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. 2010 Nov 1;202(9):1362-8.
doi: 10.1086/656476.

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

Franka Teuscher  1 , Michelle L Gatton, Nanhua Chen, Jennifer Peters, Dennis E Kyle, Qin Cheng
Affiliations

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

Franka Teuscher et al. J Infect Dis. .

Abstract

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 approximately 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.

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Conflict of interest statement

The authors do not have a commercial or other association that might pose a conflict of interest.

Figures

Figure 1
Figure 1
Experimental design to A) monitor recovery in bulk cultures; B) to determine rates and duration of recovery of parasites following treatment with single or multiple doses of DHA or DHA in combination with mefloquine.
Figure 2
Figure 2
Effect of 200 ng/ml DHA on bulk cultures of three parasite strains (W2, HB3 and D6) with and without the use of a magnetic column on Days 1, 2 and 3. The starting parasitemias were 0.20% and 2% for control and DHA treated samples, respectively.
Figure 3
Figure 3
Cumulative recovery rates for W2 at three DHA concentrations.
Figure 4
Figure 4
Cumulative recovery rates for 5 parasite strains each treated with 200 ng/ml DHA for 6 hours on Day 1.
Figure 5
Figure 5
Parasite recovery after repeated treatment with DHA and combination treatment with DHA and mefloquine (MQ).
See this image and copyright information in PMC

Comment in

  • Waking the sleeping beauty.
    Nosten F. Nosten F. J Infect Dis. 2010 Nov 1;202(9):1300-1. doi: 10.1086/656478. J Infect Dis. 2010. PMID: 20863226 Free PMC article. No abstract available.

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