Artemisinin induced dormancy in Plasmodium falciparum : duration, recovery rates and implications in treatment failure

Teuscher, Franka, Gatton, Michelle L., Chen, Nanhua, Peters, Jennifer, Kyle, Dennis E., & Cheng, Qin (2010) Artemisinin induced dormancy in Plasmodium falciparum : duration, recovery rates and implications in treatment failure. Journal of Infectious Diseases, 202(9), pp. 1362-1368.

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Abstract

This article is free to read on the publisher's website

Background

Despite the remarkable activity of artemisinin and its derivatives, monotherapy with these agents has been associated with high rates of recrudescence. The temporary arrest of the growth of ring-stage parasites (dormancy) after exposure to artemisinin drugs provides a plausible explanation for this phenomenon.

Methods

Ring-stage parasites of several Plasmodium falciparum lines were exposed to different doses of dihydroartemisinin (DHA) alone or in combination with mefloquine. For each regime, the proportion of recovering parasites was determined daily for 20 days.

Results

Parasite development was abruptly arrested after a single exposure to DHA, with some parasites being dormant for up to 20 days. Approximately 50% of dormant parasites recovered to resume growth within the first 9 days. The overall proportion of parasites recovering was dose dependent, with recovery rates ranging from 0.044% to 1.313%. Repeated treatment with DHA or with DHA in combination with mefloquine led to a delay in recovery and an ∼10-fold reduction in total recovery. Strains with different genetic backgrounds appeared to vary in their capacity to recover.

Conclusions

These results imply that artemisinin-induced arrest of growth occurs readily in laboratory-treated parasites and may be a key factor in P. falciparum malaria treatment failure.

Impact and interest:

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ID Code: 75112
Item Type: Journal Article
Refereed: Yes
Additional Information: Articles free to read on journal website after 12 months
Keywords: malaria, Plasmodium, falciparum, artemisinin, dormancy
DOI: 10.1086/656476
ISSN: 1537-6613
Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > MICROBIOLOGY (060500) > Infectious Agents (060502)
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
Funding:
Deposited On: 25 Aug 2014 03:14
Last Modified: 19 May 2017 01:12

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