Through the largest randomized controlled trials ever conducted on antimalarials in Africa, a considerable body of evidence has now been collected showing that artemisinin-based combinations improve cure rates, decrease gametocyte carriage, and are well tolerated with few serious adverse effects. In the first of these multicenter trials to be published, 941 children who had uncomplicated P. falciparum malaria were randomly assigned 3 days treatment with amodiaquine plus artesunate, or amodiaquine plus placebo. Both regimens were well tolerated. The combination of artesunate and amodiaquine significantly improved treatment efficacy in Gabon (85 versus 71 percent, p=0.02) and in Kenya (68 vs. 41 percent, p<0.0001). In Senegal, however, the two regimens were equivalent: day-28 cure rates for amodiaquine-artesunate versus amodiaquine were 82 versus 79 percent (p=0.5) (Adjuik et al., 2002).

The efficacy and safety of artesunate in combination with sulfadoxine-pyrimethamine (SP) has been evaluated in randomized controlled trials involving 2,865 patients in sub-Saharan Africa. Results from the first study published from The Gambia (von Seidlein et al., 2000) (where the cure rate with SP monotherapy was then 93 percent), showed that both cure rate and parasite clearance were significantly higher in patients who received 3 days of artesunate plus a single dose of SP compared with those who received SP alone. Gametocyte carriage was 68 percent following solo SP treatment in comparison with 21 percent following the artesunate-SP combination (p=0.001).

In contrast, underlying SP resistance in Uganda led to unacceptable rates of late recrudescence when artesunate-SP was used there (Dorsey et al., 2002). This finding underscores that combining an artemisinin with a longer-acting drug without any underlying resistance may prove the optimal regimen in many areas. On the other hand, in Thailand, where drug resistance is particularly severe, artesunate plus mefloquine was highly effective, even in areas where mefloquine resistance was previously quite common (Price et al., 1997). In the largest-ever series of therapeutic efficacy studies with ACTs, artesunate plus mefloquine produced a sustained, increased cure rate (almost 100 percent from 1998 onward) despite established resistance to high-dose mefloquine alone seen between 1990 and 1994 (Nosten et al., 2000). Cure rates with other ACTs (atovaquone-proguanil-artesunate, artemether-lumefantrine) in Asia have also been consistently above 90 percent (van Vugt et al., 1998, 1999).

Coartem (artemether-lumefantrine) is the first fixed-dose ACT whose

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)