Optimal Treatments for Severe Malaria and the Threat Posed by Artemisinin Resistance.

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.

• Authors: Sam Jones, Eva Maria Hodel, Raman Sharma, Katherine Kay, Ian M Hastings
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 219 Issue 8 Pg. 1243-1253 (04 08 2019) ISSN: 1537-6613 [Electronic] United States
• PMID: 30517708 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America.

Chemical References

• Antimalarials
• Artemisinins
• Artesunate
• artemisinin

Topics

• Acute Disease
• Antimalarials (administration & dosage, therapeutic use)
• Artemisinins (therapeutic use)
• Artesunate (administration & dosage, therapeutic use)
• Drug Resistance
• Humans
• Malaria, Falciparum (drug therapy, parasitology, pathology)
• Models, Biological
• Parasitemia (drug therapy, parasitology)
• Plasmodium falciparum (drug effects)
• Treatment Outcome