Prevalence of Molecular Markers Associated With Sulphadoxine-Pyrimethamine Resistance in Plasmodium Falciparum at Bahir Dar, Northwest Ethiopia

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Addis Ababa University


Ethiopia changed the first-line antimalarial drug for uncomplicated P.falciparum malaria from Sulphadoxine-Pyrimethamine (SP) to Coartem in 2004 following nation-wide assessment of the efficacy of both drugs in 2003. The present study was conducted to assess the impact of this policy change on the frequency of Sulphadoxine-Pyrimethamine resistance-associated mutations in dhfr and dhps genes of P.falciparum three years after SP withdrawal in Bahir Dar, Northwest Ethiopia. A total of 165 blood spot samples were collected from P.falciparum mono-infected patients in Bahir Dar Health Center in 2005(n=78) and 2008 (n=87) using whatman filter papers. The blood spots were screened for the three dhfr codons (dhfr108, dhfr 51 and dhfr 59) and the two dhps codons (dhfr 437 and 540) which are believed to determine SP resistance in malaria endemic countries by using nested PCR-based dot blot- hybridization technique. In dhfr, only the dhfr59Arg mutant-type showed statistically significant reduction from 80.3% in 2005 to 56.4% in 2008 (X2=8.844, 95% CI= -38.7—9.0, P=0.003) with a significant increase of the wild type dhfr59Cys haplotypes from 4.9% to 29.5% in 2008 (X2=13.588, 95% CI=13.1-36.1, P= 0.0002). Double mutant dhfr alleles, 51Ile+108Asn and/or 59Arg+108Asn were detected and the former was prevalent in 98.4% of the samples in 2005 and in 98.7% in 2008 (p>0.05) while the later was observed among 78.6% (2005) and 56.4% (2008) of the participants (X2=7.591, 95% CI=-37.3-7.1, P=0.006). Furthermore, a significant decrease in the triple dhfr (108Asn+51Ile+59Arg) mutation was observed from 2005 (78.6%) to 2008 (56.4%) after the change in treatment policy (X2 =7.591, 95% CI=-37.3—7.1, P=0.006). With regard to dhps, the quadruple mutation that comprises dhfr (108Asn+51Ile+59Arg) + dhps 437Gly showed a significant decline from 78.6% in 2005 to 53.8% in 2008 (X2=9.22, 95% CI=9.6-39.9, P=0.002). The quintuple mutations (dhfr (108Asn+51Ile+59Arg) + dhps437Gly+dhps540Glu) showed a reduction from 60.6% to 37.2% after three years (X2 Key words: Drug resistance; Sulphadoxine-Pyrimethamine; P.falciparum; dhfr; dhps; dot-blot hybridization; Bahir Dar; Ethiopia =7.565, 95% CI=-39.7—7.1, P= 0.006). Overall, there was a decline in the frequency of dhfr/dhps combination mutations which are predictors of SP treatment failure indicating the re-emergence of sensitive parasites in the population following its withdrawal. Therefore, further monitoring and assessment of these molecular markers in P.falciparum parasites is important to determine the feasibility of re-introduction of SP in the future as a more affordable and safer drug in the future in Ethiopia.



Drug resistance, Sulphadoxine-Pyrimethamine, P.falciparum, P.falciparum; dhfr; dhps; dot-blot, hybridization; Bahir Dar; Ethiopia