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Review
. 2016 Jan-Jun;6(1):30-41.
doi: 10.4103/2229-5070.175081.

Antimalarial drug resistance: An overview

Hiasindh Ashmi Antony  1 , Subhash Chandra Parija  1
Affiliations
Review

Antimalarial drug resistance: An overview

Hiasindh Ashmi Antony et al. Trop Parasitol. 2016 Jan-Jun.

Abstract

Malaria is a major public health burden throughout the world. Resistance to the antimalarial drugs has increased the mortality and morbidity rate that is achieved so far through the malaria control program. Monitoring the drug resistance to the available antimalarial drugs helps to implement effective drug policy, through the in vivo efficacy studies, in vitro drug susceptibility tests and detection of molecular markers. It is important to understand the mechanism of the antimalarial drugs, as it is one of the key factors in the emergence and spread of drug resistance. This review summarizes the commonly used antimalarial drugs, their mechanism of action and the genetic markers validated so far for the detection of drug-resistant parasites.

Keywords: Antimalarial drugs; Plasmodium falciparum; Plasmodium vivax; drug resistance markers; malaria.

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Figures

Figure 1
Figure 1
Malaria transmission and its distribution worldwide. World map adapted from “World Malaria Report 2014” illustrating the malaria transmission in various countries in 2013
Figure 2
Figure 2
Prevalence of drug resistance distributed in various regions and countries. Antimalarial drug resistance surveillance obtained from WWARN Molecular Surveyor: (a) exhibiting the chloroquine drug resistance with incidence of Plasmodium falciparum chloroquine resistance transporter K76T mutation, (b) presenting the frequency of Pfdhfr gene with 51I mutation in association with resistance to sulfadoxine-pyrimethamine drug, (c) the prevalence of Kelch 13 propeller mutation for artemisinin resistance in the Southeast Asia region
Figure 3
Figure 3
Proposed model for the mechanism and target localization of the antimalarial drugs (a and b) the 4-aminoquinolones such as chloroquine and amodiaquine and the amino alcohol derivatives such as mefloquine, quinine binds to the β-hematin molecule and inhibits the heme detoxification pathway in the parasiteæs digestive vacuole. (c) The antifolate derivatives target the Phdhps and Plasmodium falciparum bifunctional dihydrofolate reductase-thymidylate synthase gene involved in the folate biosynthesis in the cytoplasm of the parasite. (d) Atovaquone binds to the cytochrome b and interferes the electron transport mechanism in the mitochondria of the parasite
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