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The genomic architecture of antimalarial drug resistance

November 26, 2019 - 20:17 -- Open Access
Annie N Cowell, Elizabeth A Winzeler
Briefings in Functional Genomics, Volume 18, Issue 5, September 2019, Pages 314–328

Plasmodium falciparum and Plasmodium vivax, the two protozoan parasite species that cause the majority of cases of human malaria, have developed resistance to nearly all known antimalarials. The ability of malaria parasites to develop resistance is primarily due to the high numbers of parasites in the infected person’s bloodstream during the asexual blood stage of infection in conjunction with the mutability of their genomes.

Not Open Access | Phenotypic Screening of Small Molecules with Antimalarial Activity for Three Different Parasitic Life Stages.

May 10, 2018 - 15:56 -- NOT Open Access
Kato N, March S, Bhatia SN, Marti M
Methods Mol Biol. 2018;1787:41-52

Despite a renewed effort to identify compounds with antimalarial activity, the drug discovery and development pipeline lacks target diversity and availability of compounds that target liver- and gametocyte-stage parasites. 

A novel validated assay to support the discovery of new anti-malarial gametocytocidal agents

July 27, 2016 - 06:59 -- Open Access
Noemí Bahamontes-Rosa, María G. Gomez-Lorenzo, Joël Lelièvre, Ane Rodriguez Alejandre, María Jesus Almela, Sonia Lozano, Esperanza Herreros and Francisco-Javier Gamo
Malaria Journal 2016 15:385, 22 July 2016

This study describes a novel assay for characterizing the activity of anti-malarial drugs against the later stages of P. falciparum gametocyte development using qPCR in genetically unmodified parasites.

Medical Condition: 

Examining Plasmodium falciparum and P. vivax clearance subsequent to antimalarial drug treatment in the Myanmar-China border area based on quantitative real-time polymerase chain reaction

April 21, 2016 - 16:26 -- Open Access
Lo E, Nguyen J, Oo W, Hemming-Schroeder E, Zhou G, Yang Z, Cui L, Yan G
BMC Infectious Diseases 2016, 16 :154 (16 April 2016)

This study aims to examine clearance time of P. falciparum and P. vivax parasitemia as well as putative gene mutations associated with residual or recurred parasitemia in Myanmar.

A combined within-host and between-hosts modelling framework for the evolution of resistance to antimalarial drugs.

April 19, 2016 - 14:49 -- Open Access
Legros M, Bonhoeffer S
J R Soc Interface. 2016 Apr;13(117)

We show that the spread of resistance is generally less likely in areas of intense transmission, and therefore of increased competition between strains, an effect exacerbated when costs of resistance are higher. 

Not Open Access | Artemisinin nanoformulation suitable for intravenous injection: Preparation, characterization and antimalarial activities

November 25, 2015 - 08:36 -- NOT Open Access
Nehal Ibrahim, Hany Ibrahim, Alicia Moreno Sabater, Dominique Mazier, Alexis Valentin, Françoise Nepveu
International Journal of Pharmaceutics, Volume 495, Issue 2, 30 November 2015, Pages 671-679

Here, we report the preparation, characterization, and in vitro and in vivo biological evaluation of biodegradable albumin-bound artemisinin nanoparticles. 

Parasite clearance after malaria therapy: staying a step ahead of drug resistance

October 7, 2015 - 15:14 -- Open Access
Harin A. Karunajeewa
BMC Medicine 2015, 13:251

If this were also to occur in Africa, it would have disastrous implications for the continent subject to the world’s greatest burden of Plasmodium falciparum. The earliest indications of incipient artemisinin resistance may be a slowing of the rate at which parasites are cleared from the blood following treatment. 

Clinical determinants of early parasitological response to ACTs in African patients with uncomplicated falciparum malaria: a literature review and meta-analysis of individual patient data

September 9, 2015 - 15:38 -- Open Access
WWARN Artemisinin based Combination Therapy (ACT) Africa Baseline Study Group
BMC Medicine 2015, 13:212

This study was designed to establish the baseline values for clearance in patients from Sub-Saharan African countries with uncomplicated malaria treated with artemisinin-based combination therapies (ACTs).

Carboxymefloquine, the major metabolite of the antimalarial drug mefloquine, induces drug-metabolizing enzyme and transporter expression by activation of pregnane X receptor.

September 2, 2015 - 16:36 -- Open Access
Piedade R, Traub S, Bitter A, Nüssler AK, Gil JP, Schwab M, Burk O
Antimicrob Agents Chemother. 2015 Jan;59(1):96-104

Therefore, this study aimed to elucidate the potential of nonartemisinin antimalarial drugs and drug metabolites to activate PXR. We screened 16 clinically used antimalarial drugs and six major drug metabolites for binding to PXR using the two-hybrid PXR ligand binding domain assembly assay; this identified carboxymefloquine, the major and pharmacologically inactive metabolite of the antimalarial drug mefloquine, as a potential PXR ligand. 

Plasmodium falciparum Thioredoxin Reductase (PfTrxR) and Its Role as a Target for New Antimalarial Discovery

July 6, 2015 - 15:30 -- Open Access
Sara E. McCarty, Amanda Schellenberger, Douglas C. Goodwin, Ngolui Rene Fuanta, Babu L. Tekwani and Angela I. Calderón
Molecules 2015, 20(6), 11459-11473

This review paper provides an overview of the structure and function of TrxR, discusses similarities and differences between the thioredoxin reductases (TrxRs) of different Plasmodium species and the human forms of the enzyme, gives an overview of modeling Plasmodium infections in animals, and suggests the role of Trx functions in antimalarial drug resistance. 


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