The effect of Point Mutations in Dihydrofolate reductase genes and 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.

Applicability of an oligonucleotide probe in radioisotope ³²P-based dot blot hybridization for detection of hepatitis C virus in large sample numbers: a preliminary study

“…16 For these reasons, numerous researchers have used this approach to detect and identify pathogenic microorganisms. [17][18][19] Therefore, the dot blot hybridization using oligonucleotide designed in this study is suitable for detection of HCV, particularly for screening of large sample numbers and for surveillance purposes. Other researchers have used the method for large sample numbers for detection and identification of Dendrobium species, 20 multi-drug resistant Mycobacterium tuberculosis, 9 and Echoviruses.…”

BCRP Expression in VX2 Rabbit Liver Tumours and its Effects on Tumour Recurrence, Metastasis and Treatment Tolerability

“…It is cross-resistance phenomenon of tumor cells to a variety of unrelated drugs with different molecular structures, cellular targets and action mechanisms. The emergence of MDR is a complicated process involving multiple factors (Yusuf et al, 2010). At present, the known involved mechanisms of MDR are as follows: 1) expression of ATP binding cassette (ABC) transporters including BCRP, P-glycoprotein, etc.…”

“…Most data show that, MDR can be used as an indicator for prognosis. In tumor patients with MDR, the prognosis is generally poor (Maier et al, 2010;Yusuf et al, 2010). For tumor MDR reversal, a variety of effective reversal agents to P-gp, MRP, GST, DNA repair related enzymes (TOPO) and MDR protein have been discovered.…”