Journal articles: 'Schizonte'

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Pipano, E., and V. Shkap. "Observations sur la multiplication in vitro de cellules lymphoïdes bovines infectées par des schizontes de Theileria annulata." Revue d’élevage et de médecine vétérinaire des pays tropicaux 43, no. 4 (April 1, 1990): 485–88. http://dx.doi.org/10.19182/remvt.8767.

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La multiplication des cellules bovines de lignée lymphoïde infectées par les schizontes de Theileria annulata a été étudiée. Dans les cellules à division par mitose, le schizonte occupait une position centrale pendant les dernières phases de la division, partagée en deux cellules nouvellement formées. Des cellules binucléées avec des schizontes situés entre les noyaux ont également été observées. On ne peut tirer aucune conclusion définitive quant au fait de savoir si ces cellules appartiennent à des phases situées dans la division sans mitose, ou si elles sont le résultat de la fusion de cellules infectées. On a noté de larges variations dans le nombre de noyaux des schizontes par cellule infectée, avec une moyenne de 12,2 noyaux par schizonte. La grande majorité des cellules en contenait 4 à 16.

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Pang, Xin-Li, Toshihide Mitamura, and Toshihiro Horii. "Antibodies Reactive with the N-Terminal Domain ofPlasmodium falciparum Serine Repeat Antigen Inhibit Cell Proliferation by Agglutinating Merozoites and Schizonts." Infection and Immunity 67, no. 4 (April 1, 1999): 1821–27. http://dx.doi.org/10.1128/iai.67.4.1821-1827.1999.

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ABSTRACT The serine repeat antigen (SERA) is a vaccine candidate antigen ofPlasmodium falciparum. Immunization of mice withEscherichia coli-produced recombinant protein of the SERA N-terminal domain (SE47′) induced an antiserum that was inhibitory to parasite growth in vitro. Affinity-purified mouse antibodies specific to the recombinant protein inhibited parasite growth between the schizont and ring stages but not between the ring and schizont stages. When Percoll-purified schizonts were cultured with the affinity-purified SE47′-specific antibodies, schizonts and merozoites were agglutinated. Indirect-immunofluorescence assays with unfixed parasite cells showed that SE47′-specific immunoglobulin G (IgG) bound to SERA molecules on rupturing schizonts and merozoites but the IgG did not react with the schizont-infected erythrocytes (RBC). Furthermore, double-fluorescence staining against SE47′-specific IgG and anti-human RBC membrane IgG showed that the RBC membrane disappeared from SE47′-specific-IgG-bound schizonts after cultivation. These observations suggest that the SE47′-specific antibodies inhibit parasite growth by cross-linking SERA molecules that are associated with merozoites in rupturing schizonts with partly broken RBC and parasitophorous vacuole membranes, blocking merozoite release.

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LINDSAY, D. S., J. P. DUBEY, K. M. HORTON, and D. D. BOWMAN. "Development of Sarcocystis falcatula in cell cultures demonstrates that it is different from Sarcocystis neurona." Parasitology 118, no. 3 (March 1999): 227–33. http://dx.doi.org/10.1017/s003118209800376x.

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The development of Sarcocystis falcatula merozoites in bovine turbinate (BT) cell cultures is described and compared with development of Sarcocystis neurona merozoites. Merozoites of S. falcatula entered BT cell cultures and increased in size until 3 days post-inoculation when the nucleus of some merozoites developed lobes. Developing schizonts present at 4 days contained a lobed nucleus or appeared multinucleate. A single mature schizont was observed 4 days p.i. Schizonts were numerous 5 and 6 days p.i. Merozoites were produced from blastophores on the schizont. S. neurona merozoites developed to mature schizonts by 3 days p.i. in BT cells and a residual body was often present. Transmission electron microscopy revealed that S. falcatula merozoites possessed more micronemes than did S. neurona merozoites. Our study demonstrates that S. falcatula and S. neurona are not the same parasite.

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Khoury, David S., Deborah Cromer, Shannon E. Best, Kylie R. James, Peter S. Kim, Christian R. Engwerda, Ashraful Haque, and Miles P. Davenport. "Effect of Mature Blood-Stage Plasmodium Parasite Sequestration on Pathogen Biomass in Mathematical andIn VivoModels of Malaria." Infection and Immunity 82, no. 1 (October 21, 2013): 212–20. http://dx.doi.org/10.1128/iai.00705-13.

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ABSTRACTParasite biomass and microvasculature obstruction are strongly associated with disease severity and death inPlasmodium falciparum-infected humans. This is related to sequestration of mature, blood-stage parasites (schizonts) in peripheral tissue. The prevailing view is that schizont sequestration leads to an increase in pathogen biomass, yet direct experimental data to support this are lacking. Here, we first studied parasite population dynamics in inbred wild-type (WT) mice infected with the rodent species of malaria,Plasmodium bergheiANKA. As is commonly reported, these mice became moribund due to large numbers of parasites in multiple tissues. We then studied infection dynamics in a genetically targeted line of mice, which displayed minimal tissue accumulation of parasites. We constructed a mathematical model of parasite biomass dynamics, incorporating schizont-specific host clearance, both with and without schizont sequestration. Combined use of mathematical andin vivomodeling indicated, first, that the slowing of parasite growth in the genetically targeted mice can be attributed to specific clearance of schizonts from the circulation and, second, that persistent parasite growth in WT mice can be explained solely as a result of schizont sequestration. Our work provides evidence that schizont sequestration could be a major biological process driving rapid, early increases in parasite biomass during blood-stagePlasmodiuminfection.

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Spooner, P. R. "The effects of oxytetracycline on Theileria parva in vitro." Parasitology 100, no. 1 (February 1990): 11–17. http://dx.doi.org/10.1017/s0031182000060066.

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SummaryWhen bovine peripheral blood leucocytes were infected with Theileria parva sporozoites, immediate treatment with oxytetracycline (OTC) inhibited the development of sporozoites to mature schizonts. The extent of inhibition was dependent on drug concentration and duration of treatment. Concentrations of 5 μg/ml OTC, or higher, for 8 days completely inhibited the establishment of schizonts and their ability to transform host cells. A cytostatic effect on schizont-infected cell lines was found with three tetracyclines and was also demonstrated on uninfected lymphoblasts. The parasites were found to be sensitive t OTC during development to schizonts, but when mature and established within host cells, schizonts were not demonstrably affected. The infectivity of sporozoites and the binding of sporozoites to lymphocytes were not directly inhibited by OTC. The results may explain the action of tetracyclines when used prophylactically during immunization against East Coast fever, and also the reasons for the ineffectiveness of these drugs when used therapeutically during patent disease.

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LaDouceur, Elise E. B., Judy St Leger, Alexandria Mena, Ashley Mackenzie, Jacob Gregg, Maureen Purcell, William Batts, and Paul Hershberger. "Ichthyophonus sp. Infection in Opaleye (Girella nigricans)." Veterinary Pathology 57, no. 2 (February 21, 2020): 316–20. http://dx.doi.org/10.1177/0300985819900015.

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Over a 3-year-period, 17 wild-caught opaleye ( Girella nigricans) housed in a public display aquarium were found dead without premonitory signs. Grossly, 4 animals had pinpoint brown or black foci on coelomic adipose tissue. Histologically, liver, spleen, heart, and posterior kidney had mesomycetozoan granulomas in all cases; other organs were less commonly infected. Four opaleye had goiter; additional substantial lesions were not identified. Granulomas surrounded melanized debris, leukocytes, and mesomycetozoa represented by folded membranes (collapsed schizont walls), intact schizonts (50- to >200 µm in diameter with a multilaminate membrane), plasmodia (budding from schizonts or free in tissue), or rarely germinal tubes (budding from schizonts). Ichthyophonus was grown from fresh tissues in tissue explant broth cultures of the heart, liver, and/or spleen. Polymerase chain reaction using 18S ribosomal DNA primers amplified a 1730-bp region, and the DNA sequence was most similar to Ichthyophonus hoferi, which is often associated with freshwater aquaculture fish.

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SILVESTRINI, F., P. ALANO, and J. L. WILLIAMS. "Commitment to the production of male and female gametocytes in the human malaria parasite Plasmodium falciparum." Parasitology 121, no. 5 (November 2000): 465–71. http://dx.doi.org/10.1017/s0031182099006691.

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Commitment to the production of female and male gametocytes was studied in the NF54 line of the human malaria parasite Plasmodium falciparum. The development of sibling parasites derived from individual schizonts was followed, and 2 antisera against the female gametocyte-specific protein Pfg377 and the male gametocyte-specific protein α-tubulin II were used to determine the sex of sibling gametocytes. The experiment showed that individual cohorts of sibling gametocytes were stained in a mutually exclusive fashion by only one or the other antiserum, indicating that individual schizonts committed to yield sexual parasite progeny produce gametocytes of the same sex. This work suggests that in P. falciparum commitment to sexual differentiation occurs prior to schizont maturation, at the same moment when the sex of the resulting gametocytes is determined.

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Waterfall, Martin, Antony Black, and Eleanor Riley. "γδ+ T Cells Preferentially Respond to Live Rather than Killed Malaria Parasites." Infection and Immunity 66, no. 5 (May 1, 1998): 2393–98. http://dx.doi.org/10.1128/iai.66.5.2393-2398.1998.

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ABSTRACT We have compared the in vitro responses of peripheral blood T cells from malaria-unexposed donors to live Plasmodium falciparumschizonts, freeze-thawed schizont extracts (P. falciparumschizont extracts [PfSE]), and parasite culture supernatants. We show that the cells responding to PfSE and parasite culture supernatants are predominantly CD4+ TCRαβ+ while in the presence of live schizonts there is an additional activation of TCRγδ+ cells. Activation of TCRγδ+cells in response to PfSE was seen only when irradiated autologous feeder cells or recombinant interleukin-2 (IL-2) was added to the cultures. Live schizonts but not PfSE induced significant IL-2 production in vitro in the first 5 days after stimulation, suggesting that induction of early IL-2 by live parasites may contribute to the marked activation of the TCRγδ+ population.

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Smeijsters, L. J., N. M. Zijlstra, F. F. Franssen, and J. P. Overdulve. "Simple, fast, and accurate fluorometric method to determine drug susceptibility of Plasmodium falciparum in 24-well suspension cultures." Antimicrobial Agents and Chemotherapy 40, no. 4 (April 1996): 835–38. http://dx.doi.org/10.1128/aac.40.4.835.

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An in vitro test which quantifies drug inhibition of Plasmodium falciparum replication by measuring the fluorescence intensity of Hoechst 33258 dye bound to DNA is described. The procedure does not require expensive reagents or equipment and can be completed in less than 10 min. The assay was highly accurate and sensitive: cultures with as few as 0.4% schizont-infected erythrocytes could reliably be analyzed. The method was not biased by the actual parasite stage used; i.e., the amount of fluorescence detected in a sample of a culture of mature schizonts equaled the amount detected with the ring form culture derived from these schizonts. Even the presence of large proportions of free merozoites, which are easily neglected in microscopic estimates, did not bias the results. Furthermore, measurement of the chloroquine susceptibility of the multidrug-resistant K1 strain and the chloroquine-susceptible NF54 strain showed that the method is most suitable for quantifying the drug resistance of P. falciparum.

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Stephen W. Carmichael and Jon E. Rosenblatt. "Imaging New Paths for Malarial Parasites." Microscopy Today 14, no. 4 (July 2006): 3–5. http://dx.doi.org/10.1017/s1551929500050215.

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In general terms, parasites that cause malaria are injected into the skin by mosquitoes. They then travel into the bloodstream and then to the liver where they invade liver cells and mature into forms called schizonts. Within each schizont, cell division produces thousands of tiny new forms called merozoites, each of which, when released into the bloodstream, is capable of infecting a red blood cell. This “traditional” pathway for malarial parasites may not be the only way these parasites travel through the body. Using some increasingly more powerful immuno-imaging tools, Rogerio Amino, Sabine Thiberge, Béatrice Martin, Susanna Celli, Spencer Shorte, Friedrich Frischknecht, and Robert Ménard have demonstrated an additional route that could have profound implications for developing effective vaccines for this major worldwide disease.

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ALLARY, M., J. SCHREVEL, and I. FLORENT. "Properties, stage-dependent expression and localization of Plasmodium falciparum M1 family zinc-aminopeptidase." Parasitology 125, no. 1 (July 2002): 1–10. http://dx.doi.org/10.1017/s0031182002001828.

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A Plasmodium falciparum single copy gene predicting a 122 kDa protein belonging to the M1 family of zinc-metallopeptidases was previously reported and related to erythrocytic schizont proteins of 96 (p96) and 68 (p68) kDa. By using protease inhibitors during parasite harvest and enzyme preparations, and polyclonal antibodies specific for 2 peptidic domains deduced from the gene, we identified the 120 kDa precursor and demonstrated its processing into p96 and p68. The N-terminal ends of p96 and p68 were mapped between glycine-123 and lysine-163, both proteins thus containing the catalytic domain. The purified enzyme, here named PfA-M1 (p96/p68), displayed strict aminopeptidase activity, optimal at pH 7·4, with broad substrate spectrum. Its inhibition and reactivation profiles were typical of zinc-metalloaminopeptidases. By Western blotting, PfA-M1 was detected in trophozoites, in addition to schizonts, but not in early rings. PfA-M1 was localized by indirect immunofluorescence confocal microscopy. In trophozoites, the labelling was diffuse in the parasite cytoplasm, with accumulations around the food vacuole. In schizonts, it turned progressively to a vesicle-like pattern, ending as a clear spot in released merozoites. The involvement of PfA-M1 in haemoglobin breakdown and erythrocyte reinvasion is discussed in light of the dual functions recently reported for several P. falciparum proteases.

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Rosenthal, P. J., K. Kim, J. H. McKerrow, and J. H. Leech. "Identification of three stage-specific proteinases of Plasmodium falciparum." Journal of Experimental Medicine 166, no. 3 (September 1, 1987): 816–21. http://dx.doi.org/10.1084/jem.166.3.816.

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We have identified and characterized three stage-specific proteinases of Plasmodium falciparum that are active at neutral pH. We analyzed ring-, trophozoite-, schizont-, and merozoite-stage parasites by gelatin substrate PAGE and characterized the identified proteinases with class-specific proteinase inhibitors. No proteinase activity was detected with rings. Trophozoites had a 28 kD proteinase that was inhibited by inhibitors of cysteine proteinases. Mature schizonts had a 35-40 kD proteinase that also was inhibited by cysteine proteinase inhibitors. Merozoite fractions had a 75 kD proteinase that was inhibited by serine proteinase inhibitors. The stage-specific activity of these proteinases and the correlation between the effects of proteinase inhibitors on the isolated enzymes with the effects of the inhibitors on whole parasites suggest potential critical functions for these proteinases in the life cycle of malaria parasites.

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Wilson, Danny W., Christine Langer, Christopher D. Goodman, Geoffrey I. McFadden, and James G. Beeson. "Defining the Timing of Action of Antimalarial Drugs against Plasmodium falciparum." Antimicrobial Agents and Chemotherapy 57, no. 3 (January 14, 2013): 1455–67. http://dx.doi.org/10.1128/aac.01881-12.

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ABSTRACTMost current antimalarials for treatment of clinicalPlasmodium falciparummalaria fall into two broad drug families and target the food vacuole of the trophozoite stage. No antimalarials have been shown to target the brief extracellular merozoite form of blood-stage malaria. We studied a panel of 12 drugs, 10 of which have been used extensively clinically, for their invasion, schizont rupture, and growth-inhibitory activity using high-throughput flow cytometry and new approaches for the study of merozoite invasion and early intraerythrocytic development. Not surprisingly, given reported mechanisms of action, none of the drugs inhibited merozoite invasionin vitro. Pretreatment of erythrocytes with drugs suggested that halofantrine, lumefantrine, piperaquine, amodiaquine, and mefloquine diffuse into and remain within the erythrocyte and inhibit downstream growth of parasites. Studying the inhibitory activity of the drugs on intraerythrocytic development, schizont rupture, and reinvasion enabled several different inhibitory phenotypes to be defined. All drugs inhibited parasite replication when added at ring stages, but only artesunate, artemisinin, cycloheximide, and trichostatin A appeared to have substantial activity against ring stages, whereas the other drugs acted later during intraerythrocytic development. When drugs were added to late schizonts, only artemisinin, cycloheximide, and trichostatin A were able to inhibit rupture and subsequent replication. Flow cytometry proved valuable forin vitroassays of antimalarial activity, with the free merozoite population acting as a clear marker for parasite growth inhibition. These studies have important implications for further understanding the mechanisms of action of antimalarials, studying and evaluating drug resistance, and developing new antimalarials.

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SCHAAP, D., G. ARTS, J. KROEZE, R. NIESSEN, S. V. ROOSMALEN-VOS, K. SPREEUWENBERG, C. M. KUIPER, et al. "AnEimeriavaccine candidate appears to be lactate dehydrogenase; characterization and comparative analysis." Parasitology 128, no. 6 (May 13, 2004): 603–16. http://dx.doi.org/10.1017/s0031182004005104.

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AnEimeria acervulinaprotein fraction was identified which conferred partial protection against anE. acervulinachallenge infection. From this fraction a 37 kDa protein was purified and its corresponding cDNA was cloned and shown to encode a lactate dehydrogenase (LDH). Full length cDNAs encoding LDH from two related species,E. tenellaandE. maxima, were also cloned. The homology between the primary amino acid sequences of these threeEimeriaLDH enzymes was rather low (66–80%), demonstrating an evolutionary divergence. ThePlasmodiumLDH crystal structure was used to generate a 3D-model structure ofE. tenellaLDH, which demonstrated that the many variations in the primary amino acid sequences (P. falciparumLDH andE. tenellaLDH show only 47% identity) had not resulted in altered 3D-structures. Only a single LDH gene was identified inEimeria, which was active as a homotetramer. The protein was present at similar levels throughout different parasitic stages (oocysts, sporozoites, schizonts and merozoites), but its corresponding RNA was only observed in the schizont stage, suggesting that its synthesis is restricted to the intracellular stage.

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Murakami, K., and K. Tanabe. "An antigen of Plasmodium yoelii that translocates into the mouse erythrocyte membrane upon entry into the host cell." Journal of Cell Science 73, no. 1 (February 1, 1985): 311–20. http://dx.doi.org/10.1242/jcs.73.1.311.

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Monoclonal antibodies against the rodent malaria parasite, Plasmodium yoelii, have been prepared and characterized by indirect immunofluorescence on acetone-fixed infected mouse erythrocytes. The antibody of clone K2 reacted strongly with late trophozoites and schizonts, whereas it did so weakly and diffusely with ring forms and early trophozoites. Strong fluorescence was confined to granular structures in schizonts and merozoites. Parasites that invaded erythrocytes in vitro lost the strong fluorescence. Instead, immunofluorescence appeared in the membranes of erythrocytes infected in vitro with merozoites. Erythrocytes infected with more than one merozoite had intensified immunofluorescence in their membranes. Staining of the invaded erythrocytes with 4′,6-diamidino-2-phenylindole (DAPI) hydrochloride demonstrated that membranes of all the invaded erythrocytes acquired the P. yoelii antigen. These results suggest that the P. yoelii antigen in merozoites is translocated into erythrocyte membranes upon entry into the host cell. Immunofluorescence continued to appear in membranes of infected erythrocytes throughout the intra-erythrocytic parasite growth. Staining of unfixed infected erythrocytes with the K2 antibody failed to detect the parasite antigen. In contrast, immunofluorescence was present in unfixed membranes of erythrocyte ghosts, which had been spontaneously formed after rupture of schizont-infected erythrocytes by merozoite release. No immunofluorescence appeared in either acetone-fixed or unfixed ghosts of normal erythrocytes. These results suggest the antigenic determinant of the P. yoelii antigen is exposed at the cytoplasmic surface of the infected erythrocyte membrane. Immunoprecipitation has revealed that the K2 antibody recognizes a 160 X 10(3) Mr P. yoelii antigen.

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Clift, Sarah J., Nicola E. Collins, Marinda C. Oosthuizen, Johan C. A. Steyl, John A. Lawrence, and Emily P. Mitchell. "The Pathology of Pathogenic Theileriosis in African Wild Artiodactyls." Veterinary Pathology 57, no. 1 (December 19, 2019): 24–48. http://dx.doi.org/10.1177/0300985819879443.

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The published literature on schizont-“transforming,” or pathogenic theileriosis, in African wild artiodactyls is dated and based on limited information. Here the authors review the taxonomy, diagnosis, epidemiology, hematology, pathology, and aspects of control in various species. Molecular studies based on 18S and 16S rRNA gene sequences have shown that African wild artiodactyls are commonly infected with diverse Theileria spp., as well as nontheilerial hemoprotozoa and rickettsia-like bacteria, and coinfections with pathogenic and nonpathogenic Theileria species are often recorded. Although theileriosis is still confusingly referred to as cytauxzoonosis in many species, the validity of a separate Cytauxzoon genus in artiodactyls is debated. The epidemiology of theileriosis is complex; the likelihood of fatal disease depends on the interplay of parasite, vertebrate host, tick vector, and environmental factors. Roan calves ( Hippotragus equinus) and stressed animals of all host species are more susceptible to fatal theileriosis. Even though regenerative anemia is common, peripheral blood piroplasm parasitemia does not correlate with disease severity. Other than anemia, common macroscopic lesions include icterus, hemorrhages (mucosal, serosal, and tissue), fluid effusions into body cavities, lung edema, and variably sized raised cream-colored foci of leukocyte infiltration in multiple organs. Histopathologic findings include vasocentric hyperproliferation and lysis of atypical leukocytes with associated intracellular schizonts, parenchymal necrosis, hemorrhage, thromboembolism, and edema. Immunophenotyping is required to establish the identity of the schizont-transformed leukocytes in wild ungulates. Throughout the review, we propose avenues for future research by comparing existing knowledge on selected aspects of theileriosis in domestic livestock with that in African wild artiodactyls.

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HOUT, S., N. AZAS, A. DARQUE, M. ROBIN, C. DI GIORGIO, M. GASQUET, J. GALY, and P. TIMON-DAVID. "Activity of benzothiazoles and chemical derivatives onPlasmodium falciparum." Parasitology 129, no. 5 (October 5, 2004): 525–42. http://dx.doi.org/10.1017/s0031182004006031.

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Malaria is a major health concern particularly in Africa which has about 90% of the worldwide annual clinical cases. The increasing number of drug-resistantPlasmodium falciparumjustifies the search for new drugs in this field. Antimalarial activity of 2-substituted 6-nitro- and 6-amino-benzothiazoles and their anthranilic acids has been tested. Anin vitrostudy has been performed on W2 and 3D7 strains ofP. falciparumand on clinical isolates from malaria-infected patients. Toxicity has been assessed on THP1 human monocytic cells. For the most active drug candidates, thein vitrostudy was followed byin vivoassaysonP. berghei-infected mice and byin vitroassays in order to determine the stage-dependency and the mechanism of action. Of 39 derivatives testedin vitro, 2 had specific antimalarial properties. Each compound was active on all stages of the parasite, but one was markedly active on mature schizonts, while the other was more active on young schizont forms. Both drugs were also active on mitochondrial membrane potential.In vivodata confirmed efficiency with a sustained decrease of parasitaemia. Products A12 and C7 may be considered as potential antimalarial worthy of further chemical and biological research.

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Bannister, L. H., G. H. Mitchell, G. A. Butcher, and E. D. Dennis. "Lamellar membranes associated with rhoptries in erythrocytic merozoites of Plasmodium knowlesi: a clue to the mechanism of invasion." Parasitology 92, no. 2 (April 1986): 291–303. http://dx.doi.org/10.1017/s0031182000064064.

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SUMMARYIn merozoites of Plasmodium knowlesi, rhoptries have a dense substructure of fine (2·5 nm diameter) granules and short rods. These are not altered by lipid extraction, and stain with ethanolic phosphotungstate indicating a proteinaceous composition. Various types of fixation also show multilamellar whorls with a periodicity of 5–7 rim in the tips of rhoptries or extruded at the merozoite apex. In merozoites fixed during invasions of red cells, membrane continuity typically occurs between the rim of the rhoptry canal and the red cell membrane, but where this contact has apparently been lost, extensive membranous whorls and blebs are often found at the apex of the parasite. Similar structures occur at the spices of merozoites within late-stage schizonts. It is suggested that the same mechanism which generates these lamellae forms the parasitophorous vacuole by inserting membranous elements formed by the parasite into the red cell membrane, so causing its invagination. A similar mechanism may be responsible for the release of merozoites from the late-stage schizont.

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NICHANI, A. K., B. H. THORP, C. G. D. BROWN, J. D. M. CAMPBELL, D. J. BROWN, M. RITCHIE, and R. L. SPOONER. "In vivo development of Theileria annulata: major changes in efferent lymph following infection with sporozoites or allogeneic schizont-infected mononuclear cells." Parasitology 118, no. 4 (April 1999): 327–33. http://dx.doi.org/10.1017/s0031182098003904.

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The object of these experiments was to study the pathogenesis and kinetics of Theileria annulata infection in the efferent lymph of the draining lymph nodes of calves. Efferent lymphatics of calves were cannulated prior to infection with T. annulata sporozoite or an allogeneic schizont cell line. Potentially lethal sporozoite challenge induced cell shut-down from days 4–6 and then a massive increase in output of blasting cells (both infected and non-infected) in the efferent lymph. The rate of lymph flow and total cell output increased to 5 to 10-fold from day 6 onwards. Sporozoites were never isolated from the efferent lymph. However, large numbers of parasite-infected cells were seen in efferent lymph from the sixth day of infection. The animals inoculated with an allogeneic T. annulata-infected cell line exhibited only a small increase in flow rate and cell output. Parasite-infected cells of recipient origin were seen in efferent lymph from day 11 onwards. However, cells of donor origin were never isolated either from efferent lymph or peripheral blood. Thus the parasite transferred from the inoculated donor cell line to the cells of the recipient before schizonts appeared in efferent lymph.

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MARGOS, G., L. H. BANNISTER, A. R. DLUZEWSKI, J. HOPKINS, I. T. WILLIAMS, and G. H. MITCHELL. "Correlation of structural development and differential expression of invasion-related molecules in schizonts ofPlasmodium falciparum." Parasitology 129, no. 3 (August 23, 2004): 273–87. http://dx.doi.org/10.1017/s0031182004005657.

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During asexual developmentPlasmodiumschizonts undergo a series of complex biochemical and structural changes. Using tightly synchronized cultures of 2P. falciparumlines (clone C10 and strain ITO4) for light microscopy and fluorescence imaging we monitored the timing and sequence of expression of proteins associated with invasion-related organelles. Antibodies to rhoptry, micronemal and dense granule proteins (Rhoptry Associated Protein 1, Apical Membrane Antigen 1, Erythrocyte Binding Antigen 175, Ring-infected Erythrocyte Surface Antigen) and to pellicle-associated proteins (Merozoite Surface Protein 1, PfMyosin-A) were used. Clone C10 developed faster than ITO4; this difference was also found in the timing of protein expression seen by immunofluorescence. Light microscopic data were combined with transmission electron microscopic analysis using serial sectioning of ITO4 schizonts to determine nuclear number and organellar development. Thus a timetable of schizont structural maturation was established. Generally, the timing of organelle-specific antigen expression correlates well with the ultrastructural data. Rhoptries are formed mainly between second and fourth nuclear divisions, micronemes between the end of the fourth nuclear division and merozoite separation from the residual body, while dense granules are generated mainly after the micronemes. PfAMA-1 appears in micronemes before EBA-175, suggesting micronemal heterogeneity.

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Stuart, M. K., and T. J. Green. "Monoclonal IgM rheumatoid factor-like anti-globulins enhance the inhibitory effects ofPlasmodium falciparum-specific monoclonal antibodiesin vitro." Parasitology 101, no. 2 (October 1990): 177–85. http://dx.doi.org/10.1017/s0031182000063216.

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Monoclonal IgM rheumatoid factor-like anti-globulins were produced byin vitrostimulation of naive BALB/c spleen cells with lipopolysaccharide, and by hyperimmunization of mice with merozoites ofPlasmodium falciparum, followed by fusion of the spleen cells to mouse myelomas.In vitro, these anti-globulins augmented the inhibitory effects ofP. falciparum-specific polyclonal mouse sera and monoclonal IgG1 and IgG2b antibodies by binding to Fc fragments of IgG molecules attached to blood-stage parasites. In some instances, the presence of anti-globulins correlated with an increase in the number of schizonts which failed to disperse merozoites. In other cases, parasitaemia remained low in the absence of the schizont inhibition phenomenon, suggesting that anti-globulins contribute to host cell protection not only by agglutinating merozoites, but also by increasing the density of the antibody coat surrounding the parasites, thus interfering with parasite receptor-erythrocyte ligand interactions. The anti-globulins were not inhibitory when added to parasite cultures containing IgG not specific for P. falciparum. These results may help explain the function of IgM anti-globulins found at elevated serum levels in some patients with malaria or other chronic infectious diseases.

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Aley, Stephen B., John W. Barnwell, Michelle D. Bates, William E. Collins, and Michael R. Hollingdale. "Plasmodium vivax: Exoerythrocytic schizonts recognized by monoclonal antibodies against blood-stage schizonts." Experimental Parasitology 64, no. 2 (October 1987): 188–94. http://dx.doi.org/10.1016/0014-4894(87)90142-1.

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Bruce, M. C., P. Alano, S. Duthie, and R. Carter. "Commitment of the malaria parasite Plasmodium falciparum to sexual and asexual development." Parasitology 100, no. 2 (April 1990): 191–200. http://dx.doi.org/10.1017/s0031182000061199.

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SUMMARYBlood-stage malaria parasites in the vertebrate host can develop either into the asexual, multiplying forms, called schizonts, or into gametocytes, the sexual stages of the parasite. In the present work we studied the differentiation into asexual parasites or gametocytes of the progeny of single, isolated schizonts of the clone 3D7A of Plasinodium falciparum, using monoclonal antibodies specific for the sexual or asexual stages of the parasite. We observed that schizonts obtained from a continuous culture undergoing serial cycles of growth and dilution with fresh red blood cells produced either only gametocytes or only asexual parasites, showing a high degree of commitment to one or the other developmental pathway.The relative proportion of schizonts which produced gametocytes was very low at low parasite densities in culture, while at high parasite densities a much greater proportion of schizonts produced gametocytes. Nevertheless, at both low and high parasite densities individual schizonts were almost always fully committed to producing only gametocytes or only asexual parasites.

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Isobe, Takashi, and Kazuo Akiba. "Early Schizonts of Leucocytozoon caulleryi." Journal of Parasitology 76, no. 4 (August 1990): 587. http://dx.doi.org/10.2307/3282850.

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BANNISTER, L. H., and G. H. MITCHELL. "Lipidic Vacuoles inPlasmodium knowlesiErythrocytic Schizonts." Journal of Protozoology 33, no. 2 (May 1986): 271–75. http://dx.doi.org/10.1111/j.1550-7408.1986.tb05605.x.

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Kassim, Olakunle O., Mark Loyevsky, Biaffra Elliott, Andrew Geall, Henrietta Amonoo, and Victor R. Gordeuk. "Effects of Root Extracts of Fagara zanthoxyloides on the In Vitro Growth and Stage Distribution of Plasmodium falciparum." Antimicrobial Agents and Chemotherapy 49, no. 1 (January 2005): 264–68. http://dx.doi.org/10.1128/aac.49.1.264-268.2005.

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ABSTRACT The development of resistance by Plasmodium falciparum to conventional drugs poses a threat to malaria control. There is therefore a need to find new, effective, and affordable remedies for malaria, including those derived from plants. This study demonstrates that crude, reverse-phase high-pressure liquid chromatography (RP-HPLC)-semipurified, and RP-HPLC-purified root extracts of Fagara zanthoxyloides inhibit the growth of P. falciparum in vitro, with 50% inhibitory concentrations (IC50s) of 4.90, 1.00, and 0.13 μg/ml, respectively. Roots of F. zanthoxyloides, known as chewing sticks, are widely used for tooth cleaning in West Africa. Microscopic examination of Giemsa-stained slides showed a virtual absence of schizonts in ring-stage synchronized cultures treated with crude extracts at concentrations of 30 to 60 μg/ml during 36 to 48 h of incubation. These observations suggest that the active constituent in the extract may be cytotoxic for P. falciparum trophozoites, thereby inhibiting their development to the schizont stage. A pure bioreactive fraction was subsequently obtained from the chromatographic separations. When this fraction was mixed with pure fagaronine, the mixture coeluted as a single peak on the analytical RP-HPLC column, suggesting that fagaronine may be the active antimalarial constituent of Fagara root extracts. Additional experiments showed that fagaronine also inhibited P. falciparum growth, with an IC50 of 0.018 μg/ml. The results of this study suggest that the antimalarial activity of fagaronine deserves further investigation.

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Hatabu, Toshimitsu, Tsuyoshi Takada, Nao Taguchi, Mamoru Suzuki, Kumiko Sato, and Shigeyuki Kano. "Potent Plasmodicidal Activity of a Heat-Induced Reformulation of Deoxycholate-Amphotericin B (Fungizone) against Plasmodium falciparum." Antimicrobial Agents and Chemotherapy 49, no. 2 (February 2005): 493–96. http://dx.doi.org/10.1128/aac.49.2.493-496.2005.

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ABSTRACT The emergence and spread of drug-resistant Plasmodium falciparum continue to pose problems in malaria chemotherapy. Therefore, it is necessary to identify new antimalarial drugs and therapeutic strategies. In the present study, the activity of a heat-treated form of amphotericin B (HT-AMB) against P. falciparum was evaluated. The efficacy and toxicity of HT-AMB were also compared with those of the standard formulation (AMB). HT-AMB showed significant activity against a chloroquine-resistant strain (strain K-1) and a chloroquine-susceptible strain (strain FCR-3) in vitro. The 50% inhibitory concentrations of HT-AMB were 0.32 ± 0.03 μg/ml for strain K-1 and 0.33 ± 0.03 μg/ml for strain FCR-3. In the presence of 1.0 μg of HT-AMB per ml, only pyknotic parasites were observed after 24 h of incubation of early trophozoites (ring forms). However, when late trophozoites and schizonts were cultured with 1.0 μg of HT-AMB per ml, those forms multiplied to ring forms but the number of infected erythrocytes did not increase. These results indicate that HT-AMB possesses potent antiplasmodial activity and that the drug is more effective against the ring-form stage than against the late trophozoite and schizont stages. HT-AMB was observed to have little cytotoxic effect against a human liver cell line (Chang liver cells). In conclusion, the results suggest that HT-AMB has promising properties and merits further in vivo investigations as a treatment for falciparum malaria.

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Aminake, Makoah N., Sebastian Schoof, Ludmilla Sologub, Monika Leubner, Marc Kirschner, Hans-Dieter Arndt, and Gabriele Pradel. "Thiostrepton and Derivatives Exhibit Antimalarial and Gametocytocidal Activity by Dually Targeting Parasite Proteasome and Apicoplast." Antimicrobial Agents and Chemotherapy 55, no. 4 (January 18, 2011): 1338–48. http://dx.doi.org/10.1128/aac.01096-10.

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ABSTRACTRibosome-targeting antibiotics exert their antimalarial activity on the apicoplast of the malaria parasite, an organelle of prokaryote origin having essential metabolic functions. These antibiotics typically cause a delayed-death phenotype, which manifests in parasite killing during the second replication cycle following administration. As an exception, treatment with the antibiotic thiostrepton results in an immediate killing. We recently demonstrated that thiostrepton and its derivatives interfere with the eukaryotic proteasome, a multimeric protease complex that is important for the degradation of ubiquitinated proteins. Here, we report that the thiostrepton-based compounds are active against chloroquine-sensitive and -resistantPlasmodium falciparum, where they rapidly eliminate parasites before DNA replication. The minor parasite fraction that escapes the fast killing of the first replication cycle is arrested in the schizont stage of the following cycle, displaying a delayed-death phenotype. Thiostrepton further exhibits gametocytocidal activity by eliminating gametocytes, the sexual precursor cells that are crucial for parasite transmission to the mosquito. Compound treatment results in an accumulation of ubiquitinated proteins in the blood stages, indicating an effect on the parasite proteasome. In accordance with these findings, expression profiling revealed that the proteasome is present in the nucleus and cytoplasm of trophozoites, schizonts, and gametocytes. In conclusion, thiostrepton derivatives represent promising candidates for malaria therapy by dually acting on two independent targets, the parasite proteasome and the apicoplast, with the capacity to eliminate both intraerythrocytic asexual and transmission stages of the parasite.

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Cawthorn, R. J., R. J. F. Markham, N. D. Hitt, and D. Despres. "In vitro cultivation of the vascular phase of Sarcocystis hirsuta (Apicomplexa)." Canadian Journal of Zoology 68, no. 5 (May 1, 1990): 1068–70. http://dx.doi.org/10.1139/z90-157.

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Sporozoites of Sarcocystis hirsuta (Apicomplexa), although they also penetrated into bovine monocytes, developed to the schizogonous phase only in bovine pulmonary artery endothelial cells. Schizonts were evident beginning 14 days after sporozoite inoculation (DAI) and persisted to 62 DAI, when experiments were terminated. Merozoites and schizonts were most numerous 35–53 DAI. The number of schizogonous generations was not determined. In vitro cultivation of schizonts of S. hirsuta will facilitate comparisons with development of S. cruzi, and this will aid elucidation of mechanisms of pathogenesis and immunologic responses caused by these two important cattle parasites.

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Shapiro, Ben. "Lo schizoide flaccido." GROUNDING, no. 1 (June 2014): 73–80. http://dx.doi.org/10.3280/gro2014-001006.

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Baier, Karl. "Die schizoide Leiblichkeit." Daseinsanalyse 9, no. 2-3 (1992): 247–62. http://dx.doi.org/10.1159/000456386.

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32

Chabala, David Chipuku, Martin Simuunza, and Boneface Namangala. "Prevalence and Risk Factors of East Coast Fever in the Copperbelt and Central Provinces of Zambia." University of Zambia Journal of Agricultural and Biomedical Sciences 4, no. 3 (July 1, 2020): 32–39. http://dx.doi.org/10.53974/unza.jabs.4.3.400.

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East Coast fever (ECF) is an infectious tick-borne disease of cattle, caused by a protozoan parasite Theileria parva. It is a disease of major economic importance in Zambia as it is the main cause of cattle morbidity and mortality. Despite its economic importance, the epidemiology of ECF in Zambia is poorly understood, thereby making ECF prevention and control difficult. Further, there is limited published literature on this disease in Zambia, with little available research concentrating on Southern and Eastern provinces. Such literature is mostly based on serological techniques such as indirect fluorescent antibody test (IFAT) which have limited sensitivity and specificity. Thus, this study was conducted to determine the prevalence and associated risk factors of ECF in Copperbelt and Central provinces of Zambia. The study was cross-sectional in design. Multistage cluster sampling was used involving district, veterinary camp, herd and individual animals. The provinces and districts were selected based on their vast potential for livestock production and the previously reported incidence of ECF. From each district, two veterinary camps were randomly selected. From each camp, herds were randomly selected from which individual animals were randomly sampled. Samples were collected from Mpongwe and Masaiti districts (Copperbelt province) and Kapiri Mposhi and Chibombo districts (Central province). Samples were examined for the presence of schizonts on Giemsa stained lymph smears. The lymph smear examinations revealed that 6.4% (95%, CI=4.9-7.9) of the samples were positive for T. parva schizonts. In Central province, the overall prevalence was 6.7% (95%, CI=4.0-8.2), while in the Copperbelt province it was 6.1% (95%, CI=4.0-8.2). Among the districts in these provinces, Kapiri Mposhi did not record any schizont positive cattle, while Masaiti recorded 2.4% (95%, CI=0.5-4.3). Mpongwe had a prevalence of 9.7% (95%, CI=6.0-13.4) and Chibombo had the highest prevalence at 13.6% (95%, CI=9.4-17.9). Risk factors that were identified to be associated with ECF were the district, frequency of veterinary service provision, tick control frequency, age and previous experience of ECF. The results indicate that ECF is prevalent in Copperbelt and Central provinces and hindering livestock production. There is hence the need for concerted efforts to control ticks and prevent ECF transmission through farmer sensitization, routine, regular, mandatory and supervised dipping and spraying of cattle and stringent livestock movement control.

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Zeeman, Anne-Marie, Sandra M. van Amsterdam, Case W. McNamara, Annemarie Voorberg-van der Wel, Els J. Klooster, Alexander van den Berg, Edmond J. Remarque, et al. "KAI407, a Potent Non-8-Aminoquinoline Compound That Kills Plasmodium cynomolgi Early Dormant Liver Stage ParasitesIn Vitro." Antimicrobial Agents and Chemotherapy 58, no. 3 (December 23, 2013): 1586–95. http://dx.doi.org/10.1128/aac.01927-13.

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ABSTRACTPreventing relapses ofPlasmodium vivaxmalaria through a radical cure depends on use of the 8-aminoquinoline primaquine, which is associated with safety and compliance issues. For future malaria eradication strategies, new, safer radical curative compounds that efficiently kill dormant liver stages (hypnozoites) will be essential. A new compound with potential radical cure activity was identified using a low-throughput assay ofin vitro-cultured hypnozoite forms ofPlasmodium cynomolgi(an excellent and accessible model forPlasmodium vivax). In this assay, primary rhesus hepatocytes are infected withP. cynomolgisporozoites, and exoerythrocytic development is monitored in the presence of compounds. Liver stage cultures are fixed after 6 days and stained with anti-Hsp70 antibodies, and the relative proportions of small (hypnozoite) and large (schizont) forms relative to the untreated controls are determined. This assay was used to screen a series of 18 known antimalarials and 14 new non-8-aminoquinolines (preselected for blood and/or liver stage activity) in three-point 10-fold dilutions (0.1, 1, and 10 μM final concentrations). A novel compound, designated KAI407 showed an activity profile similar to that of primaquine (PQ), efficiently killing the earliest stages of the parasites that become either primary hepatic schizonts or hypnozoites (50% inhibitory concentration [IC50] for hypnozoites, KAI407, 0.69 μM, and PQ, 0.84 μM; for developing liver stages, KAI407, 0.64 μM, and PQ, 0.37 μM). When given as causal prophylaxis, a single oral dose of 100 mg/kg of body weight prevented blood stage parasitemia in mice. From these results, we conclude that KAI407 may represent a new compound class forP. vivaxmalaria prophylaxis and potentially a radical cure.

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de Souza, J. Brian, Manohursingh Runglall, Patrick H. Corran, Lucy C. Okell, Sanjeev Kumar, D. Channe Gowda, Kevin N. Couper, and Eleanor M. Riley. "Neutralization of Malaria Glycosylphosphatidylinositol In Vitro by Serum IgG from Malaria-Exposed Individuals." Infection and Immunity 78, no. 9 (June 21, 2010): 3920–29. http://dx.doi.org/10.1128/iai.00359-10.

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ABSTRACT Parasite-derived glycosylphosphatidylinositol (GPI) is believed to be a major inducer of the pathways leading to pathology and morbidity during Plasmodium falciparum infection and has been termed a malaria “toxin.” The generation of neutralizing anti-GPI (“antitoxic”) antibodies has therefore been hypothesized to be an important step in the acquisition of antidisease immunity to malaria; however, to date the GPI-neutralizing capacity of antibodies induced during natural Plasmodium falciparum infection has not been evaluated. Here we describe the development of an in vitro macrophage-based assay to assess the neutralizing capacity of malarial GPI-specific IgG. We demonstrate that IgG from Plasmodium falciparum-exposed individuals can significantly inhibit the GPI-induced activation of macrophages in vitro, as shown by reduced levels of tumor necrosis factor production and attenuation of CD40 expression. The GPI-neutralizing capacity of individual IgG samples was directly correlated with the anti-GPI antibody titer. IgG from malaria-exposed individuals also neutralized the macrophage-activating effects of P. falciparum schizont extract (PfSE), but there was only a poor correlation between PfSE-neutralizing activity and the anti-GPI antibody titer, suggesting that PfSE contains other macrophage-activating moieties, in addition to GPI. In conclusion, we have established an in vitro assay to test the toxin-neutralizing activities of antimalarial antibodies and have shown that anti-GPI antibodies from malaria-immune individuals are able to neutralize GPI-induced macrophage activation; however, the clinical relevance of anti-GPI antibodies remains to be proven, given that malarial schizonts contain other proinflammatory moieties, in addition to GPI.

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Florent, Isabelle, Betina M. Porcel, Elodie Guillaume, Corinne Da Silva, François Artiguenave, Eric Maréchal, Laurent Bréhélin, et al. "A Plasmodium falciparum FcB1-schizont-EST collection providing clues to schizont specific gene structure and polymorphism." BMC Genomics 10, no. 1 (2009): 235. http://dx.doi.org/10.1186/1471-2164-10-235.

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Russell, B., F. Chalfein, B. Prasetyorini, E. Kenangalem, K. Piera, R. Suwanarusk, A. Brockman, et al. "Determinants of In Vitro Drug Susceptibility Testing of Plasmodium vivax." Antimicrobial Agents and Chemotherapy 52, no. 3 (January 7, 2008): 1040–45. http://dx.doi.org/10.1128/aac.01334-07.

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ABSTRACT In Papua, Indonesia, the antimalarial susceptibility of Plasmodium vivax (n = 216) and P. falciparum (n = 277) was assessed using a modified schizont maturation assay for chloroquine, amodiaquine, artesunate, lumefantrine, mefloquine, and piperaquine. The most effective antimalarial against P. vivax and P. falciparum was artesunate, with geometric mean 50% inhibitory concentrations (IC50s) (95% confidence intervals [CI]) of 1.31 nM (1.07 to 1.59) and 0.64 nM (0.53 to 0.79), respectively. In contrast, the geometric mean chloroquine IC50 for P. vivax was 295 nM (227 to 384) compared to only 47.4 nM (42.2 to 53.3) for P. falciparum. Two factors were found to significantly influence the in vitro drug response of P. vivax: the initial stage of the parasite and the duration of the assay. Isolates of P. vivax initially at the trophozoite stage had significantly higher chloroquine IC50s (478 nM [95% CI, 316 to 722]) than those initially at the ring stage (84.7 nM [95% CI, 45.7 to 157]; P < 0.001). Synchronous isolates of P. vivax and P. falciparum which reached the target of 40% schizonts in the control wells within 30 h had significantly higher geometric mean chloroquine IC50s (435 nM [95% CI, 169 to 1,118] and 55.9 nM [95% CI, 48 to 64.9], respectively) than isolates that took more than 30 h (39.9 nM [14.6 to 110.4] and 36.9 nM [31.2 to 43.7]; P < 0.005). The results demonstrate the marked stage-specific activity of chloroquine with P. vivax and suggest that susceptibility to chloroquine may be associated with variable growth rates. These findings have important implications for the phenotypic and downstream genetic characterization of P. vivax.

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Cole, R. A., D. S. Lindsay, J. P. Dubey, and B. L. Blagburn. "Detection of Neospora Caninum in Tissue Sections Using a Murine Monoclonal Antibody." Journal of Veterinary Diagnostic Investigation 5, no. 4 (October 1993): 579–84. http://dx.doi.org/10.1177/104063879300500413.

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A murine monoclonal antibody (MAb 6G7), isotype IgG2a, produced against tachyzoites of Neospora caninum (isolate NC-l) reacted specifically with tachyzoites of N. caninum in an indirect immunofluorescent antibody test. MAb 6G7 did not react with tachyzoites of Toxoplasma gondii, sporozoites of Isospora suis, Eimeria bovis, or E. tenella, or merozoites of E. bovis in the indirect immunofluorescent antibody test. MAb 6G7 reacted positively with both tachyzoites and bradyzoites of N. caninum in an avidin-biotin peroxidase complex immunohistochemical test on formalin-fixed paraffin-embedded tissues. No reaction was observed with the following: tachyzoites and bradyzoites of T. gondii, T. gondii-like parasites, or Hammondia hammondi; bradyzoites of Frenkelia microti; schizonts and merozoites of Sarcocystis-like organisms; schizonts, sarcocysts, and oocysts/sporocysts of S. cruzi; schizonts and merozoites of S. canis; schizonts of S. hirsuta, S. tenella, and S. capracanis; merozoites of S. neurona and S. neurona-like organisms, E. bovis, or Haemoproteus sp.; bradyzoites and merozoites of S. montanaensis; bradyzoites of S. odocoileocanis, S. cruzi, and S. tenella; meronts, sexual stages, and caryocysts of Caryospora sp. and C. bigenetica; micromerozoites, macromerozoites, and schizonts of Hepatozoon canis; sporozoites, sexual stages, and oocysts of Cryptosporidium parvum and C. baileyi; trophozoites of Monocystis Zumbrici, Tritrichomonas foetus, and Balantidium coli; tissue cysts and bradyzoites of Besnoitia sp. and B. jellisoni; amastigotes of Leishmania sp.; and trophic theronts of Ichthyopthirius multifilis. MAb 6G7 reacted with tachyzoites and bradyzoites of N. caninum in natural and experimental infections in dogs, cattle, mice, rats, sheep, and goats, indicating that host origin of the tissues did not affect the performance of the test.

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Ouarzane, Meryem, Marie Labbe, and Pierre Pery. "Purification of First-Generation Eimeria tenella Schizonts." Journal of Parasitology 84, no. 5 (October 1998): 1027. http://dx.doi.org/10.2307/3284637.

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Witschi, M., D. Xia, S. Sanderson, M. Baumgartner, J. M. Wastling, and D. A. E. Dobbelaere. "Proteomic analysis of the Theileria annulata schizont." International Journal for Parasitology 43, no. 2 (February 2013): 173–80. http://dx.doi.org/10.1016/j.ijpara.2012.10.017.

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Markus, Miles B. "Transition from Plasmodial Hypnozoite to Schizont Demonstrated." Trends in Parasitology 36, no. 5 (May 2020): 407–8. http://dx.doi.org/10.1016/j.pt.2020.01.011.

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Manuja, Anju, A. K. Nichani, Rakesh Kumar, N. K. Rakha, Balvinder Kumar, and R. D. Sharma. "Comparison of cellular schizont, soluble schizont and soluble piroplasm antigens in ELISA for detecting antibodies against Theileria annulata." Veterinary Parasitology 87, no. 2-3 (January 2000): 93–101. http://dx.doi.org/10.1016/s0304-4017(99)00166-1.

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ZECHINI, B., L. CORDIER, E. NGONSEU, U. D'ALESSANDRO, M. WERY, and S. CHATTERJEE. "Plasmodium berghei development in irradiated sporozoite-immunized C57BL6 mice." Parasitology 118, no. 4 (April 1999): 335–38. http://dx.doi.org/10.1017/s0031182099003959.

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The C57BL6 strain of mice is highly susceptible to Plasmodium berghei sporozoite infections and consequently requires repeated immunizations with irradiated sporozoites to obtain protective immunity. After a live sporozoite challenge in the immunized hosts, hepatic-stage parasites found in the liver after 48 h are of different sizes – small schizonts corresponding to blocked forms (derived from irradiated sporozoites), and schizonts of intermediate size (derived from live sporozoites). Large schizonts corresponding to mature hepatic forms are found only in unimmunized but challenged C57BL6 mice. Using monoclonal and polyclonal antibodies directed to liver-stage parasites, different patterns of binding reactivity to the above forms are observed. More than 20% of the irradiated sporozoites transform into blocked forms after immunization and persist in the liver. Upon sporozoite challenge in such immunized animals the rate of transformation of sporozoites into hepatic parasites is less than 2%. These observations shed light on the fate of live sporozoite development in irradiated sporozoite-immunized C57BL6 mice.

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BRACCHI-RICARD, Valerie, Sailen BARIK, Cherie DELVECCHIO, Christian DOERIG, Ratna CHAKRABARTI, and Debopam CHAKRABARTI. "PfPK6, a novel cyclin-dependent kinase/mitogen-activated protein kinase-related protein kinase from Plasmodium falciparum." Biochemical Journal 347, no. 1 (March 27, 2000): 255–63. http://dx.doi.org/10.1042/bj3470255.

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We have isolated a novel protein kinase cDNA, PfPK6, by differential display RT-PCR (DDRT-PCR) of mRNA obtained from different asexual erythrocytic stages of Plasmodium falciparum, which shows sequence similarity to both cyclin-dependent kinase (CDK) and mitogen-activated protein kinase (MAPK) family members. The 915 bp open reading frame (ORF) is interrupted by seven introns and encodes a 305-residue polypeptide with a predicted molecular mass of 35848 Da. Several cDNA clones with some of the intron sequences were isolated, indicating alternate or defective splicing of PfPK6 transcripts because the gene seems to be a single copy located on chromosome 13. The similarity of the catalytic domain of PfPK6 to those of CDK2 and MAPK is 57.3% and 49.6%, respectively. The signature PSTAIRE (single-letter amino acid codes) CDK motif is changed to SKCILRE in PfPK6. The TXY residues that are phosphorylated in MAPKs for their activation are T173PT in PfPK6. Three size classes of PfPK6 transcripts of 6.5, 2.0 and 1.1 kb are up-regulated during the transition of P. falciparum from ring to trophozoite. Western blot analysis suggested the expression of a 35 kDa polypeptide in trophozoites and schizonts. Immunofluorescence studies indicated both nuclear and cytoplasmic localization of PfPK6 in trophozoite, schizont and segmenter stages. In vitro, recombinant PfPK6 phosphorylated itself and also exogenous substrates, histone and the small subunit of the malarial ribonucleotide reductase (R2). The kinase activity of PfPK6 is sensitive to CDK inhibitors such as olomoucine and roscovitine. PfPK6 showed a preference for Mn2+ over Mg2+ ions as a cofactor. The Lys38 → Arg mutant is severely defective in its interaction with ATP and bivalent cations and somewhat defective in catalytic rate for R2 phosphorylation.

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Obaldia, Nicanor, Elamaran Meibalan, Juliana M. Sa, Siyuan Ma, Martha A. Clark, Pedro Mejia, Roberto R. Moraes Barros, et al. "Bone Marrow Is a Major Parasite Reservoir inPlasmodium vivaxInfection." mBio 9, no. 3 (May 8, 2018): e00625-18. http://dx.doi.org/10.1128/mbio.00625-18.

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ABSTRACTPlasmodium vivaxcauses heavy burdens of disease across malarious regions worldwide. MatureP. vivaxasexual and transmissive gametocyte stages occur in the blood circulation, and it is often assumed that accumulation/sequestration in tissues is not an important phase in their development. Here, we present a systematic study ofP. vivaxstage distributions in infected tissues of nonhuman primate (NHP) malaria models as well as in blood from human infections. In a comparative analysis of the transcriptomes ofP. vivaxandPlasmodium falciparumblood-stage parasites, we found a conserved cascade of stage-specific gene expression despite the greatly different gametocyte maturity times of these two species. Using this knowledge, we validated a set of conserved asexual- and gametocyte-stage markers both by quantitative real-time PCR and by antibody assays of peripheral blood samples from infected patients and NHP (Aotussp.). Histological analyses ofP. vivaxparasites in organs of 13 infected NHP (AotusandSaimirispecies) demonstrated a major fraction of immature gametocytes in the parenchyma of the bone marrow, while asexual schizont forms were enriched to a somewhat lesser extent in this region of the bone marrow as well as in sinusoids of the liver. These findings suggest that the bone marrow is an important reservoir for gametocyte development and proliferation of malaria parasites.IMPORTANCEPlasmodium vivaxmalaria continues to cause major public health burdens worldwide. Yet, significant knowledge gaps in the basic biology and epidemiology ofP. vivaxmalaria remain, largely due to limited available tools for research and diagnostics. Here, we present a systematic examination of tissue sequestration duringP. vivaxinfection. Studies of nonhuman primates and malaria patients revealed enrichment of developing sexual stages (gametocytes) and mature replicative stages (schizonts) in the bone marrow and liver, relative to those present in peripheral blood. Identification of the bone marrow as a majorP. vivaxtissue reservoir has important implications for parasite diagnosis and treatment.

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Lytton, SD, B. Mester, J. Libman, A. Shanzer, and ZI Cabantchik. "Mode of action of iron (III) chelators as antimalarials: II. Evidence for differential effects on parasite iron-dependent nucleic acid synthesis." Blood 84, no. 3 (August 1, 1994): 910–15. http://dx.doi.org/10.1182/blood.v84.3.910.910.

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Abstract Iron chelation treatment of red blood cells infected with Plasmodium falciparum selectively intervenes with iron-dependent metabolism of malaria parasites and inhibits their development. Highly permeant hydroxamate iron chelator RSFileum2 affects all parasite stages when cultures are continuously exposed to drug, but affects primarily ring stages when assessed for irreversible effects, ie, sustained inhibition remaining after drug removal. On the other hand, the hydrophilic and poorly permeant desferrioxamine (DFO) affects primarily trophozoite/schizont stages when tested either in the continuous mode or irreversible mode. Unlike parasites, mammalian cells subjected to similar drug treatment show complete growth recovery once drugs are removed. Our studies indicate that parasites display a limited capacity to recover from intracellular iron depletion evoked by iron chelators. Based on these findings we provide a working model in which the irreversible effects of RSFs on rings are explained by the absence of pathways for iron acquisition/utilization by early forms of parasites. Trophozoite/schizonts can partially recover from RSFileum2 treatments, but show no DNA synthesis following DFO treatment even after drug removal and iron replenishment by permeant iron carriers. At trophozoite stage, the parasite uses a limited pathway for refurnishing its iron-containing enzymes, thus overcoming iron deprivation caused by permeant RSFileum2, but not by DFO because this latter drug is not easily removable from parasites. Their DNA synthesis is blocked by the hydroxamate iron chelators probably by affecting synthesis of ribonucleotide reductase (RNRase). Presumably in parasites, prolonged repression of the enzyme leads also to irreversible loss of activity. The action profiles of RSFileum2 and DFO presented in this study have implications for improved chemotherapeutic performance by combined drug treatment and future drug design based on specific intervention at parasite DNA synthesis.

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Lytton, SD, B. Mester, J. Libman, A. Shanzer, and ZI Cabantchik. "Mode of action of iron (III) chelators as antimalarials: II. Evidence for differential effects on parasite iron-dependent nucleic acid synthesis." Blood 84, no. 3 (August 1, 1994): 910–15. http://dx.doi.org/10.1182/blood.v84.3.910.bloodjournal843910.

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Abstract:

Iron chelation treatment of red blood cells infected with Plasmodium falciparum selectively intervenes with iron-dependent metabolism of malaria parasites and inhibits their development. Highly permeant hydroxamate iron chelator RSFileum2 affects all parasite stages when cultures are continuously exposed to drug, but affects primarily ring stages when assessed for irreversible effects, ie, sustained inhibition remaining after drug removal. On the other hand, the hydrophilic and poorly permeant desferrioxamine (DFO) affects primarily trophozoite/schizont stages when tested either in the continuous mode or irreversible mode. Unlike parasites, mammalian cells subjected to similar drug treatment show complete growth recovery once drugs are removed. Our studies indicate that parasites display a limited capacity to recover from intracellular iron depletion evoked by iron chelators. Based on these findings we provide a working model in which the irreversible effects of RSFs on rings are explained by the absence of pathways for iron acquisition/utilization by early forms of parasites. Trophozoite/schizonts can partially recover from RSFileum2 treatments, but show no DNA synthesis following DFO treatment even after drug removal and iron replenishment by permeant iron carriers. At trophozoite stage, the parasite uses a limited pathway for refurnishing its iron-containing enzymes, thus overcoming iron deprivation caused by permeant RSFileum2, but not by DFO because this latter drug is not easily removable from parasites. Their DNA synthesis is blocked by the hydroxamate iron chelators probably by affecting synthesis of ribonucleotide reductase (RNRase). Presumably in parasites, prolonged repression of the enzyme leads also to irreversible loss of activity. The action profiles of RSFileum2 and DFO presented in this study have implications for improved chemotherapeutic performance by combined drug treatment and future drug design based on specific intervention at parasite DNA synthesis.

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Pinder, J. C., R. E. Fowler, A. R. Dluzewski, L. H. Bannister, F. M. Lavin, G. H. Mitchell, R. J. Wilson, and W. B. Gratzer. "Actomyosin motor in the merozoite of the malaria parasite, Plasmodium falciparum: implications for red cell invasion." Journal of Cell Science 111, no. 13 (July 1, 1998): 1831–39. http://dx.doi.org/10.1242/jcs.111.13.1831.

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The genome of the malaria parasite, Plasmodium falciparum, contains a myosin gene sequence, which bears a close homology to one of the myosin genes found in another apicomplexan parasite, Toxoplasma gondii. A polyclonal antibody was generated against an expressed polypeptide of molecular mass 27,000, based on part of the deduced sequence of this myosin. The antibody reacted with the cognate antigen and with a component of the total parasite protein on immunoblots, but not with vertebrate striated or smooth muscle myosins. It did, however, recognise two components in the cellular protein of Toxoplasma gondii. The antibody was used to investigate stage-specificity of expression of the myosin (here designated Pf-myo1) in P. falciparum. The results showed that the protein is synthesised in mature schizonts and is present in merozoites, but vanishes after the parasite enters the red cell. Pf-myo1 was found to be largely, though not entirely, associated with the particulate parasite cell fraction and is thus presumably mainly membrane bound. It was not solubilised by media that would be expected to dissociate actomyosin or myosin filaments, or by non-ionic detergent. Immunofluorescence revealed that in the merozoite and mature schizont Pf-myo1 is predominantly located around the periphery of the cell. Immuno-gold electron microscopy also showed the presence of the myosin around almost the entire parasite periphery, and especially in the region surrounding the apical prominence. Labelling was concentrated under the plasma membrane but was not seen in the apical prominence itself. This suggests that Pf-myo1 is associated with the plasma membrane or with the outer membrane of the subplasmalemmal cisterna, which forms a lining to the plasma membrane, with a gap at the apical prominence. The results lead to a conjectural model of the invasion mechanism.

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Dubey, J. P., and M. C. Jenkins. "Re-evaluation of the life cycle of Eimeria maxima Tyzzer, 1929 in chickens (Gallus domesticus)." Parasitology 145, no. 8 (December 14, 2017): 1051–58. http://dx.doi.org/10.1017/s0031182017002153.

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AbstractA time-course study was conducted to resolve discrepancies in the literature and better define aspects of the Eimeria maxima life cycle such, as sites of development and both morphology and number of asexual stages. Broiler chickens were inoculated orally with five million E. maxima oocysts (APU1), and were necropsied at regular intervals from 12 to 120 h p.i. Small intestine tissue sections and smears were examined for developmental stages. The jejunum contained the highest numbers of developmental stages. At 12 h p.i., sporozoites were observed inside a parasitophorous vacuole (PV) in the epithelial villi and the lamina propria. By 24 h, sporozoites enclosed by a PV were observed in enterocytes of the glands of Lieberkühn. At 48 h p.i., sporozoites, elongated immature and mature schizonts, were all seen in the glands with merozoites budding off from a residual body. By 60 h, second-generation, sausage-shaped schizonts containing up to 12 merozoites were observed around a residual body in the villar tip of invaded enterocytes. At 72 and 96 h, profuse schizogony associated with third- and fourth-generation schizonts was observed throughout the villus. At 120 h, another generation (fifth) of schizonts were seen in villar tips as well as in subepithelium where gamonts and oocysts were also present; a few gamonts were in epithelium. Our finding of maximum parasitization of E. maxima in jejunum is important because this region is critical for nutrient absorption and weight gain.

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Speer, C. A., and J. P. Dubey. "Ultrastructure of schizonts and merozoites of Sarcocystis neurona." Veterinary Parasitology 95, no. 2-4 (February 2001): 263–71. http://dx.doi.org/10.1016/s0304-4017(00)00392-7.

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Morse, David, Wesley Webster, Ming Kalanon, Gordon Langsley, and Geoffrey I. McFadden. "Plasmodium falciparum Rab1A Localizes to Rhoptries in Schizonts." PLOS ONE 11, no. 6 (June 27, 2016): e0158174. http://dx.doi.org/10.1371/journal.pone.0158174.

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Journal articles on the topic 'Schizonte'

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