Studies on a West African strain of plasmodium falciparum II. The efficacy of paludrine (proguanil) as a therapeutic agent

Abstract

1. 1. An account is given of a series of therapeutic trials with paludrine carried out at Horton Hospital, Epsom, against infections with a strain of P. falciparum obtained from an African child resident. in Lagos, Nigeria, West Africa. 2. 2. Paludrine effectually controlled the clinical attack produced by infections with this strain of parasite, but its action in this respect and in clearance of asexual parasites from the peripheral blood was somewhat less rapid than that achieved with mepacrine or quinine. 3. 3. Paludrine without reinforcement failed to effect radical cure of infections with this strain, nine out of ten cases so treated relapsing within 3 weeks after completion of the course. This finding was in marked contrast with the results reported by FAIRLEY and his colleagues in their researches on infections with New Guinea strains of P. falciparum. 4. 4. Radical cure of infections with the Lagos strain of P. falciparum was effected in a limited series of cases treated with paludrine reinforced with mepacrine or with quinine on the first day of treatment, and with quinine alone. 5. 5. Following a course of paludrine mg. 300 twice daily for 10 days, gametocytes were found to be non-infectioe to mosquitoes for as long as they continued to be present in the peripheral blood in sufficient numbers for infection to occur. 6. 6. Reinforcement of a 10 days' course of paludrine with mepacrine given on the first day of treatment shortened the average duration of pyrexia and clinical symptoms by approximately 24 hours. Similar reinforcement with quinine did not have this effect. 7. 7. It is considered that a course of paludrine mg. 300 twice daily for 10 days, reinforced with mepacrine mg. 900 given in three doses on the first day of treatment and followed by a maintenance dose of paludrine mg. 100 daily for the ensuing 6 weeks would fulfil the main objectives in the treatment of falciparum malaria, namely, rapid termination of the clinical attack, a high radical cure rate, sterilization of gametocytes and minimum risk of injurious side effects.