Effect of pyrimethamine on gametocytogenesis, exflagellation and asexual growth in southern African isolates of Plasmodium Falciparum.
Year: 1995
Type: dissertation
Abstract: Pyrimethamine efficacy was investigated in vitro on the blood asexual stages, the sexual stages \nand exflagellation in Plasmodium falciparum. Gametocytogenesis was stimulated following the \nstandard methods on five isolates of Plasmodium falciparum. From these five isolates, RSA \n2, 3 and 5 produced gametocytes which reached maturity within seven days and the \ngametocytes were able to exflagellate. Isolate MW2 produced young gametocytes which \ndisappeared within ten days. NF54 produced mature gametocytes which lasted for 24 hours \nonly. \nThere were no statistically significant differences between the static and the synchronization \nmethods of gametocyte stimulation for any of the isolates. The effect of pyrimethamine was \ninvestigated by adding a known concentration of the drug (For RSA 2, MW2 and NF54, \nl00nmol/ℓ; RSA 3 and 5, 3000nmol/ℓ pyrimethamine) to the culture medium for seven days \nduring gametocyte stimulation. The results of this investigation show that there was \ngametocytocidal activity on the isolates that were used and pyrimethamine also had a \nschizontocidal action on NF54 and the young gametocytes of this isolate were destroyed by \nthe drug. At concentrations which were inhibitory to asexual parasites, the drug had a \nsporontocidal effect on isolate RSA 2 but not on isolate RSA 5. The pyrimethamine MIC \nvalues for asexual parasites ranged from 300nmol/ℓ to > 3000nmol/ℓ (RSA 2 and 5 were not \ninhibited at 3000nmol/ℓ ). These results are consistent with those found in previous studies \nwhen pyrimethamine resistance was first detected in South Africa. The chloroquine MICs indicate a good correlation with the results obtained from previous drug \nsensitivity tests for all the isolates examined using both the 48-hour in vitro test and isotope \nincorporation for growth assessment. The isobolograms constructed to determine relationship \nbetween chloroquine and pyrimethamine indicated no synergism for isolates RSA 2 and 5, but \nthe Σ relative IC[50]s indicated a weak synergism. Both the isobolograms and the Σ relative IC[50]s \nfor the isolates RSA 6, 9 and 14 indicated an antagonistic action between chloroquine and \npyrimethamine. The results obtained from this study have important implications for malaria \ncontrol in South Africa.
Author: Joyce Mahlako. Tsoka
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2114512918