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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
- 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.
- Subjects :
- lcsh:Arctic medicine. Tropical medicine
Combination therapy
lcsh:RC955-962
030231 tropical medicine
Genes, Protozoan
Plasmodium falciparum
Drug Resistance
Protozoan Proteins
Drug resistance
Biology
Pfk13
Parasitemia
law.invention
lcsh:Infectious and parasitic diseases
03 medical and health sciences
Antimalarials
0302 clinical medicine
Pfpm2
law
parasitic diseases
medicine
Prevalence
Anti-malarial drug resistance
Humans
lcsh:RC109-216
030212 general & internal medicine
Copy-number variation
Artemisinin
Malaria, Falciparum
Polymerase chain reaction
Pfmdr1
Pfcrt
Research
Infant
biology.organism_classification
Virology
Kenya
Multiple drug resistance
Infectious Diseases
Parasitology
Child, Preschool
Biomarkers
medicine.drug
Subjects
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