Intravascular Coagulation in Falciparum Malaria

Jaroonvesama, N

doi:10.1016/s0140-6736(72)90621-6

Cited by 71 publications

(36 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…junct treatment for complications of malaria (77)(78)(79), the use of heparin was abandoned due to severe bleeding and the deaths of some children under treatment (47). When we analyzed the effects of modified compounds derived from native FucCS, we noted marked differences between these compounds ( Fig.…”

Section: Discussionmentioning

confidence: 99%

Fucosylated Chondroitin Sulfate Inhibits Plasmodium falciparum Cytoadhesion and Merozoite Invasion

Bastos

Albrecht

Kozlowski

et al. 2014

Antimicrob Agents Chemother

View full text Add to dashboard Cite

e Sequestration of Plasmodium falciparum-infected erythrocytes (Pf-iEs) in the microvasculature of vital organs plays a key role in the pathogenesis of life-threatening malaria complications, such as cerebral malaria and malaria in pregnancy. This phenomenon is marked by the cytoadhesion of Pf-iEs to host receptors on the surfaces of endothelial cells, on noninfected erythrocytes, and in the placental trophoblast; therefore, these sites are potential targets for antiadhesion therapies. In this context, glycosaminoglycans (GAGs), including heparin, have shown the ability to inhibit Pf-iE cytoadherence and growth. Nevertheless, the use of heparin was discontinued due to serious side effects, such as bleeding. Other GAG-based therapies were hampered due to the potential risk of contamination with prions and viruses, as some GAGs are isolated from mammals. In this context, we investigated the effects and mechanism of action of fucosylated chondroitin sulfate (FucCS), a unique and highly sulfated GAG isolated from the sea cucumber, with respect to P. falciparum cytoadhesion and development. FucCS was effective in inhibiting the cytoadherence of Pf-iEs to human lung endothelial cells and placenta cryosections under static and flow conditions. Removal of the sulfated fucose branches of the FucCS structure virtually abolished the inhibitory effects of FucCS. Importantly, FucCS rapidly disrupted rosettes at high levels, and it was also able to block parasite development by interfering with merozoite invasion. Collectively, these findings highlight the potential of FucCS as a candidate for adjunct therapy against severe malaria.

show abstract

Section: Discussionmentioning

confidence: 99%

Fucosylated Chondroitin Sulfate Inhibits Plasmodium falciparum Cytoadhesion and Merozoite Invasion

Bastos

Albrecht

Kozlowski

et al. 2014

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…In addition, there is marked suppression of erythropoiesis, even in the presence of adequate functional erythropoietin production. Several alternative models have been proposed for the mechanism of anemia: sequestration of PRBC (2), rupture of PRBC during schizogony, macrophage-mediated ingestion of PRBC, bone marrow hypoxia due to blockage of microvasculature by PRBC, low iron availability, immune-mediated hemolysis mediated by RBC surface IgG and complement receptor C3 (1,18,38), disseminated intravascular coagulation (16,20; H. A. Reid, letter, Lancet i:167-168, 1975), and decreased survivability of uninfected RBCs (23,48). However, none of the above models adequately account for the severity of anemia nor the active suppression of erythropoiesis in the presence of erythropoietin.…”

Section: Discussionmentioning

confidence: 99%

Macrophage Migration Inhibitory Factor Release by Macrophages after Ingestion ofPlasmodium chabaudi-Infected Erythrocytes: Possible Role in the Pathogenesis of Malarial Anemia

et al. 2000

View full text Add to dashboard Cite

Human falciparum malaria, caused by Plasmodium falciparum infection, results in 1 to 2 million deaths per year, mostly children under the age of 5 years. The two main causes of death are severe anemia and cerebral malaria. Malarial anemia is characterized by parasite red blood cell (RBC) destruction and suppression of erythropoiesis (the mechanism of which is unknown) in the presence of a robust host erythropoietin response. The production of a host-derived erythropoiesis inhibitor in response to parasite products has been implicated in the pathogenesis of malarial anemia. The identity of this putative host factor is unknown, but antibody neutralization studies have ruled out interleukin-1␤, tumor necrosis factor alpha, and gamma interferon while injection of interleukin-12 protects susceptible mice against lethal P. chabaudi infection. In this study, we report that ingestion of P. chabaudi-infected erythrocytes or malarial pigment (hemozoin) induces the release of macrophage migration inhibitory factor (MIF) from macrophages. MIF, a proinflammatory mediator and counter-regulator of glucocorticoid action, inhibits erythroid (BFU-E), multipotential (CFU-GEMM), and granulocyte-macrophage (CFU-GM) progenitor-derived colony formation. MIF was detected in the sera of P. chabaudi-infected BALB/c mice, and circulating levels correlated with disease severity. Liver MIF immunoreactivity increased concomitant with extensive pigment and parasitized RBC deposition. Finally, MIF was elevated three-to fourfold in the spleen and bone marrow of P. chabaudi-infected mice with active disease, as compared to early disease, or of uninfected controls. In summary, the present results suggest that MIF may be a host-derived factor involved in the pathophysiology of malaria anemia.Malaria is a disease caused by an intracellular parasitic protozoa of the genus Plasmodium and is transmitted by the infected female Anopheles mosquito during blood meals. Malaria is still a major cause of death and severe illness in most of the world, with 300 to 500 million new infections per year resulting in approximately 1 to 2 million deaths, mostly in children under the age of 5 years (28). The complications of severe anemia and cerebral malaria are the major causes of morbidity and mortality due to malaria. Of the four strains which infect humans, Plasmodium falciparum is the most prevalent and accounts for most malaria-related deaths.The P. falciparum life cycle includes a nonpathogenic, asymptomatic hepatic stage (extraerythrocytic), which is followed by the invasion of mature erythrocytes by infective forms (merozoites) and the initiation of the pathogenic intraerythrocytic stages. The intraerythrocytic parasite derives most of its amino acid requirements from host hemoglobin catabolism within a specialized acidic organelle, the food vacuole (19). Heme is released during hemoglobin digestion and rendered nontoxic by cross-linking into an insoluble polymer, hemozoin, through a parasite-specific biochemical activity (44). The fate of hemozoin is conne...

show abstract

“…In other disease states characterized by systemic macrophage stimulation, such as transfusion related lung injury, macrophages accumulate in the lungs, causing hypoxia and extensive radiographic opacification [10]. Disseminated intravascular coagulation is a recognized feature of severe malaria, and autopsy studies have demonstrated microthrombi in many tissues [11]. …”

Section: Introductionmentioning

confidence: 99%

Pulmonary pathology in pediatric cerebral malaria

Milner

Factor

Whitten³

et al. 2013

Human Pathology

View full text Add to dashboard Cite

Respiratory signs are common in African children where malaria is highly endemic and, thus, parsing the role of pulmonary pathology in illness is challenging. We examined the lungs of 100 children from an autopsy series in Blantyre, Malawi, in many of whom death was attributed to P falciparum malaria. Our aim was to describe the pathological manifestations of fatal malaria, to understand the role of parasites, pigment, and macrophages, and to catalogue co-morbidities. From available patients which included 55 patients with cerebral malaria and 45 controls, we obtained 4 cores of lung tissue for immunohistochemistry and morphological evaluation. We found that in patients with cerebral malaria, large numbers of malaria parasites were present in pulmonary alveolar capillaries, together with extensive deposits of malaria pigment (hemozoin). The number of pulmonary macrophages in this vascular bed did not differ between patients with cerebral malaria, non-cerebral malaria and non-malarial diagnoses. Co-morbidities found in some cerebral malaria patients included pneumonia, pulmonary edema, hemorrhage, and systemic activation of coagulation. We conclude that the respiratory distress seen in patients with cerebral malaria does not appear to be anatomic in origin but that increasing malaria pigment is strongly associated with cerebral malaria at autopsy.

show abstract

Intravascular Coagulation in Falciparum Malaria

Cited by 71 publications

References 5 publications

Fucosylated Chondroitin Sulfate Inhibits Plasmodium falciparum Cytoadhesion and Merozoite Invasion

Fucosylated Chondroitin Sulfate Inhibits Plasmodium falciparum Cytoadhesion and Merozoite Invasion

Macrophage Migration Inhibitory Factor Release by Macrophages after Ingestion ofPlasmodium chabaudi-Infected Erythrocytes: Possible Role in the Pathogenesis of Malarial Anemia

Pulmonary pathology in pediatric cerebral malaria

Contact Info

Product

Resources

About