Malaria, erythrocytic infection, and anemia.
Kasturi Haldar,Narla Mohandas +1 more
TLDR
Because of the complexities involved, the study of severe malarial anemia may need a "systems approach" to yield comprehensive understanding of defects in both erythropoiesis and immunity associated with disease.Abstract:
Malaria is a major world health problem. It results from infection of parasites belonging to the genus Plasmodium. Plasmodium falciparum and Plasmodium vivax cause the major human malarias, with P falciparum being the more virulent. During their blood stages of infection, both P falciparum and P vivax induce anemia. Severe malarial anemia caused by P falciparum is responsible for approximately a third of the deaths associated with disease. Malarial anemia appears to be multi-factorial. It involves increased removal of circulating erythrocytes as well as decreased production of erythrocytes in the bone marrow. The molecular mechanisms underlying malarial anemia are largely unknown. Over the last five years, malaria parasite ligands have been investigated for their remodeling of erythrocytes and possible roles in destruction of mature erythrocytes. Polymorphisms in cytokines have been associated with susceptibility to severe malarial anemia: these cytokines and malaria "toxins" likely function by perturbing erythropoiesis. Finally a number of co-infections increase susceptibility to malarial anemia, likely because they exacerbate inflammation caused by malaria. Because of the complexities involved, the study of severe malarial anemia may need a "systems approach" to yield comprehensive understanding of defects in both erythropoiesis and immunity associated with disease. New and emerging tools such as (i) mathematical modeling of the dynamics of host control of malarial infection, (ii) ex vivo perfusion of human spleen to measure both infected and uninfected erythrocyte retention, and (iii) in vitro development of erythroid progenitors to dissect responsiveness to cytokine imbalance or malaria toxins, may be especially useful to develop integrated mechanistic insights and therapies to control this major and fatal disease pathology.read more
Citations
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Journal ArticleDOI
Reconstruction and flux‐balance analysis of the Plasmodium falciparum metabolic network
TL;DR: A metabolic network reconstruction and flux‐balance analysis of Plasmodium falciparum, the primary agent of malaria, is presented and the model can be used to make clinically relevant predictions.
Journal ArticleDOI
Splenic Macrophage Subsets and Their Function during Blood-Borne Infections.
Henrique Borges da Silva,Raissa Fonseca,Rosana M Pereira,Alexandra dos Anjos Cassado,José M. Alvarez,Maria Regina D'Império Lima +5 more
TL;DR: Current data on how different macrophage subsets recognize and help eliminate blood-borne pathogens are reviewed, and how the inflammatory microenvironment in different phases of infection (acute, chronic, and after pathogen clearance) influences macrophages function and survival are reviewed.
Journal ArticleDOI
Malaria and human red blood cells.
Narla Mohandas,Xiuli An +1 more
TL;DR: A number of mechanism(s) are likely responsible for the protective effect of various red cell abnormalities including decreased invasion, impaired intraerythrocytic development of the parasites and altered interaction between exported parasite proteins and the red cell membrane skeleton.
Journal ArticleDOI
Major Burden of Severe Anemia from Non-Falciparum Malaria Species in Southern Papua: A Hospital-Based Surveillance Study
Nicholas M. Douglas,Daniel A. Lampah,Enny Kenangalem,Julie A. Simpson,Jeanne Rini Poespoprodjo,Paulus Sugiarto,Nicholas M. Anstey,Ric N. Price +7 more
TL;DR: Hospital-based surveillance data is used to estimate the risk of severe anemia and mortality associated with endemic Plasmodium species in southern Papua, Indonesia.
Journal ArticleDOI
Oxidative stress, eryptosis and anemia: a pivotal mechanistic nexus in systemic diseases.
Rosi Bissinger,Abdulla Al Mamun Bhuyan,Syed M. Qadri,Syed M. Qadri,Florian Lang,Florian Lang +5 more
TL;DR: The role of oxidative stress in reducing erythrocyte survival is discussed and novel insights into the possible use of antioxidants as putative antieryptotic and antianemic agents in a variety of systemic diseases are provided.
References
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Journal ArticleDOI
Targeting Malaria Virulence and Remodeling Proteins to the Host Erythrocyte
TL;DR: It is shown that a conserved pentameric sequence plays a central role in protein export into the host cell and the exported proteome in Plasmodium falciparum is predicted, with implications for the development of new antimalarials.
Journal ArticleDOI
A host-targeting signal in virulence proteins reveals a secretome in malarial infection.
N. Luisa Hiller,Souvik Bhattacharjee,Christiaan van Ooij,Konstantinos Liolios,Travis Harrison,Carlos López-Estraño,Kasturi Haldar +6 more
TL;DR: Functional studies indicated the predictive value of the signal and its role in targeting virulence proteins to the erythrocyte and implicated its recognition by a receptor/transporter, and bioinformatics predicted a secretome of >320 proteins and conservation of the signals across parasite species.
Journal ArticleDOI
Erythroblastic islands: niches for erythropoiesis
TL;DR: An increased molecular understanding of processes operating within erythroid niches, including cell-cell and cell-extracellular matrix adhesion, positive and negative regulatory feedback, and central macrophage function is obtained.
Journal ArticleDOI
Invasion of erythrocytes by malaria merozoites
TL;DR: In this paper, an electro-optical system was developed to record microscope images with high resolution at low light intensities, which was used to study the invasion of erythrocytes by malaria merozoites.
Journal ArticleDOI
A Brief Illustrated Guide to the Ultrastructure of Plasmodium falciparum Asexual Blood Stages
TL;DR: An illustrated overview of the three-dimensional (3-D) organization of the merozoite, ring, trophozoite and schizont stages of the parasite, based on available data that include 3-D reconstruc-tion from serial electron microscope sections is given.
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