Molecular Monitoring of Plasmodium falciparum Resistance to Sulfadoxine-pyrimethamine in Western Kenya, 14 Years after its Withdrawal
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Date
2019
Authors
Kishoyian, Gabriel
Njagi, Eliud N.M
Orinda, George O
Kimani, Francis T
Thiongo, Kevin
Muhia, Damaris Matoke
Journal Title
Journal ISSN
Volume Title
Publisher
Annals of Medical and Health Sciences Research
Abstract
Background: The application of chloroquine (CQ) as an antimalarial drug for over half a century
and subsequent development of CQ-resistant Plasmodium strains has led to its withdrawal and
replacement with sulphadoxine-pyrimethamine (SP). In 2004, SP was replaced with artemisininbased combination therapy (ACT) as a first-line against uncomplicated malaria in Kenya with
SP being recommended for intermittent preventive in pregnancy (IPTp). Several mutations of
Plasmodium falciparum have been implicated in SP resistance but it is unclear if the prevalence
of these mutations is decreasing or increasing after it was restricted to expectant mothers. This
study was design to assess the current status pfdhfr and pfdhps gene mutation which encodes
enzymes targeting SP. Method: Blood from a finger prick was collected onto a filter paper from P.
falciparum positive children attending health facility in Chulaimbo between May and November
2015. Using chelex-100 extraction DNA, genotyping was done for mutations on codon 51, 59
and 108 of pfdhr and 437 and 540 of pfdhps genes using polymerase chain reaction-restriction
fragment length polymorphism (PCR-RFLP) technology. Results: All the 76 P. falciparum isolates
were successfully genotyped for the detection of Pfdhfr and Pfdhps mutations associated with SP
resistance. The P. falciparum isolates were found to carry the mutant type N51I with a prevalence
of 94% while C59R and S108N had 92% each. The prevalence of mutation at Pfdhps codons
A437G and K540E stood at 94% and 91% respectively. Conclusion: The present study observed
that there is no statistical significant on codon 51I and 437G (χ2
=3.3099 df=1 p>0.05) change in
the proportion of resistant genotypes. However, there was a statistical significant on codon 59R
and 108N (χ2
=4.338 df=1 p<0.05) and 540E (χ2
=5.391 df=1 p<0.05) indicating a slow but steady
decreased resistance despite its withdrawal. In addition, the evidence of quintuple mutations
in the study population is threatening the future of SP especially in intermittent preventive
treatment prophylaxis (IPTp) programs and also future combination with another antimalarial
drug. These findings highlight the need for continual monitoring of parasites genotypes as
indicators of therapeutic efficacy of antimalarial.
Keywords: Sulfadoxine-pyrimethamine; Drug resistance; Plasmodium falciparum; pfdhfr; pfdhps
Description
Research Article
Keywords
Sulfadoxine-pyrimethamine, Drug resistance, Plasmodium falciparum, Pfdhfr, Pfdhps
Citation
Kishoyian, G., Njagi, E. N., Orinda, G. O., Kimani, F. T., Thiongo, K., & Matoke-Muhia, D. (2019). Molecular Monitoring of Plasmodium falciparum Resistance to Sulfadoxine-pyrimethamine in Western Kenya, 14 Years after its Withdrawal. Annals of Medical and Health Sciences Research, 9(4).