Abstract
BackgroundA reversal of chloroquine (CQ) resistance following a period of withdrawal has raised the possibility of its re-introduction. This study evaluated the current prevalence of Pfcrt and Pfmdr1 alleles in Plasmodium falciparum isolates, 11 years after CQ withdrawal in Southeast Nigeria.MethodsFilter-paper blood samples were collected from 725 non-febrile individuals, comprising 250 children (≤ 12 years), 250 pregnant women and 225 other adults, between October 2014 and February 2015 in Nnewi town, Southeast Nigeria. Nested PCR followed by direct sequencing was employed for the genotyping of Pfcrt and Pfmdr1 genes.ResultsA total of 103 parasites-positive samples were recovered, comprising of 48 (19.20%) among children, 20 (20.00%) among pregnant women and 35 (15.50%) among other adults cohort. The frequency of the mutant genotype of Pfcrt 76T, 75E and 74I was 94.50% each. Parasite isolates from children had a frequency of 100% for mutant alleles in all Pfcrt codons while isolates from pregnant women and other adults had a frequency of 91% each in all codons. Haplotype distribution of pfcrt gene were 5.45, 0.00 and 76.37% for CVMNK, SVMNT and CVIET, respectively. For Pfmdr1 gene, the frequency of 86Y, 184F and 1246Y mutant alleles were 8.54, 29.27 and 3.66%, respectively. Amongst the Pfmdr1 haplotypes analysed, NFD had the highest frequency of 24.4%, followed by YFD at 6.10%. NYF and NYY occurred the least (1.20%).ConclusionThe high level of Pfcrt mutations is suggestive of a sustained CQ pressure on P. falciparum isolates in the study area, despite the change of first line treatment from CQ to artemisinin combination therapy for 11 years. A new strategy to ensure the complete withdrawal of CQ from the country is recommended.
Highlights
A reversal of chloroquine (CQ) resistance following a period of withdrawal has raised the possibility of its re-introduction
Drug resistance in Plasmodium falciparum has led to a major setback in the control and eradication of malaria across the globe, including Nigeria [1, 2]
The current study investigated the prevalence of Plasmodium falciparum CQ resistance transporter (Pfcrt) and Pfmdr1 alleles that have been recognized as CQ markers in P. falciparum isolates collected from asymptomatic individuals eleven years after withdrawal of CQ
Summary
A reversal of chloroquine (CQ) resistance following a period of withdrawal has raised the possibility of its re-introduction. This study evaluated the current prevalence of Pfcrt and Pfmdr alleles in Plasmodium falciparum isolates, 11 years after CQ withdrawal in Southeast Nigeria. Drug resistance in Plasmodium falciparum has led to a major setback in the control and eradication of malaria across the globe, including Nigeria [1, 2]. The emergence of CQresistant malaria parasites, first reported in Southeast Asia along the Thai-Cambodian border during the late 1950s, and spread across the globe, has greatly hampered the usefulness of this drug [4]. Published reports have shown that the switch from CQ to ACT in areas where CQ-resistant P. falciparum is prevalent has resulted in the re-emergence of CQ-sensitive strains, a few years after the cessation of CQ use [7], some other studies have reported otherwise [8, 9]
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