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MAIP: a web service for predicting blood-stage malaria inhibitors

February 25, 2021 - 08:15 -- Open Access
Bosc N, Felix E, Leach AR, et al.
J Cheminform. 2021 Feb 22;13(1):13

Malaria is a disease affecting hundreds of millions of people across the world, mainly in developing countries and especially in sub-Saharan Africa. It is the cause of hundreds of thousands of deaths each year and there is an ever-present need to identify and develop effective new therapies to tackle the disease and overcome increasing drug resistance. Here, we extend a previous study in which a number of partners collaborated to develop a consensus in silico model that can be used to identify novel molecules that may have antimalarial properties.

NOT Open Access | Host-pathogen interaction in the tissue environment during Plasmodium blood-stage infection

February 3, 2021 - 15:11 -- NOT Open Access
Yui K, Inoue SI
Parasite Immunol. 2021 Feb;43(2):e12763

Human malarial infection occurs after an infectious Anopheles mosquito bites. Following the initial liver-stage infection, parasites transform into merozoites, infecting red blood cells (RBCs). Repeated RBC infection then occurs during the blood-stage infection, while patients experience various malarial symptoms. Protective immune responses are elicited by this systemic infection, but excessive responses are sometimes harmful for hosts.

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
Wattanakul T, Baker M, Mohrle J, McWhinney B, Hoglund RM, McCarthy JS, Tarning J
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.

NOT Open Access | gammadelta T cells suppress Plasmodium falciparum blood-stage infection by direct killing and phagocytosis

January 13, 2021 - 11:07 -- NOT Open Access
Junqueira C, Polidoro RB, Lieberman J, et al.
Nat Immunol. 2021 Jan 11

Activated Vγ9Vδ2 (γδ2) T lymphocytes that sense parasite-produced phosphoantigens are expanded in Plasmodium falciparum-infected patients. Although previous studies suggested that γδ2 T cells help control erythrocytic malaria, whether γδ2 T cells recognize infected red blood cells (iRBCs) was uncertain. Here we show that iRBCs stained for the phosphoantigen sensor butyrophilin 3A1 (BTN3A1). γδ2 T cells formed immune synapses and lysed iRBCs in a contact, phosphoantigen, BTN3A1 and degranulation-dependent manner, killing intracellular parasites.

B cell intrinsic expression of IFNlambda receptor suppresses the acute humoral immune response to experimental blood-stage malaria

December 2, 2020 - 09:49 -- Open Access
Hahn WO, Pepper M, Liles WC
Virulence. 2020 Dec;11(1):594-606

Antibodies play a critical protective role in the host response to blood-stage malaria infection. The role of cytokines in shaping the antibody response to blood-stage malaria is unclear. Interferon lambda (IFNλ), a type III interferon, is a cytokine produced early during blood-stage malaria infection that has an unknown physiological role during malaria infection.

Balancing in a black box: Potential immunomodulatory roles for TGF-beta signaling during blood-stage malaria

December 2, 2020 - 08:04 -- Open Access
Drewry LL, Harty JT
Virulence. 2020 Dec;11(1):159-169

Malarial disease caused by Plasmodium parasites challenges the mammalian immune system with a delicate balancing act. Robust inflammatory responses are required to control parasite replication within red blood cells, which if unchecked, can lead to severe anemia and fatality. However, the same inflammatory response that controls parasite replication is also associated with immunopathology and severe disease, as is exemplified by cerebral malaria.

Not Open Access | Designed Parasite-Selective Rhomboid Inhibitors Block Invasion and Clear Blood-Stage Malaria

November 24, 2020 - 13:37 -- NOT Open Access
Gandhi S, Baker RP, Cho S, Stanchev S, Strisovsky K, Urban S
Cell Chem Biol. 2020 Nov 19;27(11):1410-1424.e6

Rhomboid intramembrane proteases regulate pathophysiological processes, but their targeting in a disease context has never been achieved. We decoded the atypical substrate specificity of malaria rhomboid PfROM4, but found, unexpectedly, that it results from "steric exclusion": PfROM4 and canonical rhomboid proteases cannot cleave each other's substrates due to reciprocal juxtamembrane steric clashes.

Characterization of a Plasmodium falciparum PHISTc protein, PF3D7_0801000, in blood- stage malaria parasites

November 7, 2020 - 12:38 -- Open Access
Nagaoka H, Kanoi BN, Morita M, Nakata T, Palacpac NMQ, Egwang TG, Horii T, Tsuboi T, Takashima E
Parasitol Int. 2020 Nov 1:102240

During intraerythrocytic development Plasmodium falciparum deploys numerous proteins to support erythrocyte invasion, intracellular growth and development, as well as host immune evasion. Since these proteins are key for parasite intraerythrocytic survival and propagation, they represent attractive targets for antimalarial vaccines. In this study we sought to characterize a member of the PHISTc family of proteins, PF3D7_0801000, as a potential vaccine target.

A comprehensive RNA handling and transcriptomics guide for high-throughput processing of Plasmodium blood-stage samples

October 13, 2020 - 12:36 -- Open Access
Michal Kucharski, Jaishree Tripathi, Sourav Nayak, Lei Zhu, Grennady Wirjanata, Rob W. van der Pluijm, Mehul Dhorda, Arjen Dondorp and Zbynek Bozdech
Malaria Journal 2020 19:363, 9 October 2020

Sequencing technology advancements opened new opportunities to use transcriptomics for studying malaria pathology and epidemiology. Even though in recent years the study of whole parasite transcriptome proved to be essential in understanding parasite biology there is no compiled up-to-date reference protocol for the efficient generation of transcriptome data from growing number of samples. Here, a comprehensive methodology on how to preserve, extract, amplify, and sequence full-length mRNA transcripts from Plasmodium-infected blood samples is presented that can be fully streamlined for high-throughput studies.

NOT Open Access | First-in-human randomised trial and follow-up study of Plasmodium falciparum blood-stage malaria vaccine BK-SE36 with CpG-ODN(K3)

October 7, 2020 - 14:28 -- NOT Open Access
Ezoe S, Palacpac NMQ, Horii T, et al.
Vaccine. 2020 Oct 1:S0264-410X(20)31227-5

BK-SE36 is blood-stage malaria vaccine candidate that is undergoing clinical trials. Here, the safety and immunogenicity of BK-SE36 with a novel adjuvant, CpG-ODN(K3) (thus, BK-SE36/CpG) was assessed in a phase 1a trial in Japan.


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