Prevalence of pfcrt point mutations and level of chloroquine resistance in Plasmodium falciparum isolates from Africa

• Published in: Infection, genetics and evolution Vol. 6; no. 4; pp. 262 - 268
• Main Authors: Severini, Carlo, Menegon, Michela, Sannella, Anna Rosa, Paglia, Maria Grazia, Narciso, Pasquale, Matteelli, Alberto, Gulletta, Maurizio, Caramello, Pietro, Canta, Francesca, Xayavong, Maniphet V., Moura, Iaci N.S., Pieniazek, Norman J., Taramelli, Donatella, Majori, Giancarlo
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-07-2006
• Subjects: Adolescent; Adult; Animals; Antimalarials - pharmacology; Child; Child, Preschool; Chloroquine - pharmacology; Chloroquine resistance; Democratic Republic of the Congo; Drug Resistance - genetics; Female; Humans; Italy; Malaria, Falciparum - drug therapy; Malaria, Falciparum - epidemiology; Malaria, Falciparum - parasitology; Male; Membrane Proteins - genetics; Membrane Proteins - metabolism; Membrane Transport Proteins; Middle Aged; Molecular epidemiology; Molecular markers; pfcrt point mutations; Plasmodium falciparum; Plasmodium falciparum - drug effects; Plasmodium falciparum - genetics; Plasmodium falciparum - isolation & purification; Point Mutation; Protozoan Proteins; Tanzania; Italy; Tanzania; Democratic Republic of the Congo; Africa; Molecular epidemiology; Plasmodium falciparum; Molecular markers; Chloroquine resistance; pfcrt point mutations
• ISSN: 1567-1348; 1567-7257
• DOI: 10.1016/j.meegid.2005.07.002

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.