Similar trends of pyrimethamine resistance-associated mutations in Plasmodium vivax and P. falciparum.
The antifolate drugs sulfadoxine and pyrimethamine are commonly used to treat Plasmodium falciparum malaria. However, they can also affect the Plasmodium vivax parasite if it coexists with P. falciparum, as both species have common drug targets. Resistance to the antifolate drugs arises due to point mutations in the target enzymes of the respective parasite. To assess the cross-species impact of antifolate drug treatment, we describe here the dihydrofolate reductase (DHFR) mutations among field isolates of P. vivax and P. falciparum. The overall DHFR mutation rate for P. vivax was lower than that for P. falciparum. However, both species of Plasmodium followed similar trends of DHFR mutations. Similar to P. falciparum, the DHFR mutation rate of P. vivax also varied from region to region. It was lower in P. vivax-dominant regions but higher in the P. falciparum-dominated areas and highest where antifolates are used as the first line of antimalarial treatment. In conclusion, the antifolate treatment of falciparum malaria is proportionately affecting the DHFR mutations of P. vivax, suggesting that the drug should be used with caution to minimize the development of cross-species resistance in the field.
Alam
Mohammad Tauqeer
MT
Department of Biotechnology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.
Bora
Hema
H
Bharti
Praveen K
PK
Saifi
Muheet A
MA
Das
Manoj K
MK
Dev
Vas
V
Kumar
Ashwani
A
Singh
Neeru
N
Dash
Aditya P
AP
Das
Brahmananda
B
Wajihullah
Sharma
Yagya D
YD
D000483:Alleles; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D016054:DNA, Protozoan / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics; D005493:Folic Acid Antagonists / Q000494:pharmacology*; D005838:Genotype; D007194:India / Q000453:epidemiology; D008288:Malaria / Q000453:epidemiology* / Q000469:parasitology*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics / Q000502:physiology; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics*; D010966:Plasmodium vivax / Q000187:drug effects* / Q000235:genetics*; D011739:Pyrimethamine / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics
D000962:Antimalarials; D016054:DNA, Protozoan; D005493:Folic Acid Antagonists; D013762:Tetrahydrofolate Dehydrogenase; D011739:Pyrimethamine