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Parasite Versus Host: Pathology and Disease
Published in Eric S. Loker, Bruce V. Hofkin, Parasitology, 2023
Eric S. Loker, Bruce V. Hofkin
Hemozoin, produced as an insoluble waste of hemoglobin digestion by Plasmodium, has also been cited as a true toxin (Figure 5.15). Ironically, although hemozoin has been described as toxic to host cells, it is produced by Plasmodium to avoid being killed by heme, an initial product in the breakdown of hemoglobin. Following infection of erythrocytes, malaria parasites take up host hemoglobin, which they digest into amino acids. The initial cleavage event, mediated by aspartic acid proteases called plasmepsins, releases the iron-containing heme group and globin protein. The globin is then digested into its component amino acids by various proteases. Heme, on the other hand, is toxic in its free state because it can lyse membranes and inhibit the activity of certain enzymes. To eliminate this toxic substance, Plasmodium induces heme dimerization, forming molecules of hemozoin. This process appears to be catalyzed by a recently characterized molecule called heme detoxification protein (HDP). When it is expressed by the parasite, HDP is first secreted into the cytosol of the infected erythrocyte. It subsequently re-enters the parasite via endocytosis and is delivered to the food vacuole, where conversion of heme to hemozoin takes place.
Chemical Hybridization Approaches Applied to Natural and Synthetic Compounds for the Discovery of Drugs Active Against Neglected Tropical Diseases
Published in Venkatesan Jayaprakash, Daniele Castagnolo, Yusuf Özkay, Medicinal Chemistry of Neglected and Tropical Diseases, 2019
Elena Petricci, Paolo Governa, Fabrizio Manetti
Another intriguing approach to kill S. mansoni is based on its feature to be a hematophagous worm. The parasites digest human hemoglobin, leading to the formation of significant amounts of free heme that are in turn aggregated to give hemozoin crystals within the food vacuole. Hemozoin (also known as malaria pigment because Plasmodium follows the same catabolic pathway found in S. mansoni) can be considered as the result of a detoxification pathway that avoids iron ions to be involved in redox machinery that eventually yields reactive oxygen species, highly toxic to the parasites. With this in mind, compounds able to block heme polymerization to hemozoin could be of great interest as antischistosoma and antiplasmodial agents. Inhibition of hemozoin formation could be achieved by affecting monomer-monomer assembly by means of alkylating agents or heme-stacking compounds. For this purpose, chemicals bearing the 1,2,4-trioxane moiety are known to alkylate heme moieties, while compounds with a quinoline core are able to give stacking with the π-system of heme.
Mechanisms of action
Published in Fazal-I-Akbar Danish, Ahmed Ehsan Rabbani, Pharmacology in 7 Days for Medical Students, 2018
Fazal-I-Akbar Danish, Ahmed Ehsan Rabbani
Plasmodium fulfils its need for essential amino acids by digesting the host cells haemoglobin. This process occurs in the food vacuoles of the organism and releases large amounts of heme, which is ordinarily toxic to plasmodium. The organism protects itself from the toxic effects of heme by polymerising the heme to non-toxic hemozoin. Chloroquine is also concentrated in the food vacuoles where it binds to heme-polymerase preventing heme polymerisation. Heme accumulation results in oxidative damage to the membranes leading to lysis of the parasite.
The Green Placental Disk: Massive Placental Disk Bilirubin Deposition Due to Maternal Hyperbilirubinemia
Published in Fetal and Pediatric Pathology, 2023
Caitlin Hughes, Jiancong Liang
Microscopically, the differential diagnosis for brown pigment deposition in the placenta on H&E sections includes hemosiderin, melanin, bilirubin and hemozoin. Hemosiderin deposition is usually seen within the membranes in circumvallate placentas or at the decidual surface in instances of retroplacental hematomas. Hemosiderin has a dark, golden-brown refractile appearance and can be demonstrated as blue granules by a Prussian blue iron stain. Melanin granules are brown, non-refractile, and finely granular, and stain black with a Fontana-Masson special stain. In so-called “dermatopathic melanosis of the placenta,” melanin can be identified in Hofbauer cells, villous basement membranes, intervillous fibrin, degenerating syncytial knots and within calcifications [3]. Malaria pigment, hemozoin, appears in the tissues as brown-black granules with deposition in the basal plate, fibrin material, necrotic syncytium and within monocytes in the intervillous space [4]. To conclude, not all grossly green placentas with microscopic brown pigment deposition are due to meconium-staining.
The role of sialic acid-binding immunoglobulin-like-lectin-1 (siglec-1) in immunology and infectious disease
Published in International Reviews of Immunology, 2023
Shane Prenzler, Santosh Rudrawar, Mario Waespy, Sørge Kelm, Shailendra Anoopkumar-Dukie, Thomas Haselhorst
In malaria, Plasmodium parasites elicit robust host expansion of macrophages and monocytes. In a P. chabaudi infection model it has been shown that myeloid expansion is dependent upon both CD4+ T-cells and the cytokine macrophage colony stimulating factor (MCSF). Selective deletion of the colony stimulating factor 1 (CSF1) in CD4+ cells during P. chabaudi infection diminished expansion and activation of lymph node-resident CD169+ macrophages resulting in an increased parasite burden and decreased recovery of infected mice [121]. Depletion of CD169+ macrophages during infection also led to increased parasitemia and significant host mortality, confirming a previously unappreciated role for these cells in control of P. chabaudi. Another study reported that infection with Plasmodium berghei ANKA (PbA) in the absence of tissue-resident CD169+ macrophages resulted in an increased parasite sequestration, leading to vascular occlusion and leakage and increased tissue deposition of hemozoin with consequent tissue damage and multiple organ inflammation [122]. There is no doubt that CD169+ macrophages play a crucial rule to contain the parasite’s burden to limit infection-induced inflammation and pathogenesis.
Diagnosis of clinical malaria in endemic settings
Published in Expert Review of Anti-infective Therapy, 2021
Rosauro Varo, Núria Balanza, Alfredo Mayor, Quique Bassat
Automated analyzers that detect unusual light scatter patterns generated during routine full blood count may offer accurate, rapid and cost-effective malaria screening, but need microscopy for confirmation of malaria parasites [183]. One of these systems has been used for clinical diagnosis with promising results [184]. Hemozoin, the parasites’ waste product, is considered a potential biomarker for malaria diagnosis and represents an alternative indicator of malaria infection. For its detection, apart from flow cytometry, other technologies can be used as well (e.g. spectroscopy, ELISA) [185]. Remarkably, magneto-optical detection of hemozoin is an inexpensive and sensitive method which has been reported to provide results in less than one minute [186]. Additionally, advances in magnetic resonance relaxometry [187] microfluidics [188], biosensing technologies [189] and molecular biology have led to progress in lab-on-chip diagnostic platforms [190]. These devices adapt common laboratory tests to a self-contained, portable, micro-scale format surpassing the logistical and financial constraints that avoid the introduction of high specialized technology in low-resourced settings [191]. Although at a very preliminary stage, they hold promise as novel POC platforms for developing countries.