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plasmodium

A phase 1, placebo controlled, randomised, single ascending dose study and a volunteer infection study to characterize the safety, pharmacokinetics and antimalarial activity of the Plasmodium phosphatidylinositol 4-kinase inhibitor MMV390048

April 6, 2020 - 15:38 -- Open Access
Author(s): 
McCarthy JS, Donini C, Möhrle JJ, et al.
Reference: 
Clin Infect Dis. 2020 Apr 2. pii: ciaa368

MMV390048 is the first Plasmodium phosphatidylinositol 4-kinase inhibitor to reach clinical development as a new antimalarial. We aimed to characterize the safety, pharmacokinetics and antimalarial activity of a tablet formulation of MMV390048.

Safety, Tolerability, Pharmacokinetics, and Antimalarial Activity of the Novel Plasmodium Phosphatidylinositol 4-Kinase Inhibitor MMV390048 in Healthy Volunteers

March 30, 2020 - 10:47 -- Open Access
Author(s): 
Sinxadi P, Donini C, Johnstone H, Langdon G, Wiesner L, Allen E, Duparc S, Chalon S, McCarthy JS, Lorch U, Chibale K, Möhrle J, Barnes KI
Reference: 
Antimicrob Agents Chemother. 2020 Mar 24;64(4). pii: e01896-19

MMV390048 is a novel antimalarial compound that inhibits Plasmodium phosphatidylinositol-4-kinase. The safety, tolerability, pharmacokinetic profile, and antimalarial activity of MMV390048 were determined in healthy volunteers in three separate studies. A first-in-human, double-blind, randomized, placebo-controlled, single-ascending-dose study was performed. Additionally, a volunteer infection study investigated the antimalarial activity of MMV390048 using the Plasmodium falciparum induced blood-stage malaria (IBSM) model.

NOT Open Access | Plasmodium stage-selective antimalarials from Lophira lanceolata stem bark

March 23, 2020 - 14:53 -- NOT Open Access
Author(s): 
Soré H, Lopatriello A, Ebstie YA, Tenoh Guedoung AR, Hilou A, Pereira JA, Kijjoa A, Habluetzel A, Taglialatela-Scafati O
Reference: 
Phytochemistry Volume 174, June 2020, 112336

Targeting the transmissible stages of the Plasmodium parasite that develop in the human and mosquito host is a crucial strategy for malaria control and elimination. Medicinal plants offer a prolific source for the discovery of new antimalarial compounds. The recent identification of the gametocytocidal activity of lophirone E, obtained from the African plant Lophira lanceolata (Ochnaceae), inspired the evaluation of the plant also against early sporogonic stages of the parasite development.

Triple hit against Plasmodium

March 10, 2020 - 16:14 -- Open Access
Tags: 
Author(s): 
Hofer U
Reference: 
Nat Rev Microbiol. 2020 Mar 4

With rising rates of antimalarial drug resistance, new compounds with novel targets and mechanisms of action are urgently needed. Screening a library of aspartic protease inhibitors has now identified compounds that target two essential proteases of Plasmodium falciparum: plasmepsin IX and X. Further in vitro and in vivo experiments revealed that the inhibitors block liver, blood and mosquito stages of Plasmodium spp.

NOT Open Access | Asymptomatic Submicroscopic Plasmodium Infection Is Highly Prevalent and Is Associated with Anemia in Children Younger than 5 Years in South Kivu/Democratic Republic of Congo

March 9, 2020 - 14:37 -- NOT Open Access
Author(s): 
Lufungulo Bahati Y, Delanghe J, Bisimwa Balaluka G, Sadiki Kishabongo A, Philippe J
Reference: 
Am J Trop Med Hyg. 2020 Mar 2

One of the most important problems in controlling malaria is the limited access to effective and accurate diagnosis of malaria parasitemia. In the Democratic Republic of Congo (DRC), malaria is one of the leading causes of morbidity and mortality. The purpose of this study was to assess the prevalence of anemia and the relationship with asymptomatic submicroscopic Plasmodium infection.

NOT Open Access | Capture and Detection of Plasmodium vivax Lactate Dehydrogenase in a Bead-Based Multiplex Immunoassay

March 9, 2020 - 14:30 -- NOT Open Access
Author(s): 
Rogier E, Nace D, Ljolje D, Lucchi NW, Udhayakumar V, Aidoo M
Reference: 
Am J Trop Med Hyg. 2020 Mar 2

Laboratory detection of malaria antigens has proved valuable for research and epidemiological purposes. We recently developed a bead-based multiplex antigen assay for pan-Plasmodium and Plasmodium falciparum targets. Here, we report integration of a Plasmodium vivax–specific target to this multiplex panel: P. vivax lactate dehydrogenase (PvLDH).

NOT Open Access | Early endothelial activation precedes glycocalyx degradation and microvascular dysfunction in experimentally induced Plasmodium falciparum and Plasmodium vivax infection

March 9, 2020 - 14:24 -- NOT Open Access
Author(s): 
Woodford J, Yeo TW, Piera KA, Butler K, Weinberg JB, McCarthy JS, Anstey NM, Barber BE
Reference: 
Infect Immun. 2020 Mar 2. pii: IAI.00895-19

Endothelial activation and microvascular dysfunction are key pathogenic processes in severe malaria. We evaluated the early role of these processes in experimentally induced P. falciparum and P. vivax infection.

NOT Open Access | Plasmodium infection-cure cycles induce modulation of conventional dendritic cells

March 2, 2020 - 15:15 -- NOT Open Access
Author(s): 
Adachi R, Tamura T
Reference: 
Microbiol Immunol. 2020 Feb 25

Malaria is one of the most widespread human infectious diseases worldwide and a cause of mortality. It is difficult to induce immunological memory against malarial parasites, Plasmodium. The immunity to clinical malaria disease is acquired with multiple infection and treatment cycles, along with substantial reduction in parasite burden. However, the mechanism of the acquired immunity remains largely unclear. Conventional dendritic cells (cDCs) play a pivotal role in orchestration of immune responses. The purpose of this study is to analyze the characterization of cDCs after the infection and cure treatment cycles.

Use of real-time multiplex PCR, malaria rapid diagnostic test and microscopy to investigate the prevalence of Plasmodium species among febrile hospital patients in Sierra Leone

February 25, 2020 - 15:56 -- Open Access
Author(s): 
Tomasz A. Leski, Chris Rowe Taitt, David A. Stenger, et al.
Reference: 
Malaria Journal 2020 19:84, 21 February 2020

Malaria continues to affect over 200 million individuals every year, especially children in Africa. Rapid and sensitive detection and identification of Plasmodium parasites is crucial for treating patients and monitoring of control efforts. Compared to traditional diagnostic methods such as microscopy and rapid diagnostic tests (RDTs), DNA based methods, such as polymerase chain reaction (PCR) offer significantly higher sensitivity, definitive discrimination of Plasmodium species, and detection of mixed infections. While PCR is not currently optimized for routine diagnostics, its role in epidemiological studies is increasing as the world moves closer toward regional and eventually global malaria elimination. This study demonstrates the field use of a novel, ambient temperature-stabilized, multiplexed PCR assay in a small hospital setting in Sierra Leone.

Plasmodium-infected erythrocytes induce secretion of IGFBP7 to form type II rosettes and escape phagocytosis

February 22, 2020 - 17:21 -- Open Access
Author(s): 
Lee WC, Russell B, Sobota RM, Ghaffar K, Howland SW, Wong ZX, Maier AG, Dorin-Semblat D, Biswas S, Gamain B, Lau YL, Malleret B, Chu C, Nosten F, Renia L
Reference: 
Elife. 2020 Feb 18;9. pii: e51546

In malaria, rosetting is described as a phenomenon where an infected erythrocyte (IRBC) is attached to uninfected erythrocytes (URBC). In some studies, rosetting has been associated with malaria pathogenesis. Here, we have identified a new type of rosetting. Using a step-by-step approach, we identified IGFBP7, a protein secreted by monocytes in response to parasite stimulation, as a rosette-stimulator for Plasmodium falciparum- and P. vivax-IRBC. IGFBP7-mediated rosette-stimulation was rapid yet reversible.

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