An in vivo test to assess mefloquine 25 mg/kg for the treatment of uncomplicated falciparum malaria in Rondônia, Brazil

Drug-resistant Plasmodium falciparum is undermining malaria control efforts worldwide. In Brazil, mefloquine (MQ) at a dose of 15 mg/kg body weight is used to treat P. falciparum. At this dose, MQ resistance developed rapidly in Thailand. Use of a higher MQ dose may retard the development of resistance. We treated 50 patients aged one to 67 years who had acute, uncomplicated P falciparum malaria using MQ 25 mg/kg. There were no serious adverse events. Two patients complained of dizziness and insomnia. Assessing evaluable patients, the day 42 cure rate was 40/42 [95.2 percent (95 percent confidence interval 83.8 to 99.4 percent)]. Mefloquine was efficacious and well tolerated in this small cohort from the state of Rôndonia.

Developing artemisinin based drug combinations for the treatment of drug resistant falciparum malaria: A review.

The emergence and spread of drug resistant malaria represents a considerable challenge to controlling malaria. To date, malaria control has relied heavily on a comparatively small number of chemically related drugs, belonging to either the quinoline or the antifolate groups. Only recently have the artemisinin derivatives been used but mostly in south east Asia. Experience has shown that resistance eventually curtails the life-span of antimalarial drugs. Controlling resistance is key to ensuring that the investment put into developing new antimalarial drugs is not wasted. Current efforts focus on research into new compounds with novel mechanisms of action, and on measures to prevent or delay resistance when drugs are introduced. Drug discovery and development are long, risky and costly ventures. Antimalarial drug development has traditionally been slow but now various private and public institutions are at work to discover and develop new compounds. Today, the antimalarial development pipeline is looking reasonably healthy. Most development relies on the quinoline, antifolate and artemisinin compounds. There is a pressing need to have effective, easy to use, affordable drugs that will last a long time. Drug combinations that have independent modes of action are seen as a way of enhancing efficacy while ensuring mutual protection against resistance. Most research work has focused on the use of artesunate combined with currently used standard drugs, namely, mefloquine, amodiaquine, sulfadoxine/pyrimethamine, and chloroquine. There is clear evidence that combinations improve efficacy without increasing toxicity. However, the absolute cure rates that are achieved by combinations vary widely and depend on the level of resistance of the standard drug. From these studies, further work is underway to produce fixed dose combinations that will be packaged in blister packs. This review will summarise current antimalarial drug developments and outline recent clinical research that aims to bring artemisinin based combinations to those that need them most.