ACTIONS OF SOME ANTIMALARIA AGENTS ON PLAMODIUM BERGHEI BERGHEI AND PLASMODIUM FALCIPARUM IN IN-VIVI AND IN-VITRO MODELS

Abstract

The antimalarial actions of four drugs,Chloroquine, WR33063, Primaquine and Tetracycline have been studied on P. berqheiberghei in albino Swiss mice and P.falciparum culturein vitro. In the rodent model,the Schizontocidal action of the drugs were investigated both at the early stage of P.berghel berghei infection and at advanced stage. In the early stage,the ’4-Day Test' was employed while at the advanced infection ‘28-Day Test' was used as an index of cure. All the four drugs demonstrated blood Schizontocidal action with Chloroquine and WR 33063 showing greater activity than Primaquineand Tetracycline in the ‘4-Day Test’. WR33063 demonstrated a high cure rate in the 28-Day Test, eliminating relapses at high doses. Others followed inthe following sequence, primaquine>>chloroquine >Tetracyline. The drugs were combined to seeif this would offer any advantage and the result indicated potentiation with Chloroquine/WR33063,and Chloroquine /Primaquine combination with a simple addition in chloroquine/Tetracycline combination. The respository action of the drugs was assessed by observing the degree of protection of mice when challenged with an inoculum of 107 parasites at weekly intervals after the administration of drugs WR33063 showed a high degree of residual action and the other drugs showed little or no activities.

The toxicity studies undertaken revealed that the drugs are relatively safe with LD50 of WR33063 ranging above 2cm/kg. An incidence study undertaken in the G.O.P. U.C.H., Ibadan among children to see if human malaria still constitutes a health harzard beyond doubt showed that malaria 1s a major problem. The malaria Infected blood collected from such children provided sample for In vitro culture of p. falciparum which was found In the course of this study as the most prevalent species of human malaria parasite. Investigation Into various culture techniques,were made and Jensen and Trager's (1977)method employing the use of RMP1 1640 wss found to support cultures better than other techniques. Drug trials. based on Inhibition of Maturation of p.falciparum in vitro were also made, and each of the drug, demonstrated some blood schlzonticidal action In vitro on the species The hue and cry on the emergence of chloroquine resistantstrain of p.falciparum from various parts of the world stimulated an investigation into the sensitivity of p falciparum.Ibadan strain to chloroquine in vitro. This was backed up by subjecting the name patients to the W.H.O. recommended chloroquine therapy. Both results revealed that there were no chloroquine resistant strains of p.falciparum in Ibadan as yet among the population studied and at the time of investigation.

The mode of action studies revealed that Chloroquine might be acting by clumping the pigment of the malaria parasites. All the four drugs have been shown to interact with DNA and to impart some morphological disorders on P. berghei berghei in mice.