A barcode of multilocus nuclear DNA identifies genetic relatedness in pre- and post-Artemether/Lumefantrine treated Plasmodium falciparum in Nigeria.

Autor: Oyebola KM; Medical Research Council Unit of The London School of Hygiene and Tropical Medicine, Bakau, The Gambia. oyebolakolapo@yahoo.com.; Parasitology and Bioinformatics, Department of Zoology, Faculty of Science, University of Lagos, Lagos, Nigeria. oyebolakolapo@yahoo.com.; West African Centre for Cell Biology of Infectious Pathogens, College of Basic and Applied Sciences, University of Ghana, Legon, Accra, Ghana. oyebolakolapo@yahoo.com., Aina OO; Malaria Research Group, Nigerian Institute of Medical Research, Lagos, Nigeria., Idowu ET; Parasitology and Bioinformatics, Department of Zoology, Faculty of Science, University of Lagos, Lagos, Nigeria., Olukosi YA; Parasitology and Bioinformatics, Department of Zoology, Faculty of Science, University of Lagos, Lagos, Nigeria.; Malaria Research Group, Nigerian Institute of Medical Research, Lagos, Nigeria., Ajibaye OS; Malaria Research Group, Nigerian Institute of Medical Research, Lagos, Nigeria., Otubanjo OA; Parasitology and Bioinformatics, Department of Zoology, Faculty of Science, University of Lagos, Lagos, Nigeria., Awolola TS; Malaria Research Group, Nigerian Institute of Medical Research, Lagos, Nigeria., Awandare GA; West African Centre for Cell Biology of Infectious Pathogens, College of Basic and Applied Sciences, University of Ghana, Legon, Accra, Ghana., Amambua-Ngwa A; Medical Research Council Unit of The London School of Hygiene and Tropical Medicine, Bakau, The Gambia.
Jazyk: angličtina
Zdroj: BMC infectious diseases [BMC Infect Dis] 2018 Aug 13; Vol. 18 (1), pp. 392. Date of Electronic Publication: 2018 Aug 13.
DOI: 10.1186/s12879-018-3314-3
Abstrakt: Background: The decline in the efficacy of artemisinin-based combination treatment (ACT) in some endemic regions threatens the progress towards global elimination of malaria. Molecular surveillance of drug resistance in malaria-endemic regions is vital to detect the emergence and spread of mutant strains.
Methods: We observed 89 malaria patients for the efficacy of artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum infections in Lagos, Nigeria and determined the prevalence of drug resistant strains in the population. Parasite clearance rates were determined by microscopy and the highly sensitive var gene acidic terminal sequence (varATS) polymerase chain reaction for 65 patients with samples on days 0, 1, 3, 7, 14, 21 and 28 after commencement of treatment. The genomic finger print of parasite DNA from pre- and post-treatment samples were determined using 24 nuclear single nucleotide polymorphisms (SNP) barcode for P. falciparum. Drug resistance associated alleles in chloroquine resistance transporter gene (crt-76), multidrug resistance genes (mdr1-86 and mdr1-184), dihydropteroate synthase (dhps-540), dihydrofolate reductase (dhfr-108) and kelch domain (K-13580) were genotyped by high resolution melt analysis of polymerase chain reaction (PCR) fragments.
Results: By varATS qPCR, 12 (18.5%) of the participants had detectable parasite DNA in their blood three days after treatment, while eight (12.3%) individuals presented with genotypable day 28 parasitaemia. Complexity of infection (CoI) was 1.30 on day 0 and 1.34 on day 28, the mean expected heterozygosity (H E ) values across all barcodes were 0.50 ± 0.05 and 0.56 ± 0.05 on days 0 and 28 respectively. Barcode (π) pairwise comparisons showed high genetic relatedness of day 0 and day 28 parasite isolates in three (37.5%) of the eight individuals who presented with re-appearing infections. Crt-76 mutant allele was present in 38 (58.5%) isolates. The mdr1-86 mutant allele was found in 56 (86.2%) isolates. No mutation in the K-13580 was observed.
Conclusions: Persistence of DNA-detectable parasitaemia in more than 18% of cases after treatment and indications of genetic relatedness between pre- and post-treatment infections warrants further investigation of a larger population for signs of reduced ACT efficacy in Nigeria.
Databáze: MEDLINE
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