title: Prevailing Plasmodium falciparum dihydrofolate reductase 108-asparagine in Hodeidah, Yemen: a questionable sulfadoxine-pyrimethamine partner within the artemisinin-based combination therapy.
abstract: Given that the evolution and spread of resistance to sulfadoxine-pyrimethamine (SP) have been documented at a quick pace worldwide, the present study investigated the mutant Plasmodium falciparum dihydrofolate reductase 108-asparagine (dhfr 108 N) as a key marker of resistance to the combination among parasite isolates from Hodeidah. The association of parasitologic indices with the dhfr 108 N mutant allele was also studied. Ninety patients with microscopically confirmed P. falciparum infection from Hodeidah were included in the present study. Polymerase chain reaction-restriction fragment length polymorphism approach was adopted for the molecular detection of this marker. The dhfr 108 N was detected among about 61% of P. falciparum isolates, in its pure and mixed-type forms, from Hodeidah. Age, gender and residence of patients were not significant predictors for the presence of the mutant allele among parasite isolates. In contrast, a history of malaria and antimalarial drug intake in the year preceding the study as well as frequent antimalarial drug intake were significantly associated with this mutant allele. The high frequency of dhfr 108 N among parasites isolates makes the role of SP questionable as a partner with outstanding effectiveness within the ACT, at least, in the near future. SP plus artesunate should be monitored for its antimalarial efficacy at regular intervals, preferably through the molecular detection of resistance-associated mutations.
authors.affiliation: Department of Parasitology, Medical Research Institute, Alexandria University, Alexandria, Egypt; Department of Parasitology, Faculty of Medicine and Health Sciences, Sana'a University, Sana'a, Yemen. Electronic address: rashadqb@yahoo.com.
authors.forename: Rashad
authors.initials: R
authors.lastname: Abdul-Ghani
authors.affiliation: Department of Parasitology, Medical Research Institute, Alexandria University, Alexandria, Egypt.
authors.forename: Hoda F
authors.initials: HF
authors.lastname: Farag
authors.affiliation: Department of Parasitology, Medical Research Institute, Alexandria University, Alexandria, Egypt.
authors.forename: Amal F
authors.initials: AF
authors.lastname: Allam
authors.affiliation: Department of Microbiology, Medical Research Institute, Alexandria University, Alexandria, Egypt.
authors.forename: Sherine M
authors.initials: SM
authors.lastname: Shawky
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use*; D001216:Asparagine / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D016054:DNA, Protozoan / Q000235:genetics; D004338:Drug Combinations; D004351:Drug Resistance; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000469:parasitology*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010963:Plasmodium falciparum / Q000201:enzymology* / Q000235:genetics / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011739:Pyrimethamine / Q000627:therapeutic use*; D013413:Sulfadoxine / Q000627:therapeutic use*; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*; D015006:Yemen; D055815:Young Adult
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D016054:DNA, Protozoan; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D001216:Asparagine; D013413:Sulfadoxine; C031327:artemisinin; D013762:Tetrahydrofolate Dehydrogenase; D011739:Pyrimethamine
keywords: Antimalarial drug resistance; Dihydrofolate reductase; Hodeidah; Sulfadoxine–pyrimethamine