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Assessment of molecular markers of anti-malarial drug resistance among children participating in a therapeutic efficacy study in western Kenya

Assessment of molecular markers of anti-malarial drug resistance among children participating in a therapeutic efficacy study in western Kenya

Authors :
Ya Ping Shi
Winnie Chebore
Simon Kariuki
Venkatachalam Udhayakumar
Benard Guyah
Kelsey Anne Rondini
Samaly S. Svigel
Sheila Sergent
Kephas Otieno
Aaron M. Samuels
Eric S. Halsey
Nelli Westercamp
Zhiyong Zhou
Source :
Malaria Journal, Vol 19, Iss 1, Pp 1-12 (2020), Malaria Journal
Publication Year :
2020
Publisher :
BMC, 2020.

Abstract

BackgroundAnti-malarial drug resistance remains a major threat to global malaria control efforts. In Africa,Plasmodium falciparumremains susceptible to artemisinin-based combination therapy (ACT), but the emergence of resistant parasites in multiple countries in Southeast Asia and concerns over emergence and/or spread of resistant parasites in Africa warrants continuous monitoring. The World Health Organization recommends that surveillance for molecular markers of resistance be included within therapeutic efficacy studies (TES). The current study assessed molecular markers associated with resistance to Artemether−lumefantrine (AL) and Dihydroartemisinin−piperaquine (DP) from samples collected from children aged 6–59 months enrolled in a TES conducted in Siaya County, western Kenya from 2016 to 2017.MethodsThree hundred and twenty-three samples collected pre-treatment (day-0) and 110 samples collected at the day of recurrent parasitaemia (up to day 42) were tested for the presence of drug resistance markers in thePfk13propeller domain, and thePfmdr1andPfcrtgenes by Sanger sequencing. Additionally, thePfpm2gene copy number was assessed by real-time polymerase chain reaction.ResultsNo mutations previously associated with artemisinin resistance were detected in thePfk13propeller region. However, other non-synonymous mutations in thePfk13propeller region were detected. The most common mutation found on day-0 and at day of recurrence in thePfmdr1multidrug resistance marker was at codon 184F. Very few mutations were found in thePfcrtmarker (Pfpm2gene copy number had a single gene copy. None of the associations between observed mutations and treatment outcomes were statistically significant.ConclusionThe results indicate absence ofPfk13mutations associated with parasite resistance to artemisinin in this area and a very high proportion of wild-type parasites forPfcrt. Although the frequency ofPfmdr1184Fmutations was high in these samples, the association with treatment failure did not reach statistical significance. As the spread of artemisinin-resistant parasites remains a possibility, continued monitoring for molecular markers of ACT resistance is needed to complement clinical data to inform treatment policy in Kenya and other malaria-endemic regions.

Details

Language :
English
ISSN :
14752875
Volume :
19
Issue :
1
Database :
OpenAIRE
Journal :
Malaria Journal
Accession number :
edsair.doi.dedup.....cef9504b00d6545486113cdd84b0f677
Full Text :
https://doi.org/10.1186/s12936-020-03358-7