The lack of K13-propeller mutations associated with artemisinin resistance in Plasmodium falciparum in Democratic Republic of Congo (DRC).
Artemisinin-based combination therapies (ACTs) have been recommended by the World Health Organization (WHO) as first-line treatment of uncomplicated Plasmodium falciparum (P. falciparum) malaria since 2005 in Democratic Republic of Congo (DRC) and a regular surveillance of the ACT efficacy is requir...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2020-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0237791 |
| _version_ | 1819012304516153344 |
|---|---|
| author | Doudou Malekita Yobi Nadine Kalenda Kayiba Dieudonné Makaba Mvumbi Raphael Boreux Sebastien Bontems Pius Zakayi Kabututu Patrick De Mol Niko Speybroeck Georges Lelo Mvumbi Marie-Pierre Hayette |
| author_facet | Doudou Malekita Yobi Nadine Kalenda Kayiba Dieudonné Makaba Mvumbi Raphael Boreux Sebastien Bontems Pius Zakayi Kabututu Patrick De Mol Niko Speybroeck Georges Lelo Mvumbi Marie-Pierre Hayette |
| author_sort | Doudou Malekita Yobi |
| collection | DOAJ |
| description | Artemisinin-based combination therapies (ACTs) have been recommended by the World Health Organization (WHO) as first-line treatment of uncomplicated Plasmodium falciparum (P. falciparum) malaria since 2005 in Democratic Republic of Congo (DRC) and a regular surveillance of the ACT efficacy is required to ensure the treatment effectiveness. Mutations in the propeller domain of the pfk13 gene were identified as molecular markers of artemisinin resistance (ART-R). This study investigated the pfk13-propeller gene polymorphism in clinical isolates of P. falciparum collected in the DRC. In 2017, ten geographical sites across DRC were selected for a cross-sectional study that was conducted first in Kinshasa from January to March, then in the nine other sites from September to December. Dried blood samples were collected from patients attending health centers for fever where diagnosis of Malaria was first made by rapid diagnostic test (RDT) available on site (SD Bioline malaria Ag Pf or CareStart Malaria Pf) or by thick blood smear and then confirmed by a P. falciparum real-time PCR assay. A pfk13-propeller segment containing a fragment that codes for amino acids at positions 427-595 was amplified by conventional PCR before sequencing. In total, 1070 patients were enrolled in the study. Real-time PCR performed confirmed the initial diagnosis of P. falciparum infection in 806 samples (75.3%; 95% CI: 72.6%- 77.9%). Of the 717 successfully sequenced P. falciparum isolates, 710 (99.0%; 95% CI: 97.9% - 99.6) were wild-type genotypes and 7 (1.0%; 95% CI: 0.4% - 2.1%) carried non-synonymous (NS) mutations in pfk13-propeller including 2 mutations (A578S and V534A) previously detected and 2 other (M472I and A569T) not yet detected in the DRC. Mutations associated with ART-R in Southeast Asia were not observed in DRC. However, the presence of other mutations in pfk13-propeller gene calls for further investigations to assess their implication in drug resistance. |
| first_indexed | 2024-12-21T01:41:56Z |
| format | Article |
| id | doaj.art-256d582b5e16492599cc038668e11bcd |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T01:41:56Z |
| publishDate | 2020-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-256d582b5e16492599cc038668e11bcd2022-12-21T19:20:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01158e023779110.1371/journal.pone.0237791The lack of K13-propeller mutations associated with artemisinin resistance in Plasmodium falciparum in Democratic Republic of Congo (DRC).Doudou Malekita YobiNadine Kalenda KayibaDieudonné Makaba MvumbiRaphael BoreuxSebastien BontemsPius Zakayi KabututuPatrick De MolNiko SpeybroeckGeorges Lelo MvumbiMarie-Pierre HayetteArtemisinin-based combination therapies (ACTs) have been recommended by the World Health Organization (WHO) as first-line treatment of uncomplicated Plasmodium falciparum (P. falciparum) malaria since 2005 in Democratic Republic of Congo (DRC) and a regular surveillance of the ACT efficacy is required to ensure the treatment effectiveness. Mutations in the propeller domain of the pfk13 gene were identified as molecular markers of artemisinin resistance (ART-R). This study investigated the pfk13-propeller gene polymorphism in clinical isolates of P. falciparum collected in the DRC. In 2017, ten geographical sites across DRC were selected for a cross-sectional study that was conducted first in Kinshasa from January to March, then in the nine other sites from September to December. Dried blood samples were collected from patients attending health centers for fever where diagnosis of Malaria was first made by rapid diagnostic test (RDT) available on site (SD Bioline malaria Ag Pf or CareStart Malaria Pf) or by thick blood smear and then confirmed by a P. falciparum real-time PCR assay. A pfk13-propeller segment containing a fragment that codes for amino acids at positions 427-595 was amplified by conventional PCR before sequencing. In total, 1070 patients were enrolled in the study. Real-time PCR performed confirmed the initial diagnosis of P. falciparum infection in 806 samples (75.3%; 95% CI: 72.6%- 77.9%). Of the 717 successfully sequenced P. falciparum isolates, 710 (99.0%; 95% CI: 97.9% - 99.6) were wild-type genotypes and 7 (1.0%; 95% CI: 0.4% - 2.1%) carried non-synonymous (NS) mutations in pfk13-propeller including 2 mutations (A578S and V534A) previously detected and 2 other (M472I and A569T) not yet detected in the DRC. Mutations associated with ART-R in Southeast Asia were not observed in DRC. However, the presence of other mutations in pfk13-propeller gene calls for further investigations to assess their implication in drug resistance.https://doi.org/10.1371/journal.pone.0237791 |
| spellingShingle | Doudou Malekita Yobi Nadine Kalenda Kayiba Dieudonné Makaba Mvumbi Raphael Boreux Sebastien Bontems Pius Zakayi Kabututu Patrick De Mol Niko Speybroeck Georges Lelo Mvumbi Marie-Pierre Hayette The lack of K13-propeller mutations associated with artemisinin resistance in Plasmodium falciparum in Democratic Republic of Congo (DRC). PLoS ONE |
| title | The lack of K13-propeller mutations associated with artemisinin resistance in Plasmodium falciparum in Democratic Republic of Congo (DRC). |
| title_full | The lack of K13-propeller mutations associated with artemisinin resistance in Plasmodium falciparum in Democratic Republic of Congo (DRC). |
| title_fullStr | The lack of K13-propeller mutations associated with artemisinin resistance in Plasmodium falciparum in Democratic Republic of Congo (DRC). |
| title_full_unstemmed | The lack of K13-propeller mutations associated with artemisinin resistance in Plasmodium falciparum in Democratic Republic of Congo (DRC). |
| title_short | The lack of K13-propeller mutations associated with artemisinin resistance in Plasmodium falciparum in Democratic Republic of Congo (DRC). |
| title_sort | lack of k13 propeller mutations associated with artemisinin resistance in plasmodium falciparum in democratic republic of congo drc |
| url | https://doi.org/10.1371/journal.pone.0237791 |
| work_keys_str_mv | AT doudoumalekitayobi thelackofk13propellermutationsassociatedwithartemisininresistanceinplasmodiumfalciparumindemocraticrepublicofcongodrc AT nadinekalendakayiba thelackofk13propellermutationsassociatedwithartemisininresistanceinplasmodiumfalciparumindemocraticrepublicofcongodrc AT dieudonnemakabamvumbi thelackofk13propellermutationsassociatedwithartemisininresistanceinplasmodiumfalciparumindemocraticrepublicofcongodrc AT raphaelboreux thelackofk13propellermutationsassociatedwithartemisininresistanceinplasmodiumfalciparumindemocraticrepublicofcongodrc AT sebastienbontems thelackofk13propellermutationsassociatedwithartemisininresistanceinplasmodiumfalciparumindemocraticrepublicofcongodrc AT piuszakayikabututu thelackofk13propellermutationsassociatedwithartemisininresistanceinplasmodiumfalciparumindemocraticrepublicofcongodrc AT patrickdemol thelackofk13propellermutationsassociatedwithartemisininresistanceinplasmodiumfalciparumindemocraticrepublicofcongodrc AT nikospeybroeck thelackofk13propellermutationsassociatedwithartemisininresistanceinplasmodiumfalciparumindemocraticrepublicofcongodrc AT georgeslelomvumbi thelackofk13propellermutationsassociatedwithartemisininresistanceinplasmodiumfalciparumindemocraticrepublicofcongodrc AT mariepierrehayette thelackofk13propellermutationsassociatedwithartemisininresistanceinplasmodiumfalciparumindemocraticrepublicofcongodrc AT doudoumalekitayobi lackofk13propellermutationsassociatedwithartemisininresistanceinplasmodiumfalciparumindemocraticrepublicofcongodrc AT nadinekalendakayiba lackofk13propellermutationsassociatedwithartemisininresistanceinplasmodiumfalciparumindemocraticrepublicofcongodrc AT dieudonnemakabamvumbi lackofk13propellermutationsassociatedwithartemisininresistanceinplasmodiumfalciparumindemocraticrepublicofcongodrc AT raphaelboreux lackofk13propellermutationsassociatedwithartemisininresistanceinplasmodiumfalciparumindemocraticrepublicofcongodrc AT sebastienbontems lackofk13propellermutationsassociatedwithartemisininresistanceinplasmodiumfalciparumindemocraticrepublicofcongodrc AT piuszakayikabututu lackofk13propellermutationsassociatedwithartemisininresistanceinplasmodiumfalciparumindemocraticrepublicofcongodrc AT patrickdemol lackofk13propellermutationsassociatedwithartemisininresistanceinplasmodiumfalciparumindemocraticrepublicofcongodrc AT nikospeybroeck lackofk13propellermutationsassociatedwithartemisininresistanceinplasmodiumfalciparumindemocraticrepublicofcongodrc AT georgeslelomvumbi lackofk13propellermutationsassociatedwithartemisininresistanceinplasmodiumfalciparumindemocraticrepublicofcongodrc AT mariepierrehayette lackofk13propellermutationsassociatedwithartemisininresistanceinplasmodiumfalciparumindemocraticrepublicofcongodrc |