Cambodian border around 1957 (Harinasuta et al., 1965); Venezuela and the nearby Magdalena Valley of Colombia around 1960 (Moore and Lanier, 1961); and Port Moresby, Papua New Guinea, in the mid-1970s (Grimmond et al., 1976). In Africa, CRPF was first found in 1978 in nonimmune travelers to Kenya and Tanzania (Lobel et al., 1985), spreading next to inland coastal areas and by 1983, to Sudan, Uganda, Zambia, and Malawi (Talisuna et al., 2004). Current evidence suggests that CRPF strains seen in Africa originated in Asia.

The pyrimidine derivative, proguanil, was another drug that emerged from the antimalarial pipeline during World War II. Proguanil’s success in treating humans (Curd et al., 1945) stimulated further study of its pharmaceutical class (agents that block folate synthesis in parasites and bacteria), and the development of pyrimethamine (Falco et al., 1951). However, as both monotherapies came into common use, it became apparent that malaria parasites could quickly alter the target enzyme of the two drugs, leading to resistance. Resistance to proguanil, for example, was observed within a year of introduction in Malaya in 1947 (Peters, 1987).

Sulfones and sulfonamides (drugs which act on another enzyme which helps the malaria parasite synthesize folic acid) were then combined with proguanil or pyrimethamine in the hopes of increasing efficacy, and forestalling or preventing the development of resistance (Cowman, 1998). P. falciparum strains resistant to pyrimethamine, and cross-resistant to proguanil and related compounds emerged in 1953 in Muheza, Tanzania; eight years later, these strains constituted 40 percent of P. falciparum isolates in a 15-mile radius (Clyde, 1966). Sulfadoxine-pyrimethamine (SP), today the most widely used antifolate antimalarial combination, was introduced in Thailand in 1967. Resistance to SP was first reported in Thailand later that year (Wernsdorfer and Payne, 1991). Although parasite resistance to SP spread quickly throughout Southeast Asia, it remained low in Africa until 5 or 6 years ago. Since then it has rapidly spread throughout Africa as well.

The development of mefloquine was a collaborative achievement of the U.S. Army Medical Research and Development Command, the World Health Organization (WHO/TDR), and Hoffman-La Roche, Inc. After World War II, about 120 compounds were produced at the Walter Reed Army Institute of Research (WRAIR) in an attempt to find replacements for quinine. Preclinical trials coincided with the appearance of chloroquine-

Front Matter (R1-R20)

Executive Summary (1-16)

Part 1: A Response to the Current Crisis1 Malaria Today (17-60)

2 The Cost and Cost-Effectiveness of Antimalarial Drugs (61-78)

3 The Case for a Global Subsidy of Antimalarial Drugs (79-111)

4 An International System for Procuring Anitmalarial Drugs (112-122)

Part 2: Malaria Basics5 A Brief History of Malaria (123-135)

6 The Parasite, the Mosquito, and the Disease (136-167)

7 The Human and Economic Burden of Malaria (168-196)

8 Malaria Control (197-251)

9 Antimalarial Drugs and Drug Resistance (252-298)

Part 3: Advancing Toward Better Malaria Control10 Research and Development for New Antimalarial Drugs (299-311)

11 Maximizing the Effective Use of Antimalarial Drugs (312-328)

Acronyms and Abbreviations (329-333)

Glossary (334-346)

Index (347-364)