학술논문

Changing Molecular Markers of Antimalarial Drug Sensitivity across Uganda.
Document Type
article
Source
Antimicrobial Agents and Chemotherapy. 63(3)
Subject
Medical Microbiology
Biomedical and Clinical Sciences
Clinical Sciences
Malaria
Vector-Borne Diseases
Rare Diseases
Genetics
Antimicrobial Resistance
Orphan Drug
Infectious Diseases
HIV/AIDS
5.1 Pharmaceuticals
Development of treatments and therapeutic interventions
Infection
Good Health and Well Being
Antimalarials
Artemether
Lumefantrine Drug Combination
Artemisinins
Aspartic Acid Endopeptidases
Child
Chloroquine
Drug Resistance
Folic Acid Antagonists
Humans
Lumefantrine
Malaria
Falciparum
Membrane Transport Proteins
Multidrug Resistance-Associated Proteins
Plasmodium falciparum
Polymorphism
Single Nucleotide
Protozoan Proteins
Quinolines
Uganda
antimalarial drug sensitivity
molecular markers
Microbiology
Pharmacology and Pharmaceutical Sciences
Medical microbiology
Pharmacology and pharmaceutical sciences
Language
Abstract
The potential spread of antimalarial drug resistance to Africa, in particular for artemisinins and key partner drugs, is a major concern. We surveyed Plasmodium falciparum genetic markers associated with drug sensitivity on 3 occasions at ∼6-month intervals in 2016 and 2017 at 10 sites representing a range of epidemiological settings in Uganda. For putative drug transporters, we found continued evolution toward wild-type sequences associated with increased sensitivity to chloroquine. For pfcrt K76T, by 2017 the prevalence of the wild type was >60% at all sites and >90% at 6 sites. For the pfmdr1 N86Y and D1246Y alleles, wild type prevalence ranged from 80 to 100%. We found low prevalence of K13 propeller domain mutations, which are associated with artemisinin resistance in Asia, but one mutation previously identified in northern Uganda, 675V, was seen in 2.0% of samples, including 5.5% of those from the 3 northernmost sites. Amplification of the pfmdr1 and plasmepsin2 genes, associated elsewhere with decreased sensitivity to lumefantrine and piperaquine, respectively, was seen in