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Scientific Articles

Reference and point-of-care testing for G6PD deficiency: Blood disorder interference, contrived specimens, and fingerstick equivalence and precision

September 23, 2021 - 09:04 -- Open Access
Author(s): 
Pal S, Myburgh J, Domingo GJ, et al.
Reference: 
PLoS One. 2021 Sep 20;16(9):e0257560

Certain clinical indications and treatments such as the use of rasburicase in cancer therapy and 8-aminoquinolines for Plasmodium vivax malaria treatment would benefit from a point-of-care test for glucose-6-phosphate dehydrogenase (G6PD) deficiency. Three studies were conducted to evaluate the performance of one such test: the STANDARD™ G6PD Test (SD BIOSENSOR, South Korea). First, biological interference on the test performance was evaluated in specimens with common blood disorders, including high white blood cell (WBC) counts.

An extended DNA-free intranuclear compartment organizes centrosome microtubules in malaria parasites

September 23, 2021 - 09:02 -- Open Access
Author(s): 
Simon CS, Funaya C, Bauer J, Voβ Y, Machado M, Penning A, Klaschka D, Cyrklaff M, Kim J, Ganter M, Guizetti J
Reference: 
Life Sci Alliance. 2021 Sep 17;4(11):e202101199

Proliferation of Plasmodium falciparum in red blood cells is the cause of malaria and is underpinned by an unconventional cell division mode, called schizogony. Contrary to model organisms, P. falciparum replicates by multiple rounds of nuclear divisions that are not interrupted by cytokinesis. Organization and dynamics of critical nuclear division factors remain poorly understood. Centriolar plaques, the centrosomes of P. falciparum, serve as microtubule organizing centers and have an acentriolar, amorphous structure. The small size of parasite nuclei has precluded detailed analysis of intranuclear microtubule organization by classical fluorescence microscopy.

NOT Open Access | How can we develop an effective subunit vaccine to achieve successful malaria eradication

September 23, 2021 - 09:00 -- NOT Open Access
Author(s): 
Pirahmadi S, Afzali S, Zargar M, Zakeri S, Mehrizi AA
Reference: 
Microb Pathog. 2021 Sep 18:105203

Malaria, a mosquito-borne infection, is the most widespread parasitic disease. Despite numerous efforts to eradicate malaria, this disease is still a health concern worldwide. Owing to insecticide-resistant vectors and drug-resistant parasites, available controlling measures are insufficient to achieve a malaria-free world. Thus, there is an urgent need for new intervention tools such as efficient malaria vaccines.

NOT Open Access | Insight into Recent Drug Discoveries against Trypanosomatids and Plasmodium spp Parasites: New Metal-based Compounds

September 23, 2021 - 08:58 -- NOT Open Access
Author(s): 
Scarim CB, de Farias RL, Chiba DE, Chin CM
Reference: 
Curr Med Chem. 2021 Sep 16


Scaffolds of metal-based compounds can act as pharmacophore groups in several ligands to treat various diseases, including tropical infectious diseases (TID). In this review article, we investigate the contribution of these moieties to medicinal inorganic chemistry in the last seven years against TID, including American trypanosomiasis (Chagas disease), human African trypanosomiasis (HAT, sleeping sickness), leishmania, and malaria.

Identification of host tRNAs preferentially recognized by the Plasmodium surface protein tRip

September 23, 2021 - 08:54 -- Open Access
Author(s): 
Cela M, Théobald-Dietrich A, Rudinger-Thirion J, Wolff P, Geslain R, Frugier M
Reference: 
Nucleic Acids Res. 2021 Sep 16:gkab769

Malaria is a life-threatening and devastating parasitic disease. Our previous work showed that parasite development requires the import of exogenous transfer RNAs (tRNAs), which represents a novel and unique form of host-pathogen interaction, as well as a potentially druggable target. This import is mediated by tRip (tRNA import protein), a membrane protein located on the parasite surface. tRip displays an extracellular domain homologous to the well-characterized OB-fold tRNA-binding domain, a structural motif known to indiscriminately interact with tRNAs.

NOT Open Access | Improved Liver Delivery of Primaquine by Phospholipid-Free Small Unilamellar Vesicles with Reduced Hemolytic Toxicity

September 23, 2021 - 08:51 -- NOT Open Access
Author(s): 
Al Fayez N, Böttger R, Rouhollahi E, Cullis PR, Witzigmann D, Li SD
Reference: 
Mol Pharm. 2021 Sep 21

Hemolytic toxicity caused by primaquine (PQ) is a high-risk condition that hampers the wide use of PQ to treat liver-stage malaria. This study demonstrated that phospholipid-free small unilamellar vesicles (PFSUVs) composed of Tween80 and cholesterol could encapsulate and deliver PQ to the hepatocytes with reduced exposure to the red blood cells (RBCs). Nonionic surfactant (Tween80) and cholesterol-forming SUVs with a mean diameter of 50 nm were fabricated for delivering PQ. Drug release/retention, drug uptake by RBCs, pharmacokinetics, and liver uptake of PFSUVs-PQ were evaluated in in vitro and in vivo models in comparison to free drugs.

Novel transdermal bioadhesive surfactant-based system for release and solubility improvement of antimalarial drugs Artemether-Lumefantrine

September 23, 2021 - 08:35 -- Open Access
Author(s): 
Volpe-Zanutto F, Fonseca-Santos B, Foglio MA, et al.
Reference: 
Biomed Mater. 2021 Sep 20

Artemether (ART) and lumefantrine (LUM) are the gold standard antimalarial drugs used for the treatment of malaria in children and pregnant women. Typically, ART and LUM are delivered orally in the form of a combined tablet, however, the appropriateness of this route of administration for these drugs is questionable due to the poor absorption and therefore bioavailability observed unless administered alongside lipid-rich foods.Transdermal drug delivery in the form of a patch-type system has been identified as a viable alternative to the conventional tablet-based therapy.

NOT Open Acess | Novel naphthyl based 1,2,4-trioxanes: Synthesis and in vivo efficacy in the Plasmodium yoelii nigeriensis in Swiss mice

September 23, 2021 - 08:31 -- NOT Open Access
Author(s): 
Karnatak M, Hassam M, Vanangamudi M, Sharma S, Kumar Yadav D, Singh C, Puri SK, Rawat V, Prakash Verma V
Reference: 
Bioorg Med Chem Lett. 2021 Sep 18:128372

A new series of 1,2,4-trioxanes9a1-a4,9b1-b4, 10-13and9c1-c4were synthesized and evaluated against multidrug-resistantPlasmodium yoelii nigeriensisin Swiss mice via oral and intramuscular (i.m.) routes. Adamantane-based trioxane9b4, the most active compound of the series, provided 100% protection to the infected mice at the dose 48 mg/kg x 4 days and 100% clearance of parasitemia at the dose 24 mg/kg × 4 days via oral route.

NOT Open Access | Gene editing in Plasmodium berghei made easy: Development of a CRISPR/Cas9 protocol using linear donor template and ribozymes for sgRNA generation

September 23, 2021 - 08:26 -- NOT Open Access
Author(s): 
Deligianni E, Kiamos IS
Reference: 
Mol Biochem Parasitol. 2021 Sep 16:111415

Efficient reverse genetics approaches are critical for the study of many organisms. The CRISPR/Cas9 gene editing system has led to a plethora of new tools for geneticists. Here, we successfully established a simplified CRISPR/Cas9 system for the malaria model parasite Plasmodium berghei. The homologous directed repair (HDR) template is provided as a linear template with homologous arms of 600-700bp while the CRISPR elements sgRNA and Cas9 are encoded from a single plasmid utilizing the Ribozyme-Guide-Ribozyme (RGR) expression strategy. Our approach eliminates the need for negative selection markers since the plasmid cannot be incorporated into the genome.

Microsporidia MB is found predominantly associated with Anopheles gambiae s.s and Anopheles coluzzii in Ghana

September 23, 2021 - 08:25 -- Open Access
Author(s): 
Akorli J, Akorli EA, Tetteh SNA, Amlalo GK, Opoku M, Pwalia R, Adimazoya M, Atibilla D, Pi-Bansa S, Chabi J, Dadzie SK
Reference: 
Sci Rep. 2021 Sep 20;11(1):18658

A vertically transmitted microsporidian, Microsporidia MB, with the ability to disrupt Plasmodium development was reported in Anopheles arabiensis from Kenya, East Africa. To demonstrate its range of incidence, archived DNA samples from 7575 Anopheles mosquitoes collected from Ghana were screened. MB prevalence was observed at 1.8%. An. gambiae s.s constituted 87% of positive mosquitoes while the remaining were from An. coluzzii.

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