title: Prevalence of polymorphisms in the dihydrofolate reductase and dihydropteroate synthetase genes of Plasmodium falciparum isolates from southern Mauritania.
abstract: The increasing resistance of Plasmodium falciparum in the treatment of uncomplicated malaria with pyrimethamine/sulphadoxine has been associated in several studies with the occurrence of point mutations in the genes of dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS). In this study, the prevalence of these mutations was examined in samples from south-east Mauritania, where atypically strong rainfalls in 1998 and 1999 led to a severe outbreak of falciparum malaria. We analysed 386 samples by polymerase chain reaction (PCR) for infection with P. falciparum, of which 162 (41.97%) were positive. These isolates were examined for point mutations in the genes of DHFR (codons 16, 51, 59, 108 and 164) and DHPS (codons 436, 437, 540, 581 and 613) by nested PCR and subsequent mutation-specific restriction enzyme digest. We found a low overall prevalence of DHFR gene mutations (up to 18.6% of isolates), but a high overall prevalence of DHPS gene mutations (up to 49.1% of isolates). Thus, emerging resistance to antifolate drugs may be expected to develop soon in the investigated area. This study demonstrates the utility of simple, relatively rapid and inexpensive molecular methods and their application in surveillance programmes. Testing for prevalence of point mutations conferring antifolate resistance might help to identify the developing of drug resistance at a very early stage.
authors.affiliation: Department of Infectious Diseases and Tropical Medicine, University of Munich, Munich, Germany.
authors.forename: K J
authors.initials: KJ
authors.lastname: Eberl
authors.forename: T
authors.initials: T
authors.lastname: Jelinek
authors.forename: A O
authors.initials: AO
authors.lastname: Aida
authors.forename: G
authors.initials: G
authors.lastname: Peyerl-Hoffmann
authors.forename: C
authors.initials: C
authors.lastname: Heuschkel
authors.forename: A O
authors.initials: AO
authors.lastname: el Valy
authors.forename: E M
authors.initials: EM
authors.lastname: Christophel
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000494:pharmacology / Q000627:therapeutic use; D004094:Dihydropteroate Synthase / Q000235:genetics*; D004196:Disease Outbreaks; D004338:Drug Combinations; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000453:epidemiology*; D008297:Male; D008435:Mauritania / Q000453:epidemiology; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D015995:Prevalence; D011739:Pyrimethamine / Q000494:pharmacology / Q000627:therapeutic use; D013413:Sulfadoxine / Q000494:pharmacology / Q000627:therapeutic use; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D002738:Chloroquine; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase; D011739:Pyrimethamine