Optimal treatments for severe malaria and the threat posed by artemisinin resistance

Jones, Sam, Hodel, EvaMaria ORCID: https://orcid.org/0000-0001-5821-1685, Sharma, Raman, Kay, Katherine and Hastings, Ian ORCID: https://orcid.org/0000-0002-1332-742X (2019) 'Optimal treatments for severe malaria and the threat posed by artemisinin resistance'. Journal of Infectious Disease, Vol 219, Issue 8, pp. 1243-1253.

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Abstract

Background
Standard treatment for severe malaria is with artesunate; patient survival in the 24 hours immediately posttreatment is the key objective. Clinical trials use clearance rates of circulating parasites as their clinical outcome, but the pathology of severe malaria is attributed primarily to noncirculating, sequestered, parasites, so there is a disconnect between existing clinical metrics and objectives.
Methods
We extend existing pharmacokinetic/pharmacodynamic modeling methods to simulate the treatment of 10000 patients with severe malaria and track the pathology caused by sequestered parasites.
Results
Our model recovered the clinical outcomes of existing studies (based on circulating parasites) and showed a “simplified” artesunate regimen was noninferior to the existing World Health Organization regimen across the patient population but resulted in worse outcomes in a subgroup of patients with infections clustered in early stages of the parasite life cycle. This same group of patients were extremely vulnerable to resistance emerging in parasite early ring stages.
Conclusions
We quantify patient outcomes in a manner appropriate for severe malaria with a flexible framework that allows future researchers to implement their beliefs about underlying pathology. We highlight with some urgency the threat posed to treatment of severe malaria by artemisinin resistance in parasite early ring stages.

Item Type:	Article
Subjects:	QV Pharmacology > Anti-Inflammatory Agents. Anti-Infective Agents. Antineoplastic Agents > QV 256 Antimalarials QX Parasitology > Protozoa > QX 135 Plasmodia WC Communicable Diseases > Tropical and Parasitic Diseases > WC 680 Tropical diseases (General) WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
Faculty: Department:	Biological Sciences > Department of Tropical Disease Biology Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):	https://doi.org/10.1093/infdis/jiy649
Depositing User:	Stacy Murtagh
Date Deposited:	06 Dec 2018 16:49
Last Modified:	19 Sep 2019 11:29
URI:	https://archive.lstmed.ac.uk/id/eprint/9644

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