scholarly journals Molecular surveillance of Plasmodium falciparum resistance to artemisinin-based combination therapies in the Democratic Republic of Congo

PLoS ONE ◽  
2017 ◽  
Vol 12 (6) ◽  
pp. e0179142 ◽  
Author(s):  
Dieudonné Makaba Mvumbi ◽  
Thierry Lengu Bobanga ◽  
Jean-Marie Ntumba Kayembe ◽  
Georges Lelo Mvumbi ◽  
Hippolyte Nani-Tuma Situakibanza ◽  
...  
2020 ◽  
Author(s):  
Doudou M. Yobi ◽  
Nadine K. Kayiba ◽  
Dieudonné M. Mvumbi ◽  
Raphael Boreux ◽  
Pius Z. Kabututu ◽  
...  

Abstract 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.


2019 ◽  
Author(s):  
Molly N/A Deutsch-Feldman ◽  
Ozkan Aydemir ◽  
Margaret Carrel ◽  
Nicholas F. Brazeau ◽  
Samir Bhatt ◽  
...  

Abstract Background: Drug resistant malaria is a growing concern in the Democratic Republic of the Congo (DRC), where previous studies indicate that parasites resistant to sulfadoxine/pyrimethamine or chloroquine are spatially clustered. This study explores longitudinal changes in spatial patterns to understand how resistant malaria may be spreading within the DRC, using samples from nation-wide population-representative surveys. Methods: We selected 552 children with PCR-detectable Plasmodium falciparum infection and identified known variants in the pfdhps and pfcrt genes associated with resistance. We compared the proportion of mutant parasites in 2013 to those previously reported from adults in 2007, and identified risk factors for carrying a resistant allele using multivariate mixed-effects modeling. Finally, we fit a spatial-temporal model to the observed data, providing smooth allele frequency estimates over space and time. Results: The proportion of co-occurring pfdhps K540E/A581G mutations increased by 16% between 2007 and 2013. The spatial-temporal model suggests that the spatial range of the pfdhps double mutants expanded over time, while the prevalence and range of pfcrt mutations remained steady. Conclusions: This study uses population-representative samples to describe the changing landscape of SP resistance within the DRC, and the persistence of chloroquine resistance. Vigilant molecular surveillance is critical for controlling the spread of resistance.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Molly Deutsch-Feldman ◽  
Ozkan Aydemir ◽  
Margaret Carrel ◽  
Nicholas F. Brazeau ◽  
Samir Bhatt ◽  
...  

Abstract Background Drug resistant malaria is a growing concern in the Democratic Republic of the Congo (DRC), where previous studies indicate that parasites resistant to sulfadoxine/pyrimethamine or chloroquine are spatially clustered. This study explores longitudinal changes in spatial patterns to understand how resistant malaria may be spreading within the DRC, using samples from nation-wide population-representative surveys. Methods We selected 552 children with PCR-detectable Plasmodium falciparum infection and identified known variants in the pfdhps and pfcrt genes associated with resistance. We compared the proportion of mutant parasites in 2013 to those previously reported from adults in 2007, and identified risk factors for carrying a resistant allele using multivariate mixed-effects modeling. Finally, we fit a spatial-temporal model to the observed data, providing smooth allele frequency estimates over space and time. Results The proportion of co-occurring pfdhps K540E/A581G mutations increased by 16% between 2007 and 2013. The spatial-temporal model suggests that the spatial range of the pfdhps double mutants expanded over time, while the prevalence and range of pfcrt mutations remained steady. Conclusions This study uses population-representative samples to describe the changing landscape of SP resistance within the DRC, and the persistence of chloroquine resistance. Vigilant molecular surveillance is critical for controlling the spread of resistance.


2006 ◽  
Vol 75 (1) ◽  
pp. 152-154 ◽  
Author(s):  
SANDRA COHUET ◽  
MICHEL VAN HERP ◽  
UMBERTO D’ALESSANDRO ◽  
MARYLINE BONNET ◽  
CHANTAL VAN OVERMEIR ◽  
...  

2019 ◽  
Author(s):  
Molly N/A Deutsch-Feldman ◽  
Ozkan Aydemir ◽  
Margaret Carrel ◽  
Nicholas F. Brazeau ◽  
Samir Bhatt ◽  
...  

Abstract Background: Drug resistant malaria is a growing concern in the Democratic Republic of the Congo (DRC), where previous studies indicate that parasites resistant to sulfadoxine/pyrimethamine or chloroquine are spatially clustered. This study explores longitudinal changes in spatial patterns to understand how resistant malaria may be spreading within the DRC, using samples from nation-wide population-representative surveys. Methods: We selected 552 children with PCR-detectable Plasmodium falciparum infection and identified known variants in the pfdhps and pfcrt genes associated with resistance. We compared the proportion of mutant parasites in 2013 to those previously reported from adults in 2007, and identified risk factors for carrying a resistant allele using multivariate mixed-effects modeling. Finally, we fit a spatial-temporal model to the observed data, providing smooth allele frequency estimates over space and time. Results: The proportion of co-occurring pfdhps K540E/A581G mutations increased by 16% between 2007 and 2013. The spatial-temporal model suggests that the spatial range of the pfdhps double mutants expanded over time, while the prevalence and range of pfcrt mutations remained steady. Conclusions: This study uses population-representative samples to describe the changing landscape of SP resistance within the DRC, and the persistence of chloroquine resistance. Vigilant molecular surveillance is critical for controlling the spread of resistance.


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