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 1,027 records · Page 57Linked to original sources
PubMed2002

Ligands of the peripheral benzodiazepine receptor are potent inhibitors of Plasmodium falciparum and Toxoplasma gondii in vitro.

The increase in resistance of the malaria parasite Plasmodium falciparum to currently available drugs demands the development of new antimalarial agents. In this quest, we have found that ligands to the peripheral benzodiazepine receptor such as flurazepam, an agonist of the benzodiazepine family, and PK11195, an antagonist derived from isoquinoline, were active against Plasmodium falciparum. These two compounds effectively and rapidly inhibited parasite growth in vitro, irrespective of parasite resistance to chloroquine and mefloquine. Treatment with both drugs induced a sharp and consistent decline in parasitemia, a complete inhibition of parasite replication, and the destruction of parasites within the host red blood cells. Using electron microscopy, we showed that dramatic morphological changes, involving swollen endoplasmic reticulum and the reduction of hemozoin, were consistent with parasite death. The potent activities of flurazepam and PK11195 were also evaluated for antagonist or synergistic effects with currently used antimalarial drugs such as chloroquine and mefloquine. Moreover, flurazepam was found to be active against Toxoplasma gondii, another member of the phylum Apicomplexa. Taken together, our results indicated that benzodiazepines could be considered promising candidates in the treatment of both malaria and toxoplasmosis.

Animals↗
PubMed1994

[Biology of the vectors and transmission of Plasmodium falciparum, P. malariae and P. ovale in a village in the savanna of west Africa (Dielmo, Senegal)].

From April 1990 to March 1992 a longitudinal entomological study was carried out in Dielmo village, Senegal, an area of Sudan-type savanna. Mosquitoes were sampled by night-bite collections and pyretnrum spray collections. Seven anopheles species were identified: An. gambiae s.s. An. arabiensis, An. funestus, An. pharoensis, An. rufipes, An. squamosus and An. ziemanni. Present throughout the year, An. gambiae s.l. and An. funestus represented more than 98% of anopheles captured on man. A yearly wave of An. gambiae s.l. was observed in the rainy season and An. funestus was generally more abundant in the dry season. The sporozoite rate was 1.5% and 1.3%, respectively, for these two species. Sporozoite typing by monoclonal antibodies indicated that the proportion of infected salivary glands was 92.7% P. falciparum, 18.2% P malariae and 8.2% P. ovale. The inoculation rate was calculated to be respectively 111, 21 and 8 infective bites per human for P. falciparum, P. malariae and P. ovale during the first year. Transmission was highest in the second year, with respectively 272, 54 and 25 infective bites per human.

Adolescent↗
PubMed2001

PlasmoDB: An integrative database of the Plasmodium falciparum genome. Tools for accessing and analyzing finished and unfinished sequence data. The Plasmodium Genome Database Collaborative.

The PLASMODIUM: falciparum Genome Database (http://PlasmoDB.org) integrates sequence information, automated analyses and annotation data emerging from the P.falciparum genome sequencing consortium. To date, raw sequence coverage is available for >90% of the genome, and two chromosomes have been finished and annotated. Data in PlasmoDB are organized by chromosome (1-14), and can be accessed using a variety of tools for graphical and text-based browsing or downloaded in various file formats. The GUS (Genomics Unified Schema) implementation of PlasmoDB provides a multi-species genomic relational database, incorporating data from human and mouse, as well as P.falciparum. The relational schema uses a highly structured format to accommodate diverse data sets related to genomic sequence and gene expression. Tools have been designed to facilitate complex biological queries, including many that are specific to PLASMODIUM: parasites and malaria as a disease. Additional projects seek to integrate genomic information with the rich data sets now becoming available for RNA transcription, protein expression, metabolic pathways, genetic and physical mapping, antigenic and population diversity, and phylogenetic relationships with other apicomplexan parasites. The overall goal of PlasmoDB is to facilitate Internet- and CD-ROM-based access to both finished and unfinished sequence information by the global malaria research community.

Animals↗
PubMed2006

Clinical atovaquone-proguanil resistance of Plasmodium falciparum associated with cytochrome b codon 268 mutations.

Plasmodium falciparum resistance to atovaquone-proguanil has so far been associated with Y268S or Y268N mutations in cytochrome b, although these changes were identified in only seven of the 11 treatment failures. Here, we describe 10 new cases of atovaquone-proguanil treatment failures among which the parasite resistance was confirmed in six cases, either by identifying correct plasma drug concentrations or by observing in vitro atovaquone resistance. Resistance was consistently associated with codon 268 mutations (Y268S or a previously unidentified mutation, Y268C). Notably, mutations were not detected before the treatment but only after the drug exposure.

Adolescent↗
PubMed2006

Characterization of peripheral blood lymphocyte subsets in patients with acute Plasmodium falciparum and P. vivax malaria infections at Wonji Sugar Estate, Ethiopia.

We investigated the absolute counts of CD4+, CD8+, B, NK, and CD3+ cells and total lymphocytes in patients with acute Plasmodium falciparum and Plasmodium vivax malaria. Three-color flow cytometry was used for enumerating the immune cells. After slide smears were stained with 3% Giemsa stain, parasite species were detected using light microscopy. Data were analyzed using STATA and SPSS software. A total of 204 adults of both sexes (age, >15 years) were included in the study. One hundred fifty-eight were acute malaria patients, of whom 79 (50%) were infected with P. falciparum, 76 (48.1%) were infected with P. vivax, and 3 (1.9%) were infected with both malaria parasites. The remaining 46 subjects were healthy controls. The leukocyte count in P. falciparum patients was lower than that in controls (P=0.015). Absolute counts of CD4+, CD8+, B, and CD3+ cells and total lymphocytes were decreased very significantly during both P. falciparum (P<0.0001) and P. vivax (P<0.0001) infections. However, the NK cell count was an exception in that it was not affected by either P. falciparum or P. vivax malaria. No difference was found in the percentages of CD4, CD8, and CD3 cells in P. falciparum or P. vivax patients compared to controls. In summary, acute malaria infection causes a depletion of lymphocyte populations in the peripheral blood. Thus, special steps should be taken in dealing with malaria patients, including enumeration of peripheral lymphocyte cells for diagnostic purposes and research on peripheral blood to evaluate the immune status of patients.

Acute Disease↗
PubMed1994

Analysis of expressed sequence tags from Plasmodium falciparum.

An initiative was undertaken to sequence all genes of the human malaria parasite Plasmodium falciparum in an effort to gain a better understanding at the molecular level of the parasite that inflicts much suffering in the developing world. 550 random complimentary DNA clones were partially sequenced from the intraerythrocytic form of the parasite as one of the approaches to analyze the transcribed sequences of its genome. The sequences, after editing, generated 389 expressed sequence tag sites and over 105 kb of DNA sequences. About 32% of these clones showed significant homology with other genes in the database. These clones represent 340 new Plasmodium falciparum expressed sequence tags.

Animals↗
PubMed1989

Differential antibody responses to Plasmodium falciparum and P. vivax circumsporozoite proteins in a human population.

Papua New Guineans exposed to hyperendemic malaria in the Madang area showed different antibody responses to Plasmodium falciparum and Plasmodium vivax sporozoites despite comparable entomological inoculation rates. Although there was a significant trend of increasing prevalence of anti-P. falciparum circumsporozoite (CS) protein immunoglobulin G (IgG) with age, there was no significant increase in the antibody units of IgG recognizing P. falciparum CS proteins. Antibodies recognizing P. vivax CS proteins steadily increased in prevalence and antibody units with age. Significant trends of increasing prevalence of antibody responders (both IgG and IgM) with increasing splenic enlargement were found in the younger age groups for P. falciparum CS proteins but not for P. vivax CS proteins. When antibody responders were analyzed by quartiles, there was a trend of increasing antibody response with age against P. vivax CS peptide, but not for P. falciparum CS protein. There was no evidence for increasing protection against blood-stage infections with increasing antibody levels for either P. falciparum or P. vivax. Neither were any significant relationships found between entomological inoculation rates and either CS antibody prevalence or concentration among the villages studied.

Adolescent↗
PubMed1992

Capture ELISA for IgM antibodies against Plasmodium falciparum glutamate rich protein.

This report describes a novel mu chain capture ELISA for the detection of IgM antibodies against a Plasmodium falciparum antigen. A fragment of the 220 kDa P. falciparum glutamate rich protein containing amino acid residues 489-1271 was expressed in E. coli as a recombinant chimeric beta-galactosidase fusion protein and used as antigen after purification and biotinylation. Specific IgM antibodies were found in 51% (39/77) of sera from adult Liberians immune to malaria. The binding of IgM antibodies was specific for the malaria portion of the fusion protein and no cross-reactivity was found in sera from patients with IgM antibodies due to other diseases. Inhibition studies with a fusion protein containing amino acid residues 816-1134 (GLURP816-1134) representing the carboxy-terminal repeat region suggested a different use of epitopes for IgM antibodies in different individuals.

Animals↗
PubMed2004

An improved chloramphenicol acetyltransferase assay for Plasmodium falciparum transfection.

Chloramphenicol acetyltransferase (CAT) is a popular choice as a reporter gene in transgenic studies in many different organisms, including Plasmodium falciparum. For experimental investigations into transfection efficiency and gene expression a robustly quantitative assay is of great value. On investigation the published protocol for CAT assay of P. falciparum was found to be prone to saturation due to the long incubation time; moreover, cellular material extracted from the parasite increased the enzyme activity. A new protocol was developed which is quantitative across a range of three orders of magnitude of CAT activity, takes account of the cellular extract effect, and is more rapid than the established method. The value of these improvements was demonstrated by analysing the effects of parasitaemia and amount of plasmid on transfection efficiency with both old and new methods.

Animals↗
PubMedDate not supplied

Infectivity of Plasmodium falciparum gametocytes to Anopheles arabiensis after treatment with sulfadoxine-pyrimethamine.

Sulfadoxine-pyrimethamine induces increased gametocytaemia when used for treating Plasmodium falciparum malaria. Laboratory-reared Anopheles arabiensis mosquitoes were fed with blood from patients with post-therapeutic gametocytaemia using a membrane feeder. Fourteen days later the heads and thoraxes of 613 mosquitoes were negative for P. falciparum sporozoites by enzyme-linked immunosorbent assay.

Animals↗
PubMed2002

Truncation of merozoite surface protein 3 disrupts its trafficking and that of acidic-basic repeat protein to the surface of Plasmodium falciparum merozoites.

Merozoite surface protein 3 (MSP3), an important vaccine candidate, is a soluble polymorphic antigen associated with the surface of Plasmodium falciparum merozoites. The MSP3 sequence contains three blocks of heptad repeats that are consistent with the formation of an intramolecular coiled-coil. MSP3 also contains a glutamic acid-rich region and a putative leucine zipper sequence at the C-terminus. We have disrupted the msp3 gene by homologous recombination, resulting in the expression of a truncated form of MSP3 that lacks the putative leucine zipper sequence but retains the glutamic acid-rich region and the heptad repeats. Here, we show that truncated MSP3, lacking the putative leucine zipper region, does not localize to the parasitophorous vacuole or interact with the merozoite surface. Furthermore, the acidic-basic repeat antigen (ABRA), which is present on the merozoite surface, also was not localized to the merozoite surface in parasites expressing the truncated form of MSP3. The P. falciparum merozoites lacking MSP3 and ABRA on the surface show reduced invasion into erythrocytes. These results suggest that MSP3 is not absolutely essential for blood stage growth and that the putative leucine zipper region is required for the trafficking of both MSP3 and ABRA to the parasitophorous vacuole.

Animals↗
PubMed2004

Plasmodium falciparum cysteine protease falcipain-1 is not essential in erythrocytic stage malaria parasites.

Among potential new targets for antimalarial chemotherapy are Plasmodium falciparum cysteine proteases, known as falcipains. Falcipain-2 and falcipain-3 are food vacuole hemoglobinases that may have additional functions. The function of falcipain-1 remains uncertain. To better characterize the role of falcipain-1 in erythrocytic parasites, we disrupted the falcipain-1 gene and characterized recombinant parasites. Disruption of the falcipain-1 gene was confirmed with Southern blots, and loss of expression of falcipain-1 was confirmed with immunoblots and by loss of labeling with a specific protease inhibitor. Compared with wild-type parasites, falcipain-1 knockout parasites developed normally, with the same morphology, multiplication rate, and invasion efficiency, and without significant differences in sensitivity to cysteine protease inhibitors. In wild-type and knockout parasites, cysteine protease inhibitors blocked hemoglobin hydrolysis in trophozoites, with a subsequent block in rupture of erythrocytes by mature schizonts, but they did not inhibit erythrocyte invasion by merozoites. Our results indicate that although falcipain-1 is expressed by erythrocytic parasites, it is not essential for normal development during this stage or for erythrocyte invasion.

Animals↗
PubMed1999

The diagnosis of Plasmodium falciparum infection in Gambian children, by field staff using the rapid, manual, ParaSight-F test.

A rapid immunodiagnostic test for Plasmodium falciparum, the ParaSight-F test, was evaluated in the diagnosis of malaria in 139 children with uncomplicated malaria, who presented at the Medical Research Council's clinic at Basse in Upper River division, The Gambia. The aim was to evaluate the performance and usefulness of the test as a diagnostic method in a malaria-endemic area, when performed by a field worker. Compared with microscopy, the test had a sensitivity of 96.5%, a specificity of 90.5%, a negative predictive value of 94.2% and a positive predictive value of 94.3%. Because of its sensitivity, specificity and simplicity, the ParaSight-F test will be of value in situations where microscopy is not possible.

Animals↗
PubMed1994

Plasmodium falciparum circumsporozoite antibody prevalence in Madagascar: a longitudinal study in three different epidemiologic areas.

A longitudinal study on the prevalence of Plasmodium falciparum circumsporozoite antibodies (Ab-CS) was carried out in 15 villages of three epidemiologic areas of Madagascar: the highlands, east coast, and the southwest region. A total of 3,967 blood samples were collected from November 1989 to April 1991 from cohorts of resident schoolchildren. The prevalence of Ab-CS in the examined population varied greatly according to the different ecoepidemiologic areas of the country. A correlation analysis was made between Ab-CS and P. falciparum parasite prevalence in the same population. High Ab-CS prevalence rates (25-75%) and levels (optical density = 0.28-0.76) were observed in the villages of the east coast (mesoendemic stable malaria). The Ab-CS prevalence rates varied from 0 to 37% in the highlands and southwest region villages (unstable malaria). The use of Ab-CS prevalence is proposed to be a useful and reliable seroepidemiologic marker of malaria endemicity in those areas of Madagascar in which malaria transmission is high and continues for more than four months a year.

Adolescent↗
PubMed2000

Efficacy of chloroquine in febrile Plasmodium falciparum infected children in Mewat region of Haryana.

During 1996, Mewat region of Gurgaon district in Haryana experienced high incidence of Plasmodium falciparum malaria, assuming epidemic proportion in large number of villages affected by floods. Mortality due to fever was also high. In vivo 7 days study amongst 32 febrile P. falciparum infected children of 1 to 14 years age group in flood affected villages of Ferozpur Jhirka Community Health Centre of Mewat region was carried out. All the 32 cases showed good response to chloroquine suggesting that drug was effective and useful as first line of treatment, reducing severity of P. falciparum infection and resolving fever due to infection of the species. The study also indicated that chloroquine was an effective drug in controlling epidemic situation and mortality in areas of high incidence of P. falciparum. Pyrogenic stimulus was variable among different developmental stages of P. falciparum and suggestive of the need of earliest possible initiation of anti-malaria treatment, community based fever survey and blood smear examination. Increase in incidence of fever in an endemic community, particularly in children, should be considered as an indicator of impending outbreak of P. falciparum malaria. Effectiveness of diagnostic and control measures taken can be evaluated on the basis of incidence of malaria particularly due to P. falciparum infection and also incidence of fever in an endemic community.

Adolescent↗
PubMed1993

Prospective in-vivo study of chloroquine resistance of Plasmodium falciparum in Zambian under-fives.

Zambian under-fives with malaria were selected on a positive thick blood smear for Plasmodium falciparum of at least 1000 parasites/microliter on the day of admission. During a chloroquine course, daily follow-up of parasitaemia was performed. Bloodsamples were taken on day 0 and day 3 to measure chloroquine levels before admission and after treatment. Eighty four patients were evaluated in this study. Forty eight patients did not meet all criteria. Thirty six patients met all criteria, of which 16 (44.5%) patients were infected with sensitive strains (S) and 20 (55.5%) with resistant strains (R) of P.falciparum.

Animals↗
PubMed2003

Erythrocyte invasion phenotypes of Plasmodium falciparum in The Gambia.

In vitro experimentation with Plasmodium falciparum has determined that a number of different receptor-ligand interactions are involved in the invasion of erythrocytes. Most culture-adapted parasite isolates use a mechanism of invasion that depends primarily on the erythrocyte sialoglycoprotein glycophorin A (GYPA) and erythrocyte-binding antigen 175 (EBA-175) of the parasite blood-stage merozoite. However, a minority of culture-adapted parasites and a majority of Indian field isolates can apparently invade by other means. Here, erythrocyte invasion phenotypes of P. falciparum field isolates in Africa were studied. For 38 Gambian isolates, invasion of neuraminidase-treated and trypsin-treated erythrocytes was inhibited, on average, by more than 60 and 85%, respectively, indicating a high level of dependence on sialic acid and trypsin-sensitive proteins on the erythrocyte surface. These results support the hypothesis that African P. falciparum parasites use GYPA as a primary receptor for invasion. However, the considerable variation among isolates confirms the idea that alternative receptors are also used by many parasites. Three amino acid polymorphisms in the GYPA-binding region of EBA-175 (region II) were not significantly associated with invasion phenotype. There was variation among isolates in the selectivity index (i.e., a statistical tendency toward aggregation or multiple invasions of host erythrocytes), but this variation did not correlate with enzyme-determined invasion phenotype or with eba-175 alleles. Overall, these invasion phenotypes in Africa support a vaccine strategy of inhibiting EBA-175 binding to GYPA but suggest that parasites with alternative phenotypes would be selected for if this strategy were used alone.

Adolescent↗