Determinants of in vitro drug susceptibility testing of Plasmodium vivax.

Antimicrob Agents Chemother 2008 Mar 7;52(3):1040-5. Epub 2008 Jan 7.

International Health Program, Infectious Diseases Division, Menzies School of Health Research and Charles Darwin University, Darwin, Australia.

In Papua, Indonesia, the antimalarial susceptibility of Plasmodium vivax (n = 216) and P. falciparum (n = 277) was assessed using a modified schizont maturation assay for chloroquine, amodiaquine, artesunate, lumefantrine, mefloquine, and piperaquine. The most effective antimalarial against P. vivax and P. falciparum was artesunate, with geometric mean 50% inhibitory concentrations (IC50s) (95% confidence intervals [CI]) of 1.31 nM (1.07 to 1.59) and 0.64 nM (0.53 to 0.79), respectively. In contrast, the geometric mean chloroquine IC50 for P. vivax was 295 nM (227 to 384) compared to only 47.4 nM (42.2 to 53.3) for P. falciparum. Two factors were found to significantly influence the in vitro drug response of P. vivax: the initial stage of the parasite and the duration of the assay. Isolates of P. vivax initially at the trophozoite stage had significantly higher chloroquine IC50s (478 nM [95% CI, 316 to 722]) than those initially at the ring stage (84.7 nM [95% CI, 45.7 to 157]; P < 0.001). Synchronous isolates of P. vivax and P. falciparum which reached the target of 40% schizonts in the control wells within 30 h had significantly higher geometric mean chloroquine IC50s (435 nM [95% CI, 169 to 1,118] and 55.9 nM [95% CI, 48 to 64.9], respectively) than isolates that took more than 30 h (39.9 nM [14.6 to 110.4] and 36.9 nM [31.2 to 43.7]; P < 0.005). The results demonstrate the marked stage-specific activity of chloroquine with P. vivax and suggest that susceptibility to chloroquine may be associated with variable growth rates. These findings have important implications for the phenotypic and downstream genetic characterization of P. vivax.

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.01334-07DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2258486PMC
March 2008

Publication Analysis

Top Keywords

vivax
9
chloroquine ic50s
8
plasmodium vivax
8
isolates vivax
8
vivax falciparum
8
vitro drug
8
geometric chloroquine
8
chloroquine
6
stage higher
4
478 [95%
4
[95% 316
4
[95%
4
316 722]
4
ic50s 478
4
higher chloroquine
4
ring stage
4
457 157]
4
157] 0001
4
0001 synchronous
4
[95% 457
4

Altmetric Statistics

Similar Publications