Paludrine in the Treatment of Malaria

Mechanisms of Resistance of Malaria Parasites to Antifolates

“…Proguanil. Early reports on the use of proguanil (Paludrine) for both prophylaxis and treatment were very encouraging (Maegraith et al, 1945(Maegraith et al, , 1946Jones et al, 1948;Seaton and Lourie, 1949), despite a slower schizontocidal action (defined as activity against any asexual blood stage parasite, not only schizonts) compared with quinine or mepacrine (Covell et al, 1949). Thereafter, when proguanil was used in the late 1940s and the early 1950s as prophylaxis for plantation workers in Southeast Asia and elsewhere, it provided an opportunity for widespread drug selection pressure on the parasite and the subsequent development of resistance to this drug.…”

The Effect of Paludrine on Human Gastric Secretion

“…Abdominal discomfort, nausea, and vomiting have been noted by Fairley (1946) and Maegraith (1946) with doses of 1.0 g. a day, and Fairley also observed diarrhoea and haematuria. The toxic symptoms usually subsided without reduction of the dose as the malaria for which the paludrine was given was relieved.…”

The Therapeutic Effectiveness of Large Doses of Paludrine in Acute Attacks of Sporozoite-Induced Viv Ax Malaria (Chesson Strain) 1

“…This dosage was chosen because earlier work of British investigators had demonstrated that 0.97 gram of the base per day produced minimal symptoms of toxicity. This dosage was the largest that had been used in man at the time our studies were begun, and was many times greater than the dosage which has been found effective in other strains of malaria (5,6).…”

“…Maegraith, Adams and their co-workers (3, 4, 5) tested this compound in human infections and found that it was a highly effective agent in the treatment of both srvax and falciparum malaria in man. Paludrine has been studied extensively by English (5) and Australian investigators (6) and its activity and usefulness have been confirmed. Maegraith et al (5) produce clinical cure of relapses and delayed primary attacks of naturally acquired zivax malaria.…”

“…Paludrine has been studied extensively by English (5) and Australian investigators (6) and its activity and usefulness have been confirmed. Maegraith et al (5) produce clinical cure of relapses and delayed primary attacks of naturally acquired zivax malaria. The drug is well tolerated in doses as high as 1.5 grams a day for 14 to 28 days.…”