title: High frequency of Plasmodium falciparum CICNI/SGEAA and CVIET haplotypes without association with resistance to sulfadoxine/pyrimethamine and chloroquine combination in the Daraweesh area, in Sudan.
abstract: Estimation of the prevalence of the molecular markers of sulfadoxine/pyrimethamine (SP) and chloroquine (CQ) resistance and validation of the association of mutations with resistance in different settings is needed for local policy guidance and for contributing to a global map for anti-malarial drug resistance. In this study, malaria patients treated with SP alone (60) and SP with CQ (194) had a total treatment failure (TF) of 35.4%, with no difference between the two arms. The polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELISA) method was used to identify polymorphisms in 15 loci in the dhfr, dhps and pfcrt genes in a subset of 168 infections. The results revealed a similar frequency of all single nucleotide polymorphisms (SNPs) in the two arms, except dhps 581G, which was over-represented in infections that failed to respond to SP alone (TF). In all infections, a high frequency of dhfr CICNI haplotype (51I and 108N) was found, but without discrimination between the adequate clinical and parasitological response (ACPR, 75.6%) and TF (82.9%). Similarly, the dhps SGEAA haplotype (437G and 540E) (ACPR, 60.5%; TF, 65.9%) and the combined CICNI/SGEAA haplotype (ACPR, 50%; TF 55%) were not associated with TF. In contrast to other studies in Africa, the triple 51I/59R/108N mutation was rare (0.6%). In addition, the pfcrt CVIET haplotype (93%) was found to be associated with the CICNI/SGEAA haplotype. Finally, these data represent a baseline for SP resistance molecular markers needed before the deployment of SP/artesunate combination therapy in the Sudan.
authors: Malaria Research Centre (MalRC), Department of Biochemistry, Faculty of Medicine, University of Khartoum, P.O. Box 102, Khartoum, Sudan. ishraga20@yahoo.co.uk
authors: I E
authors: IE
authors: A-Elbasit
authors: I F
authors: IF
authors: Khalil
authors: M I
authors: MI
authors: Elbashir
authors: E M
authors: EM
authors: Masuadi
authors: I C
authors: IC
authors: Bygbjerg
authors: M
authors: M
authors: Alifrangis
authors: H A
authors: HA
authors: Giha
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology; D004338:Drug Combinations; D004351:Drug Resistance; D006801:Humans; D009154:Mutation; D010963:Plasmodium falciparum / Q000145:classification / Q000187:drug effects* / Q000235:genetics; D011739:Pyrimethamine / Q000494:pharmacology; D013397:Sudan; D013413:Sulfadoxine / Q000494:pharmacology
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; D013413:Sulfadoxine; D002738:Chloroquine; D011739:Pyrimethamine