RESUMEN
The progressive spread in Asia and South America of falciparum malaria resistant to 4-aminoquinolines, and the focal occurrence in all malarious regions of infections resistant to dihydrofolate dehydrogenase inhibitors such as pyrimethamine and proguanil, make it everywhere necessary to be alert to the failure of accepted curative, prophylactic, or sporontocidal chemotherapeutic agents. Resistance to 4-aminoquinolines may be met curatively with courses of treatment lasting 1-14 days, or more, the longer courses relying on quinine, often with a sulfonamide, or on tetracyclines, and the shorter courses on associations of sulfonamides or sulfones with pyrimethamine or trimethoprim. Suppressive prophylaxis of these infections is obtained by the injection at 3-month intervals of a repository mixture of acedapsone and cycloguanil, or by the weekly ingestion of sulfadoxine, sulfalene, or diformyl-dapsone associated with pyrimethamine, or the daily ingestion of dapsone with proguanil. Primaquine, although continuing to be an efficient sporontocide of P. falciparum when pyrimethamine and proguanil no longer suffice, is becoming less effective in preventing relapses of P. vivax in countries around New Guinea.
Asunto(s)
Malaria/tratamiento farmacológico , África , Antimaláricos/administración & dosificación , Antimaláricos/farmacología , Antimaláricos/uso terapéutico , Asia , América Central , Dapsona/uso terapéutico , Resistencia a Medicamentos , Quimioterapia Combinada , Humanos , Malaria/prevención & control , Masculino , Plasmodium falciparum/efectos de los fármacos , América del Sur , Sulfonamidas/uso terapéutico , Tetraciclina/uso terapéutico , Factores de TiempoRESUMEN
WR 33063, a phenanthrene methanol, was studied in human volunteers for tolerance and toxicity. In normal volunteers, it was possible to give 4.6 g in four divided doses without adverse effect for 10 days. At this dose level, there was neither evidence of photosensitivity nor adverse renal or cardiac effect. At a dose level of 1.6 g in four divided doses for 6 days, WR 33063 cured 18 of 23 nonimmune volunteers infected with the Smith strain of Plasmodium falciparum from Vietnam. In addition, infections due to the Marks and Braithwaite Vietnam strains were also treated because these strains represent a major therapeutic challenge to chloroquine; six of six and two of three volunteers, respectively, were cured. With the Malayan Camp strain, 1.6 g in four divided doses for 6 days cured all of five volunteers. The African Uganda I strain of chloroquine-responsive malaria was even more responsive to WR 33063; all of six men who received 1.6 g in four divided doses for 6 days were cured, and all of three men who received this same dosage for 3 days were cured. One subject infected with a Haitian strain of P. falciparum was treated and cured. Blood-induced infections with the Chesson strain of P. vivax also responded well to WR 33063 with four of five men cured. In all, 52 men received WR 33063 in tolerance trials, and 59 men with experimental malaria and one man with clinical malaria were treated with WR 33063.