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Determinants of In Vitro Drug Susceptibility Testing of Plasmodium vivax

Russell, Bruce, Chalfein, Ferryanto, Prasetyorini, B., Kenangalem, Enny, Piera, Kim A., Suwanarusk, Rossarin, Brockman, Alan, Prayoga, Pak, Sugiarto, P., Cheng, Qi, Tjitra, Emiliana, Anstey, Nicholas M. and Price, Erin P. (2008). Determinants of In Vitro Drug Susceptibility Testing of Plasmodium vivax. Antimicrobial Agents and Chemotherapy,52(3):1040-1045.

Document type: Journal Article
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IRMA ID 10026xPUB8
Title Determinants of In Vitro Drug Susceptibility Testing of Plasmodium vivax
Author Russell, Bruce
Chalfein, Ferryanto
Prasetyorini, B.
Kenangalem, Enny
Piera, Kim A.
Suwanarusk, Rossarin
Brockman, Alan
Prayoga, Pak
Sugiarto, P.
Cheng, Qi
Tjitra, Emiliana
Anstey, Nicholas M.
Price, Erin P.
Journal Name Antimicrobial Agents and Chemotherapy
Publication Date 2008
Volume Number 52
Issue Number 3
ISSN 0066-4804   (check CDU catalogue open catalogue search in new window)
Start Page 1040
End Page 1045
Total Pages 6
Place of Publication Washington, United States
Publisher American Society for Microbiology
Field of Research 0605 - Microbiology
1108 - Medical Microbiology
HERDC Category C1 - Journal Article (DEST)
Abstract 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.
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