Paper: Researches on paludrine (M.4888) in Malaria An experimental investigation undetaken by the L.H.Q. Medical Research Unit (A.I.F.), Cairns, Australia

Abstract

Inasmuch as paludrine (N1-p-chlorophenyl-N5-isopropylbiguanide acetate) showed definite prophylactic and therapeutic actions against Plasmodium cathemerium, P. gallinaceum, P. lophurae, and P. relictum in birds, it was tried on both artificially and naturally induced strains (New Guinea) of P. falciparum, P. vivax, and P. malariae in man. Paludrine served as a complete causal prophylactic in 17 cases of attempted infection with P. falciparum and as a partial causal prophylactic in 10 cases of attempted infection with P. vivax. Delayed attacks developed in some instances after paludrine administration ceased, but in no case did any symptom of the disease appear during the period of treatment. Both field and laboratory tests supported these conclusions. Paludrine seems to attack and destroy or retard erythrocytic parasite development and also shows schizonticidal action. Daily doses of as little as 25 mg./day served to give complete prophylactic protection (doses of as much as 300 mg./day gave no signs of toxicity in any case). Radical cure of falciparum infections was attained in nearly every case (99%) through the use of a standard treatment of 100 mg. given 3 times daily for a period of 10 days (3 gm. total). Gametocytes were not destroyed although trophozoites were quickly killed. P. vivax infections required a greater total dosage (14 gm.) with paludrine to effect clinical cure. The matter of radical cure is still undetermined as some patients suffered relapses while others have not as yet (12 mo.) done so. P. malariae infections responded to paludrine therapy readily, but radical cures or complete prophylactic protection are not as yet shown to be possible. It seems probable that carrier mosquitoes may be largely sterilized of their infections if they feed at a later date on persons who have received paludrine prophylaxis. Few infected salivary glands could be found under such conditions of feeding. Only plasmoquine approaches paludrine in efficiency, but does so at dosages very close to the toxic threshold of the drug and therefore is far from satisfactory. Use of DDT and paludrine may serve as a very efficient team in wiping out malaria-at least in epidemic form-among non-immune populations.