Novel mutations in the antifolate drug resistance marker genes among Plasmodium vivax isolates exhibiting severe manifestations

• Published in: Experimental parasitology 2012-12, Vol.132 (4), p.410-416
• Main Authors: Garg, Shilpi, Saxena, Vishal, Lumb, Vanshika, Pakalapati, Deepak, Boopathi, P.A., Subudhi, Amit Kumar, Chowdhury, Shibasish, Kochar, Sanjay K., Kochar, Dhanpat K., Sharma, Y.D., Das, Ashis
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; alleles; Antifolate drug resistance; chloroquine; Chloroquine - pharmacology; Chloroquine - therapeutic use; Dihydropteroate Synthase - genetics; drug resistance; Drug Resistance - genetics; drugs; Female; Folic Acid Antagonists - pharmacology; Folic Acid Antagonists - therapeutic use; genetic markers; Genetic Markers - genetics; Genotype; Humans; India; loci; malaria; Malaria, Vivax - blood; Malaria, Vivax - drug therapy; Malaria, Vivax - parasitology; Male; Middle Aged; molecular models; mutants; Mutation; Novel mutations; parasites; parasitology; patients; Plasmodium falciparum; Plasmodium vivax; Plasmodium vivax - drug effects; Plasmodium vivax - genetics; Polymorphism, Genetic; Severe manifestations; Tetrahydrofolate Dehydrogenase - genetics; Young Adult
• ISSN: 0014-4894; 1090-2449
• DOI: 10.1016/j.exppara.2012.09.018

[Display omitted] ► Novel mutations were observed in both DHFR and DHPS of Plasmodium vivax. ► Presence of novel mutations in PvDHPS gene suggests its polymorphic nature. ► Frequency of PvDHFR–PvDHPS two locus mutations were higher among the severe isolates. Plasmodium vivax is the predominant species of the human malaria parasite present in the Indian subcontinent. There have been recent reports on Chloroquine (CQ) resistance and severe manifestations shown by P. vivax from different regions of the world including India. This study focuses on Bikaner, India where during the last few years there have been continuous reports of severe manifestations by both Plasmodium falciparum and P. vivax. This region has a widespread use of Chloroquine and Sulfadoxine–Pyrimethamine for the treatment of malaria, but the resistance profiles of these drugs are not available. We report here the profile of mutations in marker genes associated with Chloroquine and antifolate drug resistance among the P. vivax parasites obtained from patients with severe (n=30) and non-severe (n=48) manifestations from this region. Most isolates showed the wild type alleles for both the Chloroquine and antifolate resistance markers (P