Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “PLASMODIUM”

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 1,387 records · Page 77Linked to original sources
PubMed2000

Inhibition of the mosquito transmission of Plasmodium berghei by Malarone (atovaquone-proguanil).

Sera from patients treated with atovaquone-proguanil (Malarone) have previously been shown to inhibit the mosquito transmission of Plasmodium falciparum, though the inhibition was not complete and the effect declined 2 weeks after treatment. In marked contrast, the inhibition of transmission of P. berghei by human sera (fed to mosquitoes, with P. berghei gametocytes, via membrane feeders) from volunteers treated with atovaquone-proguanil was total up to day 28 post-treatment and still very significant at day 56. In view of the short half-lives of atovaquone and proguanil, this was unexpected, and further experiments, reported here, were undertaken. In contrast to the incomplete blockade of infectivity of P. falciparum by serum taken 4 days post-treatment, such serum was totally inhibitory against P. berghei at a 1:10,000 dilution, indicating a remarkable sensitivity of P. berghei and demonstrating an unusual difference between the two Plasmodium species in response to a drug. The inhibitory effect on P. berghei after day 4 was caused by atovaquone and mainly through blockade of development from ookinete to oocyst. Despite previous information on the rapid elimination of atovaquone by patients, the present data indicate that low concentrations of this drug may persist in the plasma for some weeks after treatment.

Animals↗
PubMed2000

Formation of Plasmodium falciparum gametocytes in vivo and in vitro relates to transmission intensity.

Plasmodium falciparum isolates were collected during a cross-sectional survey of fever cases in an endemic area of northern India, over a period of 6 months (July-December 1996). Smears of peripheral blood from 118 cases were found to contain Plasmodium falciparum. Isolates of the parasites were successfully cultured in vitro, under identical conditions, from blood samples from 58 of the smear-positives who had asexual parasitaemias of at least 0.05%. Gametocytes developed from 50 of the 58 isolates, with a variable range of gametocytaemia. An isolate was most likely to produce gametocytes and to produce high gametocytaemias (i.e. > or = 1.0%) in vitro if it had been collected when the intensity of transmission (as reflected in bloodsmear positivity) was relatively high. A young child (< 6 years) with fever was more likely to be smear-positive for the asexual and sexual stages of P. falciparum, but less likely to be seropositive for antibodies to these stages, than the older cases of fever.

Adolescent↗
PubMedDate not supplied

Detection of extracellular forms of babesia in the blood by electron microscopy: a diagnostic method for differentiation from Plasmodium falciparum.

Light microscopic examination of blood smears is the traditional approach for the diagnosis of babesiosis, but there is morphological overlap with Plasmodium falciparum. The authors describe 3 patients with babesial infection in whom the diagnosis was made by identifying extracellular merozoites in a buffy coat preparation using electron microscopy. This method resulted in a high yield of extracellular babesia, even in a case where virtually no extracellular babesia were detectable in the blood smear. The test had a reasonably fast turnaround time and allowed detailed visualization of the organisms and reliable distinction from Plasmodium falciparum.

Aged↗
PubMed1996

Sensitive detection of Plasmodium vivax in blood by a cell-ELISA using a monoclonal antibody.

An IgM monoclonal antibody (7C5B71) which reacted with the blood stages of Plasmodium vivax, but not with those of Plasmodium falciparum was used in a cell-ELISA to detect parasites in samples of peripheral blood. Blood thin smears were probed with monoclonal antibody 7C5B71 and then reacted with a peroxidase conjugate of the appropriate specificity and the insoluble chromogen amino-ethyl-carbazole. Infected cells which appeared dark red coloured were rapidly identified under a light microscope using a low magnification. The conventional microscopic examination of thin films coloured with Giemsa was used as reference test. Under laboratory conditions the test showed a positive result in samples with a level of parasitaemia of < or = 500 parasites/microliter of blood. In a preliminary field trial the test showed 100 % specificity for the diagnosis of P. vivax malaria.

Animals↗
PubMed1996

Open comparison of artemether and mefloquine in uncomplicated Plasmodium falciparum hyperparasitaemia in children.

The efficacy of intramuscular artemether given for 5 days and a single oral dose of mefloquine, 25 mg/kg/body-weight, was evaluated in 84 children with uncomplicated Plasmodium falciparum hyperparasitaemia ( > 5% parasitized erythrocytes). Follow-up was for 14 days in the artemether group and 28 days in the mefloquine group. Artemether produced a significantly higher parasite reduction at 24 hours [mean 90.6 vs 63.3%, 95% confidence interval 10.7-43.9] and significantly shorter parasite clearance time [mean 38.4 vs 49.3 hours, 95% confidence interval 5.5-16.3] than mefloquine. Fever clearance times were similar, presumably because of the use of an antipyretic in both treatment groups. Cure rate was 98% with artemether on day 14 and 100% with mefloquine on day 28. One child in the artemether group who had recurrence of parasitaemia on day 14 responded promptly to mefloquine with clearance of parasitaemia and fever at 24 hours. Although both drugs were well tolerated, mefloquine produced more episodes of abdominal pain with or without diarrhoea and vomiting. These results suggest that both drugs are effective in uncomplicated Plasmodium falciparum hyperparasitaemia in children from an endemic area of south-west Nigeria.

Administration, Oral↗
PubMed1998

Plasmodium vivax congenital malaria in a newborn of a Zairian immigrant.

We report a case of congenital malaria in a newborn whose mother is a native of Zaire now living in Italy. The baby developed remittent fever in the 3rd week of life with anaemia and hepatosplenomegaly. Malaria parasites found in blood smears and erroneously diagnosed initially as Plasmodium falciparum were subsequently recognized as Plasmodium vivax. On the basis of the first diagnosis, treatment with quinine chlorhydrate was successfully undertaken without significant side-effects. P. vivax parasites were also recovered a posteriori in blood smears of the mother who was febrile during the week of her delivery. This report suggests that symptomatic congenital malaria may be more common than is generally thought and should be suspected in non-malarious countries in febrile newborns born to mothers who have travelled in or immigrated from malaria-endemic areas.

Animals↗
PubMed2004

Structural characterization of vivapain-2 and vivapain-3, cysteine proteases from Plasmodium vivax: comparative protein modeling and docking studies.

Malaria remains one of the most important infectious diseases in the world. Plasmodial cysteine proteases are proposed to be promising targets for novel antimalarial drug design. Vivapain-2 and vivapain-3 are cysteine proteases from Plasmodium vivax and apparent orthologs of falcipain-2 and falcipain-3 from Plasmodium falciparum. Model structures of vivapain-2 and vivapain-3 have been derived using the comparative protein modeling approach and validated by various structure/geometry verification tools. Correlation between the interaction energies calculated based on the docking studies of the inhibitors and the corresponding association constants (k(ass)) provide additional validation for the structures. Moreover, some of the biochemical differences observed between the vivapains may be explained by the results of the docking studies. The overall structures of the two vivapains are similar to each other as well as to the falcipains with most of the catalytic residues conserved. At the same time, some important differences are observed between the sizes of the binding pockets as well as some of the residues involved in binding. The study suggests a likelihood of developing common inhibitors for these enzymes provided the interesting differences in the binding pockets of these enzymes are critically considered during such an attempt. The results of the current study can be utilized in de novo drug design for effective treatment of malaria.

Amino Acid Sequence↗
PubMed2004

Adenylyl and guanylyl cyclases from the malaria parasite Plasmodium falciparum.

Completion of several malaria parasite genome sequences and advances in Plasmodium gene manipulation technology, will lead to significant advances in our knowledge of the biology of these organisms. Biochemical analysis of the cyclic nucleotide signalling pathways of P. falciparum has provided important information on malaria parasite development. The Plasmodium purine nucleotide cyclase enzymes have extremely unusual structures and the regulatory mechanisms controlling parasite enzyme activity are distinct from those operating on the analogous host molecules. Study of these enzymes could therefore lead to novel strategies for anti-malarial intervention in addition to providing unique insights into the intriguing biology of the parasite.

Adenylyl Cyclases↗
PubMed2003

Influence of chloroquine treatment and Plasmodium falciparum malaria infection on some enzymatic and non-enzymatic antioxidant defense indices in humans.

BACKGROUND: It is known that malaria infection is accompanied by increased production of reactive oxygen species (ROS) and that malaria parasites are sensitive to oxidative damage. This has been proved by the efficacy of some antimalarial drugs that are known to act via generation of ROS when administered clinically or experimentally. OBJECTIVE: There is lack of information on the effect of chloroquine on the antioxidant defense systems of normal and malaria infected humans. Since chloroquine has remained the mainstay of therapeutic regimen in malaria endemic zones, the present investigation was therefore undertaken to study the status of blood antioxidant defense mechanism, and oxidative stress following chloroquine treatment in normal and plasmodium infected humans. METHODS: Ten healthy persons (5 males and 5 females) with the same age range (18-35 years) were taken as control group. Ten other individuals were treated with 25 mg/kg body with chloroquine over three days. Ten patients with malaria, not under antimalarial therapy were taken as another group, while another set of 10 patients with malaria were treated with 25 mg/kg body weight over three days. RESULTS: The activity of superoxide dismutase was increased by 23% in individuals treated with chloroquine compared to controls while the activity of the enzyme decreased by 26% in malaria patients and by 43% in malaria patients treated with chloroquine. In all the treatment groups, the activities of catalase and glutathione peroxidase were lowered (P < 0.001). Similarly the levels of vitamins A, C, and beta-carotene were decreased in the treatment groups while plasma ceruloplasmin was increased in the groups. Glutathione and cholesterol levels were decreased while malondialdehyde level was increased significantly. CONCLUSION: Chloroquine treatment mediated oxidative stress in the host and this effect was exacerbated in Plasmodium falciparum infected patients administered with the drug.

Adolescent↗
PubMed2003

Cross-binding between Plasmodium falciparum CTL epitopes and HLA class I molecules.

Plasmodium falciparum CTL epitope minigenes containing HLA-A2 and HLA-B7 subtype supermotifs were cloned into a plasmid expression vector; this expression was measured in eight human HLA class I molecule specific cell lines. Three assays for in vitro antigen presentation analysis were developed to examine the cross-binding between CTL epitopes and HLA class I molecules, including cell surface peptide-MHC class I binding assay, binding stabilization assay and MHC class I assembling assay. The results demonstrated that the HLA-B51 restricted CTL epitope of Plasmodium falciparum could be presented by other HLA class I molecules; however, no other presentation was found for HLA-A2.1 CTL epitope. This work suggests the possibility for improved vaccine-coverage rates by development of a CTL vaccine which contains epitopes capable of cross-binding among different MHC class I alleles.

Animals↗
PubMed1991

Lipid traffic between high density lipoproteins and Plasmodium falciparum-infected red blood cells.

Several intraerythrocytic growth cycles of Plasmodium falciparum could be achieved in vitro using a serum free medium supplemented only with a human high density lipoprotein (HDL) fraction (d = 1.063-1.210). The parasitemia obtained was similar to that in standard culture medium containing human serum. The parasite development was incomplete with the low density lipoprotein (LDL) fraction and did not occur with the VLDL fraction. The lipid traffic from HDL to the infected erythrocytes was demonstrated by pulse labeling experiments using HDL loaded with either fluorescent NBD-phosphatidylcholine (NBD-PC) or radioactive [3H]palmitoyl-PC. At 37 degrees C, the lipid probes rapidly accumulated in the infected cells. After incubation in HDL medium containing labeled PC, a subsequent incubation in medium with either an excess of native HDL or 20% human serum induced the disappearance of the label from the erythrocyte plasma membrane but not from the intraerythrocytic parasite. Internalization of lipids did not occur at 4 degrees C. The mechanism involved a unidirectional flux of lipids but no endocytosis. The absence of labeling of P. falciparum, with HDL previously [125I]iodinated on their apolipoproteins or with antibodies against the apolipoproteins AI and AII by immunofluorescence and immunoblotting, confirmed that no endocytosis of the HDL was involved. A possible pathway of lipid transport could be a membrane flux since fluorescence videomicroscopy showed numerous organelles labeled with NBD-PC moving between the erythrocyte and the parasitophorous membranes. TLC analysis showed that a partial conversion of the PC to phosphatidylethanolamine was observed in P. falciparum-infected red cells after pulse with [3H]palmitoyl-PC-HDL. The intensity of the lipid traffic was stage dependent with a maximum at the trophozoite and young schizont stages (38th h of the erythrocyte life cycle). We conclude that the HDL fraction appears to be a major lipid source for Plasmodium growth.

Animals↗
PubMed1994

Plasmodium falciparum exports the Golgi marker sphingomyelin synthase into a tubovesicular network in the cytoplasm of mature erythrocytes.

This work describes two unusual features of membrane development in a eukaryotic cell. (a) The induction of an extensive network of tubovesicular membranes by the malaria parasite Plasmodium falciparum in the cytoplasm of the mature erythrocyte, and its visualization with two ceramide analogues C5-DMB-ceramide and C6-NBD-ceramide. "Sectioning" of the infected erythrocytes using laser confocal microscopy has allowed the reconstruction of detailed three-dimensional images of this novel membrane network. (b) The stage-specific export of sphingomyelin synthase, a biosynthetic activity concentrated in the Golgi of mammalian cells, to this tubovesicular network. Evidence is presented that in the extracellular merozoite stage the parasite retains sphingomyelin synthase within its plasma membrane. However, intracellular ring- and trophozoite-stage parasites export a substantial fraction (approximately 26%) of sphingomyelin synthase activity to membranes beyond their plasma membrane. Importantly we do not observe synthesis of new enzyme during these intracellular stages. Taken together these results strongly suggest that the export of this classic Golgi enzyme is developmentally regulated in Plasmodium. We discuss the significance of this export and the tubovesicular network with respect to membrane development and function in the erythrocyte cytosol.

Animals↗
PubMed1996

A developmental defect in Plasmodium falciparum male gametogenesis.

Asexually replicating populations of Plasmodium parasites, including those from cloned lines, generate both male and female gametes to complete the malaria life cycle through the mosquito. The generation of these sexual forms begins with the induction of gametocytes from haploid asexual stage parasites in the blood of the vertebrate host. The molecular processes that govern the differentiation and development of the sexual forms are largely unknown. Here we describe a defect that affects the development of competent male gametocytes from a mutant clone of P. falciparum (Dd2). Comparison of the Dd2 clone to the predecessor clone from which it was derived (W2'82) shows that the defect is a mutation that arose during the long-term cultivation of asexual stages in vitro. Light and electron microscopic images, and indirect immunofluorescence assays with male-specific anti-alpha-tubulin II antibodies, indicate a global disruption of male development at the gametocyte level with at least a 70-90% reduction in the proportion of mature male gametocytes by the Dd2 clone relative to W2'82. A high prevalence of abnormal gametocyte forms, frequently containing multiple and unusually large vacuoles, is associated with the defect. The reduced production of mature male gametocytes may reflect a problem in processes that commit a gametocyte to male development or a progressive attrition of viable male gametocytes during maturation. The defect is genetically linked to an almost complete absence of male gamete production and of infectivity to mosquitoes. This is the first sex-specific developmental mutation identified and characterized in Plasmodium.

Animals↗
PubMed1979

Two Plasmodium knowlesi-specific antigens on the surface of schizont-infected Rhesus monkey erythrocytes induce antibody production in immune hosts.

Purified schizonts (6--10 nuclei) and membranes of schizont-infected erythrocytes from the Malaysian and Philippine strain of Plasmodium knowlesi are analyzed immunochemically using immunoglobulin of rhesus monkey hyperimmune sera against schizonts and of sera from naturally immune monkeys. The anti-schizont Ig identifies less than 20 immune components in Triton X-100-solubilized schizonts and membranes of infected cells. Of these antigens, 9 (component 1, 3, 4, 5, 6, 10, 11, 18, and 20) are common to parasites and membranes of infected erythrocytes, and 12 (2A,B, 6, 8, 9, 12, 13p, 14, 16A,B, 19 A,Bp, 21, 22p, and 23) are predominantly found in the parasite; 4 components (13i, 19A,Bi, 22A, B, and 24) are unique to the membrane of infected erythrocytes. Only three parasite-specific components (1, 13, and 19) are exposed on the surface of parasitized erythrocytes as revealed by both lactoperoxidase-catalyzed radioiodination and extensive absorption of anti-schizont Ig using intact infected erythrocytes. Two plasmodium-specific antigens (1 and 13) on the surface of infected erythrocytes are recognized by sera of rhesus monkeys rendered naturally immune against P. knowlesi infections and, therefore, represent antigens in vivo. Analyses of schizonts and membranes of parasitized erythrocytes of the two different strains of P. knowlesi yields only some minor quantitative, but no qualitative differences when analyzed with both types of antisera. Importantly, components 1 and 13 appear identical in both strains.

Animals↗
PubMed1987

A new human Duffy blood group specificity defined by a murine monoclonal antibody. Immunogenetics and association with susceptibility to Plasmodium vivax.

A new Duffy specificity, Fy6, defined by a murine monoclonal antibody of the IgG1 kappa class, is related to susceptibility to malarial invasion. In humans, Fy6 is present on the red cells of all persons except those of the Fy(a-b-) type, a distribution resembling that of Fy3. However proteolytic enzyme treatment of red cells enhances the reactivity of Fy3, whereas Fy6, like Fya and Fyb, is susceptible to degradation by this process. The number of Fy6 sites on human red cells was found to be 12,200 per cell, in close agreement with earlier estimates of the number of Fya sites. Anti-Fy6 reacted in western blots with a membrane glycoprotein of approximately 46,000 Mr, not significantly different from that of a molecule known to bear the Fya determinant. The Fy6 epitope is shown to be present on the red cells of some but not all nonhuman primate species, where it has a distribution not only distinctly different from Fya, Fyb, and Fy3, but in close accordance with susceptibility to penetration by Plasmodium vivax. Thus, the red cells of two species of macaques (Macaca mulatta and M. fascicularis), which are invaded by Plasmodium knowlesi but not by P. vivax are shown to have other Duffy antigens but to be devoid of Fy6. It appears, therefore, that the red cell epitopes used by these closely related species are distinct, and that susceptibility to P. vivax merozoite penetration is dependent on the presence of Fy6.

Animals↗
PubMed2001

Evidence for different mechanisms of chloroquine resistance in 2 Plasmodium species that cause human malaria.

Chloroquine (CQ)-resistant Plasmodium vivax malaria was first reported 12 years ago, nearly 30 years after the recognition of CQ-resistant P. falciparum. Loss of CQ efficacy now poses a severe problem for the prevention and treatment of both diseases. Mutations in a digestive vacuole protein encoded by a 13-exon gene, pfcrt, were shown recently to have a central role in the CQ resistance (CQR) of P. falciparum. Whether mutations in pfcrt orthologues of other Plasmodium species are involved in CQR remains an open question. This report describes pfcrt homologues from P. vivax, P. knowlesi, P. berghei, and Dictyostelium discoideum. Synteny between the P. falciparum and P. vivax genes is demonstrated. However, a survey of patient isolates and monkey-adapted lines has shown no association between in vivo CQR and codon mutations in the P. vivax gene. This is evidence that the molecular events underlying P. vivax CQR differ from those in P. falciparum.

Amino Acid Sequence↗
PubMed2003

Associations between anti-Schistosoma mansoni and anti-Plasmodium falciparum antibody responses and hepatosplenomegaly, in Kenyan schoolchildren.

Schoolchildren from 2 areas of Kenya, Kangundo and Kambu, have contrasting prevalences of hepatosplenomegaly, despite having similar prevalences and intensities of Schistosoma mansoni infection. However, in individual children, S. mansoni infection intensity is positively correlated with organomegaly. In a previous study, hepatosplenomegaly was associated with Th1-type anti-schistosome cytokine responses. Although the high-morbidity Kambu area had higher malaria transmission than did low-morbidity Kangundo, hepatosplenomegaly was not associated with clinical malaria or with patent malarial parasitemia. However, chronic exposure to malaria might be involved. Here, retrospectively, we assayed plasma from this original study, for anti-Plasmodium falciparum and anti-S. mansoni antibodies, to test whether greater exposure to Plasmodium was a cofactor for hepatosplenomegaly. We found that hepatosplenic children had significantly higher levels of anti-P. falciparum antibodies, compared with nonhepatosplenic children, a finding that strongly suggests that some experience of P. falciparum influenced the development of hepatosplenomegaly in these S. mansoni-infected children.

Animals↗
PubMedDate not supplied

Thioredoxin networks in the malarial parasite Plasmodium falciparum.

The intraerythrocytic protozoan parasite Plasmodium falciparum is responsible for more than 500 million clinical cases of tropical malaria annually. Although exposed to high fluxes of reactive oxygen species, Plasmodium lacks the antioxidant enzymes catalase and glutathione peroxidase. Thus, the parasite depends on the antioxidant capacity of its host cell and its own peroxidases. These are fuelled by the thioredoxin system and are considered to represent the major defense line against peroxides. Five peroxidases that act in different compartments have been described in P. falciparum. They include two typical 2-Cys peroxiredoxins (Prx), a 1-Cys Prx, the so-called antioxidant protein (AOP), which is a further Prx acting on the basis of a 1-Cys mechanism, and a glutathione peroxidase-like thioredoxin peroxidase. Because of their central function in redox regulation and antioxidant defense, some of these proteins might represent highly interesting targets for structure-based drug development. In this article we summarize the present knowledge on the thioredoxin and peroxiredoxin metabolism in malaria parasitized red blood cells. We furthermore report novel data on the biochemical and kinetic characterization of different thioredoxins, of AOP, and of the classic 1-Cys peroxiredoxin of P. falciparum.

Amino Acid Sequence↗