Molecular surveillance of Plasmodium falciparum drug resistance in the Republic of Congo: four and nine years after the introduction of artemisinin-based combination therapy
Open Access
- 19 April 2017
- journal article
- research article
- Published by Springer Science and Business Media LLC in Malaria Journal
- Vol. 16 (1), 1-7
- https://doi.org/10.1186/s12936-017-1816-x
Abstract
Resistance to anti-malarial drugs hinders efforts on malaria elimination and eradication. Following the global spread of chloroquine-resistant parasites, the Republic of Congo adopted artemisinin-based combination therapy (ACT) in 2006 as a first-line treatment for uncomplicated malaria. To assess the impacts after implementation of ACT, a molecular surveillance for anti-malarial drug resistance was conducted in Congo 4 and 9 years after the introduction of ACT. Blood samples of 431 febrile children aged 1–10 years were utilized from two previous studies conducted in 2010 (N = 311) and 2015 (N = 120). All samples were screened for malaria parasites using nested PCR. Direct sequencing was used to determine the frequency distribution of genetic variants in the anti-malarial drug-resistant Plasmodium falciparum genes (Pfcrt, Pfmdr1, Pfatp6, Pfk13) in malaria-positive isolates. One-hundred and nineteen (N = 70 from 2010 and N = 49 from 2015) samples were positive for P. falciparum. A relative decrease in the proportion of chloroquine-resistant haplotype (CVIET) from 100% in 2005, 1 year before the introduction and implementation of ACT in 2006, to 98% in 2010 to 71% in 2015 was observed. Regarding the multidrug transporter gene, a considerable reduction in the frequency of the mutations N86Y (from 73 to 27%) and D1246Y (from 22 to 0%) was observed. However, the prevalence of the Y184F mutation remained stable (49% in 2010 compared to 54% in 2015). Isolates carrying the Pfatp6 H243Y was 25% in 2010 and this frequency was reduced to null in 2015. None of the parasites harboured the Pfk13 mutations associated with prolonged artemisinin clearance in Southeast Asia. Nevertheless, 13 new Pfk13 variants are reported among the investigated isolates. The implementation of ACT has led to the decline in prevalence of chloroquine-resistant parasites in the Republic of Congo. However, the constant prevalence of the PfMDR1 Y184F mutation, associated with lumefantrine susceptibility, indicate a selective drug pressure still exists. Taken together, this study could serve as the basis for epidemiological studies monitoring the distribution of molecular markers of artemisinin resistance in the Republic of Congo.Keywords
Funding Information
- European and Developing Countries Clinical Trials Partnership (CANTAM, CANTAM, CANTAM)
This publication has 42 references indexed in Scilit:
- Two Techniques for Simultaneous Identification of Plasmodium ovale curtisi and Plasmodium ovale wallikeri by Use of the Small-Subunit rRNA GeneJournal of Clinical Microbiology, 2012
- Molecular assessment of atpase6 mutations associated with artemisinin resistance among unexposed and exposed Plasmodium falciparum clinical isolates to artemisinin-based combination therapyMalaria Journal, 2012
- Genetic polymorphism of merozoite surface protein 2 and prevalence of K76T pfcrt mutation in Plasmodium falciparum field isolates from Congolese children with asymptomatic infectionsMalaria Journal, 2012
- Spontaneous Mutations in the Plasmodium falciparum Sarcoplasmic/ Endoplasmic Reticulum Ca 2+ -ATPase (PfATP6) Gene among Geographically Widespread Parasite Populations Unexposed to Artemisinin-Based Combination TherapiesAntimicrobial Agents and Chemotherapy, 2011
- Investigations into the Role of the Plasmodium falciparum SERCA (PfATP6) L263E Mutation in Artemisinin Action and ResistanceAntimicrobial Agents and Chemotherapy, 2010
- In Vitro Activities of Piperaquine, Lumefantrine, and Dihydroartemisinin in Kenyan Plasmodium falciparum Isolates and Polymorphisms in p fcrt and p fmdr1Antimicrobial Agents and Chemotherapy, 2009
- A systematic review and meta-analysis of evidence for correlation between molecular markers of parasite resistance and treatment outcome in falciparum malariaMalaria Journal, 2009
- World Antimalarial Resistance Network (WARN) III: Molecular markers for drug resistant malariaMalaria Journal, 2007
- Transporters involved in resistance to antimalarial drugsTrends in Pharmacological Sciences, 2006
- Artemisinins target the SERCA of Plasmodium falciparumNature, 2003