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Title: Temporal trends in molecular markers of drug resistance in Plasmodium falciparum in human blood and profiles of corresponding resistant markers in mosquito oocysts in Asembo, western Kenya
Abstract Background

Over the last two decades, the scale-up of vector control and changes in the first-line anti-malarial, from chloroquine (CQ) to sulfadoxine-pyrimethamine (SP) and then to artemether-lumefantrine (AL), have resulted in significant decreases in malaria burden in western Kenya. This study evaluated the long-term effects of control interventions on molecular markers ofPlasmodium falciparumdrug resistance using parasites obtained from humans and mosquitoes at discrete time points.

Methods

Dried blood spot samples collected in 2012 and 2017 community surveys in Asembo, Kenya were genotyped by Sanger sequencing for markers associated with resistance to SP (Pfdhfr, Pfdhps), CQ, AQ, lumefantrine (Pfcrt, Pfmdr1)and artemisinin (Pfk13).Temporal trends in the prevalence of these markers, including data from 2012 to 2017 as well as published data from 1996, 2001, 2007 from same area, were analysed. The same markers from mosquito oocysts collected in 2012 were compared with results from human blood samples.

Results

The prevalence of SPdhfr/dhpsquintuple mutant haplotype C50I51R59N108I164/S436G437E540A581A613increased from 19.7% in 1996 to 86.0% in 2012, while an increase in the sextuple mutant haplotype C50I51R59N108I164/H436G437E540A581A613containingPfdhps-436H was found from 10.5% in 2012 to 34.6% in 2017. ResistantPfcrt-76 T declined from 94.6% in 2007 to 18.3% in 2012 and 0.9% in 2017. MutantPfmdr1-86Y decreased across years from 74.8% in 1996 to zero in 2017, mutantPfmdr1-184F and wildPfmdr1-D1246 increased from 17.9% to 58.9% in 2007 to 55.9% and 90.1% in 2017, respectively.Pfmdr1haplotype N86F184S1034N1042D1246 increased from 11.0% in 2007 to 49.6% in 2017. No resistant mutations inPfk13were found. Prevalence ofPfdhps-436H was lower while prevalence ofPfcrt-76 T was higher in mosquitoes than in human blood samples.

Conclusion

This study showed an increased prevalence ofdhfr/dhpsresistant markers over 20 years with the emergenceof Pfdhps-436H mutant a decade ago in Asembo. The reversal ofPfcrtfrom CQ-resistant to CQ-sensitive genotype occurred following 19 years of CQ withdrawal. NoPfk13markers associated with artemisinin resistance were detected, but the increased haplotype ofPfmdr1N86F184S1034N1042D1246was observed. The differences in prevalence ofPfdhps-436H andPfcrt-76 T SNPs between two hosts and the role of mosquitoes in the transmission of drug resistant parasites require further investigation.

 
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NSF-PAR ID:
10371391
Author(s) / Creator(s):
; ; ; ; ; ; ; ; ; ; ; ; ; ; ;
Publisher / Repository:
Springer Science + Business Media
Date Published:
Journal Name:
Malaria Journal
Volume:
21
Issue:
1
ISSN:
1475-2875
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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