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G. P. Dutta - One of the best experts on this subject based on the ideXlab platform.

  • Plasmodium cynomolgi gametocytocidal activity of the anti malarial compound cdri 80 53 elubaquine in rhesus monkeys
    Experimental Parasitology, 2005
    Co-Authors: S.k. Puri, G. P. Dutta
    Abstract:

    The gametocytocidal action of a new enamine analogue of primaquine, elubaquine (compound CDRI 80/53, bulaquine), has been evaluated against Plasmodium cynomolgi B in rhesus monkeys. Colony bred Anopheles stephensi mosquitoes were fed on gametocyte carrying rhesus monkeys prior to and at varying intervals after oral administration of a single dose of elubaquine at doses ranging between 0.63 and 5.00 mg/kg. Complete loss of oocyst development and mosquito infectivity was observed within 24 h after administering a single 1.25 mg/kg dose, while higher dose of 3.75 mg/kg inhibited oocyst development within 5 h, indicating gametocytocidal action of the compound. Elubaquine did not show any action against developing oocysts in the vector.

  • Plasmodium cynomolgi: gametocytocidal activity of the anti-malarial compound CDRI 80/53 (elubaquine) in rhesus monkeys.
    Experimental parasitology, 2005
    Co-Authors: Surendra Puri, G. P. Dutta
    Abstract:

    The gametocytocidal action of a new enamine analogue of primaquine, elubaquine (compound CDRI 80/53, bulaquine), has been evaluated against Plasmodium cynomolgi B in rhesus monkeys. Colony bred Anopheles stephensi mosquitoes were fed on gametocyte carrying rhesus monkeys prior to and at varying intervals after oral administration of a single dose of elubaquine at doses ranging between 0.63 and 5.00 mg/kg. Complete loss of oocyst development and mosquito infectivity was observed within 24 h after administering a single 1.25 mg/kg dose, while higher dose of 3.75 mg/kg inhibited oocyst development within 5 h, indicating gametocytocidal action of the compound. Elubaquine did not show any action against developing oocysts in the vector.

  • Blood schizontocidal activity of WR 238605 (Tafenoquine) against Plasmodium cynomolgi and Plasmodium fragile infections in rhesus monkeys.
    Acta tropica, 2003
    Co-Authors: Surendra Puri, G. P. Dutta
    Abstract:

    Abstract A new 8-aminoquinoline antimalarial WR 238605 (Tafenoquine), developed initially as a primaquine alternative for prevention of Plasmodiumvivax relapses was evaluated for blood schizontocidal activity against two simian malaria infections namely Plasmodium cynomolgi B and Plasmodium fragile in rhesus monkeys. Treatment with WR 238605 at a dose of 3.16 mg(base)/kg/day×7 days cured established trophozoite induced infections in monkeys with both these parasites. The lower dose of 1.00 mg/kg/day cured 9 out of 12 monkeys infected with P. cynomolgi B and 10 out of 11 monkeys infected with P. fragile. Primaquine was only partially curative at 10.0 mg(base)/kg/day×7 dose regimen against both these infections. The potent blood schizontocidal activity of tafenoquine adds to the armoury of antimalarial drugs.

  • comparative evaluation of the colony stimulating factors induction potential of Plasmodium cynomolgi infected monkey erythrocytes and soluble antigens
    Acta Tropica, 1992
    Co-Authors: P P Singh, G. P. Dutta
    Abstract:

    Plasmodium cynomolgi total antigens soluble in culture medium (P.c.SA), and noninfective P. cynomolgi-infected monkey erythrocytes (P.c.IE) were compared for their potential to induce colony-stimulating factors (CSFs). When injected intravenously in monkeys, both preparations induced an increase in the serum CSFs levels; P.c.IE appeared to be 1.6-fold more potent than the P.c.SA. In vitro P.c.IE induced 1.8-fold more CSF by monkey blood monocyte-derived macrophages than P.c. However, both in vivo and in vitro, the peak CSFs levels induced by P.c.SA were attained apparently 8 h earlier. CSF generated by P.c.SA and P.c.IE induced the formation of macrophage, granulocyte and granulocyte-macrophage colonies, in vitro; P.c.IE-generated CSF induced the formation of significantly (P<0.01) higher numbers of granulocyte-macrophage colonies, indicating that the CSF induced by them stimulated different biological responses. The CSF induction appeared to be LPS-independent.

  • Comparative evaluation of the colony-stimulating factors induction potential of Plasmodium cynomolgi-infected monkey erythrocytes and soluble antigens.
    Acta tropica, 1992
    Co-Authors: P P Singh, G. P. Dutta
    Abstract:

    Plasmodium cynomolgi total antigens soluble in culture medium (P.c.SA), and noninfective P. cynomolgi-infected monkey erythrocytes (P.c.IE) were compared for their potential to induce colony-stimulating factors (CSFs). When injected intravenously in monkeys, both preparations induced an increase in the serum CSFs levels; P.c.IE appeared to be 1.6-fold more potent than the P.c.SA. In vitro P.c.IE induced 1.8-fold more CSF by monkey blood monocyte-derived macrophages than P.c. However, both in vivo and in vitro, the peak CSFs levels induced by P.c.SA were attained apparently 8 h earlier. CSF generated by P.c.SA and P.c.IE induced the formation of macrophage, granulocyte and granulocyte-macrophage colonies, in vitro; P.c.IE-generated CSF induced the formation of significantly (P

Alan W. Thomas - One of the best experts on this subject based on the ideXlab platform.

  • Suppression of Plasmodium cynomolgi in rhesus macaques by coinfection with Babesia microti.
    Infection and immunity, 2010
    Co-Authors: Leonie M. Van Duivenvoorde, Clemens H. M. Kocken, Annemarie Voorberg-van Der Wel, Nicole Van Der Werff, Gerco Braskamp, Edmond J. Remarque, Ivanela Kondova, Alan W. Thomas
    Abstract:

    Both Plasmodium and Babesia species are intraerythrocytic protozoans that infect a wide range of hosts, including humans, and they elicit similar inflammatory responses and clinical manifestations that differ markedly in severity. We recently reported that a rhesus macaque that was chronically infected with Babesia microti was able to control infection with Plasmodium cynomolgi (a parasite of macaques with characteristics very similar to those of Plasmodium vivax) better than naive monkeys. To confirm this and to investigate the underlying immunopathology, six naive rhesus monkeys were infected with B. microti. After 24 days, four of these monkeys and four naive rhesus monkeys were challenged with P. cynomolgi blood-stage parasites. B. microti persisted at low levels in all monkeys, and the clinical parameters were comparable to those of noninfected controls. There was a significant decrease in P. cynomolgi parasitemia in animals coinfected with B. microti compared to the parasitemia in animals infected with P. cynomolgi alone. This decrease in P. cynomolgi parasitemia correlated with increases in the levels of proinflammatory monocytes at the time of P. cynomolgi infection and with higher C-reactive protein (CRP) serum levels 1 week after malaria infection. Therefore, we conclude that ongoing infection with B. microti parasites leads to suppression of malaria infection.

  • Statistical Model To Evaluate In Vivo Activities of Antimalarial Drugs in a Plasmodium cynomolgi-Macaque Model for Plasmodium vivax Malaria
    Antimicrobial agents and chemotherapy, 2008
    Co-Authors: Clemens H. M. Kocken, Annemarie Van Der Wel, Edmond J. Remarque, Martin A. Dubbeld, Sharon Wein, R. Joyce Verburgh, Henri Vial, Alan W. Thomas
    Abstract:

    Preclinical animal models informing antimalarial drug development are scarce. We have used asexual erythrocytic Plasmodium cynomolgi infections of rhesus macaques to model Plasmodium vivax during preclinical development of compounds targeting parasite phospholipid synthesis. Using this malaria model, we accumulated data confirming highly reproducible infection patterns, with self-curing parasite peaks reproducibly preceding recrudescence peaks. We applied nonlinear mixed-effect (NLME) models, estimating treatment effects in three drug studies: G25 (injected) and the bisthiazolium prodrugs TE4gt and TE3 (oral). All compounds fully cured P. cynomolgi-infected macaques, with significant effects on parasitemia height and time of peak. Although all three TE3 doses tested were fully curative, NLME models discriminated dose-dependent differential pharmacological antimalarial activity. By applying NLME modeling treatment effects are readily quantified. Such drug development studies are more informative and contribute to reduction and refinement in animal experimentation.

  • Detection of new Babesia microti-like parasites in a rhesus monkey (Macaca mulatta) with a suppressed Plasmodium cynomolgi infection.
    The American journal of tropical medicine and hygiene, 2008
    Co-Authors: Annemarie Voorberg-v.d. Wel, Clemens H. M. Kocken, Anne-marie Zeeman, Alan W. Thomas
    Abstract:

    A new type of piroplasm, phylogenetically closest to Babesia microti-like parasites previously detected in Eurasian red squirrels (Sciurus vulgaris orientis), was identified in a rhesus monkey (Macaca mulatta) imported from China. After challenge with Plasmodium cynomolgi M strain blood-stage parasites, the rhesus monkey repeatedly showed markedly reduced levels of Plasmodium parasitemia when compared with animals not infected with this organism.

  • Plasmodium cynomolgi: Transfection of Blood-Stage Parasites Using Heterologous DNA Constructs☆
    Experimental parasitology, 1999
    Co-Authors: Clemens H. M. Kocken, Annemarie Van Der Wel, Alan W. Thomas
    Abstract:

    Abstract Kocken, C. H. M., van der Wel, A. M., and Thomas A. W. 1999. Plasmodium cynomolgi: Transfection of blood-stage parasites using heterologous DNA constructs. Experimental Parasitology93, 58–60.

Clemens H. M. Kocken - One of the best experts on this subject based on the ideXlab platform.

  • an improved Plasmodium cynomolgi genome assembly reveals an unexpected methyltransferase gene expansion
    Wellcome Open Research, 2017
    Co-Authors: Erica M Pasini, Clemens H. M. Kocken, Ulrike Bohme, Gavin G Rutledge, Annemarie Voorbergvan Der Wel, Mandy Sanders, Matthew Berriman, Thomas D Otto
    Abstract:

    Background: Plasmodium cynomolgi, a non-human primate malaria parasite species, has been an important model parasite since its discovery in 1907. Similarities in the biology of P. cynomolgi to the closely related, but less tractable, human malaria parasite P. vivax make it the model parasite of choice for liver biology and vaccine studies pertinent to P. vivax malaria. Molecular and genome-scale studies of P. cynomolgi have relied on the current reference genome sequence, which remains highly fragmented with 1,649 unassigned scaffolds and little representation of the subtelomeres.  Methods: Using long-read sequence data (Pacific Biosciences SMRT technology), we assembled and annotated a new reference genome sequence, PcyM, sourced from an Indian rhesus monkey. We compare the newly assembled genome sequence with those of several other Plasmodium species, including a re-annotated P. coatneyi assembly. Results: The new PcyM genome assembly is of significantly higher quality than the existing reference, comprising only 56 pieces, no gaps and an improved average gene length. Detailed manual curation has ensured a comprehensive annotation of the genome with 6,632 genes, nearly 1,000 more than previously attributed to P. cynomolgi . The new assembly also has an improved representation of the subtelomeric regions, which account for nearly 40% of the sequence. Within the subtelomeres, we identified more than 1300 Plasmodium interspersed repeat ( pir ) genes, as well as a striking expansion of 36 methyltransferase pseudogenes that originated from a single copy on chromosome 9. Conclusions: The manually curated PcyM reference genome sequence is an important new resource for the malaria research community. The high quality and contiguity of the data have enabled the discovery of a novel expansion of methyltransferase in the subtelomeres, and illustrates the new comparative genomics capabilities that are being unlocked by complete reference genomes.

  • Suppression of Plasmodium cynomolgi in rhesus macaques by coinfection with Babesia microti.
    Infection and immunity, 2010
    Co-Authors: Leonie M. Van Duivenvoorde, Clemens H. M. Kocken, Annemarie Voorberg-van Der Wel, Nicole Van Der Werff, Gerco Braskamp, Edmond J. Remarque, Ivanela Kondova, Alan W. Thomas
    Abstract:

    Both Plasmodium and Babesia species are intraerythrocytic protozoans that infect a wide range of hosts, including humans, and they elicit similar inflammatory responses and clinical manifestations that differ markedly in severity. We recently reported that a rhesus macaque that was chronically infected with Babesia microti was able to control infection with Plasmodium cynomolgi (a parasite of macaques with characteristics very similar to those of Plasmodium vivax) better than naive monkeys. To confirm this and to investigate the underlying immunopathology, six naive rhesus monkeys were infected with B. microti. After 24 days, four of these monkeys and four naive rhesus monkeys were challenged with P. cynomolgi blood-stage parasites. B. microti persisted at low levels in all monkeys, and the clinical parameters were comparable to those of noninfected controls. There was a significant decrease in P. cynomolgi parasitemia in animals coinfected with B. microti compared to the parasitemia in animals infected with P. cynomolgi alone. This decrease in P. cynomolgi parasitemia correlated with increases in the levels of proinflammatory monocytes at the time of P. cynomolgi infection and with higher C-reactive protein (CRP) serum levels 1 week after malaria infection. Therefore, we conclude that ongoing infection with B. microti parasites leads to suppression of malaria infection.

  • Statistical Model To Evaluate In Vivo Activities of Antimalarial Drugs in a Plasmodium cynomolgi-Macaque Model for Plasmodium vivax Malaria
    Antimicrobial agents and chemotherapy, 2008
    Co-Authors: Clemens H. M. Kocken, Annemarie Van Der Wel, Edmond J. Remarque, Martin A. Dubbeld, Sharon Wein, R. Joyce Verburgh, Henri Vial, Alan W. Thomas
    Abstract:

    Preclinical animal models informing antimalarial drug development are scarce. We have used asexual erythrocytic Plasmodium cynomolgi infections of rhesus macaques to model Plasmodium vivax during preclinical development of compounds targeting parasite phospholipid synthesis. Using this malaria model, we accumulated data confirming highly reproducible infection patterns, with self-curing parasite peaks reproducibly preceding recrudescence peaks. We applied nonlinear mixed-effect (NLME) models, estimating treatment effects in three drug studies: G25 (injected) and the bisthiazolium prodrugs TE4gt and TE3 (oral). All compounds fully cured P. cynomolgi-infected macaques, with significant effects on parasitemia height and time of peak. Although all three TE3 doses tested were fully curative, NLME models discriminated dose-dependent differential pharmacological antimalarial activity. By applying NLME modeling treatment effects are readily quantified. Such drug development studies are more informative and contribute to reduction and refinement in animal experimentation.

  • Detection of new Babesia microti-like parasites in a rhesus monkey (Macaca mulatta) with a suppressed Plasmodium cynomolgi infection.
    The American journal of tropical medicine and hygiene, 2008
    Co-Authors: Annemarie Voorberg-v.d. Wel, Clemens H. M. Kocken, Anne-marie Zeeman, Alan W. Thomas
    Abstract:

    A new type of piroplasm, phylogenetically closest to Babesia microti-like parasites previously detected in Eurasian red squirrels (Sciurus vulgaris orientis), was identified in a rhesus monkey (Macaca mulatta) imported from China. After challenge with Plasmodium cynomolgi M strain blood-stage parasites, the rhesus monkey repeatedly showed markedly reduced levels of Plasmodium parasitemia when compared with animals not infected with this organism.

  • Plasmodium cynomolgi: Transfection of Blood-Stage Parasites Using Heterologous DNA Constructs☆
    Experimental parasitology, 1999
    Co-Authors: Clemens H. M. Kocken, Annemarie Van Der Wel, Alan W. Thomas
    Abstract:

    Abstract Kocken, C. H. M., van der Wel, A. M., and Thomas A. W. 1999. Plasmodium cynomolgi: Transfection of blood-stage parasites using heterologous DNA constructs. Experimental Parasitology93, 58–60.

P P Singh - One of the best experts on this subject based on the ideXlab platform.

  • comparative evaluation of the colony stimulating factors induction potential of Plasmodium cynomolgi infected monkey erythrocytes and soluble antigens
    Acta Tropica, 1992
    Co-Authors: P P Singh, G. P. Dutta
    Abstract:

    Plasmodium cynomolgi total antigens soluble in culture medium (P.c.SA), and noninfective P. cynomolgi-infected monkey erythrocytes (P.c.IE) were compared for their potential to induce colony-stimulating factors (CSFs). When injected intravenously in monkeys, both preparations induced an increase in the serum CSFs levels; P.c.IE appeared to be 1.6-fold more potent than the P.c.SA. In vitro P.c.IE induced 1.8-fold more CSF by monkey blood monocyte-derived macrophages than P.c. However, both in vivo and in vitro, the peak CSFs levels induced by P.c.SA were attained apparently 8 h earlier. CSF generated by P.c.SA and P.c.IE induced the formation of macrophage, granulocyte and granulocyte-macrophage colonies, in vitro; P.c.IE-generated CSF induced the formation of significantly (P<0.01) higher numbers of granulocyte-macrophage colonies, indicating that the CSF induced by them stimulated different biological responses. The CSF induction appeared to be LPS-independent.

  • Comparative evaluation of the colony-stimulating factors induction potential of Plasmodium cynomolgi-infected monkey erythrocytes and soluble antigens.
    Acta tropica, 1992
    Co-Authors: P P Singh, G. P. Dutta
    Abstract:

    Plasmodium cynomolgi total antigens soluble in culture medium (P.c.SA), and noninfective P. cynomolgi-infected monkey erythrocytes (P.c.IE) were compared for their potential to induce colony-stimulating factors (CSFs). When injected intravenously in monkeys, both preparations induced an increase in the serum CSFs levels; P.c.IE appeared to be 1.6-fold more potent than the P.c.SA. In vitro P.c.IE induced 1.8-fold more CSF by monkey blood monocyte-derived macrophages than P.c. However, both in vivo and in vitro, the peak CSFs levels induced by P.c.SA were attained apparently 8 h earlier. CSF generated by P.c.SA and P.c.IE induced the formation of macrophage, granulocyte and granulocyte-macrophage colonies, in vitro; P.c.IE-generated CSF induced the formation of significantly (P

  • induction of colony stimulating factors by Plasmodium cynomolgi components
    Journal of Biological Regulators and Homeostatic Agents, 1991
    Co-Authors: P P Singh, G. P. Dutta
    Abstract:

    Plasmodium cynomolgi total parasite antigens soluble in culture medium (P.c.SA), when injected in monkeys (Macaca mulatta) intravenously, induced the synthesis and secretion of serum colony-stimulating factors (CSFs). In vitro cultured monkey splenic macrophages and blood monocytes, following incubation with P.c.SA, also elaborated CSFs: the splenic macrophages responded more. Peak CSFs levels, both in vivo and in vitro, were attained after 8 hours of P.c.SA stimulation, and thereafter declined to baseline values within 48 hours. CSFs, both in serum and in conditioned medium, induced the formation of macrophage, granulocyte and granulocyte-macrophage colonies in vitro, in the same proportion, indicating that committed progenitor cells responded to CSF from both sources in a similar way. Polymyxin B treatment had no effect on P.c.SA stimulated CSF elaboration by macrophages, suggesting an LPS-independent mechanism of CSF induction. CSF synthesis appeared to be de novo, as cycloheximide treatment of macrophages completely inhibited CSF production. These observations indicate that P. cynomolgi components can induce CSF synthesis.

Pascal Millet - One of the best experts on this subject based on the ideXlab platform.

  • Immunologic characterization of Plasmodium vivax antigens using Plasmodium cynomolgi liver stage-primed immune sera.
    The American journal of tropical medicine and hygiene, 1994
    Co-Authors: Chunfu Yang, William E. Collins, Pascal Millet
    Abstract:

    Abstract We have shown in a previous study that immunization of a rhesus monkey (Macaca mulatta) with inactivated liver stages of the simian malaria parasite Plasmodium cynomolgi (B strain) produced high antibody titers against sporozoites, liver stages, and blood stages of P. cynomolgi. In the present study, we demonstrate that these anti-P. cynomolgi immune sera recognized P. vivax (Salvador I) antigens. In an indirect immunofluorescence assay, both postimmunization and postchallenge sera reacted with antigens of sporozoite, liver-, and blood-stage parasites. In Western blot analysis, postimmunization sera recognized four bands of 97, 93, 70, and 65 kD in sporozoite antigens; postchallenge sera further recognized three doublet (set of two) bands of 86–90, 73–78, and 44–52 kD. When blood-stage extracts were used as antigens, five bands of 118, 105, 76, 68, and 47 kD reacted with postimmunization sera; two doublet bands of 81–87 and 49–52 kD further reacted with postchallenge sera. None of these sera reacted with asexual blood-stage extracts of P. falciparum and P. malariae, or with a recombinant circumsporozoite protein of P. vivax.

  • Plasmodium cynomolgi: Immunization of a rhesus monkey with exoerythrocytic stages cultured in autologous hepatocytes
    Experimental parasitology, 1991
    Co-Authors: Pascal Millet, J. R. Broderson, William E. Collins, Carter T. Atkinson, Gary H. Campbell, Bobby G. Brown, Valeria Filipski, Masamichi Aikawa, Phuc Nguyen-dinh
    Abstract:

    To investigate the immune response to exoerythrocytic stages of malaria parasites, a rhesus monkey was immunized with autologous primary hepatocyte cultures infected with 7-day-old liver stage parasites of Plasmodium cynomolgi. A primary antibody response against EE stage antigens was obtained, and boosted after injection of homologous viable sporozoites. Antibodies directed against sporozoites and blood stages were also detected. The polyvalent immune response observed demonstrates the antigenicity of the liver stages and suggests their involvement in the general immune response against malaria.