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Scientific Articles

Marked reduction in antibiotic usage following intensive malaria control in a cohort of Ugandan children

December 7, 2021 - 21:30 -- Open Access
Author(s): 
Krezanoski PJ, Roh ME, Rek J, Nankabirwa JI, Arinaitwe E, Staedke SG, Nayiga S, Hsiang MS, Smith D, Kamya M, Dorsey G
Reference: 
BMC Med. 2021 Nov 30;19(1):294

Intensive malaria control may have additional benefits beyond reducing the incidence of symptomatic malaria. We compared antibiotic treatment of children before and after the implementation of highly effective malaria control interventions in Tororo, a historically high transmission area of Uganda.

NOT Open Access | The parasitophorous vacuole nutrient channel is critical for drug access in malaria parasites and modulates the artemisinin resistance fitness cost

December 7, 2021 - 21:27 -- NOT Open Access
Author(s): 
Mesén-Ramírez P, Bergmann B, Spielmann T, et al.
Reference: 
Cell Host Microbe. 2021 Nov 30:S1931-3128(21)00508-4

Intraerythrocytic malaria parasites proliferate bounded by a parasitophorous vacuolar membrane (PVM). The PVM contains nutrient permeable channels (NPCs) conductive to small molecules, but their relevance for parasite growth for individual metabolites is largely untested. Here we show that growth-relevant levels of major carbon and energy sources pass through the NPCs.

Characterization and utility of immobilized metal affinity-functionalized cellulose membranes for point-of-care malaria diagnostics

December 7, 2021 - 21:26 -- Open Access
Author(s): 
Moore CP, Pieterson K, DeSousa JM, Toote LE, Wright DW
Reference: 
J Chromatogr B Analyt Technol Biomed Life Sci. 2021 Dec 1;1186:123023

Immobilized metal affinity chromatography (IMAC) is a well-established technique for protein separation and purification. IMAC has been previously utilized to capture the malaria biomarker histidine-rich protein 2 (HRP2) from blood, enhancing the sensitivity of field-appropriate diagnostic tools such as lateral flow assays. However, little work has been done to translate this technique to a truly field-usable design. In this study, IMAC-functionalized cellulose membranes are created and characterized fully for future use in applied malaria diagnostics.

NOT Open Access | Property activity refinement of 2-anilino 4-amino substituted quinazolines as antimalarials with fast acting asexual parasite activity

December 7, 2021 - 21:24 -- NOT Open Access
Author(s): 
Ashton TD, Ngo A, Sleebs BE, et al.
Reference: 
Bioorg Chem. 2021 Dec;117:105359

Malaria is a devastating disease caused by Plasmodium parasites. Emerging resistance against current antimalarial therapeutics has engendered the need to develop antimalarials with novel structural classes. We recently described the identification and initial optimization of the 2-anilino quinazoline antimalarial class. Here, we refine the physicochemical properties of this antimalarial class with the aim to improve aqueous solubility and metabolism and to reduce adverse promiscuity. We show the physicochemical properties of this class are intricately balanced with asexual parasite activity and human cell cytotoxicity.

NOT Open Access | Structure-activity relationship and molecular modelling studies of quinazolinedione derivatives MMV665916 as potential antimalarial agent

December 7, 2021 - 21:20 -- NOT Open Access
Author(s): 
Mourot L, Schmitt M, Mouray E, Spichty M, Florent I, Albrecht S
Reference: 
Bioorg Med Chem. 2021 Dec 1;51:116513

A series of new quinazolinedione derivatives have been readily synthesized and evaluated for their in vitro antiplasmodial growth inhibition activity. Most of the compounds inhibited P. falciparum FcB1 strain in the low to medium micromolar concentration.

Repeated Plasmodium falciparum infection in humans drives the clonal expansion of an adaptive gammadelta T cell repertoire

December 7, 2021 - 21:19 -- Open Access
Author(s): 
von Borstel A, Chevour P, Davey MS, et al.
Reference: 
Sci Transl Med. 2021 Dec;13(622):eabe7430

Repeated Plasmodium falciparum infections drive the development of clinical immunity to malaria in humans; however, the immunological mechanisms that underpin this response are only partially understood. We investigated the impact of repeated P. falciparum infections on human γδ T cells in the context of natural infection in Malian children and adults, as well as serial controlled human malaria infection (CHMI) of U.S. adults, some of whom became clinically immune to malaria.

NOT Open Access | Artemisinin Cocrystals for Bioavailability Enhancement. Part 2: In Vivo Bioavailability and Physiologically Based Pharmacokinetic Modeling

December 7, 2021 - 21:16 -- NOT Open Access
Author(s): 
Kaur M, Yardley V, Wang K, Masania J, Arroo RRJ, Turner DB, Li M
Reference: 
Mol Pharm. 2021 Dec 6;18(12):4272-4289

We report the evaluation and prediction of the pharmacokinetic (PK) performance of artemisinin (ART) cocrystal formulations, that is, 1:1 artemisinin/orcinol (ART-ORC) and 2:1 artemisinin/resorcinol (ART2-RES), using in vivo murine animal and physiologically based pharmacokinetic (PBPK) models. The efficacy of the ART cocrystal formulations along with the parent drug ART was tested in mice infected with Plasmodium berghei.

Early life adversity, biological adaptation, and human capital: evidence from an interrupted malaria control program in Zambia

December 7, 2021 - 21:14 -- Open Access
Author(s): 
Fink G, Venkataramani AS, Zanolini A
Reference: 
J Health Econ. 2021 Dec;80:102532

Growing evidence from evolutionary biology demonstrates how early life shocks trigger physiological changes. We report the evaluation and prediction of the pharmacokinetic (PK) performance of artemisinin (ART) cocrystal formulations, that is, 1:1 artemisinin/orcinol (ART-ORC) and 2:1 artemisinin/resorcinol (ART2-RES), using in vivo murine animal and physiologically based pharmacokinetic (PBPK) models.

NOT Open Access | Cutting Edge: Subunit Booster Vaccination Confers Sterilizing Immunity against Liver-Stage Malaria in Mice Initially Primed with a Weight-Normalized Dose of Radiation-Attenuated Sporozoites

December 7, 2021 - 21:10 -- NOT Open Access
Author(s): 
Lefebvre MN, Drewry LL, Pewe LL, Hancox LS, Reyes-Sandoval A, Harty JT
Reference: 
J Immunol. 2021 Dec 1;207(11):2631-2635

Radiation-attenuated sporozoite (RAS) vaccination offers hope for global malaria control through induction of protective liver-stage-specific memory CD8 T cells. Effective RAS vaccination regimens exist; however, widespread implementation remains unfeasible. A key difficulty resides in the need to administer three or more doses i.v. to achieve sufficient immunity.

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