TY - JOUR T1 - Assessment of pfcrt 72-76 haplotypes eight years after chloroquine withdrawal in Kinshasa, Democratic Republic of Congo. JF - Malar J Y1 - 2013 A1 - Dieudonné Makaba Mvumbi A1 - Raphael Boreux A1 - Rosalie Sacheli A1 - Lelo, Mvumbi A1 - T Lengu Bobanga A1 - Nani-Tuma, Situakibanza A1 - Pierrette Melin A1 - Ntumba, Kayembe A1 - Kalala Lunganza A1 - Patrick De Mol A1 - Marie-Pierre Hayette KW - Antimalarials KW - Child, Preschool KW - Chloroquine KW - Democratic Republic of the Congo KW - DNA, Protozoan KW - Drug Resistance KW - Female KW - Gene Frequency KW - Haplotypes KW - Humans KW - Infant KW - Infant, Newborn KW - Malaria, Falciparum KW - Male KW - Membrane Transport Proteins KW - Mutant Proteins KW - Plasmodium falciparum KW - Protozoan Proteins KW - Real-Time Polymerase Chain Reaction KW - Sequence Analysis, DNA AB -

BACKGROUND: In 2001, the World Health Organization (WHO) has recommended the use of artemisinin-based combination therapy (ACT) as the first-line treatment of uncomplicated malaria cases, as monotherapies had become ineffective in many parts of the world. As a result, the Democratic Republic of Congo (DRC) withdrew chloroquine (CQ) from its malaria treatment policy in 2002 and an artesunate (AS)-amodiaquine (AQ) combination became the ACT of choice in DRC in 2005. AQ-resistance (AQR) has been reported in several parts of the world and mutations in codons 72-76 of the Plasmodium falciparum chloroquine-resistance transporter (pfcrt) gene have been strongly correlated with resistance, especially mutations encoding the SVMNT haplotype. This haplotype was first identified in Southeast Asia and South America but was recently reported in two African countries neighbouring DRC. These facts raised two questions: the first about the evolution of CQ resistance (CQR) in DRC and the second about the presence of the SVMNT haplotype, which would compromise the use of AQ as a partner drug for ACT.

METHODS: A total of 213 thick blood films were randomly collected in 2010 from a paediatric clinic in Kinshasa, DRC. Microscopy controls and real-time polymerase chain reaction (RT-PCR) were performed for Plasmodium species identification. Haplotypes of the pfcrt gene were determined by sequencing.

RESULTS: The K76T mutation was detected in 145 out of 198 P. falciparum-positive samples (73.2%). In these 145 resistant strains, only the CVIET haplotype was detected.

CONCLUSIONS: This study is the first to assess the molecular markers of resistance to CQ and AQ after the introduction of ACT in DRC. The results suggest first that CQR is decreasing, as wild-type pfcrt haplotypes were found in only 26.8% of the samples and secondly that the SVMNT haplotype is not yet present in Kinshasa, suggesting that AQ remains valid as a partner drug for ACT in this region.

VL - 12 M3 - 10.1186/1475-2875-12-459 ER -