Prevalence of Polymorphisms in Antifolate Drug Resistance Molecular Marker Genes pvdhfr and pvdhps in Clinical Isolates of Plasmodium vivax from Kolkata, India

Abstract

Sulfadoxine-pyrimethamine has never been recommended for the treatment of Plasmodium vivax malaria as the parasite is intrinsically resistant to pyrimethamine. The combination was introduced as a promising agent to treat Plasmodium falciparum malaria in many countries but was withdrawn after a few years due to development and spread of resistant strains. Presently, sulfadoxine-pyrimethamine is used as a partner drug of artemisinin-based combination therapy to treat uncomplicated falciparum malaria, and a combination of artesunate-sulfadoxine-pyrimethamine is currently in use in India. In countries like India, where both P. vivax and P. falciparum are equally prevalent, some proportion of P. vivax bacteria is exposed to sulfadoxinepyrimethamine due to misdiagnosis and mixed infections. As reports on the in vivo therapeutic efficacy of sulfadoxine-pyrimethamine in P. vivax are rare, the study of mutations in the marker genes P. vivax dhfr (pvdhfr) and pvdhps is important for predicting drug selection pressure and sulfadoxine-pyrimethamine resistance monitoring. We studied the prevalence of point mutations and haplotypes of both the genes in 80 P. vivax isolates collected from urban Kolkata, India, by the DNA sequencing method. Point mutation rates in both the genes were low.

Geographic distribution of amino acid mutations in DHFR and DHPS in Plasmodium vivax isolates from Lao PDR, India and Colombia

“…This information provides some points of view for epidemiological mapping of SP resistance and their background situations in vivax malaria. Plasmodium vivax parasites from India were found to have a high frequency of dhfr and dhps mutations [ 37 ]. Recent studies of PvDHFR genotypes in India have reported high frequencies of 58R and 117 N double mutations [ 37 ], which is similar to the results for PfDHFR mutations [ 38 , 39 ].…”

“…Plasmodium vivax parasites from India were found to have a high frequency of dhfr and dhps mutations [ 37 ]. Recent studies of PvDHFR genotypes in India have reported high frequencies of 58R and 117 N double mutations [ 37 ], which is similar to the results for PfDHFR mutations [ 38 , 39 ]. The results from this study showed that P. vivax parasites from India carried the wild-type DHFR allele at approximately the same high frequency (51.4 %) as they carried the 58R/117 N double mutation (40.5 %), suggesting that the double mutation and wild-type alleles are still common in India.…”

Antimalarial Drug Resistance: Literature Review and Activities and Findings of the ICEMR Network

“… 89 , 90 Perhaps not surprisingly, sulfadoxine/pyrimethamine resistance in P. vivax appeared in Asia and the Pacific Islands, where P. falciparum and P. vivax coexist. 91 – 94 …”

Next-Generation Sequencing of Plasmodium vivax Patient Samples Shows Evidence of Direct Evolution in Drug-Resistance Genes

“…Pyrimethamine was added to table salt in some countries, including Brazil in the 1950s. 4,5 Although P. vivax alleles conferring resistance to pyrimethamine are well known 6-9 and are found in the Amazon basin, alleles conferring resistance to chloroquine, artemisinin, and primaquine (the only therapy that prevents vivax malaria relapse) in P. vivax remain obscure.…”