Prevalence of sulfadoxine-pyrimethamine resistance-associated mutations in dhfr and dhps genes of Plasmodium falciparum three years after SP withdrawal in Bahir Dar, Northwest Ethiopia.

Abstract Ethiopia changed the first-line anti-malarial drug for uncomplicated Plasmodium falciparum malaria from sulfadoxine–pyrimethamine (SP) to Coartem ® in 2004 following nation-wide assessment of the efficacy of both drugs in 2003. This study was conducted to assess the prevalence of sulfadoxine–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 patients infected with P. falciparum in Bahir Dar Health Center in 2005 ( n  = 78) and 2008 ( n  = 87) using Whatman (3M) filter papers. The three dhfr codons ( dhfr 108, dhfr 51 and dhfr 59) and the two dhps codons ( dhfr 437 and 540) which are believed to determine SP resistance were detected by using nested PCR-based dot blot-hybridization technique. In dhfr , only the dhfr 59Arg mutant-type showed statistically significant reduction from 80.3% in 2005 to 56.4% in 2008 ( p dhfr 59Cys haplotypes from 4.9% in 2005 to 29.5% in 2008 ( p dhfr 108Asn/51Ile were detected at rate of 98.4% in 2005 and 98.7% in 2008. A significant decrease in the triple dhfr (108Asn/51Ile/59Arg) mutation was observed from 2005 (78.6%) to 2008(56.4%) ( p dhfr (108Asn/51Ile/59Arg)/ dhps 437Gly were significantly declined from 78.6% in 2005 to 53.8% in 2008 ( p dhfr (108Asn/51Ile/59Arg)/ dhps 437Gly/ dhps 540Glu) showed a reduction from 60.6% to 37.2% after three years ( p dhfr / dhps combination mutations might indicate the re-emergence of sensitive parasites in the population following SP withdrawal. Therefore, further monitoring and assessment is important to determine the feasibility of re-introduction of SP alone or in combination as a more affordable and safer drug in the future in Ethiopia.