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blood stage

Mechanistic within-host models of the asexual Plasmodium falciparum infection: a review and analytical assessment

July 14, 2021 - 11:02 -- Open Access
Flavia Camponovo, Tamsin E. Lee, Jonathan R. Russell, Lydia Burgert, Jaline Gerardin and Melissa A. Penny
Malaria Journal 2021 20:309, 10 July 2021

Malaria blood-stage infection length and intensity are important drivers of disease and transmission; however, the underlying mechanisms of parasite growth and the host’s immune response during infection remain largely unknown. Over the last 30 years, several mechanistic mathematical models of malaria parasite within-host dynamics have been published and used in malaria transmission models.

Inter-study and time-dependent variability of metabolite abundance in cultured red blood cells

July 7, 2021 - 14:42 -- Open Access
Shivendra G. Tewari, Krithika Rajaram, Russell P. Swift, Bobby Kwan, Jaques Reifman, Sean T. Prigge and Anders Wallqvist
Malaria Journal 2021 20:299, 2 July 2021

Cultured human red blood cells (RBCs) provide a powerful ex vivo assay platform to study blood-stage malaria infection and propagation. In recent years, high-resolution metabolomic methods have quantified hundreds of metabolites from parasite-infected RBC cultures under a variety of perturbations. In this context, the corresponding control samples of the uninfected culture systems can also be used to examine the effects of these perturbations on RBC metabolism itself and their dependence on blood donors (inter-study variations).

The plasma membrane calcium ATPase 4 does not influence parasite levels but partially promotes experimental cerebral malaria during murine blood stage malaria

July 7, 2021 - 08:05 -- Open Access
Ana Villegas-Mendez, Nicholas Stafford, Delvac Oceandy, et al.
Malaria Journal 2021 20:297, 2 July 2021

Recent genome wide analysis studies have identified a strong association between single nucleotide variations within the human ATP2B4 gene and susceptibility to severe malaria. The ATP2B4 gene encodes the plasma membrane calcium ATPase 4 (PMCA4), which is responsible for controlling the physiological level of intracellular calcium in many cell types, including red blood cells (RBCs). It is, therefore, postulated that genetic differences in the activity or expression level of PMCA4 alters intracellular Ca2+ levels and affects RBC hydration, modulating the invasion and growth of the Plasmodium parasite within its target host cell.

NOT Open Access | Plasmodium vivax Latent Liver Stage Infection and Relapse: Biological Insights and New Experimental Tools

July 6, 2021 - 14:40 -- NOT Open Access
Schäfer C, Zanghi G, Vaughan AM, Kappe SHI
Annu Rev Microbiol. 2021 Jul 1

Plasmodium vivax is the most widespread human malaria parasite, in part because it can form latent liver stages known as hypnozoites after transmission by female anopheline mosquitoes to human hosts. These persistent stages can activate weeks, months, or even years after the primary clinical infection; replicate; and initiate relapses of blood stage infection, which causes disease and recurring transmission.

NOT Open Access | Comprehensive Analysis of Transcript and Protein Relative Abundance During Blood Stages of Plasmodium falciparum Infection

January 27, 2021 - 10:57 -- NOT Open Access
Kamaliddin C, Guillochon E, Salnot V, Rombaut D, Huguet S, Guillonneau F, Houzé S, Cot M, Deloron P, Argy N, Bertin GI
J Proteome Res. 2021 Jan 21

Plasmodium falciparum is the main causative agent of human malaria. During the intraerythrocytic development cycle, the P. falciparum morphology changes dramatically from circulating young rings to sequestered mature trophozoites and schizonts. Sequestered forms contribute to the pathophysiology of severe malaria as the infected erythrocytes obstruct the microvascular flow in deep organs and induce local inflammation. However, the sequestration mechanism limits the access to the corresponding parasitic form in the clinical samples from patients infected with P. falciparum. To complement this deficiency, we aimed to evaluate the relevance of mRNA study as a proxy of protein expression in sequestered parasites.

Safety and feasibility of apheresis to harvest and concentrate parasites from subjects with induced blood stage Plasmodium vivax infection

January 20, 2021 - 08:23 -- Open Access
Anand Odedra, Kari Mudie, Fiona Amante, et al.
Malaria Journal 2021 20:43, 14 January 2021

In the absence of a method to culture Plasmodium vivax, the only way to source parasites is ex vivo. This hampers many aspects of P. vivax research. This study aimed to assess the safety of apheresis, a method for selective removal of specific components of blood as a means of extracting and concentrating P. vivax parasites.

Disruption of Plasmodium falciparum histidine-rich protein 2 may affect haem metabolism in the blood stage

December 15, 2020 - 16:03 -- Open Access
Yang Y, Tang T, Feng B, Li S, Hou N, Ma X, Jiang L, Xin X, Chen Q
Parasit Vectors. 2020 Dec 9;13(1):611

Haem is a key metabolic factor in the life cycle of the malaria parasite. In the blood stage, the parasite acquires host haemoglobin to generate amino acids for protein synthesis and the by-product haem for metabolic use. The malaria parasite can also synthesize haem de novo on its own. Plasmodium falciparum-specific histidine-rich protein 2 (PfHRP2) has a haem-binding site to mediate the formation of haemozoin, a biocrystallized form of haem aggregates. Notably, the gene regulates the mechanism of haemoglobin-derived haem metabolism and the de novo haem biosynthetic pathway in the Pfhrp2-disrupted parasite line during the intraerythrocytic stages.

Defining the antimalarial activity of cipargamin in healthy volunteers experimentally infected with blood stage Plasmodium falciparum

November 18, 2020 - 12:18 -- Open Access
McCarthy JS, Abd-Rahman AN, Collins KA, Marquart L, Griffin P, Kümmel A, Fuchs A, Winnips C, Mishra V, Csermak-Renner K, Jain JP, Gandhi P
Antimicrob Agents Chemother. 2020 Nov 16:AAC.01423-20

The spiroindolone cipargamin, a new antimalarial compound that inhibits Plasmodium ATP4, is currently in clinical development. This study aimed to characterize the antimalarial activity of cipargamin in healthy volunteers experimentally infected with blood-stage Plasmodium falciparum Eight subjects were intravenously inoculated with parasite-infected erythrocytes and received a single oral dose of 10 mg cipargamin 7 days later. Blood samples were collected to monitor the development and clearance of parasitemia, and plasma cipargamin concentrations.

NOT Open Access | The endoplasmic reticulum-resident serpentine receptor SR10 has important functions for asexual and sexual blood stage development of Plasmodium falciparum

September 15, 2020 - 15:09 -- NOT Open Access
Njila Tchoufack EJ, Hahnfeld L, Pitschelatow G, Bennink S, Pradel G
Mol Biochem Parasitol. 2020 Sep 2:111315

Serpentine receptors (SRs) are transmembrane proteins generally acting as mediators to facilitate the communication between a cell and its environment. At least six putative SR-like proteins are encoded in the genome of the malaria parasite Plasmodium falciparum.

Contributions of IFN-γ and granulysin to the clearance of Plasmodium yoelii blood stage

September 15, 2020 - 10:59 -- Open Access
Hojo-Souza NS, de Azevedo PO, de Castro JT, Teixeira-Carvalho A, Lieberman J, Junqueira C, Gazzinelli RT
PLoS Pathog. 2020 Sep 10;16(9):e1008840

P. vivax-infected Retics (iRetics) express human leukocyte antigen class I (HLA-I), are recognized by CD8+ T cells and killed by granulysin (GNLY) and granzymes. However, how Plasmodium infection induces MHC-I expression on Retics is unknown. In addition, whether GNLY helps control Plasmodium infection in vivo has not been studied. Here, we examine these questions using rodent infection with the P. yoelii 17XNL strain, which has tropism for Retics.


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