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antimalarials. 14. 5-(aryloxy)-4-methylprimaquine analogues. a highly effective series of blood and tissue schizonticidal agents.a series of five 5-(aryloxy)-4-methylprimaquine analogues has been prepared and evaluated for antimalarial activity. the compounds were tested for suppressive activity against plasmodium berghei in mice and for radical curative activity against plasmodium cynomolgi in the rhesus monkey. the compounds were not only significantly superior to primaquine as radical curative agents but also were suprisingly highly effective as suppressive agents.19827131488
response to plasmodium cynomolgi infection in a protein deficient host. 19827152561
observations on early and late post-sporozoite tissue stages in primate malaria. ii. the hypnozoite of plasmodium cynomolgi bastianellii from 3 to 105 days after infection, and detection of 36- to 40-hour pre-erythrocytic forms.confirmation of the existence of a persistent, uninucleate, dormant pre-erythrocytic stage, the hypnozoite, of the relapsing simian malaria parasite, plasmodium cynomolgi bastianellii, has been obtained by means of experiments involving the intravenous injection into susceptible monkeys of 48 to 85 x 10(6) sporozoites derived from mosquitoes of a different species and source than employed previously. the development of these hypnozoites was traced from 3 days until 105 days after sporozoite inoc ...19827041663
antimalarials. 13. 5-alkoxy analogues of 4-methylprimaquine.a series of nuclear and side-chain analogues of 4-methylprimaquine incorporating an alkoxy group in the 5-position of the quinoline nucleus has been prepared. the compounds were tested for suppressive antimalarial activity against plasmodium berghei in mice and for radical curative antimalarial activity against plasmodium cynomolgi in the rhesus monkey. although the toxicity problems characteristic of the 8-aminoquinolines were not overcome, several of the compounds, surprisingly, were highly ef ...19826750123
[establishment of monkey model of plasmodium cynomolgi-anopheles stephensi system and its use for tissue shizontocide test]. 19826216007
[effects of nitroquine on sporogenic cycle of plasmodium cynomolgi]. 19826219546
presbytis entellus and macaca radiata as new hosts for experimental plasmodium cynomolgi bastianellii infection. 19827174004
malaria parasites--discovery of the early liver form.infections of mammalian malaria parasites start when sporozoites from an infected anopheline mosquito are injected into the bloodstream of the host. the sporozoites enter the hepatocytes and become transformed into exoerythrocytic schizonts. since the discovery of the primate parasite plasmodium cynomolgi in monkey hepatocytes and the rodent parasite plasmodium berghei in hamster hepatocytes, the ultrastructure of these stages has been extensively studied both in primate and rodent plasmodia. th ...19836339945
relationships between chemical structures of 8-aminoquinolines and their capacities for radical cure of infections with plasmodium cynomolgi in rhesus monkeys.evaluation of 200 8-aminoquinolines for the capacities to effect radical cure of infections with sporozoites of plasmodium cynomolgi in rhesus monkeys led to identification of 34 derivatives with activity equal or superior to that of primaquine and to characterization of substituents on the quinoline nucleus and side chain that favored or prejudiced curative activity. of the 34 derivatives, 19 were as active as primaquine, 9 were twice as active, and 6 were four times as active. with respect to ...19836660845
appraisals of compounds of diverse chemical classes for capacities to cure infections with sporozoites of plasmodium cynomolgi.compounds (265) of widely diverse structures were appraised for radical curative activity in rhesus monkeys infected with sporozoites of the b strain of plasmodium cynomolgi, using an evaluation system that provided a preliminary assessment with from 0.1-1.0 g of compound and tests against one to five active infections. none of 32 compounds in a miscellaneous structure category, none of seven agents of antibiotic origin, none of 12 1,5-naphthyridines, and none of seven 7-aminoquinolines exhibite ...19836837838
timing of stages and changes in numbers of multiply-infected erythrocytes during the asexual cycle of plasmodium cynomolgi bastianellii.previous evaluations of the timing of developing stages in the erythrocytic cycle of the simian malaria parasite, plasmodium cynomolgi, a frequently used model for relapsing malaria in man, have depended on procurement of blood samples at 4- or 6-hourly intervals. this brief report describes the blood cycle as determined from hourly bleedings, thus providing a more discriminating sequence usable for immunochemical or biochemical study of specific stages. the approximate timing of development for ...19836859395
[biological characteristics of simian malaria model of plasmodium cynomolgi-anopheles stephensi system and its response to antimalarials]. 19836679168
sporozoite-induced plasmodium cynomolgi infections in captive born macaca fascicularis.capability of captive born cynomolgus monkeys to substitute for rhesus in the plasmodium cynomolgi radical curative antimalarial drug development model was examined. eighteen monkeys divided into 3 groups were given standard or high doses of sporozoites intravenously. one group of 4 received 0.8 - 1.6 x 10(6) and a second group of 8 received 0.3 - 1.0 x 10(7) sporozoites. the third group of 6 was splenectomized and then received 3.0 - 4.0 x 10(6). the 2 groups of intact monkeys developed a persi ...19846740373
[continuous cultivation of erythrocytic plasmodium cynomolgi in vitro]. 19846509747
[studies on the biological characteristics and the strain-type of plasmodium cynomolgi maintained in china]. 19846518634
[a combined regimen of pyronaridin-artemether-chloroquine (pac) for the treatment of plasmodium cynomolgi infection in the rhesus monkey]. 19846536163
activities of respository preparations of cycloguanil pamoate and 4,4'-diacetyldiaminodiphenylsulfone, alone and in combination, against infections with plasmodium cynomolgi in rhesus monkeys.the studies summarized in this report were concerned with the capacities of repository preparations of cycloguanil pamoate (cgt-p) to protect rhesus monkeys against infections with drug-susceptible and pyrimethamine-resistant strains of plasmodium cynomolgi. administered intramuscularly as a suspension in an oleaginous vehicle, cgt-p (i) provided long-term protection against single and repetitive challenges of rhesus monkeys with sporozoites of the drug-susceptible b and ro strains, (ii) effecte ...19846393864
[antimalarial activities of hydroxypiperaquine and its phosphate against plasmodium berghei and plasmodium cynomolgi]. 19846232823
interactions between oral contraceptives and malaria infections in rhesus monkeys.the interaction of oral contraceptives with malaria infection (plasmodium cynomolgi b and p. coatneyi) in adult female rhesus monkeys (macaca mulatta) was studied. the oral contraceptives (norinyl and ovral-28) were administered for 12 consecutive menstrual cycles, from day 5 to 25 of each cycle, at either (1/3) of the human dose of norinyl (norethisterone 0.33 mg + ethinylestradiol 0.012 mg) or (1/6) of the human dose of ovral-28 (norgestrel 0.083 mg + ethinylestradiol 0.008 mg).the animals wer ...19846335851
evaluation of plasmodium cynomolgi b antigen in enzyme linked immunosorbent assay (elisa) test for human malaria. 19846399263
continuous in vitro cultivation of erythrocytic plasmodium cynomolgi. 19846432472
an evaluation of plasmodium cynomolgi bastianellii and plasmodium knowlesi antigens in the seroepidemiology of human malaria using indirect haemagglutination test. 19846536544
circumsporozoite gene of plasmodium cynomolgi (gombak):cdna cloning and expression of the repetitive circumsporozoite epitope.we report the identification, sequence, and expression in escherichia coli of the immunodominant epitope of the circumsporozoite (cs) gene of plasmodium cynomolgi (gombak), a simian malaria parasite. this epitope is encoded by a dna sequence that is tandemly repeated 10 times in the cdna clone. subclones that contain and express only repeats and in variable number have been constructed. we show that the binding of a specific anti-cs protein monoclonal antibody correlates positively with the numb ...19846209717
evolutionary relatedness of plasmodium species as determined by the structure of dna.malaria parasites can be grouped evolutionarily by analysis of dna composition and genome arrangement. those that vary widely with regard to host range, morphology, and biological characteristics fit into only a small number of distinctive groups. the dna of the human parasite plasmodium falciparum fits into a group that includes rodent and avian malarias and is unlike the dna of other primate malaria parasites. the dna of plasmodium vivax, which is also a human parasite, fits into a distinctly ...19846382604
4-substituted 5-[m-(trifluoromethyl)phenoxy]primaquine analogues as potential antimalarial agents.five 4-substituted 5-[m-(trifluoromethyl)phenoxy]primaquine analogues were synthesized and tested for radical curative activity against plasmodium cynomolgi in rhesus monkeys and for blood schizonticidal antimalarial activity against plasmodium berghei in mice. in addition, they were evaluated for causal prophylactic antimalarial activity against plasmodium berghei yoelii in mice. one compound, 4-ethyl-5-[m-(trifluoromethyl)phenoxy]primaquine (2b), showed radical curative activity equivalent to ...19854067985
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
enhancement of the curative activity of primaquine by concomitant administration of mirincamycin.mirincamycin, a lincomycin derivative with unequivocal but limited activity against the pre-erythrocytic and persisting exoerythrocytic stages of plasmodium cynomolgi, has been evaluated for capacity to enhance the radical curative potential of the conventional primaquine-chloroquine combination. established infections with sporozoites of the above plasmodium in rhesus monkeys served this evaluation. the results showed that the dose of primaquine required for cure of 50% of active infections was ...19853885847
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
observations on early and late post-sporozoite tissue stages in primate malaria. iii. further attempts to find early forms and to correlate hypnozoites with growing exo-erythrocytic schizonts and parasitaemic relapses in plasmodium cynomolgi bastianellii infections.rhesus monkeys were heavily infected with sporozoites of plasmodium cynomolgi bastianellii in an attempt to demonstrate the site of invasion of sporozoites into tissue cells and their growth there. further attempts were made to correlate the appearance and loss of hypnozoites with parasitaemic relapses. hypnozoites were demonstrated and once again shown to decrease in numbers over 229 days during which time the infection showed parasitaemic relapses. liver biopsies taken at two-day intervals for ...19854002302
sulfur-interrupted 8-amino side chain analogues of 4-methyl-5-[m-(trifluoromethyl)phenoxy]primaquine as potential antimalarial agents.two isomeric sulfur-interrupted 8-amino side chain analogues of 4-methyl-5-[m-(trifluoromethyl)phenoxy]primaquine (2) were prepared and tested for antimalarial activity. the compounds were evaluated for blood schizonticidal activity against plasmodium berghei in mice and radical curative activity against plasmodium cynomolgi in rhesus monkeys. in addition, they were evaluated for causal prophylactic activity against plasmodium berghei yoelii in mice. both compounds were more active and less toxi ...19854068013
[therapeutic effect of pyronaridine given intragastrically on plasmodium cynomolgi-infected rhesus monkeys]. 19854072704
antimalarial activities and subacute toxicity of rc-12, a 4-amino-substituted pyrocatechol.rc-12 [1,2-dimethoxy-4-(bis-diethylaminoethyl)-amino-5-bromobenzene] was evaluated for prophylactic, radical curative, and suppressive activities against infections with plasmodium cynomolgi and subacute toxicity in rhesus monkeys. applied as a prophylactic agent, rc-12, administered in doses of 6.25 to 25.0 mg/kg daily throughout the incubation period, provided near-complete to complete protection against 10(5) to 10(6) times the minimum infective dose of sporozoites. applied as a suppressive a ...19854091527
infection of aotus azarae boliviensis monkeys with the ro strain of plasmodium cynomolgi. 19854093822
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
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
correlation of survival rates of anopheles dirus a (diptera: culicidae) with different infection densities of plasmodium cynomolgi.the survival rates are described for 36 paired replicates of anopheles dirus a mosquitos that had been allowed to engorge themselves on rhesus monkeys that were either infected or non-infected with plasmodium cynomolgi. the survival rates of infected mosquitos with a mean number of oocysts less than 10 did not differ significantly from those that were non-infected; however, there was a significant difference in the survival rates of non-infected groups and those with a mean number of oocysts in ...19863493859
genetic selection of a plasmodium-refractory strain of the malaria vector anopheles gambiae.the anopheline mosquito is the target in most malaria control programs, primarily through the use of residual insecticides. a mosquito was studied that is refractory to most species of malaria through a genetically controlled mechanism. a strain of anopheles gambiae, which was selected for complete refractoriness to the simian malaria parasite plasmodium cynomolgi, also has varying degrees of refractoriness to most other malaria species examined, including the human parasites p. falciparum, p. o ...19863532325
evolutionary profile of the circumsporozoite gene of the plasmodium cynomolgi complex.the circumsporozoite genes and flanking sequences of the ceylon, gombak, london, nih and mulligan strains of the plasmodium cynomolgi complex were isolated by molecular cloning and compared. about 11,000 bases of the gombak clone were mapped in detail and found to have their exact counterparts in all the other strains. in contrast the epitope-encoding region, a 600-base sequence consisting of short tandem repeats, exhibited no homology with any of the other clones. these findings show that diffe ...19863735434
4,5-disubstituted primaquine analogues as potential antimalarial agents.three 4,5-disubstituted primaquine analogues were synthesized and evaluated for radical curative activity against plasmodium cynomolgi in rhesus monkeys. one of the compounds showed moderate activity; however, none of the three compounds were as active as the lead compounds 5-methoxy-4-methylprimaquine and 4-(methoxy-methyl)-5-[m-(trifluoromethyl)phenoxy]primaquine.19863746825
[further studies on the relapse of plasmodium cynomolgi in rhesus monkeys]. 19863769157
[on the residual activity of pyronaridine against plasmodium cynomolgi in rhesus monkeys]. 19863769158
[action of nitroquine on tissue schizonts of plasmodium cynomolgi]. 19862945393
compatibility of relapse patterns of plasmodium cynomolgi infections in rhesus monkeys with continuous cyclical development and hypnozoite concepts of relapse.this report encompasses the results of two studies on the relapse patterns of infections with the b strain of plasmodium cynomolgi treated repetitively with chloroquine. one study of sizeable dimensions dealt primarily with relapses that occurred within 120 days of onset of patency in infections induced with inocula of 10(5) to 7 x 10(6) sporozoites. the second study, of more limited dimensions, dealt with relapses that occurred over a 689-day period after inoculation with 5 x 10(0) to 5 x 10(6) ...19863538919
sequential changes in ifa titres and protein fractions of sera from plasmodium cynomolgi b infected simian hosts. 19863570370
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
[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
[study on the treatment of plasmodium cynomolgi infections of the macaque with ketotifen]. 19873450138
modifications of primaquine as antimalarials. 4. 5-alkoxy derivatives of primaquine.thirty-two 5-alkoxyprimaquines have been synthesized and evaluated as blood schizonticides (plasmodium berghei, mouse) and tissue schizonticides (plasmodium cynomolgi, monkey). several of these compounds were extremely active in both screens. such a broad spectrum of antimalarial efficacy offers the possibility of a single drug that could cure the various relapsing and nonrelapsing malarias.19873599024
relapse patterns in plasmodium cynomolgi malaria. 19873661833
attenuation of the virulence of the m strain of plasmodium cynomolgi during prolonged multiplication in splenectomized rhesus monkeys.the primary data in this report showed that prolonged multiplication of the m strain of plasmodium cynomolgi in splenectomized rhesus monkeys led frequently to emergence of parasites whose virulence for monkeys with intact spleens was markedly attenuated while that for splenectomized monkeys was unimpaired. expressions of attenuation regularly included reductions in the height of the peak parasitemia and in some instances failure to induce infection with inocula 1,000-fold those infective for sp ...19873688305
the circumsporozoite gene of the plasmodium cynomolgi complex.an analysis of the circumsporozoite (cs) genes of six closely related plasmodia is presented. like other plasmodial antigens, the cs protein contains tandem repeats flanked by conventional nonrepeated sequences. our analysis shows that the repeats, which encode the immunodominant epitope of the cs protein, diverge more rapidly than the remainder of the gene, and that the maintenance and evolution of the repeats cannot be explained as the result of selection at the protein level. we argue that a ...19873802196
[in vitro cultivation of plasmodium cynomolgi bastianelli in hepatocytes of the macaca rhesus].primary cultures of rhesus monkey were infected with sporozoites of p. c. bastianelli. despite a high level of contamination, two schizonts were seen at days 6 and 11.19873566091
[suppressive effect of 3 combinations of antimalarials against plasmodium cynomolgi]. 19873450444
tissue schizontocidal activity of minocycline against a relapsing malaria parasite plasmodium cynomolgi b. 19873666853
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
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
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
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
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
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
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
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
[comparison in susceptibility of anopheles dirus and anopheles stephensi to b strain of plasmodium cynomolgi].this paper reports on the comparative susceptibility of a. dirus (hainan strain) and a. stephensi (hor strain) to the b strain of p. cynomolgi in paired feeding experiments. in the most susceptible infective period, the infection rate in midgut and salivary gland of the two species was over 90%, the difference is not statistically significant. in relatively infective period, three experiments were performed, the infection rate in midgut of a. dirus was 24.4-60.4% with an average of 46.5% (53/114 ...19892591037
enhancement of in vitro infectivity of simian malaria sporozoites to hepatocytes by centrifugation.sporozoites of plasmodium cynomolgi, plasmodium knowlesi, and plasmodium coatneyi were deposited onto monolayers of hepatocytes from rhesus monkeys (macaca mulatta). when sporozoites were centrifuged (1,600 g for 5 min), 4-13-fold more schizonts were observed than were found in noncentrifuged control cultures. centrifugation of hepatocyte monolayers before adding sporozoites did not modify the number of parasites.19892614610
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
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
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
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
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
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
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
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
homologous sequences in plasmodium cynomolgi and the gene of the histidine-rich knob protein of plasmodium falciparum. 19902183051
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
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
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
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
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
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
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
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
[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
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
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
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
[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
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
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
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
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