Temporal trends in prevalence of Plasmodium falciparum molecular markers selected for by artemether–lumefantrine treatment in pre-ACT and post-ACT parasites in western Kenya

Autor: Luicer A. Ingasia, Bernhards Ogutu, Peninah Muiruri, Hoseah M. Akala, Benjamin Opot, Redemptah Yeda, Angela O. Achieng, Ben Andagalu, Bidii S. Ngalah, Dennis W. Juma, Edwin Kamau
Jazyk: angličtina
Předmět:
Veterinary medicine
Artemether/lumefantrine
Time Factors
Plasmodium falciparum
Protozoan Proteins
Lumefantrine
Article
lcsh:Infectious and parasitic diseases
chemistry.chemical_compound
Artemisinin-based combination therapies
Polymorphism (computer science)
Genotype
parasitic diseases
medicine
Genetics
Parasite hosting
Humans
Pharmacology (medical)
lcsh:RC109-216
Artemether
Malaria
Falciparum
Selection
Genetic
Western Kenya
Drug-resistance
Pharmacology
Fluorenes
biology
Haplotype
Artemether
Lumefantrine Drug Combination
Membrane Transport Proteins
Molecular markers
Chloroquine
biology.organism_classification
Kenya
Artemisinins
Drug Combinations
Infectious Diseases
chemistry
Gene Expression Regulation
Haplotypes
Ethanolamines
Africa
Parasitology
Multidrug Resistance-Associated Proteins
Artemether–lumefantrine
Biomarkers
medicine.drug
Zdroj: International Journal for Parasitology: Drugs and Drug Resistance, Vol 5, Iss 3, Pp 92-99 (2015)
International Journal for Parasitology: Drugs and Drug Resistance
ISSN: 2211-3207
DOI: 10.1016/j.ijpddr.2015.05.005
Popis: Artemether–lumefantrine (AL) became the first-line treatment for uncomplicated malaria in Kenya in 2006. Studies have shown AL selects for SNPs in pfcrt and pfmdr1 genes in recurring parasites compared to the baseline infections. The genotypes associated with AL selection are K76 in pfcrt and N86, 184F and D1246 in pfmdr1. To assess the temporal change of these genotypes in western Kenya, 47 parasite isolates collected before (pre-ACT; 1995–2003) and 745 after (post-ACT; 2008–2014) introduction of AL were analyzed. In addition, the associations of parasite haplotype against the IC50 of artemether and lumefantrine, and clearance rates were determined. Parasite genomic DNA collected between 1995 and 2014 was analyzed by sequencing or PCR-based single-base extension on Sequenom MassARRAY. IC50s were determined for a subset of the samples. One hundred eighteen samples from 2013 to 2014 were from an efficacy trial of which 68 had clearance half-lives. Data revealed there were significant differences between pre-ACT and post-ACT genotypes at the four codons (chi-square analysis; p
Graphical abstract
Highlights • The prevalence of pfcrt K76 increased from 6.4% in 1995 to 93.2% in 2014 and pfmdr1 N86 from 0% in 2002 to 92.4% in 2014. • 100% of pre-ACTs parasites carried T+YYY haplotype whereas 99.3% post-ACTs parasites carried K+NFD haplotype. • There is resurgence of chloroquine sensitive parasite in western Kenya. • AL is still highly efficacious but there are drastic genetic changes taking place in the parasite population.
Databáze: OpenAIRE
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