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

August 25, 2021 - 16:10 -- Open Access
Egwu CO, Pério P, Augereau JM, Tsamesidis I, Benoit-Vical F, Reybier K
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.

NOT Open Access | Dual Inhibition of Parasitic Targets: a Valuable Strategy to Treat Malaria and Neglected Tropical Diseases

August 11, 2021 - 14:42 -- NOT Open Access
Previti S, Di Chio C, Ettari R, Zappalà M
Curr Med Chem. 2021 Aug 10

Despite the countless efforts made in the last decades, malaria and neglected tropical diseases remain a high-impact health problem in developing countries. Malaria is one of the most severe parasitic diseases, with over 200 million cases and 400 000 deaths in 2019. Parasitic diseases caused by trypanosomatidae, namely Human African Trypanosomiasis, Chagas disease, and leishmaniasis, register the highest rates of mortality amongst all the neglected tropical diseases.

Clinical and In Vitro Resistance of Plasmodium falciparum to Artesunate-Amodiaquine in Cambodia

August 4, 2021 - 16:07 -- Open Access
Mairet-Khedim M, Leang R, Witkowski B, et al.
Clin Infect Dis. 2021 Aug 2;73(3):406-413

Artesunate-amodiaquine is a potential therapy for uncomplicated malaria in Cambodia.

NOT Open Access | First report of N1575Y mutation in Anopheles gambiae in Sierra Leone

August 4, 2021 - 11:54 -- NOT Open Access
Yin J, Yamba F, Zheng C, Smith SJ, Wang L, Li H, Xia Z, Zhou S, Xiao N
Infect Genet Evol. 2021 Aug;92:104852

The resistance of mosquito vectors to insecticides is one of the biological obstacles in the fight against malaria. Understanding of the status and mechanisms underlying the insecticide resistance in Anopheles gambiae species is necessary for success of vector control efforts. The study aimed to determine the molecular forms of An. gambiae from four districts in Sierra Leone during May and June 2018, and the level of N1575Y mutation.

Characterization of resistance profile (intensity and mechanisms) of Anopheles gambiae in three communes of northern Benin, West Africa

July 28, 2021 - 15:13 -- Open Access
Casimir Dossou Kpanou, Hermann W. Sagbohan, Martin Akogbéto, et al.
Malaria Journal 2021 20:328, 27 July 2021

The selection and the spread of insecticide resistance in malaria vectors to the main classes of insecticides used in vector control tools are a major and ongoing challenge to malaria vector control programmes. This study aimed to determine the intensity of vector resistance to insecticides in three regions of Benin with different agro-ecological characteristics.

The newly discovered role of endocytosis in artemisinin resistance

July 28, 2021 - 14:37 -- Open Access
Behrens HM, Schmidt S, Spielmann T
Med Res Rev. 2021 Jul 26

Artemisinin and its derivatives (ART) are the cornerstone of malaria treatment as part of artemisinin combination therapy (ACT). However, reduced susceptibility to artemisinin as well as its partner drugs threatens the usefulness of ACTs. Single point mutations in the parasite protein Kelch13 (K13) are necessary and sufficient for the reduced sensitivity of malaria parasites to ART but several alternative mechanisms for this resistance have been proposed.

The antimalarial MMV688533 provides potential for single-dose cures with a high barrier to Plasmodium falciparum parasite resistance

July 28, 2021 - 12:53 -- Open Access
Murithi JM, Pascal C, Leroy D, et al.
Sci Transl Med. 2021 Jul 21;13(603):eabg6013

The emergence and spread of Plasmodium falciparum resistance to first-line antimalarials creates an imperative to identify and develop potent preclinical candidates with distinct modes of action. Here, we report the identification of MMV688533, an acylguanidine that was developed following a whole-cell screen with compounds known to hit high-value targets in human cells.

NOT Open Access | Evaluation of the usefulness of intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine in a context with increased resistance of Plasmodium falciparum in Kingasani Hospital, Kinshasa in the Democratic Re

July 21, 2021 - 18:04 -- NOT Open Access
Kalenda NK, Yobi DM, Speybroeck N, et al.
Infect Genet Evol. 2021 Jul 17:105009

Increasing resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine (SP) threatens its usefulness for intermittent preventive treatment in pregnancy (IPTp-SP). The prophylactic effects of IPTp-SP on maternal malaria and adverse pregnancy outcomes were evaluated in Kingasani Hospital, Kinshasa in the Democratic Republic of Congo (DRC).

Markov chain Monte Carlo Gibbs sampler approach for estimating haplotype frequencies among multiple malaria infected human blood samples

July 14, 2021 - 11:06 -- Open Access
Gie Ken-Dror and Pankaj Sharma
Malaria Journal 2021 20:311, 10 July 2021

Malaria patients can have two or more haplotypes in their blood sample making it challenging to identify which haplotypes they carry. In addition, there are challenges in measuring the type and frequency of resistant haplotypes in populations. This study presents a novel statistical method Gibbs sampler algorithm to investigate this issue.

Balanced impacts of fitness and drug pressure on the evolution of PfMDR1 polymorphisms in Plasmodium falciparum

July 7, 2021 - 07:56 -- Open Access
Marvin Duvalsaint, Melissa D. Conrad, Stephen Tukwasibwe, Patrick K. Tumwebaze, Jennifer Legac, Roland A. Cooper and Philip J. Rosenthal
Malaria Journal 2021 20:292, 30 June 2021

Anti-malarial drug resistance may be limited by decreased fitness in resistant parasites. Important contributors to resistance are mutations in the Plasmodium falciparum putative drug transporter PfMDR1.


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