Polymorphisms in Plasmodium Falciparum Dihydropteroate Synthetase and Dihydrofolate Reductase Genes in Nigerian Children with Uncomplicated Malaria using High‑Resolution Melting Technique
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Date
2021-01-12
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Scientifc Reports
Abstract
In 2005, the Nigerian Federal Ministry of Health revised the treatment policy for uncomplicated
malaria with the introduction of artemisinin-based combination therapies (ACTs). This policy
change discouraged the use of Sulphadoxine-pyrimethamine (SP) as the second-line treatment of
uncomplicated falciparum malaria. However, SP is used as an intermittent preventive treatment
of malaria in pregnancy (IPTp) and seasonal malaria chemoprevention (SMC) in children aged
3–59 months. There have been increasing reports of SP resistance especially in the non-pregnant
population in Nigeria, thus, the need to continually monitor the efcacy of SP as IPTp and SMC by
estimating polymorphisms in dihydropteroate synthetase (dhps) and dihydrofolate reductase (dhfr)
genes associated with SP resistance. The high resolution-melting (HRM) assay was used to investigate
polymorphisms in codons 51, 59, 108 and 164 of the dhfr gene and codons 437, 540, 581 and 613
of the dhps gene. DNA was extracted from 271 dried bloodspot flter paper samples obtained from
children (<5 years old) with uncomplicated malaria. The dhfr triple mutant I51R59N108, dhps double
mutant G437G581 and quadruple dhfr I51R59N108 +dhpsG437 mutant haplotypes were observed in 80.8%,
13.7% and 52.8% parasites, respectively. Although the quintuple dhfr I51R59N108 +dhpsG437E540 and
sextuple dhfr I51R59N108 +dhpsG437E540G581 mutant haplotypes linked with in-vivo and in-vitro SP
resistance were not detected, constant surveillance of these haplotypes should be done in the country
to detect any change in prevalence.