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drug-resistant

NOT Open Access | STK35L1 regulates host cell cycle-related genes and is essential for Plasmodium infection during the liver stage of malaria

August 11, 2021 - 14:34 -- NOT Open Access
Author(s): 
Sharma PK, Kalia I, Kaushik V, Brünnert D, Quadiri A, Kashif M, Chahar KR, Agrawal A, Singh AP, Goyal P
Reference: 
Exp Cell Res. 2021 Aug 3:112764

Protein kinases of both the parasite and the host are crucial in parasite invasion and survival and might act as drug targets against drug-resistant malaria. STK35L1 was among the top five hits in kinome-wide screening, suggesting its role in malaria's liver stage. However, the role of host STK35L1 in malaria remains elusive. In this study, we found that STK35L1 was highly upregulated during the infection of Plasmodium berghei (P. berghei) in HepG2 cells and mice liver, and knockdown of STK35L1 remarkably suppressed the sporozoites' infection in HepG2 cells.

Not Open Access | Strategies for the Syntheses of Pactamycin and Jogyamycin

June 22, 2021 - 15:15 -- NOT Open Access
Author(s): 
Gerstner NC, Nicastri KA, Schomaker JM
Reference: 
Angew Chem Int Ed Engl. 2021 Jun 21;60(26):14252-14271

Pactamycin and jogyamycin are aminocyclopentitol natural products, where each core carbon bears a stereodefined alcohol or amine moiety. Their structural complexity, coupled with the diversity of functional groups coexisting in a condensed space, make them fascinating synthetic targets in their own right.

Drug-Resistant Malaria Detected in Africa Will Require Monitoring

June 16, 2021 - 15:19 -- Open Access
Author(s): 
Kuehn BM
Reference: 
JAMA. 2021 Jun 15;325(23):2335

Evidence in Africa that the malaria parasite Plasmodium falciparum has developed genetic variants that confer partial resistance to the antimalarial drug artemisinin is a warning of potential treatment failure on the horizon, a drug-resistance monitoring study suggested.

Repurposing of existing therapeutics to combat drug-resistant malaria

April 1, 2021 - 09:06 -- Open Access
Author(s): 
Yadav K, Shivahare R, Shaham SH, Joshi P, Sharma A, Tripathi R
Reference: 
Biomed Pharmacother. 2021 Apr;136:111275

In the era of drug repurposing, speedy discovery of new therapeutic options for the drug-resistant malaria is the best available tactic to reduce the financial load and time in the drug discovery process. Six anticancer drugs, three immunomodulators and four antibiotics were selected for the repositioning against experimental malaria owing to their mode of action and published literature. The efficacy of existing therapeutics was evaluated against chloroquine-resistant in vitro and in vivo strains of Plasmodium falciparum and P. yoelii, respectively. All the pre-existing FDA-approved drugs along with leptin were primarily screened against chloroquine-resistant (PfK1) and drug-sensitive (Pf3D7) strains of P. falciparum using SYBR green-based antiplasmodial assay.

NOT Open Access | Robenidine Analogues Are Potent Antimalarials in Drug-Resistant Plasmodium falciparum

March 17, 2021 - 09:31 -- NOT Open Access
Author(s): 
Krollenbrock A, Li Y, Kelly JX, Riscoe MK
Reference: 
ACS Infect Dis. 2021 Mar 16

Robenidine is a veterinary drug used in the poultry industry to treat coccidiosis caused by parasites in the Eimeria genus. Though this compound and related aminoguanidines have recently been studied in other pathogens, the chemotype has not been systematically explored to optimize antimalarial activity despite the close genetic relationship between Eimeria and Plasmodium (both are members of the Apicomplexa phylum of unicellular, spore-forming parasites).

Changes in the frequencies of Plasmodium falciparum dhps and dhfr drug-resistant mutations in children from Western Kenya from 2005 to 2018: the rise of Pfdhps S436H

October 22, 2020 - 15:45 -- Open Access
Author(s): 
M. Andreína Pacheco, Kristan A. Schneider, Qiuying Cheng, Elly O. Munde, Caroline Ndege, Clinton Onyango, Evans Raballah, Samuel B. Anyona, Collins Ouma, Douglas J. Perkins and Ananias A. Escalante
Reference: 
Malaria Journal 2020 19:378, 22 October 2020

Sulfadoxine-pyrimethamine (SP) is the only anti-malarial drug formulation approved for intermittent preventive treatment in pregnancy (IPTp). However, mutations in the Plasmodium falciparum dhfr (Pfdhfr) and dhps (Pfdhps) genes confer resistance to pyrimethamine and sulfadoxine, respectively. Here, the frequencies of SP resistance-associated mutations from 2005 to 2018 were compared in samples from Kenyan children with malaria residing in a holoendemic transmission region.

Identification and the potential involvement of miRNAs in the regulation of artemisinin biosynthesis in A. annua

August 18, 2020 - 14:40 -- Open Access
Author(s): 
Khan S, Ali A, Saifi M, Saxena P, Ahlawat S, Abdin MZ
Reference: 
Sci Rep. 2020 Aug 12;10(1):13614

Micro RNAs (miRNAs) play crucial regulatory roles in multiple biological processes. Recently they have garnered the attention for their strong influence on the secondary metabolite production in plants. Their role in the regulation of artemisinin (ART) biosynthesis is, however, not fully elucidated. ART is a potent anti-malarial compound recommended by WHO for the treatment of drug-resistant malaria. It is produced by Artemisia annua (A. annua).

K13-Mediated Reduced Susceptibility to Artemisinin in Plasmodium falciparum Is Overlaid on a Trait of Enhanced DNA Damage Repair

August 10, 2020 - 14:32 -- Open Access
Author(s): 
Xiong A, Prakash P, Gao X, Chew M, Tay IJJ, Woodrow CJ, Engelward BP, Han J, Preiser PR
Reference: 
Cell Rep. 2020 Aug 4;32(5):107996

Southeast Asia has been the hotbed for the development of drug-resistant malaria parasites, including those with resistance to artemisinin combination therapy. While mutations in the kelch propeller domain (K13 mutations) are associated with artemisinin resistance, a range of evidence suggests that other factors are critical for the establishment and subsequent transmission of resistance in the field.

NOT Open Access | Interactions Between Antenatal Sulfadoxine-Pyrimethamine, Drug-Resistant Plasmodium falciparum Parasites, and Delivery Outcomes in Malawi

July 27, 2020 - 12:29 -- NOT Open Access
Author(s): 
Taylor SM, Levitt B, Freedman B, Madanitsa M, Thwai KL, Kalilani-Phiri L, Khairallah C, Mwapasa V, Ter Kuile FO, Meshnick SR
Reference: 
J Infect Dis. 2020 Jul 23; 222(4):661-669

Sulfadoxine-pyrimethamine (SP) is used as intermittent preventive therapy in pregnancy (IPTp) for malaria in sub-Saharan Africa. The resistance marker dhps A581G has been associated with reduced IPTp-SP efficacy and enhanced morbidity in SP recipients.

Plasmodium vivax AMA1: Implications of distinct haplotypes for immune response

July 9, 2020 - 08:45 -- Open Access
Author(s): 
Bittencourt NC, da Silva ABIE, Albrecht L, et al.
Reference: 
PLoS Negl Trop Dis 14(7): e0008471

In Brazil, Plasmodium vivax infection accounts for around 80% of malaria cases. This infection has a substantial impact on the productivity of the local population as the course of the disease is usually prolonged and the development of acquired immunity in endemic areas takes several years. The recent emergence of drug-resistant strains has intensified research on alternative control methods such as vaccines.

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