Genetic Polymorphism of Plasmodium falciparum Candidate Genes: A Global Problem in Malaria Control

Malaria is one of the deadliest infectious diseases worldwide. This review elucidates the genetic cause of treatment failure in Plasmodium falciparum infection. One hundred ninety eight (198) million of malaria cases are reported globally and estimated 584000 deaths occur in 2013. Single point mutation of asparagine to tyrosine in codon 86 (N86Y) of pfmdr-I gene and some other polymorphisms, like 184Y, 1034N, N1042D and D1246Y is associated with CQ resistance. Different point mutations including K76T in pfcrt gene were highly associated with chloroquine resistance. Antifolate Sulfadoxine/ pyrimethamine (SP) combination has been used as a second-line therapy against chloroquine-resistant Plasmodium falciparum malaria. Polymorphism in pfdhfr codon 108 (S108N) and other point mutation in pfdhfr N51I and C59R confer higher levels of resistance. Mutation in pfdhps A437 is associated with sulfadoxine resistance, while additional changes (S436A, K540E, A581G, A613T/S) appear to increase the degree of resistance. Perseverance of SP resistance in relation to treatment outcome is visualized when at least two pfdhfr and one pfdhps mutation occurs. Increasing failure of predominantly used chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) has been a serious obstacle towards the global malaria control. The combination of artesunate (AS) and sulfadoxinepyrimethamine (SP) (ACT) has replaced the single use of CQ and SP. Artemisinin resistance is strongly associated with an increase in parasite clearance half-life (PCHL), which imitates the reduced susceptibility of ring-stage parasites. Different codon of pfkelch13 gene point mutation (441codon and other) was highly correlated with ACT failure as well as increased PCHL and RSA thereby resistance to AS. Genetic polymorphism of different candidate genes leads to drug resistance in malaria parasite which makes a global problem to eradicate malaria.

Author(s): Somenath Roy

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