Effect of pyrimethamine on gametocytogenesis, exflagellation and asexual growth in southern African isolates of Plasmodium Falciparum.
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Date
1995
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Abstract
Pyrimethamine efficacy was investigated in vitro on the blood asexual stages, the sexual stages
and exflagellation in Plasmodium falciparum. Gametocytogenesis was stimulated following the
standard methods on five isolates of Plasmodium falciparum. From these five isolates, RSA
2, 3 and 5 produced gametocytes which reached maturity within seven days and the
gametocytes were able to exflagellate. Isolate MW2 produced young gametocytes which
disappeared within ten days. NF54 produced mature gametocytes which lasted for 24 hours
only.
There were no statistically significant differences between the static and the synchronization
methods of gametocyte stimulation for any of the isolates. The effect of pyrimethamine was
investigated by adding a known concentration of the drug (For RSA 2, MW2 and NF54,
l00nmol/ℓ; RSA 3 and 5, 3000nmol/ℓ pyrimethamine) to the culture medium for seven days
during gametocyte stimulation. The results of this investigation show that there was
gametocytocidal activity on the isolates that were used and pyrimethamine also had a
schizontocidal action on NF54 and the young gametocytes of this isolate were destroyed by
the drug. At concentrations which were inhibitory to asexual parasites, the drug had a
sporontocidal effect on isolate RSA 2 but not on isolate RSA 5. The pyrimethamine MIC
values for asexual parasites ranged from 300nmol/ℓ to > 3000nmol/ℓ (RSA 2 and 5 were not
inhibited at 3000nmol/ℓ ). These results are consistent with those found in previous studies
when pyrimethamine resistance was first detected in South Africa. The chloroquine MICs indicate a good correlation with the results obtained from previous drug
sensitivity tests for all the isolates examined using both the 48-hour in vitro test and isotope
incorporation for growth assessment. The isobolograms constructed to determine relationship
between chloroquine and pyrimethamine indicated no synergism for isolates RSA 2 and 5, but
the Σ relative IC[50]s indicated a weak synergism. Both the isobolograms and the Σ relative IC[50]s
for the isolates RSA 6, 9 and 14 indicated an antagonistic action between chloroquine and
pyrimethamine. The results obtained from this study have important implications for malaria
control in South Africa.
Description
Thesis (M.Sc.)-University of Natal, Pietermaritzburg, 1995.
Keywords
Plasmodium falciparum., Malaria--Prevention., Antimalarials., Drug resistance in microorganisms., Theses--Entomology.