The effect of Point Mutations in Dihydrofolate reductase genes and the Multidrug resistance gene 1-86 on treatment of falciparum malaria in Sudan

Abstract

Background: This study investigated the prevalence of antimalarial drug resistance markers in P. falciparum isolates, involving the detection of mutations at the mdr1-86, which associates with amodiaquine resistance, and dhfr mutations associated with SP resistances.Methods: The dot-blot/probe hybridization was used to determine multidrug resistance (mdr1-86) and assess the correlation of Amodiaquine (AQ) resistance and PCR/ RFLP was used to determine dihydrofolate reductase (dhfr) baseline resistance to Sulphadoxine- Pyrimethamine (SP) resistance in the Nubian region of Southern Sudan. A randomized open-label trial of Artesunate (AS) + SP and AQ + SP was conducted in children younger than five years. Molecular analysis of the samples was performed to provide a baseline estimate of allele prevalences. Results: Baseline allele prevalence of the mdr1-86 locus in the AS + AQ was successful for 80 isolates: 71(8.11%) carried parasites harbouring the mdr1-86 Tyr resistance allele, while 7 (89.19%) carried mdr1-86 Asn sensitivity allele, and 2 (2.7%) were of mixed infection, having both resistance and wild type allele. Overall, the prevalence of the dhfr point mutation, codon 51, 59 and 108: 82.5% (132/160) carried mutations at dhfr (N51I, C59R or S108N), but triple mutants were rare (3.1%) in the AS + SP arm. Conclusion: The results show that mutations present in dhfr and mdr1-86 have a significant effect on the type of treatment following SP and AQ chemotherapy. SP resistance may spread rapidly, and AS + AQ is likely a better option, provided AQ use is restricted to the combination.