Artemisinin-induced parasite dormancy : a plausible mechanism for treatment failure
Codd, Andrea , Teuscher, Franka , Kyle, Dennis E, Cheng, Qin , & Gatton, Michelle L (2011) Artemisinin-induced parasite dormancy : a plausible mechanism for treatment failure. Malaria Journal, 10, p. 56.
Background Artemisinin-combination therapy is a highly effective treatment for uncomplicated falciparum malaria but parasite recrudescence has been commonly reported following artemisinin (ART) monotherapy. The dormancy recovery hypothesis has been proposed to explain this phenomenon, which is different from the slower parasite clearance times reported as the first evidence of the development of ART resistance. Methods In this study, an existing P. falciparum infection model is modified to incorporate the hypothesis of dormancy. Published in vitro data describing the characteristics of dormant parasites is used to explore whether dormancy alone could be responsible for the high recrudescence rates observed in field studies using monotherapy. Several treatment regimens and dormancy rates were simulated to investigate the rate of clinical and parasitological failure following treatment. Results The model output indicates that following a single treatment with ART parasitological and clinical failures occur in up to 77% and 67% of simulations, respectively. These rates rapidly decline with repeated treatment and are sensitive to the assumed dormancy rate. The simulated parasitological and clinical treatment failure rates after 3 and 7 days of treatment are comparable to those reported from several field trials. Conclusions Although further studies are required to confirm dormancy in vivo, this theoretical study adds support for the hypothesis, highlighting the potential role of this parasite sub-population in treatment failure following monotherapy and reinforcing the importance of using ART in combination with other anti-malarials.
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|Item Type:||Journal Article|
|Keywords:||faliciparum, dormancy, artemisinin, mathematical modelling|
|Subjects:||Australian and New Zealand Standard Research Classification > MATHEMATICAL SCIENCES (010000) > APPLIED MATHEMATICS (010200) > Biological Mathematics (010202)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > PUBLIC HEALTH AND HEALTH SERVICES (111700) > Public Health and Health Services not elsewhere classified (111799)
|Divisions:||Current > QUT Faculties and Divisions > Faculty of Health
Current > Schools > School of Public Health & Social Work
|Copyright Owner:||Copyright 2011 Codd et al; licensee BioMed Central Ltd.|
|Copyright Statement:||This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.|
|Deposited On:||18 Aug 2014 03:24|
|Last Modified:||19 Aug 2014 00:54|
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