Impacts of antimalarial drugs on plasmodium falciparum drug resistance markers, Western Kenya, 2003-2015

Elizabeth Hemming-Schroeder, Emuejevuoke Umukoro, Eugenia Lo, Becky Fung, Pedro Tomás-Domingo, Guofa Zhou, Daibin Zhong, Amruta Dixit, Harrysone Atieli, Andrew Githeko, Anne Vardo-Zalik, Guiyun Yan

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Antimalarial drug resistance has threatened global malaria control since chloroquine (CQ)-resistant Plasmodium falciparum emerged in Asia in the 1950s. Understanding the impacts of changing antimalarial drug policy on resistance is critical for resistance management. Plasmodium falciparum isolates were collected from 2003 to 2015 in western Kenya and analyzed for genetic markers associated with resistance to CQ (Pfcrt), sulfadoxine-pyrimethamine (SP) (Pfdhfr/Pfdhps), and artemether-lumefantrine (AL) (PfKelch13/Pfmdr1) antimalarials. In addition, household antimalarial drug use surveys were administered. Pfcrt 76T prevalence decreased from 76% to 6% from 2003 to 2015. Pfdhfr/ Pfdhps quintuple mutants decreased from 70% in 2003 to 14% in 2008, but increased to near fixation by 2015. SP “super resistant” alleles Pfdhps 581G and 613S/T were not detected in the 2015 samples that were assessed. The Pfmdr1 N86-184F-D1246 haplotype associated with decreased lumefantrine susceptibility increased significantly from 4% in 2005 to 51% in 2015. No PfKelch13 mutations that have been previously associated with artemisinin resistance were detected in the study populations. The increase in Pfdhfr/Pfdhps quintuple mutants that associates with SP resistance may have resulted from the increased usage of SP for intermittent preventative therapy in pregnancy (IPTp) and for malaria treatment in the community. Prevalent Pfdhfr/Pfdhps mutations call for careful monitoring of SP resistance and effectiveness of the current IPTp program in Kenya. In addition, the commonly occurring Pfmdr1 N86-184F-D1246 haplotype associated with increased lumefantrine tolerance calls for surveillance of AL efficacy in Kenya, as well as consideration for a rotating artemisinin-combination therapy regimen.

Original languageEnglish (US)
Pages (from-to)692-699
Number of pages8
JournalAmerican Journal of Tropical Medicine and Hygiene
Volume98
Issue number3
DOIs
StatePublished - Jan 1 2018

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Kenya
Antimalarials
Plasmodium falciparum
Drug Resistance
Chloroquine
Haplotypes
Malaria
Pregnancy
Mutation
Genetic Markers
Therapeutics
Alleles
pyrimethamine drug combination fanasil
lumefantrine
Population
artemisinine
artemether

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Infectious Diseases
  • Virology

Cite this

Hemming-Schroeder, Elizabeth ; Umukoro, Emuejevuoke ; Lo, Eugenia ; Fung, Becky ; Tomás-Domingo, Pedro ; Zhou, Guofa ; Zhong, Daibin ; Dixit, Amruta ; Atieli, Harrysone ; Githeko, Andrew ; Vardo-Zalik, Anne ; Yan, Guiyun. / Impacts of antimalarial drugs on plasmodium falciparum drug resistance markers, Western Kenya, 2003-2015. In: American Journal of Tropical Medicine and Hygiene. 2018 ; Vol. 98, No. 3. pp. 692-699.
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abstract = "Antimalarial drug resistance has threatened global malaria control since chloroquine (CQ)-resistant Plasmodium falciparum emerged in Asia in the 1950s. Understanding the impacts of changing antimalarial drug policy on resistance is critical for resistance management. Plasmodium falciparum isolates were collected from 2003 to 2015 in western Kenya and analyzed for genetic markers associated with resistance to CQ (Pfcrt), sulfadoxine-pyrimethamine (SP) (Pfdhfr/Pfdhps), and artemether-lumefantrine (AL) (PfKelch13/Pfmdr1) antimalarials. In addition, household antimalarial drug use surveys were administered. Pfcrt 76T prevalence decreased from 76{\%} to 6{\%} from 2003 to 2015. Pfdhfr/ Pfdhps quintuple mutants decreased from 70{\%} in 2003 to 14{\%} in 2008, but increased to near fixation by 2015. SP “super resistant” alleles Pfdhps 581G and 613S/T were not detected in the 2015 samples that were assessed. The Pfmdr1 N86-184F-D1246 haplotype associated with decreased lumefantrine susceptibility increased significantly from 4{\%} in 2005 to 51{\%} in 2015. No PfKelch13 mutations that have been previously associated with artemisinin resistance were detected in the study populations. The increase in Pfdhfr/Pfdhps quintuple mutants that associates with SP resistance may have resulted from the increased usage of SP for intermittent preventative therapy in pregnancy (IPTp) and for malaria treatment in the community. Prevalent Pfdhfr/Pfdhps mutations call for careful monitoring of SP resistance and effectiveness of the current IPTp program in Kenya. In addition, the commonly occurring Pfmdr1 N86-184F-D1246 haplotype associated with increased lumefantrine tolerance calls for surveillance of AL efficacy in Kenya, as well as consideration for a rotating artemisinin-combination therapy regimen.",
author = "Elizabeth Hemming-Schroeder and Emuejevuoke Umukoro and Eugenia Lo and Becky Fung and Pedro Tom{\'a}s-Domingo and Guofa Zhou and Daibin Zhong and Amruta Dixit and Harrysone Atieli and Andrew Githeko and Anne Vardo-Zalik and Guiyun Yan",
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Hemming-Schroeder, E, Umukoro, E, Lo, E, Fung, B, Tomás-Domingo, P, Zhou, G, Zhong, D, Dixit, A, Atieli, H, Githeko, A, Vardo-Zalik, A & Yan, G 2018, 'Impacts of antimalarial drugs on plasmodium falciparum drug resistance markers, Western Kenya, 2003-2015', American Journal of Tropical Medicine and Hygiene, vol. 98, no. 3, pp. 692-699. https://doi.org/10.4269/ajtmh.17-0763

Impacts of antimalarial drugs on plasmodium falciparum drug resistance markers, Western Kenya, 2003-2015. / Hemming-Schroeder, Elizabeth; Umukoro, Emuejevuoke; Lo, Eugenia; Fung, Becky; Tomás-Domingo, Pedro; Zhou, Guofa; Zhong, Daibin; Dixit, Amruta; Atieli, Harrysone; Githeko, Andrew; Vardo-Zalik, Anne; Yan, Guiyun.

In: American Journal of Tropical Medicine and Hygiene, Vol. 98, No. 3, 01.01.2018, p. 692-699.

Research output: Contribution to journalArticle

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AU - Hemming-Schroeder, Elizabeth

AU - Umukoro, Emuejevuoke

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AU - Fung, Becky

AU - Tomás-Domingo, Pedro

AU - Zhou, Guofa

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AU - Dixit, Amruta

AU - Atieli, Harrysone

AU - Githeko, Andrew

AU - Vardo-Zalik, Anne

AU - Yan, Guiyun

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