Sulfadoxine-resistant Plasmodium falciparum undermines malaria prevention with sulfadoxine/pyrimethamine. Parasites with a highly resistant mutant dihydropteroate synthase (dhps) haplotype have recently emerged in eastern Africa; they negated preventive benefits of sulfadoxine/pyrimethamine, and might exacerbate placental malaria. We explored emerging lineages of dhps mutant haplotypes in Malawi, the Democratic Republic of the Congo, and Tanzania by using analyses of genetic microsatellites flanking the dhps locus. In Malawi, a triple-mutant dhps SGEG (mutant amino acids are underlined) haplotype emerged in 2010 that was closely related to pre-existing double-mutant SGEA haplotypes, suggesting local origination in Malawi. When we compared mutant strains with parasites from the Democratic Republic of the Congo and Tanzania by multiple independent analyses, we found that SGEG parasites were partitioned into separate lineages by country. These findings support a model of local origination of SGEG dhps haplotypes, rather than geographic diffusion, and have implications for investigations of emergence and effects of parasite drug resistance.
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http://dx.doi.org/10.3201/eid2007.131720 | DOI Listing |
Molecules
October 2023
Natural Product and Environmental Chemistry Group (NAPEC), Department of Chemistry, Higher Teachers' Training College, University of Maroua, Maroua P.O. Box 55, Cameroon.
Metabolites
February 2023
Department of Chemistry, Faculty of Science, University of Dschang, Dschang P.O. Box 67, Cameroon.
The chemical investigation of the EtOH extract from the stem bark of (Thonn.) J. J.
View Article and Find Full Text PDFMaterials (Basel)
November 2021
Division of Pharmacy and Optometry, School of Health Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
Erythromycin A is an established anti-bacterial agent against Gram-positive bacteria, but it is unstable to acid. This led to an evaluation of erythromycin B and its derivatives because these have improved acid stability. These compounds were investigated for their anti-malarial activities, by their molecular docking into segments of the exit tunnel of the apicoplast ribosome from .
View Article and Find Full Text PDFActa Trop
October 2021
Department of Tropical Medicine and Parasitology, Faculty of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan. Electronic address:
Genetic changes conferring drug resistance are generally believed to impose fitness costs to pathogens in the absence of the drug. However, the fitness of resistant parasites against sulfadoxine/pyrimethamine has been inconclusive in Plasmodium falciparum. This is because resistance is conferred by the complex combination of mutations in dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr), which makes it difficult to separately assess the extent and magnitude of the costs imposed by mutations in dhps and dhfr.
View Article and Find Full Text PDFMalar J
February 2021
Malaria Branch, Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Background: In 2004, in response to high levels of treatment failure associated with sulfadoxine-pyrimethamine (SP) resistance, Benin changed its first-line malaria treatment from SP to artemisinin-based combination therapy for treatment of uncomplicated Plasmodium falciparum malaria. Resistance to SP is conferred by accumulation of single nucleotide polymorphisms (SNPs) in P. falciparum genes involved in folate metabolism, dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps), targeted by pyrimethamine and sulfadoxine, respectively.
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