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

Balogun, Sulayman Tunde; Sandabe, Umar Kyari; Sodipo, O. A.; Okon, Kenneth O.; Akanmu, Ayodele Oluwasoji

doi:10.1155/2021/8840089

Cited by 2 publications

(1 citation statement)

References 30 publications

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“…A double-blind, randomized, and controlled superiority clinical trial comparing a three-course IPTp with SP, and a three-course IPTp with DP was conducted at a tertiary hospital in Maiduguri, Nigeria. The trial setting is a high transmission and mesoendemic area for malaria infections with emerging SP resistance [13,14].…”

Section: Trial Design and Settingmentioning

confidence: 99%

Superiority trial of intermittent treatment with dihydroartemisinin–piperaquine versus sulfadoxine–pyrimethamine for the prevention of malaria during pregnancy

et al. 2023

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Background Malaria in pregnancy is responsible for various adverse maternal and birth outcomes. The emerging resistance to sulfadoxine–pyrimethamine (SP) raises important concerns about its use for intermittent preventive treatment in pregnancy (IPTp) in Africa. This trial aimed to assess the efficacy and safety of IPTp with dihydroartemisinin–piperaquine (DP) as an alternative to IPTp with SP. Results The double-blind, randomized, and controlled superiority trial was conducted between July 2020 and June 2021. A total of 250 women were enrolled and randomly assigned to receive SP (n = 125) or DP (n = 125). Two hundred and six (82.4%) participants that contributed to the outcomes were included in the modified intention-to-treat (ITT) analysis, while 84 participants that completed the three courses of the study drugs were included in the per protocol (PP) analysis. The ITT analysis results showed that the incidence of histopathologically confirmed placental malaria was nonsignificantly higher in the DP group compared with the SP group (62.5% vs. 51.1%, P = 0.098). After adjusting for confounders, the risk of histopathologically confirmed placental malaria was also nonsignificantly higher in the DP group (Adjusted Relative Risk [RR] = 1.27, 95% CI 0.94–1.71) compared with the SP group. In contrast, the risk of a low APGAR score was significantly lower in the DP group (RR = 0.45, 95% CI 0.38–0.52) compared with the SP group. Also, the risk of a composite adverse birth outcome (low birth weight or preterm delivery or neonates small for the gestational age) was nonsignificantly lower in the DP group (Adjusted RR = 0.82, 95% CI 0.55–1.21) compared with the SP group. Both drugs were well tolerated, although nausea and vomiting occurred in a significant number of participants in the SP group. Conclusions A three-course IPTp with DP was safe and was not found to be superior to IPTp with SP in the prevention of placental malaria. Although IPTp with DP was associated with a significant lower risk of low APGAR score and nonsignificant lower risks of other adverse birth outcomes compared with IPTp with SP. Trial registration PACTR, PACTR202002644579177. Registered 20 February 2020, https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=9753.

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Section: Trial Design and Settingmentioning

confidence: 99%

Superiority trial of intermittent treatment with dihydroartemisinin–piperaquine versus sulfadoxine–pyrimethamine for the prevention of malaria during pregnancy

et al. 2023

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A snapshot of the prevalence of dihydropteroate synthase-431V mutation and other sulfadoxine-pyrimethamine resistance markers in Plasmodium falciparum isolates in Nigeria

Adegbola

Ijarotimi

Ubom

et al. 2023

Malar J

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Background Malaria is a major public health issue with substantial risks among vulnerable populations. Currently, the World Health Organization (WHO) recommends SP-IPTp in the second and third trimesters. However, the efficacy of SP-IPTp is threatened by the emergence of sulfadoxine-pyrimethamine resistant malaria parasites due to single nucleotide polymorphisms in the Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthetase genes. This study aimed to assess the current prevalence of Pfdhfr/Pfdhps mutations in P. falciparum isolates collected from individuals residing in Ile-Ife, Nigeria, and also present maps of the prevalence of Pfdhps 431V and 581G within Nigeria and surrounding countries. Methods Between October 2020 and April 2021, samples were collected as dried blood spots among 188 participants who showed malaria positivity with a histidine-rich-protein-based rapid diagnostic test (RDT). Nested PCR assays were used to confirm falciparum in the samples with RDT positivity, and to amplify fragments of the Pfdhfr/Pfdhps genes followed by targeted amplicon sequencing. Published data since 2007 on the prevalence of the Pfdhps genotypes in Nigeria and the neighbouring countries were used to produce maps to show the distribution of the mutant genotypes. Results Only 74 and 61 samples were successfully amplified for the Pfdhfr and Pfdhps genes, respectively. At codons resulting in N51I, C59R, and S108N, Pfdhfr carried mutant alleles of 97.3% (72/74), 97.3% (72/74) and 98.6% (73/74), respectively. The Pfdhps gene carried mutations at codons resulting in amino acid changes at 431–436-437–540-581–613; I431V [45.9%, (28/61)], A581G [31.1% (19/61)] and A613S [49.2% (30/61)]. Constructed haplotypes were mainly the triple Pfdhfr mutant 51I-59R-108N (95.9%), and the most common haplotypes observed for the Pfdhps gene were the ISGKAA (32.8%), ISGKGS (8.2%), VAGKAA (14.8%), VAGKAS (9.8%) and VAGKGS (14.8%). In the context of the previously published data, a high prevalence of 431V/581G mutations was found in the study population. It seems quite evident that the Pfdhps 431V, 581G and 613S often co-occur as Pfdhps-VAGKGS haplotype. Conclusion This study showed that the prevalence of VAGKGS haplotype seems to be increasing in prevalence. If this is similar in effect to the emergence of 581G in East Africa, the efficacy of SP-IPTp in the presence of these novel Pfdhps mutants should be re-assessed.

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

Cited by 2 publications

References 30 publications

Superiority trial of intermittent treatment with dihydroartemisinin–piperaquine versus sulfadoxine–pyrimethamine for the prevention of malaria during pregnancy

Superiority trial of intermittent treatment with dihydroartemisinin–piperaquine versus sulfadoxine–pyrimethamine for the prevention of malaria during pregnancy

A snapshot of the prevalence of dihydropteroate synthase-431V mutation and other sulfadoxine-pyrimethamine resistance markers in Plasmodium falciparum isolates in Nigeria

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