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drug resistance

Measurement of gene amplifications related to drug resistance in Plasmodium falciparum using droplet digital PCR

March 3, 2021 - 15:47 -- Open Access
Suttipat Srisutham, Kanokon Suwannasin, Rungniran Sugaram, Arjen M. Dondorp and Mallika Imwong
Malaria Journal 2021 20:120, 28 February 2021

Copy number variations (CNVs) of the Plasmodium falciparum multidrug resistance 1 (pfmdr1), P. falciparum plasmepsin2 (pfplasmepsin2) and P. falciparum GTP cyclohydrolase 1 (pfgch1) genes are associated with anti-malarial drug resistance in P. falciparum malaria. Droplet digital PCR (ddPCR) assays have been developed for accurate assessment of CNVs in several human genes. The aim of the present study was to develop and validate ddPCR assays for detection of the CNVs of P. falciparum genes associated with resistance to anti-malarial drugs.

NOT Open Access | Leveraging Peptaibol Biosynthetic Promiscuity for Next-Generation Antiplasmodial Therapeutics

February 11, 2021 - 09:29 -- NOT Open Access
Lee JW, Collins JE, Wendt KL, Chakrabarti D, Cichewicz RH
J Nat Prod. 2021 Feb 10

Malaria remains a worldwide threat, afflicting over 200 million people each year. The emergence of drug resistance against existing therapeutics threatens to destabilize global efforts aimed at controlling Plasmodium spp. parasites, which is expected to leave vast portions of humanity unprotected against the disease. To address this need, systematic testing of a fungal natural product extract library assembled through the University of Oklahoma Citizen Science Soil Collection Program has generated an initial set of bioactive extracts that exhibit potent antiplasmodial activity (EC50 < 0.30 μg/mL) and low levels of toxicity against human cells (less than 50% reduction in HepG2 growth at 25 μg/mL).

NOT Open Access | In-silico profiling and structural insights into the impact of nSNPs in the P. falciparum acetyl-CoA transporter gene to understand the mechanism of drug resistance in malaria

February 3, 2021 - 14:34 -- NOT Open Access
Sardar R, Katyal N, Ahamad S, Jade DD, Ali S, Gupta D
J Biomol Struct Dyn. 2021 Feb;39(2):558-569

The continuous emergence of resistance to the available drugs poses major constraints in the development of effective therapeutics against malaria. Malaria drug resistance has been attributed to be the manifestation of numerous factors. For example, mutations in the parasite transporter protein acetyl-CoA transporter (Pfact) can remarkably affect its uptake affinity for a drug molecule against malaria, and hence enhance its susceptibility to resistance. To identify major contributors to its loss of functionality, we have thoroughly scrutinized eight such recently reported resistant mutants, via in-silico tools in terms of alterations in different properties.

Progress and challenges in the use of fluorescence‐based flow cytometric assays for anti‐malarial drug susceptibility tests

January 27, 2021 - 11:48 -- Open Access
Kasem Kulkeaw
Malaria Journal 2021 20:57, 21 January 2021

Drug-resistant Plasmodium is a frequent global threat in malaria eradication programmes, highlighting the need for new anti-malarial drugs and efficient detection of treatment failure. Plasmodium falciparum culture is essential in drug discovery and resistance surveillance. Microscopy of Giemsa-stained erythrocytes is common for determining anti-malarial effects on the intraerythrocytic development of cultured Plasmodium parasites. Giemsa-based microscopy use is conventional but laborious, and its accuracy depends largely on examiner skill.

Drug resistance markers within an evolving efficacy of anti-malarial drugs in Cameroon: a systematic review and meta-analysis (1998–2020)

January 13, 2021 - 10:01 -- Open Access
Peter Thelma Ngwa Niba, Akindeh M. Nji, Wilfred F. Mbacham, et al.
Malaria Journal 2021 20:32, 9 January 2021

Malaria remains highly endemic in Cameroon. The rapid emergence and spread of drug resistance was responsible for the change from monotherapies to artemisinin-based combinations. This systematic review and meta-analysis aimed to determine the prevalence and distribution of Plasmodium falciparum drug resistance markers within an evolving efficacy of anti-malarial drugs in Cameroon from January 1998 to August 2020.

KASP: a genotyping method to rapid identification of resistance in Plasmodium falciparum

January 9, 2021 - 13:10 -- Open Access
Ana Alvarez-Fernandez, María J. Bernal, Isabel Fradejas, Alexandra Martin Ramírez, Noor Azian Md Yusuf, Marta Lanza, Shamilah Hisam, Ana Pérez de Ayala and José M. Rubio
Malaria Journal 2021 20:16, 6 January 2021

The emergence and spread of anti-malarial resistance continues to hinder malaria control. Plasmodium falciparum, the species that causes most human malaria cases and most deaths, has shown resistance to almost all known anti-malarials. This anti-malarial resistance arises from the development and subsequent expansion of Single Nucleotide Polymorphisms (SNPs) in specific parasite genes. A quick and cheap tool for the detection of drug resistance can be crucial and very useful for use in hospitals and in malaria control programmes. It has been demonstrated in different contexts that genotyping by Kompetitive Allele Specific PCR (KASP), is a simple, fast and economical method that allows a high-precision biallelic characterization of SNPs, hence its possible utility in the study of resistance in P. falciparum.

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.


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