. mikurensis-positive individuals were identified. The majority were immunocompetent and asymptomatic. Both spontaneous clearance and persistence was observed. Two of 102 tick-bitten individuals were N. mikurensis-positive. Both presented with erythema migrans, but borreliosis was a more probable cause in both. The findings do not support a change in practice regarding first-line treatment of erythema migrans, but further studies are warranted.Persistence of N. mikurensis in blood raises questions regarding the possibility of transmission by transfusion and the risk of activating the infection if immune status is altered. N. mikurensis was identified in seven out of 1 006 blood donors. Look-back and tracing identified 12 recipients who were transfused with blood components from N. mikurensis-positive donors. Several recipients had multiple risk factors for severe neoehrlichiosis, but transfusion-transmitted neoehrlichiosis was not detected. Nevertheless, the possibility that N. mikurensis can be transmitted by transfusion cannot be excluded.Isolates from birds and blood donors were identical to previously reported Swedish human isolates. Migrating birds can act as dispersal vectors of N. mikurensis, but their role as transmission hosts is still unclear.The disease burden and public health impact of neoehrlichiosis is probably small, but information is lacking in several areas. Suspicion of neoehrlichiosis is warranted in immunocompromised and/or splenectomised patients with persistent fever, with or without thromboembolic and vascular events. Furthermore, neoehrlichiosis should be included in the differential diagnosis of anaplasmosis. Besides raised awareness, a possible mandatory notification is proposed as well as a comprehensive surveillance system for transfusion-transmitted infections. One of the priority issues is the possible need for screening of patients living in N. mikurensis-endemic areas before and during immunosuppressive treatment.