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Evidence of Artemisinin-Resistant Malaria in Africa

September 23, 2021 - 11:38 -- Open Access
Balikagala B, Fukuda N, Mita T, et al.
N Engl J Med. 2021 Sep 23;385(13):1163-1171

In the six Southeast Asian countries that make up the Greater Mekong Subregion, Plasmodium falciparum has developed resistance to derivatives of artemisinin, the main component of first-line treatments for malaria. Clinical resistance to artemisinin monotherapy in other global regions, including Africa, would be problematic.

NOT Open Access | Pharmacotherapy for artemisinin-resistant malaria

July 28, 2021 - 14:58 -- NOT Open Access
Koehne E, Adegnika AA, Held J, Kreidenweiss A
Expert Opin Pharmacother. 2021 Jul 27

Malaria, the most devastating parasitic disease, is currently treated with artemisinin-based combination therapies (ACTs). Unfortunately, some ACTs are unable to rapidly clear Plasmodium falciparum parasites from the blood stream and are failing to cure malaria patients; a problem, so far, largely confined to Southeast Asia. There is a fear of resistant Plasmodium falciparum emerging in other parts of the world including Sub-Sahara Africa. Strategies for alternative treatments, ideally non-artemisinin based, are needed.

Mass drug administration for the acceleration of malaria elimination in a region of Myanmar with artemisinin-resistant falciparum malaria: a cluster-randomised trial

June 22, 2021 - 15:07 -- Open Access
McLean ARD, Indrasuta C, Smithuis FM, et al.
Lancet Infect Dis. 2021 Jun 17:S1473-3099(20)30997-X

To contain multidrug-resistant Plasmodium falciparum, malaria elimination in the Greater Mekong subregion needs to be accelerated while current antimalarials remain effective. We evaluated the safety, effectiveness, and potential resistance selection of dihydroartemisinin–piperaquine mass drug administration (MDA) in a region with artemisinin resistance in Myanmar.

NOT Open Access | Novel molecule combinations and corresponding hybrids targeting artemisinin-resistant Plasmodium falciparum parasites

May 5, 2021 - 11:03 -- NOT Open Access
Ouji M, Nguyen M, Mustière R, Jimenez T, Augereau JM, Benoit-Vical F, Deraeve C
Bioorg Med Chem Lett. 2021 May 1;39:127884

Malaria is still considered as the major parasitic disease and the development of artemisinin resistance does not improve this alarming situation. Based on the recent identification of relevant malaria targets in the artemisinin resistance context, novel drug combinations were evaluated against artemisinin-sensitive and artemisinin-resistant Plasmodium falciparum parasites.

Diversity-oriented synthesis derived indole based spiro and fused small molecules kills artemisinin-resistant Plasmodium falciparum

February 20, 2021 - 08:37 -- Open Access
Akshaykumar Nayak, Himani Saxena, Chandramohan Bathula, Tarkeshwar Kumar, Souvik Bhattacharjee, Subhabrata Sen and Ashish Gupta
Malaria Journal 2021 20:100, 17 February 2021

Despite numerous efforts to eradicate the disease, malaria continues to remain one of the most dangerous infectious diseases plaguing the world. In the absence of any effective vaccines and with emerging drug resistance in the parasite against the majority of anti-malarial drugs, the search for new drugs is urgently needed for effective malaria treatment.

Orthosteric-allosteric dual inhibitors of PfHT1 as selective antimalarial agents

January 20, 2021 - 07:40 -- Open Access
Huang J, Yuan Y, Yin H, et al.
Proc Natl Acad Sci U S A. 2021 Jan 19;118(3):e2017749118

Artemisinin-resistant malaria parasites have emerged and have been spreading, posing a significant public health challenge. Antimalarial drugs with novel mechanisms of action are therefore urgently needed. In this report, we exploit a "selective starvation" strategy by inhibiting Plasmodium falciparum hexose transporter 1 (PfHT1), the sole hexose transporter in P. falciparum, over human glucose transporter 1 (hGLUT1), providing an alternative approach to fight against multidrug-resistant malaria parasites. The crystal structure of hGLUT3, which shares 80% sequence similarity with hGLUT1, was resolved in complex with C3361, a moderate PfHT1-specific inhibitor, at 2.3-Å resolution.

Emergence of artemisinin-resistant Plasmodium falciparum with kelch13 C580Y mutations on the island of New Guinea

December 16, 2020 - 09:38 -- Open Access
Miotto O, Sekihara M, Mita T, et al.
PLoS Pathog. 2020 Dec 15;16(12):e1009133

The rapid and aggressive spread of artemisinin-resistant Plasmodium falciparum carrying the C580Y mutation in the kelch13 gene is a growing threat to malaria elimination in Southeast Asia, but there is no evidence of their spread to other regions. We conducted cross-sectional surveys in 2016 and 2017 at two clinics in Wewak, Papua New Guinea (PNG) where we identified three infections caused by C580Y mutants among 239 genotyped clinical samples. One of these mutants exhibited the highest survival rate (6.8%) among all parasites surveyed in ring-stage survival assays (RSA) for artemisinin.

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.


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