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Choosing interventions to eliminate forest malaria: preliminary results of two operational research studies inside Cambodian forests

January 21, 2021 - 15:43 -- Open Access
Author(s): 
Amber Kunkel, Chea Nguon, Patrice Piola, et al.
Reference: 
Malaria Journal 2021 20:51, 20 January 2021

Rapid elimination of Plasmodium falciparum malaria in Cambodia is a goal with both national and international significance. Transmission of malaria in Cambodia is limited to forest environments, and the main population at risk consists of forest-goers who rely on forest products for income or sustenance. The ideal interventions to eliminate malaria from this population are unknown.

The use of dried tube specimens of Plasmodium falciparum in an external quality assessment programme to evaluate health worker performance for malaria rapid diagnostic testing in healthcare centres in Togo

January 21, 2021 - 15:38 -- Open Access
Author(s): 
Ameyo M. Dorkenoo, Kafui Codjo Kouassi, Adjane K. Koura, Martin L. Adams, Komivi Gbada, Gnatoulma Katawa, Kossi Yakpa, Remi Charlebois, Ekaterina Milgotina, Michele O. Merkel and Michael Aidoo
Reference: 
Malaria Journal 2021 20:50, 20 January 2021

The use of rapid diagnostic tests (RDTs) to diagnose malaria is common in sub-Saharan African laboratories, remote primary health facilities and in the community. Currently, there is a lack of reliable methods to ascertain health worker competency to accurately use RDTs in the testing and diagnosis of malaria. Dried tube specimens (DTS) have been shown to be a consistent and useful method for quality control of malaria RDTs; however, its application in National Quality Management programmes has been limited.

Malaria in the USA: How Vulnerable Are We to Future Outbreaks

January 21, 2021 - 15:35 -- Open Access
Author(s): 
Dye-Braumuller KC, Kanyangarara M
Reference: 
Curr Trop Med Rep. 2021 Jan 14:1-9

Malaria poses a threat to nearly half of the world’s population, and recent literature in the USA is lacking regarding understanding risk for local outbreaks. This article aims to review Anopheles mosquito data, vector-borne disease outbreak preparedness, and human travel data from large international gateway cities in an effort to examine risk for localized outbreaks.

Erythrocyte sphingosine kinase regulates intraerythrocytic development of Plasmodium falciparum

January 21, 2021 - 15:31 -- Open Access
Author(s): 
Sah RK, Pati S, Saini M, Singh S
Reference: 
Sci Rep. 2021 Jan 13;11(1):1257

The sphingolipid pool is key regulator of vital cellular functions in Plasmodium falciparum a causative agent for deadly malaria. Erythrocytes, the host for asexual stage of Plasmodium, are major reservoir for Sphingosine-1-phosphate (S1P). Erythrocyte possesses Sphingosine kinase (SphK) that catalyzed its biosynthesis from sphingosine (Sph). Since, Plasmodium lacks SphK homologous protein it can be envisaged that it co-opts sphingolipids from both intraerythrocytic as well as extracellular pools for its growth and development. Herein, by sphingosine-NBD probing, we report that infected erythrocytes imports Sph from extracellular pool, which is converted to S1P and thereby taken by P. falciparum.

Semi-mechanistic pharmacokinetic and pharmacodynamic modelling of piperaquine in a volunteer infection study with Plasmodium falciparum blood-stage malaria

January 21, 2021 - 15:29 -- Open Access
Author(s): 
Wattanakul T, Baker M, Mohrle J, McWhinney B, Hoglund RM, McCarthy JS, Tarning J
Reference: 
Antimicrob Agents Chemother. 2021 Jan 19:AAC.01583-20

Dihydroartemisinin-piperaquine is a recommended first-line artemisinin combination therapy for falciparum malaria. Piperaquine is also under consideration for other antimalarial combination therapies. The aim of this study was to develop a pharmacokinetic-pharmacodynamic model that could be used to optimize the use of piperaquine in new antimalarial combination therapies. The pharmacokinetic-pharmacodynamic model was developed using data from a previously reported dose-ranging study where 24 healthy volunteers were inoculated 1,800 blood-stage Plasmodium falciparum parasites.

Phosphorylation of the Canonical Histone H2A Marks Foci of Damaged DNA in Malaria Parasites

January 21, 2021 - 15:28 -- Open Access
Author(s): 
Goyal M, Heinberg A, Mitesser V, Kandelis-Shalev S, Singh BK, Dzikowski R
Reference: 
mSphere. 2021 Jan 13;6(1):e01131-20

Plasmodium falciparum parasites proliferate within circulating red blood cells and are responsible for the deadliest form of human malaria. These parasites are exposed to numerous intrinsic and external sources that could cause DNA damage; therefore, they have evolved efficient mechanisms to protect their genome integrity and allow them to proliferate under such conditions. In higher eukaryotes, double-strand breaks rapidly lead to phosphorylation of the core histone variant H2A.X, which marks the site of damaged DNA. We show that in P. falciparum that lacks the H2A.X variant, the canonical P. falciparum H2A (PfH2A) is phosphorylated on serine 121 upon exposure to sources of DNA damage.

Histone acetyltransferase PfGCN5 regulates stress responsive and artemisinin resistance related genes in Plasmodium falciparum

January 21, 2021 - 15:26 -- Open Access
Author(s): 
Rawat M, Kanyal A, Sahasrabudhe A, Vembar SS, Lopez-Rubio JJ, Karmodiya K
Reference: 
Sci Rep. 2021 Jan 13;11(1):852

Plasmodium falciparum has evolved resistance to almost all front-line drugs including artemisinin, which threatens malaria control and elimination strategies. Oxidative stress and protein damage responses have emerged as key players in the generation of artemisinin resistance. In this study, we show that PfGCN5, a histone acetyltransferase, binds to the stress-responsive genes in a poised state and regulates their expression under stress conditions.

Pathogenic Pore Forming Proteins of Plasmodium Triggers the Necrosis of Endothelial Cells Attributed to Malaria Severity

January 21, 2021 - 15:24 -- Open Access
Author(s): 
Shivappagowdar A, Garg S, Srivastava A, Hada RS, Kalia I, Singh AP, Garg LC, Pati S, Singh S
Reference: 
Toxins (Basel). 2021 Jan 15;13(1):E62

Severe malaria caused by Plasmodium falciparum poses a major global health problem with high morbidity and mortality. P. falciparum harbors a family of pore-forming proteins (PFPs), known as perforin like proteins (PLPs), which are structurally equivalent to prokaryotic PFPs. These PLPs are secreted from the parasites and, they contribute to disease pathogenesis by interacting with host cells. The severe malaria pathogenesis is associated with the dysfunction of various barrier cells, including endothelial cells (EC). Several factors, including PLPs secreted by parasites, contribute to the host cell dysfunction.

Value regimes and pricing in the pharmaceutical industry: financial capital inflation (hepatitis C) versus innovation and production capital savings for malaria medicines

January 21, 2021 - 15:22 -- Open Access
Author(s): 
Cassier M
Reference: 
Biosocieties. 2021 Jan 13:1-19

The idea of this paper is to draw a parallel between two diametrically opposed political economies of medicine that coexist today. The first is embodied in the invention, appropriation, and distribution of antivirals for hepatitis C, particularly sofosbuvir, which was commercialized at an initial price of $85,000 in the United States, €56,000 in France, and $8000 in Brazil.

A chemokine-fusion vaccine targeting immature dendritic cells elicits elevated antibody responses to malaria sporozoites in infant macaques

January 21, 2021 - 15:21 -- Open Access
Author(s): 
Luo K, Gordy JT, Zavala F, Markham RB
Reference: 
Sci Rep. 2021 Jan 13;11(1):1220

Infants and young children are the groups at greatest risk for severe disease resulting from Plasmodium falciparum infection. We previously demonstrated in mice that a protein vaccine composed of the chemokine macrophage inflammatory protein 3α genetically fused to the minimally truncated circumsporozoite protein of P. falciparum (MCSP) elicits high concentrations of specific antibody and significant reduction of liver sporozoite load in a mouse model system.

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