Date Published: October 4, 2018
Publisher: Public Library of Science
Author(s): Petra Bogovič, Lara Lusa, Daša Stupica, Tereza Rojko, Miša Korva, Tatjana Avšič-Županc, Klemen Strle, Gary P. Wormser, Franc Strle, Alessandro Marcello.
Although statins have anti-inflammatory and potentially also antimicrobial (including antiviral) activity, their therapeutic impact on infectious diseases is controversial. In this study, we evaluated whether pre-existing statin use influenced the course and outcome of tick-borne encephalitis.
To assess the influence of statin usage on the severity of acute illness and the outcome of tick-borne encephalitis, univariate and multivariable analyses were performed for 700 adult patients with tick-borne encephalitis of whom 77 (11%) were being treated with statins, and for 410 patients of whom 53 (13%) were receiving statins, respectively.
Multivariable analyses found no statistically significant association between statin usage and having a milder acute illness. There was also no statistically significant benefit with respect to a favorable outcome defined by the absence of post-encephalitic syndrome (ORs for a favorable outcome at 6 months was 0.96, 95% CI: 0.46–2.04, P = 0.926; at 12 months 0.29, 95% CI: 0.06–1.33, P = 0.111; at 2–7 years after acute illness 0.44, 95% CI: 0.09–2.22, P = 0.321), by a reduction in the frequency of six nonspecific symptoms (fatigue, myalgia/arthralgia memory disturbances, headache, concentration disturbances, irritability) occurring during the 4 week period before the last examination, or by higher SF-36 scores in any of the eight separate domains of health as well as in the physical and mental global overall component. Furthermore, there were no significant differences between patients receiving statins and those who were not in the cerebrospinal fluid or serum levels for any of the 24 cytokines/chemokines measured.
In this observational study, we could not prove that pre-existing use of statins affected either the severity of the acute illness or the long-term outcome of tick-borne encephalitis.
Tick-borne encephalitis (TBE) is a central nervous system infection caused by three subtypes of TBE virus, i.e. European, Siberian and Far-Eastern. It is transmitted to humans by tick bite of the same Ixodes species that transmit Borrelia burgdorferi sensu lato, and very rarely by consumption of infected (usually goat) milk or milk products. TBE caused by the European virus subtype has a milder course and better outcome than TBE caused by the Siberian or Far-Eastern subtypes [1–3]. In the majority of patients with TBE caused by the European virus subtype, the disease has a biphasic course that begins with a nonspecific febrile illness with headache (which corresponds to viremia), followed by improvement of a few days duration, and then by the development of higher fever and signs of central nervous system involvement. However, in up to one-third of patients, the initial phase is absent or very mild. The clinical spectrum of TBE ranges from mild meningitis to severe meningoencephalitis, with or without pareses . In central Europe the case fatality rate is between 0.5 and 2%, about 5% of patients are affected by permanent pareses, and at least 30% suffer from a postencephalitic syndrome (PES). There is no specific antiviral treatment for TBE [1, 3, 4]. Although potentially preventable by vaccination, infection by the TBE virus (TBEV) is responsible for more than 10,000 hospitalizations every year in endemic areas of Europe and Asia .
Because of their widespread use as a cholesterol lowering drug, coupled with their anti-inflammatory and anti-microbial properties, statins have gained increasing interest in having a potentially beneficial role in infectious disease. The attractive concept is that statins could reduce inflammation-induced tissue pathology without altering the risk or worsening of the infection. However, this topic remains highly controversial.
In the present study we were not able to demonstrate a favorable impact of statins on the severity of the acute illness or on the long-term outcome of TBE. Overall, our study adds to the knowledge base on the impact of statins on various infections. Some studies have shown benefit [10–12, 15], while others have not [8, 13, 14, 16, 18, 25]. Our study provides compelling evidence that studies evaluating the risk-to-benefit ratio of pre-existing statin treatment on the outcome of infections must control for other variables associated with taking statins that could significantly affect outcome.