Molecular surveillance of anti-malarial drug resistance in Democratic Republic of Congo: high variability of chloroquinoresistance and lack of amodiaquinoresistance
Open Access
- 20 March 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Malaria Journal
- Vol. 19 (1), 1-8
- https://doi.org/10.1186/s12936-020-03192-x
Abstract
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. 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. 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. 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.Keywords
Other Versions
This publication has 32 references indexed in Scilit:
- Molecular surveillance of Plasmodium falciparum resistance to artemisinin-based combination therapies in the Democratic Republic of CongoPLOS ONE, 2017
- Molecular surveillance of Plasmodium falciparum drug resistance in the Republic of Congo: four and nine years after the introduction of artemisinin-based combination therapyMalaria Journal, 2017
- Molecular surveillance of Plasmodium falciparum drug resistance markers reveals partial recovery of chloroquine susceptibility but sustained sulfadoxine-pyrimethamine resistance at two sites of different malaria transmission intensities in RwandaActa Tropica, 2016
- Antimalarial Drug Resistance: Literature Review and Activities and Findings of the ICEMR NetworkThe American Journal of Tropical Medicine and Hygiene, 2015
- Pfcrt haplotypes and the evolutionary history of chloroquine-resistant Plasmodium falciparumMemórias do Instituto Oswaldo Cruz, 2012
- Validation of a four-primer real-time PCR as a diagnostic tool for single and mixed Plasmodium infectionsClinical Microbiology & Infection, 2011
- Amodiaquine Resistance in Plasmodium falciparum Malaria in Afghanistan Is Associated with the pfcrt SVMNT Allele at Codons 72 to 76Antimicrobial Agents and Chemotherapy, 2010
- Resistance-mediating polymorphisms in Plasmodium falciparum infections in Kinshasa, Democratic Republic of the Congo.The American Journal of Tropical Medicine and Hygiene, 2009
- Occurrence of the Southeast Asian/South American SVMNT Haplotype of the Chloroquine‐Resistance Transporter Gene inPlasmodium falciparumin TanzaniaThe Journal of Infectious Diseases, 2006
- Withdrawing antimalarial drugs: impact on parasite resistance and implications for malaria treatment policiesDrug Resistance Updates, 2004