title: Carriage of Mutant Dihydrofolate Reductase and Dihydropteroate Synthase Genes among Plasmodium falciparum Isolates Recovered from Pregnant Women with Asymptomatic Infection in Lagos, Nigeria.
abstract: OBJECTIVE
  To assess N51I, C59R and S108N polymorphisms of dihydrofolate reductase (dhfr) and A437G and K540E of dihydropteroate synthase (dhps) genes of P. falciparum isolates recovered from pregnant women with asymptomatic malaria in a coastal setting in Nigeria.
  
  
  METHODS
  A total of 107 consenting and consecutively enrolled pregnant women (mean age ± standard deviation, 26.6 ± 4.5 years) attending antenatal care at the Iru/Victoria Island Primary Health Centre, Lagos, were screened for peripheral malaria by microscopy, by a histidine-rich protein-2-based rapid diagnostic test (RDT) and by polymerase chain reaction (PCR) using finger-pricked and dot blood samples. DNA was extracted from the blood and used for dhfr and dhps gene polymorphism analyses by PCR and restriction fragment length polymorphism. The sociodemographic and parasite data obtained were analysed.
  
  
  RESULTS
  Of the 107 patients, 34 (31.8%), 46 (43%) and 40 (37.4%) were found to be P. falciparum infected using microscopy, RDT and corrected RDT-PCR, respectively (p < 0.05). The prevalence of P. falciparum isolates with mutant and mixed genotypes of dhfr at codons 51, 59 and 108 was 70, 75 and 80%, respectively, and the triple mutation in the homozygous form was 35%. The prevalence of the homozygous quintuple dhfr plus dhps mutant was 5%, while that of the P. falciparum isolates with mutant or mixed genotypes of dhps at codons 437 and 540 was 37.5 and 22.5%, respectively.
  
  
  CONCLUSIONS
  This study revealed the emergence of the K540E mutation among the parasite population in Lagos. However, it supports the implementation of the intermittent preventive treatment of malaria during pregnancy with sulphadoxine-pyrimethamine with continuous effectiveness monitoring in the study area.
authors.affiliation: Department of Biochemistry and Nutrition, Nigerian Institute of Medical Research, Yaba, Lagos, Nigeria.
authors.forename: Bamidele Abiodun
authors.initials: BA
authors.lastname: Iwalokun
authors.forename: Senapon O
authors.initials: SO
authors.lastname: Iwalokun
authors.forename: Victor
authors.initials: V
authors.lastname: Adebodun
authors.forename: Modinat
authors.initials: M
authors.lastname: Balogun
mesh_terms: D000328:Adult; D058345:Asymptomatic Infections; D002353:Carrier State; D016054:DNA, Protozoan; D004094:Dihydropteroate Synthase / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D016778:Malaria, Falciparum / Q000453:epidemiology* / Q000235:genetics*; D009154:Mutation; D009549:Nigeria / Q000453:epidemiology; D010963:Plasmodium falciparum / Q000235:genetics* / Q000302:isolation & purification*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D012959:Socioeconomic Factors; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*
chemical_list: D016054:DNA, Protozoan; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase