Assessment of pfcrt 72-76 haplotypes eight years after chloroquine withdrawal in Kinshasa, Democratic Republic of Congo

Mvumbi Lelo,Dieudonné Makaba Mvumbi,Situakibanza Nani-Tuma,Patrick Demol,Raphael Boreux,Marie-Pierre Hayette,Kayembe Ntumba,Kalala Lunganza,Rosalie Sacheli,Pierrette Melin,Bobanga Lengu

doi:10.1186/1475-2875-12-459

Mvumbi Lelo, Dieudonné Makaba Mvumbi + Show 9 more

Open Access

https://doi.org/10.1186/1475-2875-12-459

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Journal: Malaria Journal	Publication Date: Dec 1, 2013
Citations: 21	License type: cc-by

Affiliation: University of Kinshasa, University of Liège

Abstract

BackgroundIn 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.MethodsA 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.ResultsThe 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.ConclusionsThis 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.

Highlights

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
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 because monotherapies had become ineffective in many parts of the world due to the spread of Plasmodium falciparum strains resistant to almost all anti-malarial drugs in use [1]
Resistance to chloroquine (CQ), the drug that had been widely used for decades for malaria treatment [2], has been well characterized and it is established that a mutation (K76T) occurring in the P. falciparum chloroquine-resistance transporter gene is the key element [3,4,5]

Summary

Introduction

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. 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. 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 because monotherapies had become ineffective in many parts of the world due to the spread of Plasmodium falciparum strains resistant to almost all anti-malarial drugs in use [1]. In vivo evidence of this link has been given by Beshir et al who found that the presence of the SVMNT haplotype was sufficient to confer AQ resistance [10]

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Conclusion