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the number of sporozoites produced by individual malaria oocysts.mature oocysts of plasmodium falciparum and p. vivax from western thailand were separated from the midguts of anopheles dirus by collagenase digestion, and the number of sporozoites contained in each was counted. for 26 p. vivax oocysts, the mean count was 3, 688 (range 1, 954-5, 577) and for 14 p. falciparum, the mean count was 3, 385 (range 1, 359-4, 554); a single p. cynomolgi oocyst contained 7, 521. counts were not significantly correlated with oocyst density, oocyst age, or identity of the ...19911951866
cytokines kill malaria parasites during infection crisis: extracellular complementary factors are essential.malaria infection crisis, at which the parasitemia drops precipitously and the parasite loses infectivity to the mosquito vector, occurs in many natural malaria systems, and has not been explained. we demonstrate that in a simian malaria parasite (plasmodium cynomolgi in its natural host, the toque monkey), the loss of infectivity during crisis is due to the death of circulating intraerythrocytic gametocytes mediated by crisis serum. these parasite-killing effects in crisis serum are due to the ...19911900073
induction of colony-stimulating factors by plasmodium cynomolgi components.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 ...19911897383
evaluation of ayush-64 for blood schizontocidal activity against rodent and simian malaria parasites.ayush-64, a new herbal antimalarial drug developed by the central council for ayurveda and siddha, was evaluated for direct parasiticidal action against p. berghei and p. yoelii nigeriensis in swiss mice and p. cynomolgi b and p. knowlesi in rhesus monkeys. no blood schizontocidal activity could be demonstrated against any of the four malaria parasites.19911824361
minisatellite-like repeat sequences in the genome of rodent malaria parasites.using minisatellite dna probes and various southern blots containing dna samples from rodent malaria parasites it was shown that minisatellite-like sequences occur in the genome of these plasmodium species. in contrast to the high copy number as observed in higher eukaryotes, the use of fingerprinting techniques on dna from these parasites reveals that minisatellite sequences are only present at a small number of loci. when parasite lines which differ in biological parameters are compared, no fr ...19911820717
enkephalins-modulation of plasmodium cynomolgi antigens-induced colony-stimulating factors elaboration by macrophages.methionine-enkephalin (m-enk) and its analogue compound 82/205 (10(-5) and 10(-6) m) inhibited elaboration of plasmodium cynomolgi total antigens soluble in culture medium (p.c.sa)-induced colony-stimulating factors (csfs) by monkey blood monocyte-derived macrophages, in vitro. paradoxically, lower concentrations (10(-7)-10(-9) m) of both the peptides greatly augmented csfs elaboration; 82/205 appeared to be nearly 2.3-fold more potent. naloxone (10(-5) m) pretreatment of macrophages inhibited o ...19911803861
immune responses against sexual stages of plasmodium vivax during human malarial infections in sri lanka.during natural infections of p. vivax malaria a variety of immune responses to the infection affect infectivity of the parasites to mosquitoes. sexual stage antigens present in the blood stage parasites induce antibodies which may either enhance or suppress the infectivity of the sexual parasites to mosquitoes. subsequent infections of p. vivax do not, unless occurring within less than 4 months, boost this response indicating a very short immune memory for the relevant antigens. blood infection ...19911688139
use of a restriction fragment length polymorphism (rflp) as a genetic marker in crosses of anopheles gambiae (diptera: culicidae): independent assortment of a diphenol oxidase rflp and an esterase locus.analysis of restriction fragment length polymorphism (rflp) is a powerful tool for analyzing linkage relationships in species where few genetic markers have been described and where conduct of crosses is difficult. it also permits integration of genetic and physical (cytogenetic) data when the probes have been mapped by in situ hybridization. to illustrate the utility of the method, and because some mutations of a diphenol oxidase gene might conceivably produce the malaria refractoriness phenoty ...19911674545
differential sensitivity of the pre-erythrocytic stages of plasmodium cynomolgi b to the prophylactic action of primaquine.the sensitivity of the developing pre-erythrocytic stages of plasmodium cynomolgi bastianelli to primaquine in single, two or three dose regimens administered at varying times during the incubation period has been investigated. the study reveals that the early pre-erythrocytic stages of the parasite are more susceptible to primaquine than the later stages. regimens of 5.34 mg/kg x 1 dose on day 0 or day + 1; 2.67 mg/kg x 2 doses on days 0 and 1 and 1.78 mg/kg x 3 doses on days -1, 0, + 1 or days ...19921598515
malaria: from quinine to the vaccine. 19921541651
effect of adjuvant formulations on the selection of b-cell epitopes expressed by a malaria peptide vaccine.because subunit vaccines may create artificial epitopes, the goal of this study was to concentrate the immune response toward protective epitopes contained in a peptide, [(nagg)5]y. this peptide consisted of five repeat sequences of the immunodominant epitope of the circumsporozoite protein of the simian malaria parasite plasmodium cynomolgi and a terminal tyrosine. it was conjugated to bovine serum albumin and mixed with various adjuvant formulations, including block copolymers l121, l141, l180 ...19921377851
comparative evaluation of the colony-stimulating factors induction potential of plasmodium cynomolgi-infected monkey erythrocytes and soluble antigens.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 viv ...19921359752
[studies on the establishment of malarial animal model of short-term relapse. i. asynchronous growth of exoerythrocytic schizonts of plasmodium cynomolgi].a monkey was infected with sporozoites of plasmodium cynomolgi from vietnam. parasitemia was detected on the 8th day with a starting density of 17/100 white blood cells. 22 hours after that time, many ee schizonts appeared with an average density of 3.74 +/- 0.66 per mm3 hepatic tissue in liver biopsy specimens from the monkey. most of the ee schizonts were immature and grew at an uneven rate, having an average diameter of 34.22 +/- 7.28 microns but some of them even remained 15.75 +/- 2.47 micr ...19921307269
[studies on the establishment of malarial animal model of short-term relapse. ii. the phenomenon of sustained special ring form parasitemia in plasmodium cynomolgi infection].our previous report that the ee merozites of plasmodium cynomolgi from vietnam continuously released from the liver to the blood circulation was further demonstrated in this report. monkeys were given pyronaridine 24 mg/kg.d x 6 after being inoculated intravenously with 32 x 10(5) sporzoites of p. cynomolgi. thick blood film examination was conducted two times daily till the day when trophozoites were detected. under the residual action of blood schizontocied, a special ring form parasitemia at ...19921303329
[effects of dexamethasone and cyclophosphamide on development of exo-erythrocytic form of plasmodium cynomolgi bastianellii in rhesus monkey].the rhesus monkeys (macaca mulatta) challenged with plasmodium cynomolgi bastianellii sporozoites were treated with im dexamethasone (dex) 1 mg.kg-1.d-1 x 7 d and cyclophosphamide (cyc) 25 mg.kg-1.d-1 x 3d, respectively. on d 7 after challenge, serial sections of liver biopsy stained with he revealed that the distributive density and size of exo-erythrocytic (ee) form of the parasites showed no difference between medicated and control monkeys. the prepatent period of the primary attack and the r ...19921300058
two-site pan-species monoclonal antibody elisa for detection of blood stage malaria antigen.a two-site pan-species monoclonal antibody sandwich elisa (mab-mab elisa) was developed to detect both plasmodium vivax and p. falciparum antigens in whole blood impregnated on filter paper. in this assay, the plates were coated with pan-species mab 3f9 and another pan-species mab m26-32 conjugated with alkaline phosphatase was used for detection of bound antigen. the sensitivity of this assay was 5, 10 and 10 parasites per 10(6) erythrocytes for cultured p. falciparum, patient-derived p. vivax ...19921298083
detection of circulating plasmodial antigens in human sera by sandwich elisa with monoclonal antibodies.two monoclonal antibodies (mabs), one produced against plasmodium falciparum (pf-ig8) and the other against p. cynomolgi (pc-ie12) schizont antigens were used in a sandwich elisa for the detection of circulating plasmodial antigens in sera of patients infected with either p. falciparum, p. vivax or p. malariae. the mean +/- sd optical density (od) values for the normal control group using pf-108 and pc-1e12 were 0.351 +/- 0.036 and 0.205 +/- 0.044, respectively. mean od values for the three infe ...19921298082
plasmodium cynomolgi: the hsp 70 gene.the hsp 70 gene of plasmodium cynomolgi was isolated and characterized. as expected the gene is highly similar to that of the hsp 70 gene of plasmodium falciparum (98% at the protein level, 82% at the nucleotide level). surprisingly, the hsp 70 gene appears to be present in a single copy in all the p. cynomolgi strains tested, a finding that has implications for the parasite's ability to undergo a heat shock response.19921426134
a method for screening drugs against the liver stages of malaria using plasmodium gallinaceum and aedes mosquitos.1. the radical cure of human malaria caused by plasmodium vivax requires two drugs, i.e., a blood schizontocide such as chloroquine to clear the circulating parasites, and primaquine aimed at the liver stages (hyponozoites) responsible for the late relapses of this parasite. primaquine is unique as a radical curative drug but is highly toxic. the only useful model currently available for screening drugs to replace primaquine is plasmodium cynomolgi-induced malaria in rhesus monkeys. because of t ...19921341921
evolutionary relatedness of some primate models of plasmodium.primate--and, specifically, monkey--malaria infections are commonly used for understanding the pathology of and immune response to the human disease because they are thought to resemble most closely the host-parasite relationship found in humans. plasmodium cynomolgi is used extensively as a model for the human parasite, p. vivax, and p. knowlesi is used primarily as a model for the development of erythrocytic-stage vaccines. both of these simian parasites can naturally infect man, resulting in ...19937689135
[studies on residual antimalarial activity of tripynadine in mice and monkeys].this paper reports the experiments in which tripynadine free base at a dose 4.5 times that of ed50 was given to mice by intragastric administration. on the 20th day following the administration the mice were inoculated with 1 x 10(7) rbc infected with plasmodium berghei anka strain. the infection rate was zero, implying that all mice had acquired protection. although the residual activity time of tripynadine phosphate was longer than that of tripynadine free base or piperaquine phosphate, but tr ...19938168241
[studies on the establishment of malarial animal model of short-term relapse. iv. short-term relapse in rhesus monkeys infected with sporozoites of plasmodium cynomolgi].the present paper reports that the short-term relapse could be artificially made by the application of the experimental method, and thus we established the monkey model of the short-term relapse. according to the experimental design, when the parasitemia was detected in rhesus monkeys infected with sporozoites of plasmodium cynomolgi, a combined therapy of pyronaridine 6 mg/kg body weight, artemether 10 mg/kg and chloroquine 20 mg/kg once daily for 3 days was carried out to clear the erythrocyti ...19938082260
association of two esterase genes, a chromosomal inversion, and susceptibility to plasmodium cynomolgi in the african malaria vector anopheles gambiae.the ability of a selected strain of the malaria vector anopheles gambiae to encapsulate the early oocysts of the malaria parasite plasmodium cynomolgi b has previously been shown to be genetically linked to specific esterase phenotypes. this association between plasmodium susceptibility and esterase phenotype is found in the an. gambiae g3 strain from which the plasmodium-refractory and -susceptible mosquito strains were derived. genetic crosses had suggested that the esterase phenotypes reflect ...19938372956
hydrolytic enzymes of rhesus placenta during plasmodium cynomolgi infection: ultrastructural and biochemical studies.placenta in monkey demonstrated altered pathophysiology after p cynomolgi infection. the electronmicroscopic observations showed slight complete focal necrosis of the placental tissue, besides alterations in total protein, phosphatases and proteinases. these changes in cellular constituents of placenta during malaria infection may be responsible for malfunctioning of the organ and in turn, abnormal development of foetus.19938500817
[studies on the establishment of malarial animal model of short-term relapse. iii. combined therapy with pyronaridine-artemether-chloroquine for parasitemia clearance].to establish a plasmodium cynomolgi-monkey model of short-term relapse, different antimalarials have been used to inhibit recrudescence so as to elude the confusion between the two different onsets. when a single dose of effective schizonticides pyronaridine, artemether or chloroquine was administered, recrudesence readily occurred. this paper reports the results of the combined therapy with the above three drugs. seven rhesus monkeys from guangxi autonomous region infected with plasmodium cynom ...19938168239
causal prophylactic and radical curative activity of wr182393 (a guanylhydrazone) against plasmodium cynomolgi in macaca mulatta.primaquine is the only currently available drug effective against persistent tissue stages of relapsing malaria in humans. causal prophylactic and radical curative properties of wr182393 (a guanylhydrazone) were investigated as part of an effort to evaluate alternatives to primaquine in the rhesus monkey (macaca mulatta)/plasmodium cynomolgi test model. the drug was suspended in dimethylsulfoxide for intramuscular (im) injection. a pilot study indicated causal prophylactic activity in a regimen ...19938214277
[progress on the study of the distribution of plasmodium cynomolgi in the world]. 19948082460
evaluation of wr250417 (a proguanil analog) for causal prophylactic activity in the plasmodium cynomolgi-macaca mulatta model.the plasmodium cynomolgi-macaca mulatta model has been used to test the antimalarial activity of new drugs for both radical cure and casual prophylaxis. the proguanil analog wr250417 (also known as ps-15) was evaluated for causal prophylactic activity in rhesus monkeys infected with p. cynomolgi bastianelli. four monkeys were orally dosed with 40 mg/kg/day of wr250417 over three days (-1, 0, and +1). sporozoite-induced infection of p. cynomolgi was initiated on day 0 with 1 x 10(6) sporozoites t ...19948116810
role of fatty infiltration during malaria in rhesus monkey.p. cynomolgi b-rhesus monkey model of malarial infection has been used to study lipid infiltration in host tissues in early (exoerythrocytic) and late (chronic) stages of malaria infection. histochemically we could demonstrate significant infiltration of neutral & total lipids in liver during the exoerythrocytic stage and in liver and kidney in the erythrocytic stage. the parasite used in the study closely resembles the human parasite p. vivax. it has a defined prepatent period, can be cyclicall ...19948196503
removal of leucocytes from plasmodium vivax-infected blood. 19948067817
proguanil plus sulfamethoxazole is not causally prophylactic in the macaca mulatta--plasmodium cynomolgi model.new drugs for causal prophylaxis of malaria are needed. a proguanil/sulfamethoxazole combination was investigated using a rhesus monkey model (macaca mulatta infected with plasmodium cynomolgi) to determine whether causal prophylaxis could be achieved. when a five-day regimen of proguanil (40 mg/kg/day) combined with sulfamethoxazole (100 mg/kg/day) was used, infection of all animals (6 of 6) was observed, with an extended prepatent period (median 40 days). two control animals became infected on ...19948203715
immunologic characterization of plasmodium vivax antigens using plasmodium cynomolgi liver stage-primed immune sera.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 ...19947943558
the small ribosomal subunit rna isoforms in plasmodium cynomolgi.we report the isolation, characterization and analysis of the small subunit rrna genes in plasmodium cynomolgi (ceylon). as in other plasmodium species, these genes are present in low copy number, are unlinked and form two types that are distinct in sequence and are expressed stage specifically. the asexually expressed (type a) genes are present in four copies in the ceylon- and in five copies in the berok-strain. surprisingly, the sexually expressed (type b) gene is present in a single copy. th ...19948005440
use of the rhesus monkey as an experimental model to test the degree of efficacy of an anti-sporozoite peptide malaria vaccine candidate combined with copolymer-based adjuvants.humoral response against sporozoites is not effective in protecting individuals from getting malaria. reduction in the infectivity of sporozoites has not been quantified for most anti-sporozoite vaccines tested. quantification requires animal models providing predictable prepatent periods, e.g., time elapsed between sporozoite inoculation and detection of parasitemia, to be used as an indicator of activity against sporozoites. a delay in prepatent period from vaccinated animals would therefore r ...19957741171
sequence analysis of apical membrane antigen 1 (ama-1) of plasmodium cynomolgi bastianelli. 19958577338
the plasmodium cynomolgi merozoite surface protein 1 c-terminal sequence and its homologies with other plasmodium species. 19958719250
sodium beta-artelinate--a new potential gametocytocide.the water-soluble artemisinin analogue sodium beta-artelinate, a fast-acting blood schizontocide, was evaluated for gametocytocidal action against simian malaria plasmodium cynomolgi b, and a single dose of the compound has been found to be an effective gametocytocide by both oral and intravenous routes. the compound was able to sterilize the circulating gametocytes in rhesus monkey, resulting in loss of mosquito infectivity and oocyst development in the anopheles stephensi. however, no sporonto ...19968631376
poly iclc inhibits plasmodium cynomolgi b malaria infection in rhesus monkeys.prophylatic treatment with a single dose of 1.0 or 2.0 mg/kg (body weight) of polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose (poly iclc), a potent interferon (ifn) inducer and immune enhancer, 18 h before intravenous inoculation of sporozoites (1.04 x 10(5)-0.70 x 10(6) sporozoites) of plasmodium cynomolgi b in the rhesus monkey, completely abolished the infectivity of sporozoites. the inhibitory effect of poly iclc is dose dependent in monkeys infected wit ...19968640451
in-vitro cultivation of exoerythrocytic stages of plasmodium cynomolgi in hepatocytes of macaca radiata.hepatocytes from bonet monkey (macaca radiata) obtained by perfusion of a liver biopsy were infected in-vitro with plasmodium cynomolgi bastianellii sporozoites raised in anopheles stephensi. the development of exoerythrocytic (ee) stages was seen under phase contrast microscope and by giemsa staining. multinucleated ee-stages were seen in the cultured hepatocytes on day 7-8 post-sporozoite inoculation.19968952170
histochemical changes in host tissues from plasmodium cynomolgi b infected rhesus monkey (macaca mulatta).plasmodium cynomolgi b has been used to infect the rhesus monkey to study the histochemical changes (lipid infiltration, glycogen, protein, dna and rna) in liver, kidney and spleen during early (exoerythrocytic) and late (chronic) stages of malarial infection. infected liver showed significant lipid infiltration during exoerythrocytic and erythrocytic (acute phase) stage of infection. kidney showed lipid deposition during acute phase of infection while spleen sections were negative for lipid dep ...19968641716
gametocytocidal activity of alpha/beta arteether by the oral route of administration.arteether (alpha/beta) (a mixture of alpha and beta enantioners) has been reported to possess gametocytocidal activity against plasmodium cynomolgi b when the drug is given by the intramuscular route, but it would be preferable to use oral route therapy for gametocyte carriers. this is a report of a study of the gametocytocidal action of arteether administered by the oral route. the results indicate high levels of activity at 10 mg/kg in a single dose or in two divided doses when given orally.19968686787
a shared genetic mechanism for melanotic encapsulation of cm-sephadex beads and a malaria parasite, plasmodium cynomolgi b, in the mosquito, anopheles gambiae.a plasmodium-refractory strain of anopheles gambiae that melanizes ookinetes and intrathoracically inoculated cm-sephadex beads was mated to a plasmodium-susceptible strain that does not melanize the parasite or the beads. the f1 progeny were then backcrossed to the susceptible strain. backcross progeny were given a blood meal containing infective plasmodium cynomolgi b, and the parasites were allowed to develop for 6-7 days, at which time the infected mosquitoes were injected with cm-sephadex b ...19968948327
sterile protection of monkeys against malaria after administration of interleukin-12.an estimated 300-500 million new infections and 1.5-2.7 million deaths attributed to malaria occur annually in the developing world, and every year tens of millions of travelers from countries where malaria is not transmitted visit countries with malaria. because the parasites that cause malaria have developed resistance to many antimalarial drugs, new methods for prevention are required. intraperitoneal injection into mice of one dose of 150 ng (approximately 7.5 micrograms per kg body weight) ...19978986746
cloning and sequence analysis of a gene encoding an erythrocyte binding protein from plasmodium cynomolgi. 19979364974
characterization of c-terminal merozoite surface protein-1 baculovirus recombinant proteins from plasmodium vivax and plasmodium cynomolgi as recognized by the natural anti-parasite immune response. 19979364976
cloning and sequence analysis of the thrombospondin-related adhesive protein (trap) gene of plasmodium cynomolgi bastianelli. 19979497063
quantitative trait loci for refractoriness of anopheles gambiae to plasmodium cynomolgi b.the severity of the malaria pandemic in the tropics is aggravated by the ongoing spread of parasite resistance to antimalarial drugs and mosquito resistance to insecticides. a strain of anopheles gambiae, normally a major vector for human malaria in africa, can encapsulate and kill the malaria parasites within a melanin-rich capsule in the mosquito midgut. genetic mapping revealed one major and two minor quantitative trait loci (qtls) for this encapsulation reaction. understanding such antiparas ...19979103203
a genetic study of a melanization response to sephadex beads in plasmodium-refractory and -susceptible strains of anopheles gambiae.a previously selected plasmodium-refractory strain of anopheles gambiae melanotically encapsulates many species of plasmodium. genetic studies of this strain have shown that this refractory phenotype is controlled by a limited number of genes, and the existence of two such genes, pif-b and pif-c, has been demonstrated. further work to determine the molecular basis for this mode of refractoriness led to the discovery that the host-parasite interaction is mimicked by the mosquito's response to car ...19979158056
phage-displayed mimotopes elicit monoclonal antibodies specific for a malaria vaccine candidate.the phage-displayed peptide cgrvclrc (c15) has been isolated from a random library by affinity screening with the d14-3 monoclonal antibody, which was raised to the 42 kda c-terminal fragment of the major merozoite surface protein 1 of plasmodium vivax (pv42). in order to investigate the use of such mimotopes as possible vaccine components, we studied the antibody response in biozzi mice immunized with c15. high titers of antibodies cross-reacting with pv42 were generated and the ic50 of all imm ...19989504719
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
baculovirus merozoite surface protein 1 c-terminal recombinant antigens are highly protective in a natural primate model for human plasmodium vivax malaria.a successful anti-blood stage malaria vaccine trial based on a leading vaccine candidate, the major merozoite surface antigen-1 (msp1), is reported here. the trial was based on plasmodium cynomolgi, which is a primate malaria parasite which is highly analogous to the human parasite plasmodium vivax, in its natural host, the toque monkey, macaca sinica. two recombinant baculovirus-expressed p. cynomolgi msp1 proteins, which are analogous to the 42- and 19-kda c-terminal fragments of p. falciparum ...19989529073
plasmodium cynomolgi: transfection of blood-stage parasites using heterologous dna constructs. 199910464040
plasmodium vivax, p. cynomolgi, and p. knowlesi: identification of homologue proteins associated with the surface of merozoites.we have identified a plasmodium vivax merozoite surface protein (msp) that migrates on sds-polyacrylamide gels at a mr of about 185 kda. this protein was recognized by a p. vivax monoclonal antibody (mab) that localizes the protein by immunofluorescence to the surface of merozoites and also immunoprecipitates this protein from np-40 detergent extracts of [35s]methionine metabolically radiolabeled p. vivax schizonts. the p. vivax msp does not become biosynthetically radiolabeled with [3h]glucoami ...199910072326
high-level expression of plasmodium vivax apical membrane antigen 1 (ama-1) in pichia pastoris: strong immunogenicity in macaca mulatta immunized with p. vivax ama-1 and adjuvant sbas2.the apical membrane antigen 1 (ama-1) family is a promising family of malaria blood-stage vaccine candidates that have induced protection in rodent and nonhuman primate models of malaria. correct conformation of the protein appears to be essential for the induction of parasite-inhibitory responses, and these responses appear to be primarily antibody mediated. here we describe for the first time high-level secreted expression (over 50 mg/liter) of the plasmodium vivax ama-1 (pv66/ama-1) ectodomai ...19999864194
studies on infections with the berok strain of plasmodium cynomolgi in monkeys and mosquitoes.infections with the berok strain of plasmodium cynomolgi were induced in macaca mulatta, macaca fascicularis, macaca nemestrina, aotus lemurinus griseimembra, aotus azarae boliviensis, and saimiri boliviensis monkeys. transmission was obtained with sporozoites developing in anopheles peditaeniatus, anopheles maculatus, anopheles quadrimaculatus, anopheles culicifacies, and anopheles dirus mosquitoes. this strain of p. cynomolgi offers significant potential for a number of experimental studies. t ...199910219307
rna helicase-related genes of plasmodium falciparum and plasmodium cynomolgi.rna helicases play many essential roles including cell development and growth. using degenerate oligonucleotide primers designed to amplify dna fragments flanked by the highly conserved helicase motifs vldead and yihrig and genomic dnas from the malarial parasites as a template, we have cloned two putative rna helicase genes (546 and 540 bp) from p. falciparum and one gene (546 bp) from p. cynomologi. southern blot analysis revealed that these could be multiple and single-copy genes in p. falcip ...199910049705
linkage of a gene causing malaria refractoriness to diphenol oxidase-a2 on chromosome 3 of anopheles gambiae.an inbred line of the african malaria vector anopheles gambiae is refractory to development of malaria parasites. it is homozygous for a 4.3-kb sal i restriction fragment at the dox-a2 locus, whereas the parent population is polymorphic at this locus, and a susceptible line is homozygous for an alternate 3.85-kb fragment. the dox-a2 locus is located in the middle of chromosome 3r, in division 33b, and is tightly linked to a cluster of genes including dopa decarboxylase that are involved in the p ...19999988317
the crystal structure of c-terminal merozoite surface protein 1 at 1.8 a resolution, a highly protective malaria vaccine candidate.the c-terminal proteolytic processing product of merozoite surface protein 1 (msp1) appears essential for successful erythrocyte invasion by the malarial parasite, plasmodium. we have determined the crystal structure at 1.8 a resolution of a soluble baculovirus-recombinant form of the protein from p. cynomolgi, which confers excellent protective efficacy in primate vaccination trials. the structure comprises two egf-like domains, and sequence comparisons strongly suggest that the same conformati ...199910230398
azithromycin: antimalarial profile against blood- and sporozoite-induced infections in mice and monkeys.the spectrum of antimalarial activity of the new macrolide antibiotic azithromycin was evaluated against blood- and sporozoite-induced infections with a chloroquine-resistant strain of plasmodium yoelii nigeriensis (n-67) in swiss mice and with simian parasite plasmodium cynomolgi b in rhesus monkeys. against experimental rodent malaria, a 70 mg/kg/day dose showed curative blood-schizontocidal activity in a four-dose regimen administered orally from day 0 to day 3 or from day 2 to day 5 to mice ...200010631075
demonstration of a persisting exo-erythrocytic cycle in plasmodium cynomolgi and its bearing on the production of relapses. 1948. 200011196492
[practicability of ifat using plasmodium cynomolgi and plasmodium falciparum antigens in different malarious areas].to compare the practicability of ifat in different malarious areas using plasmodium cynomolgi(p.c.) and plasmodium falciparum(p.f.) antigens.200012567477
merozoite surface protein-9 of plasmodium vivax and related simian malaria parasites is orthologous to p101/abra of p. falciparum.plasmodium vivax merozoite surface protein-9 (pvmsp-9) is characterized here along with orthologues from the related simian malarias plasmodium cynomolgi and plasmodium knowlesi. we show that although the corresponding msp-9 proteins do not have acidic-basic repeated amino acid (aa) motifs, they are related to the plasmodium falciparum acidic-basic repeat antigen (abra) also known as p101. recognition of this new interspecies plasmodium msp family stems from the prior identification of related m ...200211849704
isolation and characterization of an eif-4a homologue from plasmodium cynomolgi. 200212387853
cytokine responses during acute simian plasmodium cynomolgi and plasmodium knowlesi infections.experimental infection of non-human primates with simian malaria parasites offers a controlled system to study malarial immunity. plasmodium cynomolgi (p. vivax-like) and p. knowlesi (p. falciparum-like) infections in the rhesus monkey were used as a model to test the hypothesis that initial acute infection stimulates type 1/pro-inflammatory cytokine expression followed by a gradual type 2/anti-inflammatory response upon re-infection. this study analyzed cytokine gene expression (interleukin-12, ...200212518848
a class of potent antimalarials and their specific accumulation in infected erythrocytes.during asexual development within erythrocytes, malaria parasites synthesize considerable amounts of membrane. this activity provides an attractive target for chemotherapy because it is absent from mature erythrocytes. we found that compounds that inhibit phosphatidylcholine biosynthesis de novo from choline were potent antimalarial drugs. the lead compound, g25, potently inhibited in vitro growth of the human malaria parasites plasmodium falciparum and p. vivax and was 1000-fold less toxic to m ...200211847346
immunogenicity and protective efficacy of three dna vaccines encoding pre-erythrocytic- and erythrocytic-stage antigens of plasmodium cynomolgi in rhesus monkeys.although several malaria vaccine candidate antigens have been identified, the most suitable methods for their delivery are still being investigated. in this regard, direct immunization with dna encoding these vaccine target antigens is an attractive alternative. here, we have investigated the immune responses to dna immunization with three major vaccine target antigens: the apical membrane antigen-1 and the 19-kda c-terminal fragment of merozoite surface protein-1 from the erythrocytic stage, an ...200212208604
replication fork-stimulated eif-4a from plasmodium cynomolgi unwinds dna in the 3' to 5' direction and is inhibited by dna-interacting compounds.plasmodium cynomolgi dead-box dna helicase 45 (pcddh45) is an atp-dependent dna-unwinding enzyme with intrinsic dna-dependent atpase activity and is highly homologous to eif-4a. in this study, we have further characterized and tested the effect of various dna-interacting compounds on the dna-unwinding activity of pcddh45. the results show that pcddh45 translocates in the 3' to 5' direction along the bound strand, a replication fork-like structure of the substrate stimulates its dna-unwinding act ...200312745261
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
quantitative trait loci in anopheles gambiae controlling the encapsulation response against plasmodium cynomolgi ceylon.anopheles gambiae females are the world's most successful vectors of human malaria. however, a fraction of these mosquitoes is refractory to plasmodium development. l3-5, a laboratory selected refractory strain, encapsulates transforming ookinetes/early oocysts of a wide variety of plasmodium species. previous studies on these mosquitoes showed that one major (pen1) and two minor (pen2, pen3) autosomal dominant quantitative trait loci (qtls) control the melanotic encapsulation response against p ...200314577840
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
dna prime-protein boost immunization in monkeys: efficacy of a novel construct containing functional domains of plasmodium cynomolgi cs and trap.we report the efficacy of a bimodal immunization regimen that involved priming with naked dna (multiple doses) followed by a booster with recombinant protein in rhesus monkeys with a chimeric construct containing the n-terminus of thrombospondin-related adhesive protein and the c-terminus of circumsporozoite protein of plasmodium cynomolgi. the vaccinated animals developed high titer antibodies against the chimeric antigen, the two components of the hybrid and the native proteins of sporozoites. ...200314642309
prodrugs of bisthiazolium salts are orally potent antimalarials.we created neutral antimalarial prodrugs that deliver bisthiazolium compounds with antimalarial activity in the nanomolar range. these drugs primarily affect early intraerythrocytic stages through rapid, nonreversible cytotoxicity. the compounds are suitable for both parenteral and oral use and plasma promotes rapid conversion of the prodrug into the drug. we demonstrate that very low doses offer protection in a murine model of malaria. the drugs show great potential for curing high parasitemia ...200415492221
[induction of protective immunity in rhesus monkey by inoculation with recombinant fusion protein of cholera toxin b subunit-multivalent epitopes of plasmodium falciparum].rhesus monkeys (5 in each group) were inoculated with recombinant fusion protein of cholera toxin b subunit and multi-valent epitopes of plasmodium falciparum intranasal or intramuscular (i.m.). immune-responses and protective effect were evaluated. the antibody titer (geometry mean) against ctb reached 1:512 (intranasal) and 1:10000 (i.m.) 14 day after 3rd immunization, and antibodies against p. falciparum were also elucidated, the titers in i.m. group were also significantly higher than that i ...200415968980
transcriptome profiles of host gene expression in a monkey model of human malaria.we used human microarrays to examine gene expression in a rhesus monkey model of human plasmodium vivax malaria (p. cynomolgi in macaca mulatta). whole-blood cells were collected for extraction of rna before infection, during both the initial liver phase of infection and bloodstream infection, and during the course of 2 bloodstream relapses. clustering analysis showed that similarities in gene expression were greater at similar stages of the protocol for the 2 different monkeys than for the same ...200415633100
hydrolytic enzyme activity in rhesus monkey placenta during early gestational malaria: histochemical studies.early gestational malaria is found to be more fatal than late gestational infection but the pathophysiology of early gestational placenta, the maternofoetal organ responsible for maintenance of pregnancy, remains unexplored. present study dealing with hydrolytic enzymes in early gestational placenta of rhesus monkeys during plasmodium cynomolgi infection was anticipated to provide a better insight into the functional impairment of this organ during early gestational maternal malaria.200516457382
structure identification and prophylactic antimalarial efficacy of 2-guanidinoimidazolidinedione derivatives.the reported synthetic procedure of wr182393, a 2-guanidinoimidazolidinedione derivative with high prophylactic antimalarial activity, was found to be a mixture of three closely related products. poor solubility of wr182393 in both water and organic solvents and its impractical synthetic method have made the purification and structure identification of the reaction mixture a highly challenging task. the problems were circumvented by prodrug approach involving carbamate formation of the mixture, ...200515653337
plasmodium cynomolgi: gametocytocidal activity of the anti-malarial compound cdri 80/53 (elubaquine) in rhesus monkeys.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 ...200516005457
studies on two strains of plasmodium cynomolgi in new world and old world monkeys and mosquitoes.infections that cause the gombak and smithsonian strains of plasmodium cynomolgi were induced in macaca mulatta, aotus lemurinus griseimembra, aotus nancymai, and saimiri boliviensis monkeys. transmission of the gombak strain to aotus spp. monkeys was obtained by the injection of sporozoites dissected from the salivary glands of experimentally infected anopheles dirus and by the bites of infected an. dirus and anopheles farauti mosquitoes. two s. boliviensis monkeys were infected via the injecti ...200515986601
merozoite surface protein 1 of plasmodium vivax induces a protective response against plasmodium cynomolgi challenge in rhesus monkeys.the 42-kda fragment of the merozoite surface protein 1 (msp-1(42)) is a leading candidate for the development of a vaccine to control malaria. we previously reported a method for the production of plasmodium vivax msp-1(42) (pvmsp-1(42)) as a soluble protein (s. dutta, l. w. ware, a. barbosa, c. f. ockenhouse, and d. e. lanar, infect. immun. 69:5464-5470, 2001). we report here a process to manufacture the same pvmsp-1(42) protein but as an insoluble inclusion body-derived protein which was then ...200516113314
the reticulocyte binding proteins of plasmodium cynomolgi: a model system for studies of p. vivax. 200515990180
8-(1-naphthalen-2-yl-vinyl)-6,7,10-trioxaspiro (4.5) decane, a new 1,2,4-trioxane effective against rodent and simian malaria.a new series of 8-(1-aryl-vinyl)-6,7,10-trioxaspiro [4.5] decanes 7a-e and 3-(1-aryl-vinyl)-l,2,5-trioxaspiro [5.5] undecanes 8a-e have been prepared and screened against multi-drug resistant plasmodium yoelii in mice. 8-(1-naphthalen-2-yl-vinyl)-6,7,10-trioxaspiro [4.5] decane 7b, the most active trioxane of the series, has also shown promising activity against plasmodium cynomolgi in rhesus monkeys.200616275088
observations on the exoerythrocytic stages of different isolates of plasmodium cynomolgi in hepatocytes of new world aotus and saimiri monkeys.sporozoites of 3 isolates of plasmodium cynomolgi dissected from the salivary glands of anopheles dirus and anopheles quadrimaculatus were injected intravenously into 9 new world monkeys. liver stage parasites were demonstrated in all 9 animals; 7 of these animals also produced blood stages after prepatent periods of 9 to 23 days.200616629341
[molecular identification of naturally acquired plasmodium knowlesi infection in a human case].to confirm the diagnosis of a human case with atypical vivax-malaria from yunnan province by molecular technique.200617094597
new adamantane-based spiro 1,2,4-trioxanes orally effective against rodent and simian malaria.new 6-arylvinyl- and 6-adamantylvinyl-substituted 1,2,4-trioxanes (13a-g and 14a,b) have been prepared and evaluated for antimalarial activity against multidrug resistant plasmodium yoelii nigeriensis in mice by both oral and intramuscular routes. while all the 6-arylvinyl-substituted trioxanes, 13a-f, showed promising activity, none of the 6-adamantylvinyl-substituted trioxanes, 13g and 14a,b, exhibited significant activity. trioxane, 13f, the most active compound of the series, provided 100% a ...200717266204
recent independent evolution of msp1 polymorphism in plasmodium vivax and related simian malaria parasites.the plasmodium msp-1 is a promising malaria vaccine candidate. however, the highly polymorphic nature of the msp-1 gene (msp1) presents a potential obstacle for effective vaccine development. to investigate the evolutionary history of msp1 polymorphism in p. vivax, we construct phylogenetic trees of msp1 from p. vivax and related monkey malaria parasite species. all p. vivax msp1 alleles cluster in the p. vivax lineage and are not distributed among other species. similarly, all p. cynomolgi msp1 ...200717706800
synthesis and antimalarial activity of new 1,12-bis(n,n'-acetamidinyl)dodecane derivatives.amidoxime and o-substituted derivatives of the bis-alkylamidine 1,12-bis(n,n'-acetamidinyl)dodecane were synthesized and evaluated as in vitro and in vivo antimalarial prodrugs. the bis-o-methylsulfonylamidoxime 8 and the bis-oxadiazolone 9 derivatives show relatively potent antimalarial activity after oral administration.200717123818
malaria causal prophylactic activity of imidazolidinedione derivatives.a series of acid-stable carboxamide derivatives of 2-guanidinoimidazolidinedione (5a-c and 6a-c) were prepared as potential malaria prophylactic and radical cure agents. the new compounds showed moderate to good causal prophylactic activity in mice infected with plasmodium yoelii sporozoites. three compounds were further tested for causal prophylactic activity in rhesus monkeys infected with plasmodium cynomolgi sporozoites, and all showed a delay in patency from 13 to 40 days at 30 mg/kg/day x ...200717967003
biochemical and immunological characterization of e. coli expressed 42 kda fragment of plasmodium vivax and p. cynomolgi bastianelli merozoite surface protein-1.plasmodium vivax is one of the most widely distributed human malaria parasites and due to drug-resistant strains, its incidence and prevalence has increased, thus an effective vaccine against the parasites is urgently needed. one of the major constraints in developing p. vivax vaccine is the lack of suitable in vivo models for testing the protective efficacy of the vaccine. p. vivax and p. cynomolgi bastianelli are the two closely related malaria parasites and share a similar clinical course of ...200718320841
cross-reactivity studies of an anti-plasmodium vivax apical membrane antigen 1 monoclonal antibody: binding and structural characterisation.apical membrane antigen 1 (ama1) has an important, but as yet uncharacterised, role in host cell invasion by the malaria parasite, plasmodium. the protein, which is quite conserved between plasmodium species, comprises an ectoplasmic region, a single transmembrane segment and a small cytoplasmic domain. the ectoplasmic region, which can induce protective immunity in animal models of human malaria, is a leading vaccine candidate that has entered clinical trials. the monoclonal antibody f8.12.19, ...200717229439
oxidoreductases in early gestational monkey placenta during maternal malarial infection: histochemical localisation.early gestational malaria is more deleterious than late gestational infection. still the pathophysiology of maternofoetal organ--the placenta in malaria remains almost unexplored during early gestation. present study dealing with oxidoreductases in early gestational placenta during maternal malarial infection of plasmodium cynomolgi bastianellii in rhesus monkeys was anticipated to provide a better insight into the functional impairment of this organ leading to foetal abnormalities.200717722865
detection of new babesia microti-like parasites in a rhesus monkey (macaca mulatta) with a suppressed plasmodium cynomolgi infection.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.200818385363
evidence for strain-specific protective immunity against blood-stage parasites of plasmodium cynomolgi in toque monkey.we have conducted experiments to test the induction of strain-specific protective immunity against plasmodium cynomolgi infections in toque monkeys. plasmodium cynomolgi is closely related biologically and genetically to the human malaria parasite, p. vivax. two groups of monkeys were immunized against either of two strains of p. cynomolgi, namely pcceylon and pc746, by giving two successive drug-cured infections with asexual blood-stage parasites of one or the other strain, 12-weeks apart. to t ...200819067844
orangutans not infected with plasmodium vivax or p. cynomolgi, indonesia.after orangutans in indonesia were reported as infected with plasmodium cynomolgi and p. vivax, we conducted phylogenetic analyses of small subunit ribosomal rna gene sequences of plasmodium spp. we found that these orangutans are not hosts of p. cynomolgi and p. vivax. analysis of >or=1 genes is needed to identify plasmodium spp. infecting orangutans.200919861067
statistical model to evaluate in vivo activities of antimalarial drugs in a plasmodium cynomolgi-macaque model for plasmodium vivax malaria.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, es ...200919015340
methylparaben in anopheles gambiae s.l. sugar meals increases longevity and malaria oocyst abundance but is not a preferred diet.the antimicrobial and antifungal chemical methylparaben (methyl-4-hydroxybenzoate) was added to the adult sucrose diet of anopheles gambiae and anopheles arabiensis, and its effect on longevity was determined. in all cases, significant increases in longevity were observed when 0.2% (w/v) methylparaben was added to meals that were refreshed weekly. when fresh sugar diet was refreshed daily, no increase in longevity was observed due to methylparaben suggesting that the effect of methylparaben is t ...200919041323
altered immune responses in rhesus macaques co-infected with siv and plasmodium cynomolgi: an animal model for coincident aids and relapsing malaria.dual epidemics of the malaria parasite plasmodium and hiv-1 in sub-saharan africa and asia present a significant risk for co-infection in these overlapping endemic regions. recent studies of hiv/plasmodium falciparum co-infection have reported significant interactions of these pathogens, including more rapid cd4+ t cell loss, increased viral load, increased immunosuppression, and increased episodes of clinical malaria. here, we describe a novel rhesus macaque model for co-infection that supports ...200919774084
transmission of different strains of plasmodium cynomolgi to aotus nancymaae monkeys and relapse.forty-four splenectomized aotus nancymaae monkeys were infected with 6 different strains of plasmodium cynomolgi, 11 via trophozoites and 33 via sporozoites. sporozoites from anopheles dirus, anopheles freeborni, anopheles gambiae, anopheles maculatus, and anopheles stephensi resulted in prepatent periods ranging from 9 to 39 days (median of 15 days). importantly, relapse was demonstrated in 5 of 5 sporozoite-induced infections with the rossan strain following treatment with chloroquine.200918788885
rapid resolution liquid chromatography-mass spectrometry determination of sar97276 in monkey matrices. pharmacokinetics in rhesus monkey infected by plasmodium cynomolgi.since several years, we developed a new class of antimalarial drugs targeting the phospholipid metabolism of the plasmodium falciparum malaria parasite. the bis-thiazolium compound, sar97276, is the lead compound and is now in clinical development. in this paper, we applied the fast rapid resolution liquid chromatography-mass spectrometry technique to the analysis of sar97276 in monkey matrices. the sample pre-treatment procedure involved an acidic precipitation of proteins followed by solid-pha ...200919303732
new imidazolidinedione derivatives as antimalarial agents.a series of new n-alky- and n-alkoxy-imidazolidinediones was prepared and assessed for prophylactic and radical curative activities in mouse and rhesus monkey models. new compounds are generally metabolically stable, weakly active in vitro against plasmodium falciparum clones (d6 and w2) and in mice infected with plasmodium berghei sporozoites. representative compounds 8e and 9c showed good causal prophylactic activity in rhesus monkeys dosed 30 mg/kg/day for 3 consecutive days by im, delayed pa ...201021282058
a taqman real-time pcr assay for the detection and quantitation of plasmodium knowlesi.the misdiagnosis of plasmodium knowlesi by microscopy has prompted a re-evaluation of the geographic distribution, prevalence and pathogenesis of this species using molecular diagnostic tools. in this report, a specific probe for p. knowlesi, that can be used in a previously described taqman real-time pcr assay for detection of plasmodium spp., and plasmodium falciparum, plasmodium vivax, plasmodium malariae and plasmodium ovale, was designed and validated against clinical samples.201021114872
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