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a malaria merozoite surface protein (msp1)-structure, processing and function.merozoite surface protein-1 (msp-1, also referred to as p195, pmmsa or msa 1) is one of the most studied of all malaria proteins. the protein is found in all malaria species investigated and structural studies on the gene indicate that parts of the molecule are well-conserved. studies on plasmodium falciparum have shown that the protein is in a processed form on the merozoite surface, a result of proteolytic cleavage of the large precursor molecule. recent studies have identified some of these c ...19921343716
transmission factors in malaria epidemiology and control in africa.genetic and environmental components of factors contributing in malaria transmission are reviewed. particular attention is given to density dependent regulation of vector populations in relation to the survival rate of anophelines. the expectation of vector control activities are different according to the epidemiological characteristics of malaria, mainly its stability. in areas with perennial and high transmission (stable malaria) vector control could reduce malaria related morbidity and morta ...19921343718
mechanisms of protective immunity against asexual blood stages of plasmodium falciparum in the experimental host saimiri.in the saimiri monkey, an experimental host for human malaria, acquired protection against plasmodium falciparum blood stages depends on the igg antibody populations developed. in vivo protective anti-falciparum activity of igg antibodies is correlated with the in vitro opsonizing activity promoting phagocytosis of parasitized red blood cells. in contrast, non protective antibodies inhibit this mechanism by competing at the target level. a similar phenomenon can be observed in human infection. a ...19921343720
protection of aotus monkeys after immunization with recombinant antigens of plasmodium falciparum.the genus aotus spp. (owl monkey) is one of the who recommended experimental models for plasmodium falciparum blood stage infection, especially relevant for vaccination studies with asexual blood stage antigens of this parasite. for several immunization trials with purified recombinant merozoite/schizont antigens, the susceptible aotus karyotypes ii, iii, iv and vi were immunized with escherichia coli derived fusion proteins containing partial sequences of the proteins msai (merozoite surface an ...19921343721
efficiency of human plasmodium falciparum malaria vaccine candidates in aotus lemurinus monkeys.the protective efficacy of several recombinant and a synthetic plasmodium falciparum protein was assessed in aotus monkeys. the rp41 aldolase, the 190l fragment of the msa-1 protein and fusion 190l-cs. t3 protein containing the cs.t3 helper "universal" epitope were emulsified in freund's adjuvants and injected 3 times in groups of 4-5 monkeys each one. the synthetic polymer spf (66)30 also emulsified in freund's adjuvants was injected 6 times. control groups for both experiments were immunized w ...19921343722
study of humoral immune response in mammals immunized with plasmodium falciparum antigenic preparations.six plasmodium falciparum protein fractions, isolated under reducing conditions, were used to immunize mice, rabbits and the squirrel monkey saimiri sciureus. five or seven subcutaneous injections of each antigenic preparation, in conjunction with freund's complete or incomplete adjuvants, were administered. this led to the development of specific antibodies detected by ifat, elisa or immunoblotting which inhibited merozoite reinvasion in in vitro p. falciparum cultures. this activity seems to b ...19921343723
impaired renal function in owl monkeys (aotus nancymai) infected with plasmodium falciparum.impaired renal function was observed in sixteen aotus nancymai 25 and 3 months following infection with the uganda palo alto strain of plasmodium falciparum. decrease were noted in the clearance of endogenous creatinine, creatinine excretion, and urine volume while increases were observed in serum urea nitrogen, urine protein, urine potassium, fractional excretion of phosphorus and potassium, and activities of urinary enzymes. the results were suggestive of glomerulonephropathy and chronic renal ...19921343724
molecular approaches to malaria and babesiosis diagnosis.the development of additional methods for detecting and identifying babesia and plasmodium infections may be useful in disease monitoring, management and control efforts. the preliminary evaluate synthetic peptide-based serodiagnosis, a hydrophilic sequence (ddesefdkek) was selected from the published babr gene of b. bovis. immunization of rabbits and cattle with the hemocyanin-conjugated peptide elicited antibody responses that specifically detected both p. falciparum and b. bovis antigens by i ...19921343727
new approaches in in vitro cultures of plasmodium falciparum and babesia divergens by using serum-free medium based on human high density lipoproteins. 19921343728
human igg responses against the n-terminal region of the merozoite surface protein 1 of plasmodium vivax.the complete primary structure of the gene encoding the merozoite surface protein 1 of plasmodium vivax (pvmsp-1) revealed the existence of interspecies conserved regions among the analogous proteins of other plasmodia species. here, three dna recombinant clones expressing 50, 200 and 500 amino acids from the n-terminal region of the pvmsp-1 protein were used on elisa and protein immunoblotting assays to look at the igg antibody responses of malaria patients from the brazilian amazon region of r ...19921343729
a chromosome 9 deletion in plasmodium falciparum results in loss of cytoadherence.many lines of plasmodium falciparum undergo a deletion of the right end of chromosome 9 during in vitro culture accompanied by loss of cytoadherence and gametocytogenesis. selection of cytoadherent cells from a mixed population co-selects for those with an undeleted chromosome 9 and the selected cells produce gametocytes. the deletion also results in loss of expression of pfemp1, the putative cytoadherence ligand, suggesting that pfemp1 or a regulatory gene controlling pfemp1 expression and game ...19921343730
characterization of a plasmodium falciparium mutant that has deleted the majority of the gametocyte-specific pf11-1 locus.we identified a gametocyte-specific protein of plasmodium falciparum called pf11-1 and provide experimental evidence that this molecule is involved in the emergence of gametes of the infected erythrocyte (gametogenesis). a mutant parasite clone, which has deleted over 90% of the pf11-1 gene locus, was an important control to establish the gametocyte-specific expression of the pf11-1. molecular analysis of the pf11-1 deletion indicates that it is presumably due to a chromosome breakage with subse ...19921343731
importance of mean parasite clearance time and recrudescence time and their role in gradation of plasmodium falciparum resistance.the present paper describes the relationship of mean parasite clearance time (mpct) and mean parasite recrudescence time (mprt) in the epidemiology of plasmodium falciparum. the role of mpct in grading the resistance of an area has been discussed. further, mprt revealed a positive correlationship with the percentage of ri resistant cases, and showed an increase with age. the ratio of mprt/mpct is an indicator of stability status of the resistance.19921344170
malarial placental infection and low birth weight babies.two-hundred fifty-six mothers and their newborns were subjected to clinical and haematological tests for the evidence of malaria. placentae of these were examined histopathologically for malarial parasites and malarial pigment. forty six placentae showed scanty malarial pigment ingested by monocytes. these appearances were associated with focal syncytial necrosis and proliferation of cytotrophoblastic cells. plasmodium falciparum was found in cord blood of six cases. the mean weight of newborns ...19921344172
evaluation of indirect immunofluorescent antibody test for detection of igm specific antibodies in malaria.indirect immunofluorescent antibody test using plasmodium falciparum antigen from in vitro culture was evaluated for detecting igm antibodies in order to determine the feasibility of its application in serodiagnosis of malaria. test was compared with the already adapted igg-iif test using the same antigen. it was found that none of the healthy controls and slide negative fever cases had malaria igm antibodies whereas 8 per cent of healthy controls and 49.01 per cent of the slide negative fever c ...19921344176
lipid transport in plasmodium.during intraerythrocytic development, the human malaria parasite plasmodium falciparum actively internalizes phospholipids from its erythrocyte membrane and the extracellular medium. the import of exogenous lipids is not due to endocytosis, but to energy-dependent, transbilayer movement of phospholipids induced by the parasite in the erythrocyte surface. novel tubular membranes that appear to emerge from the vacuole of the parasite and extend into the erythrocyte cytoplasm are labeled by exogeno ...19921344664
[malaria and sickle-cell anemia. a correlation of the clinical and epidemiological aspects].a study was carried out on susceptibility of sicklemia patients to plasmodium falciparum (pf) malaria in 151 hemoglobin s carriers (homozygous and heterozygous), assisted at the cotonú hospital, benin, for 1 year. these diseased did not have any serious malaria complications. the results were compared to a control group without sickle-cell anemia who had 21.5% of complications due to the disease. prevalence of genetic anomaly was higher than 20% among the general population under study.19921344691
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
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
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 evolutionary origin of plasmodium falciparum. 19921350795
expression of thrombospondin-related anonymous protein in plasmodium falciparum sporozoites. 19921350818
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
chemoresistance of plasmodium falciparum in central africa. 19921355183
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
"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
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
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
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
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
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
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
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
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
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
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 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
"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
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
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 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
molecular cloning, stage-specific expression and cellular distribution of a putative protein kinase from plasmodium falciparum.a putative protein kinase gene (pfpk2) has been isolated from the human parasite plasmodium falciparum by using a mixed oligonucleotide pool which corresponds to a highly conserved region of serine/threonine protein kinases. the complete nucleotide sequence of 5 kb suggests the existence of a second transcriptional unit besides that of the pfpk2 gene, separated by a highly (a+t)-rich region and transcribed in a different orientation. no intron sequence exists in pfpk2. the predicted amino acid s ...19921378403
immunization with soluble protein-pulsed spleen cells induces class i-restricted cytotoxic t lymphocytes that recognize immunodominant epitopic peptides from plasmodium falciparum and hiv-1.ctl lines specific for two different proteins derived from the human pathogens, plasmodium falciparum (malaria) circumsporozoite protein and hiv-1 reverse transcriptase, were obtained by immunizing mice with protein-pulsed syngeneic spleen cells. the lysis of the target cells was dependent on a class i mhc molecule and the accessory molecule cd8. immunodominant epitopic peptides were identified previously in the two proteins using murine ctl derived after immunization with recombinant virus or s ...19921380039
a recombinant malaria protein that can induce th1 and cd8+ t cell responses without antibody formation.inbred strains of mice were immunized with p190-3, a 38-kda recombinant protein derived from p190, a major merozoite surface ag of the malaria parasite plasmodium falciparum. ag-specific proliferative t cell responses were obtained in h-2b, h-2d, and h-2k mouse strains. surprisingly, mice of the h-2b haplotype (e.g., c57bl/6) did not give a measurable antibody response to the recombinant protein administered in freund's adjuvant, but cd8+/cd4- as well as cd4+/cd8- t cells specific for p190-3 cou ...19921380040
further characterization of interactions between gamete surface antigens of plasmodium falciparum.target antigens of malaria transmission blocking immunity include a complex of 3 gamete surface proteins of 230-kda and 48/45-kda glycoproteins. previous studies have shown that epitopes recognized by blocking antibodies are conformational (reduction sensitive) in nature. studies were conducted to characterize the interactions between the target antigens and role of disulfide groups in the formation of the complex. treatment of detergent extracts of gametes with chaotropic agents and extremes of ...19921380124
plasmodium falciparum-infected erythrocyte receptor(s) for cd36 and thrombospondin are restricted to knobs on the erythrocyte surface.adherence of plasmodium falciparum-infected rbcs (prbc) to endothelial cells causes prbc sequestration in cerebral microvessels and is considered to be a major contributor to the pathogenesis of cerebral malaria. both cd36 and thrombospondin (tsp) are glycoproteins that mediate prbc adherence to endothelial cells in vitro. because they are both expressed on the surface of endothelial cells, they probably contribute to prbc sequestration and vascular occlusion in vivo. by applying affinity labeli ...19921380530
development of a malaria t-cell vaccine for blood stage immunity.we have defined a strategy for the development of a t-cell vaccine for blood stage immunity, taking into consideration the central role of t cells and mhc restriction in malaria immune responses. we have used the amphi computer algorithm to identify putative t-cell epitopes from conserved regions of 11 plasmodium falciparum asexual stage proteins. ten of the eleven proteins are currently candidates for vaccine development. using this algorithm we selected 22 putative t-cell epitope peptides and ...19921381110
involvement of cd36 on erythrocytes as a rosetting receptor for plasmodium falciparum-infected erythrocytes.plasmodium falciparum-infected erythrocytes (parasitized red blood cells [prbcs]) can adhere to uninfected erythrocytes (rbcs) to form rosettes, and adhere to the endothelial cell (ec) surface antigen cd36. these adherence phenomena have previously been considered quite different. we show that anti-cd36 monoclonal antibodies (moabs) reverse rosetting of prbcs from both a culture-adapted line (malayan camp [mc] strain) and a natural isolate, gam425. three moabs that block adherence of prbcs to ec ...19921382720
normal human erythrocytes express cd36, an adhesion molecule of monocytes, platelets, and endothelial cells.we have recently shown that rosetting of plasmodium falciparum (mc r+ line)-infected erythrocytes (parasitized red blood cells [prbcs]) with uninfected erythrocytes (rbcs) is blocked by coating of the rbcs with anti-cd36 monoclonal antibodies (moabs; handunnetti et al, blood 80:2097, 1992). adult rbcs have previously been considered negative for cd36. however, using fluorescence-activated cell sorter analysis with the anti-cd36 moabs 8a6, okm5, and okm8, which reverse rosetting, we consistently ...19921382721
cytoadherence characteristics of rosette-forming plasmodium falciparum.sequestration of plasmodium falciparum-infected erythrocytes to the capillary endothelium can cause obstruction and localized tissue damage. occlusion of vessels in falciparum malaria infection has been related to two properties of the parasite: adhesion to endothelial cells and rosette formation. our study on p. falciparum isolates from thailand producing variable numbers of rosettes suggests the involvement of rosettes in capillary blockage caused by direct adhesion of the rosette-forming infe ...19921383150
human vascular endothelial cell adhesion receptors for plasmodium falciparum-infected erythrocytes: roles for endothelial leukocyte adhesion molecule 1 and vascular cell adhesion molecule 1.the clinical complications associated with severe and cerebral malaria occur as a result of the intravascular mechanical obstruction of erythrocytes infected with the asexual stages of the parasite, plasmodium falciparum. we now report that a primary p. falciparum-infected erythrocyte (parasitized red blood cell [prbc]) isolate from a patient with severe complicated malaria binds to cytokine-induced human vascular endothelial cells, and that this adhesion is in part mediated by endothelial leuko ...19921383378
soluble intercellular adhesion molecule 1-immunoglobulin g1 immunoadhesin mediates phagocytosis of malaria-infected erythrocytes.we describe an immunoadhesin molecule containing intercellular adhesion molecule 1 (icam-1) molecularly fused to hinge and ch2 and ch3 domains of the human immunoglobulin g1 h chain that binds plasmodium falciparum-infected erythrocytes. this receptor-based immunoadhesin is an effective and specific inhibitor of p. falciparum-infected erythrocyte adhesion to icam-1-bearing surfaces, but does not inhibit leukocyte function antigen 1 (lfa-1) interaction with icam-1. furthermore, the immunoadhesin ...19921383388
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