Studies on the Drug Resistance Genes in Plasmodium falciparum and Plasmodium vivax from India

Abstract

Malaria remains the world s most devastating human parasitic infection, afflicting more than 500 million people and causing about 1.7 million to 2.5 million deaths each year. Efforts to combat malaria have received a major setback due to the development of parasite resistance to the various drug regimens used. Due to increased resistance, a regular monitoring in the field is required for effective malaria control strategies. Molecular probes that reliably predict susceptibility of P. falciparum or P. vivax to various drugs like Chloroquine and Sulfadoxine - Pyrimethamine can provide information supporting rational policy decisions and practice with regard to malaria treatment. newline newlineThis study is focused on Bikaner, situated in the North western part of Rajasthan, India, near Indo Pak border. This region is characterized by unstable episodes of P. falciparum and P.vivax malaria after every rainy season with both species showing severe manifestations. To predict the profile of the drug resistance patterns in the parasite population of Bikaner, we analyzed the point mutations in genes responsible for Chloroquine (Pfcrt and Pfmdr-1) and Sulfadoxine Pyrimethamine (dhps and dhfr respectively) resistance. The PfCRT showed the mutant 76T for almost all the samples, while the Pfmdr-1 showed the wild type 86N in more than half of the isolates, indicating a rise in Chloroquine resistance in this region. In contrast, a different resistance pattern was seen in case of Sulfadoxine Pyrimethamine. The DHFR in P. falciparum was predominantly double mutant but in P.vivax the wild genotype was more predominant. In contrast, for both P. falciparum and P.vivax, the DHPS showed the wild genotype for most of the samples. A number of novel mutations were found in DHPS of both P. falciparum and P.vivax. While the novel mutations in PfDHPS showed reduction in binding affinity of Sulfadoxine to the DHPS enzyme, no effect on drug binding was seen for mutated PvDHPS.