Malarial parasites, drug-resistant

Potential Antimetabolites — Several new types are reported to be active against drug-resistant malarial parasites in experimental animals. Tetra-hydrohomopterolc acid (Va) was effective against both normal and pyrimethamine-resistant P. cynomolgi in monkeys, but tetrahydrohomofolic acid (Vb)... 

One reason for the rapid growth in the use of pesticides worldwide has been the "Green Revolution" (5), Although there have been some benefits from pesticide use in agriculture, they also cause significant environmental and public health problems. The same is true in public health where Insecticides have been used to control malaria. However, today Increased resistance to insecticides in mosquitoes and Increased resistance to drugs by the malarial parasite are resulting in an explosive increase of malaria worldwide (5). 

Pyrimethamine may also be combined with other antimalarials such as artemisinin derivatives, but these regimens should only be used if the malarial parasites are not resistant to the specific drugs in the regimen.13 Pyrimethamine can also be combined with a sulfonamide drug such as dapsone, sulfadiazine, or sulfamethoxazole to treat protozoal infections that cause toxoplasmosis, or fungal infections that cause Pneumocystis pneumonia.These agents are administered orally. 

Following the development of synthetic antimalarial agents, such as chloroquine and mefloquine, the use of Cinchona alkaloid quinine declined. However, with the emergence of chloroquine-resistant and multiple-drug-resistant strains of malarial parasites, its use has become firmly reestablished. Quinine is the drug of choice for severe chloroquine-resistant malaria due to Plasmodium falciparum. In the U.S., the related alkaloid quinidine is recommended because of its wide availability and use as an antiarrhythmic agent. In many clinics in the tropics, quinine is the only effective treatment for severe malaria unfortunately, decreasing sensitivity of P. falciparum to quinine has already been reported from Southeast Asia. 

Scientists at the University of Michigan Medical School, in collaboration with those at the Indian Institute of Science in Bangalore, have carried out tests on curcumin that show it to inhibit the drug-resist-ant forms of malaria and reported their findings in the Journal of Biological Chemistry in December 2004. Mice infected with the related parasite, Plasmodium falciparum, which causes rodent malaria, were fed curcumin and this reduced the number of parasites in the blood by as much as 90%, and completely protected more than a quarter of mice to whom it was given. Whether it could be a treatment for human malarial infection remains to be seen. 

Mefloquine is a long-acting blood schizontocide with high efficacy against malarial parasites resistant to quinine, chloroquine and sulphonamide-pyrimethamine combinations [124-129], A single oral dose of the drug of 15 mg/kg (with a maximum of 750-1000 mg/adult) produces cure rates above 90%, Detailed clinical trials carried out in Zimbabwe, Thailand, Burma, Brazil and Europe have established mefloquine as an effective drug both for prophylaxis and treatment of vi-vax and falciparum malaria [125-130],... 

There are a few efforts to synthesize analogs of already effective antimalarial drugs, e.g. quinine and artemisinin and these will be discussed in this paper (vide infra). These studies are mainly targeted at finding less toxic entities and/or compounds that overcome the rapid resistance that the malarial parasite seems to acquire. 

A variety of factors have contributed to the resurgence of malaria, and continue to foster the disease (47). These include socioeconomic and political problems, as well as inadequacies in public health care. Two principal causes of malarial resurgence were (i) the emergence of insecticide-resistant strains of the anopheline mosquitos which are the vectors for transmission of the disease, and (ii) drug-resistant strains of the parasite responsible for the pathology of the most lethal form of the disease, Plasmodium falciparum. Due to the latter, P. falciparum strains which are resistant to the antimalarial effect of chloroquine are spread throughout most of the areas where the disease is endemic, and resistance to more recently introduced antimalarial... 

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