Excerpt Since Moore And Lanier's (1) report of two patients with chloroquine-resistantPlasmodium falciparuminfections acquired in the Magdalena Valley of Columbia in 1961, a fear has existed among ...

Treatment of Chloroquine-resistant Plasmodium falciparum Infections in Vietnam

From 1936 until 1996, the drug dapsone treated a diverse array of diseases, including tuberculosis, leprosy, malaria, and AIDS-related pneumonia This article explores how dapsone transformed from a cure for one disease into a treatment for a totally different malady This process of reinvention in the clinic represents an alternative model of drug development that the historical literature, focused on success in the laboratory, has largely ignored The core of the paper discusses the reinvention of dapsone as an antimalarial in the Vietnam War through trials led by Robert J T Joy, a physician and military officer As a case study, it offers a fresh perspective on the clinic-as-laboratory approach that other scholars have addressed in a civilian context Viewing the randomized clinical trial (RCT) through a military prism will demonstrate how a combat environment combined with the regimentation of the armed forces affected the standard methodology of the RCT

A Short History of Dapsone, or an Alternative Model of Drug Development

Malaria remains a formidable global problem. Although substantial progress has been made in efforts to combat and to eliminate this protozoan scourge, much remains to be done. This review dealing with the chemotherapy of malaria presents: a brief resume of historical aspects relating to the development of synthetic antimalarial drugs; a discussion of apposite considerations with respect to parasites that cause human malaria, classification of antimalarial drugs, and terminology; a summary of available information concerning the uses and effects of quinine and widely employed synthetic antimalarial drugs; a short account of certain other antimalarial agents, some developed recently, that are of considerable experimental interest; and a discussion of resistance of malaria parasites to drugs, with particular emphasis on recently detected parasites that are resistant to chloroquine and to other synthetic antimalarial drugs.

The chemotherapy of malaria.

The purpose of this report is to summarize the results of recent studies concerning the antimalarial and hemolytic effects of 4,4'-diaminodiphenyl sulfone (DDS; dapsone; diaphenylsulfone ). It has long been known that DDS possesses antimalarial activity and that hemolysis represents one of the major undesirable effects of DDS. Because of the superiority of other synthetic antimalarial drugs such as chloroquine, DDS has been of little value as an antimalarial agent; however, recent observations, particularly studies with strains of Plasmodium falciparum that are resistant to chloroquine and to other widely used syn-

The antimalarial and hemolytic properties of 4,4-diaminodiphenyl sulfone (DDS).

The review of antimalarial pharmacology and the examination of results in recent studies of malaria in Vietnam revealed that (1) quinoline derivatives have multiple actions which include interference with nucleic acid replication and glucose metabolism; (2) sulfonamides and sulfones competitively antagonize aminobenzoic acid (PABA); and (3) folic acid reductase inhibitors interfere with the conversion of folic acid to folinic acid. No single agent produced satisfactory cure rates in recent trials with malaria in Vietnam. A combination of quinine and pyrimethamine appeared to give additive results. A combination of pyrimethamine and a sulfonamide gave superior results consistent with their proved synergism. A combination therapy of a long-acting sulfonamide with pyrimethamine, possibly with the addition of quinine, is recommended as the most rational therapy at this time.

The Pharmacology of the Antimalarials: A Rational Approach to the Therapy of Resistant Falciparum Malaria

Treatment of Human Malaria by Diamino-Diphenyl-Sulphone (DDS), Singly and in Combination with Pyrimethamine. A Preliminary Study of their Effects in P. vivax and P. falciparum Infections in Rajasthan, India.

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Treatment of Human Malaria by Diamino-Diphenyl-Sulphone (DDS), Singly and in Combination with Pyrimethamine. A Preliminary Study of their Effects in P. vivax and P. falciparum Infections in Rajasthan, India.