Malaria in the Nuba Mountains of Sudan: baseline genotypic resistance and efficacy of the artesunate plus sulfadoxine–pyrimethamine and artesunate plus amodiaquine combinations

Both northern and southern Sudan are deploying artemisinin-based combinations against uncomplicated Plasmodium falciparum malaria (artesunate + sulfadoxine–pyrimethamine [AS + SP] in the north, artesunate + amodiaquine [AS + AQ] in the south). In 2003, we tested the efficacy of 3 day AS + SP and AS + AQ regimens in vivo in the isolated, seasonally endemic Nuba Mountains region (the first study of AS combinations in southern Sudan). We also analysed pre-treatment blood samples for mutations at the P. falciparum chloroquine transporter ( Pfcrt) gene (associated with CQ resistance), and at the dihydrofolate reductase ( Dhfr) gene (associated with pyrimethamine resistance). Among 161 randomized children under 5 years, PCR-corrected cure rates after 28 days were 91.2% (52/57, 95% CI 80.7–97.1) for AS + SP and 92.7% (51/55, 95% CI 82.4–98.0) for AS + AQ, with equally rapid parasite and fever clearance. The Pfcrt K76T mutation occurred in 90.0% (144/160) of infections, suggesting CQ would work poorly in this region. Overall, 82.5% (132/160) carried mutations at Dhfr (N51I, C59R or S108N, but not I164L), but triple mutants (more predictive of in vivo SP failure) were rare (3.1%). CQ use should be rapidly discontinued in this region. SP resistance may propagate rapidly, and AS + AQ is likely to be a better long-term option, provided AQ use is limited to the combination.