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Chemoprotective Antimalarial Activity of P218 against Plasmodium falciparum: A Randomized, Placebo-Controlled Volunteer Infection Study

February 10, 2021 - 09:44 -- Open Access
Chughlay MF, El Gaaloul M, Chalon S, et al.
Am J Trop Med Hyg. 2021 Feb 8:tpmd201165

P218 is a highly selective dihydrofolate reductase inhibitor with potent in vitro activity against pyrimethamine-resistant Plasmodium falciparum. This single-center, randomized, double-blind, placebo-controlled phase Ib study evaluated P218 safety and chemoprotective efficacy in a P. falciparum sporozoite (PfSPZ) volunteer infection study (VIS). Consecutive dose safety and tolerability were evaluated (cohort 1), with participants receiving two oral doses of P218 1,000 mg 48 hours apart (n = 6), or placebo (n = 2). P218 chemoprotective efficacy was assessed (cohorts 2 and 3) with direct venous inoculation of 3,200 aseptic, cryopreserved PfSPZ (NF54 strain) followed 2 hours later with two P218 doses of 1,000 mg (cohort 2, n = 9) or 100 mg (cohort 3, n = 9) administered 48 hours apart, or placebo (n = 6).

NOT Open Access | Phylogenetic analysis suggests single and multiple origins of dihydrofolate reductase mutations in Plasmodium vivax

January 7, 2021 - 10:30 -- NOT Open Access
Shaukat A, Ali Q, Raud L, Wahab A, Khan TA, Rashid I, Rashid M, Hussain M, Saleem MA, Sargison ND, Chaudhry U
Acta Trop. 2021 Jan 3:105821

Pyrimethamine was first introduced for the treatment of malaria in Asia and Africa during the early 1980s, replacing chloroquine, and has become the first line of drugs in many countries. In recent years, development of pyrimethamine resistance in Plasmodium vivax has become a barrier to effective malaria control strategies. Here, we describe the use of meta-barcoded deep amplicon sequencing technology to assess the evolutionary origin of pyrimethamine resistance by analysing the flanking region of dihydrofolate reductase (dhfr) locus.

NOT Open Access | Multiple SNPs detection for antimalarial pyrimethamine resistance via allele-specific PCR coupled with gold nanoparticles-based lateral flow biosensor

December 30, 2020 - 13:45 -- NOT Open Access
Jiang T, Huang Y, Cheng W, Sun Y, Wei W, Wu K, Shen C, Fu X, Dong H, Li J.
Antimicrob Agents Chemother. 2020 Dec 23:AAC.01063-20

Molecular genotyping holds tremendous potential to detect antimalarial drug resistance (ADR) related to single nucleotide polymorphisms (SNPs). However, it suffers from complicated procedures and expensive instruments. Thus, rapid point-of-care testing (POCT) molecular tools are urgently needed for field survey and clinical use. Herein, a POCT platform consisted of multiple allele-specific PCR (AS-PCR) and gold nanoparticles (AuNPs) based lateral flow biosensor was designed and developed for SNPs detection of Plasmodium falciparum dihydrofolate reductase (pfdhfr) gene related to pyrimethamine resistance.

Understanding the Pyrimethamine Drug Resistance Mechanism via Combined Molecular Dynamics and Dynamic Residue Network Analysis

February 25, 2020 - 16:31 -- Open Access
Amusengeri A, Tata RB, Tastan Bishop Ö
Molecules 2020, 25(4), 904

In this era of precision medicine, insights into the resistance mechanism of drugs are integral for the development of potent therapeutics. Here, we sought to understand the contribution of four point mutations (N51I, C59R, S108N, and I164L) within the active site of the malaria parasite enzyme dihydrofolate reductase (DHFR) towards the resistance of the antimalarial drug pyrimethamine. Homology modeling was used to obtain full-length models of wild type (WT) and mutant DHFR.

Not Open Access | Prevalence of Plasmodium falciparum parasites resistant to sulfadoxine/pyrimethamine in pregnant women in Yaoundé, Cameroon: emergence of highly resistant pfdhfr/pfdhps alleles

August 18, 2015 - 16:20 -- NOT Open Access
Pamela Chauvin , Sandie Menard , Xavier Iriart , Sandrine E. Nsango , Majoline T. Tchioffo , Luc Abate , Parfait H. Awono-Ambéné , Isabelle Morlais and Antoine Berry
J. Antimicrob. Chemother. (2015) 70 (9): 2566-2571

Significant changes were found in pfdhps polymorphism. In particular, we observed several parasites carrying eight mutations in pfdhfr/pfdhps genes, which are very susceptible to having a high level of resistance to sulfadoxine/pyrimethamine.

Therapeutic efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in North-Eastern Tanzania

September 30, 2014 - 19:13 -- Open Access
Shayo A, Mandara CI, Shahada F, Buza J, Lemnge MM, Ishengoma DS
Malaria Journal 2014, 13 :376 (20 September 2014)

This study showed that AL was safe, well-tolerated and efficacious for treatment of uncomplicated falciparum malaria.

Not Open Access | Characteristics of Nigerian women taking sulfadoxine/pyrimethamine twice during pregnancy for the prevention of malaria

October 16, 2013 - 19:12 -- NOT Open Access
Nkechi G. Onyeneho, Bright C. Orji, Joseph C. Okeibunor, William R. Brieger
International Journal of Gynecology & Obstetrics, Volume 123, Issue 2, November 2013, Pages 101-104

The present findings could help in targeting health education programs to specific subgroups of women to increase compliance with the recommended 2 doses of SP for the prevention of malaria in pregnancy.

Not Open Access | Identification and Functional Analysis of the Primary Pantothenate Transporter, PfPAT, of the Human Malaria Parasite Plasmodium falciparum

July 13, 2013 - 13:15 -- NOT Open Access
Yoann Augagneur, Lise Jaubert, Choukri Ben Mamoun, et al.
July 12, 2013 The Journal of Biological Chemistry, 288, 20558-20567.

Here we report the identification and functional characterization of the first protozoan pantothenate transporter, PfPAT, from P. falciparum. We show using cell biological, biochemical, and genetic analyses that this transporter is localized to the parasite plasma membrane and plays an essential role in parasite intraerythrocytic development.

Determination of artemether and lumefantrine in anti-malarial fixed-dose combination tablets by microemulsion electrokinetic chromatography with short-end injection procedure

June 20, 2013 - 16:42 -- Open Access
Amin NC, Fabre H, Blanchin M, Montels J, Aké M
Malaria Journal 2013, 12:202 (13 June 2013)

The developed MEEKC method can be proposed as an alternative method to liquid chromatography for the determination of artemether and lumefantrine in fixed-dose combination tablet formulations.

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