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Background    Plasmodium vivax  is the second most important human malaria parasite, widely spread across the world. This parasite is associated with important issues in the process toward malaria elimination, including potential for relapse and increased resistance to chloroquine.  Plasmodium vivax  multi-drug resistant ( pvmdr1 ) is suspected to be a marker of resistance although definitive evidence is lacking. Progress has been made in knowledge of biological factors affecting parasite growth, including mechanisms of regulated cell death and the suspected role of metacaspase.  Plasmodium vivax  metacaspase1 (PvMCA1-cd) has been described with a catalytic domain composed of histidine (H372) and cysteine (C428) residues. The aim of this study was to test for a link between the conserved histidine and cysteine residues in PvMCA1-cd, and the polymorphism of the  P. vivax  multi-drug resistant gene ( pvmdr1 ).    Results  Thirty  P. vivax  isolates were collected from Mauritania, Sudan, and Oman. Among the 28  P. vivax  isolates successfully sequenced, only 4 samples showed the conserved His (372)–Cys (428) residues in PvMCA1-cd. Single nucleotide polymorphisms observed were H372 T  (46.4%), H372 D  (39.3%), and C428 R  (85.7%). A new polymorphic catalytic domain was observed at His (282)–Cys (305) residues. Sequences alignment analysis of  pvmdr1  showed SNP in the three codons 958, 976 and 1076. A single SNP was identified at the codon M958Y (60%), 2 SNPs were found at the position 976: Y976 F  (13%) and Y976 V  (57%), and 3 SNPs were identified at the position 1076: F1076 L  (40%), F1076 T  (53%) and F1076 I  (3%). Only one isolate was wildtype in all three codons (MYF), 27% were single MY L  mutants, and 10% were double M FL  mutants. Three new haplotypes were also identified: the triple mutant  YVT  was most prevalent (53.3%) distributed in the three countries, while triple  YFL  and  YVI  mutants (3%), were only found in samples from Sudan and Mauritania.    Conclusions  Triple or quadruple mutants for metacaspase genes and double or triple mutants for  Pvmdr1  were observed in 24/28 and 19/28 samples. There was no difference in the frequency of mutations between PvMCA1-cd and  Pvmdr1  (P > 0.2). Histidine and cysteine residues in PvMCA1-cd are highly polymorphic and linkage disequilibrium with SNPs of  Pvmdr1  gene may be expected from these three areas with different patterns of  P. vivax  transmission.

malaria journal

Genetic diversity of Plasmodium vivax metacaspase 1 and Plasmodium vivax multi-drug resistance 1 genes of field isolates from Mauritania, Sudan and Oman