Assessing the efficacy of chloroquine and sulfadoxine–pyrimethamine for treatment of uncomplicated <i>Plasmodium falciparum</i> malaria in the Democratic Republic of Congo

Kazadi, Walter; Vong, Sirenda; Makina, Burstein N.; Mantshumba, Jean C.; Kabuya, W; Kebela, Benoit; Ngimbi, N. P.

doi:10.1046/j.1365-3156.2003.01098.x

Cited by 31 publications

(29 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There were high rates of therapeutic failures, but those failures occurred in close to 90% of cases more than 7 days after treatment (Late Treatment Failures, LTFs) whereas in sub-Saharan Africa the proportion of LTFs is usually near 20% [29], [30], [31], [32], [33]. The proportion of isolates with detectable Pfcrt mutant parasites was totally disconnected from the rate of clinical failures.…”

Section: Discussionmentioning

confidence: 99%

Chloroquine Clinical Failures in P. falciparum Malaria Are Associated with Mutant Pfmdr-1, Not Pfcrt in Madagascar

Andriantsoanirina

Ratsimbasoa²,

Bouchier

et al. 2010

PLoS ONE

View full text Add to dashboard Cite

Molecular studies have demonstrated that mutations in the Plasmodium falciparum chloroquine resistance transporter gene (Pfcrt) play a major role in chloroquine resistance, while mutations in P. falciparum multidrug resistance gene (Pfmdr-1) act as modulator. In Madagascar, the high rate of chloroquine treatment failure (44%) appears disconnected from the overall level of in vitro CQ susceptibility (prevalence of CQ-resistant parasites <5%) or Pfcrt mutant isolates (<1%), strongly contrasting with sub-Saharan African countries. Previous studies showed a high frequency of Pfmdr-1 mutant parasites (>60% of isolates), but did not explore their association with P. falciparum chloroquine resistance. To document the association of Pfmdr-1 alleles with chloroquine resistance in Madagascar, 249 P. falciparum samples collected from patients enrolled in a chloroquine in vivo efficacy study were genotyped in Pfcrt/Pfmdr-1 genes as well as the estimation of the Pfmdr-1 copy number. Except 2 isolates, all samples displayed a wild-type Pfcrt allele without Pfmdr-1 amplification. Chloroquine treatment failures were significantly associated with Pfmdr-1 86Y mutant codon (OR = 4.6). The cumulative incidence of recurrence of patients carrying the Pfmdr-1 86Y mutation at day 0 (21 days) was shorter than patients carrying Pfmdr-1 86N wild type codon (28 days). In an independent set of 90 selected isolates, in vitro susceptibility to chloroquine was not associated with Pfmdr-1 polymorphisms. Analysis of two microsatellites flanking Pfmdr-1 allele showed that mutations occurred on multiple genetic backgrounds. In Madagascar, Pfmdr-1 polymorphism is associated with late chloroquine clinical failures and unrelated with in vitro susceptibility or Pfcrt genotype. These results highlight the limits of the current in vitro tests routinely used to monitor CQ drug resistance in this unique context. Gaining insight about the mechanisms that regulate polymorphism in Pfmdr1 remains important, particularly regarding the evolution and spread of Pfmdr-1 alleles in P. falciparum populations under changing drug pressure which may have important consequences in terms of antimalarial use management.

show abstract

Section: Discussionmentioning

confidence: 99%

Chloroquine Clinical Failures in P. falciparum Malaria Are Associated with Mutant Pfmdr-1, Not Pfcrt in Madagascar

Andriantsoanirina

Ratsimbasoa²,

Bouchier

et al. 2010

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…Both countries border the Democratic Republic of Congo (DRC), where CQ, after being widely used, was officially abandoned in 2002 to be replaced first by sulphadoxine-pyrimethamine (SP) and then by an artesunate-amodiaquine (AS-AQ) combination in 2005 [15]. …”

Section: Introductionmentioning

confidence: 99%

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

Mvumbi

Boreux

Sacheli

et al. 2013

Malar J

View full text Add to dashboard Cite

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.

show abstract

“…In Eastern Democratic Republic of Congo (DRC), resistance of Plasmodium falciparum to CQ has been documented since 1983 and was estimated at 80% in 2001 [7]. This prompted the National Malaria Control Program (NMCP) to change in 2005 the national antimalarial treatment policy and the first line treatment, from CQ to amodiaquine plus artesunate (AS+AQ).…”

Section: Introductionmentioning

confidence: 99%

Efficacy of Artesunate Plus Amodiaquine for Treatment of Uncomplicated Clinical Falciparum Malaria in Severely Malnourished Children Aged 6–59 Months, Democratic Republic of Congo

Mitangala-Ndeba¹,

D’Alessandro

Hennart³

et al. 2013

J Clin Exp Pathol

View full text Add to dashboard Cite

show abstract

Assessing the efficacy of chloroquine and sulfadoxine–pyrimethamine for treatment of uncomplicated Plasmodium falciparum malaria in the Democratic Republic of Congo

Cited by 31 publications

References 15 publications

Chloroquine Clinical Failures in P. falciparum Malaria Are Associated with Mutant Pfmdr-1, Not Pfcrt in Madagascar

Chloroquine Clinical Failures in P. falciparum Malaria Are Associated with Mutant Pfmdr-1, Not Pfcrt in Madagascar

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

Efficacy of Artesunate Plus Amodiaquine for Treatment of Uncomplicated Clinical Falciparum Malaria in Severely Malnourished Children Aged 6–59 Months, Democratic Republic of Congo

Contact Info

Product

Resources

About