Polymorphisms in Plasmodium falciparum chloroquine resistance transporter (Pfcrt) and multidrug-resistant gene 1 (Pfmdr-1) in Nigerian children 10 years post-adoption of artemisinin-based combination treatments

Kayode, Adeyemi T.; Akano, Kazeem; Ajogbasile, Fehintola V.; Uwanibe, Jessica N.; Oluniyi, Paul E.; Bankole, Bolajoko E.; Eromon, Philomena; Sowunmi, A.; Folarin, Onikepe A.; Volkman, Sarah K.; McInnis, Bronwyn; Sabeti, Pardis C.; Wirth, Dyann F.; Happi, Christian

doi:10.1016/j.ijpara.2020.10.001

Cited by 8 publications

(9 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…falciparum multidrug resistant gene-1 ( pfmdr1 ) and P . falciparum chloroquine resistance transporter ( pfcrt ) gene have been linked to resistance in artemisinin (and derivatives) partner drugs such as lumefantrine, amodiaquine, mefloquine and piperaquine [ 13 – 18 ]. Due to these mutations, the efficacy of ACTs may be compromised [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular profiling of the artemisinin resistance Kelch 13 gene in Plasmodium falciparum from Nigeria

et al. 2022

Self Cite

View full text Add to dashboard Cite

Accurate assessment and monitoring of the Plasmodium falciparum Kelch 13 (pfk13) gene associated with artemisinin resistance is critical to understand the emergence and spread of drug-resistant parasites in malaria-endemic regions. In this study, we evaluated the genomic profile of the pfk13 gene associated with artemisinin resistance in P. falciparum in Nigerian children by targeted sequencing of the pfk13 gene. Genomic DNA was extracted from 332 dried blood (DBS) spot filter paper samples from three Nigerian States. The pfk13 gene was amplified by nested polymerase chain reaction (PCR), and amplicons were sequenced to detect known and novel polymorphisms across the gene. Consensus sequences of samples were mapped to the reference gene sequence obtained from the National Center for Biotechnology Information (NCBI). Out of the 13 single nucleotide polymorphisms (SNPs) detected in the pfk13 gene, five (F451L, N664I, V487E, V692G and Q661H) have not been reported in other endemic countries to the best of our knowledge. Three of these SNPs (V692G, N664I and Q661H) and a non-novel SNP, C469C, were consistent with late parasitological failure (LPF) in two States (Enugu and Plateau States). There was no validated mutation associated with artemisinin resistance in this study. However, a correlation of our study with in vivo and in vitro phenotypes is needed to establish the functional role of detected mutations as markers of artemisinin resistance in Nigeria. This baseline information will be essential in tracking and monitoring P. falciparum resistance to artemisinin in Nigeria.

show abstract

Section: Introductionmentioning

confidence: 99%

Molecular profiling of the artemisinin resistance Kelch 13 gene in Plasmodium falciparum from Nigeria

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…For example, to supplement slide microscopy, molecular detection assays on DNA from dried blood spots would offer more highly sensitive and specific detection of infection, and would improve detection of rarer malaria parasite species that tend to occur as coinfections along with P. falciparum. The same samples could be used for monitoring of antimalarial drug resistance allele frequency changes, which will be a vital part of resistance management to direct policy on drugs to be used for antimalarial therapy 32 33 as well as other drugs for targeted prevention by SMC for young children 27 34 and intermittent preventive treatment for pregnant women 34-36 and potentially for infants. The benefits of such additional survey measures would become increasingly apparent over time, given the incremental value of repeated surveys that apply standardised laboratory methods as illustrated here.…”

Section: Discussionmentioning

confidence: 99%

Geographical and temporal variation in reduction of malaria infection among children under five years of age throughout Nigeria

Oyibo

Ntadom

Uhomoibhi

et al. 2021

Preprint

View full text Add to dashboard Cite

BackgroundGlobal progress in reducing malaria has stalled since 2015. Analysis of the situation is particularly needed in Nigeria, the country with by far the largest share of the burden, where approximately a quarter of all cases in the world are estimated to occur.MethodsWe analysed data from three nationwide surveys (Malaria Indicator Surveys in 2010 and 2015, and a National Demographic and Health Survey in 2018), with malaria parasite prevalence in children under five years of age determined by sampling from all 36 states of Nigeria, and blood slide microscopy performed in the same accredited laboratory for all samples. Changes over time were evaluated by calculating prevalence ratio (PR) values with 95% confidence intervals (CI) for each state, together with Mantel-Haenszel adjusted prevalence ratios (PRadj) for each of the six major geopolitical zones of the country.ResultsBetween 2010 and 2018 there were significant reductions in parasite prevalence in 25 states, but not in the remaining 11 states. Prevalence decreased most in southern zones of the country (South West PRadj = 0.53; South East PRadj = 0.59; South South PRadj = 0.51) and the North Central zone (PRadj = 0.36). Changes in the north were less marked, but were significant and indicated overall reductions by more than 20% (North West PRadj = 0.74; North East PRadj = 0.76). Changes in the south occurred mostly between 2010 and 2015, whereas those in the north were more gradual and most continued after 2015. Recent changes were not correlated with survey-reported variation in use of preventive measures.ConclusionReductions in malaria infection in children under five have occurred in most individual states in Nigeria since 2010, but substantial geographical variation in the timing and extent indicate challenges to be overcome to enable global malaria reduction.

show abstract

“…Furthermore, regeneration of chloroquine-sensitive parasites was reported in some other African countries including Kenya, and Zambia after its withdrawal as first-line chemotherapy for uncomplicated malaria [16,17]. However, in Nigeria, evidence suggests that a strong background of the chloroquine-resistant Plasmodium falciparum persists even after a similar period of replacement by the ACTs [18,19]. Despite its withdrawal as first-line antimalaria, chloroquine is still in circulation and available over-the-counter in many pharmacies in Nigeria [18,20,21].…”

Section: Introductionmentioning

confidence: 99%

“…However, in Nigeria, evidence suggests that a strong background of the chloroquine-resistant Plasmodium falciparum persists even after a similar period of replacement by the ACTs [18,19]. Despite its withdrawal as first-line antimalaria, chloroquine is still in circulation and available over-the-counter in many pharmacies in Nigeria [18,20,21].…”

Section: Introductionmentioning

confidence: 99%

Declining Frequency of Chloroquine-resistant Haplotype of <em>Plasmodium falciparum</em> (CVIET) in an Endemic Area of Southwest Nigeria 17 Years After Withdrawal of Chloroquine

Amusan¹,

Akinola²,

Akano³

et al. 2023

Preprint

View full text Add to dashboard Cite

The replacement of chloroquine with artemisinin-based combination therapies (ACTs) for over a decade has had varying impacts on the ability of malaria parasite to sustain its chloroquine resistance prowess in different malaria-endemic regions. We evaluated the frequency of Plasmodium falciparum chloroquine resistance transporter (PfCRT) mutations in an endemic area of southwest Nigeria 17 years after replacement of chloroquine with ACTs for malaria treatment. Genomic DNA was isolated from dried blood spot samples obtained from 129 patients (aged 1-35 years) with microscopically confirmed P. falciparum infection. PfCRT fragments covering codons 72-76, CVMNK (wildtype) and A220 were amplified and sequenced. Two mutant PfCRT haplotypes on residues 72-76 (CVIET and CVINT) were identified with a prevalence of 18.6% and 2.3%, respectively. Interestingly, the CVINT haplotype was identified for the first time in this region. A220S changes were found in 16.3% of samples occurring concurrently with the CVIET haplotype, while a Q271E mutation occurred in a wildtype isolate. The reduced prevalence of the PfCRT mutant alleles in this study may suggest a gradual disappearance of chloroquine-resistant malaria parasites following reduced drug pressure. It may also be an indicator of the ability of malaria parasites to develop resistance gradually against the current first-line regimen.

show abstract

Polymorphisms in Plasmodium falciparum chloroquine resistance transporter (Pfcrt) and multidrug-resistant gene 1 (Pfmdr-1) in Nigerian children 10 years post-adoption of artemisinin-based combination treatments

Cited by 8 publications

References 62 publications

Molecular profiling of the artemisinin resistance Kelch 13 gene in Plasmodium falciparum from Nigeria

Molecular profiling of the artemisinin resistance Kelch 13 gene in Plasmodium falciparum from Nigeria

Geographical and temporal variation in reduction of malaria infection among children under five years of age throughout Nigeria

Declining Frequency of Chloroquine-resistant Haplotype of <em>Plasmodium falciparum</em> (CVIET) in an Endemic Area of Southwest Nigeria 17 Years After Withdrawal of Chloroquine

Contact Info

Product

Resources

About