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intramolecular mapping of plasmodium falciparum p126 proteolytic fragments by n-terminal amino acid sequencing.protein p126 (also called p140, p113, sera, serp1) is a major parasitophorous vacuole antigen of plasmodium falciparum. this protein is processed upon merozoite release into 2 fragments of 73 kda (p73) and 50 kda (p50), which are found in the culture medium. p73 is composed of 2 polypeptides of 47 and 18 kda linked by disulfide bridges. in the presence of leupeptin, an inhibitor of serine and cysteine proteases which inhibits merozoite release, a 56-kda intermediate product (p56) is recovered in ...19921501648
desferrioxamine in the treatment of plasmodium falciparum malaria. 19921503106
ingestion of plasmodium falciparum sporozoites during transmission by anopheline mosquitoes.we investigated the process of sporozoite transmission during blood feeding for anopheles gambiae and an. stephensi experimentally infected with plasmodium falciparum. when infective mosquitoes were fed 22-25 days postinfection on an anesthetized rat, sporozoites were detected in the midgut of 96.5% of 57 an. gambiae (geometric mean [gm] = 32.5, range 3-374) and in 96.2% of 26 an. stephensi (gm = 19.5, range 1-345). there were no significant differences between species either in salivary gland s ...19921503188
pathology of falciparum malaria in vietnam.autopsy samples from the brains of 20 patients who died of falciparum malaria were examined by light microscopy and by an immunohistologic method. particular attention was paid to a comparison of the pathologic features of the white matter and the cortex. in the high-sequestration (greater than 50%) group (n = 8), the mean +/- sd percentage of cerebral microvessels that showed parasitized red blood cell (prbc) sequestration was 71.2 +/- 8.1% in the cortex and 84.0 +/- 6.7% in the white matter. t ...19921503193
molecular targets of 5-fluoroorotate in the human malaria parasite, plasmodium falciparum.5-fluoroorotate is known to have potent antimalarial activity against chloroquine-susceptible as well as chloroquine-resistant clones of plasmodium falciparum. it was hypothesized that this activity was mediated through synthesis of 5-fluoro-2'-deoxyuridylate, an inactivator of thymidylate synthase, or through incorporation of 5-fluoropyrimidine residues into nucleic acids. treatment of p. falciparum in culture with 100 nm 5-fluoroorotate resulted in rapid inactivation of malarial thymidylate sy ...19921503432
localization and characterization of hemoglobin-degrading aspartic proteinases from the malarial parasite plasmodium falciparum.three hemoglobin-degrading proteinases were partially purified from food vacuoles isolated from trophozoite-stage forms of the malarial parasite plasmodium falciparum. two of the proteinases (m1 and m2) were solubilized by repeated sonication. the remaining proteinase (m3) was solubilized by treatment of the particulate fraction with taurocholic acid, suggesting that proteinase m3 is a membrane-bound proteinase whereas proteinases m1 and m2 are weakly associated with parasite membrane. the locat ...19921504087
efficacy of dapsone with pyrimethamine (maloprim) for malaria prophylaxis in maputo, mozambique.in a randomized controlled study of malaria prophylaxis, dapsone-pyrimethamine at a weekly dosage of dapsone 50-100 mg with pyrimethamine 6.25-12.5 mg or placebo was administered to 166 school children for 17 weeks. fortnightly parasitological controls revealed 28 infections in the placebo group and none in the dapsone-pyrimethamine group. it is concluded that weekly dapsone-pyrimethamine is effective for the prophylaxis of falciparum malaria in mozambique.19921505413
in vivo and in vitro response of plasmodium falciparum to chloroquine in pregnant women in kilifi district, kenya.in a malaria-endemic area of the coast of kenya with chloroquine resistant plasmodium falciparum, we determined the prevalence and density of falciparum infection in gravid women and assessed the in vivo and in vitro parasite response to a regimen of chloroquine 25 mg/kg body weight divided over three days. p. falciparum infections were present in 65 (21.7%) of 300 pregnant women. the proportion of primigravidae who were parasitaemic was 41.8% which was significantly higher than that of the mult ...19921505414
origins of the parasitophorous vacuole membrane of the malaria parasite, plasmodium falciparum, in human red blood cells.we have attempted to determine whether the parasitophorous vacuole membrane, in which the malaria parasite (merozoite) encapsulates itself when it enters a red blood cell, is derived from the host cell plasma membrane, as the appearance of the invasion process in the electron microscope has been taken to suggest, or from lipid material stored in the merozoite. we have incorporated into the red cell membrane a haptenic phospholipid, phosphatidylethanolamine, containing an nbd (n-(7-nitrobenz-2-ox ...19921506432
[the search for new antiparasitic agents. 10. the synthesis, toxicological and antimalarial properties of nitrogen-containing heterocycles with a 4-(4-alkylpiperazinyl-1) phenylamine substituent (the preparation quinoprazine)].synthesis is described and acute toxicity and antimalaria action is studied in new derivatives of quinoline and benzo(g)quinoline containing a 4-(4-alkylpiperazinyl-1)phenylamine substitute. only the derivatives of benzo(g)quinoline were found to have a high antimalaria effect and to have advantages over the standard agent chloroquine on their tolerance and protective action. one of the compounds, 4-[4-(4-ethylpiperazinyl-1)phenylamino] benzo(g)quinoline, named quinoprazine, showed some action a ...19921508078
effects of cinnamic acid derivatives on in vitro growth of plasmodium falciparum and on the permeability of the membrane of malaria-infected erythrocytes.cinnamic acid derivatives (cads) are known inhibitors of monocarboxylate transport across plasma and mitochondrial membranes. all derivatives were found to inhibit the growth of intraerythrocytic plasmodium falciparum in culture, which is in correlation with their hydrophobic character. parasites at the ring and trophozoite stages were equally susceptible to the different derivatives. this result could be attributed to their inhibition of the transport of lactate, the major product of parasite e ...19921510401
stereochemical evaluation of the relative activities of the cinchona alkaloids against plasmodium falciparum.quinine and quinidine were over 100 times more active than 9-epiquinine and 9-epiquinidine against chloroquine-sensitive plasmodium falciparum and over 10 times more active against chloroquine-resistant p. falciparum. since the only structural difference between quinine, quinidine, 9-epiquinine, and 9-epiquinidine is their three-dimensional configuration, the three-dimensional structures of these four alkaloids were examined in order to explain the large difference in relative activities between ...19921510452
anaemia of plasmodium falciparum malaria.the pathophysiology of the anaemia of falciparum malaria is both complex and multifactorial, and results in a condition which is a major cause of mortality and morbidity in patients, especially children and pregnant women, living in malarial endemic areas. the importance of anaemia as a cause of death in malaria may well be underestimated because of difficulty in diagnosis, especially where parasitaemia may be low and the clinical picture may be confused with other causes of anaemia. two clinica ...19921511178
identification of anti-plasmodium falciparum antibodies in human breast milk.malarial infections are rarely observed in neonates. it has been postulated that some immunity may be passively transferred during nursing, but anti-malarial antibodies (abs) have not been detected in human milk. in this study, milk samples, collected 2-14 days after parturition from women at the central maternity hospital, yaounde, were evaluated for total igg and iga antibody levels by radial diffusion, protein composition by sds-page, anti-malarial antibodies using an isotype-specific immunof ...19921514035
cytokines inhibit the development of liver schizonts of the malaria parasite plasmodium berghei in vivo.the effect of induction of an acute-phase response and its mediators on the development of liver schizonts of the rodent malaria parasite plasmodium berghei was investigated in brown norway rats. subcutaneous injection of turpentine oil 24 h or 5 min before inoculation of sporozoites resulted in 80% and 35% reduction of schizont development, respectively. turpentine oil induced high plasma levels of interleukin-6 (il-6). intraperitoneal administration of il-1, il-6 or both, significantly reduced ...19921516619
plasmodium falciparum: a simple polymerase chain reaction method for differentiating strains.laboratory studies of the protozoan parasite plasmodium falciparum have been hampered by difficulties in defining differences between isolates. we have developed a method based on the polymerase chain reaction (pcr) that allowed us to identify quickly the various strains with which we routinely work. we also adapted methods for easily purifying enough dna to produce a pcr product from a small volume of culture: 100 microliters of an in vitro culture infected at 1% parasitemia. the primers were c ...19921516668
plasmodium chabaudi: estradiol suppresses acquiring, but not once-acquired immunity.this study investigates the effect of estradiol (e) on self-healing of plasmodium chabaudi malaria in mice of the inbred strain c57bl/10. our data show: (1) female mice and male castrates are capable of self-healing infections when challenged with 10(6) p. chabaudi-infected erythrocytes. self-healing is completely suppressed after pretreatment of mice with 12 micrograms e injected sc twice a week for 3 weeks. (2) the suppressive effect of e is prevented by the estrogen receptor blockers tamoxife ...19921516672
plasmodium falciparum: release of circumsporozoite protein by sporozoites in the mosquito vector.the release of circumsporozoite (cs) protein by plasmodium falciparum sporozoites was investigated to identify factors regulating this process within infected anopheles gambiae mosquitoes. the potential for sporozoites to release cs protein in vitro was not dependent upon their site-specific developmental stage (i.e., mature oocysts, hemolymph, salivary glands), their duration in the vector, or their exposure to mosquito-derived components such as salivary glands or hemolymph. the capacity of sp ...19921516673
adherence of infected erythrocytes to venular endothelium selects for antigenic variants of plasmodium falciparum.erythrocytes (e) infected with asexual forms of malaria parasites exhibit surface antigenic variation. in plasmodium falciparum infections, the variant ag is the p. falciparum e membrane protein 1 (pfemp1). this molecule may also mediate the adherence of infected e to host venular endothelium. we show here that parasite lines selected for increased adherence to endothelial cells have undergone antigenic variation. three adherent lines selected from the same p. falciparum clone reacted with the s ...19921517569
a t cell clone directed at the circumsporozoite protein which protects mice against both plasmodium yoelii and plasmodium berghei.clone b is a cytotoxic t cell clone induced by immunization with plasmodium yoelii sporozoites which recognizes an epitope on both the p. yoelii and plasmodium berghei circumsporozoite proteins. it is cd8, uses the v beta 8.1 tcr, and is kd restricted. when adoptively transferred, it protects mice against infection by both species of malaria sporozoites, and this protection is dependent on ifn-gamma. clone b cells are more broadly reactive and protective than previously described murine t cell c ...19921517574
binding of malarial circumsporozoite protein to sulfatides [gal(3-so4)beta 1-cer] and cholesterol-3-sulfate and its dependence on disulfide bond formation between cysteines in region ii.region ii of the malaria circumsporozoite (cs) protein is highly conserved between the cs proteins of different species of malaria. amino acid sequences homologous to that of region ii are found in thrombospondin, properdin, von willebrand factor and a few other proteins. we show here that the native cs protein from the rodent parasite plasmodium berghei, and recombinant plasmodium vivax and plasmodium falciparum cs proteins containing region ii, but not recombinant proteins lacking region ii, s ...19921518521
identification of a plasmodium falciparum histone 2a gene. 19921518525
the plasmodium falciparum hypoxanthine-guanine phosphoribosyl transferase gene has a 5' upstream intron. 19921518526
second form in a segment of the merozoite surface protein 1 gene of plasmodium vivax among isolates from rondônia (brazil). 19921518527
ribosomal dna sequence comparison of babesia and theileria.previous studies on the taxonomy of babesia spp. (phylum apicomplexa) using morphological and life cycle characteristics have resulted in their classification into 3 subgenera, with the genus theileria being most closely related to them. using a strategy based on the direct sequence analysis of products derived by asymmetric pcr to determine the nucleotide sequences, we have tested the validity of this classification by sequencing the small subunit ribosomal rna genes amplified from 2 babesia sp ...19921518535
prophylaxis for malaria. helping world travelers come home healthy.malaria is largely preventable, so travelers should be taught general protective measures and given appropriate chemoprophylaxis before they leave on their trip. chloroquine phosphate (aralen) is still the drug of choice in locations where malaria remains chloroquine-sensitive. however, chloroquine-resistant areas infested with plasmodium falciparum are becoming more numerous. in such areas, mefloquine hydrochloride (lariam), doxycycline, or proguanil (paludrine) (obtainable outside the united s ...19921518752
proposals for a new therapeutic strategy for simple plasmodium falciparum malaria attacks in cameroon.from simplified in vivo tests, authors set up a cartography of the sensitivity of plasmodium falciparum to amino-4-quinolines in cameroon; they also evaluated the clinical and parasitological efficacy of different therapeutic protocols which make use of amino-4-quinolines, quinine, mefloquine and halofantrine. all these drugs are administered orally. they recommend maintaining home medication with chloroquine at the dose of 25 mg/kg over 3 days, conserving quinine for use in the case of a possib ...19921519023
superantigens, t cells, and microbes.it is well recognized that toxins of staphylococcus aureus and streptococcus pyogenes are responsible for a wide range of clinical conditions, although their precise mode of action remains unclear. recently, there has been a resurgence of interest in these toxins, now grouped with superantigens, because they cause profound alterations in the immune system homeostasis. superantigens are molecules, including endogenous retroviral gene products and microbial toxins, that share a unique set of chara ...19921520765
imported malaria in pregnancy: report of four cases and review of management.malaria is a common infection worldwide. increased travel by pregnant women makes it likely that physicians in the united states will see cases of malaria in this population. we observed four cases of malaria during pregnancy over an 8-month period at a general hospital in the united states. these cases illustrate the association between pregnancy and severe malaria in the mother and congenital infection in the newborn. we also noted delays in diagnosis because malaria was mistaken for other com ...19921520785
studies on glycolytic enzymes of plasmodium knowlesi, a simian malaria parasite, and infected host erythrocytes.almost all of the important enzymes of glycolytic sequence were studied in isolated schizonts of plasmodium knowlesi as well as in normal and p. knowlesi parasitized rhesus red blood cells. significant activities of all the glycolytic enzymes assayed were observed in cell-free schizonts and the levels of all were found to be considerably elevated in infected host erythrocytes, confirming that the consumption of glucose is dramatically increased in host red cells, consequent to malaria infection.19921520983
plasmodium falciparum: differential sensitivity in vitro to e-64 (cysteine protease inhibitor) and pepstatin a (aspartyl protease inhibitor).we investigated the effect of a cysteine proteinase inhibitor (e-64) and an aspartyl proteinase inhibitor (pepstatin a) on asexual erythrocytic stages of plasmodium falciparum in culture. these two protease inhibitors showed different patterns of activity. e-64 acted preferentially against trophozoite and schizont stages. after 48 h incubation at high concentrations of e-64 (28, 140, 280 microm), growth was totally abolished and the parasites presented characteristic enlarged food vacuoles. morp ...19921522541
continuous cultivation and drug susceptibility testing of plasmodium falciparum in a malaria endemic area.isolates (uch-23 and om) and cloned strains of plasmodium falciparum (clones w-2 and d-6) were maintained in continuous culture for 28 to 150 days using culture media supplemented with 10% (v/v) heat inactivated semi-immune human plasma. microscopic appearance and growth rates (r) of the parasites in media supplemented with semi-immune human plasma [r = 1.13 (w-2), 0.92 (d-6), 0.75 (om) and 0.84 (uch-23)] were comparable to those of parallel cultures maintained in media supplemented with 10% (v/ ...19921522542
codon usage in giardia lamblia.a codon usage table for the intestinal parasite giardia lamblia was generated by analysis of the nucleotide sequences of eight genes comprising 3,135 codons. codon usage revealed a biased use of synonymous codons with a preference for nnc codons (42.1%). the codon usage of g. lamblia more closely resembles that of the prokaryote halobacterium halobium (correlation coefficient r = 0.73) rather than that of other eukaryotic protozoans, i.e. trypanosoma brucei (r = 0.434) and plasmodium falciparum ...19921522548
thrombocytopenia in malaria.the relationship between platelet counts and platelet bound (direct) or platelet directed (indirect) serum antibody concentrations was studied in 17 patients with plasmodium falciparum malaria and 12 patients with p. vivax malaria. platelet counts rose with recovery from infection from 196 +/- 84 x 10(9)/l (mean +/- sd) and 195 +/- 34 x 10(9)/l to 319 +/- 99 and 283 +/- 62 x 10(9)/l respectively (p less than 0.002), but there was no relationship between either absolute platelet count or changes ...19921523477
comparative trial on the response of plasmodium falciparum to halofantrine and mefloquine in trat province, eastern thailand.with the appearance of strains of plasmodium falciparum in the trat province, eastern thailand, reported to have developed resistance to mefloquine there is a need for an alternative drug. this comparative trial with mefloquine and halofantrine has demonstrated extremely low cure rates with both drugs (33.3% and 28.13% respectively), cross-resistance is suggested.19921523479
comparison of effects of pyronaridine, amodiaquine, mefloquine and qinghaosu on rodent malaria.blood schizontocidal effect of antimalarials were compared by 4-day suppressive test with an extended observation period of 31 days. on a drug-sensitive plasmodium berghei anka strain, pyronaridine (pnd) exhibited the best effect, followed by amodiaquine (adq), mefloquine (mfq), and qinghaosu (qhs). on a moderately chloroquine-resistant p. berghei ns line, the order of effects was the same, pnd greater than adq greater than mfq greater than qhs. on a highly pyronaridine-resistant p. berghei rp l ...19921523480
malaria--the mime revisited: fifteen more years of experience at a new york city teaching hospital.purpose and patients: a previous review of the new york hospital experience with malaria during 1968 to 1975 summarized clinical and parasitologic features in 24 travelers and highlighted deficiencies in both chemoprophylaxis and diagnosis. to extend this original study, we describe 86 patients with malaria seen at the same hospital during the subsequent 15 years. results: eighty patients were infected with a single plasmodium species, and 60% had plasmodium falciparum infection primarily acquir ...19921524074
ovalocytosis protects against severe malaria parasitemia in the malayan aborigines.the malaria parasite rates and densities were compared in 79 ovalocytic-normocytic pairs of malayan aborigines matched for age, sex, proximity of residence to each other, and use of bed nets when sleeping in their jungle settlement in central peninsular malaysia. malaria infection was determined from thick and thin giemsa-stained blood films collected monthly for a period of six months. blood films from ovalocytic individuals were found to be positive for malaria less often than in persons with ...19921524139
the effectiveness of permethrin-impregnated bed nets against malaria for migrant workers in eastern thailand.a randomized, double-blind, field trial was carried out to compare the effectiveness of permethrin-treated bed nets with that of untreated nets as a method of malaria control for migrant workers in eastern thailand. the study was conducted using 261 subjects in eastern rural areas that are known to be highly endemic for multidrug-resistant plasmodium falciparum infection. one hundred twenty-six subjects used treated nets, while 135 used untreated nets. during the 35 weeks of observation, 23 subj ...19921524143
heightened transmission of stable malaria in an isolated population in the highlands of irian jaya, indonesia.malaria at an elevation of 1,500 meters is uncommon and is usually unstable when it occurs. to confirm reports of a recent increase in transmission of stable malaria in the oksibil valley, which is at an elevation of 1,250-1,500 meters in the jayawijaya mountains of irian jaya, indonesia, five malariometric surveys were conducted in four villages between may 1990 and july 1991. a total of 3,380 blood smears, representative of 1,949 persons, was examined. prevalence rates over the survey period w ...19921524148
mefloquine-halofantrine cross-resistance in plasmodium falciparum induced by intermittent mefloquine pressure.the study was designed to evaluate how exposure of plasmodium falciparum to mefloquine modifies the sensitivity of the parasite to four major antimalarial drugs. a recently culture-adapted strain of p. falciparum was subjected to intermittent drug pressure at three different mefloquine concentrations (2.34, 4.68, and 9.37 ng/ml). growth was monitored by daily evaluation of parasitemia on thin smears. drug sensitivity tests were done weekly, using a radioisotope microdilution method. mefloquine w ...19921524151
in vitro activity of the enantiomers of mefloquine, halofantrine and enpiroline against plasmodium falciparum.the in vitro activity of the enantiomers of mefloquine, halofantrine and enpiroline was compared against chloroquine-resistant and -susceptible strains of plasmodium falciparum using a semi-micro drug susceptibility test. for each strain, the corresponding enantiomers exhibited similar activities. the enantiomers of halofantrine were the most active against both susceptible and resistant strains, followed by the enantiomers of mefloquine and enpiroline.19921524966
subcellular fractionation of the two organelle dnas of malaria parasites.malaria parasites contain two extrachromosomal dnas, a 6 kb repetitive linear molecule which is assigned on the basis of its genetic content to the mitochondria, and a 35 kb transcriptionally active circular molecule whose intracellular location is not known. we used the polymerase chain reaction to detect and estimate the numbers of both molecules in sub-cellular fractions derived from the rodent parasite plasmodium yoelii. the two dna molecules were not coordinately partitioned by the fraction ...19921525866
assessment of chloroquine resistance of plasmodium falciparum in children of wad medani (central sudan).the study reports on chloroquine resistance of plasmodium falciparum among sudanese children (6 month to 16 years) living at wad medani, central sudan. all ri-iii levels of resistant response were confirmed, while in vitro sensitivity test indicated that 25 per cent of p. falciparum isolates examined had exhibited maturation of schizonts at cq level greater than or equal to 1.6 pmol/microliters blood. cq was sufficiently retained for 7 days after drug administration whereas an average peak level ...19921527810
antimalarial activities of oligodeoxynucleotide phosphorothioates in chloroquine-resistant plasmodium falciparum.synthetic oligonucleotides and their chemical modifications have been shown to inhibit viral and cellular gene expression by sequence-specific antisense hybridization to target mrnas. we now report that oligodeoxynucleotide phosphorothioates and their nuclease-resistant modifications are effective in micromolar and submicromolar concentrations against the growth of both chloroquine-resistant and chloroquine-sensitive strains of plasmodium falciparum in vitro. parasitized human erythrocytes were ...19921528864
profound thrombocytopenia due to plasmodium vivax malaria. 19921530541
energy dependence of chloroquine accumulation and chloroquine efflux in plasmodium falciparum.chloroquine inhibits the growth of susceptible malaria parasites at low (nanomolar) concentrations because of an energy-requiring drug-concentrating mechanism in the parasite secondary lysosome (food vacuole) which is dependent on the acidification of that vesicle. chloroquine resistance results from another energy-requiring process: efflux of chloroquine from the resistant parasite with a half-time of 2 min. chloroquine efflux is inhibited reversibly by the removal of metabolizable substrate (g ...19921531176
[severe plasmodium falciparum malaria attacks during chemoprophylaxis with chloroquine and proguanil]. 19921531267
human peripheral blood gamma delta t cells respond to antigens of plasmodium falciparum.peripheral blood lymphocytes from donors previously unexposed to malaria parasites proliferate in vitro when stimulated with whole parasitized red blood cells of several different strains of plasmodium falciparum. here we show that both cells enriched for both memory (cd45r0+) and naïve (cd45r0-) phenotype can respond. cells involved in these responses occur at frequencies similar to those observed for recall antigens such as tetanus toxoid but at lower frequencies than observed for the superant ...19921531764
a specific t-cell receptor genotype preference in the immune response to a synthetic plasmodium falciparum malaria vaccine.in recent studies with 63 and 122 volunteers vaccinated with the spf 66 synthetic malaria vaccine, specific antibody patterns were classified as high or low responders. using the polymerase chain reaction (pcr), a specific and selective preference was shown for the v beta arrangement of the t-cell receptor in the high responder group involving the v beta-8 gene. the low responder group showed the rearrangement of a different set of genes, and a particular association with v beta-10.19921532634
preferential expansion of v gamma 9 v delta 2 t cells following stimulation of peripheral blood lymphocytes with extracts of plasmodium falciparum.a plasmodium falciparum schizont lysate has been previously described as being a powerful inducer of proliferation for human peripheral t lymphocytes. in this report we study the phenotype of cycling t cells from unexposed donors and examine how the p. falciparum lysate compares with the conventional t cell mitogen phytohemagglutinin (pha), a known superantigen staphylococcal enterotoxin b (seb), and a classical antigen pure protein derivative (ppd). we show that for this lymphoproliferative act ...19921533150
alterations in host regulatory glycolytic enzymes during pathogenesis of primate malaria and following chloroquine therapy.hexokinase, phosphofructokinase and pyruvate kinase, the regulatory enzymes of the glycolytic sequence, showed progressive increases in their activities with the rise of parasitaemia in plasmodium knowlesi-infected rhesus monkey serum and red blood cells. chloroquine therapy cleared the parasitaemia in 72 h and brought the elevated levels of these enzymes back to almost normal in about 30 days.19921534081
[resistance of plasmodium falciparum to the chloroquine-proguanil combination. a case from benin]. 19921534624
multi-drug resistant falciparum malaria in cameroon in 1987-1988. i. stable figures of prevalence of chloroquine- and quinine-resistant isolates in the original foci.the status of drug-resistant plasmodium falciparum in cameroon was determined in 1987-1988 in 221 children who were selected for chloroquine and quinine in vitro microtests. resistance to quinine was found in 17% of 72 isolates from the southern part of the country, and in 7% of 87 isolates from the northern part of the country. the effective concentrations of 50% and 90% (ec50 and ec90) differed little from those observed in 1986. in southern cameroon, 38 (51%) of 74 individuals harbored chloro ...19921536378
effect of chloroquine chemoprophylaxis during pregnancy on birth weight: results of a randomized trial.to determine the effect of chloroquine chemoprophylaxis during pregnancy on birth weights, a randomized trial was carried out in 1987 and 1988 in banfora, burkina faso (west africa). seven hundred forty-five randomly selected women treated with chloroquine sulfate were compared to with 719 controls who received no treatment. in spite of an unquestionable effect of chloroquine in preventing placental infection (4.1% infected placentas in the treated group versus 19.0% in the controls), the mean d ...19921536379
is anopheles mascarensis a new malaria vector in madagascar?anopheles mascarensis de meillon, 1947, a mosquito that is native to madagascar, is reported for the first time to act as a vector of plasmodium falciparum malaria. from september 1989 to march 1990, 2, 499 an. mascarensis specimens from different regions of madagascar were tested by an enzyme-linked immunosorbent assay (elisa), using monoclonal antibodies against the circumsporozoite (cs) protein of the four human species of plasmodium. the salivary glands of 237 specimens were also dissected. ...19921536380
construction of a genomic dna library of the toxoplasma gondii zs2 strain, screening of specific clones, and dna diagnosis of toxoplasmosis.we have constructed a genomic dna library of the toxoplasma gondii zs2 strain and isolated a specific cloned dna sequence from this organism. the restriction map of this cloned 1.1-kb dna fragment was analyzed. southern and dot-blot analyses showed that the 32p-labeled dna fragment hybridized to parasite dna, to dnas from peripheral blood leukocytes and the thymus of baby pigs that were artificially infected with t. gondii, and to dnas of t. gondii-positive anencephalic and hydrocephalic fetuses ...19921536384
multi-drug resistant falciparum malaria in cameroon in 1987-1988. ii. mefloquine resistance confirmed in vivo and in vitro and its correlation with quinine resistance.to further document the phenomenon of plasmodium falciparum resistance to mefloquine formerly described in cameroon, complementary in vivo and in vitro studies were conducted. two hundred six p. falciparum isolates were studied in vitro using an isotopic microassay with mefloquine solutions prepared daily. using the cutoff limit of 30 nmol, 26 (20%) of 133 isolates from the northern part of the country were defined as being resistant to mefloquine. in contrast, only one of 73 isolates collected ...19921536387
cross-reaction of antibodies to the nine-amino acid repeats of plasmodium falciparum antigen 11.1 with human serum albumin.mice immunized with the recombinant antigen 11.1 beta-galactosidase, consisting of 22 repeats of the nine-amino acid unit from plasmodium falciparum antigen 11.1, produced antibodies reacting with human serum albumin. a positive reaction was observed in dot-blot assays, in enzyme-linked immunosorbent assay and on immunoblots of sodium dodecyl sulfate polyacrylamide gels as well as two-dimensional gels. binding was specific for human albumin, as no reaction could be detected on bovine serum album ...19921537376
detection of plasmodium falciparum dna in a microtitration plate-based hybridization test.a rapid dna-test, depending on the affinity based hybrid collection principle, was developed for the detection of plasmodium falciparum dna from clinical specimens. in this method, hybridization takes place in solution and the hybrids are collected onto a solid phase for measurement. two probes are used, one labelled with an affinity tag (biotin) and the other with a detectable label (32p). in the present test a single oligonucleotide complementary to a 21-base pair sequence which is highly repe ...19921537547
tumour necrosis factor induction by malaria exoantigens depends upon phospholipid.in patients with malaria, the clinical manifestations of the disease are associated with the presence of high concentrations of tumour necrosis factor (tnf) in the serum. blood-stage parasites of human and rodent malarial parasites release serologically related exoantigens which induce the production of tnf in vitro and in vivo and which can kill mice made hypersensitive to tnf by pretreatment with d-galactosamine. they also elicit the production of t-independent antibody, which blocks these eff ...19921537589
the statistical analysis of data from immunoepidemiological studies.immune responses encountered in human populations display a higher level of heterogeneity than is typically seen with laboratory animals, and the expected clear distinction between responders and non-responders to particular antigens may not be apparent. in such a situation, the methods of statistical analysis traditionally used in laboratory studies may no longer be appropriate, and there is no consensus among immunologists about how such data should be analysed. using data from a large study o ...19921538144
smear-negative cerebral malaria due to mefloquine-resistant plasmodium falciparum acquired in the amazon. 19921538173
basis of unique red cell membrane properties in hereditary ovalocytosis.hereditary ovalocytes from a mauritian subject are extremely rigid, with a shear elastic modulus about three times that of normal cells, and have increased resistance to invasion by the malaria parasite plasmodium falciparum in vitro. the genetic anomaly resides in band 3; the protein gives rise to chymotryptic fragments with reduced mobility in sds/polyacrylamide gel electrophoresis, but this is a result of anomalous binding of sds and not a higher molecular weight. analysis of the band 3 gene ...19921538405
gametocytocidal and sporontocidal activity of antimalarials against plasmodium berghei anka in icr mice and anopheles stephensi mosquitoes.the gametocytocidal and sporontocidal activity of three 8-aminoquinolines (primaquine, wr-238605, and wr-242511), three dihydroacridine-diones (floxacrine, wr-250547, and wr-250548), a 1,4-naphthoquinone (menoctone), a synthetic aminoalcohol (halofantrine), and a guanide (wr-182393) was determined against a cloned line of plasmodium berghei anka. gametocytocidal activity was assessed by treating mice with a single intraperitoneal inoculation of a given compound (25 mg base drug/kg mouse body wei ...19921539752
intraspecific chromosomal polymorphism in the anopheles gambiae complex as a factor affecting malaria transmission in the kisumu area of kenya.the paracentric inversion polymorphisms of anopheles gambiae and an. arabiensis populations in the kisumu area of western kenya were studied in relation to parameters of plasmodium falciparum transmission. anopheles gambiae (n = 1,387) was polymorphic for inversions b on chromosomal arm 2r and a on arm 2l, with frequencies of the inverted arrangements of 17% and 43%, respectively. anopheles arabiensis (n = 484) was polymorphic for inversion b on chromosomal arm 2r and a on 3r, with frequencies o ...19921539757
dictyostelium discoideum as an expression host for the circumsporozoite protein of plasmodium falciparum.we have used the cellular slime mold, dictyostelium discoideum (dd), to express the plasmodium falciparum circumsporozoite protein (cs), a potential component of a subunit vaccine against malaria. this was accomplished via an expression vector based on the discoidin i-encoding gene promoter, in which we linked a sequence coding for a dd leader peptide to the almost complete cs coding region (pedii-cs). cs production at both the mrna and protein levels is induced by starving cells in a simple pho ...19921541397
serological relationship of tumor necrosis factor-inducing exoantigens of plasmodium falciparum and plasmodium vivax.exoantigens of plasmodium vivax-parasitized erythrocytes stimulated macrophages to secrete tumor necrosis factor, and antisera raised against the exoantigens inhibited this secretion. the antisera also inhibited the activity of plasmodium falciparum and plasmodium yoelii exoantigens, and conversely, antisera against the latter cross-reacted with the exoantigens of p. vivax.19921541540
malaria: from quinine to the vaccine. 19921541651
antimalarial properties of n-3 and n-6 polyunsaturated fatty acids: in vitro effects on plasmodium falciparum and in vivo effects on p. berghei.the polyunsaturated fatty acids docosahexaenoic acid (c22:6,n-3), eicosapentaenoic acid, arachidonic acid, and linoleic acid caused marked in vitro growth inhibition of plasmodium falciparum, assessed by a radiometric assay. in contrast, negligible parasite killing was seen with oleic acid or docosanoic acid. parasite killing was significantly increased when oxidized forms of polyunsaturated fatty acids were used. antioxidants greatly reduced the fatty acid-induced killing. mice infected with p. ...19921541684
immunization with synthetic peptides containing a defined malaria epitope induces a highly diverse cytotoxic t lymphocyte response. evidence that two peptide residues are buried in the mhc molecule.in the present study, we have explored ways of inducing a ctl response to a previously defined h-2kd mhc class i restricted epitope in the circumsporozoite (cs) protein of plasmodium berghei, and studied in detail the fine specificity of the response. we found that the s.c. injection of a variety of synthetic peptides emulsified in freund's adjuvant efficiently induced a specific ctl response in (balb/c x c57bl/6)f1 (h-2d x h-2b) mice. in contrast, balb/c mice responded only marginally, consiste ...19921541825
a toxoplasma gondii rhoptry protein associated with host cell penetration has unusual charge asymmetry.the monoclonal antibody tg49 both recognizes a toxoplasma gondii rhoptry protein (rop1) and inhibits penetration enhancing factor. the latter is a proteinaceous factor found in toxoplasma lysates or conditioned media that increases the efficiency with which parasites invade host cells. tg49 was used to screen a lambda gt11 cdna library and the clone obtained was identified as the cognate gene for rop1 by several criteria: (1) recombinant protein reacted with the monoclonal; (2) antiserum against ...19921542304
the 42-kilodalton rhoptry-associated protein of plasmodium falciparum.the gene coding for a 42-kda rhoptry protein of plasmodium falciparum has been cloned. on the basis of prior monkey vaccination studies, this protein is regarded as an important vaccine candidate, but its identity has been the subject of considerable uncertainty. analysis of the cloned sequence shows that it is a basic, hydrophobic protein, without repetitive elements, unrelated to any of the previously postulated gene products and shows minimal sequence diversity. the availability of the corres ...19921542308
purification and properties of plasmodium falciparum malate dehydrogenase.asexual intraerythrocytic plasmodium falciparum were shown to have a single isoenzyme of malate dehydrogenase. this malate dehydrogenase was purified to apparent homogeneity using a three-step purification protocol. the parasite malate dehydrogenase had an apparent subunit molecular weight of 32 kda, a ph optimum of 7.0 for the reduction of oxaloacetate, and a sharp thermal transition between 40 degrees c and 45 degrees c. these characteristics distinguish p. falciparum malate dehydrogenase from ...19921542310
single amino acid variation in the ookinete vaccine antigen from field isolates of plasmodium falciparum. 19921542311
two novel alleles within subfamilies of the merozoite surface antigen 2 (msa-2) of plasmodium falciparum. 19921542312
two types of sequence polymorphism in the circumsporozoite gene of plasmodium falciparum.here we demonstrate two characteristically different classes or types of gene sequence variation in the circumsporozoite protein from plasmodium falciparum. some patterns of sequence variation suggest, or are at least consistent with, mendelian inheritance. we show here that patterns of sequence variation at specific positions, however, introduce homoplasy (similarity or identity not directly attributable to common ancestry) into the relationship between parasites. the demonstration of extensive ...19921542315
homologies between the contiguous and fragmented rrnas of the two plasmodium falciparum extrachromosomal dnas are limited to core sequences.plasmodium falciparum contains two extrachromosomal dnas, a 6 kb linear element and a 35 kb circular dna; both encode rdna sequences. the 6 kb element rdnas comprise fragments of both large and small subunit rrnas. comparison of these with corresponding rdna sequences from the 35 kb dna and e. coli show that sequences conserved between the three are largely confined to highly conserved core regions; in fact, most of the 6 kb rdna sequences correspond to core regions. both the 6 kb element and 35 ...19921542578
the pf332 gene of plasmodium falciparum codes for a giant protein that is translocated from the parasite to the membrane of infected erythrocytes.we studied the gene structure of the plasmodium falciparum antigen 332 (ag332). the gene size was estimated to be approx. 20 kb based on the large size of both the transcript found in mature asexual blood stage parasites and mung bean nuclease fragment generated from genomic dna. sequence analysis of genomic and cdna clones representing different regions of the pf332 locus showed that the gene product contains a large number of highly degenerated glutamic acid (glu)-rich repeats (32% glu). the g ...19921544579
treatment of chloroquine-resistant malaria in african children: a cost-effectiveness analysis.because chloroquine (cq)-resistant plasmodium falciparum (crpf) has now spread throughout most of africa, the efficacy and practicability of other drugs such as amodiaquine (aq), and pyrimethamine-sulfadoxine (ps), for the treatment of fever needs to be assessed. we used a decision-analysis model to compare the cost and effectiveness of cq, aq, and ps. the variables considered were the probability of p. falciparum infection, drug compliance, minor and lethal side effects of the drug, the level o ...19921544746
antiparasitic agents.in recent years, introduction of new and more effective agents has improved the overall therapy for parasitic infections. this field, however, is still plagued by numerous problems, including the development of resistance to antimicrobial agents (especially with malaria), unavailability of agents in the united states or lack of approval by the food and drug administration, and major toxicities or lack of experience in pregnant women and children, which limits use in these groups of patients. wid ...19921545596
malaria vaccine on trial at last? 19921546305
transcription of the gene for the merozoite surface antigen msa2 of the human malaria parasite plasmodium falciparum during the asexual cycle.the transcription of the plasmodium falciparum gene for the msa2 antigen has been studied throughout the parasite's asexual growth cycle. for this purpose poly(a)+ rna from different times of the cycle was tested for the presence of the mrna encoding msa2 by in vitro translation and subsequent analysis of the translation products by immunoprecipitation with an antibody against msa2. the results revealed that this mrna is present in trophozoites, reaches the highest concentration during the trans ...19921547892
roles of conserved and allelic regions of the major merozoite surface protein (gp195) in immunity against plasmodium falciparum.the plasmodium falciparum major merozoite surface protein gp195 is a candidate antigen for a vaccine against human malaria. the significance of allelism and polymorphism in vaccine-induced immunity to gp195 was investigated in this study. rabbits were immunized with each of two allelic forms of gp195 that were affinity purified from the fup and fvo parasite isolates. gp195-specific antibodies raised against one allelic form of gp195 cross-reacted extensively with the gp195 of the heterologous al ...19921548068
plasmodium falciparum malaria: evidence for an isotype imbalance which may be responsible for delayed acquisition of protective immunity.in view of the recent demonstration that antibodies that are protective against plasmodium falciparum malaria may act in collaboration with blood monocytes, we investigated the isotype content of sera from individuals with defined clinical states of resistance or susceptibility to malaria. profound differences in the distribution of each immunoglobulin subclass were found. immunoglobulin g1 (igg1) and igg3, two cytophilic isotypes, predominated in protected subjects. in nonprotected subjects, i. ...19921548071
the disposition of oral and intramuscular pyrimethamine/sulphadoxine in kenyan children with high parasitaemia but clinically non-severe falciparum malaria.1. h.p.l.c. methods are described for the measurement of pyrimethamine and sulphadoxine in small volumes of plasma dried on filter paper strips. 2. pyrimethamine/sulphadoxine (fansidar, hoffman laroche) was given by mouth and by intramuscular injection to children with uncomplicated falciparum malaria but with high parasitaemia (n = 8 for both routes; pyrimethamine 1.25 mg kg-1, sulphadoxine 25 mg kg-1). 3. plasma concentrations of pyrimethamine and sulphadoxine associated with synergistic effec ...19921550695
roles of tnf in malaria and other parasitic infections.comprehension of the involvement of cytokines in the host response against invading parasites, to the detriment of the parasite and (in larger doses) to the host, is expanding rapidly. most of these studies, largely for historic reasons and availability, have been done with tnf rather than the other mediators. as is emerging in other fields, study of interleukin-1 alone, and synergistically with tnf and ifn-gamma, warrants further exploration in parasitic diseases. there may well be a similar st ...19921550869
t-cell responses in malaria.malaria is caused by infection with protozoan parasites of the genus plasmodium. it remains one of the most severe health problems in tropical regions of the world, and the rapid spread of resistance to drugs and insecticides has stimulated intensive research aimed at the development of a malaria vaccine. despite this, no efficient operative vaccine is currently available. a large amount of information on t-cell responses to malaria antigens has been accumulated, concerning antigens derived from ...19921554496
plasmodium falciparum malaria in pregnancy: a review. 19921554661
the susceptibility of the indonesian i/cdc strain of plasmodium vivax to chloroquine.a strain of plasmodium vivax from indonesia was adapted to splenectomized aotus and saimiri monkeys and tested for its susceptibility to chloroquine. animals were infected by intravenous inoculation of heparinized parasitized blood and subsequently treated with 8 or 15 mg (base) of chloroquine by oral intubation. recrudescence of infection occurred in 4 of 4 aotus and 5 of 6 saimiri monkeys treated with 15 mg base of chloroquine, indicating a level of resistance between that of the standard ches ...19921556649
in human malaria protective antibodies are directed mainly against the lys-glu ion pair within the lys-glu-lys motif of the synthetic vaccine spf 66.the kek (lysine-glutamic acid-lysine) motif is frequently found in the primary structure of certain malaria proteins involved in invasion, and plays an important role in the interaction of these proteins with the erythrocyte. this motif is contained in a peptide which forms part of the polymeric synthetic malaria vaccine spf 66, currently undergoing extensive human trials. analysis of the antibody titres against the subunit peptides that comprise this vaccine has shown that protection is associa ...19921557226
anti-circumsporozoite protein antibodies measure age related exposure to malaria in kataragama, sri lanka.antibodies to two peptides ddaad and (nanp)40 representing the repetitive sequence of circumsporozoite antigens (cs protein) of p. vivax and p. falciparum respectively were measured in a cohort of 149 and 107 individuals respectively at four, 6 monthly blood surveys performed on residents of kataragama, a p. vivax malaria endemic region in southern sri lanka. the prevalence of antibodies to the cs protein of both species was relatively low being less than 20% to either peptide in the population ...19921557232
determination of the immunization schedule for field trials with the synthetic malaria vaccine spf 66.the synthetic malaria vaccine spf 66 has been shown to be safe, immunogenic and effective in trials performed with controlled groups naturally and experimentally exposed to the disease. in order to continue the trials in open populations, it was necessary to standardize the vaccination characteristics. we have performed four field trials with soldier volunteers with the aim, among others, of defining the number of doses required, the intervals between applications, the protein concentration, and ...19921557233
localization of circumsporozoite protein in the sporogonic stages of plasmodium vivax. 19921557329
the effect of nosematosis on the development of plasmodium falciparum in anopheles stephensi.to quantify the effect of nosema algerae (microsporidia, nosematidae) on the development of plasmodium falciparum in anopheles stephensi (diptera, culicidae), we carried out infection experiments under standardized laboratory conditions. apart from a mean reduction of 69% in oocyst development, smaller numbers of oocysts and fewer sporozoites were found in the nosema-infected mosquitoes. in addition, nosematosis resulted in higher mortality. the potential role of nosema algerae as a biological c ...19921557330
study of the safety and immunogenicity of the synthetic malaria spf66 vaccine in children aged 1-14 years.safety and immunogenicity tests of the spf66 malaria vaccine have been carried out on a population of children, aged 1 to 14 years, in the town of tumaco, colombia. adverse reactions measured after each vaccination were local and minimal, and observed in only a small percentage of the vaccinated children. one year later, no delayed reaction was evident. the majority of the child population developed high antibody titres against spf66 and the degree of response did not vary with age. these induce ...19921557933
the first field trials of the chemically synthesized malaria vaccine spf66: safety, immunogenicity and protectivity.this paper reports the results of the first field study performed to assess the safety, immunogenicity and protectivity of the synthetic malaria vaccine spf66 directed against the asexual blood stages of plasmodium falciparum. clinical and laboratory tests were performed on all volunteers prior to and after each immunization, demonstrating that no detectable alteration was induced by the immunization process. the vaccines were grouped as high, intermediate or low responders according to their an ...19921557934
antibodies to a recombinant glutamate-rich plasmodium falciparum protein: evidence for protection of individuals living in a holoendemic area of liberia.a plasmodium falciparum antigen gene coding for a 220-kd glutamate-rich protein (glurp) has been cloned, and the 783 c-terminal amino acids of this protein (glurp489-1271) have been expressed as a beta-galactosidase fusion protein in escherichia coli. the encoded 783 amino acid residues contain two areas of repeated amino acid sequences. antibodies against recombinant glurp489-1271, as well as against a synthetic peptide corresponding to glurp899-916, and against a synthetic peptide representing ...19921558270
immunoenzymatic labeling of multiple plasmodial salivary gland sporozoites in a single test.a direct, double- and triple-staining immunoenzymatic method detected and differentiated sporozoites by color in anopheles stephensi salivary glands and in mixed sporozoite slide preparations. a double-staining method used beta-galactosidase- and alkaline phosphatase-labeled monoclonal antibodies to the circumsporozoite (cs) proteins of plasmodium berghei and p. falciparum in mosquito salivary glands. the cs proteins were distinguished clearly by the blue-green and red substrate products of beta ...19921558271
reinforcement of immunity in saimiri monkeys following immunization with irradiated sporozoites of plasmodium vivax.to determine the duration of immunity to plasmodium vivax following immunization, six saimiri sciureus boliviensis monkeys were vaccinated with irradiated sporozoites of p. vivax and challenged multiple times with sporozoites. over a period of almost four years, complete protection from repeated challenge with infective sporozoites was demonstrated in one monkey; protection in two monkeys was obtained on eight of nine occasions, in one monkey on seven of nine occasions, in one monkey on six or n ...19921558272
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