Efficacy of intranasal administration of artesunate in experimental cerebral malariaReport as inadecuate




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Malaria Journal

, 13:501

First Online: 16 December 2014Received: 17 November 2014Accepted: 12 December 2014

Abstract

BackgroundImproving management of patients suffering from cerebral malaria is needed to reduce the devastating mortality and morbidity of the disease in endemic areas. Intravenous artesunate is currently the first-line treatment, but the lack of material and skills in the field make it difficult to implement in endemic areas. Intranasal route provides a very easy and direct gateway to blood and brain to deliver medications, by-passing the brain blood barrier. Therefore, it could be helpful and suitable to administer artesunate in the context of cerebral malaria, especially in young children. In this study, intranasal administration of artesunate to rescue from cerebral malaria using a murine model was tested.

MethodsCBA-J mice infected with Plasmodium berghei ANKA strain received artesunate 20 mg-kg or a placebo solution intranasally, either on day 5, 6 or 7 post-infection, during a controlled, blinded, randomized trial. Primary endpoint was mortality on day 12 post-infection. Secondary endpoints were parasitaemia and clinical stage. Pharmacokinetics data following administration were collected in blood and brains of treated mice. Local toxicity was evaluated by histopathologic examination of brain and nasal sections in blinded manner.

ResultsIntranasal administration of artesunate dramatically reduced the mortality rate p < 0.001, preventing death in most cases. Parasitaemia loads decreased by 88.7% 61.8-100% within 24 hours after administration. Symptoms of cerebral malaria were prevented or reversed. Dihydroartemisinin was detected in mice blood and brain within 15 minutes of intranasal administration. No direct nasal or brain toxicity was detected.

ConclusionIntranasal delivery is an efficient route to timely and efficiently administer artesunate and therefore may contribute to decreasing malaria-related mortality.

KeywordsCerebral malaria Artesunate Intranasal administration Pharmacokinetic Toxicity AbbreviationsACTArtemisinin combined therapy

INIntranasal

OLFOlfactory

BBBBlood–brain barrier

HPSHaematoxylin phloxine saffron

DHADihydroartemisinin.

Electronic supplementary materialThe online version of this article doi:10.1186-1475-2875-13-501 contains supplementary material, which is available to authorized users.

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Author: Anne Marijon - Guillaume Bonnot - Anthony Fourier - Coralie Bringer - Adeline Lavoignat - Marie-Claude Gagnieu - Anne-Lise 

Source: https://link.springer.com/







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