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artemisinin combination therapies

A novel multistage antiplasmodial inhibitor targeting Plasmodium falciparum histone deacetylase 1

December 15, 2020 - 14:27 -- Open Access
Huang Z, Li R, Jiang L, et al.
Cell Discov. 2020 Dec 11;6(1):93

Although artemisinin combination therapies have succeeded in reducing the global burden of malaria, multidrug resistance of the deadliest malaria parasite, Plasmodium falciparum, is emerging worldwide. Innovative antimalarial drugs that kill all life-cycle stages of malaria parasites are urgently needed. Here, we report the discovery of the compound JX21108 with broad antiplasmodial activity against multiple life-cycle stages of malaria parasites.

Adoption of evidence-based global policies at the national level: intermittent preventive treatment for malaria in pregnancy and first trimester treatment in Kenya, Malawi, Mali and The Gambia

November 14, 2020 - 16:19 -- Open Access
Webster J, Hoyt J, Hill J, et al.
Health Policy Plan. 2020 Nov 12:czaa132

In 2012, the World Health Organization (WHO) updated its policy on intermittent preventive treatment in pregnancy with sulphadoxine-pyrimethamine (IPTp-SP). A global recommendation to revise the WHO policy on the treatment of malaria in the first trimester is under review. We conducted a retrospective study of the national policy adoption process for revised IPTp-SP dosing in four sub-Saharan African countries.

Retargeting azithromycin analogues to have dual-modality antimalarial activity

October 1, 2020 - 15:25 -- Open Access
Burns AL, Sleebs BE, Wilson DW, et al.
BMC Biol. 2020 Sep 29;18(1):133

Resistance to front-line antimalarials (artemisinin combination therapies) is spreading, and development of new drug treatment strategies to rapidly kill Plasmodium spp. malaria parasites is urgently needed. Azithromycin is a clinically used macrolide antibiotic proposed as a partner drug for combination therapy in malaria, which has also been tested as monotherapy. However, its slow-killing ‘delayed-death’ activity against the parasite’s apicoplast organelle and suboptimal activity as monotherapy limit its application as a potential malaria treatment. Here, we explore a panel of azithromycin analogues and demonstrate that chemical modifications can be used to greatly improve the speed and potency of antimalarial action.

Quality of clinical management of children diagnosed with malaria: A cross-sectional assessment in 9 sub-Saharan African countries between 2007-2018

September 15, 2020 - 14:40 -- Open Access
Cohen JL, Leslie HH, Saran I, Fink G
PLoS Med. 2020 Sep 14;17(9):e1003254

Appropriate clinical management of malaria in children is critical for preventing progression to severe disease and for reducing the continued high burden of malaria mortality. This study aimed to assess the quality of care provided to children under 5 diagnosed with malaria across 9 sub-Saharan African countries.

Synthesis and biological evaluation of novel quinoline-piperidine scaffolds as antiplasmodium agents

July 15, 2020 - 14:25 -- Open Access
Van de Walle T, Boone M, Van Puyvelde J, Combrinck J, Smith PJ, Chibale K, Mangelinckx S, D'hooghe M
Eur J Med Chem. 2020 Jul 15; 198:112330

The parasitic disease malaria places almost half of the world's population at risk of infection and is responsible for more than 400,000 deaths each year. The first-line treatment, artemisinin combination therapies (ACT) regimen, is under threat due to emerging resistance of Plasmodium falciparum strains in e.g. the Mekong delta. Therefore, the development of new antimalarial agents is crucial in order to circumvent the growing resistance.

Advances and Roadblocks in the Treatment of Malaria

July 14, 2020 - 15:45 -- Open Access
Hanboonkunupakarn B, White NJ
Br J Clin Pharmacol. 2020 Jul 12

The deployment of artesunate for severe malaria and the artemisinin combination therapies (ACTs) for uncomplicated malaria has been a major advance in antimalarial therapeutics. These drugs have reduced treated mortality, accelerated recovery, and reduced treatment failure rates and transmission from the treated infection. Artemisinin derivatives remain highly effective against falciparum malaria in most malaria endemic areas but significant resistance has emerged in the Greater Mekong subregion of Southeast Asia.

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