Malaria, drug resistance

In malaria chemotherapy, resistant parasites have significantly reduced the efficiency of classic antifolate drugs. In the search for novel inhibitors of... 

White NJ, Pongtavompinyo W. (2003) The de-novo selection of drug resistance in malaria parasites. Philos Trans R Soc LondBBiol Sci 270 545-554. 

Plasmodium (P.) falciparum, responsible for the most dangerous form of malaria, is particularly prone to develop drug resistance. The incidence of resistant strains rises with increasing frequency of drug use. Resistance has been reported for chloroquine and also for the combination pyrimethamine/ sulfadoxine. 

Drug resistance is accelerating in many endemic areas malaria vaccines may hold the greatest hope for control of infection. 

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. 

Wernsdorfer, W. H. 1994. Epidemiology of drug resistance in malaria. Acta Tropical, 56 143-156. 

Kain KC, Shanks D, and Keystone JS. Malaria chemoprophylaxis in the age of drug resistance. I. Currently recommended drug regimens. Clin Infect Dis 2001 33 226-234. 

It is indicated in drug resistant P. falciparum malaria and in the treatment of giardiasis. 

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... 

Chloroquine has been the drug of choice for both treatment and chemoprophylaxis of malaria since the 1940s, but its usefulness against P falciparum has been seriously compromised by drug resistance. It remains the drug of choice in the treatment of sensitive P falciparum and other species of human malaria parasites. 

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. 

Peters, W. Chemotherapy and Drug Resistance in Malaria, 2nd ed Academic Press London, 1987. 

Farooq U, Mahajan RC. Drug resistance in malaria. J Vector Borne Dis. 2004 41 45-53. 

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. 

De, D. Byers, L. D. Krogstad, D. J. Antimalar-ials synthesis of 4-aminoquinolines that circumvent drug resistance in malaria parasites. 

Malaria is one of the most prevalent diseases in the world. Although there are numerous drugs on the market for both the treatment and prevention of the disease, multiple drug resistance by parasites is now ubiquitous in all parts of the world where malaria is endemic.55 Therefore, there is an increasing need for the development of new antimalarial drugs, especially ones that possess novel modes of action. The antimalarial properties of nonalkaloidal compounds such as artemisinin (54) and yingzhaosu A (55) have attracted considerable attention because of the limited availability of the natural product by extraction from the Chinese Artemisia annua plant.56 58... 

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