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

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

doi:10.1186/1475-2875-12-459

Cited by 25 publications

(35 citation statements)

References 31 publications

(35 reference statements)

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“…Such a shift in the parasite population after the interruption of CQ use has been observed in several countries in Africa 10, 12, 13, 36 . This reversal to the wild type form of the PfCRT gene indicates that parasites carrying the mutant PfCRT may have a substantial fitness cost in the absence of CQ, thus leading to their decline in frequency once drug pressure is removed 14 .…”

Section: Discussionmentioning

confidence: 65%

In-Vivo Efficacy of Chloroquine to Clear Asymptomatic Infections in Mozambican Adults: A Randomized, Placebo-controlled Trial with Implications for Elimination Strategies

Galatas

Nhamússua

Candrinho

et al. 2017

Sci Rep

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Recent reports regarding the re-emergence of parasite sensitivity to chloroquine call for a new consideration of this drug as an interesting complementary tool in malaria elimination efforts, given its good safety profile and long half-life. A randomized (2:1), single-blind, placebo-controlled trial was conducted in Manhiça, Mozambique, to assess the in-vivo efficacy of chloroquine to clear plasmodium falciparum (Pf) asymptomatic infections. Primary study endpoint was the rate of adequate and parasitological response (ACPR) to therapy on day 28 (PCR-corrected). Day 0 isolates were analyzed to assess the presence of the PfCRT-76T CQ resistance marker. A total of 52 and 27 male adults were included in the CQ and Placebo group respectively. PCR-corrected ACPR was significantly higher in the CQ arm 89.4% (95%CI 80–98%) compared to the placebo (p < 0.001). CQ cleared 49/50 infections within the first 72 h while placebo cleared 12/26 (LRT p < 0.001). The PfCRT-76T mutation was present only in one out of 108 (0.9%) samples at baseline, well below the 84% prevalence found in 1999 in the same area. This study presents preliminary evidence of a return of chloroquine sensitivity in Mozambican Pf isolates, and calls for its further evaluation in community-based malaria elimination efforts, in combination with other effective anti-malarials. Trial registration: www.clinicalTrials.gov NCT02698748.

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Section: Discussionmentioning

confidence: 65%

In-Vivo Efficacy of Chloroquine to Clear Asymptomatic Infections in Mozambican Adults: A Randomized, Placebo-controlled Trial with Implications for Elimination Strategies

Galatas

Nhamússua

Candrinho

et al. 2017

Sci Rep

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“…However, this prevalence was higher in other sites such as Bolenge (32%), Vanga (41.3%), Kinshasa (48.8%) and especially at Katana (89.5%). Previous studies have reported much higher K76T rates in Kinshasa in 2008 (83.8%)[31] and 2010 (73.2%)[21], and in Bolenge in 2014 (70.6%)[22].The simultaneous presence of very low and high prevalence of CQ resistance could be related to different levels of CQ pressure between study sites, differing from one site to another, before and after the withdrawal of this molecule. Concerning the use of CQ in DRC, data from the DHS II in 2013-2014 revealed that in provinces where our sites are located (before territorial apportionment from 11 to 26 provinces) CQ was still in use despite its withdrawal from the national policy of malaria management in 2001[32].…”

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confidence: 78%

Molecular surveillance of anti-malarial drug resistance in Democratic Republic of Congo: high variability of chloroquinoresistance and lack of amodiaquinoresistance

Yobi

Kayiba

Mvumbi

et al. 2020

Preprint

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Background: The loss of chloroquine (CQ) effectiveness has led to its withdrawal from national policies as a first-line treatment for uncomplicated malaria in several endemic countries, such as the Democratic Republic of Congo (DRC). The K76T mutation on the pfcrt gene has been identified as a marker of CQ resistance and the SVMNT haplotype in codons 72–76 on the same gene has been associated with resistance to amodiaquine (AQ). In the DRC, the prevalence of K76T has decreased from 100% in 2000 to 63.9% in 2014. The purpose of this study was to determine the prevalence of K76T mutations in circulating strains of Plasmodium falciparum, sixteen years after CQ withdrawal in the DRC and to investigate the presence of the SVMNT haplotype. Methods : In 2017, ten geographical sites across the DRC were selected. Dried blood samples were collected from patients attending health centres. Malaria was first detected by a rapid diagnostic test (RDT) available on site (SD Bioline Malaria Ag Pf or CareStart Malaria Pf) or thick blood smear and then confirmed by a P. falciparum species-specific real-time PCR assay. A pfcrt gene segment containing a fragment that encodes amino acids at positions 72-76 was amplified by conventional PCR before sequencing. Results: A total of 1070 patients were enrolled. Of the 806 PCR-confirmed P. falciparum positive samples, 764 were successfully sequenced. The K76T mutation was detected in 218 samples (28.5%; 95% CI: 25.4%–31.9%), mainly (96%) with the CVIET haplotype. Prevalence of CQ resistance marker was unequally distributed across the country, ranging from 1.5% in Fungurume to 89.5% in Katana. The SVMNT haplotype, related to AQ resistance, was not detected. Conclusion: Overall, the frequency of the P. falciparum CQ resistance marker has decreased significantly and no resistance marker to AQ was detected in the DRC in 2017. However, the between regions variability of CQ resistance remains high in the country. Further studies are needed for continuous monitoring of the CQ resistance level for its prospective re-use in malaria management. The absence of the AQ resistance marker is in line with the use of this drug in the current DRC malaria treatment policy.

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“…Chloroquine resistance continues to persist in most countries affected by malaria [32], and the DRC is not spared. Indeed, after removing chloroquine from the DRC's malaria treatment policy 11 years ago, still, Juliao et al [32] and Mvumbi et al [33] have identified markers of chloroquine resistance.…”

Section: Introductionmentioning

confidence: 99%

Gestational malaria in Kisangani : Efficacy of Mefloquine vs Sulfadoxine-Pyrimethamine in Intermittent Preventive Treatment : A Study Protocol for a randomized controlled clinical trial

Noël

Nguma

Mike-Antoine

et al. 2019

Preprint

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Background : In order to reduce malaria-related morbidity and mortality during pregnancy, WHO recommends : Insecticide-treated mosquito nets, Intermittent Preventive Treatment of malaria in pregnancy, Prompt and effective case management. Nevertheless, several cases of resistance to Sulfadoxine-Pyrimethamine, used in intermittent preventive treatment, and to Chloroquine are reported in sub-Saharan Africa and in the Democratic Republic of the Congo. The prevalence of malaria among pregnant women remains high in Africa in general, and in the Democratic Republic of Congo in particular. This issue leads us to conduct this study, which aims at proposing an alternative to SP for preventing malaria in pregnant women. Materials and methods : From June 1 to October 31, 2019, we enrolled pregnant women from five health facilities in Kisangani for randomized, single-blind controlled clinical trials to compare the efficacy of two intermittent preventive treatment regimens in Kisangani pregnant women, selected before 18 th weeks of amenorrhea. The first regimen consists of 4 doses of Sulfadoxine-Pyrimethamine starting at the selection time and spaced at least 4 weeks during pregnancy. Each dose is made of 3 tablets of 525 mg Sulfadoxine-Pyrimethamine. The second regimen consists of 2 doses of Mefloquine during pregnancy. The first dose is taken at the selection time and the second dose between the 28 th and 32 nd weeks of amenorrhea. Each dose is made of 3 tablets of 250 mg Mefloquine. The efficacy criteria for these two regimens are placental malaria parasitemia, low birth weight of newborn and maternal anemia at delivery. The safety criterion was the occurrence of major side effects. Discussion : There are not enough randomized clinical trials assessing the efficacy of Mefloquine for the intermittent preventive treatment of malaria in African pregnant women, hence the recommendation for clinical trials. The present study is the only one that conducts such assessment in a hyper-endemic area with resistance to Sulfadoxine-Pyrimethamine and Chloroquine. The findings are therefore intended to promote the use of Mefloquine as the best alternative to Sulfadoxine-Pyrimethamine in the intermittent preventive treatment of malaria. Clinical trial registration : PACTR201905899965726. Key words : Intermittent preventive treatment, efficacy, safety, Mefloquine, Sulfadoxine-Pyrimethamine, Kisangani.

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

Cited by 25 publications

References 31 publications

In-Vivo Efficacy of Chloroquine to Clear Asymptomatic Infections in Mozambican Adults: A Randomized, Placebo-controlled Trial with Implications for Elimination Strategies

In-Vivo Efficacy of Chloroquine to Clear Asymptomatic Infections in Mozambican Adults: A Randomized, Placebo-controlled Trial with Implications for Elimination Strategies

Molecular surveillance of anti-malarial drug resistance in Democratic Republic of Congo: high variability of chloroquinoresistance and lack of amodiaquinoresistance

Gestational malaria in Kisangani : Efficacy of Mefloquine vs Sulfadoxine-Pyrimethamine in Intermittent Preventive Treatment : A Study Protocol for a randomized controlled clinical trial

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