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synthesis of 2-substituted primaquine analogues as potential antimalarials.a series of 2-substituted primaquine analogues has been synthesized and evaluated against plasmodium berghei in the mouse and leishmania donovani in the hamster. three members (3a,d,e) of the series were evaluated against plasmodium cynomolgi in the rhesus monkey. one analogue (3d) was evaluated against trypanosoma rhodesiense in the mouse, and two (3b,e) were evaluated against schistosoma mansoni in the mouse. several analogues possessed significant activity against p. berghei (3e,f) and l. don ...1978102798
resolution of antimalarial agents via complex formation with alpha-(2,4,5,7-tetranitro-9-fluorenylideneaminooxy) propionic acid.the resolution of several antimalarial agents via pi-complex formation with alpha-(2,4,5,7-tetranitro-9-fluorenylideneaminooxy) propionic acid (tapa) is reported. since this represents the first use of this agent for the resolution of amines, some details of the separations are presented. the method proved successful for resolving weakly alkaline amines that did not form stable salts with common resolving acids, highly insoluble amines that did not form soluble salts with usual resolving acids, ...1978349156
sporozoites of rodent and simian malaria, purified by anion exchangers, retain their immunogenicity and infectivity.sporozoites of rodent malaria, plasmodium berghei, and simian malaria, plasmodium knowlesi and plasmodium cynomolgi, were partially separated from mosquito debris and microbial contaminants by passage of anopheles material through a deae-cellulose column. in addition to eliminating most of the contaminants (80-90%), this simple technic has made it possible to recover rapidly large numbers of viable sporozoites (55-75% yield), which have retained their infectivity, immunogenicity, and capacity to ...1978351177
freeze-fracture study of malaria sporozoites: antibody-induced changes of the pellicular membrane.plasmodium cynomolgi, plasmodium knowlesi, and plasmodium berghei sporozoites, before and after incubation with immune serum, were studied after freeze-fracture by electron microscopy. there were evenly distributed numerous intramembranous particles (imp) on the p face of the outer membrane. the e face of the plasma membrane had fewer imp than its p face. the e face of the intermediate membrane had few imp and also linear arrays of slightly raised ridges running the length of the parasite. the p ...1979385856
plasmodium cynomolgi: effects of malaria infection on laboratory flight performance of anopheles stephensi mosquitoes. 1977403087
the characteristics of plasmodium cynomolgi infections in various old world primates. 1977405875
comparison of the curative antimalarial activities and toxicities of primaquine and its d and l isomers.this investigation was undertaken to determine whether either d-primaquine or l-primaquine has sufficient advantage over primaquine to warrant evaluation for curative activity in human volunteers infected with plasmodium vivax. it was found: (i) that the capacities of the isomers and the racemate to cure infections with plasmodium cynomolgi in rhesus monkeys were essentially identical; (ii) that the subacute toxicities of the isomers and racemate for this monkey were qualitatively the same, but ...1977407841
quantitative aspects of pyrimethamine-sulfonamide synergism.the experiments described in this report have dealt with the dimensions of therapeutic potentiation achieved when combinations of pyrimethamine and sulfadiazine were administered to rhesus monkeys infected with a drug-susceptible strain of plasmodium cynomolgi or its pyrimethamine-resistant variant and to owl monkeys infected with strains of p. falciparum and p. vivax of varying degrees of resistance to this pyrimidine. these evaluations showed: 1) that when delivered in combination, the activit ...1977410317
radical cure of infections with plasmodium cynomolgi: a function of total 8-aminoquinoline dose. 1977413444
5-aryloxy-6-methoxy-8-aminoquinolines as potential prophylactic antimalarials.5-(p-anisyloxy)-6-methoxy-8-(5-isopropylaminopentylamino)quinoline was resynthesized for evaluation in the plasmodium berghei and monkey prophylactic (plasmodium cynomolgi) tests. a new primary amine, three secondary amines, and one structurally modified side-chain analog of the 5-aryloxy series were also prepared. none of these compounds showed significant antimalarial or prophylactic activity.1976824437
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
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
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
malaria: from quinine to the vaccine. 19921541651
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
comparative susceptibility of southeast asian anopheles mosquitoes to the simian malaria parasite plasmodium cynomolgi.seven anopheles species/isolates were compared with anopheles dirus (control) for susceptibility to plasmodium cynomolgi b strain. the mean numbers of oocysts in paired replicates of an. dirus and an. takasagoensis were not significantly different. the remaining test species had significantly fewer mean numbers of oocysts than anopheles dirus (p less than 0.01). anopheles dirus had the highest percentage of mosquitoes infected with p. cynomolgi sporozoites (82%). of the test groups, anopheles di ...19911791460
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
circumsporozoite protein genes of malaria parasites (plasmodium spp.): evidence for positive selection on immunogenic regions.the circumsporozoite (cs) protein is a cell surface protein of the sporozoite, the stage of the life cycle of malaria parasites (plasmodium spp.) that infects the vertebrate host. analysis of dna sequences supports the hypothesis that in plasmodium falciparum, positive darwinian selection favors diversity in the t-cell epitopes (peptides presented to t cells by host mhc molecules) of the cs protein. in gene regions encoding t cell epitopes of p. falciparum, the rate of nonsynonymous nucleotide s ...19911706291
an ultrastructural study of the exoerythrocytic schizonts of plasmodium cynomolgi and p. knowlesi in macaca mulatta.exoerythrocytic schizonts of plasmodium cynomolgi and p. knowlesi were examined by electron microscopy in biopsy samples of primate livers. with maturity the parasitophorous vacuole membrane becomes highly sculptured by the addition of a discontinuous dense thickening, the distribution of which can be a distinguishing character between these two species. the parasitophorous vacuole membrane follows the contours of the parasite faithfully with a minimal surrounding vacuole. the marked destruction ...19901967505
plasmodium cynomolgi: immunization of a rhesus monkey with exoerythrocytic stages cultured in autologous hepatocytes.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 antigeni ...19911993467
murine igg isotype responses to the plasmodium cynomolgi circumsporozoite peptide (nagg)5. i. effects of carrier, copolymer adjuvants, and lipopolysaccharide on isotype selection.the tandem repeat peptide of the circumsporozoite protein of plasmodium cynomolgi, (nagg)5, conjugated to bsa or salmonella flagella, was injected into mice with block copolymer and other adjuvants. the flagella carrier preferentially stimulated igg2a antibodies to (nagg)5 that constituted as much as 85% of the total igg antibody whereas the bsa carrier stimulated as much as 98% igg1. the distribution of isotypes of antibody to (nagg)5 was also modified by using the copolymer adjuvants l121 or l ...19912026882
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
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
[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
homologous sequences in plasmodium cynomolgi and the gene of the histidine-rich knob protein of plasmodium falciparum. 19902183051
incorporation of nucleic acid precursors by plasmodium cynomolgi in anopheles balabacensis.autoradiography was used to study the incorporation of tritium-labelled nucleic acid precursors into the sporogonic stages of plasmodium cynomolgi in anopheles b. balabacensis. infected mosquitoes were fed on either 3h-adenine (5, 25 and 50 muci/ml or 3h-thymidine (50 muci/ml) for various periods after the blood meal. 3h-adenine was incorporated into dna and rna of the developing oocysts and the resulting sporozoites. midgut epithelial cells incorporated label from 3h-adenine into nuclear and cy ...19751189024
reduced 8-aminoquinoline analogues as potential antimalarial agents.the synthesis of 1-alkyl-8-(aminoalkylamino)-6-methyl1-1,2,3,4-tetrahydroquinolines, 8-(4'-amino-1'-methylbutylamino)-6-methoxy-1-methyl1-1,2-dihydroquinoline, 5-substituted 8-(4'-amino-1'-methylbutylamino)-1-methyl-1,2-dihydroquinolines, 8-alkylamino-1-(2-n,n-diethylaminoethyl)-6-methoxy-1,2,3,4-tetrahydroquinolines, 1-)2-n,n-diethylaminoethyl)-6-methoxy-1,2,3,4-tetrahydroquinoline, 1-(2-n,n-diethylaminoethyl)-8-(2-n,n-diethylaminoethylamino)-6-methoxy-1,2,3,4-tetrahydroquinoline, and 2-substit ...1976824447
study of the gametocytocidal/sporontocidal action of qinghaosu (artemisinin) by electron microscopy.the gametocytocidal efficacy of artemisinin (qinghaosu) was evaluated and scanning electron microscopical evidence is given for gametocytocidal action of a single 5-10-mg/kg dose of artemisinin against simian malarial parasite (plasmodium cynomolgi b). no sporontocidal effect of artemisinin was observed.19902254819
evaluating new antimalarial drugs against trophozoite induced plasmodium cynomolgi malaria in rhesus monkeys.an antimalarial drug testing system is described which utilizes trophozoite induced plasmodium cynomolgi malaria in rhesus monkeys. the schizonticidal activity of standard antimalarial drugs in this system is reported. the system accurately predicted antimalarial activity in man of 8 of 9 compounds selected for clinical trials.1976816211
gametocytocidal activity of the antimalarial alpha/beta arteether against plasmodium cynomolgi b.a new sesquiterpene lactone alpha/beta arteether (a 30:70 mixture of enantiomers), which possesses very high blood schizontocidal activity, has been evaluated for gametocytocidal/sporontocidal action against plasmodium cynomolgi b infection in the rhesus monkey. this paper reports gametocytocidal action of this new antimalarial drug at 2.5-5 mg/kg (single im dose) against p. cynomologi b as shown by the complete absence of mosquito infectivity. no sporontocidal action was demonstrable in the vec ...19902267960
transmission of plasmodium cynomolgi to aotus trivirgatus monkeys. 1975804032
antimalarials. 10. synthesis of 4-substituted primaquine analogues as candidate antimalarials.primaquine (i) has been extensively used in combination with other drugs in the radical cure of relapsing malaria as well as for prophylaxis or the interruption of transmission. this, coupled with the activity data reported for 4-methylprimaquine (ii), has led to the synthesis of a series of 14 4-substituted analogues of i. in addition, three side-chain analogues of ii were prepared. the compounds were tested for suppressive antimalarial activity against plasmodium berghei in the rane mouse scre ...1977411930
synthesis of 2-benzyloxy and 2-benzylthio analogues of primaquine as potential antimalarials.a series of 2-benzyloxy and 2-benzylthio analogues of primaquine has been synthesized and evaluated against plasmodium berghei in the mouse and plasmodium cynomolgi in the rhesus monkey. 8-aminoquinoline toxicity, as measured in the rane mouse screen, was reduced, and these compounds showed significant blood schizonticidal antimalarial activity in mice. in monkeys, significant tissue-schizonticidal activity was observed.1977409843
primaquine analogues: derivatives of 4-amino-2-methoxyacridine.based on the antimalarial activity of primaquine (1a) and its 4-methyl analogue 1b, 4-aminoacridinyl analogues, 4-[(4-amino-1-methylbutyl)amino]-2-methoxyacridine (2a) and 4-[(4-amino-1-methylbutyl)amino]-2-methoxy-9-methylacridine (2b), were prepared and evaluated as potential tissue schizonticidal agents. these compounds were found to be substantially less active than primaquine against plasmodium cynomolgi in the rhesus monkey. the antileishmanial activity in hamsters of 4-[[6-(diethylamino)h ...1979117105
characterization of cross-reactive blood-stage antigens of the plasmodium cynomolgi complex using anti-plasmodium vivax monoclonal antibodies.five out of 18 monoclonal antibodies (moab's) produced against blood stages of a brazilian (belem) strain of plasmodium vivax were shown to cross-react with all of the 11 strains of the p. cynomolgi complex that were assayed. the 5 moab's produced 3 different patterns of immunofluorescence, identical for both p. vivax and p. cynomolgi. three of these moab's appeared to react with antigens associated with the cytoplasm or membranes of infected erythrocytes. by western blot analysis, 2 of these 3 ...19882454311
studies on the 2,4-diamino-6 substituted quinazolines. i. antimalarial activities of 2,4-diamino-6-[(3,4-dichlorobenzyl)-nitrosoamino]-quinazoline (ci-679) as exhibited in rhesus monkeys infected with the ro or ro/pm strains of plasmodium cynomolgi.this report summarizes the results of appraisals of various activities of ci-679 (a 2,4-diamino-6-amino-substituted quinazoline) in rhesus monkeys infected with the ro and ro/pm strains of plasmodium cynomolgi. in subjects inoculated with sporozoites, ci-679, administered in appropriate schedules in doses up to and including the maximum tolerated level, neither prevented development of infections with these strains nor cured those already established. although these evaluations showed that ci-67 ...1979114064
antimalarial activity of demeclocycline against plasmodium cynomolgi bastianellii in rhesus monkeys.demeclocycline was tested for causal prophylactic (at 25, 50 and 100 mg kg-1 dose levels), radical curative (at 25, 50, 100 and 200 mg kg-1 dose levels) and blood schizontocidal (at 25, 50 and 100 mg-1 dose levels) activities against plasmodium cynomolgi b in rhesus monkeys. for causal prophylactic activity, demeclocycline extended the prepatent period at all dose levels. the maximum delay in patency was observed at 100 mg kg-1 (prepatent period = 40.66 +/- 14.57 days). for radical curative acti ...19892513785
enhancement of a simian malarial infection (plasmodium cynomolgi) in mosquitoes fed on rhesus (macaca mulatta) previously infected with an unrelated malaria (plasmodium knowlesi). 1979111568
comparison of antimalarial efficacy of artemisinin (qinghaosu) and arteether against plasmodium cynomolgi b infection in monkeys.arteether (30:70 mixture of alpha and beta epimers) used as injectable intramuscular preparation (in neutralized ground-nut oil) had curative action at 5 mg/kg x 3 d against blood-induced plasmodium cynomolgi b infection in rhesus monkeys, while the curative dose of artemisinin (qinghaosu) oil suspension was 10 mg/kg x 7 d or 20 mg/kg x 3 d. parasite clearance with arteether was achieved within 24 h. neither arteether nor artemisinin exhibited any causal prophylactic or radical curative action u ...19892603208
[preliminary studies on the diagnosis of plasmodium falciparum malaria by monoclonal antibody sandwich dot-immunogold silver staining assay].in this report, the blood samples from 30 falciparum malaria patients with parasitemia 0.015-0.58% and the blood samples from 30 healthy persons were examined by monoclonal antibody (mcab) sandwich dot-immunogold silver staining assay (dot-igssa). when the mcab 11g5, 13a2 and 13a1 were used for sandwich dot-igssa with mcab 14d9 labeled with colloidal gold respectively, the 0.0001% of parasitemia could be detected and the mcab 11g5, 13a1 and 14d9 labeled with colloidal gold could also be used to ...19911959167
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
tissue schizontocidal effect of trifluoroacetyl primaquine in plasmodium yoelii infected mice and plasmodium cynomolgi infected monkeys.trifluoroacetyl primaquine oxalate (m8506) was compared with primaquine phosphate for tissue schizontocidal action in rodent and simian malaria. in plasmodium yoelii sporozoites infected mice, the causal prophylactic effects of m8506 at 5, 10 and 20 mg(base)/kg were 56.7%, 87.2% and 100%, respectively, comparable to those of primaquine (54.4%, 90.8% and 100%). in p. cynomolgi sporozoites infected rhesus monkeys 4 dosage regimens of the two agents were compared for radical curative effect. on the ...19911948265
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
association of a plasmodium-refractory phenotype with an esterase locus in anopheles gambiae.in a genetically selected strain of the malaria vector anopheles gambiae, most species of plasmodium parasites are surrounded by melanized capsules and killed in the wall of the mosquito midgut. genetic studies demonstrate a significant association between the refractory response to plasmodium cynomolgi b strain and the est a allele at an autosomal esterase locus. increased susceptibility to parasites is associated with an alternate est c allele. lines selected to be homozygous for the est a and ...19892742037
artemisinin (qinghaosu)--a new gametocytocidal drug for malaria.gametocytocidal activity of artemisinin (qinghaosu) has been demonstrated against simian malaria parasite plasmodium cynomolgi b. colony-bred anopheles stephensi were allowed to feed on gametocyte-carrying rhesus monkeys and the mosquito infectivity rate and oocyst count of the infected mosquito gut were recorded on day 8-9 postinfection. control (pretreatment) feedings of mosquito on gametocyte-carrying monkeys showed good infectivity in different batches of the mosquitoes ranging from 57.14 to ...19892766860
in-vitro exoerythrocytic development of plasmodium cynomolgi bastianellii: inhibitory activity of monoclonal antibodies against sporozoites of different p. cynomolgi strains and of p. knowlesi.the inhibitory effect of anti-sporozoite monoclonal antibodies (moab) on the in-vitro development of liver stages of plasmodium cynomolgi bastianellii (nih strain) was evaluated using primary cultures of rhesus monkey hepatocytes. moabs against the circumsporozoite proteins of five strains of p. cynomolgi (nih, london, gombak, ceylon, berok), and of p. knowlesi (h strain) were used. incubation of sporozoites of p. cynomolgi bastianellii with the anti-nih strain moabs entirely prevented liver-sta ...19892771427
the genome of plasmodium cynomolgi is partitioned into separable domains which appear to differ in sequence stability.the genome of plasmodium cynomolgi is partitioned into at least 7 distinct genetic domains. each domain is apparently uniform in dna density and is separable from the others by cscl density centrifugation in the presence of hoechst dye. the protein-encoding genes that were tested are localized in the two heaviest density domains (isochores). the ribosomal genes are in two lighter isochores as well as in one of the isochores that contains protein encoding genes. telomeric sequences are mainly, if ...19882837737
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
in vitro activity of antimalarial compounds on the exoerythrocytic stages of plasmodium cynomolgi and p. knowlesi.primary cultures of macaca mulatta hepatocytes infected with sporozoites of plasmodium knowlesi, p. cynomolgi (cambodian strain), and p. cynomolgi bastianellii were exposed in vitro to 7 antimalarial compounds. the number of exoerythrocytic schizonts present after 4-7 days of culture was used to assess the activity. with pyrimethamine, proguanil, cycloguanil, primaquine, and 2 of its analogues (wr242511 and wr238605), marked inhibition of schizont formation could be achieved at concentrations be ...19892929849
[action of nitroquine on tissue schizonts of plasmodium cynomolgi]. 19862945393
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
comparison of antimalarial efficacy of alpha, beta, and alpha/beta arteether against plasmodium cynomolgi b infection in monkeys.the blood schizontocidal activity of alpha and beta arteether has been compared with that of alpha/beta arteether (a 30:70 mixture of alpha and beta isomers), which is a fast-acting blood schizontocide undergoing phase i clinical trials at the central drug research institute. both beta and alpha/beta arteether have comparable activity and are curative at a dose of 5 mg/kg for 3 days against blood-induced plasmodium cynomolgi b infection in the rhesus monkey; alpha arteether alone is slightly les ...19912063959
cultivation of exoerythrocytic stages of plasmodium cynomolgi, p. knowlesi, p. coatneyi, and p. inui in macaca mulatta hepatocytes.exoerythrocytic stage parasites of plasmodium cynomolgi, p. knowlesi, p. coatneyi, and p. inui were cultured by inoculating primary cultures of hepatocytes from macaca mulatta with sporozoites. less than 1% of inoculated sporozoites survived. morphology and size of the liver stages in all 4 species were similar to in vivo descriptions and the time required for in vitro maturation correlated well with prepatent periods described.19883207173
observations on early and late post-sporozoite tissue stages in primate malaria. v. the effect of pyrimethamine and proguanil upon tissue hypnozoites and schizonts of plasmodium cynomolgi bastianellii.two rhesus monkeys were each infected with 2.1 x 10(6) sporozoites of plasmodium cynomolgi bastianellii; one was treated with 1.0 mg of pyrimethamine base per kg body weight for 5 d after sporozoite inoculation. a further 2 monkeys were each infected with 9.75 x 10(6) sporozoites of the same parasite; one was treated with 10 mg of proguanil per kg body weight for 4 out of 5 d after inoculation. the treated monkeys showed a delayed primary parasitaemia and relapses. in sections of liver biopsies ...19883250556
use of non-human primate hepatocytes for in vitro study of the pre-erythrocytic stages of malaria parasites.methods were developed that allow invasion of sporozoites from simian malaria parasite species (plasmodium cynomolgi, p. knowlesi, p. coatneyi, p. inui, p. gonderi, p. fragile) and development to schizont stages in rhesus and saimiri monkey hepatocytes. the p. cynomolgi-rhesus monkey model was used to study inhibition of schizont development using monoclonal antibodies (mabs) produced against the circumsporozoite (cs) protein of various strains and species of malaria parasites. immunoelectron mi ...19902094593
quinoline esters as potential antimalarial drugs: effect on relapses of plasmodium cynomolgi infections in monkeys.two compounds of the quinoline ester series, wr 197236 (6-butyl-4-hydroxy-3-methoxycarbonyl-7-beta-phenoxyethoxyquinoline ) and wr 194905 (4-acetoxy-6-decyloxy-7-isopropoxy-3-methoxycarbonylquinoline++ +), exhibit anti-relapse activity against sporozoite-induced plasmodium cynomolgi b infections in rhesus monkeys. both the compounds have been found to be curative when given intramuscularly in 7 daily doses of 15 mg/kg, and no relapses were observed during the observation period of 120 d.19902096498
pattern of relapses in sporozoite induced plasmodium cynomolgi b infection in rhesus monkeys.the pattern of sequential relapses in 10 rhesus monkeys following inoculation of sporozoites of plasmodium cynomolgi b has been studied after administering curative dose of chloroquine (5 mg/kg base x 7 days) to eliminate blood parasitaemia after each relapse. observation for periods ranging from 109 to 245 days showed that the interval between first six relapses was 19.3 +/- 6.77 days (1st relapse), 20.9 +/- 8.43 days (2nd relapse), 22.8 +/- 8.55 days (3rd relapse), 27.8 +/- 10.0 days (4th rela ...19902098417
[analysis of amino acids in hemolymph and acid hydrolysates of midguts of anopheles dirus infected with plasmodium cynomolgi].quantitative determinations of free amino acids in hemolymph and acid hydrolysates of midguts of female anopheles dirus infected with plasmodium cynomolgi bastianellii were carried out and the results were compared with those of noninfected mosquitoes. on day 10 after infected blood meal, the contents of methionine, isoleucine, leucine, ornithine, lysine in the hemolymph of infected mosquitoes markedly decreased as compared with those in the controls. however, the quantitative analysis of the am ...19902099259
anti-parasite effects of cytokines in malaria.cytokines induced during natural malaria infections, e.g., at crisis of a blood infection of plasmodium cynomolgi, and during clinical paroxysms in human plasmodium vivax infections, mediate killing of intra-erythrocytic blood stage malaria parasites. these cytokines, tnf and ifn-gamma, require additional, yet unidentified complementary factors that are present in "crisis" and "paroxysm" serum to kill intra-erythrocytic blood stage parasites. in contrast, cytokines, (mainly ifn-gamma) are able t ...19902126526
[study on the treatment of plasmodium cynomolgi infections of the macaque with ketotifen]. 19873450138
effects of interferon in malaria infection.earlier, we reported that prophylactic treatment with human interferon gamma (rhuifn-gamma) protected monkeys against plasmodium cynomolgi b malaria infection. we have tested the efficacy of rhuifn-gamma on relapsing stage of experimental p. cynomolgi b malaria infection in rhesus monkeys. no effect of rhuifn-gamma was seen against experimental relapsing stage compared with controls; however, it appears that chloroquine (chl) may have interfered with the antimalarial effect of ifn, since treatme ...19902126528
the role of cytokines in malaria infection.we have tested the prophylactic effect of escherichia coli-derived recombinant human interferon gamma (rhuifn-(gamma] against sporozoite- or trophozoite-induced plasmodium cynomolgi b malaria infection in rhesus monkeys. data show that treatment with only five doses of rhuifn-(gamma) (0.1 mg/kg body weight) given on days -2, 0, and +2 after infection protected the monkeys against sporozoite-induced p. cynomolgi infection. animals initially protected by rhuifn-(gamma) treatment remained susceptib ...19902128826
plasmodium cynomolgi: serum-mediated blocking and enhancement of infectivity to mosquitoes during infections in the natural host, macaca sinica.the infectivity of plasmodium cynomolgi in its natural host, the toque monkey, macaca sinica, to anopheles tessellatus mosquitoes was studied in relation to the evolution of anti-sexual-stage immunity in the host during the course of a blood-induced infection. the effects of serum on the infectivity of gametocytes and the intrinsic infectivity of gametocytes to mosquitoes on each day were assessed in membrane feeding experiments. mosquitoes were also directly fed on the animal on each day. our r ...19902209788
[effect of artesunate transdermal preparation on plasmodium cynomolgi].artensunate transdermal preparation at 5, 10, or 15 mg/kg, bid, for 3 days applied locally on the shaved skin of the back of monkeys showed reliable therapeutic effects on plasmodium cynomolgi, but recrudescence of the parasites was not controlled. if some azone was added in the artesunate transdermal preparation at the dosage of 5 mg/kg, bid, for 3 days, the parasitemia of plasmodium cynomolgi could be cleared and recrudescence prevented, thus, the antimalarial effects was enhanced.19902239338
natural killer activity against human k562 tumour cells during plasmodium cynomolgi malarial infection of rhesus monkeys.this study assessed the natural killer (nk) cell activity profile during plasmodium cynomolgi infection in rhesus monkeys. there was a significant decrease in the nk cell activity in the peripheral blood leukocytes of infected monkeys during the early, ascending phase of infection. however, as the parasite load decreased, nk cell activity returned to normal levels. this could be correlated with the peak increase in lymphocyte counts. this indicated that a decrease in nk cell activity observed at ...19902257166
plasmodium yoelii nigeriensis circumsporozoite gene structure and its implications for the evolution of the repeat regions.the circumsporozoite (cs) gene encodes the most immunogenic component of the plasmodial sporozoites. the immunodominant epitope-encoding domain of the cs gene shows sequences that are repeated in tandem. a detailed analysis of the cs repeats of certain closely related malaria parasites (strains of plasmodium cynomolgi, plasmodium knowlesi, and plasmodium vivax) showed that they evolve rapidly yet are well conserved within the gene. we were interested in studying whether the cs repeats of plasmod ...19902290446
causal prophylactic activity of a new 8-aminoquinoline derivative against plasmodium cynomolgi b in rhesus monkeys.a new 8-aminoquinoline derivative, n1-(3-acetyl-4-5-dihydro-2 furanyl)-n4-(6-methoxy-8-quinolinyl)1,4-pentanediamine, synthesized at cdri, lucknow, showed causal prophylactic activity at 3.16 mg/kg x 3 doses (on day -1, 0 and +1) against sporozoite induced p. cynomolgi b infection in rhesus monkeys. single dose of 10 mg/kg of this compound on day 0 also prevented establishment of patient infection. activity of the compound was comparable to that of primaquine (with causal prophylactic activity a ...19902397941
circumsporozoite protein of plasmodium vivax: gene cloning and characterization of the immunodominant epitope.the gene encoding the circumsporozoite (cs) protein of the human malaria parasite plasmodium vivax has been cloned. the deduced sequence of the protein consists of 373 amino acids with a central region of 19 tandem repeats of the nonapeptide asp-arg-ala-asp/ala-gly-gln-pro-ala-gly. a synthetic 18-amino acid peptide containing two tandem repeats binds to a monoclonal antibody directed to the cs protein of plasmodium vivax and inhibits the interaction of this antibody with the native protein in sp ...19852414847
tissue schizontocidal activity of minocycline against a relapsing malaria parasite plasmodium cynomolgi b. 19873666853
further studies on the antigenic diversity of the circumsporozoite proteins of the plasmodium cynomolgi complex.the circumsporozoite (cs) proteins of strains of the plasmodium cynomolgi complex have been examined using antisporozoite monoclonal antibodies (mab) in various immunologic assays. we found extensive antigenic diversity in the repeating immunodominant epitope of the cs proteins of the various strains. based on the antigenicity and the electrophoretic mobility of their cs protein, the 11 strains that we examined can be placed in 7 distinct groups. our data also indicate homology between the immun ...19862422969
ultrastructural localization of phenoloxidase in the midgut of refractory anopheles gambiae and association of the enzyme with encapsulated plasmodium cynomolgi.a melanogenic enzyme, phenoloxidase, was localized ultrastructurally in the midgut epithelia of 2 strains of anopheles gambiae, a refractory strain that melanotically encapsulates plasmodium cynomolgi ookinetes on the midgut, and a susceptible strain that does not. midguts were incubated with either dopa or dopamine, and the resultant electron-dense product of phenoloxidase activity was localized on the basal lamina (bl) and cellular basal membrane labyrinth (bml) in uninfected mosquitoes of bot ...19892503600
infectivity studies on anopheles stephensi using plasmodium cynomolgi b infection in rhesus monkeys.the characteristics of primary and secondary asexual peak parasitaemia during sporozoite induced plasmodium cynomolgi b infections in 40 rhesus monkeys have been studied. colony bred anopheles stephensi were fed on different days on the gametocyte carrying monkeys and the infectivity of mosquitoes as determined by oocyst count on day 8 post-feeding was recorded. following the day of sporozoite inoculation, the mean prepatent period was 8.58 +/- 0.87 days. the primary asexual peak was attained on ...19892623421
radical curative activity of a new 8-aminoquinoline derivative (cdri 80/53) against plasmodium cynomolgi b in monkeys.an analogue of primaquine, n1-(3-acetyl-4-5-dihydro-2-furanyl)-n4-(6-methoxy-8-quinolinyl) 1,4-pentanediamine, cdri code 80/53), has been evaluated for anti-relapse activity against sporozoite induced plasmodium cynomolgi b infection in rhesus monkeys. the compound has shown 100% curative anti-relapse activity at 1.25 mg/kg x 7 day dose schedule, thereby giving a primaquine index of 0.8. the compound is currently under phase-i clinical trials.19892641640
a general system of resistance to malaria infection in anopheles gambiae controlled by two main genetic loci.genetic analysis of a system of plasmodium refractoriness in anopheles gambia suggests that the joint action of 2 unlinked genetic loci substantially controls expression of the susceptible and refractory phenotypes. one genetic component, here named pif-b (for plasmodium infectivity factor), is closely linked or identical to a polymorphic autosomal esterase locus which can be visualized by gel electrophoresis. this locus exerts the major controlling effect on susceptibility to plasmodium cynomol ...19892742036
localization of circumsporozoite antigen in exoerythrocytic schizonts of plasmodium cynomolgi.we used colloidal gold probes and post-embedding immunoelectron microscopy to localize circumsporozoite (cs) antigen in 5- and 8-day-old in vitro cultures of plasmodium cynomolgi exoerythrocytic (ee) schizonts. both small uninucleated and large multinucleated ee schizonts were found in 5-day-old cultures. a mouse monoclonal antibody to the repeat region of the p. cynomolgi cs protein densely labeled the plasma membrane and surface of 5-day-old ee schizonts as well as the surrounding parasitophor ...19892919723
does biased gene conversion influence polymorphism in the circumsporozoite protein-encoding gene of plasmodium vivax?variation between north korean and latin american isolates in the circumsporozoite (cs) protein encoding gene of the human malaria parasite plasmodium vivax was studied. polymorphic positions are confined to the central tandemly repeated sequences. nucleotide substitutions in the tandem repeats produce variants; these substituted positions within the repeat array tend to be conserved between genes. the north korean cs gene has a short insertion after the repeats encoding a 4-amino acid repeat (a ...19883054880
antigenic diversity of the circumsporozoite proteins in the plasmodium cynomolgi complex.antigenic diversity was observed in the circumsporozoite (cs) proteins of five of the six plasmodium cynomolgi isolates (nih, mulligan, london, gombak, ceylon, ro) that we examined. monoclonal antibodies were produced against salivary gland sporozoites of three of the isolates. interaction of these monoclonal antibodies with the sporozoites was isolate specific, the exception being the anti-nih monoclonals which also reacted with mulligan strain sporozoites. inhibition of binding between the dif ...19853982450
activities of the tetrahydrofuran derivative, ba-41,799, against plasmodium cynomolgi infections in rhesus monkeys.ba-41,799, a tetrahydrofuran derivative that at one time attracted considerable interest as an antimalarial agent because of a combination of structural novelty with activities against infections with plasmodium berghei and plasmodium berghei yoelii in mice, has been evaluated for its capacities to effect prophylaxis and radical cure in rhesus monkeys challenged or already infected with sporozoites of the drug-susceptible ro strain or the pyrimethamine-resistant ro/pm strain of plasmodium cynomo ...19853985599
recombinant human gamma interferon inhibits simian malaria.prophylactic treatment with 0.1 mg of human gamma interferon per kg (body weight) per day completely suppressed experimental infection with plasmodium cynomolgi b sporozoites in rhesus monkeys. treatment with lower doses partially suppressed this infection. prophylactic treatment with human gamma interferon, however, had no protective effect against trophozoite-induced infection, suggesting that the interferon effect was limited to the exoerythrocytic stage of parasitic development.19863091507
human interferon-gamma protects rhesus monkeys against sporozoite-induced plasmodium cynomolgi malaria infection.earlier we reported that prophylactic treatment with recombinant human interferon gamma (rhuifn-gamma) for a prolonged duration completely suppressed experimental infection with plasmodium cynomolgi b sporozoites in rhesus monkeys. we now show that reducing the rhuifn-gamma treatment to three administrations given close to the time (on days -1, 0, and +1) of infection was sufficient for complete protection. animals initially protected by rhuifn-gamma treatment are susceptible to reinfection. stu ...19883132512
peptide derivatives of primaquine as potential antimalarial agents.three peptide derivatives of primaquine were synthesized. the compounds were tested for radical curative antimalarial activity against plasmodium cynomolgi in rhesus monkeys and blood schizonticidal antimalarial activity against plasmodium berghei in mice. all three peptide derivatives showed activity against p. cynomolgi greater than that expected for the primaquine content of each prodrug. the toxicity of one of the peptide derivatives was less than that of primaquine in mice.19883280798
[detection of antibodies to vivax-malaria by elisa using in vitro cultured erythrocytic plasmodium cynomolgi as antigen]. 19883289786
ultrastructure of the encapsulation of plasmodium cynomolgi (b strain) on the midgut of a refractory strain of anopheles gambiae.using transmission electron microscopy, we investigated the encapsulation of the simian malaria parasite, plasmodium cynomolgi, in a refractory strain of the mosquito, anopheles gambiae. after the ookinete penetrates the mosquito midgut epithelium and lodges between the basal membrane and the basal lamina, an electron-dense, melanin-like substance begins to coalesce around the parasite. completely encapsulated parasites were found as early as 16 hr after the blood meal. granules of the melanin-l ...19883379524
infection of aotus azarae boliviensis monkeys with the ro strain of plasmodium cynomolgi. 19854093822
detection of early exoerythrocytic schizonts of plasmodium cynomolgi by immunofluorescence. 19734123941
immune response of man to inoculation with plasmodium cynomolgi and challenge with p. vivax. 19664161488
gametocytocidal and sporontocidal effects of antimalarial drugs on malaria parasites. i. effect of single and multiple doses of primaquine on plasmodium cynomolgi. 19734200769
letter: the antimalarial activity of rc-12 against gametocytes and sporogony of plasmodium cynomolgi. 19734204929
plasmodium cynomolgi: influence of x-irradiation and sporozoite dilution on relapse patterns in infected rhesus monkeys. 19744206933
accidental human infection with plasmodium cynomolgi bastianellii. 19734207080
studies on the antimalarial effects of rc-12 and wr 14,997 on the development of plasmodium cynomolgi in mosquitoes and rhesus monkeys. 19744207342
[establishment of plasmodium cynomolgi bastianellii-anopheles stephensi-macaca mulatta simian malaria model]. 19873447780
experimental studies on the effect of artesunate sustained released tablet on plasmodium cynomolgi. 19873449712
[susceptibility of various anopheles species to the pathogenic agent of simian malaria, plasmodium cynomolgi bastinelli]. 19684386476
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