*Corresponding Author Address: Dr. Ndubuisi N. Nwobodo MBBS,Ph.D,FRSTMH,FRSM(Lond.), Division of Clinical Pharmacology and Translational Medicine, Department of Pharmacology & Therapeutics, Faculty of Clinical Medicine, Ebonyi State University, PMB 53, Abakaliki, Nigeria; E-mail: nnwobodo@yahoo.com World Journal of Pharmaceutical Sciences ISSN (Print): 2321-3310; ISSN (Online): 2321-3086 Published by Atom and Cell Publishers © All Rights Reserved Available online at: http://www.wjpsonline.org/ Original Article Statin treatment enhances clinical response to artesunate in acute uncomplicated malaria *Ndubuisi N. Nwobodo 1 , Paul O. Okonkwo 2 1 Department of Pharmacology & Therapeutics, Ebonyi State University, Abakaliki, Nigeria 2 Department of Pharmacology & Therapeutics, University of Nigeria, Nigeria Received: 05-08-2014 / Revised: 21-08-2014 / Accepted: 23-08-2014 ABSTRACT Several reports have emerged on widespread clinical failures since the introduction of artesunate as first-line treatment for malaria. This study sought to evaluate the synergistic effects of simvastatin plus artesunate combination in antimalarial chemotherapy. Patients in attendance at primary health facilities (n=60) suffering from malaria infection were selected for the study and informed consent obtained. Ethical clearance certification was obtained (NHREC/05/01/2008B) and patients categorized into artesunate plus simvastatin (test) and artesunate alone (control) groups. The patients were followed up on days D0, D3, D7, D14 and D28 post- treatment and in line with WHO criteria. Graphpad Prism version 4.0 was employed in the analysis of data. Results revealed statistically significant difference (p<0.05) in clinical response between test and control groups involving all the parameters assessed. The post-treatment mean geometric parasite density was given as 0±0.0/μL and 139±19.0/μL in the test and control groups. The mean total treatment failure was given as 1.9±0.13% in the test group compared to 19.3±0.44% in the control. A mean parasite clearance time of 1.2±0.9 days in the test group as compared to 2.9±0.29 days in the control was reported. Mean fever clearance time of 12.1±0.8 hours and 38.6±2.8 hours was reported in the test and control groups. The recrudescence rate of 1.1±0.05% given in the test differed from 8.7±0.09% given in the control. Consequently, simvastatin plus artesunate may be considered as novel approach for combinational therapy aimed at enhancing clinical response to artesunate. Key words: Artesunate, clinical response, fever clearance, parasite clearance, simvastatin, treatment failure, uncomplicated malaria. INTRODUCTION Statins are known to inhibit 3-hydroxy 3-methyl glutaryl coenzyme A reductase, that catalyses the rate limiting step in cholesterol biosynthesis. They are generally reputed to be beneficial in reducing incidence of mortality and morbidity associated with cardiovascular disease[1]. However, studies have shown that statins exhibited other effects independent of cholesterol lowering including the potential to inhibit the growth of bacteria and protozoa[2,3]. Simvastatin has been found to have antimalarial effects inhibiting in vitro intraerythrocytic development of malaria parasite[4]. . World Health Organisation has since recommended the adoption of artesunate as first line treatment of malaria in endemic regions. The effectiveness and contribution of artemisinins in the reduction of malaria burden have been acknowledged globally[5]. The emergence of treatment failure or prolonged parasite clearance time along the Thai- Cambodian border has raised major public health concern due to the risk of possible spread to other regions particularly in Africa where artemisinins are widely recommended and used as first line antimalarial therapy[6,7]. Hence, the need to improve the efficacy of artesunate and enhance its antimalarial effect can never be over-emphasized. This study, therefore, sought to evaluate the synergistic effects of simvastatin plus artesunate combination in antimalarial chemotherapy.