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artemisinin resistance

Plasmodium falciparum K13 mutations in Africa and Asia impact artemisinin resistance and parasite fitness

July 21, 2021 - 17:11 -- Open Access
Author(s): 
Stokes BH, Dhingra SK, Fidock DA, et al.
Reference: 
Elife. 2021 Jul 19;10:e66277

The emergence of mutant K13-mediated artemisinin (ART) resistance in Plasmodium falciparum malaria parasites has led to widespread treatment failure across Southeast Asia. In Africa, K13-propeller genotyping confirms the emergence of the R561H mutation in Rwanda and highlights the continuing dominance of wild-type K13 elsewhere.

NOT Open Access | Implicating extracellular vesicles in Plasmodium falciparum artemisinin resistance development

April 22, 2021 - 08:23 -- NOT Open Access
Author(s): 
Tandoh KZ, Wilson MD, Quashie NB, Duah-Quashie NO
Reference: 
Traffic. 2021 Apr 15

Plasmodium falciparum malaria remains a disease of significant public health impact today. With the risk of emerging artemisinin resistance stalling malaria control efforts, the need to deepen our understanding of the parasite's biology is dire. Extracellular vesicles (EVs) are vital to the biology of P. falciparum and play a role in the pathogenesis of malaria.

Histone acetyltransferase PfGCN5 regulates stress responsive and artemisinin resistance related genes in Plasmodium falciparum

January 21, 2021 - 15:26 -- Open Access
Author(s): 
Rawat M, Kanyal A, Sahasrabudhe A, Vembar SS, Lopez-Rubio JJ, Karmodiya K
Reference: 
Sci Rep. 2021 Jan 13;11(1):852

Plasmodium falciparum has evolved resistance to almost all front-line drugs including artemisinin, which threatens malaria control and elimination strategies. Oxidative stress and protein damage responses have emerged as key players in the generation of artemisinin resistance. In this study, we show that PfGCN5, a histone acetyltransferase, binds to the stress-responsive genes in a poised state and regulates their expression under stress conditions.

Plasmodium berghei K13 Mutations Mediate In Vivo Artemisinin Resistance That Is Reversed by Proteasome Inhibition

November 11, 2020 - 14:33 -- Open Access
Author(s): 
Simwela NV, Stokes BH, Aghabi D, Bogyo M, Fidock DA, Waters AP
Reference: 
mBio. 2020 Nov 10;11(6):e02312-20

The recent emergence of Plasmodium falciparum parasite resistance to the first line antimalarial drug artemisinin is of particular concern. Artemisinin resistance is primarily driven by mutations in the P. falciparum K13 protein, which enhance survival of early ring-stage parasites treated with the artemisinin active metabolite dihydroartemisinin in vitro and associate with delayed parasite clearance in vivo However, association of K13 mutations with in vivo artemisinin resistance has been problematic due to the absence of a tractable model.

Multisectoral Approach to Support Use of Insecticide-Treated Net for Malaria Prevention Among Mobile and Migrant Populations in Myanmar: A Systematic Review

November 3, 2020 - 15:22 -- Open Access
Author(s): 
Naing C, Whittaker MA, Tanner M
Reference: 
J Infect Dis. 2020 Oct 29;222(Supplement_8):S717-S725

Myanmar is a premalaria elimination country with artemisinin-resistant malaria. A strategy for transmission control is focused on vulnerable groups such as mobile and migrant populations (MMPs), and includes improving access to insecticide-treated bed nets in the Myanmar artemisinin resistance containment (MARC) zones using multisectoral approaches (MSA).

NOT Open Access | Absence of association between polymorphisms in the pfcoronin and pfk13 genes and the presence of Plasmodium falciparum parasites after treatment with artemisinin derivatives in Senegal

October 15, 2020 - 08:36 -- NOT Open Access
Author(s): 
Delandre O, Daffe SM, Pradines B, et al.
Reference: 
Int J Antimicrob Agents. 2020 Oct 9:106190

Due to resistance to chloroquine and sulfadoxine-pyrimethamine, treatment for uncomplicated Plasmodium falciparum malaria switched to artemisinin-based combination therapy (ACT) in 2006 in Senegal. Several mutations in the gene coding the kelch13 helix (pfk13-propeller) were identified to be associated with in vitro and in vivo artemisinin resistance in Southeast Asia.

Importance of kelch 13 C580Y mutation in the studies of artemisinin resistance in Plasmodium falciparum in Greater Mekong Subregion

October 7, 2020 - 16:23 -- Open Access
Author(s): 
Zaw MT, Lin Z, Emran NA
Reference: 
J Microbiol Immunol Infect. 2020 Oct;53(5):676-681

The mortality caused by Plasmodium falciparum was reduced by Artemisinin (ART) and ART combination therapy (ACT). However, Artemisinin resistance (ART-R) emerge during 2008 in Cambodia and spread to Greater Mekong Subregion (GMS).

The lack of K13-propeller mutations associated with artemisinin resistance in Plasmodium falciparum in Democratic Republic of Congo (DRC)

August 25, 2020 - 07:55 -- Open Access
Author(s): 
Yobi DM, Kayiba NK, Mvumbi DM, Boreux R, Bontems S, Kabututu PZ, De Mol P, Speybroeck N, Mvumbi GL, Hayette MP
Reference: 
PLoS One. 2020 Aug 21;15(8):e0237791

Artemisinin-based combination therapies (ACTs) have been recommended by the World Health Organization (WHO) as first-line treatment of uncomplicated Plasmodium falciparum (P. falciparum) malaria since 2005 in Democratic Republic of Congo (DRC) and a regular surveillance of the ACT efficacy is required to ensure the treatment effectiveness. Mutations in the propeller domain of the pfk13 gene were identified as molecular markers of artemisinin resistance (ART-R).

Not Open Access | Artemisinin Resistance and the Unique Selection Pressure of a Short-acting Antimalarial

August 10, 2020 - 16:11 -- NOT Open Access
Author(s): 
Khoury DS, Cao P, Zaloumis SG, Davenport MP
Reference: 
Trends Parasitol. 2020 Aug 5:S1471-4922(20)30187-2

Resistance to the artemisinin derivatives, our most effective antimalarial drugs, has not manifest as a classical resistance phenotype in which parasites can tolerate higher drug concentrations.

NOT Open Access | Plasmodium falciparum Artemisinin Resistance: The Effect of Heme, Protein Damage, and Parasite Cell Stress Response

July 15, 2020 - 14:37 -- NOT Open Access
Author(s): 
Rosenthal MR, Ng CL
Reference: 
ACS Infect Dis. 2020 Jul 10; 6(7):1599-1614

Despite a significant decline in morbidity and mortality over the last two decades, in 2018 there were 228 million reported cases of malaria and 405000 malaria-related deaths. Artemisinin, the cornerstone of artemisinin-based combination therapies, is the most potent drug in the antimalarial armamentarium against falciparum malaria. Heme-mediated activation of artemisinin and its derivatives results in widespread parasite protein alkylation, which is thought to lead to parasite death.

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