| Autor: |
Fola AA; Department of Biological Sciences, Purdue University, West Lafayette, IN, USA.; Department of Pathology and Laboratory Medicine, Brown University, Providence, RI 02903, USA., Ciubotariu II; Department of Biological Sciences, Purdue University, West Lafayette, IN, USA.; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA., Dorman J; Department of Biological Sciences, Purdue University, West Lafayette, IN, USA., Mwenda MC; PATH Malaria Control and Elimination Partnership in Africa (MACEPA), Lusaka, Zambia., Mambwe B; PATH Malaria Control and Elimination Partnership in Africa (MACEPA), Lusaka, Zambia., Mulube C; PATH Malaria Control and Elimination Partnership in Africa (MACEPA), Lusaka, Zambia., Kasaro R; PATH Malaria Control and Elimination Partnership in Africa (MACEPA), Lusaka, Zambia., Hawela MB; National Malaria Elimination Centre, Zambia Ministry of Health, Chainama Hospital Grounds, Lusaka, Zambia., Hamainza B; National Malaria Elimination Centre, Zambia Ministry of Health, Chainama Hospital Grounds, Lusaka, Zambia., Miller JM; PATH Malaria Control and Elimination Partnership in Africa (MACEPA), Lusaka, Zambia., Bailey JA; Department of Pathology and Laboratory Medicine, Brown University, Providence, RI 02903, USA., Moss WJ; The Johns Hopkins Malaria Research Institute, W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA., Bridges DJ; PATH Malaria Control and Elimination Partnership in Africa (MACEPA), Lusaka, Zambia., Carpi G; Department of Biological Sciences, Purdue University, West Lafayette, IN, USA.; The Johns Hopkins Malaria Research Institute, W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. |
| Abstrakt: |
The emergence of antimalarial drug resistance is a major threat to malaria control and elimination. Using whole genome sequencing of 282 P. falciparum samples collected during the 2018 Zambia National Malaria Indicator Survey, we determined the prevalence and spatial distribution of known and candidate antimalarial drug resistance mutations. High levels of genotypic resistance were found across Zambia to pyrimethamine, with over 94% (n=266) of samples having the Pfdhfr triple mutant (N51 I , C59 R , and S108 N ), and sulfadoxine, with over 84% (n=238) having the Pfdhps double mutant (A437 G and K540 E ). In northern Zambia, 5.3% (n=15) of samples also harbored the Pfdhps A581 G mutation. Although 29 mutations were identified in Pfkelch13 , these mutations were present at low frequency (<2.5%), and only three were WHO-validated artemisinin partial resistance mutations: P441 L (n=1, 0.35%), V568 M (n=2, 0.7%) and R622 T (n=1, 0.35%). Notably, 91 (32%) of samples carried the E431 K mutation in the Pfatpase6 gene, which is associated with artemisinin resistance. No specimens carried any known mutations associated with chloroquine resistance in the Pfcrt gene (codons 72-76). P. falciparum strains circulating in Zambia were highly resistant to sulfadoxine and pyrimethamine but remained susceptible to chloroquine and artemisinin. Despite this encouraging finding, early genetic signs of developing artemisinin resistance highlight the urgent need for continued vigilance and expanded routine genomic surveillance to monitor these changes. |
