Antimalarial drugs resistance

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Olliaro, P. L. and Bloland, P. B. (2001) Clinical and public health implicationsof antimalarial drug resistance, in Antimalarial Chemotherapy Mechanisms of Action, Resistance, and New Directions in Drug Discovery (ed. P. J. Rosenthal), Humana Press, Totowa, NJ, pp. 65-83. 

Plowe C V (2005). Antimalarial drug resistance in Africa Strategies for monitoring and deterrence. Curr. Top. Microbiol. Immunol. 295 55-79. 

Malaria is still one of the world s most devastating infectious diseases. An estimated 270 million people are affected by the parasite every year, and close to 2 million children die. The most deadly species, Plasmodium falciparum, has become widely resistant to most of the available antimalarial drugs such as quinolines. 

Antimalarial drug choice takes into account tolerability and plasmodial resistance. 

Quinidine (6) and quinine (7) are diastereomeric quinoline alkaloids obtained from Cinchona spp. Quinidine (6) is included in many pharmacopeias for its antiarrhythmic effects.Quinine was the first antimalarial drug and served as an effective remedy for this deadly infectious disease in colonial times, making European settlement in many tropical and subtropical parts of the world possible.Owing to the development of resistance to synthetic antimalarials, quinine is still reverted to some extent for this... 

Malaria is the cause for approximately 20% of child deaths in Africa and for more than 1 million deaths around the world each year. The appearance and spread of drug resistance of the Plasmodium falciparum parasites to common antimalarial drugs, such as chloroquine and hydroxychloroquine, have posed the urgent challenge of developing effective, safe and affordable antimalarial drugs. 

Knowledge of local resistance patterns is important to determine the treatment regimen. There is increasing chloroquine and pyrimethamine-sulfado-xine (Fansidar) resistance in Africa and in some areas at the border of Thailand there is resistance for almost all antimalarial drugs including halofantrine, mefloquine and quinine. In these areas only the artemisinin derivatives (artemether, arteether, arte-sunate, dihydroartemisinin) are effective. 

Halofantrine was an important antimalarial drug. It is now infrequently used because of worldwide strain resistance phenomena. Tafenoquine is a new 8-amino-quinoline currently in clinical trials (Phase III) (Figure 8.26). ... 

Tresochin/Bayer Imagon/Astra (it was until recently the best antimalarial drug, now rendered useless in most areas drug resistance acquired by the parasite)... 

Mefloquine is effective in treating most falciparum malaria. The drug is not appropriate for treating individuals with severe or complicated malaria, since quinine, quinidine, and artemisinins are more rapidly active, and since drug resistance is less likely with those agents. The combination of artesunate plus mefloquine showed excellent antimalarial efficacy in regions of Southeast Asia with some resistance to mefloquine, and this regimen is now one of the combination therapies recommended by the WHO for the treatment of uncomplicated falciparum malaria (Table 52-4). Artesunate-mefloquine is the first-line therapy for uncomplicated malaria in a number of countries in Asia and South America. 

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