Flow cytometry for the evaluation of anti-plasmodial activity of drugs on Plasmodium falciparum gametocytes.
BACKGROUND
The activity of promising anti-malarial drugs against Plasmodium gametocytes is hard to evaluate even in vitro. This is because visual examination of stained smears, which is commonly used, is not totally convenient. In the current study, flow cytometry has been used to study the effect of established anti-malarial drugs against sexual stages obtained from W2 strain of Plasmodium falciparum. Gametocytes were treated for 48 h with different drug concentrations and the gametocytaemia was then determined by flow cytometry and compared with visual estimation by microscopy.


CONCLUSIONS
Initially gametocytaemia was evaluated either using light microscopy or flow cytometry. A direct correlation (r2 = 0.9986) was obtained. Two distinct peaks were observed on cytometry histograms and were attributed to gametocyte populations. The activities of established anti-malarial compounds were then measured by flow cytometry and the results were equivalent to those obtained using light microscopy. Primaquine and artemisinin had IC50 of 17.6 microM and 1.0 microM, respectively. Gametocyte sex was apparently distinguishable by flow cytometry as evaluated after induction of exflagellation by xanthurenic acid. These data form the basis of further studies for developing new methods in drug discovery to decrease malaria transmission.
Chevalley
Séverine
S
Université de Toulouse-3, LPSNPR (Laboratoire Pharmacochimie des Substances Naturelles et Pharmacophores Redox), Toulouse, France.
Coste
Agnès
A
Lopez
Alexandrine
A
Pipy
Bernard
B
Valentin
Alexis
A
D000890:Anti-Infective Agents / Q000494:pharmacology / Q000627:therapeutic use; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D037621:Artemisinins / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D005434:Flow Cytometry / Q000379:methods*; D020128:Inhibitory Concentration 50; D016778:Malaria, Falciparum / Q000188:drug therapy; D008853:Microscopy; D018512:Parasitemia / Q000188:drug therapy; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development; D011319:Primaquine / Q000494:pharmacology; D014977:Xanthurenates
D000890:Anti-Infective Agents; D000962:Antimalarials; D037621:Artemisinins; D014977:Xanthurenates; C028330:xanthurenic acid; D002738:Chloroquine; C031327:artemisinin; D011319:Primaquine