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Efficacy and safety evaluation of a novel trioxaquine in the management of cerebral malaria in a mouse model

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dc.contributor.authorMalala, Bonface J.
dc.contributor.authorOdhiambo, Onyango C.
dc.contributor.authorWamakima,Hannah N.
dc.contributor.authorMagoma, Gabriel N.
dc.contributor.authorKirira, Peter G.
dc.contributor.authorMuregi, Francis W.
dc.contributor.authorKimani, Francis
dc.date.accessioned2024-07-25T06:54:37Z
dc.date.available2024-07-25T06:54:37Z
dc.date.issued2017-07-03
dc.description.abstractThe emergence of multidrug-resistant strains of Plasmodium falciparum poses a great threat of increased fatalities in cases of cerebral and other forms of severe malaria infections in which parenteral artesunate monotherapy is the current drug of choice. The study aimed to investigate in a mouse model of human cerebral malaria whether a trioxaquine chemically synthesized by covalent linking of a 4,7-dichloroquinoline pharmacophore to artesunate through a recent drug development approach termed ‘covalent bitherapy’ could improve the curative outcomes in cerebral malaria infections. Methods Human cerebral malaria rodent model, the C57BL/6 male mice were infected intraperitoneally (ip) with Plasmodium berghei ANKA and intravenously (iv) treated with the trioxaquine from day 8 post-infection (pi) at 12.5 and 25 mg/kg, respectively, twice a day for 3 days. Treatments with the trioxaquine precursors (artesunate and 4,7-dichloroquine), and quinine were also included as controls. In vivo safety evaluation for the trioxaquine was done according to Organization for Economic Co-operation and Development (OECD) guidelines 423, where female Swiss albino mice were orally administered with either 300 or 2000 mg/kg of the trioxaquine and monitored for signs of severity, and or mortality for 14 days post-treatment. Results The trioxaquine showed a potent and a rapid antiplasmodial activity with 80% parasite clearance in the first 24 h for the two dosages used. Long-term parasitaemia monitoring showed a total parasite clearance as the treated mice survived beyond 60 days post-treatment, with no recrudescence observed. Artesunate treated mice showed recrudescence 8 days post-treatment, with all mice in this group succumbing to the infection. Also, 4,7-dichloroquinoline and quinine did not show any significant parasitaemia suppression in the first 24 h post-treatment, with the animals succumbing to the infection.
dc.identifier.citationOdhiambo, O.C., Wamakima, H.N., Magoma, G.N. et al. Efficacy and safety evaluation of a novel trioxaquine in the management of cerebral malaria in a mouse model. Malar J 16, 268 (2017). https://doi.org/10.1186/s12936-017-1917-6
dc.identifier.urihttps://doi.org/10.1186/s12936-017-1917-6
dc.identifier.urihttps://erepository.mku.ac.ke/handle/123456789/6131
dc.language.isoen
dc.publisherBMC
dc.subjectCovalent bitherapy
dc.subjectPolypharmacology
dc.subjectTrioxaquine
dc.subjectCerebral malaria
dc.titleEfficacy and safety evaluation of a novel trioxaquine in the management of cerebral malaria in a mouse model
dc.typeArticle
dspace.entity.typePublication
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