scholarly journals Single Nucleotide Polymorphisms of Pfdhfr and Pfdhps Genes: Implications for Malaria Prophylactic Strategies in Maiduguri, Northeast Nigeria

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Sulayman Tunde Balogun ◽  
Umar Kyari Sandabe ◽  
Olufunke Adebola Sodipo ◽  
Kenneth Okwong Okon ◽  
Ayodele Oluwasoji Akanmu
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Geometric Mean ◽  
Intermittent Preventive Treatment ◽  
Preventive Treatment ◽  
Dried Blood Spot ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Double Mutation ◽  
Blood Spot ◽  
Northeast Nigeria

Background. The success of Intermittent Preventive Treatment in Pregnancy (IPTp), Intermittent Preventive Treatment in Infancy (IPTi), and Seasonal Malaria Chemoprevention (SMC) depends on sulfadoxine-pyrimethamine (SP) efficacy. Objective. The study determined Single Nucleotide Polymorphisms (SNPs) of Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) in Maiduguri, Northeast Nigeria. Materials and Methods. Giemsa-stained blood smears, capillary blood, and dried blood spot samples were collected from 63 subjects with uncomplicated malaria in Maiduguri between May and October 2018. Plasmodium species was determined and parasite density (PD) was estimated using the smears. Genomic DNA (gDNA) of P. falciparum was extracted from the dried blood spot samples using QIAamp DNA Mini Kit. The gDNA was subjected to nested PCR followed by restriction fragment length polymorphism (RFLP) to determine SNPs at Pfdhfr codons N51I, C59R, and S108N and Pfdhps codons S436A/F, A437G, and K540E. Results. The subjects’ mean age ± standard deviation was 23.6 ± 8.7 (2.0–67.0) years with a geometric mean PD of 8,948 (2,100–13,400) asexual parasites/µl blood. SNPs prevalence at any of the six Pfdhfr and Pfdhps codons was 85.7% (54/63); the prevalence was higher ( p < 0.05 ) in Pfdhfr (82.5%; 52/63) than Pfdhps (58.7%; 37/63). Pfdhfr allele 108N (82.5%; 52/63) was the highest ( p < 0.05 ) mutant when compared with alleles 51I (60.3%; 38/63) and 59R (66.7%; 42/63). Triple Pfdhfr mutation was observed in 60.3% (38/63) of the isolates and was higher ( p < 0.05 ) among female subjects and SP recipients. Prevalence of Pfdhps allele 436A (28.6%; 18/63) was similar ( p > 0.05 ) to allele 437G (34.9%; 22/63), with double mutation recorded in 4.8% (3/63). K540E mutation was not observed. Conclusion. Pfdhfr and Pfdhps mutations observed in Maiduguri are suggestive of SP resistance level, and this could constitute a setback to malaria prophylactic strategies in the region if unchecked. Thus, there is a need to investigate the clinical efficacy of SP.

scholarly journals Low prevalence of highly sulfadoxine‐resistant dihydropteroate synthase alleles in Plasmodium falciparum isolates in Benin

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Samaly Souza Svigel ◽  
Adicath Adeothy ◽  
Augustin Kpemasse ◽  
Ernest Houngbo ◽  
Antoine Sianou ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Intermittent Preventive Treatment ◽  
Preventive Treatment ◽  
Nucleotide Polymorphisms ◽  
Triple Mutant ◽  
Single Nucleotide ◽  
Dihydropteroate Synthase ◽  
Seasonal Malaria Chemoprevention ◽  
Study Sites ◽  
Low Prevalence

Abstract Background In 2004, in response to high levels of treatment failure associated with sulfadoxine-pyrimethamine (SP) resistance, Benin changed its first-line malaria treatment from SP to artemisinin-based combination therapy for treatment of uncomplicated Plasmodium falciparum malaria. Resistance to SP is conferred by accumulation of single nucleotide polymorphisms (SNPs) in P. falciparum genes involved in folate metabolism, dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps), targeted by pyrimethamine and sulfadoxine, respectively. Because SP is still used for intermittent preventive treatment in pregnant women (IPTp) and seasonal malaria chemoprevention (SMCP) in Benin, the prevalence of Pfdhfr and Pfdhps SNPs in P. falciparum isolates collected in 2017 were investigated. Methods This study was carried out in two sites where the transmission of P. falciparum malaria is hyper-endemic: Klouékanmey and Djougou. Blood samples were collected from 178 febrile children 6–59 months old with confirmed uncomplicated P. falciparum malaria and were genotyped for SNPs associated with SP resistance. Results The Pfdhfr triple mutant IRN (N51I, C59R, and S108N) was the most prevalent (84.6%) haplotype and was commonly found with the Pfdhps single mutant A437G (50.5%) or with the Pfdhps double mutant S436A and A437G (33.7%). The quintuple mutant, PfdhfrIRN/PfdhpsGE (A437G and K540E), was rarely observed (0.8%). The A581G and A613S mutant alleles were found in 2.6 and 3.9% of isolates, respectively. Six isolates (3.9%) were shown to harbour a mutation at codon I431V, recently identified in West African parasites. Conclusions This study showed that Pfdhfr triple IRN mutants are near fixation in this population and that the highly sulfadoxine-resistant Pfdhps alleles are not widespread in Benin. These data support the continued use of SP for chemoprevention in these study sites, which should be complemented by periodic nationwide molecular surveillance to detect emergence of resistant genotypes.

Development of a simple method for the determination of single nucleotide polymorphisms

2010 ◽  
Vol 34 (8) ◽  
pp. S75-S75
Author(s):  
Weifeng Zhu ◽  
Zhuoqi Liu ◽  
Daya Luo ◽  
Xinyao Wu ◽  
Fusheng Wan
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Nucleotide Polymorphisms ◽  
Simple Method ◽  
Single Nucleotide

Sex Differences in Childhood Associations between DNA Markers and General Cognitive Ability

2007 ◽  
Vol 28 (3) ◽  
pp. 161-164 ◽  
Author(s):  
Rosalind Arden ◽  
Nicole Harlaar ◽  
Robert Plomin
Keyword(s):  
Sex Differences ◽  
Single Nucleotide Polymorphisms ◽  
Cognitive Ability ◽  
Dna Markers ◽  
Community Sample ◽  
Nucleotide Polymorphisms ◽  
General Cognitive Ability ◽  
Single Nucleotide ◽  
The Difference

Abstract. An association between intelligence at age 7 and a set of five single-nucleotide polymorphisms (SNPs) has been identified and replicated. We used this composite SNP set to investigate whether the associations differ between boys and girls for general cognitive ability at ages 2, 3, 4, 7, 9, and 10 years. In a longitudinal community sample of British twins aged 2-10 (n > 4,000 individuals), we found that the SNP set is more strongly associated with intelligence in males than in females at ages 7, 9, and 10 and the difference is significant at 10. If this finding replicates in other studies, these results will constitute the first evidence of the same autosomal genes acting differently on intelligence in the two sexes.

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