Molecular surveillance of anti-malarial drug resistance in Democratic Republic of Congo: high variability of chloroquinoresistance and lack of amodiaquinoresistance
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...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2020-03-01
|
| Series: | Malaria Journal |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12936-020-03192-x |
| _version_ | 1828445526071181312 |
|---|---|
| author | Doudou M. Yobi Nadine K. Kayiba Dieudonné M. Mvumbi Raphael Boreux Pius Z. Kabututu Hippolyte N. T. Situakibanza Joris L. Likwela Patrick De Mol Emile W. Okitolonda Niko Speybroeck Georges L. Mvumbi Marie-Pierre Hayette |
| author_facet | Doudou M. Yobi Nadine K. Kayiba Dieudonné M. Mvumbi Raphael Boreux Pius Z. Kabututu Hippolyte N. T. Situakibanza Joris L. Likwela Patrick De Mol Emile W. Okitolonda Niko Speybroeck Georges L. Mvumbi Marie-Pierre Hayette |
| author_sort | Doudou M. Yobi |
| collection | DOAJ |
| description | 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, 16 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. |
| first_indexed | 2024-12-10T21:58:17Z |
| format | Article |
| id | doaj.art-4e053ea884d84430acb7390350582129 |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-12-10T21:58:17Z |
| publishDate | 2020-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Malaria Journal |
| spelling | doaj.art-4e053ea884d84430acb73903505821292022-12-22T01:31:58ZengBMCMalaria Journal1475-28752020-03-011911810.1186/s12936-020-03192-xMolecular surveillance of anti-malarial drug resistance in Democratic Republic of Congo: high variability of chloroquinoresistance and lack of amodiaquinoresistanceDoudou M. Yobi0Nadine K. Kayiba1Dieudonné M. Mvumbi2Raphael Boreux3Pius Z. Kabututu4Hippolyte N. T. Situakibanza5Joris L. Likwela6Patrick De Mol7Emile W. Okitolonda8Niko Speybroeck9Georges L. Mvumbi10Marie-Pierre Hayette11Department of Basic Sciences, Faculty of Medicine, University of KinshasaSchool of Public Health, Faculty of Medicine, University of KinshasaDepartment of Basic Sciences, Faculty of Medicine, University of KinshasaLaboratory of Clinical Microbiology, University of LiègeDepartment of Basic Sciences, Faculty of Medicine, University of KinshasaDepartment of Internal Medicine, Faculty of Medicine, University of KinshasaNational Malaria Control ProgrammeLaboratory of Clinical Microbiology, University of LiègeSchool of Public Health, Faculty of Medicine, University of KinshasaSchool of Public Health & Research Institute of Health and Society, Catholic University of LouvainDepartment of Basic Sciences, Faculty of Medicine, University of KinshasaLaboratory of Clinical Microbiology, University of LiègeAbstract 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, 16 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.http://link.springer.com/article/10.1186/s12936-020-03192-xMolecularSurveillanceResistanceChloroquineAmodiaquineDRC |
| spellingShingle | Doudou M. Yobi Nadine K. Kayiba Dieudonné M. Mvumbi Raphael Boreux Pius Z. Kabututu Hippolyte N. T. Situakibanza Joris L. Likwela Patrick De Mol Emile W. Okitolonda Niko Speybroeck Georges L. Mvumbi Marie-Pierre Hayette Molecular surveillance of anti-malarial drug resistance in Democratic Republic of Congo: high variability of chloroquinoresistance and lack of amodiaquinoresistance Malaria Journal Molecular Surveillance Resistance Chloroquine Amodiaquine DRC |
| title | Molecular surveillance of anti-malarial drug resistance in Democratic Republic of Congo: high variability of chloroquinoresistance and lack of amodiaquinoresistance |
| title_full | Molecular surveillance of anti-malarial drug resistance in Democratic Republic of Congo: high variability of chloroquinoresistance and lack of amodiaquinoresistance |
| title_fullStr | Molecular surveillance of anti-malarial drug resistance in Democratic Republic of Congo: high variability of chloroquinoresistance and lack of amodiaquinoresistance |
| title_full_unstemmed | Molecular surveillance of anti-malarial drug resistance in Democratic Republic of Congo: high variability of chloroquinoresistance and lack of amodiaquinoresistance |
| title_short | Molecular surveillance of anti-malarial drug resistance in Democratic Republic of Congo: high variability of chloroquinoresistance and lack of amodiaquinoresistance |
| title_sort | molecular surveillance of anti malarial drug resistance in democratic republic of congo high variability of chloroquinoresistance and lack of amodiaquinoresistance |
| topic | Molecular Surveillance Resistance Chloroquine Amodiaquine DRC |
| url | http://link.springer.com/article/10.1186/s12936-020-03192-x |
| work_keys_str_mv | AT doudoumyobi molecularsurveillanceofantimalarialdrugresistanceindemocraticrepublicofcongohighvariabilityofchloroquinoresistanceandlackofamodiaquinoresistance AT nadinekkayiba molecularsurveillanceofantimalarialdrugresistanceindemocraticrepublicofcongohighvariabilityofchloroquinoresistanceandlackofamodiaquinoresistance AT dieudonnemmvumbi molecularsurveillanceofantimalarialdrugresistanceindemocraticrepublicofcongohighvariabilityofchloroquinoresistanceandlackofamodiaquinoresistance AT raphaelboreux molecularsurveillanceofantimalarialdrugresistanceindemocraticrepublicofcongohighvariabilityofchloroquinoresistanceandlackofamodiaquinoresistance AT piuszkabututu molecularsurveillanceofantimalarialdrugresistanceindemocraticrepublicofcongohighvariabilityofchloroquinoresistanceandlackofamodiaquinoresistance AT hippolytentsituakibanza molecularsurveillanceofantimalarialdrugresistanceindemocraticrepublicofcongohighvariabilityofchloroquinoresistanceandlackofamodiaquinoresistance AT jorisllikwela molecularsurveillanceofantimalarialdrugresistanceindemocraticrepublicofcongohighvariabilityofchloroquinoresistanceandlackofamodiaquinoresistance AT patrickdemol molecularsurveillanceofantimalarialdrugresistanceindemocraticrepublicofcongohighvariabilityofchloroquinoresistanceandlackofamodiaquinoresistance AT emilewokitolonda molecularsurveillanceofantimalarialdrugresistanceindemocraticrepublicofcongohighvariabilityofchloroquinoresistanceandlackofamodiaquinoresistance AT nikospeybroeck molecularsurveillanceofantimalarialdrugresistanceindemocraticrepublicofcongohighvariabilityofchloroquinoresistanceandlackofamodiaquinoresistance AT georgeslmvumbi molecularsurveillanceofantimalarialdrugresistanceindemocraticrepublicofcongohighvariabilityofchloroquinoresistanceandlackofamodiaquinoresistance AT mariepierrehayette molecularsurveillanceofantimalarialdrugresistanceindemocraticrepublicofcongohighvariabilityofchloroquinoresistanceandlackofamodiaquinoresistance |