Publication: Standardizing the measurement of parasite clearance in falciparum malaria: the parasite clearance estimator
Accepted Date
2011-11-10
Issued Date
2011-11-10
Copyright Date
2011
Resource Type
Language
eng
ISSN
1475-2875 (electronic)
Rights
Mahidol University
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BioMed Central
Bibliographic Citation
Flegg JA, Guerin PJ, White NJ, Stepniewska K. Standardizing the measurement of parasite clearance in falciparum malaria: the parasite clearance estimator. Malar J. 2011 Nov 10;10:339.
Suggested Citation
Flegg, Jennifer A., Guerin, Philippe J., White, Nicholas J., Stepniewska, Kasia Standardizing the measurement of parasite clearance in falciparum malaria: the parasite clearance estimator. Flegg JA, Guerin PJ, White NJ, Stepniewska K. Standardizing the measurement of parasite clearance in falciparum malaria: the parasite clearance estimator. Malar J. 2011 Nov 10;10:339.. doi:10.1186/1475-2875-10-339 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/719
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Title
Standardizing the measurement of parasite clearance in falciparum malaria: the parasite clearance estimator
Corresponding Author(s)
Abstract
BACKGROUND: A significant reduction in parasite clearance rates following
artesunate treatment of falciparum malaria, and increased failure rates following
artemisinin combination treatments (ACT), signaled emergent artemisinin
resistance in Western Cambodia. Accurate measurement of parasite clearance is
therefore essential to assess the spread of artemisinin resistance in Plasmodium
falciparum. The slope of the log-parasitaemia versus time relationship is
considered to be the most robust measure of anti-malarial effect. However, an
initial lag phase of numerical instability often precedes a steady exponential
decline in the parasite count after the start of anti-malarial treatment. This
lag complicates the clearance estimation, introduces observer subjectivity, and
may influence the accuracy and consistency of reported results.
METHODS: To address this problem, a new approach to modelling clearance of
malaria parasites from parasitaemia-time profiles has been explored and
validated. The methodology detects when a lag phase is present, selects the most
appropriate model (linear, quadratic or cubic) to fit log-transformed parasite
data, and calculates estimates of parasite clearance adjusted for this lag phase.
Departing from previous approaches, parasite counts below the level of detection
are accounted for and not excluded from the calculation.
RESULTS: Data from large clinical studies with frequent parasite counts were
examined. The effect of a lag phase on parasite clearance rate estimates is
discussed, using individual patient data examples. As part of the World Wide
Antimalarial Resistance Network's (WWARN) efforts to make innovative approaches
available to the malaria community, an automated informatics tool: the parasite
clearance estimator has been developed.
CONCLUSIONS: The parasite clearance estimator provides a consistent, reliable and
accurate method to estimate the lag phase and malaria parasite clearance rate. It
could be used to detect early signs of emerging resistance to artemisinin
derivatives and other compounds which affect ring-stage clearance.