Prevalence of pfcrt point mutations and level of chloroquine resistance in Plasmodium falciparum isolates from Africa.
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.
Severini
Carlo
C
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
Menegon
Michela
M
Sannella
Anna Rosa
AR
Paglia
Maria Grazia
MG
Narciso
Pasquale
P
Matteelli
Alberto
A
Gulletta
Maurizio
M
Caramello
Pietro
P
Canta
Francesca
F
Xayavong
Maniphet V
MV
Moura
Iaci N S
IN
Pieniazek
Norman J
NJ
Taramelli
Donatella
D
Majori
Giancarlo
G
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
D000962:Antimalarials; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; D002738:Chloroquine