malaria; pfcrt; drug resistance; RT-PCR; sequencing; DR Congo
Abstract :
[en] 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.
Disciplines :
Immunology & infectious disease
Author, co-author :
Mvumbi, Dieudonné; University of Kinshasa, DR Congo > Basic Sciences, School of Medicine > 1Biochemistry and Molecular Biology Unit, > 3
BOREUX, Raphaël ; Centre Hospitalier Universitaire de Liège - CHU > Microbiologie médicale
SACHELI, Rosalie ; Centre Hospitalier Universitaire de Liège - CHU > Microbiologie médicale
Mvumbi, Lelo; University of Kinshasa, DR Congo > Department of Basic Sciences, School of Medicine, > 1Biochemistry and Molecular Biology Unit,
Bobanga, Lengu; University of Kinshasa, DR Congo > Department of Tropical Medicine and Infectious Disease, School of Medicine
Situakibanza, Hippolyte; Department of Tropical Medicine and Infectious Disease, School of Medicine, University of Kinshasa, DR Congo > Department of Tropical Medicine and Infectious Disease, School of Medicine
Melin, Pierrette ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Bactériologie, mycologie, parasitologie, virologie
Kayembe, Jean-Marie; University of Kinshasa, DR Congo > Department of Internal Medicine, School of Medicine
Kalala, Lunganza; University of Kinshasa, DR Congo > 1Biochemistry and Molecular Biology Unit, Department of Basic Sciences, School of Medicine
De Mol, Patrick ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Hayette, Marie-Pierre ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Bactériologie, mycologie, parasitologie, virologie
Language :
English
Title :
Assessment of pfcrt 72-76 haplotypes eight years after chloroquine withdrawal in Kinshasa, Democratic Republic of Congo
Alternative titles :
[fr] Détermination des haplotypes pfcrt 72-76, 8 ans après abandon de l'utilisation de la chloroquine à Kinshasa, RDC
Publication date :
20 December 2013
Journal title :
Malaria Journal
eISSN :
1475-2875
Publisher :
BioMed Central, United Kingdom
Volume :
12
Pages :
459
Peer reviewed :
Peer Reviewed verified by ORBi
Name of the research project :
Epidémiologie des résistances de Plasmodium falciparum en RDC
Funders :
CUD - Commission Universitaire pour le Développement [BE]
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