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artemisinin resistance

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.

Impact of substandard and falsified antimalarials in Zambia: application of the SAFARI model

July 13, 2020 - 16:33 -- Open Access
Author(s): 
Jackson KD, Higgins CR, Laing SK, Mwila C, Kobayashi T, Ippolito MM, Sylvia S, Ozawa S
Reference: 
BMC Public Health. 2020 Jul 9;20(1):1083

Many countries are striving to become malaria-free, but global reduction in case estimates has stagnated in recent years. Substandard and falsified medicines may contribute to this lack of progress. Zambia aims to eliminate their annual burden of 1.2 million pediatric malaria cases and 2500 child deaths due to malaria. We examined the health and economic impact of poor-quality antimalarials in Zambia.

NOT Open Access | 'Artemisinin Resistance': Something New or Old? Something of a Misnomer

June 29, 2020 - 16:18 -- NOT Open Access
Author(s): 
Wellems TE, Sá JM, Su XZ, Connelly SV, Ellis AC
Reference: 
Trends Parasitol. 2020 Jun 22:S1471-4922(20)30158-6

Artemisinin and its derivatives (ART) are crucial first-line antimalarial drugs that rapidly clear parasitemia, but recrudescences of the infection frequently follow ART monotherapy. For this reason, ART must be used in combination with one or more partner drugs that ensure complete cure.

Surveillance of genetic markers associated with Plasmodium falciparum resistance to artemisinin-based combination therapy in Pakistan, 2018–2019

June 9, 2020 - 16:16 -- Open Access
Author(s): 
Abdul Qader Khan, Leyre Pernaute-Lau, Aamer Ali Khattak, Sanna Luijcx, Berit Aydin-Schmidt, Mubashir Hussain, Taj Ali Khan, Farees Uddin Mufti and Ulrika Morris
Reference: 
Malaria Journal 2020 19:206, 8 June 2020

The spread of artemisinin resistance in the Greater Mekong Subregion of Southeast Asia poses a significant threat for current anti-malarial treatment guidelines globally. The aim of this study was to assess the current prevalence of molecular markers of drug resistance in Plasmodium falciparum in the four provinces with the highest malaria burden in Pakistan, after introducing artemether–lumefantrine as first-line treatment in 2017.

Not Open Access | C-terminal aromatic residue of Plasmodium ferredoxin important for the interaction with ferredoxin:NADP(H) oxidoreductase: possible involvement for artemisinin resistance of human malaria parasites

June 1, 2020 - 16:48 -- NOT Open Access
Author(s): 
Kimata-Ariga Y, Sakamoto A, Kamatani M, Saitoh T, Hase T
Reference: 
J Biochem. 2020 May 29:mvaa060

The malaria parasite (Plasmodium sp.) contains a plastid-derived organelle called the apicoplast, which is essential for the growth of the parasite. In this organelle, a redox system comprising plant-type ferredoxin (Fd) and Fd:NADP(H) oxidoreductase (FNR) supplies reducing power for the crucial metabolic pathways. Electron transfer between P. falciparum Fd (PfFd) and FNR (PfFNR) is performed with higher affinity and specificity than those of plant Fd and FNR. We investigated the structural basis for such superior protein-protein interaction by focusing on the Plasumodium-specific regions of PfFd.

Local emergence in Amazonia of Plasmodium falciparum k13 C580Y mutants associated with in vitro artemisinin resistance

May 13, 2020 - 14:50 -- Open Access
Author(s): 
Mathieu LC, Cox H, Musset L, et al.
Reference: 
Elife. 2020 May 12;9. pii: e51015

Antimalarial drug resistance has historically arisen through convergent de novo mutations in Plasmodium falciparum parasite populations in Southeast Asia and South America. For the past decade in Southeast Asia, artemisinins, the core component of first-line antimalarial therapies, have experienced delayed parasite clearance associated with several pfk13 mutations, primarily C580Y.

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