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drug resistance

Triple Artemisinin-Based Combination Therapies for Malaria - A New Paradigm

January 6, 2021 - 13:23 -- Open Access
van der Pluijm RW, Amaratunga C, Dhorda M, Dondorp AM
Trends Parasitol. 2021 Jan;37(1):15-24

Recent gains in the fight against malaria are threatened by the emergence and spread of artemisinin and partner drug resistance in Plasmodium falciparum in the Greater Mekong Subregion (GMS). When artemisinins are combined with a single partner drug, all recommended artemisinin-based combination therapies have shown reduced efficacy in some countries in the GMS at some point.

Polymorphisms in Plasmodium falciparum chloroquine resistance transporter (Pfcrt) and multidrug-resistant gene 1 (Pfmdr-1) in Nigerian children 10 years post-adoption of artemisinin-based combination treatments

December 30, 2020 - 13:52 -- Open Access
Kayode AT, Akano K, Happi CT, et al.
Int J Parasitol. 2020 Dec 23:S0020-7519(20)30318-0

The emergence and spread of Plasmodium falciparum parasites resistant to artemisinin derivatives and their partners in southeastern Asia threatens malaria control and elimination efforts, and heightens the need for an alternative therapy. We have explored the distribution of P. falciparum chloroquine resistance transporter (Pfcrt) and multidrug-resistant gene 1 (Pfmdr-1) haplotypes 10 years following adoption of artemisinin-based combination therapies (ACTs) in a bid to investigate the possible re-emergence of Chloroquine (CQ)-sensitive parasites in Nigeria, and investigated the effect of these P. falciparum haplotypes on treatment outcomes of patients treated with ACTs. A total of 271 children aged < 5 years with uncomplicated falciparum malaria were included in this study. Polymorphisms on codons 72-76 of the Pfcrt gene and codon 86 and 184 of Pfmdr-1 were determined using the high resolution melting (HRM) assay.

Not Open Access | Atypical molecular basis for drug resistance to mitochondrial function inhibitors in Plasmodium falciparum

December 29, 2020 - 15:19 -- NOT Open Access
Painter HJ, Morrisey JM, Mather MW, Orchard LM, Luck C, Smilkstein MJ, Riscoe MK, Vaidya AB, Llinás M
Antimicrob Agents Chemother. 2020 Dec 23:AAC.02143-20

The continued emergence of drug-resistant Plasmodium falciparum parasites hinders global attempts to eradicate malaria, emphasizing the need to identify new antimalarial drugs. Attractive targets for chemotherapeutic intervention are the cytochrome (cyt) bc1 complex, which is an essential component of the mitochondrial electron transport chain (mtETC) necessary for ubiquinone recycling and mitochondrially localized dihydroorotate dehydrogenase (DHODH) critical for de novo pyrimidine synthesis.

Effectiveness of seasonal malaria chemoprevention at scale in west and central Africa: an observational study

December 8, 2020 - 10:39 -- Open Access
ACCESS-SMC Partnership
Lancet. 2020 Dec 5;396(10265):1829-1840

Seasonal malaria chemoprevention (SMC) aims to prevent malaria in children during the high malaria transmission season. The Achieving Catalytic Expansion of SMC in the Sahel (ACCESS-SMC) project sought to remove barriers to the scale-up of SMC in seven countries in 2015 and 2016. We evaluated the project, including coverage, effectiveness of the intervention, safety, feasibility, drug resistance, and cost-effectiveness.

NOT Open Access | Assessment of in vitro and in vivo antimalarial efficacy and GC-fingerprints of selected medicinal plant extracts

December 2, 2020 - 08:38 -- NOT Open Access
Sachdeva C, Mohanakrishnan D, Kumar S, Kaushik NK
Exp Parasitol. 2020 Dec;219:108011

A hallmark of mortality and morbidity, malaria is affecting nearly half of the world's population. Emergence of drug-resistant strains of malarial parasite prompts identification and evaluation of medicinal plants and their constituents that may hold the key to a new and effective anti-malarial drug. In this context, nineteen methanolic extracts from seventeen medicinal plants were evaluated for anti-plasmodial potential against Plasmodium falciparum strain 3D7 (Chloroquine (CQ) sensitive) and INDO (CQ resistant) using fluorescence based SYBR-Green assay and for cytotoxic effects against mammalian cell lines.

Assessing the in vitro sensitivity with associated drug resistance polymorphisms in Plasmodium vivax clinical isolates from Delhi, India

November 25, 2020 - 12:42 -- Open Access
Matlani M, Kumar A, Singh V
Exp Parasitol. 2020 Nov 19:108047

The drug resistance of Plasmodium vivax in clinical cases remains largely unknown till date because of the difficulty in diagnosing the resistant P. vivax strains. The present study was undertaken to determine the prevalence of mutant alleles in drug resistance genes viz P. vivax multi-drug resistance (pvmdr-1), chloroquine resistance transporter (pvcrt-o), dihydrofolate reductase (pvdhfr) and dihydropteroate synthase (pvdhps) along with in vitro chloroquine (CQ) sensitivity in P. vivax clinical isolates.

Molecular surveillance of antimalarial partner drug resistance in sub-Saharan Africa: a spatial-temporal evidence mapping study

November 18, 2020 - 12:27 -- Open Access
Hanna Y Ehrlich, Justin Jones, Sunil Parikh
Lancet Microbe. 2020 Sep;1(5):e209-e217.

Molecular markers for antimalarial drug resistance can be used to rapidly monitor the emergence and spatial distribution of resistance to artemisinin-based combination therapies (ACTs). Little has been done to analyse molecular surveillance efforts or to assess surveillance coverage. This study aimed to develop an evidence map to characterise the spatial-temporal distribution and sampling methodologies of drug resistance surveillance in sub-Saharan Africa, specifically focusing on markers associated with ACT partner drugs.

Identification of tyrosine kinase inhibitors that halt Plasmodium falciparum parasitemia

November 17, 2020 - 13:05 -- Open Access
Kesely K, Noomuna P, Vieth M, Hipskind P, Haldar K, Pantaleo A, Turrini F, Low PS
PLoS One. 2020 Nov 12;15(11):e0242372

Although current malaria therapies inhibit pathways encoded in the parasite's genome, we have looked for anti-malaria drugs that can target an erythrocyte component because development of drug resistance might be suppressed if the parasite cannot mutate the drug's target. In search for such erythrocyte targets, we noted that human erythrocytes express tyrosine kinases, whereas the Plasmodium falciparum genome encodes no obvious tyrosine kinases.

A snapshot of Plasmodium falciparum malaria drug resistance markers in Sudan: a pilot study

November 10, 2020 - 14:22 -- Open Access
Mohamed NS, Abdelbagi H, Sibley CH, et al.
BMC Res Notes. 2020 Nov 7;13(1):512

Malaria infection is still known to be a worldwide public health problem, especially in tropical and sub-tropical African countries like Sudan. A pilot study conducted to describe the trend of P. falciparum drug resistance markers in 2017–2018 in comparison to CQ and AS/SP eras in Sudan. The Pfcrt, Pfmdr-1, Pfdhfr, and Pfdhps genes were investigated. Data deposited by the worldwide antimalarial resistance network was consulted, and the molecular markers previously reported from Sudan were analyzed.

NOT Open Access | In silico assessment of natural products and approved drugs as potential inhibitory scaffolds targeting aminoacyl-tRNA synthetases from Plasmodium

November 3, 2020 - 14:45 -- NOT Open Access
Doshi K, Pandya N, Datt M
3 Biotech. 2020 Nov;10(11):470

Malaria remains the leading cause of deaths globally, despite significant advancement towards understanding its epidemiology and availability of multiple therapeutic interventions. Poor efficacy of the approved vaccine, and the rapid emergence of antimalarial drug resistance, warrants an urgent need to expedite the process of development of new lead molecules targeting malaria.


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