Publications

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the continuous cultivation of plasmodium fragile by the method of trager-jensen.using the trager-jensen method, a second malaria species, plasmodium fragile, a simian counterpart to the human malaria p. falciparum, has been cultivated successfully. the average growth rate every 3--4 days was 5-fold and the average number of merozoites observed was 14. to date, only rhesus monkey red blood cells (rbc) would support the long-term cultivation of this parasite. short-term observations indicate that rbc from the squirrel monkey (saimiri sciureus) may support growth but human rbc ...1979110165
plasmodium fragile and macaca mulatta monkeys as a model system for the study of malaria vaccines.pladmodium fragile and the macaca mulatta monkey are presented as a model system for the study of malarial vaccines. four animals were immunized with culture-grown p. fragile merozoites and subsequently challenged with culture-produced parasites. one animal failed to develop a detectable parasitemia following primary challenge. two other immunized animals had primary infections which were short-term. the parasitemias in these three monkeys following secondary challenge were short-term and the im ...1979116557
the exoerythrocytic stages of plasmodium fragile in macaca mulatta monkeys.exoerythrocytic (ee) schizonts of plasmodium fragile were found in liver tissue acquired 7, 8, 9, and 10 days following inoculation of macaca mulatta monkeys with sporozoites from anopheles balabacensis balabacensis mosquitoes. there was little to distinguish the ee bodies of p. fragile from ee bodies of many of the other species of primate malaria.1977404416
deep vascular schizogony in plasmodium fragile: organ distribution and ultrastructure of erythrocytes adherent to vascular endothelium.erythrocytes infected with plasmodium fragile, like those infected with p. falciparum and p. coatneyi, adhere to vessels in heart, adipose tissue and, to a lesser ex00 nm knob protrusions on the plasma membrane of infected erythrocytes. the close apposition between knobs and endothelium (1 nm or less) excludes macromolecules such as fibrinogen or antibodies as the adhesive force. the components on the membrane responsible for adhesion at the knobs remain unknown.19751111348
studies on the transmission of simian malaria. vi. mosquito infection and sporozoite transmission of plasmodium fragile.anopheles b. balabacensis mosquitoes were infected with plasmodium fragile when fed upon splenectomized macaca mulatta monkeys. highest level mosquito infections were obtained when feedings were made from 2 to 4 days prior to the peak in the parasitemia. transmission to m. mulatta monkeys was obtained via mosquito bite on 2 occasions and via intrahepatic and intravenous inoculation of dissected infected salivary glands on 9 occasions. the prepatent periods ranged from 12 to 17 days with a median ...19751165555
plasmodium fragile: cytoadherence of parasitized rhesus monkey erythrocytes to human endothelial cells under shear flow conditions. 19921740182
apical membrane antigen of plasmodium fragile. 19902181309
transmission of plasmodium fragile to saimiri monkeys.saimiri monkeys from bolivia and guyana were infected with the nilgiri and ceylon strains of plasmodium fragile. of 20 attempted sporozoite transmissions of the ceylon strain involving 11 splenectomized saimiri sciureus boliviensis, only 8 were successful, 2 by mosquito bite and 6 by intravenous injection of sporozoites dissected from salivary glands. prepatent periods ranged from 18 to 30 days with a mean of 25.8 days.19902213417
plasmodium fragile: detection of a ring-infected erythrocyte surface antigen (resa).a ring-infected erythrocyte surface antigen (resa) has been detected by modified immunofluorescence assay in erythrocytes infected with the simian malaria parasite, plasmodium fragile. this resa, of mr 95,000, shares many characteristics with the resa initially found in the human malaria parasite p. falciparum. both antigens are found in the membrane of erythrocytes infected with young asexual parasite stages, in merozoite-enriched preparations, and in parasite culture supernatant. since the res ...19883276549
rosetting: a new cytoadherence property of malaria-infected erythrocytes.plasmodium fragile infection of the toque monkey is a natural host-parasite association in which parasite sequestration occurs as during p. falciparum infection of humans. we have studied parasite sequestration of p. fragile and demonstrated the existence of a new property of cytoadherence of infected erythrocytes, "rosetting," which is defined as the agglutination of uninfected erythrocytes around parasitized erythrocytes. rosetting in vitro and sequestration in vivo appear simultaneously as th ...19883354764
antigenic variation of cloned plasmodium fragile in its natural host macaca sinica. sequential appearance of successive variant antigenic types.the course of infection of plasmodium fragile in its natural host, the toque monkey macaca sinica, consists of a primary peak of parasitemia followed by several distinct, successive peaks of lower parasitemia. in the s+ host, the late intraerythrocytic asexual developmental stages of p. fragile induce the expression of antigens on the surface of infected erythrocytes, which could be detected using the technique of surface immunofluorescence. immunofluorescence using unfixed erythrocytes in suspe ...19873553414
transmission of plasmodium fragile to aotus trivirgatus monkeys. 19744212480
plasmodium fragile: inhibition of cultures by serum from rhesus monkeys immunized with homologous parasites.rhesus monkeys, macaca mulatta, that had previously been immunized with the nilgiri strain of plasmodium fragile grown in culture, together with control monkeys with and without inoculation of freund's adjuvant, were challenged with cultured parasites. after treatment with chloroquine, the monkeys were rechallenged. serum specimens from three immunized monkeys caused a specific, dose-dependent inhibition of parasite growth in culture. fifty percent inhibition of in vitro growth was obtained usin ...19846479287
a nonhuman primate model for human cerebral malaria: rhesus monkeys experimentally infected with plasmodium fragile.we studied the brains of rhesus monkeys infected with the primate malaria parasite plasmodium fragile. electron microscopy showed that, in these animals, erythrocytes infected with p. fragile undergo sequestration and that parasitized red blood cells adhere to endothelial cells in the cerebral microvessels by means of knobs. cerebral microvessels with sequestered parasitized red blood cells were shown by immunohistochemical analysis to possess the platelet glycoprotein cd36, thrombospondin, and ...19947515825
protective immunity induced in squirrel monkeys with recombinant apical membrane antigen-1 of plasmodium fragile.saimiri sciureus boliviensis monkeys were immunized with the plasmodium fragile form of the merozoite apical membrane antigen-1 produced using the baculovirus expression system and combined with montanide isa 720 adjuvant. following three immunizations, monkeys were challenged with 10,000 p. fragile trophozoite parasites. antibody titers determined by fluorescence microscopy indicated an enhanced response following the second immunization. four of five control animals had parasite counts > 5% 18 ...19947810803
presbytis entellus, a new experimental host for plasmodium fragile.the course of blood-induced plasmodium fragile infection in 3 simian hosts, macaca radiata (bonnet monkey), macaca mulatta (rhesus monkey), and presbytis entellus (indian langur), was studied. the infection in 8 bonnet monkeys was very mild and nonfatal. in m. mulatta, p. fragile produced acute initial infection followed by anemia and death in 3 of 6 monkeys. the parasite has a relatively high level of virulence for p. entellus, a new experimental host for p. fragile, in which peak parasitemia r ...19948308652
plasmodium fragile: efficacy of arteether (alpha/beta) against cerebral malaria model. 19979371096
plasmodium inui is not closely related to other quartan plasmodium species.plasmodium inui (halberstaedter and von prowazek, 1907), a malarial parasite of old world monkeys that occurs in isolated pockets throughout the celebes, indonesia, malaysia, and the philippines, has traditionally been considered to be related more closely to plasmodium malariae of humans (and its primate counterpart plasmodium brasilianum), than to other primate plasmodium species. this inference was made in part because of the similarities in the periodicities or duration of the asexual cycle ...19989576499
immunisation with recombinant ama-1 protects mice against infection with plasmodium chabaudi.the plasmodium merozoite surface antigen apical membrane antigen-1 (ama-1) has previously been shown to provide partial protection to saimiri and rhesus monkeys immunised with recombinant plasmodium fragile or parasite-derived plasmodium knowlesi ama-1, respectively. in the study reported here we have used the plasmodium chabaudi/mouse model system to extend our pre-clinical assessment of an ama-1 vaccine. we describe here the expression of the full-length plasmodium chabaudi adami ama-1 and the ...19989607037
blood schizontocidal activity of wr 238605 (tafenoquine) against plasmodium cynomolgi and plasmodium fragile infections in rhesus monkeys.a new 8-aminoquinoline antimalarial wr 238605 (tafenoquine), developed initially as a primaquine alternative for prevention of plasmodium vivax 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 x 7 days cured established trophozoite induced infections in monkeys with both these parasites. the lower dose of 1.00 mg/kg/day c ...200312711101
the development of exoerythrocytic stages of plasmodium inui shortti in new world monkeys.attempts are being made to adapt old world monkey malarial parasites to new world monkeys for vaccine and molecular studies. several of these (plasmodium cynomolgi berok, plasmodium fragile, and plasmodium knowlesi) grow readily but have failed to produce infective gametocytes. plasmodium gonderi and plasmodium fieldi develop in the liver after sporozoite inoculation but have failed to establish infection in the erythrocyte. anopheles dirus mosquitoes infected with plasmodium inui shortti by fee ...200312880277
studies on sporozoite-induced and chronic infections with plasmodium fragile in macaca mulatta and new world monkeys.plasmodium fragile continues to be investigated because of its biologic similarities to the human malaria parasite, plasmodium falciparum. two strains of p. fragile are available for study; one strain is able to infect mosquitoes, whereas the other strain is transmissible only by blood inoculation. the sri lanka strain of p. fragile was transmitted to macaca mulatta, macaca fascicularis, aotus lemurinus griseimembra, aotus nancymaae, aotus vociferans, and saimiri boliviensis monkeys via sporozoi ...200617152944
evidence for an increased risk of transmission of simian immunodeficiency virus and malaria in a rhesus macaque coinfection model.in sub-saharan africa, hiv-1 infection frequently occurs in the context of other coinfecting pathogens, most importantly, mycobacterium tuberculosis and malaria parasites. the consequences are often devastating, resulting in enhanced morbidity and mortality. due to the large number of confounding factors influencing pathogenesis in coinfected people, we sought to develop a nonhuman primate model of simian immunodeficiency virus (siv)-malaria coinfection. in sub-saharan africa, plasmodium falcipa ...201121917966
Virus infection stages and distinct Th1 or Th17/Th22 T-cell responses in malaria/SHIV coinfection correlate with different outcomes of disease.Malaria and AIDS represent 2 leading causes of death from infectious diseases worldwide, and their high geographic overlap means coinfection is prevalent. It remains unknown whether distinct immune responses during coinfection with malaria and human immunodeficiency virus (HIV) affect clinical outcomes.201121921207
immune activation and regulation in simian immunodeficiency virus-plasmodium fragile-coinfected rhesus macaques.human immunodeficiency virus (hiv) is characterized by immune activation, while chronic malaria is associated with elevated interleukin-10 (il-10) levels. how these apparently antagonizing forces interact in the coinfected host is poorly understood. using a rhesus macaque model of simian immunodeficiency virus (siv)-plasmodium fragile coinfection, we evaluated how innate immune effector cells affect the balance between immune activation and regulation. in vitro toll-like receptor (tlr) responses ...201323785209
shiv antigen immunization alters patterns of immune responses to shiv/malaria coinfection and protects against life-threatening shiv-related malaria.whether vaccination against a virus can protect against more virulent coinfection with the virus and additional pathogen(s) remains poorly characterized. overlapping endemicity of human immunodeficiency virus (hiv) and malaria suggests that hiv/malaria coinfection frequently complicates acute and chronic hiv infection. here we showed that vaccination of macaques with recombinant listeria δacta prfa* expressing simian/human immunodeficiency virus (shiv) gag and env elicited gag- and env-specific ...201323568175
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