Resistant Plasmodium species

For many years, the treatment of choice for malaria has been chloroquine. Unfortunately, chloroquine-resistant strains of Plasmodium species have developed, emphasizing the need for new antimalarials. One promising antimalarial is artemisinin. 

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. 

Host resistance Bacterial models—Listeria monocytogenes (mortality or spleen clearance) Streptococcus species (mortality) Viral models—influenza (mortality) Parasitic models—Plasmodium yoelii (parasitemia) or Trichinella spiralis (muscle larvae counts and worm expulsion) Syngeneic tumor models—PYB6 sarcoma (tumor incidence) B16F10 melanoma (lung burden). 

Four species of plasmodium typically cause human malaria Plasmodium falciparum, P vivax, P malariae, and P ovale. A fifth species, P knowlesi, is primarily a pathogen of monkeys, but has recently been recognized to cause illness, including severe disease, in humans in Asia. Although all of the latter species may cause significant illness, P falciparum is responsible for the majority of serious complications and deaths. Drug resistance is an important therapeutic problem, most notably with P... 

Dihydrofolate reductase (DHFR), a classic target in antimicrobial and anticancer chemotherapy, has been shown to be a useful therapeutic target in plasmodium, toxoplasma, and eimeria species. Pyrimethamine is the prototypical DHFR inhibitor, exerting inhibitory effects in all three groups. However, pyrimethamine resistance in P falciparum has become widespread in recent years. This is largely attributable to specific point mutations in P falciparum DHFR that have rendered the enzyme less susceptible to the inhibitor. 

Protozoal infections. Malaria is the major transmissible parasitic disease in the world. The life cycle of the plasmodium that is relevant to prophylaxis and therapy is described. Drug resistance is an increasing problem and differs with geographical location, and species of plasmodium. 

Disease control is hampered by the occurrence and increase of multi-drag-resistant strains of the malaria parasite Plasmodium sp. Many species affect humans though p. falciparum, is responsible for the most severe illnesses and deaths attributable to malaria in sub-Sahara Africa and in certain areas of South-East Asia and the Western Pacific (7). 

This still does not quite explain why this genetic disease is so common. In fact, in tropical countries human red cells often carry unwanted passengers in the form of the malaria parasite, Plasmodium. These hitch-hikers are even more upset by reactive oxygen species than the red cells themselves, so that the genetic disease actually has a positive side effect of conferring resistance against malaria. 

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