The effect of artesunate on short-term memory in Lyme borreliosis

Abstract

Lyme borreliosis is associated with memory deficits. While this may be related to cerebral infection by Borrelia bacteria, it may also be caused by concomitant co-infection by Babesia protozoa. The anti-malarial artemisinin-derivative artesunate has been shown to be effective against a number of Babesia species and to have efficacy against human cerebral malaria. We hypothesised that concomitant administration of artesunate in Lyme borreliosis patients would help alleviate the severity of self-reported short-term memory impairment. This hypothesis was tested in a small pilot study in which patients were treated with both an intravenous antibiotic and oral artesunate (20 mg four times per day); treatment was associated with a reduction in the severity of short-term memory difficulties (P ≃ 0.08). In light of these findings, we recommend that a formal randomised, placebo-controlled study be carried out.

Introduction

Compared with depression and fibromyalgia, patients with Lyme encephalopathy suffer from significant memory deficits [1], while the subjective degree of memory functioning in Lyme borreliosis is inversely correlated with the degree of self-reported depression [2]. Furthermore, over 26 per cent of Lyme borreliosis patients may have antibodies for the erythrocytic intracellular protozoal parasite Babesia microti [3], and this and other Babesia species are known to infect the mammalian brain [4], [5], [6]. Thus, it is reasonable to suppose that concomitant co-infection with Babesia species may account for some of the memory impairment suffered by Lyme borreliosis patients.

The anti-malarial water-soluble semi-synthetic artemisinin-derivative artesunate has been shown to be effective against a number of Babesia species, both in vitro and in vivo, including B. microti, B. bovis and B. gibsoni [7]. Indeed, the finding that the artemisinin derivatives artesunate and artemether show high efficacy in rescuing a murine model with late-stage cerebral malaria and rapidly diminish cerebral accumulation of leukocytes [8] has been borne out by recent human case reports of the efficacy of artesunate (in combination with antibiotic therapy) in cerebral malaria [9], [10].