title: Prevalence of pfcrt point mutations and level of chloroquine resistance in Plasmodium falciparum isolates from Africa.
abstract: The development in Plasmodium falciparum of the resistance to chloroquine (CQ) constitutes a public health priority, due to its direct influence in childhood mortality. The molecular basis for CQ resistance (CQR) is still unclear but, recently, a new relevant gene, named pfcrt, with several point mutations was identified in P. falciparum. Two mutations, K76T and A220S, have been considered crucial for CQR in further studies, making the pfcrt a good candidate as determinant for CQR in P. falciparum. To contribute to this topic, we have undertaken a molecular screening on 164 P. falciparum isolates from Africa: 120 isolates were Italian imported malaria cases, 27 and 17 isolates were from a school-children survey from Congo and Tanzania, respectively. In vitro tests (pLDH and WHO-Mark III tests) for CQ sensitivity have been also carried out on 28 plasmodial isolates and results compared to those obtained by molecular analysis in the same isolates. The SVIET pfcrt haplotype has been identified in the samples from Congo, and this is the first time that this haplotype is detected in Africa. Our results give further evidence to the reliability of the 76T (and the linked 74I-75E) pfcrt point mutation as molecular marker for CQR.
authors.affiliation: Department of Infectious, Parasitic and Immunomediated Diseases, Vector-Borne Diseases and International Health Section, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy. severini@iss.it
authors.forename: Carlo
authors.initials: C
authors.lastname: Severini
authors.forename: Michela
authors.initials: M
authors.lastname: Menegon
authors.forename: Anna Rosa
authors.initials: AR
authors.lastname: Sannella
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Paglia
authors.forename: Pasquale
authors.initials: P
authors.lastname: Narciso
authors.forename: Alberto
authors.initials: A
authors.lastname: Matteelli
authors.forename: Maurizio
authors.initials: M
authors.lastname: Gulletta
authors.forename: Pietro
authors.initials: P
authors.lastname: Caramello
authors.forename: Francesca
authors.initials: F
authors.lastname: Canta
authors.forename: Maniphet V
authors.initials: MV
authors.lastname: Xayavong
authors.forename: Iaci N S
authors.initials: IN
authors.lastname: Moura
authors.forename: Norman J
authors.initials: NJ
authors.lastname: Pieniazek
authors.forename: Donatella
authors.initials: D
authors.lastname: Taramelli
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Majori
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000494:pharmacology*; D015023:Democratic Republic of the Congo; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D006801:Humans; D007558:Italy; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000453:epidemiology / Q000469:parasitology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D026901:Membrane Transport Proteins; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification*; D017354:Point Mutation; D015800:Protozoan Proteins; D013636:Tanzania
chemical_list: D000962:Antimalarials; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; D002738:Chloroquine