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No evidence of amplified Plasmodium falciparum plasmepsin II gene copy number in an area with artemisinin-resistant malaria along the China–Myanmar border

September 15, 2020 - 10:38 -- Open Access
Fang Huang, Biraj Shrestha, Hui Liu, Lin-Hua Tang, Shui-Sen Zhou, Xiao-Nong Zhou, Shannon Takala-Harrison, Pascal Ringwald, Myaing M. Nyunt and Christopher V. Plowe
Malaria Journal 2020 19:334, 14 September 2020

The emergence and spread of artemisinin resistance in Plasmodium falciparum poses a threat to malaria eradication, including China’s plan to eliminate malaria by 2020. Piperaquine (PPQ) resistance has emerged in Cambodia, compromising an important partner drug that is widely used in China in the form of dihydroartemisinin (DHA)-PPQ. Several mutations in a P. falciparum gene encoding a kelch protein on chromosome 13 (k13) are associated with artemisinin resistance and have arisen spread in the Great Mekong subregion, including the China–Myanmar border. Multiple copies of the plasmepsin II/III (pm2/3) genes, located on chromosome 14, have been shown to be associated with PPQ resistance.

NOT Open Access | Half-Sandwich Cyclopentadienylruthenium(II) Complexes: A New Antimalarial Chemotype

August 25, 2020 - 15:34 -- NOT Open Access
Milheiro SA, Gonçalves J, Moreira R, et al.
Inorg Chem. 2020 Aug 24

A small library of "half-sandwich" cyclopentadienylruthenium(II) compounds of the general formula [(η5-C5R5)Ru(PPh3)(N-N)][PF6], a scaffold hitherto absent from the toolbox of antiplasmodials, was screened for activity against the blood stage of CQ-sensitive 3D7-GFP, CQ-resistant Dd2, and artemisinin-resistant IPC5202 Plasmodium falciparum strains and the liver stage of Plasmodium berghei.

Molecular characterization of Plasmodium falciparum DNA-3-methyladenine glycosylase

August 10, 2020 - 15:00 -- Open Access
Nattapon Pinthong, Paviga Limudomporn, Jitlada Vasuvat, Poom Adisakwattana, Pongruj Rattaprasert and Porntip Chavalitshewinkoon-Petmitr
Malaria Journal 2020 19:284, 6 August 2020

The emergence of artemisinin-resistant malaria parasites highlights the need for novel drugs and their targets. Alkylation of purine bases can hinder DNA replication and if unresolved would eventually result in cell death. DNA-3-methyladenine glycosylase (MAG) is responsible for the repair of those alkylated bases. Plasmodium falciparum (Pf) MAG was characterized for its potential for development as an anti-malarial candidate.

NOT Open Access | Identification of compounds active against quiescent artemisinin-resistant Plasmodium falciparum parasites via the quiescent-stage survival assay (QSA)

July 14, 2020 - 15:42 -- NOT Open Access
Reyser T, Paloque L, Ouji M, Nguyen M, Ménard S, Witkowski B, Augereau JM, Benoit-Vical F
J Antimicrob Chemother. 2020 Jul 12:dkaa250

Quiescence is an unconventional mechanism of Plasmodium survival, mediating artemisinin resistance. This phenomenon increases the risk of clinical failures following artemisinin-based combination therapies (ACTs) by slowing parasite clearance and allowing the selection of parasites resistant to partner drugs.

Not Open Access | Pyronaridine-artesunate Efficacy and Safety in Uncomplicated Plasmodium falciparum Malaria in Areas of Artemisinin-resistant Falciparum in Viet Nam (2017-2018)

May 13, 2020 - 06:42 -- NOT Open Access
Quang Bui P, Hong Huynh Q, Thi Ta T, et al.
Clinical Infectious Diseases, Volume 70, Issue 10, 15 May 2020, Pages 2187–2195

Multidrug-resistant Plasmodium falciparum undermines the efficacy of currently deployed antimalarial therapies in southern Viet Nam.

NOT Open Access | Pyronaridine-artesunate Shows Promise as an Effective and Well-tolerated Treatment for Artemisinin-resistant Plasmodium falciparum Malaria

May 12, 2020 - 17:51 -- NOT Open Access
Okombo J, Fidock DA
Clin Infect Dis. 2020 May 6;70(10):2196-2198

Artemisinin-based combination therapies (ACTs) are the recommended first-line antimalarials for uncomplicated malaria and comprise a short-acting artemisinin-based component for rapid reduction of Plasmodium parasite burden partnered with a longer-acting drug to eliminate surviving parasites.

NOT Open Access | A Novel Antiparasitic Compound Kills Ring-Stage Plasmodium falciparum and Retains Activity Against Artemisinin-Resistant Parasites

March 9, 2020 - 13:41 -- NOT Open Access
Clements RL, Streva V, Dumoulin P, Huang W, Owens E, Raj DK, Burleigh B, Llinás M, Winzeler EA, Zhang Q, Dvorin JD
The Journal of Infectious Diseases, Volume 221, Issue 6, 15 March 2020, Pages 956–962

Spreading antimalarial resistance threatens effective treatment of malaria, an infectious disease caused by Plasmodium parasites. We identified a compound, BCH070, that inhibits asexual growth of multiple antimalarial-resistant strains of Plasmodium falciparum (half maximal inhibitory concentration [IC50] = 1–2 µM), suggesting that BCH070 acts via a novel mechanism of action.

Laboratory Detection of Artemisinin-Resistant Plasmodium falciparum

May 15, 2014 - 06:43 -- Open Access
Kesinee Chotivanich, Rupam Tripura, Debashish Das, Poravuth Yi, Nicholas P. J. Day, Sasithon Pukrittayakamee, Char Meng Chuor, Duong Socheat, Arjen M. Dondorp, and Nicholas J. White
Antimicrob. Agents Chemother. June 2014 vol. 58 no. 6 3157-3161

Conventional 48-h in vitro susceptibility tests have low sensitivity in identifying artemisinin-resistant Plasmodium falciparum, defined phenotypically by low in vivo parasite clearance rates.

Not Open Access | Novel phenotypic assays for the detection of artemisinin-resistant Plasmodium falciparum malaria in Cambodia: in-vitro and ex-vivo drug-response studies

November 20, 2013 - 17:15 -- NOT Open Access
Benoit Witkowski, Chanaki Amaratunga, Didier Menard, et al.
The Lancet Infectious Diseases, Volume 13, Issue 12, December 2013, Pages 1043-1049

We aimed to assess whether an in-vitro ring-stage survival assay (RSA) can identify culture-adapted P falciparum isolates from patients with slow-clearing or fast-clearing infections, to investigate the stage-dependent susceptibility of parasites to dihydroartemisinin in the in-vitro RSA, and to assess whether an ex-vivo RSA can identify artemisinin-resistant P falciparum infections.

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