Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “PLASMODIUM FALCIPARUM”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 199 records · Page 11Linked to original sources
PubMed1994

Taxol arrests the development of blood-stage Plasmodium falciparum in vitro and Plasmodium chabaudi adami in malaria-infected mice.

Taxol, a natural product used to treat a variety of human cancers, is shown here to be extremely effective against chloroquine- and pyrimethamine-resistant malaria parasites. Addition of Taxol (1.0 microM) for one cycle to cultures of human erythrocytes infected with Plasmodium falciparum prevents the establishment of new infections. Blood parasitemia is eliminated in mice infected with Plasmodium chabaudi adami when they are given a single intraperitoneal injection of Taxol at 150 mg/m2. The majority of the animals treated immediately preceding parasite schizogony remain free of infection after eight replication cycles. The impressive antimalarial activity of Taxol, at a dosage that has been tolerated in humans, establishes its potential utility for treatment of severe, drug-resistant human malaria.

Animals↗
PubMed1993

Enhancement of drug susceptibility in Plasmodium falciparum in vitro and Plasmodium berghei in vivo by mixed-function oxidase inhibitors.

A number of compounds, as exemplified by verapamil and desipramine, have been shown to enhance the susceptibility of resistant malaria parasites to chloroquine. The mechanism by which these agents reverse resistance is still controversial but is though to involve alterations in drug transport causing an increase in steady-state drug concentrations. We have proposed that an alternative resistance mechanism may involve the metabolic deactivation of the drug in some resistant parasites via cytochrome P-450 mixed-function oxidases. If the hypothesis is true, it should be possible to alter drug susceptibility in malaria parasites by the use of agents known to inhibit or induce cytochrome P-450 activities. We have assessed the ability of known inhibitors of cytochrome P-450 enzymes (cimetidine, metyrapone, and alpha-naphthoflavone) to enhance chloroquine susceptibility in Plasmodium falciparum culture-adapted and wild-type isolates in vitro and P. berghei in vivo. In all three systems, the inhibitor cimetidine enhanced parasite susceptibility to chloroquine, and this increase in susceptibility was unrelated to changes in chloroquine steady-state concentrations in vitro or to alterations in host pharmacokinetics in vivo. Additionally, the cytochrome P-450 inducer phenobarbital produced slight decreases in P. falciparum drug susceptibility in vitro. We have compared the ability of the cytochrome P-450 inhibitors cimetidine and metyrapone to enhance drug susceptibility with that of verapamil by using wild-type malaria isolates obtained from Cameroon. Verapamil completely reversed resistance, i.e., to below the cutoff point of 70 nM, in all the resistant isolates. Cimetidine enhanced chloroquine susceptibility in 60% of the isolates and reduced 50% inhibitory concentrations by at least 43% in all the resistant isolates. The compounds tested had little or no effect on the 50% inhibitory concentrations for the susceptible isolates. The data support a possible role for detoxification in chloroquine resistance, and even in the absence of such a process we have observed apparent chemosensitization by agents whose common biological feature is the inhibition of cytochrome P-450 enzymes. Additionally, sensitization has been observed in wild-type isolates of P. falciparum obtained form immune residents of an area of endemicity as well as culture-adapted parasites.

Adolescent↗
PubMed2003

Changes in the levels of chemokines and cytokines in the placentas of women with Plasmodium falciparum malaria.

Plasmodium falciparum-infected erythrocytes often are sequestered in the placenta and stimulate the accumulation of maternal mononuclear cells. In this study, the role that chemokines and cytokines play in mediating the inflammatory response was investigated. Placental parasites elicited a statistically significant increase in the levels of interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-10, in plasma collected from the intervillous space. Explants of fetal tissue from malaria-positive placentas also secreted significantly enhanced amounts of IFN-gamma. Culture supernatant of maternal intervillous leukocytes obtained from infected placentas contained significantly higher levels of TNF-alpha, IL-10, monocyte chemotactic protein-1, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and IFN-gamma inducible protein-10 than did cultures of white blood cells obtained from uninfected placentas. Taken together, these results show that both fetal and maternal cells secrete inflammatory and immunoregulatory cytokines in response to P. falciparum and suggest that beta-chemokines produced by maternal cells contribute to the accumulation of macrophages in the intervillous space.

Adult↗
PubMed2004

Antimalarial activity of phenazines from lapachol, beta-lapachone and its derivatives against Plasmodium falciparum in vitro and Plasmodium berghei in vivo.

The antimalarial activity of benzo[a]phenazines synthesized from 1,2-naphthoquinone, lapachol, beta-lapachone and several derivatives have been tested against Plasmodium falciparum in vitro using isolates of parasites with various susceptibilities to chloroquine and/or mefloquine. Parasite growth in the presence of the test drugs was measured by incorporation of [(3)H]-hipoxanthine in comparison to controls with no drugs, always testing in parallel chloroquine, a standard antimalarial. Among seven benzophenazines tested, four had significant in vitro activities; important, the parasites resistant to chloroquine were more susceptible to the active phenazines in vitro. The doses of phenazines causing 50% inhibition of parasite growth varied from 1.67 to 9.44 microM. The two most active ones were also tested in vivo against Plasmodium berghei in mice, in parallel with lapachol and beta-lapachone. The 3-sulfonic acid-beta-lapachone-derived phenazine was the most active causing up to 98% inhibition of parasitaemia in long term treatment (7 doses) subcutaneously, whereas the phenazine from 3-bromo-beta-lapachone was inactive. Thus, these simple phenazines, containing polar (-Br,-I) and ionizable (-SO(3)H, -OH) groups, easily synthesized from cheap, natural or synthetic precursors (lapachol and beta-lapachone), at rather low cost, provide prototypes for development of new antimalarials aiming the chloroquine resistant parasites.

Animals↗
PubMed1995

Recombinant Pfs230, a Plasmodium falciparum gametocyte protein, induces antisera that reduce the infectivity of Plasmodium falciparum to mosquitoes.

Six regions of malaria transmission-blocking target antigen, Pfs230, encoding 80% of the 363-kDa protein, were expressed as recombinant proteins in E. coli as fusions with maltose-binding protein (MBP). Antisera generated against amylose-purified recombinant Pfs230/MBP fusion proteins (r230/MBP.A-r230/MBP.F) all recognized the 360-kDa form of parasite-produced Pfs230 by immunoblot. However, only antisera against the four carboxy regions (C-F) of Pfs230 and not the two amino regions (A and B) recognized the 310-kDa form of Pfs230, the form expressed on the surface of gametes. The data suggest that the 310-kDa form of Pfs230 arises from the cleavage of 50 kDa from the amino terminus of the 360-kDa form. Furthermore, antisera against r230/MBP.C bound to the surface of intact gametes and significantly reduced (by 71.2-89.8% (rank sum analysis, P < 0.01)) the infectivity of P. falciparum parasites to mosquitoes. This is the first report of a recombinant form of a P. falciparum gametocyte protein capable of inducing antisera that reduce malaria parasite infectivity to mosquitoes.

ATP-Binding Cassette Transporters↗
PubMed1991

Morphological characteristics of intracerebral arterioles in clinical (Plasmodium falciparum) and experimental (Plasmodium berghei) cerebral malaria.

Spastic constriction of intracerebral arterioles was identified in clinical (P. falciparum) and experimental (P. berghei) cerebral malaria. Morphological criteria were used to characterize pathologically spastic constriction of arterioles. The significance of spastic constriction of intracerebral arterioles for microcirculatory disturbance in relation to development of cerebral malaria is discussed.

Adult↗
PubMed1999

Virulence and transmission success of the malarial parasite Plasmodium falciparum.

Virulence of Plasmodium falciparum is associated with the expression of variant surface antigens designated PfEMP1 (P. falciparum erythrocyte membrane protein 1) that are encoded by a family of var genes. Data presented show that the transmission stages of P. falciparum also express PfEMP1 variants. Virulence in this host-parasite system can be considered a variable outcome of optimizing the production of sexual transmission stages from the population of disease-inducing asexual stages. Immunity to PfEMP1 will contribute to the regulation of this trade-off by controlling the parasite population with potential to produce mature transmission stages.

Animals↗
PubMed1997

Erythrocyte membrane alterations in Plasmodium falciparum malaria sequestration.

Plasmodium falciparum malaria, the most lethal form of human malaria, claims at least 2 million lives worldwide each year. Recently, there has been a significant advance in our understanding of the molecular basis of P. falciparum sequestration, a distinctive pathologic feature that often leads to fatal human cerebral malaria. Parasite-derived VAR proteins (Plasmodium falciparum-infected erythrocyte membrane protein 1) have been cloned and identified as antigenically diverse cytoadherent receptors localized to the knob protrusions that act as attachment points in parasite sequestration. Evidence now supports the hypothesis that cryptic regions of band 3 protein are parasite-induced, host-derived erythrocyte receptors mediating parasite sequestration. Knob structures have been localized to spectrin-actin-protein 4.1 junctions in intact spread membrane skeletons. A recombinant domain of knob-associated histidine-rich protein, a major protein found in both membrane-intact and isolated knobs, has been shown to associate with filamentous actin and spectrin. Parasite- and host-derived erythrocyte membrane proteins involved in P. falciparum sequestration are discussed in this review.

Animals↗
PubMed1988

Antibodies to the ring-infected erythrocyte surface antigen of Plasmodium falciparum elicited by infection with Plasmodium malariae.

The ring-infected erythrocyte surface antigen (RESA) of Plasmodium falciparum (RESA-P), found in the membrane of erythrocytes infected with young asexual stages of P. falciparum, is a promising vaccine candidate. Antibodies to RESA-P were inducible by infection with another human malaria species, P. malariae. Of 298 serum samples from inhabitants of three isolated localities in Peru where P. vivax and P. malariae were endemic and P. falciparum had never been reported, 26% had anti-RESA-P antibodies as evidenced by a modified immunofluorescent-antibody assay and confirmed by Western blot (immunoblot) analysis. These seroepidemiologic observations were corroborated by the fact that of six chimpanzees infected with P. malariae, three developed anti-RESA-P antibodies after infection. The modified immunofluorescent-antibody-reactive antibodies, purified by adsorption and elution on monolayers of glutaraldehyde-fixed and air-dried P. falciparum-infected erythrocytes, reacted in an immunofluorescent-antibody assay with both parasite structures and erythrocyte membrane in P. falciparum antigen preparations, but only with parasite structures in P. malariae antigen preparations. This serologic cross-reactivity between P. falciparum and P. malariae is of interest in view of the importance of RESA-P as a vaccine candidate and because the two species are coendemic in many areas.

Animals↗
PubMed2005

Identifying and characterising the Plasmodium falciparum merozoite surface protein 10 Plasmodium vivax homologue.

Plasmodium vivax malaria is one of the most prevalent parasitic diseases in Asia and Latin-America. The difficulty of maintaining this parasite culture in vitro has hampered identifying and characterising proteins implied in merozoite invasion of red blood cells. We have been able to identify an open reading frame in P. vivax encoding the Plasmodium falciparum merozoite surface protein 10 homologous protein using the partial sequences from this parasite's genome reported during 2004. This new protein contains 479 amino-acids, two epidermal growth factor-like domains, hydrophobic regions at the N- and C-termini, being compatible with a signal peptide and a glycosylphosphatidylinositol anchor site, respectively. The protein is expressed during the parasite's asexual stage and is recognised by polyclonal sera in parasite lysate using Western blot. P. vivax-infected patients' sera highly recognised recombinant protein by ELISA.

Amino Acid Sequence↗
PubMed1995

Antimalarial effects of C18 fatty acids on Plasmodium falciparum in culture and on Plasmodium vinckei petteri and Plasmodium yoelii nigeriensis in vivo.

Following the demonstration of the antimalarial effect of the long chain saturated alcohol n-hentriacontanol ((CH2)29CH2OH), isolated from the Bolivian endemic solanaceous plant Cuatresia sp., we have tested the effect of the C18 fatty acids oleic, elaidic, linoleic, and linoleic on malaria parasites. These fatty acids inhibited the parasitemic development in mice infected with Plasmodium vinckei petteri or with Plasmodium yoelii nigeriensis in a 4-day suppressive test. To gain a deeper discernment of the antimalarial mode of action, the effects of these compounds were evaluated on Plasmodium falciparum growth in culture. Whereas n-hentriacontanol did not show any inhibition of this parasite, on the contrary, the C18 acids displayed a considerably inhibitory activity at < or = 200 micrograms/ml both in intact infected cells and in free parasites. In order to understand the mechanism of their antimalarial action, several tests were performed. No hemolysis of infected cells could be observed up to 500 microgram/ml. No effect on the lipid peroxidation, ATP levels, transport through the parasite-induced permeability pathways, or on the phagocytosis of the infected cells could be observed. The cytotoxic effect of the fatty acids was very rapid: full inhibition of nucleic acids and protein syntheses was observed in less than 30 min. This inhibition was not relieved by the addition of deferrioxamine or FeCl3, indicating that fatty acids (FA) do not act by facilitating the transport of iron. Inhibition was relieved in neither the presence of orotic acid or its methyl ester, indicating that FA do not act at the mitochondrial level of pyrimidine synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1999

Mice immunised with synthetic peptide from N-terminal conserved region of merozoite surface antigen-2 of human malaria parasite Plasmodium falciparum can control infection induced by Plasmodium yoelii yoelii 265BY strain.

Synthetic peptides representing conserved MSA-2 sequences are being considered as a possible component of a blood stage malaria vaccine. Antibody response towards the entire N-terminal conserved region of MSA-2 and its constituent B-epitope SNTFINNA following immunisation of BALB/c and C57BL/6 mice with different peptide constructs was assessed by ELISA and immunofluorescence antibody test (IFAT). Co-linear synthesis of SNTFINNA-epitope in tandem with the entire N-terminal conserved region peptide (P23) made this construct, namely P8.P23, to be highly immunogenic in both mouse strains, with the antibody response to the SNTFINNA epitope comparable to that following tetanus toxoid protein conjugate immunisation. The antibodies raised specifically recognised the schizont stages of Plasmodium falciparum and Plasmodium yoelii. There was no protection observed upon challenge of immunised BALB/c and C57BL/6 mice with the highly lethal Plasmodium yoelii nigeriensis strain. On the contrary, BALB/c mice immunised with P8.P23 construct were able to resist blood stage infection induced by Plasmodium yoelii yoelii 265BY parasites, while animals inoculated with P23 did not control infection. Affinity purified rabbit anti-SNTFINNA IgG showed more than 60% inhibition of merozoite invasion of fresh erythrocytes in in vitro P. falciparum culture. The low prevalence of antibody response to SNTFINNA-epitope, tested in a dot-blot assay, was observed in sera of 80 individuals living in malaria endemic area in a India; the phenomenon may point out the cryptic character of epitopes residing at the N-terminal conserved region of MSA-2.

Animals↗
PubMed2004

Gametocytogenesis: the puberty of Plasmodium falciparum.

The protozoan Plasmodium falciparum has a complex life cycle in which asexual multiplication in the vertebrate host alternates with an obligate sexual reproduction in the anopheline mosquito. Apart from the apparent recombination advantages conferred by sex, P. falciparum has evolved a remarkable biology and adaptive phenotypes to insure its transmission despite the dangers of sex. This review mainly focuses on the current knowledge on commitment to sexual development, gametocytogenesis and the evolutionary significance of various aspects of gametocyte biology. It goes further than pure biology to look at the strategies used to improve successful transmission. Although gametocytes are inevitable stages for transmission and provide a potential target to fight malaria, they have received less attention than the pathogenic asexual stages. There is a need for research on gametocytes, which are a fascinating stage, responsible to a large extent for the success of P. falciparum.

Animals↗
PubMed2002

Short report: Positive correlation between rosetting and parasitemia in Plasmodium falciparum clinical isolates.

Plasmodium falciparum isolates that form rosettes with uninfected red cells are associated with severe malaria in African children, although the mechanism by which rosetting contributes to severe disease is unknown. Here we have analyzed the relationship between rosetting and parasitemia in two samples of clinical isolates from children with malaria in Kilifi, Kenya. A consistent positive correlation was found between rosetting and parasitemia (Spearman's rank correlation coefficent p = 0.467, P < .001, n = 154, for 1993 study; p = .407, P < .001, n = 74, for 2000 study). Rosetting may enhance parasite growth and survival by facilitating invasion or promoting immune evasion, thus allowing higher parasitemia to develop and increasing the likelihood of severe malaria.

Animals↗
PubMed2002

Abundant proton pumping in Plasmodium falciparum, but why?

Intraerythrocytic Plasmodium parasites depend on glycolysis for energy production. The stoichiometric amounts of lactate and protons produced are efficiently removed by a lactate:H(+) symporter. However, inhibition of recently identified plasma-membrane proton pumps result in acidification, suggesting additional mechanism(s) for proton generation. This article attempts to integrate the knowledge on the metabolic generation of protons and their disposal in the regulation of parasite cytosolic pH, and suggests additional roles for the various proton pumps that act in the parasite membrane.

Animals↗