**Part 7**

**Malaria Drug Evaluation** 

**15** 

*Paris, France* 

**Advances in Antimalarial Drug Evaluation** 

Grellier Philippe, Deregnaucourt Christiane and Florent Isabelle *National Museum of Natural History, UMR 7245 CNRS, Team APE,* 

Parasitic infections due to the protozoa *Plasmodium* are responsible for malaria, a severe disease that still caused about 225 million cases and 781,000 human deaths in 2009, despite the efforts developed during the last decade to fight this disease (Alonso et al., 2011). The international funding allocated to antimalarial strategies has increased regularly since 2003 from about 0.3 billions to 1.7 billion dollars in 2009 (Collier, 2009), allowing many countries to undertake or strengthen effective fights against the parasite, the disease and the vectors. Nonetheless, more than half of the world population still lives in area where there is a risk of malaria transmission. The difficulty in fighting malaria is that five species of *Plasmodium,*  namely *P. ovale*, *P. malariae*, *P. vivax*, *P. falciparum* and *P. knowlesi* (until recently considered as a nonhuman primate parasite) transmitted by over 30 species of *Anopheles* female mosquitoes are known to cause human malaria. The most virulent, *P. falciparum*, is responsible for severe clinical malaria and death. Furthermore, an increasing prevalence of resistance of vectors to insecticides, and of parasites to the standard antimalarial drugs has

Today, the chemotherapeutic arsenal for malaria treatment is limited to three main families of compounds: quinolines, antifolates and artemisinin derivatives. Recommended chemotherapy is based on combinations of existing drugs with artemisinin derivatives (artemisinin combination therapies or ACT), the only antimalarial drug having no clear resistance recorded but for which alarming reports of tolerance in the field indicate it could be just a question of time (Noedl et al., 2008). From 2000 to 2008, the use of ACT combined with vector control allowed to reduce considerably the number of cases of malaria in a dozen African countries, so that nowadays, about 50 % of the total cases of malaria in Africa are found in mainly five countries (Enserink, 2010). However, no new class of antimalarials has been introduced into clinical practice since 1996 due to the intrinsic difficulties in discovering and developing new antimicrobials. A recent review of the global antimalarial drug development (Figure 1), including drugs at various clinical stage development and those expected to enter in phase I studies, showed that the pipeline is rather strong but novelty in terms of drug targets that is required to circumvent resistance is relatively low (Olliaro & Wells, 2009). This situation and the complexity in developing efficient vaccines

require an urgent need for new drugs with original mechanisms of actions.

**1. Introduction** 

been observed for decades.

**and New Targets for Antimalarials** 
