administration, which included mass chemoprophylaxis, and the Pinotti method—the systematic addition of antimalarial drugs to salt.

The notion that treating symptomatic individuals might indirectly protect an entire malaria-exposed population dates back to Robert Koch and the early years of the 20th century (Harrison, 1978). At that time, with this goal partly in mind, quinine was used extensively in Italy and elsewhere. Since quinine has little effect on gametocytes, however, it had little effect on transmission overall.

Today, in contrast, artemisinin-based drugs (which do kill early-stage gametocytes as well as asexual parasites) have helped to decrease transmission in selected areas of Asia and Africa. On the Thai-Burmese border, where field studies using ACTs were first undertaken in 1991, replacing mefloquine with mefloquine-artesunate as first-line treatment for symptomatic malaria substantially reduced the incidence of local P. falciparum infection (Nosten et al., 2000). Widespread use of artemisinins and ACTs—along with ITNs or IRS—also contributed to a marked decline in the overall incidence of falciparum malaria in Vietnam (Hung et al., 2002) and South Africa (Barnes et al., 2003) (Box 8-2)—both areas with relatively low EIRs. Whether widespread use of ACTs will bring about a similar outcome in areas of higher malaria transmission (EIR > 100) is still unknown.

Unlike Southeast Asia and South Africa, many malaria infections in sub-Saharan Africa—especially in older children and adults—are asymptomatic and untreated but have parasite densities sufficient for transmission (von Seidlein et al., 2002). Under these conditions, reducing malaria transmission by use of a gametocytocidal drug requires that asymptomatic as well as symptomatic carriers be treated. This led to the concept of mass drug administration (MDA). During MDA, the entire population of a community known to contain many asymptomatic infected subjects receives treatment without first determining who is actually parasitemic.

MDA as a method of reducing malaria transmission gained momentum after the 8-aminoquinolones (of which primaquine is the leading prototype) were discovered. This class of drugs is highly effective at killing gametocytes of P. falciparum. One of the first trials to investigate 8-aminoquinolones as MDA agents took place in a Liberian rubber plantation in 1930. Mass treatment with plasmoquine led to a marked decrease in parasite prevalence and a reduction in infected mosquitoes in two treated camps (Barber et al., 1932). During the 1960s and 1970s, several more

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)