Tick range expansion to higher elevations: does Borrelia burgdorferi sensu lato facilitate the colonisation of marginal habitats?

BACKGROUND: Parasites can alter host and vector phenotype and thereby affect ecological processes in natural populations. Laboratory studies have suggested that Borrelia burgdorferi sensu lato, the causative agent of human Lyme borreliosis, may induce physiological and behavioural alterations in its main tick vector in Europe, Ixodes ricinus, which increase the tick's mobility and survival under challenging conditions. These phenotypic alterations may allow I. ricinus to colonise marginal habitats ('facilitation hypothesis'), thereby fuelling the ongoing range expansion of I. ricinus towards higher elevations and latitudes induced by climate change. To explore the potential for such an effect under natural conditions, we studied the prevalence of B. burgdorferi s.l. in questing I. ricinus and its variation with elevation in the Swiss Alps. RESULTS: We screened for B. burgdorferi s.l. infection in questing nymphs of I. ricinus (N = 411) from 15 sites between 528 and 1774 m.a.s.l to test if B. burgdorferi s.l. prevalence is higher at high elevations (i.e. in marginal habitats). Opposite of what is predicted under the facilitation hypothesis, we found that B. burgdorferi s.l. prevalence in I. ricinus nymphs decreased with increasing elevation and that Borrelia prevalence was 12.6% lower in I. ricinus nymphs collected at the range margin compared to nymphs in the core range. But there was no association between Borrelia prevalence and elevation within the core range of I. ricinus. Therefore the observed pattern was more consistent with a sudden decrease in Borrelia prevalence above a certain elevation, rather than a gradual decline with increasing elevation across the entire tick range. CONCLUSIONS: In conclusion, we found no evidence that B. burgdorferi s.l.-induced alterations of I. ricinus phenotype observed in laboratory studies facilitate the colonisation of marginal habitats in the wild. Rather, ticks in marginal habitats are substantially less likely to harbour the pathogen. These findings have implications for a better understanding of eco-evolutionary processes in natural host-parasite systems, as well as the assessment of Lyme borreliosis risk in regions where I. ricinus is newly emerging.

Rivaroxaban for Prevention of Covert Brain Infarcts and Cognitive Decline: The COMPASS MRI Substudy.

BACKGROUND AND PURPOSE: Covert brain infarcts are associated with cognitive decline. It is not known whether therapies that prevent symptomatic stroke prevent covert infarcts. COMPASS compared rivaroxaban with and without aspirin with aspirin for the prevention of stroke, myocardial infarction, and vascular death in participants with stable vascular disease and was terminated early because of benefits of rivaroxaban 2.5 mg twice daily plus aspirin over aspirin. We obtained serial magnetic resonance imagings and cognitive tests in a consenting subgroup of COMPASS patients to examine treatment effects on infarcts, cerebral microbleeds, and white matter hyperintensities. METHODS: Baseline and follow-up magnetic resonance imagings were completed in 1445 participants with a mean (SD) interval of 2.0 (0.7) years. Whole-brain T1, T2 fluid-attenuated inversion recovery, T2* sequences were centrally interpreted by blinded, trained readers. Participants had serial measurements of cognition and function. The primary end point was the proportion of participants with incident covert infarcts. Secondary end points were the composite of clinical stroke and covert brain infarcts, cerebral microbleeds, and white matter hyperintensities. RESULTS: At baseline, 493 (34.1%) participants had infarcts. Incident covert infarcts occurred in 55 (3.8%) participants. In the overall trial rivaroxaban plus aspirin reduced ischemic stroke by 49% (0.7% versus 1.4%; hazard ratio [95% CI], 0.51 [0.38-0.68]). In the magnetic resonance imaging substudy the effects of rivaroxaban+aspirin versus aspirin were: covert infarcts: 2.7% versus 3.5% (odds ratio [95% CI], 0.77 [0.37-1.60]); Covert infarcts or ischemic stroke: 2.9% versus 5.3% (odds ratio [95% CI], 0.53 [0.27-1.03]). Incident microbleeds occurred in 6.6% of participants and 65.7% of participants had an increase in white matter hyperintensities volume with no effect of treatment for either end point. There was no effect on cognitive tests. CONCLUSIONS: Covert infarcts were not significantly reduced by treatment with rivaroxaban and aspirin but estimates for the combination of ischemic stroke and covert infarcts were consistent with the effect on ischemic stroke in the overall trial. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01776424.