Anti-Malaria Chemotherapy: State-of-the-Art in Prevention and Treatment and Novel Leads for Drug Development

Malaria is an infectious disease endemic to 106 countries of the tropical and subtropical regions of the world. According to the World Health Organization there were 216 million cases of malaria in 2010 that resulted in 655000 deaths. Children under the age of 5 are the most vulnerable, but approximately half of the world’s population is at risk. Malaria is a febrile illness caused by parasitic protozoa of the genus Plasmodium, and transmitted exclusively by Anopheles mosquitoes. Control involves both prevention, through the use of indoor insecticide spraying with pyrethroids, insecticide treated bed nets, drug treatment of populations at high risk of infection and disease treatment. Malaria can be cured, but the development of resistance by Plasmodium is recurrent. Due to its high mortality and morbidity, the eradication of this disease has high priority in the UN 2000 Millennium Development Goals. As a result of renewed efforts, malaria related mortality decreased by 26% in the period 2000-2010, but control tools are limited. Presently there are no vaccines registered for this disease. The most deadly variant, caused by Plasmodium falciparum, is treated with artemisinin-based combination therapy with a 4-aminoquinoline or an amino alcohol. Recent reports of mosquito resistance to pyrethroid insecticides and of Plasmodium to artemisinin are serious causes for concern. The development of novel drugs remains a big challenge. This chapter highlights the state-of-the-art in malaria prevention and treatment. The literature published since 2000 on the development of new leads for chemotherapy is also reviewed.

Keywords: Malaria, antimalarial, Plasmodium, protozoa, Anopheles, infectious disease, pharmacology, artemisinin combination therapy, quinine, erythrocytes, antibiotics, aminoquinolines.