Plasmodium falciparum chloroquine resistance

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  1. klishpa Guest

    Plasmodium falciparum chloroquine resistance


    Rapid diagnostic assays for Pf CRT mutations are already employed as surveillance tools for drug resistance. Here, we review recent field studies that support the central role of Pf CRT mutations in chloroquine resistance.

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    Plasmodium falciparum chloroquine resistance is a major cause of worldwide increases in malaria mortality and morbidity. Recent laboratory and clinical studies have associated chloroquine resistance with point mutations in the gene pfcrt. However, direct proof of a causal relationship has remained elusive and most models have posited a multigenic basis of resistance. Increased resistance by Plasmodium falciparum parasites led to the withdrawal of the antimalarial drugs chloroquine and sulphadoxine-pyrimethamine in Ethiopia. Since 2004 artemether-lumefantrine has served to treat uncomplicated P. falciparum malaria. In retrospect, the development of resistance to chloroquine by Plasmodium falciparum was inevitable given its widespread use over a period now approaching 40 years, and the enormous and progressive quantity of the drug consumed the WHO1 gives figures of 265 052 kg base actual consumption in 1978 and 351 229 kg base estimated require- ments in 1985, representing respectively 177 million and 234 million adult therapeu- tic doses.

    Recognition of the value of chloroquine was delayed, and it was not brought forward until it was reevaluated in the United States and designated the drug of choice against malaria near the end of World War II [3]. These studies suggest chloroquine resistance arose in ⩾4 distinct geographic foci and substantiate an important role of immunity in the outcomes of resistant infections after chloroquine treatment. Investigation of the resistance mechanisms and of the role of immunity in therapeutic outcomes will support new approaches to drugs that can take the place of chloroquine or augment its efficiency Early in the 20th century, intense demands for an effective quinine substitute launched the discovery and evaluation of a series of organic compounds (beginning with methylene blue), which led to pamaquine and quinacrine after World War I and ultimately produced chloroquine in 1934 [1, 2].

    Plasmodium falciparum chloroquine resistance

    Update Chloroquine-Resistant Plasmodium falciparum -- Africa, Return of chloroquine-sensitive Plasmodium falciparum.

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  5. Reports suggest that P. falciparum has now developed resistance to most antimalarial drugs, including chloroquine and its derivatives, sulfadoxine–pyrimethamine, mefloquine, and artemisinin 2 – 6.

    • Genetic polymorphisms in Plasmodium falciparum chloroquine..
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    • Structural Investigation of Plasmodium falciparum Chloroquine..

    Abstract. The development of chloroquine as an antimalarial drug and the subsequent evolution of drug-resistant Plasmodium strains had major impacts on global public health in the 20th century. In P. falciparum the cause of the most lethal human malaria, chloroquine resistance is linked to multiple mutations in PfCRT, a protein that likely functions as a transporter in the parasite’s. Nov 27, 2019 Juge, N. et al. Plasmodium falciparum chloroquine resistance transporter is a H + -coupled polyspecific nutrient and drug exporter. Two competing models explaining chloroquine resistance in Plasmodium falciparum. Trends Parasitol 23 332–339. View Article Google Scholar 27. Sanchez CP, Stein W, Lanzer M 2003 Trans stimulation provides evidence for a drug efflux carrier as the mechanism of chloroquine resistance in Plasmodium falciparum.

     
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