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artemisinin

Plasmodium falciparum rosetting protects schizonts against artemisinin

November 11, 2021 - 10:12 -- Open Access
Author(s): 
Lee WC, Russell B, Lee B, Chu CS, Phyo AP, Sriprawat K, Lau YL, Nosten F, Rénia L
Reference: 
EBioMedicine. 2021 Nov 5;73:103680

Artemisinin (ART) resistance in Plasmodium falciparum is thought to occur during the early stage of the parasite's erythrocytic cycle. Here, we identify a novel factor associated with the late stage parasite development that contributes to ART resistance.

Time to scale up molecular surveillance for anti-malarial drug resistance in sub-saharan Africa

October 29, 2021 - 14:02 -- Open Access
Author(s): 
Christian Nsanzabana
Reference: 
Malaria Journal 2021 20:401, 13 October 2021

Artemisinin resistance has emerged and spread in the Greater Mekong Sub-region (GMS), followed by artemisinin-based combination therapy failure, due to both artemisinin and partner drug resistance. More worrying, artemisinin resistance has been recently reported and confirmed in Rwanda. Therefore, there is an urgent need to strengthen surveillance systems beyond the GMS to track the emergence or spread of artemisinin and partner drug resistance in other endemic settings. Currently, anti-malarial drug efficacy is monitored primarily through therapeutic efficacy studies (TES).

Pyronaridine-Artesunate (Pyramax) for the Treatment of Artemisinin- and Piperaquine-Resistant Plasmodium falciparum in the Central Highlands of Vietnam

October 5, 2021 - 10:48 -- Open Access
Author(s): 
Manh ND, Thanh NV, Quang HH, Van NTT, San NN, Phong NC, Birrell GW, Edstein MD, Edgel KA, Martin NJ, Chavchich M
Reference: 
Antimicrob Agents Chemother. 2021 Sep 27:AAC0027621

The rise in Plasmodium falciparum resistance to dihydroartemisinin-piperaquine in Vietnam justifies the need to evaluate alternative artemisinin-based combination therapies. Between July 2018 and October 2019, a single-arm trial of pyronaridine-artesunate (Pyramax, PA) was conducted in Dak Nong province, Vietnam. PA (3-day course) was administered to adults and children infected with P. falciparum. PA was well tolerated by the participants. The proportion of patients with Day 42 PCR-corrected adequate clinical and parasitological response was 95.2% (95% confidence interval [CI], 82.3 to 98.8, n = 40/42) for treating falciparum malaria.

New Insights into the Spread of Resistance to Artemisinin and its Analogues

September 15, 2021 - 12:04 -- Open Access
Author(s): 
Noreen N, Ullah A, Salman SM, Mabkhot Y, Alsayari A, Badshah SL
Reference: 
J Glob Antimicrob Resist. 2021 Sep 10:S2213-7165(21)00208-3

The causative agent of malaria, Plasmodium falciparum, has been developing resistance to several drugs worldwide since more than five decades. Initially, resistance was toward drugs such as chloroquine, pyrimethamine, sulfadoxine, mefloquine, and quinine. Research studies are now reporting the resistance of parasites to the most effective and novel drug used against malaria infection worldwide, that is, artemisinin; for this reason, the first-line treatment strategy, including artemisinin combination therapy, is becoming unsuccessful in areas where drug resistance is highly prevalent.

Resistance to artemisinin in falciparum malaria parasites: A redox-mediated phenomenon

August 25, 2021 - 16:10 -- Open Access
Author(s): 
Egwu CO, Pério P, Augereau JM, Tsamesidis I, Benoit-Vical F, Reybier K
Reference: 
Free Radic Biol Med. 2021 Aug 17:S0891-5849(21)00476-7

Malaria remains a major public health disease due to its high yearly mortality and morbidity. Resistance to the gold standard drug, artemisinin, is worrisome and needs better understanding in order to be overcome. In this work, we sought to study whether redox processes are involved in artemisinin resistance. As artemisinin is known to act among others via production of reactive species, we first compared the production of reactive oxygen species and concomitant protein oxidation in artemisinin-sensitive and artemisinin-resistant parasites when treated with artemisinin.

Questioning the Claimed Superiority of Malaria Parasite Ex Vivo Viability Reduction Over Observed Parasite Clearance Rate

August 17, 2021 - 14:14 -- Open Access
Author(s): 
White NJ, Watson JA
Reference: 
J Infect Dis. 2021 Aug 16;224(4):738-739

To the Editor—In a study of 10 Plasmodium falciparum–infected volunteers with submicroscopic parasitemias given a single 200-mg dose of artesunate, Rebelo et al [1] reported a substantial difference in the ex vivo growth of sequentially sampled circulating ring-stage [2] parasites comparing infections with artemisinin-sensitive (Pfkelch wild-type) and artemisinin-resistant (Pfkelch R539T) parasites.

NOT Open Access | Current and emerging strategies to combat antimalarial resistance

August 10, 2021 - 18:03 -- NOT Open Access
Author(s): 
Rasmussen C, Alonso P, Ringwald P
Reference: 
Expert Rev Anti Infect Ther. 2021 Aug 5

Since the spread of chloroquine resistance in Plasmodium falciparum in the 1960s, recommendations have been made on how to respond to antimalarial resistance. Only with the advent of artemisinin partial resistance were large scale efforts made in the Greater Mekong Subregion to carry out recommendations in a coordinated and well-funded manner. Independent emergence of parasites partially resistant to artemisinins has now been reported in Rwanda.

The key issues and development strategy of Chinese Classical Formulas pharmaceutical preparations

August 10, 2021 - 17:55 -- Open Access
Author(s): 
Luo H, Chen H, Liu C, Zhang S, Vong CT, Tan D, Dai Y, Wang Y, Chen S
Reference: 
Chin Med. 2021 Aug 4;16(1):70

It is well-known that Prof. Tu Youyou won the Nobel Prize in Physiology or Medicine in 2015 due to the research on artemisinin treating malaria, and this can be regarded as the milestone of modernization of Traditional medicine. This first Nobel Prize in Traditional Chinese medicine (TCM) has aroused profound impetus in the investigation of TCM and attracted global attention to the ancient books of TCM.

Not Open Access | Artemisinin inspired synthetic endoperoxide drug candidates: Design, synthesis, and mechanism of action studies

August 10, 2021 - 17:46 -- NOT Open Access
Author(s): 
Woodley CM, Amado PSM, Cristiano MLS, O'Neill PM
Reference: 
Med Res Rev. 2021 Aug 6

Artemisinin combination therapies (ACTs) have been used as the first-line treatments against Plasmodium falciparum malaria for decades. Recent advances in chemical proteomics have shed light on the complex mechanism of action of semi-synthetic artemisinin (ARTs), particularly their promiscuous alkylation of parasite proteins via previous heme-mediated bioactivation of the endoperoxide bond. Alarmingly, the rise of resistance to ART in South East Asia and the synthetic limitations of the ART scaffold have pushed the course for the necessity of fully synthetic endoperoxide-based antimalarials.

NOT Open Access | Combating multi-drug resistant malaria parasite by inhibiting falcipain-2 and heme-polymerization: Artemisinin-peptidyl vinyl phosphonate hybrid molecules as new antimalarials

August 10, 2021 - 17:27 -- NOT Open Access
Author(s): 
Aratikatla EK, Kalamuddin M, Rana KC, Datta G, Asad M, Sundararaman S, Malhotra P, Mohmmed A, Bhattacharya AK
Reference: 
Eur J Med Chem. 2021 Aug 5;220:113454

Artemisinin-based combination therapies (ACTs) have been able to reduce the clinical and pathological malaria cases in endemic areas around the globe. However, recent reports have shown a progressive decline in malaria parasite clearance in South-east Asia after ACT treatment, thus envisaging a need for new artemisinin (ART) derivatives and combinations. To address the emergence of drug resistance to current antimalarials, here we report the synthesis of artemisinin-peptidyl vinyl phosphonate hybrid molecules that show superior efficacy than artemisinin alone against chloroquine-resistant as well as multidrug-resistant Plasmodium falciparum strains with EC50 in pico-molar ranges.

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