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detection of malaria antigen in blood by inhibition elisa.demonstration of parasite associated antigen in blood by inhibition elisa in malaria patients and controls is described. the test was negative in all the healthy controls and positive in 90 per cent of the plasmodium vivax malaria cases. the test was found to be quite sensitive, being able to detect 5 parasites/10(6) rbc in a case of natural p. falciparum infection. there was 95.3 per cent agreement between the results of this test and igm-iif test.19921344943
immunofluorescent reactivity of plasmodium falciparum isolates of different geographic origin. 19921344959
chloroquine and proguanil prophylaxis in travellers to kenya. 19921345987
plasmodium falciparum-infected erythrocytes bind icam-1 at a site distinct from lfa-1, mac-1, and human rhinovirus.the attachment of erythrocytes infected with p. falciparum to human venular endothelium is the primary step leading to complications from severe and cerebral malaria. intercellular adhesion molecule-1 (icam-1, cd54) has been implicated as a cytoadhesion receptor for p. falciparum-infected erythrocytes. characterization of domain deletion, human/murine chimeric icam-1 molecules, and amino acid substitution mutants localized the primary binding site for parasitized erythrocytes to the first amino- ...19921346257
comparison of artemether and chloroquine for severe malaria in gambian children.artemether is an oil-soluble methyl ether of artemesinin (qinghaosu). it has been studied extensively in china, where it has been shown to be rapidly effective in severe falciparum malaria. nearly all the patients studied previously were adults. we have investigated the efficacy of artemether in children with moderate or severe falciparum malaria. in the preliminary study of moderately severe malaria, 30 gambian children were randomised in pairs to receive either intramuscular artemether (4 mg/k ...19921346408
trends in parasitology. living together. 19921346474
plasmodium falciparum: in vitro characterization and human infectivity of a cloned line.the culture-adapted nf54 isolate of plasmodium falciparum was subjected in vitro to three sequential limiting dilution titrations and the resulting clone was given the designation cvd1. dna sequence analysis of the gene encoding the circumsporozoite (cs) protein revealed differences between cvd1 and the published nf54 cs gene. cvd1 had 1191 bp, 397 amino acids, and 42 repeat units while nf54 had 1218 bp, 405 amino acids, and 44 repeat units. the cvd1 clone was more sensitive to chloroquine than ...19921346766
protection of squirrel monkeys against virulent plasmodium falciparum infections by use of attenuated parasites.we previously showed that the uganda palo alto line of plasmodium falciparum propagated in saimiri monkeys and the line maintained in culture in human erythrocytes for many years in our laboratory are genetically unrelated (t. fandeur, s. bonnefoy, and o. mercereau-puijalon, mol. biochem. parasitol. 47:167, 1991). when injected into a splenectomized saimiri monkey, the in vitro-derived palo alto population procured a long-lasting, low-grade parasitemia that was spontaneously resolved by the anim ...19921347760
distinct t cell specificities are induced with the authentic versus recombinant plasmodium berghei circumsporozoite protein.plasmodium berghei sporozoite (spz)-immune lymph node (ln) cells obtained from mice of different h-2 haplotypes were analyzed for the presence of circumsporozoite (cs) protein-reactive t cells in proliferative assays. although lymphocytes from each strain responded in vitro to the priming ag and to the soluble rcs protein, they did not respond to cs protein synthetic peptides. parallel analysis of rcs protein-primed ln cells revealed that the two ag are unequal in generating t cell specificities ...19921348519
a scanning electron microscopic study of the sporogonic development of plasmodium falciparum in anopheles stephensi.the full development of plasmodium falciparum in anopheles stephensi mosquitoes was studied by scanning electron microscopy. ookinetic development was described from in vitro cultures. growing oocysts beneath the basal lamina of the midgut wall mechanically stretch this lamina until it is torn and displaced by day 7. in young oocysts the wall appears smooth. in older oocysts wrinkles in the wall are visible after routine fixation. osmium tetroxide postfixation greatly reduced the occurrence of t ...19921348599
antimalarial activity of orotate analogs that inhibit dihydroorotase and dihydroorotate dehydrogenase.dihydroorotase and dihydroorotate dehydrogenase, two enzymes of the pyrimidine biosynthetic pathway, were purified from plasmodium berghei to apparent homogeneity. orotate and a series of 5-substituted derivatives were found to inhibit competitively the purified enzymes from the malaria parasite. the order of effectiveness as inhibitors on pyrimidine ring cleavage reaction for dihydroorotase was 5-fluoro orotate greater than 5-amino orotate, 5-methyl orotate greater than orotate greater than 5-b ...19921348618
ejection of malaria sporozoites by feeding mosquitoes. 19921348882
an rflp map of the plasmodium falciparum genome, recombination rates and favored linkage groups in a genetic cross.we report a genetic linkage map of the plasmodium falciparum genome, using the inheritance patterns of nearly 90 rflp markers in a genetic cross. markers were assigned to polymorphic loci on all 14 nuclear chromosomes. genetic recombination between parental markers was detected in each of the progeny, indicating that progeny from cross-fertilization events were favored over progeny from self-fertilization of either parent alone. inheritance patterns among the markers suggested that certain paren ...19921349423
plasmodium falciparum: characterization of gene r45 encoding a trophozoite antigen containing a central block of six amino acid repeats.we describe here an antigen, called r45, expressed by the young trophozoites of plasmodium falciparum. this antigen contains a block of tandem repeats of six amino acids which are recognized by sera from humans living in endemic areas. the r45 gene is located on chromosome 3. it is present in all strains examined and shows limited size polymorphism. the c-terminal unique region of the protein shows a strong homology with the catalytic domain of the serine protein kinases. interestingly, the cent ...19921350536
placental malaria and pregnancy outcome.malaria parasitemia was assessed in 312 placentae of singleton deliveries in benin. the prevalence rate was 45.19%. the dominant infecting specie was plasmodium falciparum. high density parasitemia of placental smear in 44.68% was associated with preterm delivery, low birthweight, intrauterine growth retardation and neonatal mortality. placental histological diagnosis of malaria in 57.69% was more frequently associated with intrauterine growth retardation. extraplacental parasitemia decreased bu ...19921350539
the role of t cells in pathogenesis and protective immunity to murine malaria.t-cell-mediated immunity to a virulent strain of plasmodium berghei nk65 (pb nk65) and to an attenuated derivative (pb xat) of the strain were examined in cba mice by the administration of monoclonal antibodies against t-cell subsets or interferon-gamma (ifn-gamma). the injection of anti-cd8+ or anti-ifn-gamma delayed the mortality of mice infected with pb nk65, although it did not affect the parasitaemia. in the late stage of pb nk65 infection, t cells, especially cd8+ t cells, were increased i ...19921350570
the evolutionary origin of plasmodium falciparum. 19921350795
expression of thrombospondin-related anonymous protein in plasmodium falciparum sporozoites. 19921350818
tumour necrosis factor-dependent parasite-killing effects during paroxysms in non-immune plasmodium vivax malaria patients.plasmodium vivax malaria infections in non-immune individuals manifest as periodic clinical episodes of fever with chills and rigors known as paroxysms. we have demonstrated that in non-immune patients the period of paroxysm is associated with the transient presence of plasma factors which kill gametocytes, the intra-erythrocytic sexual stages of the malaria parasite which transmit the infection from humans to mosquito, rendering them non-infectious to mosquitoes. gametocyte killing in paroxysm ...19921351432
treatment of primaquine-resistant plasmodium vivax malaria. 19921353224
selection for high-level chloroquine resistance results in deamplification of the pfmdr1 gene and increased sensitivity to mefloquine in plasmodium falciparum.a chloroquine resistant cloned isolate of plasmodium falciparum, fac8, which carries an amplification in the pfmdr1 gene was selected for high-level chloroquine resistance, resulting in a cell line resistant to a 10-fold higher concentration of chloroquine. these cells were found to have lost the amplification in pfmdr1 and to no longer over-produce the protein product termed p-glycoprotein homologue 1 (pgh1). the pfmdr1 gene from this highly resistant cell line was not found to encode any amino ...19921353446
vector density gradients and the epidemiology of urban malaria in dakar, senegal.the dispersion of anopheline mosquitoes from their breeding places and its impact on malaria epidemiology has been investigated in dakar, senegal, where malaria is hypoendemic and almost exclusively transmitted by anopheles arabiensis. pyrethrum spray collections were carried out along a 910-meter area starting from a district bordering on a permanent marsh and continuing into the center of the city. according to the distance from the marsh, vector density (the number of an. arabiensis per 100 r ...19921354414
epidemiology of plasmodium falciparum in a rice field and a savanna area in burkina faso. comparative study on the acquired immunoprotection in native populations.a longitudinal study, including entomological, parasitological, immunological and clinical data, was carried out in a rice field and a savanna village in burkina faso. in this study, the authors followed the evolution of several parasitological parameters in order to compare the level of immunoprotection in children of these two areas. in particular, the percentages of recently 'infected' or 'recovered' children were calculated, during the interval separating two consecutive surveys. in both are ...19921354928
the antibody response to well-defined malaria antigens after acute malaria in individuals living under continuous malaria transmission.the igg and igm antibody responses to the c-terminal 783 amino acids of the p. falciparum glutamate-rich protein, glurp489-1271, expressed as an e. coli fusion protein, the igg response to a 18-mer synthetic peptide edknekgqheiveveeil (glurp899-916) representing the c-terminal repeats of glurp, and a synthetic peptide (eenv)6 representing the c-terminal repeats from pf155/resa, were investigated longitudinally in 13 children and 7 adults living under conditions of continuous, intense malaria tra ...19921354931
mini- and micro-satellites in the genome of rodent malaria parasites.higher eukaryotes contain within their dna numerous arrays of repetitive dna, many of which are known as satellite dnas and display extensive variability. the presence of these repeats has been demonstrated for various species and they have been used for genetic identification and classification. here, it is demonstrated that southern hybridisation of dna from rodent malaria parasites allows detection of micro- and minisatellite sequences in the genome of plasmodium species. closely related line ...19921355061
chemoresistance of plasmodium falciparum in central africa. 19921355183
attenuation of malaria infection, paralysis and lesions in the central nervous system by low protein diets in rats.young wistar rats developed a fulminant infection when inoculated with the rodent malaria parasite plasmodium berghei. rats that died during the infection exhibited a progressive paralysis of the extremities, a rapidly decreasing body temperature and minute haemorrhages in the brain. increasing the level of protein in the diet from 4 to 8 and 16% was accompanied by an increase in morbidity and mortality from 15 to 40 and 90% respectively on day 6 of the infection. increasing the level of dietary ...19921356299
relationships between circulating s-antigens, naturally acquired antibodies to plasmodium falciparum exoantigens and malaria attack in a mesoendemic area.a survey involving 77 individuals living in two savannah villages near bobo dioulasso (burkina faso, west africa), was performed in june 1987 (before), august-september (during) and january 1988 after the seasonal transmission. the clinical longitudinal study during the seasonal period permitted us to define three different groups in terms of both age and occurrence of malaria attack (ma; greater than or equal to 5000 parasites/mm3 of blood and axillary fever greater than or equal to 37.8 degree ...19921356300
inhibition of the growth of plasmodium falciparum and plasmodium berghei in vitro by an extract of cochlospermum angolense (welw.).an extract of cochlospermum angolense (welw.) is used in the traditional medicine of angola for the therapy of icterus and for the prophylaxis of malaria. from the roots of this plant red crystalline substances have been isolated and tested for their effect on plasmodium falciparum in vitro and on the dna and protein synthesis of plasmodium berghei. the multiplication of p. falciparum was decreased to 50% of the control in the presence of 10 micrograms/ml extracted material and there was a total ...19921356304
de novo biosynthesis of heme offers a new chemotherapeutic target in the human malarial parasite.the human malarial parasite, plasmodium falciparum, has been found to synthesize heme de novo, despite the accumulation of large quantities of polymeric heme derived from the hemoglobin of the red cell host. the parasite delta-aminolevulinate dehydrase level is significantly lower than that of the host and its inhibition by succinylacetone leads to inhibition of parasite protein synthesis and viability.19921356337
[contribution of molecular genetics to the understanding of chemoresistance of plasmodium falciparum].resistance to pyrimethamine and proguanil is due to a single point mutation in the gene that codes for dihydrofolate reductase. a single mutation gives rise to resistance to only one of the drugs. resistance to both drugs results from several mutations. chloroquine resistance phenotype is due to a rapid efflux of the drug from the parasite's digestive vacuole. this efflux is associated with a transmembrane permeability glycoprotein, or p-gp, which is similar to the protein implicated in the mult ...19921356539
aberrations in cerebral vascular functions due to plasmodium yoelii nigeriensis infection in mice.plasmodium yoelii nigeriensis infection in mice caused an increase in uptake of 125i-labeled bovine serum albumin, 51cr-labeled erythrocytes and evans blue dye from peripheral circulation into the brain. isolated cerebral microvessels which were characterized in terms of their morphology under scanning electron microscope and enhancement of the specific activities of biochemical markers, viz. alkaline phosphatase, gamma-glutamyl transpeptidase, and monoamine oxidase, showed significant decrease ...19921356826
functional characterization of protective cd4+ t-cell clones reactive to the murine malaria parasite plasmodium chabaudi.protective immunity to asexual malaria parasites appears to be mediated predominantly by the cd4+ subset of t lymphocytes. to examine the role of this t-cell population in the immune response to the murine malaria parasite plasmodium chabaudi, cd4+ clones derived from infected mice were raised and propagated in vitro. analysis of the reactivity of clones responsive to parasite antigen demonstrated that the cd4+ cell response is heterogeneous and is consistent with the idea of two functionally di ...19921356918
"pseudo-resistant" malaria in tropical countries.tropical disease physicians are challenged by drug-resistant plasmodium falciparum. well-documented effects of resistance on malaria morbidity and mortality among people in tropical countries do not exist. observed resistant malaria in these countries may consist of true and false positive cases particularly in urban and suburban areas of sub-saharan africa. who recommends systematic treatment with an antimalarial drug for persons with fever in these areas. yet clinicians should have more in ...19921357307
halofantrine and acute intravascular haemolysis. 19921357314
most residues on the floor of the antigen binding site of the class i mhc molecule h-2kd influence peptide presentation.a panel of 15 single alanine substitutions on the floor of the peptide binding groove of the murine class i histocompatibility molecule h-2kd has been analyzed. all but two mutant molecules were expressed on the cell surface, and were tested for peptide binding and presentation to specific cytotoxic t lymphocytes. eleven out of 13 mutant molecules appeared to be functionally altered. five of the substituted residues were involved in the presentation of all peptides tested. three participated in ...19921358191
usefulness of clinical case-definitions in guiding therapy for african children with malaria or pneumonia.the world health organisation has developed disease-specific clinical case-definitions to guide management of children with fever or cough, the cardinal signs of malaria and pneumonia. to assess the usefulness of the case-definitions and to investigate their interaction, we studied children with fever or cough brought to a hospital in lilongwe, malawi. for all children, a thick blood smear was examined for plasmodium falciparum parasites. chest radiography was done only for children with parasit ...19921359219
comparison of oral artemether and mefloquine in acute uncomplicated falciparum malaria.plasmodium falciparum malaria in thailand is highly resistant to available antimalarials, and alternative drugs are needed urgently. artemether is effective against falciparum malaria but associated with a high recrudescence rate. the proper dosage regimen remains to be defined. we have done a clinical trial comparing mefloquine 1250 mg in divided doses with oral artemether at 700 mg total dose given over 5 days in acute uncomplicated falciparum malaria. 46 patients, admitted to the bangkok hosp ...19921359318
primary sequences of two p-glycoprotein genes of entamoeba histolytica.two p-glycoprotein genes (ehpgp1 and ehpgp2) from the protozoan parasite entamoeba histolytica were sequenced from a genomic library made with the dna of an emetine-resistant ameba mutant, which overexpresses mrnas homologous to segments of the human mdr1 (p-glycoprotein) gene. the open reading frames for ehpgp1 and ehpgp2 were 1302 and 1310 amino acids long, respectively, and showed a 67% positional identity with each other and 41% and 40% positional identities, respectively, with human mdr1 ge ...19921359408
identification and quantification of rodent malaria strains and species using gene probes.a dna probe pcsv4 and a subclone thereof pcsv4.1, hybridize specifically to rodent malaria dna. dna purified from a small volume (10 microliters) of infected mouse blood was used to determine the composition of the parasite population present. the hybridization signal following pcsv4 probing of slot-blotted dna correlated directly with parasitaemia. the hybridization pattern and intensity, resulting from probing restriction enzyme digested and southern-blotted genomic dna, determined the identit ...19921359498
the reservoir of plasmodium falciparum malaria in a holoendemic area of western kenya.the reservoir of infectious plasmodium falciparum gametocytes in a population living in an area of holoendemic malaria in western kenya was estimated by directly feeding mosquitoes on volunteers. resulting mosquito infections were assessed both by midgut examination for oocysts and by enzyme-linked immunosorbent assay for p. falciparum circumsporozoite antigen. calculations based on the age structure of the population and the resulting rates of mosquito infections indicated that children under 1 ...19921359683
comparative evaluation of the colony-stimulating factors induction potential of plasmodium cynomolgi-infected monkey erythrocytes and soluble antigens.plasmodium cynomolgi total antigens soluble in culture medium (p.c.sa), and noninfective p. cynomolgi-infected monkey erythrocytes (p.c.ie) were compared for their potential to induce colony-stimulating factors (csfs). when injected intravenously in monkeys, both preparations induced an increase in the serum csfs levels; p.c.ie appeared to be 1.6-fold more potent than the p.c.sa. in vitro p.c.ie induced 1.8-fold more csf by monkey blood monocyte-derived macrophages than p.c. however, both in viv ...19921359752
plasmodicidal effect of desferrioxamine b in human vivax or falciparum malaria from thailand.desferrioxamine b (dfo, desferal), an iron chelator, was earlier shown to be active against plasmodium falciparum in vitro and in vivo. the present open pilot study served to assess its clinical tolerability and efficacy in human malaria under hospital conditions. continuous intravenous dfo was administered to 28 thai males at a dose of 100 mg/kg over 24 h for 3 consecutive days. no other antimalarial therapy was administered unless recrudescence had occurred. the first 14 patients had symptomat ...19921359761
spurious malarial antibodies in hiv infection. 19921360116
"pseudo-resistant" malaria in tropical countries. 19921360133
malaria. another route to a vaccine? 19921360149
pregnancy complicated by malaria, precipitate labor and uterine rupture.a case of plasmodium falciparum malaria is reported in a 25-year-old pregnant woman with a history of three previous cesarean sections. she developed premature precipitate labor which was complicated by stillbirth, uterine rupture, bladder and vaginal tears necessitating hysterectomy.19921360427
antigenic diversity and variation in blood stages of plasmodium falciparum. 19921360446
cerebral ammonia levels and enzyme changes during plasmodium yoelii infection in mice.ammonia, lactate and glutamate levels and the activities of glutamine synthetase (gs), glutamate dehydrogenase (gdh), glutaminase (gln), aspartate transaminase (ast), phosphofructokinase (pfk) and monoamine oxidase (mao) were compared in the brain tissue of normal and p. yoelii infected mice. the brain lactate increased by 96% at peak parasitaemia. cerebral ammonia also exhibited an increase in infected mice which was parasitaemia dependent, while glutamate remained almost unchanged. the brain g ...19921361009
malaria vaccine strategy. 19921361327
the level of anti-sporozoite antibodies in a highly endemic malaria area and its relationship with exposure to mosquitoes. kilombero malaria project.the relationship between the humoral immune response to the conserved repeated epitope of the plasmodium falciparum sporozoite and exposure to the mosquito vectors was examined in a study carried out in rural southern tanzania, an area highly endemic for malaria. considerable aggregation of the immune response between houses was observed. a statistically significant portion of this aggregation could be explained by differences in individual exposure to mosquitoes. however, two-thirds of the vari ...19921362013
leukocyte integrin activation.certain stages of the immune response require interaction of leukocytes with each other and with non-hematopoietic cells. one of the systems implicated in these interactions involves an integrin, lfa-1 (lymphocyte function antigen-1), expressed by all leukocytes at their cell surface, and a molecule belonging to the immunoglobulin superfamily, icam-1 (intercellular adhesion molecule-1). the avidity of lfa-1 for icam-1 is transient. it is modulated both by regulation of icam-1 expression and by a ...19921362459
modelling the immune response to malaria with ecological concepts: short-term behaviour against long-term equilibrium.a model for the human immune response to the malaria parasite plasmodium falciparum is used to analyse the dynamics of an infection within an individual patient. previous models either looked at competition between two parasite genotypes or at one parasite clone and the immune response to it. this model describes the course of an infection caused by the blood stages of two parasite genotypes differing in reproductive rate and in the immune response they elicit. the interactions between the genot ...19921362993
preferential expression and activity of multidrug resistance gene 1 product (p-glycoprotein), a functionally active efflux pump, in human cd8+ t cells: a role in cytotoxic effector function.the multidrug resistance gene 1 (mdr 1) product, the p-glycoprotein (pgp), is a 170-kd transmembrane transport protein, whose overexpression is associated with multidrug resistance in cancer cells and in chloroquine-resistant plasmodium falciparum infection. in this study we show that normal freshly isolated human lymphocytes express low levels of mdr 1 mrna and membrane pgp. although pgp is expressed in both cd4+ and cd8+ t cells, it is preferentially expressed in cd8+ t cells. activation of t ...19921363104
malaria entomological inoculation rates in western venezuela.over 61,000 anophelines collected between january 1988 and october 1989 in three villages in western venezuela were assayed by elisa for plasmodium vivax circumsporozoite (cs) protein. the six specimens confirmed positive belonged to three species: anopheles (nyssorhynchus) nuneztovari gabaldón, 1940, a. albitarsis arribalzaga, 1878 sensu lato and a. oswaldoi (peryassu, 1922). the estimated cs protein rate for all species combined was 0.01% (95% confidence limits 0.004-0.02%). this cs protein ra ...19921363181
p-glycoprotein genes of entamoeba histolytica.six different p-glycoprotein gene segments were identified from an emetine-resistant e. histolytica mutant, which overexpresses mrnas homologous to segments of the human mdr1 (p-glycoprotein) gene. the open reading frames of two completely sequenced genes ehpgp1 and ehpgp2 were 1,302 and 1,310 amino acids long, respectively, and showed a 67% positional identity with each other and 41 and 40% positional identities, respectively, with human mdr1 gene. within each ameba p-glycoprotein were the atp- ...19921364101
malaria parasites, vectors and biologic cycle. 19921364119
the pf332 gene codes for a megadalton protein of plasmodium falciparum asexual blood stages.we characterized the plasmodium falciparum antigen 332 (ag332) which is specifically expressed during the asexual intraerythrocytic cycle of the parasite. the corresponding pf332 gene has been located in the subtelomeric region of chromosome 11. furthermore, it is present in all strains so far analyzed and shows marked restriction length fragment polymorphism. partial sequence and restriction endonuclease digestion of cloned fragments revealed that the pf332 gene is composed of highly degenerate ...19921364200
transmission immunity in malaria: reflections on the underlying immune mechanisms during natural infections and following artificial immunization.malaria transmission-blocking immunity has been studied in natural malarial infections in man, during infections in animals and following artificial immunization of animals with sexual stage malaria parasites. effective immunity, which prevents infectivity of a malarial infection to mosquitoes, has been observed under all of these circumstances. two general types of effector mechanism have been identified. one is an antibody mediated mechanism which acts against the extracellular sexual stages o ...19921364201
t cell responses to repeat and non-repeat regions of the circumsporozoite protein detected in volunteers immunized with plasmodium falciparum sporozoites.the design of a malarial vaccine based on the circumsporozoite (cs) protein, a major surface antigen of the sporozoite stage of the malaria parasite, requires the identification of t and b cell epitopes for inclusion in recombinant or synthetic vaccine candidates. we have investigated the specificity and function of a series of t cell clones, derived from volunteers immunized with plasmodium falciparum sporozoites, in an effort to identify relevant epitopes in the immune response to the pre-eryt ...19921364202
south american monkeys in the development and testing of malarial vaccines--a review.south american aotus and saimiri monkeys, which are susceptible to infection with human malarias, have been used to develop models for the testing of human malaria vaccines. studies indicate that blood-stage and sporozoite vaccines can be tested in these monkeys using appropriate strains of parasites.19921364203
the biological and epidemiological basis of drug resistance in malaria parasites.natural populations of plasmodium falciparum without previous drug exposure are mixtures of individual parasites with different levels of response to a specific medicament. exposure to sublethal drug concentrations will eliminate the highly and moderately sensitive individuals. the less sensitive part of the parasite population is being selected and given the opportunity of propagating. underdosed mass drug administration and subcurative medication have this direct effect. an indirect effect wit ...19921364857
dynamics of multi-drug resistance in plasmodium falciparum in thailand.since the initial report of resistance of plasmodium falciparum to chloroquine in 1960 in the thai-cambodian border resistance to alternative drugs occurred early after their introduction. this development is considered to be the result of population migration and excessive drug pressure along with the presence of a multi-resistance gene within the parasite population. multi-resistant strains as such have been disseminated throughout the country by returning migrant populations.19921364859
in vitro sensitivity of plasmodium falciparum to chloroquine and other antimalarials in east timor and east kalimantan, indonesia.in indonesia resistance of plasmodium falciparum to chloroquine has spread to all provinces except yogyakarta since the first report in 1974. the proportion of resistant cases is relatively low except in irian jaya and east timor. the results of in vitro tests performed in east timor showed 81.0% resistance to chloroquine, 87.5% to amodiaquine, 20.0% to sulfadoxine-pyrimethamine (s-p), 4.8% to mefloquine, and 100% sensitivity to quinine. the percentage of failures was between 11.1% and 71.4% and ...19921364861
malaria in cambodia.there are around half a million cases of malaria with 5-10,000 deaths per year in cambodia. incidence rates vary in different parts of the country. malaria control is hampered by multiple drug resistance of plasmodium falciparum, inaccessibility to the major vector, poor security in most malarious areas, and lack of resources. the control strategy emphasises improvement of clinical management and provision of prompt and accurate diagnosis in order to reduce morbidity and to prevent mortality. in ...19921364864
the malaria situation and antimalaria program in laos.malaria is endemic in all 17 provinces of laos. transmission is perennial with a "seasonal peak" coinciding with the rainy season. the vectors anopheles minimus and an. balabacensis (=dirus) remain susceptible to ddt. chloroquine-resistance of plasmodium falciparum is at the ri-rii level. multidrug resistance is not yet a problem. major constraints of the antimalaria program involve logistics and operational problems solutions to which are specifically addressed in the recommendations.19921364866
current status of malaria in malaysia.the malaria eradication program was started in 1967 in peninsular malaysia. since then and up to 1980, there was a reduction in the number of reported malaria cases from 160,385 in 1966 to 9,110 cases for peninsular malaysia. although the concept of eradication has changed to one of control in the 1980, the anti-malaria activities have remained the same. however, additional supplementary activities such as the use of impregnated bednets, and the primary health care approach, have been introduced ...19921364867
overview: immunology of malaria and progress in malaria vaccine development. 19921364871
overview: clinical pharmacology of antimalarials.the effectiveness of antimalarials depends on its pharmacodynamics ie inhibitory effect on the parasites and unwanted effects on the host. it also depends on the pharmacokinetics of the drugs. the ideal antimalarials are drugs that show curative activity in the absence of toxicity to the host. recommendation for antimalarial dosage regimens should be based on pharmacokinetic and pharmacodynamic studies in appropriate populations ie ethnic groups, adults children, and in pregnancy. chloroquine re ...19921364873
trends and controversies in the prophylaxis and treatment of malaria.several areas of clinical concern and investigation have emerged over the past year in the malaria field. mefloquine prophylaxis has required a change in its dosing regimen. continued monitoring for potential mefloquine toxicity has shown this agent to be safe for use for many populations, but not routinely for pregnant women or for young children. chloroquine-resistant plasmodium vixax may be geographically limited currently, but its presence in irian jaya has serious implications, should be pr ...19921365530
plasmodial hemoglobin degradation: an ordered pathway in a specialized organelle.during its intraerythrocytic development, the malarial parasite devours most of the hemoglobin in its host cell. this enormous catabolic process is achieved through an ordered, efficient degradative pathway that takes place in a specialized organelle, the digestive vacuole. the amino acids generated are used by the parasite for its growth and maturation; the heme released is polymerized into a crystalline matrix called hemozoin. we are beginning to understand the special enzymes that participate ...19921365547
effects of mutations altering sos regulation on a nalidixic acid-inducible system for the production of heterologous proteins in escherichia coli.the major leftward early promoter of phage lambda pl, has frequently been used to drive expression of heterologous genes in escherichia coli. pl is typically maintained fully repressed by the lambda cl protein. when induction of heterologous protein synthesis is desired, one of several potential mechanisms of destroying cl function is employed and the expression of the foreign gene commences. one method of derepressing pl involves exposing cells to nalidixic acid, which results in the "activatio ...19901366870
malaria vaccines--progress and problems.developing a vaccine against malaria is a major priority of the who. a decade of research exploiting the techniques of molecular biology has yielded a series of potentially protective vaccines. however, progress has been frustrated by the complexity of the parasite's life cycle and the antigenic diversity exhibited by each stage. although candidate vaccines are now entering human trials, questions still arise concerning the nature of a successful malaria vaccine and who will benefit from it.19911367848
malaria transmission-blocking vaccines.antibodies to surface proteins of the sexual stages of plasmodium falciparum block completely the transmission of these malaria parasites. transmission-blocking vaccines therefore represent a powerful and novel approach to controlling the spread of this lethal disease.19921368880
human dermal microvascular endothelial but not human umbilical vein endothelial cells express cd36 in vivo and in vitro.cd36 is an 88-kda glycoprotein that has been identified on platelets, monocytes, and some endothelial cells. experimental evidence suggests that cd36 mediates the binding of plasmodium falciparum-infected rbc to a variety of cells, and therefore may play a role in the vascular complications associated with malaria. additionally, cd36 may also bind the extracellular matrix proteins thrombospondin and collagen. human umbilical vein endothelial cells have been used in in vitro models examining the ...19921370173
protection against malaria in aotus monkeys immunized with a recombinant blood-stage antigen fused to a universal t-cell epitope: correlation of serum gamma interferon levels with protection.the major surface antigen p190 of the human malaria parasite plasmodium falciparum contains nonpolymorphic, immunogenic stretches of amino acids which are attractive components for a subunit vaccine against malaria. one such polypeptide, termed 190l, is contained in the 80-kda processing product of p190, which constitutes the major coat component of mature merozoites. we report here that immunization of aotus monkeys with 190l gives only poor protection against p. falciparum challenge. however, ...19921370271
promiscuous malaria peptide epitope stimulates cd45ra t cells from peripheral blood of nonexposed donors.pbl from individuals with no history of malaria exposure, as well as cord blood lymphocytes, were tested for proliferation to t cell epitopes from the malaria circumsporozoite proteins of plasmodium falciparum and plasmodium vivax. cells from many individuals proliferated in response to these peptides, but for two peptides (p. vivax317-336 and p. falciparum cs331-350) the response rate ranged from 64 to 93%, with the specific stimulation indices reaching as high as 38. the phenotype of the cells ...19921370523
the binding site on icam-1 for plasmodium falciparum-infected erythrocytes overlaps, but is distinct from, the lfa-1-binding site.the intercellular adhesion molecule-1 (icam-1, cd54) is one of three putative endothelial receptors that mediate in vitro cytoadherence of p. falciparum-infected erythrocytes. since cytoadherence to postcapillary venular endothelium is thought to be a major factor in the virulence of p. falciparum malaria, we have examined the interaction between icam-1 and the p. falciparum-infected cell, and have compared it with the interaction to the physiological counter receptor, the leukocyte integrin lfa ...19921370656
comparative study of the t cell response to two allelic forms of a malarial vaccine candidate protein.t cell responses to two allelic forms of the merozoite surface ag 2 (msa2) of plasmodium falciparum were mapped in mice using the rmsa2 proteins, ag 1609 which has the sequence of the fcq27/png strain and ag 1615 which has the sequence of the indochina 1 strain. lymph node cells of bl/10 and b10.br mice immunized with either ag 1609 or ag 1615 responded to both ag in in vitro proliferation assays. lymph node cells of balb/c mice did not respond. the t cell determinants recognized by the responde ...19921371134
structure and expression of the gene for pv200, a major blood-stage surface antigen of plasmodium vivax.molecular cloning and structure analysis of the gene encoding the pv200 protein of the sal-1 strain of plasmodium vivax revealed an overall identity of 34-37% when the deduced amino acid sequence was compared with the sequences of various major merozoite surface antigens of plasmodium falciparum, plasmodium yoelii and plasmodium chabaudi. when the sal-1 pv200 sequence was compared with the corresponding sequence from the belèm strain of p. vivax, it was found that the two merozoite surface antig ...19921371329
inhibitory activity against sporozoites induced by antibodies directed against nonrepetitive regions of the circumsporozoite protein of plasmodium vivax.in previous studies, saimiri sciureus boliviensis monkeys have been immunized with four recombinant proteins reproducing part of the circumsporozoite (cs) protein of plasmodium vivax sporozoites (ns1(81) v20, rpvcs-1, rpvcs-2, rpv-cs-3), or with irradiated sporozoites of p. vivax salvador i strain. to analyze the antibody response elicited against epitopes located outside the immunodominant repeat region of the cs protein, serum samples from these animals were tested for their ability to inhibit ...19921371470
"universal" t helper cell determinants enhance immunogenicity of a plasmodium falciparum merozoite surface antigen peptide.synthetic peptide constructs containing a limited number of epitopes are being currently investigated as subunit vaccines against a variety of pathogens. however, because of widespread nonresponsiveness to most such constructs, possibly attributable to mhc restriction, the choice of appropriate carrier molecules to enhance immunogenicity of peptides constitutes an important and essential aspect of designing synthetic immunogens for human use. widely used vaccines such as tetanus toxoid (tt) have ...19921371529
longitudinal study of plasmodium falciparum polymorphic antigens in a malaria-endemic population.plasmodium falciparum merozoite surface antigens msp1 and msp2 and an exported antigen, exp-1, exhibit allelic polymorphism in natural populations. to explain this, one hypothesis is that antigen polymorphisms are maintained by frequency-dependent immune selection. an expectation of the hypothesis is that rare variants have an advantage over common variants because of a lower level of acquired immunity against them and thus increase in frequency until an equilibrium is attained. to test this hyp ...19921371764
plasmodium falciparum-infected erythrocytes do not adhere well to c32 melanoma cells or cd36 unless rosettes with uninfected erythrocytes are first disrupted.plasmodium falciparum malaria parasites modify the human erythrocytes in which they grow so that some parasitized erythrocytes (pe) can cytoadhere (c+) to host vascular endothelial cells or adhere in rosettes (r+) to uninfected erythrocytes. these c+ and r+ adherence properties of pe appear to mediate much of the pathogenesis of severe malaria infections, in part by blocking blood flow in microvessels. from one parasite strain, pe were selected in vitro for c+ r+ or c+ r- adherence properties an ...19921371771
the movement of fluorescent endocytic tracers in plasmodium falciparum infected erythrocytes.the fluorescent lipophilic probe 1,1'-dihexadecyl-3-3'-3-3'- tetramethylindocarbocyanine (diic16) inserted in the red cell surface, functioned as a non-exchangeable lipid marker which was not metabolised or toxic in plasmodial cultures. invasion by plasmodium falciparum resulted in the internalisation of the lipid, suggesting the uptake of red cell membrane components during parasite entry. the fluorescent lipid was not transported from red cell to parasite membranes at subsequent stages of deve ...19921371847
flow cytometric two-color staining technique for simultaneous determination of human erythrocyte membrane antigen and intracellular malarial dna.a novel fixative and permeabilization method is described which allows simultaneous flow cytometric detection of red blood cell membrane antigen and intracellular malaria parasites. to illustrate the method, red blood cells from patients with paroxysmal nocturnal hemoglobinuria were infected with plasmodium falciparum and maintained in synchronous red blood cell culture. the infected red blood cells were immunolabeled with antibodies directed to the complement regulatory protein decay-accelerati ...19921372210
the in vivo cytotoxic activity of cd8+ t cell clones correlates with their levels of expression of adhesion molecules.cd8+ t cell clones specific for a defined epitope present in the circumsporozoite protein of plasmodium yoelii display striking differences in their in vivo antiplasmodial activity. the adoptive transfer of certain clones (ya23 and ya26) into naive mice inhibits by 90% or more the development of liver stages of malaria parasites and protects against malaria infection. the adoptive transfer of two other t cell clones (yb8 and ya15) results, respectively, in partial or no inhibitory activity on pa ...19921372647
antibody response to the circumsporozoite protein of plasmodium vivax in naturally infected humans.the circumsporozoite (cs) protein of plasmodium vivax consists of a central repeat region flanked by highly conserved non-repeat regions. serum samples from 33 individuals with naturally acquired infections of p. vivax were tested for antibodies to four antigens representing the vivax cs protein. three recombinant proteins containing different overlapping sequences in the non-repeat regions and either the entire central repeat region (vivax-1 and vivax-2) or two of the repeat sequences (vivax-3) ...19921373042
sequence variation in the tripeptide repeats and t cell epitopes in p190 (msa-1) of plasmodium falciparum from field isolates.the n-terminal part of p190, the precursor to the major merozoite surface antigens of plasmodium falciparum, contains the t and b cell epitopes and tripeptide repeats. the p190 gene exhibits allelic dimorphism, but the tripeptide repeat-encoding region is the only exception to the dimorphic variations of the gene. to date, sequences available to document variations in the epitopes are very limited. thus, in this study, the extent of the variation in these regions was analyzed using the polymeras ...19921373473
prevalence and level of antibodies to the circumsporozoite proteins of human malaria parasites, including a variant of plasmodium vivax, in the population of two epidemiologically distinct areas in the state of acre, brazil.a seroepidemiological study of the prevalence of antibodies against the repeating epitopes of circumsporozoite (cs) proteins of human malaria parasites was conducted in 2 different areas in the state of acre, brazil in 1987 and 1990. in 1987 antibodies against the cs protein of the vk 247 variant plasmodium vivax as well as antibodies against the cs proteins of p. falciparum and the classic p. vivax were found at relatively high rates in the 2 areas, but significant microepidemiological differen ...19921373529
apparent lack of n-glycosylation in the asexual intraerythrocytic stage of plasmodium falciparum.this study investigates protein glycosylation in the asexual intraerythrocytic stage of the malaria parasite, plasmodium falciparum, and the presence in the infected erythrocyte of the respective precursors. in in vitro cultures, p. falciparum can be metabolically labeled with radioactive sugars, and its multiplication can be affected by glycosylation inhibitors, suggesting the capability of the parasite to perform protein-glycosylation reactions. gel-filtration analysis of sugar-labeled malaria ...19921374032
a primate model for human cerebral malaria: plasmodium coatneyi-infected rhesus monkeys.a major factor in the pathogenesis of human cerebral malaria is blockage of cerebral microvessels by the sequestration of parasitized human red blood cells (prbc). in vitro studies indicate that sequestration of prbc in the microvessels is mediated by the attachment of knobs on prbc to receptors on the endothelial cell surface such as cd36, thrombospondin (tsp), and intercellular adhesion molecule-1 (icam-1). however, it is difficult to test this theory in vivo because fresh human brain tissues ...19921374220
transcription mapping of a 100 kb locus of plasmodium falciparum identifies an intergenic region in which transcription terminates and reinitiates.we have mapped plasmodium falciparum erythrocytic stage transcription units on chromosome 10 in the vicinity of the gene encoding the glycophorin binding protein (gbp130) using yeast artificial chromosomes (yacs). three erythrocytic stage transcription units are clustered in a 40 kb region. two of these genes are closely linked, separated by less than 2 kb. nuclear run-on data demonstrate that transcription of these two genes, though unidirectional, is monocistronic. within this intergenic regio ...19921374714
the increased k+ leak of malaria-infected erythrocytes is not via a ca(2+)-activated k+ channel.charybdotoxin and nitrendipine both inhibited k+(86rb+) influx via the ca(2+)-activated channel of uninfected erythrocytes but had no effect on k+(86rb+) transport in malaria-infected cells. activation of the channel in uninfected cells in which the cytoplasmic [na+]/[k+] ratio was adjusted to be comparable with that of late-stage malaria-infected erythrocytes resulted in a large (nitrendipine-sensitive) increase in k+(86rb+) influx. these results suggest that the endogenous ca(2+)-activated k+ ...19921375512
a protective monoclonal antibody with dual specificity for plasmodium falciparum and plasmodium berghei circumsporozoite proteins.an igm monoclonal antibody (mab 36) which reacts with the circumsporozoite (cs) proteins of both p. falciparum and p. berghei was isolated from plasmodium falciparum sporozoite-immunized mice. in assays of biological activity, mab 36 induces the cs precipitation reaction with live sporozoites and blocks the invasion of hepatoma cells by sporozoites in vitro at concentrations much lower than those observed for previously reported cs protein-specific monoclonal antibodies. mab 36 also provided com ...19921375561
human platelet glycoprotein iiib binds to thrombospondin fragments bearing the c-terminal region, and/or the type i repeats (csvtcg motif), but not to the n-terminal heparin-binding region.major blood membrane platelet glycoprotein iiib (gpiiib), also termed gpiv or cd365, has been identified as a receptor for thrombospondin (tsp), collagen and plasmodium falciparum-infected erythrocytes. the aim of the present study was to identify region(s) of tsp involved in binding of gpiiib. proteolytic fragments of tsp (m(r) 140 kda, 120-18 kda and 27 kda on sds/page under reducing conditions) were purified by f.p.l.c. and identified by n-terminal gas-phase sequencing, e.l.i.s.a. and western ...19921376110
human recognition of t cell epitopes on the plasmodium vivax circumsporozoite protein.in order to identify t cell epitopes recognized by human in the plasmodium vivax circumsporozoite protein, 28 overlapping synthetic peptides spanning the entire circumsporozoite protein were tested for their ability to stimulate proliferation of pbmc from 22 adults living in a malaria-endemic area of the colombian pacific coast and from four individuals who never had a history of malaria infection. in addition, balb/c mice were immunized with pools of peptides, and their lymph node cells were st ...19921376347
effect of adjuvant formulations on the selection of b-cell epitopes expressed by a malaria peptide vaccine.because subunit vaccines may create artificial epitopes, the goal of this study was to concentrate the immune response toward protective epitopes contained in a peptide, [(nagg)5]y. this peptide consisted of five repeat sequences of the immunodominant epitope of the circumsporozoite protein of the simian malaria parasite plasmodium cynomolgi and a terminal tyrosine. it was conjugated to bovine serum albumin and mixed with various adjuvant formulations, including block copolymers l121, l141, l180 ...19921377851
human antibody responses to epitopes on the plasmodium falciparum gametocyte antigen pfs 48/45 and their relationship to infectivity of gametocyte carriers.antibodies in human sera recognizing epitopes i, iia, iii, and iv on the plasmodium falciparum gametocyte antigen pfs 48/45 have been investigated by competitive enzyme-linked immunosorbent assay. more than one-third of the residents of three villages in madang, papua new guinea responded to epitopes i, iia and iii, with little variation by village or with time. there was a bimodal distribution of positive sera by age, with the highest proportion of responders in the 5-9- and greater than 20-yea ...19921377881
use of human universally antigenic tetanus toxin t cell epitopes as carriers for human vaccination.synthetic constructs were assembled as multiple ag peptide systems containing repetitive sequences of plasmodium falciparum and plasmodium berghei, the causative agents of human and murine malaria respectively, and two universal human tetanus toxin t cell epitopes 830-843 and 947-967. these constructs were tested for antibody production in mice and for their capacity to stimulate human pbl and tetanus toxin-specific t cell clones. a high antibody titer can be obtained in mice when multiple ag pe ...19921378079
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