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sem studies on blood cells of plasmodium berghei infected balb/c mice treated with artesunate and homeopathic medicine china.the therapeutic efficacy of antimalarial drugs and their effect on various organs in the form of surface morphological deformations can be analyzed using scanning electron microscopy (sem). present study has been undertaken on plasmodium berghei (nk-65), a lethal rodent malaria parasite, to monitor the morphological changes in blood cells induced by the treatment with combination of artesunate and homeopathic medicine . combination therapy of artesunate (100 mg/kg) and china ϕ was found to be hi ...201123024494
histopathological effects of sub-chronic lamivudine-artesunate co-administration on the liver of diseased adult wistar rats.lamivudine and artesunate are sometimes co administered in hiv-malaria co morbidity. both drugs are used concurrently in presumptive malaria treatment and simultaneous hiv post exposure prophylaxis.201122540106
disruption of plasmepsin-4 and merozoites surface protein-7 genes in plasmodium berghei induces combined virulence-attenuated phenotype.blood stage malaria parasites causing a mild and self limited infection in mice have been obtained with either radiation or chemical mutagenesis showing the possibility of developing an attenuated malaria vaccine. targeted disruption of plasmepsin-4 (pm4) or the merozoite surface protein-7 (msp7) genes also induces a virulence-attenuated phenotype in terms of absence of experimental cerebral malaria (ecm), delayed increase of parasitemia and reduced mortality rate. the decrease in virulence in p ...201122355558
genome comparison of human and non-human malaria parasites reveals species subset-specific genes potentially linked to human disease.genes underlying important phenotypic differences between plasmodium species, the causative agents of malaria, are frequently found in only a subset of species and cluster at dynamically evolving subtelomeric regions of chromosomes. we hypothesized that chromosome-internal regions of plasmodium genomes harbour additional species subset-specific genes that underlie differences in human pathogenicity, human-to-human transmissibility, and human virulence. we combined sequence similarity searches wi ...201122215999
malaria parasite carbonic anhydrase: inhibition of aromatic/heterocyclic sulfonamides and its therapeutic potential.plasmodium falciparum (p. falciparum) is responsible for the majority of life-threatening cases of human malaria, causing 1.5-2.7 million annual deaths. the global emergence of drug-resistant malaria parasites necessitates identification and characterization of novel drug targets and their potential inhibitors. we identified the carbonic anhydrase (ca) genes in p. falciparum. the pfca gene encodes anα-carbonic anhydrase, a zn(2+)-metalloenzme, possessing catalytic properties distinct from that o ...201123569766
[antimalarial activity of hydroalcoholic extract from bixa orellana l].bixa orellana l. is one species used in traditional herb medicine in several continents. among the medicinal properties attributed to this plant, the antimalarial action has been included.201123437529
in vitro biotransformation, in vivo efficacy and pharmacokinetics of antimalarial chalcones.4'-n-butoxy-2,4-dimethoxy-chalcone (mbc) has been described as protecting mice from an otherwise lethal infection with plasmodium yoelii when dosed orally at 50 mg/kg/dose, daily for 5 days. in contrast, we found that oral dosing of mbc at 640 mg/kg/dose, daily for 5 days, failed to extend the survivability of p. berghei-infected mice. the timing of compound administration and metabolic activation likely contribute to the outcome of efficacy testing in vivo. microsomal digest of mbc yielded 4'-n ...201121282967
anti-malarial activity of holarrhena antidysenterica and viola canescens, plants traditionally used against malaria in the garhwal region of north-west himalaya.the increasing number of multidrug-resistant plasmodium strains warrants exploration of new anti-malarials. medicinal plant research has become more important, particularly after the development of chinese anti-malarial drug artemisnin from artemisia annua. the present study shows evaluation of anti-malarial effects of two plants commonly used against malaria in the garhwal region of north-west himalaya, in order to discover the herbal-based medicine.201121288335
evidence that mutant pfcrt facilitates the transmission to mosquitoes of chloroquine-treated plasmodium gametocytes.resistance of the human malarial parasite plasmodium falciparum to the antimalarial drug chloroquine has rapidly spread from several independent origins and is now widely prevalent throughout the majority of malaria-endemic areas. field studies have suggested that chloroquine-resistant strains might be more infective to mosquito vectors. to test the hypothesis that the primary chloroquine resistance determinant, mutations in pfcrt, facilitates parasite transmission under drug pressure, we have i ...201121288823
small-scale in vitro culture and purification of plasmodium berghei for transfection experiment.the standard protocol for genetic modification of the rodent malaria parasite plasmodium berghei requires infected blood from one or more laboratory mice, followed by large-scale in vitro parasite culture and purification of mature schizonts. here, protocols are described for small-scale in vitro culture from 20 µl of mouse tail blood and purification of mature p. berghei schizonts sufficient for a single transfection experiment. all procedures are performed in 1.5-ml microcentrifuge tubes. we c ...201121291917
anopheles stephensi saliva enhances progression of cerebral malaria in a murine model.malaria accounts for the greatest morbidity and mortality of any arthropod-borne disease globally. recently, it was determined that the protective antisporozoite cd8+ t-cell response originates predominantly from cutaneous lymph nodes draining the site of parasite inoculation by an anopheles mosquito. the female mosquito inoculates sporozoites along with an assortment of salivary proteins into the skin of its mammalian host. mosquito saliva has demonstrable antihemostatic as well as various immu ...201121395422
amodiaquine analogues containing no-donor substructures: synthesis and their preliminary evaluation as potential tools in the treatment of cerebral malaria.the synthesis and physico-chemical properties of novel compounds obtained by conjugation of amodiaquine with moieties containing either furoxan or nitrooxy no-donor substructures are described. the synthesised compounds were tested in vitro against both the chloroquine sensitive, d10 and the chloroquine resistant, w-2 strains of plasmodium falciparum (p. falciparum). most of the compounds showed an antiplasmodial activity comparable to that of the parent drug. by comparing the activities of simp ...201121396743
synthesis of benzologues of nitazoxanide and tizoxanide: a comparative study of their in vitro broad-spectrum antiprotozoal activity.we have synthesized two new benzologues of nitazoxanide (nit) and tizoxanide (tiz), using a short synthetic route. both compounds were tested in vitro against six protozoa (giardia intestinalis, trichomonas vaginalis, entamoeba histolytica, plasmodium berghei, leishmania mexicana and trypanosoma cruzi). compound 1 (benzologue of nit) showed broad antiprotozoal effect against all parasites tested, showing ic(50)'s<5 ++m. this compound was five-times more active than nit, and 18-times more potent ...201121397502
Antimalaria Effect of the Ethanolic Stem Bark Extracts of Ficus platyphylla Del.The antimalarial effect of the ethanolic stem bark extract of Ficus platyphylla Del was evaluated against Plasmodium berghei infection in mice. Nontreated, experimental control mice died of fulminant parasitemia from day 7 to 9 post-infection but mice treated with the extract at 300?mg/kg showed markedly reduced parasitaemia bouts of 43.50% and a mean survival time of 28 days postinfection. The plant extract prevented a drastic reduction in PCV showing its efficacy in ameliorating anaemic condit ...201122174991
hepcidin is regulated during blood-stage malaria and plays a protective role in malaria infection.hepcidin is one of the regulators of iron metabolism. the expression of hepcidin is induced in spleens and livers of mice infected with pathogenic bacteria. recent studies have indicated that serum hepcidin level is also increased in human subjects infected with plasmodium falciparum. the mechanism of the regulation of hepcidin expression and its role in the infection of malaria remains unknown. in this study, we determined the expression of hepcidin in livers of mice infected with plasmodium be ...201122084434
heterogeneous and tissue-specific regulation of effector t cell responses by ifn-gamma during plasmodium berghei anka infection.ifn-γ and t cells are both required for the development of experimental cerebral malaria during plasmodium berghei anka infection. surprisingly, however, the role of ifn-γ in shaping the effector cd4(+) and cd8(+) t cell response during this infection has not been examined in detail. to address this, we have compared the effector t cell responses in wild-type and ifn-γ(-/-) mice during p. berghei anka infection. the expansion of splenic cd4(+) and cd8(+) t cells during p. berghei anka infection ...201121880980
Antimalarial activity of imidazo[2,1-a]isoindol-5-ol derivatives and related compounds.The synthesis of several series of imidazo[2,1-a]isoindol-5-ol derivatives and the results of their evaluation against Plasmodium falciparum are presented and discussed. The effects of electron-withdrawing or-donating substituents on different parts of the molecule, as well as those produced by the incorporation of an additional fused ring, were analyzed. Several compounds showed significant antimalarial activity in vitro with IC(50) values as low as 60 nM and a certain efficacy in vivo by reduc ...201121940072
Coartemether Induced Oxidative and Hepatic Damage in Plasmodium berghei Strain Anka Infected Mice.This study investigated the effect of coartemether on antioxidant and hepatotoxic biomarkers in Plasmodium berghei infected mice. Erythrocyte, hepatic and renal superoxide dismutase (2.71 ± 0.51; 1.96 ± 0.87; 2.84 ± 0.22 Units/mg protein respectively) and catalase (4.10 ± 0.10; 8.25 ± 1.24; 6.28 ± 0.11 Units/mg protein respectively) activities were significantly (p < 0.05) elevated in "parasitized and treated" (PnT) animals. Renal glutathione level (19.02 ± 0.20 µg/mL) was elevated in PnT animal ...201122057281
high-throughput multi-parameter flow-cytometric analysis from micro-quantities of plasmodium-infected blood.despite significant technological and conceptual advances over the last century, evaluation of the efficacy of anti-malarial vaccines or drugs continues to rely principally on direct microscopic visualisation of parasites on thick and/or thin giemsa-stained blood smears. this requires technical expertise of the microscopist, is highly subjective and error-prone, and does not account for aberrations such as anaemia. many published methods have shown that flow cytometric analysis of blood is a hig ...201121907206
experimental cerebral malaria develops independently of card9 signalling.the outcome of infection depends on multiple layers of immune regulation with innate immunity playing a decisive role in shaping protection or pathogenic sequelae of acquired immunity. the contribution of pattern recognition receptors and adaptor molecules in immunity to malaria remains poorly understood. here we interrogate the role of the caspase recruitment domain-containing protein 9 (card9) signalling pathway in the development of experimental cerebral malaria (ecm) using the murine plasmod ...201122158744
FLP/FRT-mediated conditional mutagenesis in pre-erythrocytic stages of Plasmodium berghei.We describe here a highly efficient procedure for conditional mutagenesis in Plasmodium. The procedure uses the site-specific recombination FLP-FRT system of yeast and targets the pre-erythrocytic stages of the rodent Plasmodium parasite P. berghei, including the sporozoite stage and the subsequent liver stage. The technique consists of replacing the gene under study by an FRTed copy (i.e., flanked by FRT sites) in the erythrocytic stages of a parasite clone that expresses the flip (FLP) recombi ...201121886105
A carbamate-based approach to primaquine prodrugs: Antimalarial activity, chemical stability and enzymatic activation.O-Alkyl and O-aryl carbamate derivatives of the antimalarial drug primaquine were synthesised as potential prodrugs that prevent oxidative deamination to the inactive metabolite carboxyprimaquine. Both O-alkyl and O-aryl carbamates undergo hydrolysis in alkaline and pH 7.4 phosphate buffers to the parent drug, with O-aryl carbamates being ca. 10(6)-10(10) more reactive than their O-alkyl counterparts. In human plasma O-alkyl carbamates were stable, whereas in contrast their O-aryl counterparts r ...201122189276
inactivation of a plasmodium apicoplast protein attenuates formation of liver merozoites.malaria parasites undergo a population expansion inside the host liver before disease onset. developmental arrest inside host hepatocytes elicits protective immune responses. therefore, elucidation of the molecular mechanisms leading to mature hepatic merozoites, which initiate the pathogenic blood phase, also informs anti-malaria vaccine strategies. using targeted gene deletion in the rodent model malaria parasite plasmodium berghei, we show that a plasmodium-specific apicoplast protein plays a ...201121848587
nogo-a expression in the brain of mice with cerebral malaria.cerebral malaria (cm) is associated with a high rate of transient or persistent neurological sequelae. nogo-a, a protein that is highly expressed in the endoplasmic reticulum (er) of the mammalian central nervous system (cns), is involved in neuronal regeneration and synaptic plasticity in the injured cns. the current study investigates the role of nogo-a in the course of experimental cm. c57bl/6j mice were infected with plasmodium berghei anka blood stages. brain homogenates of mice with differ ...201121980529
a gfp-actin reporter line to explore microfilament dynamics across the malaria parasite lifecycle.malaria parasite motility relies on an internal parasite actomyosin motor that, when linked to the host cell substrate, propels motile zoites forward. despite their key role in this process, attempts to visualize actin microfilaments (f-actin) during motility and under native microscopy conditions have not to date been successful. towards facilitating their visualization we present here a plasmodium berghei transgenic line in which a green fluorescent protein (gfp)-actin fusion is constitutively ...201122138565
structure-activity relationships of 4-position diamine quinoline methanols as intermittent preventative treatment (ipt) against plasmodium falciparum.a library of diamine quinoline methanols were designed based on the mefloquine scaffold. the systematic variation of the 4-position amino alcohol side chain led to analogues that maintained potency while reducing accumulation in the central nervous system (cns). although the mechanism of action remains elusive, these data indicate that the 4-position side chain is critical for activity and that potency (as measured by ic(90)) does not correlate with accumulation in the cns. a new lead compound, ...201121854078
Antimalarial activity of 6-(1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-ol (N-251) and its carboxylic acid derivatives.Malaria is one of the world's deadliest diseases and is becoming an increasingly serious problem as malaria parasites develop resistance to most of the antimalarial drugs used today. We previously reported the in vitro and in vivo antimalarial potencies of 1,2,6,7-tetraoxaspiro[7.11]nonadecane (N-89) and 6-(1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-ol (N-251) against Plasmodium falciparum and Plasmodium berghei parasites. To improve water-solubility for synthetic peroxides, a variety of cy ...201121924377
quantitation of brain edema and localisation of aquaporin 4 expression in relation to susceptibility to experimental cerebral malaria.the pathogenic mechanisms underlying the occurrence of cerebral malaria (cm) are still incompletely understood but, clearly, cerebral complications may result from concomitant microvessel obstruction and inflammation. the extent to which brain edema contributes to pathology has not been investigated. using the model of p. berghei anka infection, we compared brain microvessel morphology of cm-susceptible and cm-resistant mice. by quantitative planimetry, we provide evidence that cm is characteriz ...201121904632
reduced cd36-dependent tissue sequestration of plasmodium-infected erythrocytes is detrimental to malaria parasite growth in vivo.adherence of parasite-infected red blood cells (irbc) to the vascular endothelium of organs plays a key role in the pathogenesis of plasmodium falciparum malaria. the prevailing hypothesis of why irbc adhere and sequester in tissues is that this acts as a mechanism of avoiding spleen-mediated clearance. irbc of the rodent parasite plasmodium berghei anka sequester in a fashion analogous to p. falciparum by adhering to the host receptor cd36. to experimentally determine the significance of seques ...201122184632
plasmodium berghei nk65 induces cerebral leukocyte recruitment in vivo: an intravital microscopic study.malaria is second only to tuberculosis as the leading cause of morbidity and mortality as a consequence of a single infectious agent. much of the pathology of malaria arises from the inappropriate or excessive immune response mounted by the host in an attempt to eliminate the parasite. we here report the inflammatory changes observed in the cerebral microvasculature of c57bl/6 and balb/c mice that had been inoculated with plasmodium berghei nk65, a lethal strain of rodent malaria. although no ne ...201121722620
potential of a khaya ivorensis -alstonia boonei extract combination as antimalarial prophylactic remedy.the decoction of the combined stem barks of khaya ivorensis a. chev. (meliaceae) and alstonia boonei de wild (apocynaceae) has a history of use in traditional medicine of central cameroon for malaria treatment but also for the prevention of the disease.201121742022
vital functions of the malarial ookinete protein, ctrp, reside in the a domains.the transformation of malaria ookinetes into oocysts occurs in the mosquito midgut and is a major bottleneck for parasite transmission. the secreted ookinete surface protein, circumsporozoite- and thrombospondin-related adhesive protein (trap)-related protein (ctrp), is essential for this transition and hence constitutes a potential target for malaria transmission blockade. ctrp is a modular multidomain protein containing six tandem von willebrand factor a-like (a) domains and seven tandem throm ...201121729699
rodent blood-stage plasmodium survive in dendritic cells that infect naive mice.plasmodium spp. parasites cause malaria in 300 to 500 million individuals each year. disease occurs during the blood-stage of the parasite's life cycle, where the parasite is thought to replicate exclusively within erythrocytes. infected individuals can also suffer relapses after several years, from plasmodium vivax and plasmodium ovale surviving in hepatocytes. plasmodium falciparum and plasmodium malariae can also persist after the original bout of infection has apparently cleared in the blood ...201121690346
synthesis and antimalarial activity of new heterocyclic hybrids based on chloroquine and thiazolidinone scaffolds.a series of new 21 chloroquine heterocyclic hybrids containing either benzylamino fragment or n-(aminoalkyl)thiazolidin-4-one moiety were synthesized and screened for their antimalarial activity against chloroquine (cq)-sensitive 3d7 and multidrug-resistance dd2 strains of plasmodium falciparum. although no compounds more active than cq against 3d7 was found; against dd2 strain, six compounds, four of them with benzylamino fragment, showed an excellent activity, up to 3-fold more active than cq. ...201121723734
the ifn-+¦-inducible gtpase, irga6, protects mice against toxoplasma gondii but not against plasmodium berghei and some other intracellular pathogens.clearance of infection with intracellular pathogens in mice involves interferon-regulated gtpases of the irg protein family. experiments with mice genetically deficient in members of this family such as irgm1(lrg-47), irgm3(igtp), and irgd(irg-47) has revealed a critical role in microbial clearance, especially for toxoplasma gondii. the in vivo role of another member of this family, irga6 (iigp, iigp1) has been studied in less detail. we investigated the susceptibility of two independently gener ...201121698150
Conserved peptide sequences bind to actin and enolase on the surface of Plasmodium berghei ookinetes.SUMMARYThe description of Plasmodium ookinete surface proteins and their participation in the complex process of mosquito midgut invasion is still incomplete. In this study, using phage display, a consensus peptide sequence (PWWP) was identified in phages that bound to the Plasmodium berghei ookinete surface and, in selected phages, bound to actin and enolase in overlay assays with ookinete protein extracts. Actin was localized on the surface of fresh live ookinetes by immunofluorescence and ele ...201121816124
Cellular and humoral immune effector mechanisms required for sterile protection against sporozoite challenge induced with the novel malaria vaccine candidate CelTOS.The malarial protein CelTOS, for cell-traversal protein for ookinetes and sporozoites, from Plasmodium berghei has been shown to mediate malarial invasion of both vertebrate and insect host cells and is required for establishing their successful infections. In the vertebrate host, Plasmodium sporozoites traverse via a complex passage through cellular barriers in the skin and the liver sinusoid to infect hepatocytes. Induction of immunity targeted to molecules involved in sporozoite motility and ...201121722682
Transgenic Plasmodium parasites stably expressing Plasmodium vivax dihydrofolate reductase-thymidylate synthase as in vitro and in vivo models for antifolate screening.Plasmodium vivax is the most prevalent cause of human malaria in tropical regions outside the African continent. The lack of a routine continuous in vitro culture of this parasite makes it difficult to develop specific drugs for this disease. To facilitate the development of anti-P. vivax drugs, bacterial and yeast surrogate models expressing the validated P. vivax target dihydrofolate reductase-thymidylate synthase (DHFR-TS) have been generated; however, they can only be used as primary screeni ...201121981896
A scalable pipeline for highly effective genetic modification of a malaria parasite.In malaria parasites, the systematic experimental validation of drug and vaccine targets by reverse genetics is constrained by the inefficiency of homologous recombination and by the difficulty of manipulating adenine and thymine (A+T)-rich DNA of most Plasmodium species in Escherichia coli. We overcame these roadblocks by creating a high-integrity library of Plasmodium berghei genomic DNA (>77% A+T content) in a bacteriophage N15-based vector that can be modified efficiently using the lambda Re ...201122020067
stage-specific depletion of myosin a supports an essential role in motility of malarial ookinetes.functional analysis of plasmodium genes by classical reverse genetics is currently limited to mutants that are viable during erythrocytic schizogony, the pathogenic phase of the malaria parasite where transfection is performed. here, we describe a conceptually simple experimental approach to study the function of genes essential to the asexual blood stages in a subsequent life cycle stage by a promoter-swap approach. as a proof of concept we targeted the unconventional class xiv myosin myoa, whi ...201121899701
experimentally controlled downregulation of the histone chaperone fact in plasmodium berghei reveals that it is critical to male gamete fertility.human fact (facilitates chromatin transcription) consists of the proteins spt16 and ssrp1 and acts as a histone chaperone in the (dis)assembly of nucleosome (and thereby chromatin) structure during transcription and dna replication. we identified a plasmodium berghei protein, termed fact-l, with homology to the spt16 subunit of fact. epitope tagging of fact-l showed nuclear localization with high expression in the nuclei of (activated) male gametocytes. the gene encoding fact-l could not be dele ...201121899698
The interplay between tubulins and P450 cytochromes during Plasmodium berghei invasion of Anopheles gambiae midgut.Plasmodium infection increases the oxidative stress inside the mosquito, leading to a significant alteration on transcription of Anopheles gambiae detoxification genes. Among these detoxification genes several P450 cytochromes and tubulins were differently expressed, suggesting their involvement in the mosquito's response to parasite invasion. P450 cytochromes are usually involved in the metabolism and detoxification of several compounds, but are also regulated by several pathogens, including ma ...201121912622
comparison of the reactivity of antimalarial 1,2,4,5-tetraoxanes with 1,2,4-trioxolanes in the presence of ferrous iron salts, heme, and ferrous iron salts/phosphatidylcholine.dispiro-1,2,4,5-tetraoxanes and 1,2,4-trioxolanes represent attractive classes of synthetic antimalarial peroxides due to their structural simplicity, good stability, and impressive antimalarial activity. we investigated the reactivity of a series of potent amide functionalized tetraoxanes with fe(ii)gluconate, feso(4), feso(4)/tempo, feso(4)/phosphatidylcholine, and heme to gain knowledge of their potential mechanism of bioactivation and to compare the results with the corresponding 1,2,4-triox ...201121888440
malaria-infected mice are completely cured by one 6 mg/kg oral dose of a new monomeric trioxane sulfide combined with mefloquine.sixteen new anilide derivatives of the natural trioxane artemisinin were prepared and evaluated for antimalarial efficacy in plasmodium berghei infected mice. of these 16 new anilides administered orally as one 6 mg/kg dose combined with 18 mg/kg mefloquine hydrochloride, only sulfide 3-artesanilide 12d was completely curative: on day 30 after infection, all mice in this group had no detectable parasitemia, gained as much weight as the uninfected control mice, and behaved normally.201122128829
wolbachia strain walbb enhances infection by the rodent malaria parasite plasmodium berghei in anopheles gambiae mosquitoes.wolbachia, a common bacterial endosymbiont of insects, has been shown to protect its hosts against a wide range of pathogens. however, not all strains exert a protective phenotype on their host. here we assess the affect of two divergent wolbachia strains, walbb from aedes albopticus and wmelpop from drosophila melanogaster, on the vector competence of anopheles gambiae challenged with plasmodium berghei. we show the walbb strain significantly increases p. berghei oocyst levels in the mosquito m ...201122210220
Kinetic of humoral and memory B cell response induced by Plasmodium falciparum Merozoite Surface Protein-119 in mice.The 19-kDa carboxyl-terminal fragment of the merozoite surface protein-1 (MSP-1(19)) has been shown to mediate antibody mediated protective immunity to blood-stage malaria infection. But the serological memory to this antigen tends to be short-lived and little is known of the mechanisms that regulate the formation of B cell memory to MSP-1(19) antigen. We studied the formation of B cell memory response after immunization with recombinant PfMSP-1(19).Immunization with PfMSP-1(19) resulted in dela ...201122104109
Development and evaluation of a prototype non-woven fabric filter for purification of malaria-infected blood.Many malaria-related studies depend on infected red blood cells (iRBCs) as fundamental material; however, infected blood samples from human or animal models include leukocytes (white blood cells or WBCs), especially difficult to separate from iRBCs in cases involving Plasmodium vivax. These host WBCs are a source of contamination in biology, immunology and molecular biology studies, requiring their removal. Non-woven fabric (NWF) has the ability to adsorb leukocytes and is already used as filtra ...201121867550
deletion of a malaria invasion gene reduces death and anemia, in model hosts.malaria parasites induce complex cellular and clinical phenotypes, including anemia, cerebral malaria and death in a wide range of mammalian hosts. host genes and parasite 'toxins' have been implicated in malarial disease, but the contribution of parasite genes remains to be fully defined. here we assess disease in balb/c mice and wistar rats infected by the rodent malaria parasite plasmodium berghei with a gene knock out for merozoite surface protein (msp) 7. msp7 is not essential for infection ...201121980474
immunization with genetically attenuated p52-deficient plasmodium berghei sporozoites induces a long-lasting effector memory cd8+ t cell response in the liver.abstract:201122004696
mitochondrial lipoic acid scavenging is essential for plasmodium berghei liver stage development.lipoic acid is an essential cofactor for enzymes that participate in key metabolic pathways in most organisms. while in mammalian cells lipoylated proteins reside exclusively in the mitochondria, apicomplexan parasites of the genus plasmodium harbor two independent lipoylation pathways in the mitochondrion and the apicoplast, a second organelle of endosymbiotic origin. protein lipoylation in the apicoplast relies on de novo lipoic acid synthesis while lipoylation of proteins in the mitochondrion ...201122128915
PbGEST mediates malaria transmission to both mosquito and vertebrate host.The malaria life cycle relies on the successful transfer of the parasite between its human and mosquito hosts. We identified a Plasmodium berghei secreted protein (PBANKA_131270) that plays distinct roles in both the mammal-to-mosquito and the mosquito-to-mammal transitions. This protein, here named gamete egress and sporozoite traversal (GEST), plays an important role in the egress of male and female gametes from the vertebrate red blood cell. Interestingly, GEST is also required following the ...201121958024
In vitro culture of Plasmodium berghei-ANKA maintains infectivity of mouse erythrocytes inducing cerebral malaria.ABSTRACT: BACKGROUND: Infection with Plasmodium berghei is a widely used model of murine malaria and a powerful tool for reverse genetic and pathogenesis studies. However, the efficacy of in vitro reinvasion of erythrocytes is generally low, limiting in vitro studies. METHODS: Plasmodium berghei ANKA-infected blood obtained from a susceptible infected mouse was cultured in various conditions and in vitro parasitaemia was measured every day to evaluate the rate of reinvasion. RESULTS: High quali ...201122118493
proteolytic breakdown of cytoskeleton induces neurodegeneration during pathology of murine cerebral malaria.fatal murine cerebral malaria is known to induce cellular degeneration by altering cellular morphology and integrity of cell. the morphology and integrity of the cell mainly depends on the cytoskeletal network of the cell. increased proteolysis of cytoskeletal proteins accompanied by aggravated suicidal proteases activation leads to cellular degeneration. in the present study, we investigated the roles of apoptotic and necrotic cell death proteases, caspase-3, calpain-1 and cathepsin-b in the pr ...201121914552
Triterpenoids as inhibitors of erythrocytic and liver stages of Plasmodium infections.Bioassay-guided fractionation of the methanol extract of Momordica balsamina led to the isolation of two new cucurbitane-type triterpenoids, balsaminol F (1) and balsaminoside B (2), along with the known glycosylated cucurbitacins, cucurbita-5,24-diene-3ß,23(R)-diol-7-O-ß-d-glucopyranoside (3) and kuguaglycoside A (4). Compound 1 was acylated yielding two new triesters, triacetylbalsaminol F (5) and tribenzoylbalsaminol F (6). The structures were elucidated based on spectroscopic methods includi ...201122071523
artemisinin and artemisinin plus curcumin liposomal formulations: enhanced antimalarial efficacy against plasmodium berghei-infected mice.the therapeutic efficacies of novel liposomal delivery systems based on artemisinin or artemisinin-based combination therapy with curcumin have been investigated and reported in this study. the developed liposomal formulations had proper characteristics as drug carriers for parental administration in terms of particle size, polydispersity, encapsulation efficacy and ζ-potential. their physical and chemical stabilities were also evaluated. furthermore, the in vivo antimalarial activity of artemis ...201122142592
antimalarial activities of new guanidylimidazole and guanidylimidazoline derivatives.a series of new guanidylimidazole derivatives was prepared and evaluated in mice and rhesus monkeys infected with malarial sporozoites. the majority of the new compounds showed poor metabolic stability and weak in vitro activities in three clones of plasmodium falciparum. compounds 8a, 8h, 9a, 16a, and 16e cured the mice infected with sporozoites of p. berghei at 160 and 320 mg/kg/day × 3 po. compounds 8a showed better causal prophylactic activity than primaquine, tafenoquine, and malarone in ...201121848332
characterization and tissue-specific expression patterns of the plasmodium chabaudi cir multigene family.variant antigens expressed on the surface of parasitized red blood cells (prbcs) are important virulence factors of malaria parasites. whereas plasmodium falciparum erythrocyte membrane proteins 1 (pfemp1) are responsible for sequestration of mature parasites, little is known about putative ligands mediating cytoadherence to host receptors in other plasmodium species. candidates include members of the pir superfamily found in the human parasite plasmodium vivax (vir), in the simian pathogen plas ...201121929749
Protection from experimental cerebral malaria with a single dose of radiation-attenuated, blood-stage Plasmodium berghei parasites.Whole malaria parasites are highly effective in inducing immunity against malaria. Due to the limited success of subunit based vaccines in clinical studies, there has been a renewed interest in whole parasite-based malaria vaccines. Apart from attenuated sporozoites, there have also been efforts to use live asexual stage parasites as vaccine immunogens.201121935405
independent roles of apical membrane antigen 1 and rhoptry neck proteins during host cell invasion by apicomplexa.during invasion, apicomplexan parasites form an intimate circumferential contact with the host cell, the tight junction (tj), through which they actively glide. the tj, which links the parasite motor to the host cell cytoskeleton, is thought to be composed of interacting apical membrane antigen 1 (ama1) and rhoptry neck (ron) proteins. here we find that, in plasmodium berghei, while both ama1 and ron4 are important for merozoite invasion of erythrocytes, only ron4 is required for sporozoite inva ...201122177563
cytofluorometric detection of rodent malaria parasites using red-excited fluorescent dyes.flow cytometry is a potentially efficient approach for the quantification of parasitemias in experimental malaria infections and drug susceptibility assays using rodent malaria models such as plasmodium berghei. in this study, we used two red dna-binding fluorochromes, rhodamine 800 (r800) and ld700, to measure parasitemia levels in whole blood samples from mice infected with p. berghei. blood samples were treated with rnase a to eliminate rna-derived signals. propidium iodide, which stains both ...201122015734
critical role of the neutrophil-associated high-affinity receptor for ige in the pathogenesis of experimental cerebral malaria.the role of the ige-fcεri complex in malaria severity in plasmodium falciparum-hosting patients is unknown. we demonstrate that mice genetically deficient for the high-affinity receptor for ige (fcεriα-ko) or for ige (ige-ko) are less susceptible to experimental cerebral malaria (ecm) after infection with plasmodium berghei (pbanka). mast cells and basophils, which are the classical ige-expressing effector cells, are not involved in disease as mast cell-deficient and basophil-depleted mice devel ...201121967768
evaluation of immunity against malaria using luciferase-expressing plasmodium berghei parasites.abstract: background: measurement of liver stage development is of key interest in malaria biology and vaccine studies. parasite development in liver cells can be visualized in real-time, both in culture and in live mice, using a transgenic plasmodium berghei parasite, pbgfp-luccon, expressing the bioluminescent reporter luciferase. this study explores the benefit of using these parasites for the evaluation of immunity against malaria, compared to qrt-pcr techniques in vivo and in vitro. metho ...201122152047
blood-stage plasmodium berghei infection generates a potent, specific cd8+ t-cell response despite residence largely in cells lacking mhc i processing machinery.murine cerebral malaria is a complex disease caused by plasmodium berghei anka infection. several cell types, including cd8(+) t cells, are essential effectors of disease. although the use of transgenic parasites expressing model antigens has revealed the induction of cytotoxic t lymphocytes (ctl) specific for these model antigens, there is no direct evidence for a response to authentic blood-stage parasite antigens, nor any knowledge of its magnitude. our studies show that there is a dramatic p ...201121998471
plasmodium ookinetes coopt mammalian plasminogen to invade the mosquito midgut.ookinete invasion of the mosquito midgut is an essential step for the development of the malaria parasite in the mosquito. invasion involves recognition between a presumed mosquito midgut receptor and an ookinete ligand. here, we show that enolase lines the ookinete surface. an antienolase antibody inhibits oocyst development of both plasmodium berghei and plasmodium falciparum, suggesting that enolase may act as an invasion ligand. importantly, we demonstrate that surface enolase captures plasm ...201121949403
antiplasmodial activity of xanthium strumarium against plasmodium berghei-infected balb/c mice.the present work was undertaken to evaluate the antiplasmodial activity of ethanolic leaves extract of traditional medicinal plant xanthium strumarium in plasmodium berghei-infected balb/c mice along with phytochemical screening and acute toxicity test to support its traditional medicinal use as a malaria remedy. the ethanolic leaves extract of x. strumarium (elexs) 150, 250, 350 and 500 mg/kg/day demonstrated dose-dependent chemosuppression during early and established infection long with signi ...201121847597
the anti-malarial activity of bivalent imidazolium salts.a series of compounds containing bivalent imidazolium rings and one triazolium analog were synthesized and evaluated for their ability to inhibit the replication of plasmodium falciparum cultures. the activity and selectivity of the compounds for p. falciparum cultures were found to depend on the presence of electron-deficient rings that were spaced an appropriate distance apart. the activity of the compounds was not critically dependent on the nature of the linker between the electron-deficient ...201121944972
imaging of plasmodium liver stages to drive next-generation antimalarial drug discovery.most malaria drug development focuses on parasite stages detected in red blood cells, even though, to achieve eradication, next-generation drugs active against both erythrocytic and exo-erythrocytic forms would be preferable. we applied a multifactorial approach to a set of >4000 commercially available compounds with previously demonstrated blood-stage activity (median inhibitory concentration < 1 micromolar) and identified chemical scaffolds with potent activity against both forms. from this sc ...201122096101
cns hypoxia is more pronounced in murine cerebral than noncerebral malaria and is reversed by erythropoietin.cerebral malaria (cm) is associated with high mortality and risk of sequelae, and development of adjunct therapies is hampered by limited knowledge of its pathogenesis. to assess the role of cerebral hypoxia, we used two experimental models of cm, plasmodium berghei anka in cba and c57bl/6 mice, and two models of malaria without neurologic signs, p. berghei k173 in cba mice and p. berghei anka in balb/c mice. hypoxia was demonstrated in brain sections using intravenous pimonidazole and staining ...201121854739
reverse fosmidomycin derivatives against the antimalarial drug target ispc (dxr).reverse hydroxamate-based inhibitors of ispc, a key enzyme of the non-mevalonate pathway of isoprenoid biosynthesis and a validated antimalarial target, were synthesized and biologically evaluated. the binding mode of one derivative in complex with ecispc and a divalent metal ion was clarified by x-ray analysis. pilot experiments have demonstrated in vivo potential.201121866890
expressed sequence tag analysis of the erythrocytic stage of plasmodium berghei.rodent malaria parasites, such as plasmodium berghei, are practical and useful model organisms for human malaria research because of their analogies to the human malaria in terms of structure, physiology, and life cycle. exploiting the available genetic sequence information, we constructed a cdna library from the erythrocytic stages of p. berghei and analyzed the expressed sequence tag (est). a total of 10,040 ests were generated and assembled into 2,462 clusters. these est clusters were compare ...201122072821
nematode-induced interference with the anti-plasmodium cd8(+) t-cell response can be overcome by optimizing antigen administration.malaria is still responsible for up to 1 million deaths per year worldwide, highlighting the need for protective malaria vaccines. helminth infections that are prevalent in malaria endemic areas can modulate immune responses of the host. here we show that strongyloides ratti, a gut-dwelling nematode that causes transient infections, did not change the efficacy of vaccination against plasmodium berghei. an ongoing infection with litomosoides sigmodontis, a tissue-dwelling filaria that induces chr ...201122161305
antimalarial activity of physalins b, d, f, and g.the antimalarial activities of physalins b, d, f, and g (1-4), isolated from physalis angulata, were investigated. in silico analysis using the similarity ensemble approach (sea) database predicted the antimalarial activity of each of these compounds, which were shown using an in vitro assay against plasmodium falciparum. however, treatment of p. berghei-infected mice with 3 increased parasitemia levels and mortality, whereas treatment with 2 was protective, causing a parasitemia reduction and a ...201121954931
erythrocyte remodeling in plasmodium berghei infection: the contribution of sep family members.the malaria parasite plasmodium largely modifies the infected erythrocyte through the export of proteins to multiple sites within the host cell. this remodeling is crucial for pathology and translocation of virulence factors to the erythrocyte surface. in this study, we investigated localization and export of small exported proteins/early transcribed membrane proteins (sep/etramps), conserved within plasmodium genus. this protein family is characterized by a predicted signal peptide, a short lys ...201122106924
Quinoline antimalarials containing a dibemethin group are active against chloroquinone-resistant Plasmodium falciparum and inhibit chloroquine transport via the P. falciparum chloroquine-resistance transporter (PfCRT).A series of 4-amino-7-chloroquinolines with dibenzylmethylamine (dibemethin) side chains were shown to inhibit synthetic hemozoin formation. These compounds were equally active against cultures of chloroquine-sensitive (D10) and chloroquine-resistant (K1) Plasmodium falciparum. The most active compound had an IC(50) value comparable to that of chloroquine, and its potency was undiminished when tested in three additional chloroquine-resistant strains. The three most active compounds exhibited lit ...201121875063
the effect of nitric oxide and hydrogen peroxide in the activation of the systemic immune response of anopheles albimanus infected with plasmodium berghei.the expression of genes encoding the antimicrobial peptides (amps) attacin, cecropin and gambicin, as well as the effects of no and h(2)o(2) on their expression was investigated in midguts and fat bodies of anopheles albimanus during the midgut infection with plasmodium berghei. midgut infection induced an increase in the expression of the three amps in both tissues; while no and h(2)o(2) were present in haemolymph. treatment with l-name and vitamin c reduced the effect of p. berghei infection o ...201120708028
schistosoma co-infection protects against brain pathology but does not prevent severe disease and death in a murine model of cerebral malaria.co-infections of helminths and malaria parasites are common in human populations in most endemic areas. it has been suggested that concomitant helminth infections inhibit the control of malaria parasitemia but down-modulate severe malarial disease. we tested this hypothesis using a murine co-infection model of schistosomiasis and cerebral malaria. c57bl/6 mice were infected with schistosoma mansoni and 8-9 weeks later, when schistosoma infection was patent, mice were co-infected with plasmodium ...201120708623
antiplasmodial activity of two marine polyherbal preparations from chaetomorpha antennina and aegiceras corniculatum against plasmodium falciparum.the ocean covers more than 70% of earth surface and hosts most 300,000 described species of plants and animals to use, which have been virtually unexploited for the development of medicines. marine plants are the good source of biologically active entities which exhibit therapeutic properties, when applied single or in combination of different plant extracts (polyherbal). polyherbal preparations are always a complex mixture of different forms and thus different compounds, which might act as agon ...201120844892
antimalarial activity of traditionally used western ghats plants from india and their interactions with chloroquine against chloroquine-tolerant plasmodium berghei.an ethnopharmacological investigation was undertaken on western ghats plants traditionally used to treat malaria; 50 plants were very carefully selected from total of 372 plants, and 216 extracts were prepared and tested for in vivo antiplasmodial activity alone and in combination with chloroquine (cq) against cq-tolerant plasmodium berghei (strain nk65). in in vivo antiplasmodial activity when plant extract alone is used, 81 extracts (or 37.5%) gave 52.90% significant parasitemia inhibition on ...201120846029
gene deletion from plasmodium falciparum using flp and cre recombinases: implications for applied site-specific recombination.the ability to manipulate the genome and induce site-specific recombination using either flippase (flp) or cre recombinase has been useful in many systems including plasmodium berghei for specific deletion events or to obtain conditional gene expression. to test whether these recombinases are active in plasmodium falciparum we constructed gene knockouts that contain sequences recognised as templates for site-specific recombination. we tested the ability of flp and cre recombinases, expressed con ...201120816845
reduced activity of the epithelial sodium channel in malaria-induced pulmonary oedema in mice.lung complications during malaria infection can range from coughs and impairments in gas transfer to the development of acute respiratory distress syndrome (ards). infecting c57bl/6 mice with plasmodium berghei k173 strain (pbk) resulted in pulmonary oedema, capillaries congested with leukocytes and infected red blood cells (irbcs), and leukocyte infiltration into the lungs. this new model of malaria-associated lung pathology, without any accompanying cerebral complications, allows the investiga ...201120816846
coincident parasite and cd8 t cell sequestration is required for development of experimental cerebral malaria.cerebral malaria (cm) is a fatal complication of plasmodium falciparum infection. using a well defined murine model, we observed the effect on disease outcome of temporarily reducing parasite burden by anti-malarial drug treatment. the anti-malarial treatment regime chosen decreased parasitaemia but did not cure the mice, allowing recrudescence of parasites. these mice were protected against cm, despite their parasitaemia having increased, following treatment cessation, to levels surpassing that ...201120828575
in vivo antimalarial activities of ethanolic crude extracts and fractions of leaf and root of carpolobia lutea.carpolobia lutea (leaves and root) is used traditionally as malarial remedy by the ibibios of niger delta of nigeria and benin. this study was aimed to investigate the antiplasmodial potentials of the crude leaf and root extracts of this plant as well as their fractions in vivo in plasmodium berghei berghei-infected mice to give scientific proof to the ethnobotanical claims and correlate with the reported in vivo activity. the ethanolic extracts of carpolobia lutea leaf (245-735 mg/kg/day) and r ...201121190920
triclosan is minimally effective in rodent malaria models. 201121217674
artemether and artesunate show the highest efficacies in rescuing mice with late-stage cerebral malaria and rapidly decrease leukocyte accumulation in the brain.the murine model of cerebral malaria (ecm) caused by plasmodium berghei anka (pba) infection in susceptible mice has been extensively used for studies of pathogenesis and identification of potential targets for human cm therapeutics. however, the model has been seldom explored to evaluate adjunctive therapies for this malaria complication. a first step toward this goal is to define a treatment protocol with an effective antimalarial drug able to rescue mice presenting late-stage ecm. we evaluate ...201121220531
use of a selective inhibitor to define the chemotherapeutic potential of the plasmodial hexose transporter in different stages of the parasite's life cycle.during blood infection, malarial parasites use d-glucose as their main energy source. the plasmodium falciparum hexose transporter (pfht), which mediates the uptake of d-glucose into parasites, is essential for survival of asexual blood-stage parasites. recently, genetic studies in the rodent malaria model, plasmodium berghei, found that the orthologous hexose transporter (pbht) is expressed throughout the parasite's development within the mosquito vector, in addition to being essential during i ...201121402842
sex and death: the effects of innate immune factors on the sexual reproduction of malaria parasites.malaria parasites must undergo a round of sexual reproduction in the blood meal of a mosquito vector to be transmitted between hosts. developing a transmission-blocking intervention to prevent parasites from mating is a major goal of biomedicine, but its effectiveness could be compromised if parasites can compensate by simply adjusting their sex allocation strategies. recently, the application of evolutionary theory for sex allocation has been supported by experiments demonstrating that malaria ...201121408620
disturbance in hemoglobin metabolism and in vivo antimalarial activity of azole antimycotics.plasmodium parasites degrade host hemoglobin to obtain free amino acids, essential for protein synthesis. during this event, free toxic heme moieties crystallize spontaneously to produce a non-toxic pigment called hemozoin or ß-hematin. in this context, a group of azole antimycotics, clotrimazole (ctz), ketoconazole (ktz) and fluconazole (fcz), were investigated for their abilities to inhibit ß-hematin synthesis (ißhs) and hemoglobin proteolysis (ihbp) in vitro. the ß-hematin synthesis was recor ...201121412616
nitric oxide protection against murine cerebral malaria is associated with improved cerebral microcirculatory physiology.cerebral malaria (cm) is a leading cause of death in plasmodium falciparum infections. in the plasmodium berghei anka (pba) murine model, cm pathogenesis is associated with low nitric oxide (no) bioavailability and brain microcirculatory complications, with a marked decrease in cerebral blood flow, vasoconstriction, vascular plugging by adherent cells, and hemorrhages. using intravital microscopy through a closed cranial window, here we show that no supplementation in the form of a no donor (dip ...201121415018
development of the piggybac transposable system for plasmodium berghei and its application for random mutagenesis in malaria parasites.the genome of a number of species of malaria parasites (plasmodium spp.) has been sequenced in the hope of identifying new drug and vaccine targets. however, almost one-half of predicted plasmodium genes are annotated as hypothetical and are difficult to analyse in bulk due to the inefficiency of current reverse genetic methodologies for plasmodium. recently, it has been shown that the transposase piggybac integrates at random into the genome of the human malaria parasite p. falciparum offering ...201121418605
differential microrna expression in experimental cerebral and noncerebral malaria.micrornas (mirnas) are posttranscriptional regulatory molecules that have been implicated in the regulation of immune responses, but their role in the immune response to plasmodium infection is unknown. we studied the expression of selected mirnas following infection of cba mice with plasmodium berghei anka (pba), which causes cerebral malaria (cm), or plasmodium berghei k173 (pbk), which causes severe malaria but without cerebral complications, termed non-cm. the differential expression profile ...201121422175
aminoindoles, a novel scaffold with potent activity against plasmodium falciparum.this study characterizes aminoindole molecules that are analogs of genz-644442. genz-644442 was identified as a hit in a screen of ~70,000 compounds in the broad institute's small-molecule library and the iccb-l compound collection at harvard medical school. genz-644442 is a potent inhibitor of plasmodium falciparum in vitro (50% inhibitory concentrations [ic50s], 200 to 285 nm) and inhibits p. berghei in vivo with an efficacy of > 99% in an adapted version of peters' 4-day suppressive test (w. ...201121422215
plasmodium berghei anka infection increases foxp3, il-10 and il-2 in cxcl-10 deficient c57bl/6 mice.cerebral malaria (cm) is a major cause of malaria mortality. sequestration of infected red blood cells and leukocytes in brain vessels coupled with the production of pro-inflammatory factors contribute to cm. cxcl-10 a chemokine that is chemotactic to t cells has been linked to fatal cm. mice deficient for cxcl-10 gene are resistant to murine cm, while antibody ablation of cxcl-10 enhanced the production of regulatory t cells (cd4+cd25+foxp3+) and il-10 which regulate the immune system. interleu ...201121439091
induction of antimalaria immunity by pyrimethamine prophylaxis during exposure to sporozoites is curtailed by parasite resistance.each year, infections with the protozoan parasite plasmodium falciparum kill 1 million people, mostly children in africa. intermittent preventive treatment (ipt) with sulfadoxine-pyrimethamine (sp) reduces the incidence of malaria and aims to prevent mortality in infants, children, and pregnant women. there is contradictory evidence as to whether this strategy may generate additional protection against reinfection beyond the limited duration of the intervention. previous work established that ab ...201121444698
dendritic cells and hepatocytes use distinct pathways to process protective antigen from plasmodium in vivo.malaria-protective cd8+ t cells specific for the circumsporozoite (cs) protein are primed by dendritic cells (dcs) after sporozoite injection by infected mosquitoes. the primed cells then eliminate parasite liver stages after recognizing the cs epitopes presented by hepatocytes. to define the in vivo processing of cs by dcs and hepatocytes, we generated parasites carrying a mutant cs protein containing the h-2k(b) epitope siinfekl, and evaluated the t cell response using transgenic and mutant mi ...201121445239
plasmodium cysteine repeat modular proteins 3 and 4 are essential for malaria parasite transmission from the mosquito to the host.the plasmodium cysteine repeat modular proteins (pcrmp) are a family of four conserved proteins of malaria parasites, that contain a number of motifs implicated in host-parasite interactions. analysis of mutants of the rodent parasite plasmodium berghei lacking expression of pcrmp1 or 2 showed that these proteins are essential for targeting of p. berghei sporozoites to the mosquito salivary gland and, hence, for transmission from the mosquito to the mouse.201121453484
simple flow cytometric detection of haemozoin containing leukocytes and erythrocytes for research on diagnosis, immunology and drug sensitivity testing.malaria pigment (haemozoin, hz) has been the focus of diverse research efforts. however, identification of hz-containing leukocytes or parasitized erythrocytes is usually based on microscopy, with inherent limitations. flow cytometric detection of depolarized side-scatter is more accurate and its adaptation to common bench top flow cytometers might allow several applications. these can range from the ex-vivo and in-vitro detection and functional analysis of hz-containing leukocytes to the detect ...201121453521
toward forward genetic screens in malaria-causing parasites using the piggybac transposon.the ability to analyze gene function in malaria-causing plasmodium parasites has received a boost with a recent paper in bmc genomics that describes a genome-wide mutagenesis system in the rodent malaria species plasmodium berghei using the transposon piggybac. this advance holds promise for identifying and validating new targets for intervention against malaria. but further improvements are still needed for the full power of genome-wide molecular genetic screens to be utilized in this organism. ...201121453557
plasmodium-host interactions directly influence the threshold of memory cd8 t cells required for protective immunity.plasmodium infections are responsible for millions of cases of malaria and ~1 million deaths annually. recently, we showed that sterile protection (95%) in balb/c mice required plasmodium berghei circumsporozoite protein (cs(252-260))-specific memory cd8 t cells exceeding a threshold of 1% of all pbls. importantly, it is not known if plasmodium species affect the threshold of cs-specific memory cd8 t cells required for protection. furthermore, c57bl/6 mice immunized with radiation-attenuated par ...201121460205
experimental asexual blood stage malaria immunity.immunity to asexual blood stages of malaria is complex, involving both humoral and cell-mediated immune mechanisms. the availability of murine models of malaria has greatly facilitated the analysis of immune mechanisms involved in resistance to the asexual blood stages. this unit details the materials and methods required for inducing protective immunity toward experimental blood stage malaria parasites by vaccination, repeated infection, and drug cure, as well as adoptive transfer of antigen-sp ...201121462169
cd8+ t cells and ifn-γ mediate the time-dependent accumulation of infected red blood cells in deep organs during experimental cerebral malaria.infection with plasmodium berghei anka (pba) in susceptible mice induces a syndrome called experimental cerebral malaria (ecm) with severe pathologies occurring in various mouse organs. immune mediators such as t cells or cytokines have been implicated in the pathogenesis of ecm. red blood cells infected with pba parasites have been shown to accumulate in the brain and other tissues during infection. this accumulation is thought to be involved in pba-induced pathologies, which mechanisms are poo ...201121494565
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