MOLECULAR SURVEILLANCE OF Plasmodium vivax AND Plasmodium falciparum DHFR MUTATIONS IN ISOLATES FROM SOUTHERN IRAN

Abstract

In Iran, both Plasmodium vivax and P. falciparum malaria have been detected, but P. vivax is the predominant species. Point mutations in dihydrofolate reductase (dhfr) gene in both Plasmodia are the major mechanisms of pyrimethamine resistance. From April 2007 to June 2009, a total of 134 blood samples in two endemic areas of southern Iran were collected from patients infected with P. vivax and P. falciparum. The isolates were analyzed for P. vivax dihydrofolate reductase (pvdhfr) and P. falciparum dihydrofolate reductase (pfdhfr) point mutations using various PCR-based methods. The majority of the isolates (72.9%) had wild type amino acids at five codons of pvdhfr. Amongst mutant isolates, the most common pvdhfr alleles were double mutant in 58 and 117 amino acids (58R-117N). Triple mutation in 57, 58, and 117 amino acids (57L/58R/117N) was identified for the first time in the pvdhfr gene of Iranian P. vivax isolates. All the P. falciparumsamples analyzed (n = 16) possessed a double mutant pfdhfrallele (59R/108N) and retained a wild-type mutation at position 51. This may be attributed to the fact that the falciparum malaria patients were treated using sulfadoxine-pyrimethamine (SP) in Iran. The presence of mutant haplotypes in P. vivax is worrying, but has not yet reached an alarming threshold regarding drugs such as SP. The results of this study reinforce the importance of performing a molecular surveillance by means of a continuous chemoresistance assessment.

Surveillance of molecular markers of antimalarial drug resistance in Plasmodium falciparum and Plasmodium vivax in Federally Administered Tribal Area (FATA), Pakistan

“…Quadruple 57L/58R/61M/117T, triple 57L/58R/117 and double pvdhfr (57L/117N) mutant haplotypes have been associated with in vitro drug resistance 16 . This study found pvdhfr double mutant S58R + S117N in 25% of clinical isolates reported from neighboring countries like India, Afghanistan and Iran [27][28][29] .…”

Molecular variation of Plasmodium vivax dehydrofolate reductase in Mexico and Nicaragua contrasts with that occurring in South America

“…Mutations 58R and 117N were reported to be common in malarious areas of Asia and Indonesia; 27,30,[49][50][51][52][53][54][55] the 57L substitution, rare in South America, was more frequent in South and Southeast Asia, and Oceania, 29,30 and the double mutation 57L /58R reported in Honduras 44 has been observed in Sri Lanka. 29 Interestingly, the variant residue 173L seems to be exclusive of South González-Cerón L y col. America, while a different substitution (173F) was reported in South Korea, Myanmar, 49 India 27 and Vanuatu.…”

Mutational Analysis of Plasmodium vivax dhfr Gene Among Cases in South East of Iran

“…Attempts to control malaria are significantly challenged due to antimalarial drug resistance in endemic regions. For this reason, there is a necessity for annual monitoring of antimalarial drug usefulness and drug resistance in endemic regions (22). In the south provinces of Iran, such as Sistan and Baluchistan, however, CQ still remains efficient against the P. vivax malaria disease.…”